Neurotology, 2nd Edition

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NEUROTOLOGY Second Edition Copyright © 2005 by Mosby, Inc. All rights reserved.

ISBN: 0-323-01830-0

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NOTICE Otolaryngology is an ever-changing field. Standard safety precautions must be followed, but as new research and clinical experience broaden our knowledge, changes in treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current product information provided by the manufacturer of each drug to be administered to verify the recommended dose, the method and duration of administration, and contraindications. It is the responsibility of the licensed prescriber, relying on experience and knowledge of the patient, to determine dosages and the best treatment for each individual patient. Neither the publisher nor the authors assume any liability for any injury and/or damage to persons or property arising from this publication.

Previous edition copyrighted 1994.

Library of Congress Cataloging-in-Publication Data

Neurotology/[edited by] Robert K. Jackler, Derald E. Brackmann.—2nd ed. p. ; cm. ISBN 0-323-01830-0 1. Vestibular apparatus—Diseases. 2. Vestibular apparatus—Surgery. 3. Auditory pathways—Diseases. 4. Auditory pathways—Surgery. I. Jackler, Robert K. II. Brackmann, Derald E [DNLM: 1. Vestibular Nerve. 2. Vestibulocochlear Nerve Diseases. 3. Skull Base Neoplasms. WL 330 N497 2004] RF260.T49 2004 617.8′82—dc22 2003066638

Acquisitions Editor: Rebecca Schmidt Gaertner Developmental Editor: Anne Snyder Publishing Services Manager: Joan Sinclair Project Manager: Mary Stermel

Printed in the United States of America

Last digit is the print number:

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Dedication

To Laurie and Charlotte

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Preface

In the early 1990s, the first edition of this text helped to define the body of knowledge encompassed by neurotology, which was then a relatively new field. Over the past decade, major strides have been realized on a number of fronts. In terms of specialty organizations, the American Neurotology Society has grown to over 500 members. Across the Atlantic, neurotology has been organized through the European Academy of Otology and Neurotology, an active group of some 300 members. Perhaps no aspect of neurotology has undergone a greater degree of maturation than training. In the United States, twoyear post-residency fellowships are now formally accredited by the American Council of Graduate Medical Education. As of early 2004, approximately 20 fellowship programs are active, 10 of which have completed the accreditation process. In a major milestone, neurotology has become the first subspecialty of Otolaryngology–Head and Neck Surgery to achieve board certification by the American Board of Otolaryngology. In the clinical realm, a sizable and ever increasing number of practitioners are focusing their professional efforts in neurotology. In the operating room, microsurgical technology continues to evolve with improved microscope and drill systems, image guidance, and more capable neurophysiologic equipment to mention just a few advances. In tumor surgery, the emphasis continues to be on development of minimally invasive techniques that maximize tumor control while optimizing neural preservation. Innovative radiotherapy methods, particularly stereotactic techniques, have developed a role in selected neurotologic tumors. In the vestibular field, numerous new therapies have been devised for BPPV and entire new diagnoses, such as superior semicircular canal dehiscence, have been introduced. Research in the field is robust. The National Institute of Deafness and Other Communication Disorders budget has risen from $166.8 million in 1995 to $380.4 million in 2004—a large fraction of which is dedicated to investigation

of the ear and auditory nervous system. Among the numerous fruits of this investment are over 60,000 cochlear implant devices placed worldwide and the continued refinement of the auditory brainstem implant. Programs have been initiated in the development of a vestibular prosthesis. In genetics, over 100 genes for hereditary hearing impairment have been localized, a significant portion of which have been cloned. In neurotologic tumors, great strides have been made in understanding the molecular genetic basis for acoustic neuroma, NF-2, paragangliomas, and papillary adenocarcinomas of the endolymphatic sac. Functional imaging, in which the chemical processes within the brain and other tissues are mapped, also has a promising future. Looking forward a few decades, it seems probable that the first human sense to be directly coupled with implanted digital devices on a routine basis will be the ear. It can be envisioned that man-machine interaction with computers and communication devices will revolutionize how the ear is used. The companion surgical atlas to this text, promised in the preface of the first edition, was published in full color in 1996 (Jackler RK: Atlas of Neurotology and Skull Base Surgery. St. Louis, Mosby, 1996). A second edition is being contemplated at present. With the digital publishing revolution currently in full force, it can be envisioned that future editions of these works will appear primarily on the internet. Over the last few decades, neurotology has achieved critical mass as a field, both through the number of scientists and clinicians engaged in it as well as through the steady accumulation of new knowledge and clinical capabilities. The editors hope that this comprehensive resource, as the primary textbook in the field, will serve to foster excellence and stimulate innovation in neurotology. Robert K. Jackler, MD Derald E. Brackmann, MD

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Contributors

Kedar K. Adour, MD

Derald E. Brackmann, MD, FACS

Director of Research, Senior Consultant, Kaiser-Permanente Medical Center, Oakland, California; Emeritus President and Founder, Sir Charles Bell Society, San Francisco, California

Clinical Professor of Otolaryngology–Head and Neck Surgery and Clinical Professor of Neurosurgery, University of Southern California School of Medicine; President, House Ear Clinic; Board of Directors, House Ear Institute; Los Angeles, California

Sumit K. Agrawal, BSc, MD Resident, Department of Otolaryngology, University of Western Ontario; Resident, London Health Sciences Centre; London, Ontario, Canada

Sujana S. Chandrasekhar, MD

Stephanie Moody Antonio, MD

Associate Professor of Otolaryngology, Mount Sinai School of Medicine; Director of Otology/Neurology and Director, Cochlear Implant Program, Mount Sinai Medical Center; New York, New York

Assistant Professor, University of Maryland School of Medicine, Baltimore, Maryland

Wileen Chang, MS

John R. Arrington, MD

Audiologist, University of California-San Francisco, San Francisco, California

Professor of Radiology, University of South Florida College of Medicine; Attending Neuroradiologist, HL Moffitt Cancer and Research Center; Tampa, Florida

Douglas A. Chen, MD

Yasmine A. Ashram, MD, D ABNM

Clinical Associate Professor, University of Pittsburgh; Co-Director, Hearing and Balance Center, Allegheny General Hospital; Pittsburgh, PA

Lecturer, Neurophysiology Division, Department of Physiology, University of Alexandria, Alexandria, Egypt

Steven W. Cheung, MD

Division Chief, Neurological Surgery, St. John’s Mercy Medical Center, St. Louis, Missouri

Associate Professor-in-Residence, Otology, Neurotology and Skull Base Surgery, Department of Otolaryngology–Head and Neck Surgery, University of California-San Francisco, San Francisco, California

Thomas J. Balkany, MD

Sung J. Chung, MD

Hodgkiss Professor and Chairman, Department of Otolaryngology; Professor, Department of Pediatrics; Professor, Department of Neurosurgery; Chief, Department of Neurotology; University of Miami School of Medicine; Chief of Service, ENT, Jackson Memorial Hospital; Miami, Florida

Private Practice, ENT Surgical Consultants, Ltd, Joliet, Illinois

Robert J. Backer, MD

Loren J. Bartels, MD, FACS Clinical Professor, Department of Otolaryngology, University of South Florida College of Medicine; Immediate Past Chief of the Medical Staff, Tampa General Hospital; Tampa, Florida

Nikolas H. Blevins, MD Assistant Professor, Department of Otolaryngology–Head & Neck Surgery, Stanford University of Medicine, Palo Alto, California

Dennis I. Bojrab, MD Michigan Ear Institute, Farmington Hills, Michigan

Harold V. Clumeck, PhD Lecturer, Department of Communication Sciences and Disorders, California State University, Hayward, California; Section Chief, Speech Pathology, VA Medical Center, San Francisco, California

Newton J. Coker, MD Professor, Bobby R. Alford Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine; Attending Physician, Otorhinolaryngology, The Methodist Hospital; Attending Physician, Otorhinolaryngology, Michael E. DeBakey Veterans Affairs Medical Center; Attending Physician, Otorhinolaryngology, Harris County Hospital District (Ben Taub); Attending Physician, Otorhinolaryngology, St. Luke’s Hospital; Houston, Texas ix

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CONTRIBUTORS

Hugh D. Curtin, MD

Adrien A. Eshraghi, MD, MSc

Professor of Radiology, Harvard Medical School; Chief of Radiology, Massachusetts Eye and Ear Infirmary; Boston, Massachusetts

Assistant Professor of Otolaryngology, University of Miami School of Medicine; Attending Physician and Surgeon, Jackson Memorial Hospital, Miami Veterans Administration Hospital, and University of Miami Ear Institute; Miami, Florida

Edward J. Damrose, MD Assistant Professor of Otolaryngology, Stanford University, Stanford, California

Grace Fan, MD Diagnostic Radiology, Kaiser Permanente Oakland Medical Center, Oakland, California

C. Phillip Daspit, MD, FACS Clinical Professor of Surgery (Otolaryngology), University of Arizona; Chief, Section Neurotology, Department of Neurosurgery, Barrow Neurological Institute; Chairman, Institute Review Board, St. Joseph’s Hospital; Phoenix, Arizona

J. Diaz Day, MD Associate Professor of Neurosurgery, Drexel University College of Medicine, Philadelphia, Pennsylvania; Allegheny General Hospital, Pittsburgh, Pennsylvania

Laurel M. Fisher, PhD House Ear Institute, Los Angeles, California

David R. Friedland, MD, PhD Assistant Professor, Division of Otology and Neuro-otologic Skull Base Surgery, Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin; Attending Physician, Froedtert and Medical College Hospital; Milwaukee, Wisconsin

Rick Friedman, MD, PhD Antonio De la Cruz, MD Clinical Professor of Otolaryngology/Head and Neck Surgery, University of Southern California; Director of Education, House Ear Institute; Active Staff, St. Vincent Medical Center; Active Staff, LAC/USC Medical Center; Los Angeles, California; Active Staff, Torrance Memorial Hospital, Torrance, California

Manuel Don, PhD Head, Electrophysiology Department, House Ear Institute, Los Angeles, California

Associate Research Scientist, House Ear Institute, Los Angeles, California; Active Staff, Chapman Medical Center, Orange, California; Active Staff, St. Vincent Medical Center; CedarsSinai Medical Center; USC Medical Center; Los Angeles, California

Richard R. Gacek, MD, FACS Professor of Otolaryngology, Department of Otolaryngology–Head and Neck Surgery, University of Massachusetts Medical Center, Worchester, Massachusetts

Bruce J. Gantz, MD, MS Christopher F. Dowd, MD Clinical Professor of Radiology, Neurological Surgery, Neurology and Anesthesia and Preoperative Care; Interventional Neuroradiology, The Neurovascular Medical Group; University of California, San Francisco School of Medicine, San Francisco, California

Professor and Department Head, University of Iowa, Iowa City, Iowa

Sanjay Ghosh, MD Neurosurgeon, Senta Medical Clinic, San Diego, California

Gerard Gianoli, BSE, MD Karen Jo Doyle, MD, PhD Associate Professor, Department of Otolaryngology, Head and Neck Surgery, University of California, Davis Medical Center, Sacramento, California

Clinical Associate Professor, Departments of Otolaryngology and Pediatrics, Tulane University Medical School, New Orleans, Louisiana; North Oaks Hospital, Hammond, Louisiana; The Ear and Balance Institute, Baton Rouge, Louisiana

Colin L. W. Driscoll, MD Assistant Professor, Mayo Clinic College of Medicine; Consultant, Department of Otorhinolaryngology, Mayo Clinic and Mayo Foundation; Rochester, Minnesota

Joel A. Goebel, MD, FACS Residency Program Director and Professor and Vice Chairman, Washington University School of Medicine, St. Louis, Missouri

David R. Edelstein, MD Clinical Professor of Otorhinolaryngology, Weill Medical College of Cornell University; Chairman, Department of Otolaryngology–Head and Neck Surgery, Manhattan Eye, Ear and Throat Hospital; New York, New York

Robert A. Goldenberg, MD Professor and Chief, Department of Otolaryngology, Wright State University School of Medicine, Centerville, Ohio; Associate Clinical Professor, University of Cincinnati School of Medicine, Cincinnati, Ohio

Bruce M. Edwards, AuD Senior Audiologist, University of Michigan Health System, Department of Otolaryngology–Head and Neck Surgery, Division of Audiology and Electrophysiology, Ann Arbor, Michigan

John Grant, MB, FRCS(C), FACS Associate Professor of Neurosurgery, University of Missouri-Kansas City; Children’s Mercy Hospital and Clinics; Kansas City, Missouri

Contributors

John H. Greinwald Jr, MD

William E. Hitselberger, MD

Associate Professor, Department of Otolaryngology, University of Cincinnati; Assistant Director, Center for Hearing and Deafness Research, Cincinnati Children’s Hospital Medical Center; Cincinnati, Ohio

Neurosurgeon, St. Vincent’s Hospital; House Ear Clinic; Los Angeles, California

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Annelle V. Hodges, PhD

A. Julianna Gulya, MD, FACS

Associate Professor of Otolaryngology, University of Miami School of Medicine, Miami, Florida

Clinical Professor of Otolaryngology, George Washington University, Washington, DC

Ronald A. Hoffman, MD

Van V. Halbach, MD

Professor of Clinical Otolaryngology, Albert Einstein College of Medicine, Bronx, New York; Director of Otology, Beth Israel Medical Center, New York, New York

Clinical Professor of Radiology, Neurological Surgery, Neurology, and Anesthesia and Preoperative Care; Interventional Neuroradiology, The Neurovascular Medical Group; University of California, San Francisco School of Medicine, San Francisco, California

Karl L. Horn, MD Ear Associates, PC; Presbyterian Ear Institute; Albuquerque, New Mexico

Courtney D. Hall, PhD

Michael M. Hovsepian, MD

Assistant Professor, Department of Rehabilitation Medicine, Emory University, Atlanta, Georgia; Research Health Scientist, Rehabilitation Research and Development Center, Atlanta VAMC, Decatur, Georgia

Timothy E. Hullar, MD

Hal L. Hankinson, MD Neurosurgical Associates, Albuquerque, New Mexico

Lee A. Harker, MD Deputy Director, Boys Town National Research Hospital; Vice Chairman, Department of Otolaryngology and Human Communication, Creighton University School of Medicine; Omaha, Nebraska

Richard E. Hayden, MD Department of Otolaryngology–Head and Neck Surgery, Mayo Clinic, Scottsdale, Arizona

Carl B. Heilman, MD Associate Professor, Department of Neurosurgery, Tufts University School of Medicine; Tufts New England Medical Center; Boston, Massachusetts

Susan J. Herdman, PhD Professor, Departments of Rehabilitation Medicine and Otolaryngology–Head and Neck Surgery, Emory University, Atlanta, Georgia; Research Health Scientist, Rehabilitation Research and Development Center, Atlanta VA Medical Center, Decatur, Georgia

Staff Radiologist, Fullerton Radiology Medical Group, Inc., Fullerton, California

Assistant Professor, Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri

Robert K. Jackler, MD Sewall Professor and Chair, Department of Otolaryngology–Head and Neck Surgery, Professor, Departments of Neurosurgery and Surgery, Stanford University School of Medicine, Stanford, CA

Alexis H. Jackman, MD, BA Resident in Otolaryngology, New York University School of Medicine, New York, New York

Michael J. Kaplan, MD Professor of Otolaryngology, Professor of Head and Neck Surgery, Stanford University School of Medicine, Stanford, California

Collin S. Karmody, MD, FRCSE Professor of Otolaryngology, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts

Robert W. Keith, PhD Professor, Departments of Otolaryngology and Communication Sciences and Disorders, University of Cincinnati; Director, Division of Audiology, University of Cincinnati Medical Center; Cincinnati, Ohio

Randall T. Higashida, MD Clinical Professor of Radiology, Neurological Surgery, Neurology, and Anesthesia and Preoperative Care; Interventional Neuroradiology, The Neurovascular Medical Group; University of California, San Francisco School of Medicine, San Francisco, California

Barry E. Hirsch, MD, FACS Professor, Departments of Otolaryngology, Neurological Surgery, and Communication Sciences and Disorders; Director, Division of Otology, Department of Otolaryngology; University of Pittsburgh School of Medicine and School of Physical Medicine and Rehabilitation; Pittsburgh, Pennsylvania

Kevin E. Kelly, MD Family Practice Program, Phoenix Baptist Hospital, Phoenix, Arizona

Paul R. Kileny, PhD Professor and Director, Division of Audiology and Electrophysiology, Department of Otolaryngology, University of Michigan Health System, Ann Arbor, Michigan

Louis J. Kim, MD Resident, Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona

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CONTRIBUTORS

Karen Iler Kirk, PhD

Larry B. Lundy, MD

Associate Professor and Psi Iota Xi Scholar, Department of Otolaryngology–Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana

Assistant Professor of Otolaryngology–Head and Neck Surgery, Mayo School of Graduate Medical Education, Jacksonville, Florida

G. Robert Kletzker, MD, FACS

Lawrence R. Lustig, MD

Clinical Assistant Professor, Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine; Active Staff, St. John’s Mercy Medical Center; Barnes Jewish Hospital; Missouri Baptist Medical Center; Associate Staff, St. Luke’s Hospital; St. Louis, Missouri

Associate Professor, Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland

William M. Luxford, MD Clinical Professor, University of Southern California, Keck School of Medicine; Associate, House Ear Clinic; Los Angeles, California

John F. Kveton, MD Clinical Professor of Otolaryngology/Surgery and Neurosurgery, Yale University School of Medicine; Attending Surgeon, Yale New Haven Hospital; New Haven, Connecticut

Alexander S. Mark, MD Associate Clinical Professor of Radiology and Neurosurgery, George Washington University Medical Center; Director of MRI, Washington Hospital Center; Washington, DC

Anil K. Lalwani, MD Mendik Foundation Professor and Chairman, Department of Otolaryngology and Professor of Physiology and Neuroscience, New York University School of Medicine, New York, New York

Angela D. Martin, MD Chief Resident Associate and Instructor in Otolaryngology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, Minnesota

Paul R. Lambert, MD, FACS Professor and Chair, Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina

Michael W. McDermott, MD, FRCSC Departments of Neurological Surgery and Radiation Oncology, University of California at San Francisco, San Francisco, California

Michael J. LaRouere, MD Clinical Assistant Professor, Department of Otolaryngology–Head and Neck Surgery, Wayne State University, Detroit, Michigan; Chairman, Department of Otology, Neurotology, and Skull Base Surgery, Providence Hospital, Southfield, Michigan; Attending Neurotologist, Michigan Ear Institute, Farmington Hills, Michigan

John S. McDonald, DDS, MS, FACD Volunteer Professor, Department of Anesthesia, and Volunteer Associate Professor, Department of Pediatrics, Division of Pediatric Dentistry, University of Cincinnati College of Medicine, Cincinnati, Ohio

Arnold H. Menezes, MD John P. Leonetti, MD Professor of Otolaryngology–Head and Neck Surgery, Loyola University, Stritch School of Medicine, Chicago, Illinois; Director, Loyola Center for Cranial Base Surgery, Loyola University Medical Center, Maywood, Illinois

Professor of Neurosurgery and Vice Chairman, Department of Neurosurgery, Roy and Lucille Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Ted A. Meyer, MD, PhD Fellow in Neurotology, University of Iowa, Iowa City, Iowa

Robert E. Levine, MD Clinical Professor of Ophthalmology, University of Southern California, Keck School of Medicine; Co-Founder and Co-Director, Center for Facial Nerve Function, House Ear Clinic; Los Angeles, California

Anand N. Mhatre, PhD Assistant Professor, Department of Otolaryngology, New York University School of Medicine, New York, New York

Dawna Mills, AuD Charles J. Limb, MD Assistant Professor, Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University School of Medicine; Assistant Professor, Otology, Neurotology, and Skull Base Surgery, Johns Hopkins Hospital; Baltimore, Maryland; Staff Physician, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland

Adult Cochlear Implant Coordinator, House Ear Clinic, Los Angeles, California

Lloyd B. Minor, MD, FACS Andelot Professor and Chairman, Department of Otolaryngology–Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland

Richard T. Miyamoto, MD, MS William W. M. Lo, MD Clinical Professor of Radiology, University of Southern California, Keck School of Medicine; Section Chief, Neuroradiology, St. Vincent Medical Center; Los Angeles, California

Arilla Spence DeVault Professor and Chairman, Department of Otolaryngology–Head and Neck Surgery, Indiana University School of Medicine; Co-Chief, Otolaryngology–Head and Neck Surgery, Clarion; Indianapolis, Indiana

Contributors

Aage R. Møller, PhD

Steven R. Otto, MA

Professor, MF Johnson Endowed Chair, University of Texas at Dallas, Dallas, Texas

Advanced Research Associate, House Ear Institute, Los Angeles, California

Edwin M. Monsell, MD, PhD

Dennis Pappas, MD

Professor of Otolaryngology–Head and Neck Surgery, Wayne State University School of Medicine, Detroit, Michigan

Pappas Ear Clinic; Director of Neurotology, Healthsouth Medical Center; Birmingham, Alabama

Jean K. Moore, PhD

Lorne S. Parnes, MD, FRCSC

Emeritus Scientist, House Ear Institute, Los Angeles, California

Professor and Chair, Department of Otolaryngology, University of Western Ontario; Chief, Department of Otolaryngology, London Health Sciences Centre; London, Ontario, Canada

Karsten Munck, MD Resident, University of California, San Francisco, San Francisco, California

Haruka Nakahara, MD

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Ian F. Parney, MD, PhD, FRCSC

Assistant Professor, Department of Otolaryngology–Head and Neck Surgery, Tokyo University Medical School, Tokyo, Japan

Neuro-Oncology Service, Department of Neurological Surgery, University of California at San Francisco, San Francisco, California

J. Gail Neely, MD

Myles L. Pensak, MD

Professor and Director, Otology/Neurotology/Base of Skull Surgery, Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri

Steven A. Newman, MD Professor of Ophthalmology, University of Virginia, Charlottesville, Virginia

Thomas Nikolopoulos, MD, DM, PhD Assistant Professor, Athens University Medical School, Athens, Greece

John K. Niparko, MD George T. Nager Professor, Otolaryngology–Head and Neck Surgery, The Johns Hopkins School of Medicine; Director, Division of Otology, Neurotology, Johns Hopkins Hospital; Baltimore, Maryland

Michael A. Novak, MD Clinical Assistant Professor of Surgery, University of Illinois, School of Medicine at Urbana-Champaign; Chairman, Division of Otolaryngology, Carle Clinic Association; Urbana, Illinois

Gerard M. O’Donoghue, MD, FRCS Professor, Department of Surgery, University of Nottingham; Professor, Department of Otolaryngology, Queens Medical Centre, University Hospital; Nottingham, United Kingdom

John S. Oghalai, MD Assistant Professor, Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, Texas

Michael J. O’Leary, MD, FACS Clinical Assistant Professor, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Chief, Neurotology, Skull Base Surgery Division, Senta Medical Clinic, San Diego, California

Professor Otolaryngology–Head & Neck Surgery and Neurologic Surgery, University of Cincinnati, Cincinnati, Ohio

Markus H. F. Pfister, MD Visiting Assistant Professor, Department of Otolaryngology– Head and Neck Surgery, Stanford University School of Medicine, Stanford, California

Lawrence H. Pitts, MD Professor, Neurosurgery and Otolaryngology, University of California at San Francisco, San Francisco, California

Curtis W. Ponton, PhD Senior Scientist, Compumedics Neuroscan, El Paso, Texas

Steven D. Rauch, MD Associate Professor, Otology and Laryngology, Harvard Medical School; Surgeon, Department of Otolaryngology, Otology Service, Massachusetts Eye and Ear Infirmary; Boston, Massachusetts

Miriam I. Redleaf, MD Assistant Professor of Surgery, University of Illinois Hospitals, University of Illinois, Chicago, Illinois

Grayson K. Rodgers, MD President/Director, Birmingham Hearing and Balance Center, Birmingham, Alabama

Seth I. Rosenberg, MD, FACS Clinical Assistant Professor, Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania; Active Staff, Sarasota Memorial Hospital; Active Staff, Cape Surgery Center; Active Staff, Surgery Center of Sarasota; Vice President, Silverstein Institute; Vice President, Ear Research Foundation; Sarasota, Florida

Edwin W Rubel, PhD Vincent B. Ostrowski, MD Midwest Ear Institute, Indianapolis, Indiana

Professor, Department of Otolaryngology–Head and Neck Surgery, University of Washington, Seattle, Washington

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CONTRIBUTORS

Christina L. Runge-Samuelson, PhD

Robert W. Sweetow, PhD

Assistant Professor, Division of Otology and Neuro-otologic Skull Base Surgery, Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin; Children’s Hospital of Wisconsin/Froedtert Hospital; Milwaukee, Wisconsin

Clinical Professor of Otolaryngology and Director of Audiology, University of California San Francisco, San Francisco, California

Tammy S. Schumacher-Monfre, MSN, APNP Instructor, Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin

Mitchell K. Schwaber, MD

Mark J. Syms, MD Otologist/Neurotologist, Section of Neurotology, Department of Neurosurgery, Barrow Neurological Institute; Attending Otologist/Neurotologist, Phoenix Children’s Hospital; Phoenix, Arizona

Clinical Associate in Otolaryngology, Vanderbilt University; Medical Director, St. Thomas Neuroscience–Hearing and Balance Center, St. Thomas Hospital; Nashville, Tennessee

Thomas A. Tami, MD, FACS

Dietrich W. F. Schwarz, MD, PhD

Steven A. Telian, MD

Professor, Department of Surgery (Otolaryngology), University of British Columbia, Vancouver, British Columbia, Canada

John L. Kemink Professor of Neurotology, University of Michigan, Ann Arbor, Michigan

Samuel H. Selesnick, MD Professor and Vice Chairman, Department of Otorhinolaryngology, Weill Medical College of Cornell University; Attending Otolaryngologist, Weill Cornell Center of New York Presbyterian Hospital; New York, New York

Robert V. Shannon, PhD

Professor of Otolaryngology, University of Cincinnati, Cincinnati, Ohio

Fred F. Telischi, MEE, MD Professor of Otolaryngology, University of Miami School of Medicine; Attending Physician and Surgeon, Jackson Memorial Hospital; Director, University of Miami Ear Institute; Miami, Florida

Adjunct Professor, Biomedical Engineering, University of Southern California; Head, Department of Auditory Implants and Perception, House Ear Institute; Los Angeles, California

R. David Tomlinson, PhD

Neil T. Shepard, PhD

Debara L. Tucci, MD

School of Medicine, University of Pennsylvania; Director of Audiology, Speech Pathology, and the Balance Center, University of Pennsylvania Health System, Hospital of the University of Pennsylvania; Philadelphia, Pennsylvania

Associate Professor, Duke University Medical Center, Durham, North Carolina

Herbert Silverstein, MD, FACS

John C. Koss Professor and Chairman, Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin; Chief, Otolaryngology–Head and Neck Surgery, Froedtert and Medical College Hospital; Chief, Pediatric Otology, Children’s Hospital of Wisconsin; Milwaukee, Wisconsin

President, Silverstein Institute, Sarasota, Florida

Ameet Singh, MD Resident, Department of Otolaryngology, Strong Memorial Hospital, University of Rochester Medical Center, Rochester, New York

Associate Professor, Department of Otolaryngology, University of Toronto, Toronto, Ontario, Canada

P. Ashley Wackym, MD

Robert A. Williamson, MD Aristides Sismanis, MD, FACS Professor and Chairman of Otolaryngology–Head and Neck Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia

William H. Slattery III, MD Clinical Professor, Department of Otolaryngology, University of Southern California; Director, Clinical Studies Department and Associate, House Ear Institute and Clinic; Los Angeles, California

Peter G. Smith, MD, PhD Clinical and Assistant Professor of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri

Fellow in Otology/Neurotology, The Bobby R. Alford Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, Texas

Charles Yingling, PhD, D ABNM Otolaryngology/Head and Neck Surgery, Stanford University, Stanford, California

Nancy M. Young, MD Associate Professor, Northwestern University Feinberg School of Medicine; Head, Section of Otology and Neurotology, Children’s Memorial Hospital; Chicago, Illinois

Kenneth C. Y. Yu, MD Eric E. Smouha, MD, FACS Associate Professor of Surgery and Clinical Neurosurgery, State University of New York at Stony Brook, Stony Brook, New York

Staff Surgeon, Department of Otolaryngology–Head and Neck Surgery, United States Air Force Base, Elmendorf Air Force Base, Alaska

Foreword

THE NEUROTOLOGY SAGA: A PERSONAL PERSPECTIVE During the past few years, I have heard myself introduced on occasion as the “Father of Neurotology.” If this is true, then it is also true in my case that being this kind of a father is not something that was planned; it just happened. In looking back, I realize now that it all started during my third and last year of ear, nose, and throat (ENT) residency at Los Angeles County Hospital. The year was 1955. I was 31 years old. By then June and I had been married for 10 years, and Karen was 8 and David 7. I had completed dental school, served 2 years in the Navy as a dentist, finished medical school, and taken the ENT residency so that I could become a plastic surgeon. June was helping to hold the household together by working part time in my brother Howard’s office as an RN. ENT was not a sought-after residency at that time because it was widely believed that penicillin was eliminating the sinus, mastoid and tonsil, and adenoid problems that occupied the eye, ear, and nose specialists. In fact, we had so few residents that I was obliged to be on-call at the hospital every other night. Fortunately, the library was wellstocked so I had time to read the latest ENT literature. There was no full-time ENT faculty, but there was usually an attending physician to help in the clinics and in surgery several times a week. As I look back, I can now call the residency a learning residency instead of a teaching residency. During the last year of my residency much of my learning came through Howard, who (being 15 years older than I) had finished the 2-year Los Angeles County residency in 1939 and had established a large practice that was 95% otology. He was doing seven or eight fenestration operations a week; this included Saturday morning surgery. In addition to this, he usually had two or three ENT doctors taking a 1-month course from him in otology. The students would observe surgery during the day and come to the County Hospital morgue at night to do fenestrations on cadavers. I would often help in the morgue, and Howard encouraged me to do cadaver head and neck dissection and surgical procedures. On Saturdays, I often observed his surgery. Howard also introduced me to a very remarkable, older ENT practitioner, Gilbert Roy Owen. He had become very interested in temporal bone and sinus x-ray. As time permitted I would go to his office, and he would take me through his remarkable collection of x-ray pathology. One of the things he repeatedly showed me was the enlarged

internal auditory canal of acoustic tumors. I remember going to the library and reading as much as I could find on acoustic tumors. The recurring theme was that these were serious, although benign, lesions that should be operated on as early as possible. During the last few months of my residency, a remarkable event occurred that was to change my life. Howard had heard of some interesting work going on in Germany called “tympanoplasty.” He visited Dr. Wullstein in Wurtsburg and for the first time saw the Zeiss microscope. He immediately ordered a microscope (I believe for the large sum of $2,000) and invited Dr. Wullstein to come to Los Angeles to demonstrate his techniques. It was my job to chauffeur the doctor to his demonstrations. The film that he showed of temporal bone surgery through the microscope were astounding to me in terms of what you could see of the temporal bone structures over what we had been seeing with the headlight and loops. He took these films by working to a point in the tympanoplasty and then swinging in a microscope with a camera mounted on one eyepiece. While he worked through the other eyepiece, he filmed the procedure. When Howard’s microscope arrived he began using it in the new stapes mobilization procedures, and I would take the microscope to the morgue at night to explore the wonders of the temporal bone. On completion of my residency in July 1956, I joined Howard in his office. By then I had become fascinated with otology, and—because of Howard’s practice—I was able to spend all my time in otology. The first few hours of each day were spent making the rounds of several Los Angeles hospitals to change the dressings of Howard’s numerous fenestration patients. The remainder of the day was spent in the office cleaning fenestration cavities and seeing a never-ending stream of otology patients.

STARTING PRACTICE AND DEVELOPMENT OF THE FACIAL RECESS APPROACH It was an exciting time to be starting an otology practice. Wulstein and Zolner had introduced “tympanoplasty” surgery using a Zeiss microscope a few years earlier, and Howard was doing a few skin grafts to the middle ear at the time of mastoid surgery. John Shea (whom I had gotten to know during my residency because he had spent some time xix

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with Howard learning fenestration surgery) had boldly introduced stapedectomy because so many of the stapes mobilization procedures that had been introduced by Rosen a couple of years before were refixing. Howard, who for years had been doing 10 or 12 fenestrations a week, asked John to come to Los Angeles and demonstrate his revolutionary stapes removal operation. As the word spread of the remarkable results these stapedectomy patients were getting, the patients came flocking to Howard’s office. I was immediately busy working up these patients and getting them on Howard’s surgery schedule. It soon became apparent that Howard had no time for anything else except otosclerosis surgery. No one wanted the kid brother to do their stapes surgery. Many of the patients, hoping to get their hearing restored by this new miracle surgery, turned out to be chronic ear patients. After all, antibiotics except for sulfa drugs had only been in widespread use for 10 years. Howard was more than willing to turn these patients over to me and encouraged them to have me do their mastoid surgery. During my residency, the goal of radical and modified radical mastoid surgery was to open the mastoid to allow it to drain rather than back up into a brain abscess. Antibiotics and tympanoplasty procedures using the microscope were challenging these concepts that had been the standard of practice for the past 75 years. The microscope made it possible to see the facial nerve more clearly and, therefore, allowed much more complete removal of cholesteatoma and granulation from the middle ear rather than leaving it wherever the facial nerve might be. Indeed, I remember my instructors during my residency telling me that if you so much as touch the facial nerve, it will become paralyzed. Tympanoplasty procedures were now advocating grafting over the middle ear with skin and, thus, violating the leave open for drainage principle. It was soon found that grafting over infected granulation even with vigorous postoperative antibiotics was unsuccessful. It became obvious to me that if all the middle ear granulation and cholesteatoma was to be removed it was necessary to know where facial nerve was and treat it as a friendly landmark. The microscope made this possible through identifying the horizontal canal and lifting the granulation to locate the facial nerve in the tympanic segment. Visualization was also enhanced by developing continuous irrigation suction where the amount of water flow and suction were controlled by rotating the thumb over the suction hole. Until then, mastoid surgery had been done by drilling using two hands on the drill as taught by Lempert; then irrigating and suctioning. This was a slow, tedious process, and I remember taking 3 or 4 hours to do a mastoid in the laborious way. However, using one hand on the drill and one hand on the suction was sometimes viewed as reckless surgery. However, Howard let me do it and often came to my defense in discussions with colleagues. The principle of chronic ear surgery thus changed to remove the disease and cure the infection. The tympanoplasty grafts were now much more successful, but there were still problems. Mastoid cavities are subject to accumulation of debris and recurrent infection. It was discouraging to see a nice tympanoplasty result, with some improvement in hearing, be wiped out by a recurrent

infection that destroyed the graft. To overcome this problem, many different mastoid obliteration procedures such as swinging in muscle from the temporalis, and various plastic and tissue inserts were advocated. I tried all of these procedures and found them all to be wanting. It became obvious to me that the best answer was to avoid creating a cavity. After all, we were no longer simply opening things for drainage; we were now after a cure for the infection. But if we left the posterior boney ear canal intact, could we see well enough to remove all the infected tissue in the middle ear? The answer was “no,” so it was back to the dissection lab again. I had seen Wullstein on his type I tympanoplasties, that is, those with an intact ossicular chain drill a “control hole” and was able to visualize through this disease in the middle ear. This was done quite blindly, and it frightened me because I could visualize a good chance of hitting the mastoid part of the facial nerve. In the dissection lab, I learned how to skeletonize the mastoid part of the facial just inferior to the horizontal canal and open the area widely for good visualization of the stapes incus and posterior part of the middle ear. The chorda tympani nerve and the annulus of the ear drum were used as landmarks. I named this the “facial recess approach” because I wanted to emphasize the facial nerve as the basic landmark. Fortunately, this approach is now widely used and has become the standard in cochlear implant surgery. However, leaving the canal wall intact led to new problems. Wullstein had advocated four types of tympanoplasty. Type 1 would now be called a myringoplasty because the ossicular chain is intact. Type 2 was a graft to the head of the stapes. Type 3 was a graft to the promontory to leave the oval window open if the stapes superstructure was gone. Type 4 was fenestration of the horizontal canal if the oval window was obliterated. It is obvious that these procedures were designed to avoid reconstructing the ossicular chain. Leaving the canal wall intact made it necessary to reconstruct the ossicular chain since the graft was now in the location of the previous ear drum. As intact canal wall procedures became more widely used, a number of otologists, including myself, devised a number of prosthetic reconstruction procedures. Such reconstruction of the ossicular chain led to another problem. If the middle ear did not become aerated, the hearing result was poor and the graft would adhere to the promontory. There would also be a retraction of the graft into the attic and a new cholesteatoma formation. I tried a number of procedures to avoid this retraction, including placing wire mesh in the attic to prevent the retraction. I called the procedure the “iron curtain procedure.” Months later, to my horror, if the middle ear did not aerate I saw the skin retract through the mesh and, thus, become a worse problem than the original cholesteatoma. I learned that aeration, not obliteration, is essential for successful chronic ear surgery. I told the story of my experience with the development of chronic ear surgery in a book dedicated to neurotology to illustrate how temporal bone surgery had developed after the microscope was introduced. The use of amplification, continuous suction irrigation, and use of the facial nerve as a landmark allowed us to develop temporal bone procedures to move through the temporal bone with

Foreword

dispatch and, thus, develop the next generation of temporal bone surgery. The retrolabyrinthine, translabyrinthine, transcochlear, and middle fossa approaches would not have been possible before today’s chronic ear surgery was developed.

DEVELOPMENT OF THE MIDDLE FOSSA APPROACH Obviously, otosclerosis has been a big part of my life. To find out more about it, I read a two-volume series of articles on otosclerosis that had been collected by the American Otologic Society. One of the articles that caught my eye was a study that detailed how otosclerosis lesions commonly occurred around the cochlea above the internal auditory canal and compressed the cochlear nerve. This was theorized to be a possible cause for the sensorineural loss that I was frequently seeing in otosclerotic patients. It seemed logical to me that if you could drill away the otosclerosis and relieve the pressure on the eighth nerve, you might reverse some of the hearing loss. I have always been an early riser, and I remember sitting one morning and looking at a dissected skull that my father had given me in dental school. There was a yellow line for the greater superficial petrosal nerve, and it occurred to me that this might be the key to follow back to the geniculate ganglion and then on along the labyrinthine part of the facial to the internal auditory canal. By this time we could afford a babysitter, so June and I started going to the morgue to see if I could get to the internal auditory canal without damaging the hearing or the facial nerve. Because of my experience with diamond burrs and irrigation in dentistry, I had already adapted these procedures to my work in chronic ear surgery. June would set up the microscope and instruments and act as the scrub nurse to facilitate the dissection. Since the approach called for elevation of the temporal lobe, I recruited the help of a young neurosurgeon, Ted Kurze, and after a number of dissections I felt we were ready for our first case. For this case, I selected an attorney who had changed careers to become an accountant after he went completely deaf. His medical records clearly showed that he had otosclerosis. On August 1, 1958, June’s birthday, we did the first middle fossa decompression at St. Vincent Hospital in Los Angeles. I was very honored and not a little scared that Dr. Carl Rand, the dean of Los Angeles neurosurgery, Cushing’s last resident, and Dr. Kurze’s associate, came to watch the surgery. As far as I know, this was the first intracranial procedure in which the operating microscope was used. During the procedure, using the old Jordan Day drill with belt-driven engine arm and hand-piece, enough static electricity developed that it caused frequent stimulation of the facial nerve. I could feel facial contractions through the drapes. I had experienced this a number of times before during chronic ear surgery, so it was not an unknown phenomenon to me, but I was already so nervous that I came very close to aborting the procedure. Fortunately, the patient recovered well, with no facial weakness. I remember his wife telling me how sexy she thought he looked with his completely shaved head.

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Unfortunately, he did not recover any hearing. Some years later he was to become one of my first cochlear implant patients.

DEVELOPMENT OF ACOUSTIC NEUROMA SURGERY My discouragement because the operation did not recover any hearing was offset by my realization that the middle fossa approach had a number of other possibilities, such as vestibular nerve section and identification of the facial nerve during acoustic tumor surgery. Early in practice I had seen a very handsome young fireman with a unilateral hearing loss. I sent him to Dr. Owen for x-rays. The report came back that he had an enlarged internal auditory canal. I referred him to Dr. Kurze who concurred with my diagnosis of an acoustic neuroma. He told me that he did not want to operate at that time because the patient would trade a little hearing loss and tinnitus for certain facial paralysis and possibly ataxia. Within 2 years he had developed facial numbness and early papilledema. I attended the surgery, which was performed with the patient in the sitting position and took some hours. Unfortunately, the patient stopped spontaneous respiration and died several days later. In a later discussion with Dr. Kurze, we both agreed that he had done all he could. I will never forget what he said, “You have to realize we were dealing with a large tumor.” I realized in the aftermath of the loss of this patient that the key to early acoustic tumor surgery was preservation of the facial nerve. I remember that I dreaded seeing and evaluating patients with unilateral hearing loss because I felt that if a diagnosis of acoustic neuroma was established the patient’s doom was sealed. June and I continued our sessions in the morgue. I was trying to work out an approach to the cerebello-pontine angle through the middle fossa. The concept was to identify the facial nerve at the beginning of the procedure and then to dissect the acoustic tumor away from it. I had never operated on a acoustic tumor, but I teamed up with a young neurosurgeon, Jack Doyle, who had just finished his residency at the Mayo Clinic. We did our first acoustic in January 1960, using the microscope, with the patient in the sitting position. Drilling out the labyrinth and internal auditory canal down to the jugular bulb using a slow Jordan Day drill is a long and very tedious procedure. Jack Urban, a fantastic engineer who died some years ago and whom I still miss very much, helped me develop a special retractor and a seat with arm rests. It was a partial removal. The patient had some facial weakness but recovered well. During the next 3 years, we were to do another 20 tumors this way. The histories and the results are chronicled in our first monograph.

DEVELOPMENT OF THE TRANSLABYRINTHINE APPROACH Operating in the sitting position and removing the labyrinth through the middle fossa was very onerous to me. My experience with mastoid surgery, with the patient

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prone on the table, seemed to present some interesting possibilities. So it was back to the dissection lab and to investigations on how to remove the labyrinth and open the internal auditory canal using mastoid procedures. I soon found that the facial nerve could be skeletonized, the labyrinth removed, and the internal auditory canal opened, without having to retract any brain or drill away any bone with the dura open. Fortunately at this time, Bill Hitselberger came into my life and, for the first time, I could work with a neurosurgeon who really wanted to learn temporal bone surgery and be able to apply the expertise of neurosurgery to the problems of acoustic neuroma surgery. We soon recognized that it was safer and much easier to operate with the patient in a supine position and to approach the angle through the mastoid and the labyrinth. This eliminated the constant worry of air embolism and considerably shortened the dissection down to the angle. By now, I too, had begun teaching in Howard’s courses, and many students wanted to learn the temporal bone approaches. One of these students was Frank Ellis from Sydney, Australia. During each night of dissection, I would emphasize that the key to establishing the exact location of the facial was to identify it at the beginning of the tumor dissection at the point where it entered the fallopian canal at the lateral end of the internal auditory canal. I would say, “Frank you’ve got to see that bar of bone (the vertical crest) at the end of the canal.” It was Frank who dubbed it Bill’s bar, a name that has stuck. It is the key to saving the facial nerve and making early acoustic neuroma removal possible. Bill Hitselberger and I developed a very close working relationship and, when faced with a complication of death, we would carefully explore what we should have done differently or return to the morgue for a new look at a particular part of the surgery. We were backed up by Jack Urban who often observed surgery and developed instrumentation, microscope viewing tubes, and camera and

television equipment. It seemed like he could do it all, if it involved engineering. Over the next few years, we did a number of acoustic neuroma surgeries using the translabyrinthine approach. After 50 cases, we decided it was time to publish our results. I was very impressed with Cushing’s volume, published in 1917. Each patient that he had operated on up to that time was documented in detail and in sequence. I tried to emulate this example by publishing each of my cases in the same way. Fortunately, Dr. George Shambaugh, who was at that time the editor of the Archives of Otolaryngology, suggested that we devote an entire issue of the journal to these cases. This issue was the first significant recognition of this work, and I shall always be grateful to him. It set forth clearly the value of microsurgery in acoustic tumor surgery. This heralded a very significant change in intracranial surgery and was not met with enthusiasm by the neurosurgical community. It was through television equipment, starting with the black and white sets, that we were able to teach many students. These students have established neurotology programs and greatly advanced neutotologic procedures worldwide. I remember Dr. Wullstein saying in one of his lectures, “If a man develops a procedure that lasts for 3 years unchanged he has done a very outstanding piece of work, if it is unchanged in 10 years the man was a genius, but if the work is unchanged for 20 years he is working in a dead field. There is no question that neurotology is not a dead field. Like any father I am very proud of my many neurotology sons and daughters.”

William F. House, M.D. Staff Otologist Hoag Memorial Presbyterian Hospital Private Practice Newport Beach, California

Introduction

The History of Neurotology and Skull Base Surgery Outline Introduction Medical Thought Prior to the European Renaissance Sixteenth Century—The Vesalian Revolution Otologic Anatomists of the Renaissance Seventeenth Century Duverney’s Influence on Otologic & Neurotologic Pathophysiology Eighteenth Century Elucidation of the Membranous Labyrinth Surgical Advances in the 17th and 18th Centuries—Mastoid Trephination The Nineteenth Century Sir Charles Bell and Cranial Nerve Physiology Early 19th-Century Advances in Vestibular Science Vestibular Semicircular Canal Physiology: Flourens The State of Otology and the Neurosciences in the Mid-19th Century Joseph Toynbee and the Origins of Modern Aural Pathology The Vienna Medical School Adam Politzer—The Father of Otology Elucidation of the Organ of Corti Modern Surgery Is Born Resurrection of the Mastoidectomy The Pathophysiology of Coalescent Mastoiditis: Friedrich Bezold Sir William Macewen: The First Skull Base Surgeon? Victor Horsley and the Birth of Neurosurgery Sir Charles Ballance: Pioneering Skull Base Surgeon 19th-Century Advances in Facial Nerve Surgery Scientific Advancement in Vestibular Physiology in the late 19th Century: Prosper Mèniére and the First Description of Ménière’s Disease Twentieth Century A Tumor That Helped Defined a Specialty: Acoustic Neuroma Harvey Cushing: The Founder of Modern Neurosurgery Nylén, Holmgren, and the Birth of the Operating Microscope Walter Dandy Advances in Vestibular Science in the Early 20th Century Georges Portmann and the Endolymphatic Sac Reemergence of the Operative Intervention for Ménière’s Disease in the 1930s and 1940s: Walter Dandy’s Vestibular Nerve Section Terence Cawthorne and the Rise of the Transmastoid Labyrinthectomy Neurotologic Surgery Advances in the 1930s and 1940s: Maurice Sourdille, Julius Lempert, and the Fenestration Operation Glomus Jugulare Tumors—Harry Rosenwasser

Lawrence R. Lustig, MD

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THE HISTORY OF NEUROTOLOGY AND SKULL BASE SURGERY

Outline—Cont’d Neurotologic Surgical Advances in the 1950s William House and the Birth of Modern Neurotology and Skull Base Surgery Electrical Stimulation of the Auditory Nerve—The Birth of Cochlear Implants The Creation of the American Neurotologic Society Conclusion

“In my conception of scientific work, history and research are so indivisibly linked that I cannot even conceive of one without the other.” Theodor Billroth (1829-1894), Über das Lehren und Lernen der medicinishen Wissenbschaften, as translated by Lesky.1

INTRODUCTION When did the subspecialty of neurotology and skull base surgery begin? Was it at the first attempt to operate on the facial or hearing nerves in the 19th century? Are its origins dated to the first operation on a vestibular schwannoma in the late 1800s? Was it founded with the introduction of the operating microscope toward ear surgery in the 1920s? Was it when otologists and neurosurgeons first combined their expertise to tackle complicated skull base lesions in the 1960s? Or was it at the founding of societies devoted to solely neurotology or skull base surgery? The closer one examines the question, the quicker one realizes that there really is no specific point in time when neurotology and skull base surgery “became” an independent subspecialty. Rather, it has slowly emerged out of a confluence of interrelated disciplines and technologies over the past century to become the field that we know of today as “neurotology and skull base surgery.” Its formation required the marriage of neurosurgery and otology; the introduction of the operating microscope; and advances in surgical technique, anesthesia, and radiology. Along the way, the field also began involving specialists within ophthalmology and craniofacial and plastic and reconstructive surgery. Lastly, and perhaps most importantly, the formation of neurotology and skull base surgery required pioneering surgeons laden with confidence, daring, and foresight, who were willing to push the boundaries of their training, sometimes under the ridicule or scorn of the medical establishment. This historical review is a salute to these pioneers’ efforts. It is undeniable that the field of neurotology and skull base surgery is in a period of rapid transition, whose history is still being written. Thus, rather than wade into the academic debate on matters of primacy of current techniques that makes the practice of surgery so enlivening (and is the focus of this textbook), this historical overview will focus on the origins of the specialty up through the last quarter century, ignoring the myriad strides and accomplishments made within the past 25 years. Long

before the first skull base or neurotology fellow was trained, before the operating microscope came into use, and before the first vestibular schwannoma resection was performed, the seeds of our specialty were being sewn by visionaries in the anatomic, physiologic, and surgical sciences.

MEDICAL THOUGHT PRIOR TO THE EUROPEAN RENAISSANCE If the underpinnings of neurotology and skull base surgery are otologic and neuroanatomy and otologic physiology, then the origins of the specialty can be considered to date back to antiquity. In the age of the Romans, human society, including medicine, had advanced to new heights. Of all the ancient Roman scientific scholars, the most influential was undeniably Claudius Galen of Pergamum (c. 129–200 AD). For 1500 years the main source of European physician’s knowledge about the human body came from the writings of Galen. As one of the most prolific writers of antiquity, Galen was said to have produced more than 500 treatises on physiology, rhetoric, grammar, drama, and philosophy. Mostly, though, Galen is best known for his prolific treatises on anatomy. Since Roman custom forbade dissection of the human body, Galen performed all his dissections on monkeys for external anatomy and used pigs for internal anatomy. Predictably, this led Galen to many inaccurate conclusions. However, as the Roman empire waned, and Christianity, with its belief in the resurrection of the human body, subsequently dominated the middle ages, Galen’s inaccuracies would remain buried until the Renaissance.2 However, Arabic and Byzantium medicine flourished, based on the ancient Hellenic and galenic traditions. It was during this time that Aëtius of Amida of the Byzantine school wrote a comprehensive description of ear diseases.3 Unfortunately, due to religious restrictions like those that existed in Europe, anatomic dissection was forbidden, limiting the potential medical advances of these great civilizations. By the 13th century, the potential benefits of human cadaveric dissection began to be realized by some enlightened leaders throughout Europe. Emperor Frederick II, who founded the universities at Padua and Naples (and incidentally fought continuously with the Church over the extent of its authority) decreed that all physicians in his domain were to learn anatomy by studying the human

The History of Neurotology and Skull Base Surgery

body, and be required to provide proof of such training.4 With the arrival of the Black Death in 1348, limited necropsy was allowed by the Church in the hopes of finding the cause. However, the papacy continued its general prohibition against necropsy and only slowly relaxed its restrictions over the following 200 years. It was not until 1537 that Pope Clement VII, following the example of the leading universities at that time, finally endorsed teaching by anatomic dissection.4 This official sanction paved the way for a new anatomic revolution. Although Italian artists such as Leonardo da Vinci subsequently became known for precise and exquisite anatomic drawings during the time, this new paradigm shift in anatomy came by way of Brussels, the birthplace of Andreas Vesalius.

SIXTEENTH CENTURY—THE VESALIAN REVOLUTION Born in Brussels in 1514 as the son of the apothecary to the emperor Charles V, Andreas Vesalius (1514–1564) (Fig. I-1) received the best medical education of his time at the University of Paris, where he studied under Professor Sylvius, the celebrated champion of Galen’s writings. As professor at the University of Padua, in conducting his required “anatomy” (from the Greek anatome, for “cutting up”) he departed from the usual custom of staying seated high in the professorial cathedra (chair) while a barber-surgeon pulled out organs from the cadaver below. Instead, Vesalius himself handled the body and dissected the organs. While teaching from Galen’s text, Vesalius noted many instances where Galen’s description was not found in the human body. He soon realized that Galen’s

Figure I-1. Andreas Vesalius (1514–1564). (From Politzer A: A History of Otology, Part I, 1904.)

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anatomy was really only a compendium of statements about animals in general. Vesalius insisted that his students see, feel, and decide for themselves about the inaccuracies of Galen’s anatomy. His subsequent anatomic studies culminated in perhaps the most influential textbook of anatomy ever written. De Humanis Corporis Fabrica5 (The Structure of the Human Body) was published in 1543, the same year as Copernicus’ De Revolutionibus, and was destined to be as equally influential. Amazingly, the treatise was completed before Vesalius was 28 years old. Vesalius’ revolutionary approach helped bring anatomy from the realm of guesswork and superstition into the domain of science. As the darkness of the Middle Ages waned and coalesced into the Renaissance, the necessity of human dissection became obvious and widely accepted. Renaissance artists like Leonardo, Raphael, and Titian had broadcast a new realism in the palaces and churches of Europe, while architects such as Brunelleschi and Alberti were leading a reexamination and reinterpretation of the ancient Roman texts and traditions. What Vesalius said was unimportant compared with the path he opened for future students to learn about all organs of the body. Vesalius firmly placed anatomy on the foundations of observed facts and demonstration. Within a scant half-century, vesalian anatomy prevailed in European medical schools, and the study of anatomy would never be the same.2,4 By paving the way for a generation of otologic and neuroanatomists, Vesalius was instrumental in establishing a method for understanding the anatomy of the ear and skull base, a critical step in the formation of the specialty of neurotology and skull base surgery.

Otologic Anatomists of the Renaissance As with all great teachers, perhaps Vesalius’ greatest achievement was in his influence on a generation of scientists and anatomists. One of his students, Giovanni Ingrassia (1510– 1580) (Fig. I-2), was responsible for significant advances in the field of otologic anatomy. Initially teaching at Padua, he eventually ended up as a professor in Palermo. According to Politzer, his lectures on anatomy and medicine became so popular that it was impossible to find accommodations for all the foreign students and physicians who had come to Palermo to learn from him.6 Additionally, his humanitarianism and generosity were renown in Palermo, primarily related to his duties as sanitary counselor for the city that resulted in a marked reduction in mortality during the bubonic plague. Ingrassia was a master anatomist of his era and particularly known for his advances in bone anatomy. In the ear, he is credited with the discovery of the stapes and the description of the tympanic cavity, the oval and round windows, and the chorda tympani. He accurately described the mastoid air cell system, the cochlea, and the semicircular canals. According to Politzer, he may have also been the earliest to describe the sound conductivity of the teeth.6 Some physicians, however, were not eager to embrace the vesalian revolution. Among Vesalius’ contemporaries was Bartholommeo Eustachio (Fig. I-3), one of the foremost anatomists of his era. Living from approximately 1524–1574, Eustachio developed fame not only as an

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THE HISTORY OF NEUROTOLOGY AND SKULL BASE SURGERY

Figure I-2. Giovanni Ingrassia (1510–1580). (From Politzer A: A History of Otology, Part I, 1904.)

Figure I-3. Bartholommeo Eustachio (1520–1574). (From Politzer A: A History of Otology, Part I, 1904.)

anatomist and physician, but also as a philosopher and a linguist. He was a professor at the Sapienza hospital, the same hospital da Vinci had been denied access to only a few decades earlier for performing dissections there. As a professor, Eustachio was a fanatical supporter of Galen’s anatomic ideas. As a result, he and Vesalius became natural antagonists. Eustachio vehemently criticized Vesalius’ description of the organ of hearing, going so far as to say that Vesalius’ entire work failed to contain a shred of truth.6 He was critical of Vesalius’ description of the course and ramifications of the facial and acoustic nerves and of his superficial description of the organ of hearing. Given Vesalius’ lack of interest in the anatomy of the ear, and this being Eustachio’s field of expertise, these charges may have held some truth.7 Eustachio’s principle work was the Opuscula Anatomica, written in 1564.8 Its beautiful copper plate illustrations

were entrusted to an assistant, but somehow became lost. They were rediscovered 160 years later in the Vatican Papal Library by Lancisi, Pope Clement XI’s personal physician. On the advise of Morgagni, Eustachio’s illustrations were published with Lancisi’s own notes in 1714.9 Although he is known for his otologic discoveries, Eustachio’s findings span the entire field of anatomy. He described the tensor tympani and was the first to establish that the chorda tympani is intimately associated with the lingual nerve. Eustachio’s writings contain cross sections of the petrous portion of the temporal bone, the ossicles, and the vestibule (Fig. I-4). He described the turns of the cochlea, the osseous and membranous spiral lamina, and the modiolus. His greatest contribution to otology, however, lay in providing a precise description of the shape and course of the tubular structure bearing his name, described in Epistola de Auditus Organis (within the

Figure I-4. Eustachio’s illustrations of the cross section of the temporal bone, from Tabulae Anatomicae, 1772. (From Politzer A: A History of Otology, Part I, 1904.)

The History of Neurotology and Skull Base Surgery

Opuscula Anatomica) in 1562.8 It is the first known work dedicated exclusively to the ear. Though the existence of the eustachian tube was vaguely known to Aristotle, Celsus, Vesalius, and Ingrassia, the recognition of its exact morphology is without doubt credited to Eustachio. Furthermore, he recognized the physiologic and therapeutic importance of his discovery, though it was not until the 18th century that this discovery influenced otologic therapy. Antonio Valsalva described the structure in greater detail a little more than 100 years later and is responsible for naming the tube in Eustachio’s honor.10 Another of the great Italian Renaissance anatomists who helped provide the anatomic underpinnings of neurotology and skull base surgery was Gabrielle Fallopio (1523–1562) (Fig. I-5). Born only 9 years after Vesalius in 1523, Fallopio lived a brief 40 years. It is said that his brilliance even surpassed that of his teacher, Vesalius, and is regarded as the founder of the Italian School of Anatomy, the alma mater of the most important anatomists of that era. When Vesalius’ second edition of the Fabrica was published, Fallopio published a detailed critique, and many of his corrections were included in subsequent editions. His intelligence, charm, and humility made him one of the most admired personalities of his generation; it is only with the reportedly brusque Eustachio that Fallopio is said not to have gotten along well.6 Though Fallopio is perhaps best known for his original descriptions of the female reproductive system (the fallopian tubes), his otologic advances are significant. Fallopio’s descriptions of the ear were equaled only by Eustachio’s, but his description of the course and ramifications of the acoustic nerve, described in his most influential work, Observations Anatomicae11 (Fig. I-6), was far superior.

5

Figure I-6. Title page from Fallopio’s masterpiece of anatomical description, Observationes Anatomicae, 1561.

Fallopio also described the complete development of the ossicles at early stages of development, the communication between the mastoid cells and tympanic cavity, the function of the tympanic ring, as well as naming the tympanic cavity “tympanum” based on its similarity to a drum. He described the ossicles, the two windows, the promontory, and the chorda tympani and discovered the canalis sive aqueductus that bears his name—the fallopian canal—containing the intratemporal portion of the facial nerve.11

SEVENTEENTH CENTURY

Figure I-5. Gabrielle Fallopio (1523–1562). (From Politzer A: A History of Otology, Part I, 1904.)

It is not surprising that the earliest advances in neurotology and skull base surgery were anatomic, since anatomy is primarily a descriptive science; one simply needs to look at an anatomic preparation and accurately describe what is seen. The Renaissance anatomists, armed with a sense of discovery and a renewed interest in the reinterpretation of traditional teachings, began a journey that is still being carried out to this day. Based on the work of these pioneers, by the start of the 17th century a surprising amount of otologic anatomy was known, including a complete description of the course and ramifications of the facial and acoustic nerves, the ossicles, the turns of the cochlea, the labyrinth, and the eustachian tube, among others. Of course the finer details would have to wait for newer technologic advances such as microscopy. However, continuing even through the 18th century these remarkable achievements were principally anatomic, with theories of function and pathologic states based on ancient, speculative, and largely untested, beliefs. Invasive surgery was of course extraordinarily dangerous. Neurosurgery at that

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time simply consisted of draining pus in cases of abscess through a trephination.12 It was not until our predecessors began applying these anatomic and physiologic principles toward a rational approach to the human body, beginning about the 1700s, that the first significant advances happen in the pathophysiology of ear disease. Several fundamental changes had to occur for this transformation to take place. First, technology had to reach a certain level of expertise to enable scientists to perform the adequate investigations. The obvious example of this was the invention of the light microscope, by Anton van Leeuwenhoek (1632–1723), which brought about a renewed interest in otologic anatomic exploration, which had been waning prior to its introduction. A second important shift during the 17th century was an intellectual one; scientific investigation and its application in general began to be viewed in a new light, though it was not until the following century that this shift really took a firm hold in the scientific community. Francis Bacon of Verulam (1561–1626) started this intellectual revolution by espousing the experimental method and inductive reasoning derived from observed facts, put forth in his classic text Novum Organum in 1620. Bacon, in contrast to those before him, advocated the belief in science not only as a philosophy or purely scholarly endeavor, but also as a tool whereby humanity could exert power and control over nature. He was, in essence, the first “modern” scientist.13 As a result, knowledge regarding otologic and neuroanatomy and physiology in the 17th century advanced at an incremental pace compared with that of the prior century. Despite great advances in all natural sciences during the 17th century, there was no spectacular progress concerning the pathology and therapy of diseases of the ear or brain. There was one notable exception to this, however, brought about by Guichard Duverney.

Duverney’s Influence on Otologic and Neurotologic Pathophysiology Joseph Guichard Duverney (1648–1730) was one of otology’s great pioneers, and his influence on the pathophysiology of diseases of the ear was so far-reaching that a brief description of his achievements is merited. The precocious Duverney was only 19 years old when he was appointed anatomic demonstrator at the Jardin du Roi in Paris. There, his extraordinary knowledge, legendary lectures, and magnanimous personality made him one of the most revered European physicians of the century. It was for him that the position of the court anatomist was created in France, a position that lasted until the French Revolution. His principal work, Traite de l’organe de l’ouie (Treatise on the Organ of Hearing)14 (Figs. I-7 and I-8), initially published in 1683, was the first comprehensive work devoted solely to the ear and was instantly hailed within the European scientific community. This monumental work is considered a milestone in otology. Duverney didn’t have access to the microscopic structure of the organ of hearing, and many of his theories were based on old and incorrect misconceptions of how the ear functioned. Still, his observations on anatomy, physiology, and pathology of the organ of hearing went far beyond anything written before his time.

Figure I-7. Traite de l’organe de l’ouie (Treatise on the Organ of Hearing), was Duverney’s influential otologic masterpiece, and published in 1683. Shown in this figure is the first English edition, translated from the French by John Marshall in 1737. (From Duverney GJ: Traite de I’organe de I’ouie, contenant la structure, les usages et les maladies de toutes les parties de l’oreile. London, Samuel Baker, 1737.)

As one of the first to apply physiologic and pathologic principles to the study of the ear, Duverney indirectly influenced all those who came after him. Though known for being a superb anatomist, Duverney became convinced that knowledge of anatomy alone was insufficient for understanding how we hear, a great departure from many of his predecessors. The problem that Duverney and other otologic anatomists faced up to that time was clearly summarized in the introduction of his text: “Of all the Organs assign’d to the Use of Animals, we have the least knowledge of those of the senses; but there is none more obscure than that of Hearing: the minuteness and Delicacy of the Parts which compose it, being enclos’d by other Parts, (which by reason of their Hardness, are Scarcely penetrable) render the Enquiries into them more difficult, and their Structure something so intricate, that there is as much Trouble in explaining, as their was in discovering them.” (Translation by John Marshall, 1737)14

Duverney proceeded to introduce new and revolutionary methods of investigation, and he presented new theories on sound perception based on contemporary physical understanding. He directly addressed pathologic states of the ear, including otalgia, otorrhea, and tinnitus, and classified causes of ear obstruction and diseases of the tympanic membrane. He reported on purulent middle ear infections, challenging the prevailing belief that all aural discharge was from an intracranial source. By the end of the 17th century, Duverney was considered the leading authority of the organ of hearing in Europe and is credited with almost

The History of Neurotology and Skull Base Surgery

7

Figure I-8. Illustrations from Duverney’s Traite de l’organe de l’ouie. These plates demonstrate Duverney’s mastery of otologic anatomy. (From Duverney GJ: Traite de I’organe de I’ouie, contenant la structure, les usages et les maladies de toutes les parties de l’oreile. London, Samuel Baker, 1737.)

single-handedly sparking widespread interest in the anatomy and physiology of the ear in the following century.15 Despite Duverney’s advances and admonishments, however, pathologic-anatomic research was declining during the 17th century, and speculative hypotheses bases on the physical and chemical discoveries of this time were prominent.6 However, the end of the 17th century would see the birth of a new technology that would again revolutionize anatomic study: Guided by the discovery of the microscope by Anton van Leeuwenhoek and the subsequent scientific advances of Marcello Malpighi (including the confirmation of the existence of capillaries as the connection between the arterial and venous system), over the next 200 years otologic and neuroanatomy would advance considerably.

after Duverney’s groundbreaking work.16 Valsalva’s thesis highlighted his dissatisfaction with the scholastic and antiscientific methods of his teachers and, following Malpighi’s advice, began an extensive series of clinical investigations, pathologic-anatomic studies, and animal dissections. In 1688 he became surgeon at the Hospital of the Incurables

EIGHTEENTH CENTURY After Duverney, the 18th century witnessed an explosion in the understanding of the ear and its inner workings, brought about in large part by the groundbreaking works of such eminent physicians as Morgagni, Scarpa, Cotugno, and Santorini. Rising above all these great scientists, however, was Antonio Maria Valsalva (1666–1723) (Fig. I-9). Valsalva was born into an old noble family in Imola, a small town near Bologna, in northern Italy, in 1666. The son of a goldsmith and the third of eight children, Valsalva received his early education from the Jesuits. At 16 he was sent to the University of Bologna to study the sciences. The University of Bologna was one of the premier in Europe at that time and even included a number of women faculty.16 A student of the great Marcello Malpighi, Valsalva became his most outstanding student. Valsalva earned his degree in medicine and philosophy in 1687 with a thesis entitled, “On the superiority of the experimental method,” which was published only 4 years

Figure I-9. Antonio Maria Valsalva (1666–1723), one of the first true physician scientists who advocated correlating clinical findings with pathologic study.

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THE HISTORY OF NEUROTOLOGY AND SKULL BASE SURGERY

where he practiced for 25 years. In 1697, at the age of 31, he was appointed public dissector of anatomy by the senate of Bologna, considered to be an extraordinary honor for someone not born in the city. Eight years later he became professor and lecturer of anatomy, a rank he held until his death. Giovanni Battista Morgagni, Valsalva’s student and first biographer, described Valsalva as calm and gentle, able to tolerate many hours of work without impatience or fatigue. His zeal, courage, endurance, and self-discipline were said to have surpassed even that of the great Vesalius, since Valsalva continued to spend days and nights dissecting even when he was quite old and ill. Valsalva developed new surgical techniques and was an outstanding diagnostician who based opinions on pathologic-anatomic examinations. He was a crusader for the mentally ill and was among the first to organize their humane treatment by advocating the abolition of chains, gags, and beatings. When he died of a stroke (termed apoplexy in his day), it was noted that Valsalva had been the first to clearly recognize its anatomic basis. His principle treatise on the anatomy and physiology of the ear was the result of 16 years of work and the dissection of more than 1000 human heads. Published in 1704, it was termed the Tractatus de Aure Humana (Treatise of the Human Ear)10 (Figs. I-10 and I-11). The immense value of this work is demonstrated by the fact that the anatomic sections of all major otologic treatises up to the 19th century are based on Valsalva’s work, parts of which remain valid even today. In this work, he describes for the first time the sebaceous glands of the auricle (1c. Cap.1, V, p.11), previously unknown external ear muscles (1c. Cap.1, IV, p.11), inconsistent openings in the tegmen that would later become known as

Figure I-11. Illustrations from Valsalva’s Tractatus. These include his detailed study of the eustachian tube (named by Valsalva), which made possible his now famed “Valsalva” maneuver.

Figure I-10. Title pages from Valsalva’s monumental Tratactus de Aure Humana (Treatise of the human ear), published in 1704. This groundbreaking treatise is the basis for all otologic anatomic works up through the 19th century and represents a true milestone in otologic anatomy and medicine.

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9

Hyrtl’s fissures (1c. Cap.2, V-VII, pp. 21–23). He named the eustachian tube in Eustachio’s honor (1c. Cap.2, XVI, pp. 30–32), popularized the term labyrinth for the entire inner ear, and was the first to observe the presence of a watery fluid within the labyrinth (1c. Cap.3, XVII, p. 51). Valsalva was also the first physician to systematically inspect the tympanic membrane of living subjects. While inspecting a case in which the superior segment of the eardrum was full of pus, he observed that pus and air disappeared in the region of the foramen of Rivinus when the patient exhaled forcefully with his mouth and nose closed, which subsequently became known as Valsalva’s maneuver: “. . . I exposed the auditory passage to the sun, and stretched open the same element. I therefore saw the tympanic membrane moistened by a portion of superior liquid, and at a specific locus; from this place in like manner, I sighted a diseased fluid rushing out simultaneously along with air, whenever an ailing person held back breath by force, as I ordered, with nostrils and mouth closed.”10 (Tractatus, 1c. Cap.2, p. 20) (Translated by Lustig et al.)17

Domenico Cotugno (1736–1822) (Fig. I-12) ushered in the next great leap in understanding of labyrinthine fluid, the membranous inner ear, and endolymphatic sac. Born in poverty in 1736 in Ruvo, near Naples, diligent study and his ingeniousness led to an appointment as full professor on anatomy and surgery in Naples at the prodigious age of 30. There he taught for the remainder of his successful career. His greatest fame came as a result of his first, and smallest, work, De Aquaeductibus Auris Humanae Internae Anatomica Dissertatio18 (Figs. I-13 and I-14). In this landmark treatise, Cotugno was the first to establish that fluid

Figure I-13. Title page to Cotugno’s work, De Aquaeductibus Auris Humanae Internae Anatomica Dissertatio, 1775.

completely fills the cavities of the labyrinth, debunking an idea that had been around since the time of Galen, that air fills the inner ear. Cotugno achieved success where others had failed by dissecting fresh, as opposed to macerated temporal bones. Using this new technique, he went on to describe the cochlear and vestibular aqueducts, the ever-present occurrence of labyrinthine fluid, and the function of an aqueduct connecting the labyrinth to the endolymphatic sac. He was also the first to hypothesize on the physiology of hearing, taking this fluid into account.9,19,20

Elucidation of the Membranous Labyrinth

Figure I-12. Domenico Cotugno (1736–1822). (From Politzer A: A History of Otology, Part I, 1904.)

The detailed and painstaking studies of otologic anatomists up to the late 1700s created a nearly complete understanding of the osseous labyrinth. However, knowledge of the membranous labyrinth consisted of false ideas most likely because of poor methods of specimen preparation. Cotugno’s success demonstrated first hand the need for fresh, meticulously prepared tissue. Antonio Scarpa (1747– 1832) (Fig. I-15), employing a keen sense of observation and exquisite attention to detail and tissue preparation, would subsequently describe the correct anatomy of the membranous labyrinth, considered one of the most important advances in 18th-century otology. Born in poverty in 1747, Scarpa was educated by his uncle, a priest, and was first employed as a secretary to the great anatomist-pathologist Morgagni, at the University of Bologna. Gradually, Scarpa became well versed in all disciplines of medicine and surgery, becoming Morgagni’s

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Figure I-14. Illustration from Cotugno’s work, demonstrating his anatomical preparations of the temporal bone and bony labyrinth.

most revered student. It is said that Morgagni died in Scarpa’s arms.6 He continued his education by traveling to the leading medical centers of Europe. His first book, De Structura Fenestrae Rotundae (Fig. I-16), asserted that sound is transmitted to the labyrinth both by way of the ossicular chain and by way of air in the middle ear to the round

window.21 His greatest contribution came in1789 with the publication of Disquisitiones Anatomicae de Auditu et Olfactu, where he presented his discovery of the membranous labyrinth and the spiral cochlear duct, filled with fluid later called Scarpa’s fluid, or endolymph.22 His studies, outlined in this treatise, also elucidated much of the anatomy of other otologic sensory organs and the ganglial system, whereby the vestibular ganglion subsequently became known as Scarpa’s ganglion.

Surgical Advances in the 17th and 18th Centuries—Mastoid Trephination Surgery involving the skull in the 17th and 18th centuries was primarily concerned with trauma and infection. JeanLouis Petit (1674–1750), the eminent Paris surgeon, advised skull trephining in all cases of scalp wounds with an associated skull fracture.12 In 1736 Petit also described, for the first time, how he would trephine the mastoid process to relieve aural suppuration (Fig. I-17).23 According to Petit: “The pus is situated in bony cavities whose walls cannot collapse; it lodges there, gives rise to caries of the bone, and this caries cannot be reached by any topical application. Purulent collections bring about death by destroying some structure necessary to life or because the pus, being abundant, and not let out in time, is reabsorbed into the blood and causes rigors, fever, and other purulent deposits in certain of the viscera. These abscesses may persist for a long time before reaching a stage in which they cause death; but from the very first days of their formation they ought to be opened.” (As translated by Sonnenschein) 24 Figure I-15. Antonio Scarpa (1747–1832). (From Politzer A: A History of Otology, Part I, 1904.)

(It has been speculated that it was not Petit, but the pioneering physician and surgeon Ambrose Paré who originally

The History of Neurotology and Skull Base Surgery

11

Figure I-16. Title page of Scarpa’s first book, De Structura Fenestrae Rotundae Auris et de Tympano Secondario Anatomicae Observationes, 1772 (left), and illustrations of the inner ear from this monumental work (right).

proposed trephination of the mastoid in 1560, nearly 200 years prior to this description, on the King of France, François II. However, though technically capable, Paré in all likelihood did not attempt the surgical procedure.)25 The Prussian military surgeon Jasser also reportedly operated on a soldier for coalescent mastoiditis, postauricular swelling, and aural discharge in 1776. His technique

involved fitting the tip of a syringe into the mastoid and vigorously irrigating. After his initial success, and supported by further cadaveric studies, he subsequently made a small hole in the mastoid cortex with a trocar and again successfully cured a patient by repeated irrigations.26 Despite the successes of Petit and Jasser, however, mastoid trephination subsequently fell into disrepute. The personal

Figure I-17. Skull trephines (right) used by Jean-Louis Petit (1674–1750) (left), used to treat mastoid suppuration. (From Ballance C: Essays on Surgery of the Temporal Bone. London, Macmillan, 1919.)

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THE HISTORY OF NEUROTOLOGY AND SKULL BASE SURGERY

physician to the King of Denmark, Baron Bergen, having heard of Petit’s success with the mastoid trephination procedure, though perhaps not completely understanding the correct indications for the operation, persuaded a surgeon to operate on his own mastoid to relieve his tinnitus and hearing loss. Bergen’s well-publicized tragic and painful death 12 days later literally doomed the procedure for a hundred years, until it was again successfully reintroduced by Herman Schwartze in the late 1800s.26

THE NINETEENTH CENTURY Despite limited surgical successes in the mastoid and cranial cavity, the progress in otologic knowledge through the 18th century was primarily concerned with anatomic discoveries, with only a few advances in pathophysiology. At the beginning of the 19th century, the dissection of cadavers was widely accepted and an integral part of medical education. As a result, in the early 1800s the demand for cadavers increased dramatically. This lead to body shortages, fueling illegal body acquisitions, and in some cases murder, to obtain cadavers for dissection!4 However, by the mid-19th century the study of gross anatomy was legally standardized throughout European medical schools and has changed little until the present. Yet, despite Valsalva’s emphasis of the importance of pathologic correlation with disease states a century before, knowledge in this area was still limited, and clinical diagnosis hadn’t changed appreciably during the previous 300 years. Ear exams were still performed with available sunlight as they were before the Renaissance, and surgery of the ear was limited to a few operations of the external auditory meatus and auricle, despite soaring advances in other surgical areas. As already mentioned, the early “mastoidectomy” or mastoid trephine was nearly abandoned in the late 1700s, though not completely, being condemned by ear surgeons in the medical literature as late as 1870.27 Neurosurgery still primarily consisted of operations on the skull itself; trephination for infections, and the management of head trauma. The two primary clinical otologic advances during the 18th century were catheterization of the eustachian tube by E. G. Guyot in 1724, and paracentesis of the drum, popularized by Sir Astley Cooper in 1800.28,29 Interestingly, Guyot was the postmaster of Versailles who was said by von Tröltsch to have relieved his own deafness by injecting his eustachian tube using a curved tube introduced through his mouth.30 It is not until the 19th century that a significant understanding of otologic disease and advances in neurotology and neurosurgery finally take place. Great strides in histology, pathology, and physiology in the early 1900s led to the development of the new branch of laboratory medicine in the second half of the 19th century.31 Though this pathologic-anatomic revolution began in Paris in the early part of the century with Cruveilhier, it was quickly superseded by advancements in what is now Germany and Austria.32 Germany was at the forefront of this revolution because they had developed a large body of full-time scientists, while in the rest of Europe, research and teaching still depended mainly on the work of practicing physicians. In German universities, the organization of teaching and

research careers became centralized around the professor, enabling the gradual introduction of new specialties that incorporated the scientific advances occurring simultaneously.32 This academic organization eventually became the model for American universities. (The influential von Tröltsch later credited the “critical German spirit” for the gradual intellectual shift from England to Germany and eastern Europe during this time period.30) There was also emerging a new consensus on surgical education. Inspired by the famed 18th-century surgeon John Hunter, who saw anatomy not as a static branch of medicine, but rather as a dynamic science that incorporated pathology and functionality, anatomic teaching began to be viewed as the foundation of surgical training. With this new emphasis on anatomic and pathologic education, it is no coincidence that many operations, such as the appendectomy and hysterectomy, were successfully described for the first time during the late 1800s and early 1900s.33,34 Furthermore, the numerous European wars of the 18th and 19th centuries provided most surgeons ample trauma experience, establishing the careers of such notable surgeons as John Bell (1763–1820) and his younger brother Charles Bell (1774–1842), John Abernathy (1764–1831), and Sir Astley Cooper (1768–1841). Additionally, the physics of sound and acoustical science was advancing at a rapid pace, thanks to the works of Laplace, Jean-Daniel Colladon (1802–1893), and Félix Savart (1791–1841). All these simultaneous anatomic, physiologic, and surgical developments crystallized the understanding of the ear and skull base during the 19th century and would lead to the independent creations of otology and neurosurgery, the twin pillars of neurotology and skull base surgery.

Sir Charles Bell and Cranial Nerve Physiology Sir Charles Bell (Fig. I-18) is now most commonly remembered for the clinical facial palsy bearing his name. Yet Bell’s contributions to medical science were infinitely greater. In the early part of the 19th century, Bell would conduct a series of investigations that would radically change our understanding of neuroanatomy and neurophysiology. Charles Bell was born in 1774 in Fountainbridge, a suburb of Edinburgh. It was during his high school years that the young Charles began to assist his older brother John, a lecturer at the Anatomy School in Edinburgh, where Charles also began attending medical lectures.35 By 1799 at the precocious age of 23, the younger Charles had already displayed a surgical and anatomic skill akin to that of his master and older brother. By 1814, while practicing in London as the surgeon to the Middlesex Hospital, Charles Bell had already achieved a formidable reputation, having published A System of Dissections in 1798, contributed to his brother John’s Anatomy of the Human Body, and completed his masterful, Essays on the Anatomy of Expression in 1806. This later, magnificent four-volume publication revealed Bell not only as an expert anatomist, but as one contemporary put it, one possessed of the “. . . most exquisite taste and feeling for sculpture and painting.”35 John Flaxman (1755–1826), one of the greatest

The History of Neurotology and Skull Base Surgery

Figure I-18. Sir Charles Bell (1774–1842), whose research led to a revolutionary conception of the anatomy and physiology of the cranial and spinal nerves. His discovery that individual nerves have a defined course from the brain to the periphery, that different nerves have quite distinct functions, and that the roots of the spinal nerves have distinct, compartmentalized functions has been hailed as epoch-making as Harvey’s discovery of the circulatory system.

of English sculptors, later said that the book had done more for the arts than anyone of the age.36 These contributions alone would have merited Bell’s inclusion into the pantheon of great physicians. However, Bell would accomplish much more. In the preface to his now classic work, The Nervous System of the Human Body (Fig. I-19),37 in which his papers originally read to the Royal Society through the 1920s were reprinted, Bell summarized the prevailing attitude toward neurology at the start of his investigations: “In the period immediately preceding the publication of these papers in the Philosophical Transactions, there was a singular indifference to the study of the nerves; and an opinion very generally prevailed that as the notions of the ancients had descended to us uncontroverted and unimproved, the subject was entirely exhausted. The hypothesis that a nervous fluid was derived from the brain, and transmitted by nervous tubes, was deemed consistent with anatomical demonstrations, and there was no hope for improvement.”

Despite the anatomic knowledge, physiology of the cranial and spinal nerves was limited, and the concept that separate nerves would transmit sensory and motor information was occasionally speculated about, but never proven. It was generally accepted that a nervous fluid circulated along the nerves, indifferently one way or the other, acting both for motion and sensation. The function of the ganglia of the spinal nerves and of the large ganglion related to the posterior root of the trigeminal nerve was still a mystery.

13

It was within this milieu that Bell came to his monumental conclusions regarding the physiology of cranial and spinal nerves. That it should first occur to Bell that definite nerves have a definite course from the brain to the periphery and that different nerves have quite distinct functions entitles him to everlasting fame. His discovery that the roots of the spinal nerves have distinct, compartmentalized functions was subsequently hailed as epochmaking as Harvey’s discovery of the circulatory system. These revolutionary theories that established the functions of the anterior and posterior spinal roots were put forward following a series of experiments, which he highlighted in a letter penned to his brother John in 1810. Charles clearly realized the import of his work: “I write to tell you that I really think I am going to establish my Anatomy of the Brain on facts the most important that have been discovered in the history of science . . .”35 In August 1811, when Bell was 37 years old, 100 copies of his Idea of a New Anatomy of the Brain38 were published and sent to personal friends. So revolutionary were the ideas contained within the manuscript that it has been referred to some as the “Magna Carta” of modern neurology. Unfortunately, the limited distribution of the monumental work would later lead to confusion regarding the primacy of Bell’s contributions. Ten years later Bell read a series of papers to the Royal Society37 in which he proposed a classification of nerves into two broad groups: those involved in “respiration” (including the facial, vagus, spinal accessory, phrenic, and long thoracic nerves), and another group that included all the other “symmetrical” nerves that Bell felt were necessary for “life and motion.” Bell also made several critical observations in the living donkey that clearly established separate roles for the facial nerve (motion) and trigeminal nerve (sensation). In support of these observations, Bell quoted several of his clinical cases. Among other findings, these experiments allowed Bell to clearly differentiate a more potentially serious central facial palsy from a less serious peripheral injury and allowed him to admonish surgeons to be watchful of the facial nerve when operating in this area. Interestingly, nearly all of Bell’s cases of facial palsy that accompanied this pioneering work resulted from tumors, purulent infection, or iatrogeny, and not from what we today would consider Bell’s palsy. Based on the innovative work of Bell, François Magendie (1783–1855) in France was able to subsequently solve the riddle of the ganglion in the spinal cord. While Bell and Magendie were initially quite friendly, their relationship turned sour when each claimed primacy in the discovery of the separate function of the nerve roots. The debate turned rather rancorous at times.35 History has been kind to both scientists, however, giving neither sole credit for the discovery. It is now known as the Bell–Magendie rule, which in medical literature is used to indicate the direction of conduction in the spinal nerve roots. For a long time it also had the double entendre of signifying a compromise between the points of view of the older type of anatomist who arrived at function by way of inference and the physiologically minded investigator who insists on experimental verification.

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Figure I-19. The frontispiece to The Nervous System of the Human Body and illustrations from the work. The book, which was an embodiment of a series of lectures delivered to the Royal Society through the 1920s, outlined Bell’s theories on the anatomy and physiology of nerves. As was the case with all his publications, all the masterful illustrations were done by Bell himself. (From Bell C: The Nervous System of the Human Body: As Explained in a Series of Papers Read before the Royal Society of London, with an Appendix of Cases and Consultations on Nervous Diseases. London, Henry Renshaw, 1844.)

Early 19th-Century Advances in Vestibular Science The understanding of disorders of balance would also undergo major advances in the 19th century. The nearly universal belief that vertigo was primarily due to a central pathology persisted well into the 19th century. Erasmus

Darwin, grandfather of Charles Darwin and a famous physician in his own right, made an association between vertigo and tinnitus in 1794, but owing to the state of knowledge of the time, was limited to observation of the phenomena only.39,40 It was well known that the inner ear mediated sound perception, and a variety of competing theories sough to explain how hearing actually takes place.

The History of Neurotology and Skull Base Surgery

The semicircular canals were felt to be an extension of the auditory apparatus, also mediating the sensation of sound. Autenrieth was probably the first to propose that the semicircular canals mediated a sensation other than pure hearing, proposing in 1802 that they were used in determining the direction from which sound came.41 J. E. Purkyne (1787–1869) described opticokinetic nystagmus in 1820 and classified at least five types of vertigo. Yet he believed, as did the other physicians of his time, that the senses of motion and acceleration were mediated by cutaneous pressure receptors or alterations in blood flow and that all vertiginous disorders were due to cerebral or cerebellar pathology.42,43 These misconceptions would undergo a radical change over the course of the 19th century, spurred in part by the monumental changes that were occurring throughout the medical community.

Vestibular Semicircular Canal Physiology: Flourens Working within the flourishing European scientific environment of the early 1800s, Marie-Jean Pierre Flourens (1794–1867) (Fig. I-20) provided the first scientific clues that the semicircular canals were intimately involved in the regulation of balance. As a professor of comparative anatomy in Paris, Flourens published a series of experiments pertaining to the function of the inner ears, first in 1824, and again in 1842 and 1861.6,44,45 In these remarkable series of studies, Flourens demonstrated in pigeons that lesions in the horizontal semicircular canals caused the animal to turn on its vertical axis, while posterior canal lesions caused the birds to roll over backwards. From his experiments, Flourens observed that even after the

Figure I-20. Marie-Jean Pierre Flourens (1794–1867). (From Politzer A: A History of Otology, Part I, 1904.)

15

operation, the animals could still hear, and that the direction of the movements was exactly the same as that of the canal that had been divided. Interestingly, Flourens concluded from his results that the semicircular canals influenced the directional movements of pigeons, rather than being the organ of equilibrium.46 Furthermore, Flourens did not make the scientific leap separating the vestibular and auditory functions of the inner ear, believing still that both mediated sound perception, with the cochlea being the more essential of the two.41 Flourens’ observations only slowly permeated into the medical community. Yet it provided the first scientific clue that vertiginous disorders were not of a central nervous origin, spurring others to study this newly emerging topic. In 1836, for example, Nicholas Deleau pointed out that too often diseases of the ear (though he supposed the middle ear) were mistaken for diseases of the brain, and included vertiginous attacks simulating prodromes of “apoplexy.”47 Over the following 30 years, many other investigators reproduced and partially confirmed the results obtained by Flourens, including Harless, Brown-Sequard, and Czermak. However, none of these men provided revolutionary breakthroughs (though Brown-Sequard did discover labyrinthine calorics without realizing the full significance of his finding).41,46

The State of Otology and the Neurosciences in the Mid-19th Century The middle third of the 19th century was a time of great scientific advancement, and medicine and surgery were developing at an increasingly rapid pace. Despite this, in the mid-1830s, the treatment of ear diseases was still neglected and disdained by most surgeons. Sir Astley Cooper, inventor of the myringotomy paracentesis, had abandoned the ear for general surgery in the early 1800s. Von Tröltsch, as late as 1863 bluntly stated, “There is scarcely any department of the science of medicine in which there is, even at this day, so much ignorance of facts, and such a want of possessiveness of opinion, as in aural medicine and surgery.”30 Theodor Billroth echoed these sentiments in 1874 when he wrote that, “ . . . the instruction in diseases of the ear was in a very bad state. I remember well from my own student days how the poor deaf people were sent from one clinic to the other; nobody felt inclined to take any interest in them. With a few obvious exceptions this field is therapeutically much too barren.”48 Billroth then stated that otologic surgery called “. . . for a certain amount of heroism in a man to sacrifice himself to this, therapeutically the most thankless and limited, phase of surgery.”48 Most physicians of this time felt as Billroth and von Tröltsch did; that the ear was complicated, inaccessible, and dangerous, as demonstrated by the disastrous early attempts at mastoid surgery resulting in deafness or severe tinnitus. Though the anatomy of the ear was well described by this time, its physiology was far from completely understood, and a rational approach to pathology was barely evident, being little more than that advanced by Valsalva and Duverney 150 years earlier. All this would be radically changed by the great English otologic anatomist-pathologist, Joseph Toynbee.

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THE HISTORY OF NEUROTOLOGY AND SKULL BASE SURGERY

Joseph Toynbee and the Origins of Modern Aural Pathology Born in 1815, Joseph Toynbee (1815–1866) (Fig. I-21) was the second of 15 children of a wealthy Lincolnshire farmer. At 17 years of age he traveled to London to begin an apprenticeship. Even at an early stage, he had decided on aural surgery. At only 23, Toynbee was elected to the Royal College of Surgeons, based on his well-known dissecting ability, and he was eventually appointed to a post at the Hunterian Museum. His subsequent work led to his election as a fellow of the Royal Society, one of the youngest men ever to receive the honor.49 From the beginning, Toynbee realized that the paucity of aural pathology was the primary reason for its relegation to medicine’s backwaters. Toynbee wrote in the introduction of his text, “. . . if we carefully survey the history of the rise and progress of Aural, as a distinct branch of Scientific Surgery, one main cause of the disrepute into which it had fallen may be traced to the neglect of the Pathology of the organ of hearing—a neglect that doubtless led also to the ignorance which has prevailed as to the structure and functions of some of the most important of its parts.”50 Toynbee thus became determined at an early stage of his career to study and dissect every ear he could possibly lay his hands on. Within 20 years he had amassed a world-famous collection of over 2000 specimens, which attracted scientists from all over the world. From this collection Toynbee derived most of his observations. Though presented to the Hunterian Museum on his death, the collection was completely destroyed during

World War II. The summary of his observations were put forth in his textbook, Diseases of the Ear,50 first published in 1860, which until then was the most comprehensive work of its kind (Figs. I-22 and I-23). Additionally, Toynbee was the first to describe stapes footplate immobilization from

Figure I-22. Toynbee’s pioneering work, Diseases of the Ear, first published in 1860.

Figure I-21. Joseph Toynbee (1815–1866), the founder of aural pathology, and a master of eustachian tube function. Toynbee was one of the first physicians to correlate the clinical ear exam with pathologic findings. (From Politzer A: A History of Otology, Part I, 1904.)

Figure I-23. Illustrations from Toynbee’s Diseases of the Ear. These include the correct use of the Toynbee tube, and a device termed the explorer for eustachian tube catheterization.

The History of Neurotology and Skull Base Surgery

otosclerosis, and invented an artificial eardrum made of a disc of India-rubber sandwiched between two small silver plates.51 This artificial drum was a design standard for nearly 100 years, until replaced by tympanoplasty by Zöllner and Wullstein in the 1950s. (Toynbee was not, however, the first to propose of an artificial tympanic membrane— this concept dates back at least as early as 1640.)52

The Vienna Medical School In the second half of the 19th century the Vienna Medical School (Fig. I-24) was home to the greatest medical minds of the day, a concentration of physicians and scientists unequaled in the annals of medicine until then. These included such notable figures as Billroth, Kaposi, Chiari, Rokitansky, Czermak, Hyrtl, Skoda, Politzer, Barany, Alexander, Zuckerkandl, Ludwig, Gruber, and Brauer. According to Henry Hun, a neurologist and author of a guide for American medical students training in Europe at that time, “. . . there is, undoubtedly, no place where a student can attend so many excellent clinics with so little loss of time, or where he can so well train his eyes and hands in methods of diagnosis and treatment, as in Vienna.”53 More directly, Lesky stated that during this seminal time period, “Vienna medicine had become world medicine.”1 Much of this reputation and brilliance centered on a pathologist named Karl Rokitansky (1804–1878). Rokitansky’s three-volume Handbuch der Pathologischen Anatomie, first published in 1842, was the most extensive pathologic-anatomic text ever written and was referred to by Heyfelder of Erlangen as “. . . one of the noblest products of medical literature.”1 Virchow, champion of the cellular theory and the father of modern physiology, would later base his life’s work on many of the principles founded by Rokitansky. Utilizing the wealth and variety of material

Figure I-24. The Vienna Medical School in the late 1800s, home to the greatest physicians in the world at that time. (From Lesky E: The Vienna Medical School of the 19th Century. Baltimore, The Johns Hopkins University Press, 1976.)

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available to him in Vienna, Rokitansky’s ambition was clear and comprehensive: “First . . . sorting the facts scientifically on a purely anatomical basis and thereby creating the subject of general pathological anatomy which would justify its separate existence as such . . . second, demonstrating the applicability of the facts and their utilization for diagnosis in live patients . . .” (Rokitansky, as translated by Lesky)1

Slowly through the mid-1800s Rokitansky’s work permeated almost every branch of medicine, helping to provide a pathologic-anatomic basis for specialty after specialty, including neurology, dermatology, ophthalmology, pediatrics, and obstetrics. Otology was spared until Toynbee obtained Rokitansky’s text and proceeded to model his studies after Rokitansky’s teachings. Until Toynbee laid these scientific foundations, otology could not advance past the back-alley of medicine it inhabited. According to Anton Friedrich von Tröltsch (1829–1890) (Figs. I-25 and I-26), “. . . Toynbee contributed most to this change (in otology) . . . by his numerous sections of the auditory apparatus, as well as by various contributions to our anatomical and physiological knowledge of aural disease.”30 Thus, by the 1860s, Rokitansky’s teachings were firmly in place in otologic medicine. “I need not speak to you, gentleman, of the importance of pathologic anatomy, for medical science, any more than I need to tell you that the sun illuminates the earth over which it shines. We have already seen how late it was in the history of aural medicine and surgery before pathological investigation of the ear was undertaken, and that the slow and late development of this part of our science resulted as it necessarily must, from this neglect of the appearances of the organ on the cadaver,” wrote von Tröltsch in 1869.30 After Toynbee’s immense

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Figure I-25. Anton Friedrich von Tröltsch (1829–1890), one of the founders of modern otology. In addition to his influence on most great otologists of the 19th century, von Tröltsch was also a master otologic anatomist (remembered for the pouch of von Tröltsch) and introduced the concave head mirror now used by otolaryngologists the world over.

otologic work, the stage was set for someone to master both the clinical and pathologic-anatomic facets of the burgeoning field of otology and create an independent specialty.

Figure I-26. The title page to Anton Friedrich von Tröltsch’s highly influential otology textbook, Krankheiten des Ohres, published in 1862.

Adam Politzer—The Father of Otology While Toynbee was laying the foundations for aural pathology in England, otology was transforming itself from a discipline in surgery to a subspecialty in its own right in Vienna under the direction of one of the most influential otologists of all time. If anyone can rightly be called the “father” of otology, it must be Adam Politzer (1835–1920) (Fig. I-27). Without diminishing the work of such great men of the time as Schwartze, Gruber, and von Tröltsch, Politzer was the charismatic leader of this newly emerging specialty. Adam Politzer was born in Alberti, Hungary, in 1835, the son of a successful Jewish merchant. Following in his grandfather’s footsteps, he became a physician after graduating from the University of Vienna in 1859, spending time as a special pupil of Skoda, Ludwig, and Rokitansky.54 Under the influence of Rokitansky’s teachings in Vienna, Politzer realized that the only way to advance the field of otology was to become a master of aural morphology. For the next several years Politzer traveled throughout Europe to study under the leaders of the field. He spent time in Würzburg, the leading center for microscopic research in the world at that time, under Kölliker, Müller, and von Tröltsch. Politzer also spent time in London studying Toynbee’s famous collections of specimens, and under Ménière and Bernard in France, where the clinical-anatomic revolution started earlier in

Figure I-27. Adam Politzer (1835–1920), the “father” of otology.

The History of Neurotology and Skull Base Surgery

the century by Cruveilhier was still exerting influence.32 This extensive background made Politzer one of the great masters of specimen preparation technique at that time. His rapidly expanding collection of temporal bones was soon almost as large as Toynbee’s and was in demand throughout Europe. Politzer’s mission, a direct extension of Rokitansky’s teachings to establishing a correlation between the findings of his dissections and true clinical findings, had been partially realized by Toynbee, Wilde in Dublin, and von Tröltsch in Würzburg. However, none of these men had access to the tremendous wealth of pathology offered by the Vienna General Hospital, caring for 3 to 4 thousand patients at any given time.53 While giving ample credit to his predecessors and contemporaries, Politzer went on to define a specialty. He completely characterized a whole series of diseases previously grouped under the vague heading “dry middle ear catarrh.” He was the first to define panotitis, leukemia of the ear, labyrinthine suppuration, and established that a cholesteatoma was related to an ingrowth of squamous epithelium. His textbook Lehrbuch der Ohrenheilkunde (Textbook of the Diseases of the Ear and Adjacent Organs)55 originally published in 1878, was in its fifth edition by 1908, had been translated into multiple languages, and was used the world over as the standard of otologic practice. Politzer, along with his colleague Joseph Gruber, had made Vienna the premier destination for otologic training in the world at that time and had established otology as a respectable specialty. In 1863, together with von Tröltsch and Schwartze, Politzer started the Archiv für Ohrenheilkunde (Archives of Otology), the first journal dedicated to disorders of the ear, and later founded the Austrian Otological Society (Fig. I-28). Politzer was a talented artist who spent his evenings drawing findings from his immense collections. His unexcelled knowledge base and superb teaching abilities made him a revered professor. He could teach with equal fluency in German, English, French, and Italian. He had a mild manner was said to be unfailingly courteous, winning him the affection of all who visited him at his clinic. On Politzer’s retirement from teaching in 1907, he received a farewell message from his students, which carried the names of 366 otologists from 21 countries and included every prominent otologist in the world at that time.54 Politzer was truly one of the finest men to grace the field of otology and has left a lasting mark which is still felt today.

Figure I-28. The 50th anniversary title page of the Archiv fur Ohrenheilkunde (Archives of Otology), the first journal dedicated to disorders of the ear. The three founders of the journal are depicted: Adam Politzer, Anton Friedrich von Tröltsch, and Hermann Schwartze.

Elucidation of the Organ of Corti Marquis Alfonso Corti (1822–1888) (Fig. I-29) was born into an ancient noble Italian family in the state of Lombardy. Scarpa, who died when Corti was only 10 years old, was a family friend and great influence on Corti. Political upheaval and wars in Italy and France forced Corti to travel abroad and eventually settle in Würzburg, where most of his investigations on the anatomy of the inner ear were carried out. There he developed a close friendship with the great pathologist Virchow and took part in Virchow’s wedding.9,56 In 1850 Corti described for the first time the sensory epithelium, the spiral ganglion, the tectorial membrane, and the stria vascularis of the inner ear. These results were published in the Zeitschrift für Wissenschaftliche Zoologie in

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Figure I-29. Marquis Alfonso Corti (1822–1888), for whom the organ of Corti is named.

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involved with helping start the first journal dedicated solely to the ear, Archiv für Ohrenheilkunde, in 1863 along with von Tröltsch and Politzer. Schwartze eventually succumbed to a nervous condition of restlessness, vertigo, and delusions, dying of heart failure at the age of 73. It was Schwartze’s mentor, von Tröltsch, who was responsible for urging Schwartze to fully develop a method of treatment for suppurative processes of the temporal bone. In 1863, Schwartz published his influential work on the indications for the mastoid operation and his success with the use of specifically designed chisels and gouges (see Fig. I-33).64 According to Whiting, an American otologist in 1911, through this publication Schwartze had, “. . . clearly enunciated the technical and symptomatic principles upon which are based the steps of the modern mastoid operation as performed to-day (sic), and however much we may modify our practice the innovations result in a little more or a little less than Schwartze’s operation . . .”65 Later, in 1889 Stacke and subsequently Zaufal in 1890 described the radical mastoid operation.23

The Pathophysiology of Coalescent Mastoiditis: Friedrich Bezold It was also during this seminal time period that Friedrich Bezold (1842–1908) (Fig. I-34) published his findings pertaining to coalescent mastoiditis leading to an abscess.66 Bezold was born in Rothenburg an der Tauber (in modern day Bavaria). He studied medicine throughout the Germanic states, including München (Munich), Würzburg,

and Erlangen, graduating in 1866. Although initially an ophthalmologist, training under the great, pioneering eye surgeon von Graefe, he subsequently studied pathologic principles under the direction of Virchow. From 1866 onward, he lived and taught in Munich under the tutelage of von Tröltsch where he studied the ear while practicing ophthalmology.32 Von Tröltsch was so influential to the young Bezold, that he is repeatedly cited in Bezold’s text. According to Bezold, von Tröltsch’s text was the “codex” of otology. “. . . There is hardly a part of our branch which v. Tröltsch did not enrich with new and fruitful views.”67 In 1878, Bezold published his findings pertaining to coalescent mastoiditis leading to an abscess.66 The manuscript itself described in intricate detail the ways in which a coalescent mastoiditis could spread beyond the mastoid. In the introduction of this manuscript, Bezold outlined the prevailing lack of clinical information on the topic: “It used to be that the diseases of the mastoid were exclusively seen as in association with diseases of the tympanum. Because of this there is little in the otologic literature concerning the pathology of mastoid disease as a primary process.” He then went on to describe a case of a 6-year-old boy, who developed a coalescent mastoiditis from a cholesteatoma (which he termed an epidermoid mass) 16 years after his original presentation. Additionally, he reviewed the world literature up to that time on disease processes of the mastoid that spread to contiguous areas. Bezold would later describe the course of mastoid inflammation and infection. However, it was not until 3 years later in 1881 that he would publish a paper specifically pertaining to a mastoid infection leading to a neck abscess, which was translated in a short review by the American Journal of Otology that same year.68 In the manuscript, Bezold correctly described the pathway of extension through the digastric groove. Bezold arrived at these conclusions by boring through the mastoid into the digastric groove in cadavers, forcibly injecting colored gelatin, and studying where it had infiltrated into the neck. Bezold then recommended treatment of the disease based on his studies: “. . . perforating the digastric groove through the mastoid cells, entering the cells at the lower part of the mastoid process, and extending the opening into the incisura mastoidea.” He then presented a case treated in this fashion, which was healed in 14 days. Years later Bezold acknowledged in his textbook (as translated by Hollinger in 1908), “They (coalescent mastoiditis leading to a neck abscess) produce a very distinct clinical picture . . . and in literature are often called Bezold’s mastoiditis, because I studied its development experimentally on the cadaver.”67

Sir William Macewen: The First Skull Base Surgeon?

Figure I-34. Friedrich Bezold (1842–1908), the German otologist who thoroughly described the complications of suppurative mastoiditis, including the “Bezold’s abscess,” a coalescent mastoiditis with extension into the neck.

If one man can be named the first true skull base surgeon, then surely Sir William Macewen is he. Once called the founder of neurosurgery by Harvey Cushing, and “the unfair surgeon,” by others for his exhaustive work ethic, leaving little behind for “. . . aftercomers to improve or amend,” Sir William Macewen (1848–1924) (Fig. I-35) left behind a legacy still felt today.69,70 Macewen was born on the Scottish Island of Bute, the youngest of 12 children. As the son of a master mariner, the young Macewen learned

The History of Neurotology and Skull Base Surgery

Figure I-35. Sir William Macewen (1848–1924), perhaps one of the first true skull base surgeons. He pioneered aseptic surgery of the brain and temporal bone.

to use tools and to work with his hands at an early age. He joined the Glasgow Medical Faculty in 1865 and began his surgical work the same time Joseph Lister carried out his revolutionary antiseptic research. Lister was Macewen’s premier influence as a young faculty member and was instrumental in Macewen’s pioneering work in surgical antisepsis. In his now classic, Pyogenic Infective Diseases of the Brain and Spinal Cord, Macewen outlined his technique of treating otogenic intracranial complications.71 His results were so extraordinary for the era, they were unequaled until the era of computed tomography and have been deemed,

Figure I-36. Illustrations from Macewen’s classic medical masterpiece, Pyogenic Infective Diseases of the Brain and Spinal Cord. The illustration shows two children with acute subperiosteal squamomastoid abscesses. (From Macewan W: Pyogenic Infective Diseases of the Brain and Spinal Cord. Glasgow, Scotland, James Maclehose & Sons, 1893, p 9.)

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“. . . nothing short of extraordinary,”72 and “. . . one of the most remarkable books ever written on a neurosurgical subject.”73 Certainly, one can claim that it is also one of the most remarkable books ever written on a neurotologic subject. In the monumental work he described 94 cases of intracranial infections and reported such extraordinary results as successful evacuation of a brain abscess in 21 out of 22 cases (Fig. I-36). As later pointed out by Jefferson, Macewen may deserve the honor of the first clear description of mastoiditis.74 Macewen reported on 54 mastoidectomies for infections confined to the middle ear and mastoid, and a separate listing of mastoidectomies in which extension into the cranium occurred. As a surgeon who was “. . . as familiar and at home operating on the head and brain, as a clinician educated by past experience to recognize the signs of brain disease, and as an anatomist who had made a special study of the ear, he was triply armed immediately to follow the clues given him by the state of the patient or local extensions of the disease.”74 For these reasons, Macewen must be considered the first true skull base surgeon, equally versed in operations of the ear and brain, and pathologic processes affecting both. It is perhaps because of Macewen’s residence in Glasgow, some distance from the epicenter of British medicine in London, that he felt his accomplishments went unrecognized in his lifetime.75 In his later years, Macewen became an elder statesman of surgery. He was president of the British Medical Association, president of the International Society of Surgeons, and the surgeon to the king in Scotland. He was invited to become the chair of surgery at the newly established Johns Hopkins Medical School in 1889, but an agreement was not reached and Halstead was ultimately appointed instead. Macewen died after a severe case of pneumonia in 1924 at the age of 76.70,76,77

Victor Horsley and the Birth of Neurosurgery It wasn’t just otology that had defined itself as a unique subspecialty in the later half of the 19th century. Neurosurgery, the second pillar of neurotology and skull

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base surgery, also saw its nascent beginnings during this time. The National Hospital for Nervous and Mental Diseases, located on Queen’s Square in London, is considered by most to be the birthplace of neurologic surgery. Although Macewen was clearly one of the stars of this emerging field, his practice in distant Glasgow limited his influence among his contemporaries. The National Hospital hosted such luminaries as Charles-Édouard Brown-Séquard, John Hughlings Jackson, and Sir William Gowers, making it the center for neurologic studies in the world at that time. However, the most famous surgeon to grace the hospital staff was also credited with the founding of modern neurologic surgery: Sir Victor Horsley (1857–1916) (Fig. I-37). A contemporary of Macewen’s and also credited with some of neurosurgery’s earliest successes, it was Horsley’s, “. . . indefatigable physiological experimentation in addition to his clinical and pathological experiments,” that has led to his inclusion in neurosurgery’s pantheon.72 Horsley was also the first surgeon ever to devote a majority of his efforts to neurosurgery. His contributions to neurosurgery included the first laminectomy for a spinal neoplasm, the first carotid ligation for aneurysm, the first transcranial approach to the pituitary, pioneering intracranial trigeminal nerve sectioning for neuralgia, and the use of bone wax to stem bleeding from bone, to name but a few of his many accomplishments.78 According to Cushing, after Horsley was appointed surgeon to the, “. . . National Hospital for the Paralyzed and Epileptic, Queen Square, the birth of modern neurologic surgery may properly be assumed to have taken place.”79 Victor Horsley was present at what is widely considered the first modern brain tumor surgery. In 1884, Rickman Godlee at the Hospital for Epilepsy and Paralysis in

Figure I-37. Sir Victor Horsley (1857–1916), the father of neurologic surgery. (From Paget S: Sir Victor Horsley. New York, Harcourt, 1920.)

London operated on a tumor that had been diagnosed and localized to the right motor cortex by the neurologist Alexander Bennett.75,80 Although brain tumors had been removed previously, Bennett’s localization of the tumor and Godlee’s first use of antiseptic technique during tumor surgery made the case quite extraordinary. Using Bennett’s knowledge of neuroanatomy and pathophysiology, Godlee was able to plan his craniotomy directly over the tumor, and easily remove the tumor, which turned out to be a glioma. The patient survived the immediate operation, but succumbed to purulent cerebritis a month after surgery. The case is noteworthy for overcoming the third most challenging obstacle, following anesthesia and asepsis, that faced the development of neurosurgery; tumor localization. With this obstacle overcome, employing the help of neurologists such as Bennett, neurosurgical advances accelerated. Godlee’s case is noteworthy also from the standpoint of who attended the operation: the neurologist Hughlings Jackson, the neurosurgeons Victor Horsley and David Ferrier, and Joseph Lister (Godlee’s uncle) were reported to be there.75

Sir Charles Ballance: Pioneering Skull Base Surgeon Along with Victor Horsley, Sir Charles Ballance (1857–1936) (Fig. I-38) was another of the pioneering British neurological surgeons. Neurotology and skull base surgery can also claim Ballance as one of its instrumental founders as well, based on his landmark surgical advances within the temporal bone. Born in Middlesex, England, Ballance entered medical school in 1875 at St. Thomas’ Hospital in London. As one of the stars of his medical school class,

Figure I-38. Sir Charles Ballance, a pioneering neurotologist and skull base surgeon. (From Shambaugh GE: Surgery of the Ear. Philadelphia, WB Saunders, 1967, with permission.)

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be predicted that as the mastoidectomy became popular for treating mastoid suppuration after its introduction by Schwartz,64 the number of iatrogenic facial nerve injuries also rose, providing a further spur to facial nerve surgery repair. It is no coincidence that the first report of a facial nerve crossover repair was reported by Drobnik in 1879, only 6 years after Schwartz’s publication.89 As noted by Duel in 1933 in his historical retrospective, “. . . unskilled surgery of the temporal bone brought with it an ever increasing number of cases of accidental paralysis.”90 Sir Charles Ballance had tremendous influence on facial nerve surgery during this time, with his introduction of a spinal accessory-facial nerve crossover anastomosis in 1895, as well as the first reported attempt at rerouting the facial nerve intratemporally.26,91 Several other surgeons also attempted facial nerve crossover operations during this time, including Faure, Kennedy, and Cushing.89 Over the course of the next 25 years, nearly all the lower cranial nerves would be used as possible crossover grafts to the facial nerve, and controversy surrounded whether to perform end-to-end versus end-to-side anastomoses, issues which are still debated today.

Scientific Advancement in Vestibular Physiology in the late 19th Century: Prosper Mèniére and the First Description of Ménière’s Disease In one of the first great advances in understanding vestibular physiology in the later portion of the 19th century, Prosper Mèniére (1799–1862) (Fig. I-40) described for

Figure I-40. Prosper Mèniére (1799–1862), the first to establish that the combination of vertigo, hearing loss, nausea, and vomiting has as their basis an inner ear pathology. (From Politzer A: A History of Otology, Part I, 1904.)

the first time the disease that now bears his name. Born in the southwest of France, Mèniére completed his medical studies at the Hotel-Dieu in Paris, where he was closely influenced by Guillaume Dupuytren and later by Itard, one of the leading otologists in Europe at that time. After receiving his doctorate in 1828, he took up a position as assistant professor of the Paris Faculty of Medicine, later to become a fellow of the university. In 1848, Mèniére began a French translation of a German textbook on hearing loss by Kramer.92,93 Within this translation, Mèniére added a footnote that mentioned a case of labyrinthine hemorrhage resulting in sudden deafness.94 This was, in fact, the same case report he would describe 13 years later in his now classic description of endolymphatic hydrops. In 1861, in a series of reports before the Paris Academy of Medicine, Mèniére described a group of patients with the symptoms of vertigo, nausea, and vomiting, and sought, “. . . to attribute vertigo and falling to lesions different from those which have their site exclusively in the brain, and as a consequence to institute a rational treatment for these affections, for too long a time confused under a single title.”95 In these seminal reports, Mèniére described a series of patients with neural deafness, with the hearing loss greater in the low frequencies, and though sometimes bilateral, mostly the occurrence was unilateral. He noted that the ear exam was nearly always normal, and that the symptoms of tinnitus, vertigo, nausea, and vomiting stopped when the hearing was completely lost, typically after many years. He also reported worsening of the condition with quinine. To illustrate his basic point that vertigo, nausea, and vomiting may be due to an inner ear disorder, he again presented the case of the young girl whom he footnoted in his translation of Kramer’s work 13 years previously, but in even greater clinical detail. The girl had a sudden onset of complete deafness, vertigo, nausea, and vomiting, dying after 5 days of close observation. After a pathologic exam demonstrated no evidence of a central nervous system lesion, Mèniére himself examined the temporal bones. He identified a blood-tinged exudate within the semicircular canals, but not within the cochlea. Then, citing Flourens’ work from 33 years earlier, Mèniére asserted, “. . . that the symptoms which appear in man and which consist of vertigo, nausea, the syncopal state, which is accompanied by ear noises, and which has deafness as its consequence, may depend on an alteration which has as its site that portion of the labyrinth of which we have spoken” (translation by Williams).96 Mèniére later published the remainder of his observations in several reports, the last on September 21, 1861.26 Though controversy surrounded his report after his death, Ménière’s principle and noteworthy accomplishment was to establish that the combination of vertigo, hearing loss, nausea, and vomiting has as their basis an inner ear pathology.96 Despite Flourens’ earlier observations and Ménière’s accomplishments however, there was still prevailing confusion on the precise mechanisms of balance control within the medical community in the later half of the 19th century. This reflected, more than anything else, a lack of understanding of vestibular physiology. Friedrich Leopold Goltz (1834–1902) (Fig. I-41), a scientist from Strasbourg, took the next large step to change this, ushering in the next leap in the understanding of the labyrinth. In 1870, Goltz

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reviewed by Jackler, at an international conference of neurosurgeons, mortality for these operations was 78%, and most survivors had serious disability.106 However, these statistics would be radically changed by the most influential neurosurgeon of the 20th century, Harvey Cushing.

Harvey Cushing: The Founder of Modern Neurosurgery There is perhaps no one in the annals of neurologic surgery about whom more has been written than Harvey Cushing (1869–1939) (Fig. I-42), a man whose name is synonymous with the field. His personality and accomplishments are the stuff of legend. Born the youngest of 10 children in a long line of physicians, Cushing followed his father, grandfather, great-grandfather, and great-great-grandfather’s path into medicine. After an undergraduate education at Yale, he studied medicine at Harvard Medical School. He subsequently went to Johns Hopkins University to train under the pioneering surgeon Halsted, where he was also exposed to the other medical icon of that era, Sir William Osler. From Johns Hopkins and later at Harvard, Cushing would revolutionize the field of neurosurgery. He introduced the concept of meticulously documented anesthesia records and the use of continuous intraoperative blood pressure monitoring. He was perhaps the first surgeon to make regular use of the new technology of x-rays, including making the emulsions and developing the films himself. He described the “Cushing response,” the physiologic changes induced by a rise in intracranial pressure. He performed pioneering work in balanced salt solutions that led to modern intravenous therapy. He pioneered transsphenoidal pituitary surgery. He revolutionized surgical training by introducing canine surgery for medical students. He radically improved intracranial hemostasis with the development of surgical clips and electrocautery, and with it, drastically improved surgical morbidity during neurosurgical procedures.75,107,108 In addition to these “technical” advances, Cushing radically changed the practice of surgery. He insisted that surgeons take responsibility for their own diagnoses and

Figure I-42. The “father” of modern neurological surgery, Harvey Cushing. (Courtesy of the Alan Mason Chesney Medical Archives, Johns Hopkins University.)

decisions to operate, rather than relying on medical physicians or neurologists.107 Cushing made meticulous, anatomically based surgical technique fashionable, rather than reliance on speed. Of course, this was made possible by his improved technical advances such as hemostasis and insistence on superior anesthesia. So pervasive was his instruction, that to this day, nearly all American-trained neurologic surgeons can somehow trace their legacy back to Cushing. Cushing’s advances within the field of skull base surgery are equally monumental, particularly with regard to the treatment of acoustic neuromas. After realizing that the tumors could not be completely removed by current standards, he advised intracapsular removal of the tumor and subtotal resection (Fig. I-43).109 Combined with his other technical advances, this approach enabled Cushing to reduce surgical mortality from near 90% to 20%, as noted in his classic monograph, Tumors of the Nervus Acusticus and the Syndrome of the Cerebello-Pontine Angle, published in 1917.110 By 1920, Cushing had redefined the specialty of neurologic surgery, with its emphasis on a strong foundation of neurologic training. According to Greenblatt, “. . . with further demonstration of his successes in training, in therapeutic results, and in research productivity, the Cushing model became the world model.”108

Nylén, Holmgren, and the Birth of the Operating Microscope While Cushing was laying the foundations for modern neurologic surgery in America, two unassuming Swedish surgeons were developing a technology that would ultimately revolutionize the fields of otology, neurotology, skull base surgery, and neurosurgery.

Figure I-43. Illustrations from Cushing’s landmark treatise, Tumors of the Nervus Acusticus and the Syndrome of the Cerebello-Pontine Angle, 1917, demonstrating his technique of vestibular schwannoma tumor removal, leaving the tumor capsule intact. (From Cushing H: Tumors of the Nervus Acusticus and the Syndrome of the Cerebello-Pontine Angle. Philadelphia, WB Saunders, 1917.)

The History of Neurotology and Skull Base Surgery

The operating microscope evolved out of the optics of the microscope originally pioneered by Robert Hooke and Anton van Leeuwenhoek in the mid-1600s. Yet it was the inherent constraints of ear surgery that led to development of a microscope uniquely suited to the operating room. Otology and neurotology were uniquely poised for this transition because of the difficulties imposed by the microscopic anatomy of the inner ear, limiting what ear surgeons could do by unmagnified eyesight alone. Furthermore, with the development of improved anesthesia at the beginning of the 20th century, the need for more precise surgical technique within otology, as championed by Cushing in neurosurgery, became paramount. Carl-Olaf Nylén (Fig. I-44) was an assistant in the University Otolaryngology Clinic in Stockholm under the chief Gunnar Holmgren in the early 1920s. Prompted by Maier and Lion’s report of endolymph movements in the living pigeon using a low-power microscope,111 Nylén began work on a higher power microscope that could be used during ear surgery. Such a device would have direct relevance to Nylén’s primary clinical interest of study— labyrinthine fistulas.112 Nylén’s first monocular microscope was developed by the Brinnell-Leitz factory (see Fig. I-44, right). Nylén later recalled his initial use of the microscope, “The idea of using a larger magnification than had previously been employed, occurred to me early in 1921 when I was experimenting with labyrinthine fistula operations on temporal bone preparations from human beings and in living animals. . . . In November 1921 I used the Brinell microscope for observations and operations in two cases of chronic otitis with labyrinthine fistulas, and in one case with bilateral pseudo-fistula symptoms.”113

Nylén later modified the scope with the help of his friend and engineer Persson so it could more easily mount on the patient. These results were reported in 1922 at the

Figure I-44. Carl-Olaf Nylén (left) and his first monocular microscope (right). (From Dohlman GF, Arch Otolaryngol 90:161–165, with permission.)

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meeting of the Swedish Otolaryngologic Society and again in Paris in July of that same year.114 Unfortunately, after his initial contribution of the monocular operating microscope, Nylén found himself unable to continue to develop the instrument in the clinic of his chief, Gunnar Holmgren (Fig. I-45), where tradition and custom dictated that the chief alone could carry out the new, and still experimental otosclerosis surgery, one of the primary applications of the new “otomicroscope.” Holmgren was already known for having introduced the operating loupes to ear surgery and thus already had a substantial appreciation for the need of magnification during these procedures. After seeing his assistant Nylén use the operating microscope, Holmgren immediately recognized the added advantages of the microscope over loupes during these cases. However, Holmgren didn’t simply copy Nylén’s idea—he significantly advanced it and gave ample credit for the idea to his assistant. In one of his publications, he stated, “. . . following a good idea of my 1. Assistant surgeon Dr. Nylén I tried a microscope and found the Zeiss binocular microscope a very suitable instrument . . .”115 To the Zeiss binocular, ophthalmologic scope, Holmgren added a light source and support suitable for the operating theater and began using it that same year, in 1922 (Fig. I-46).115 Compared with Nylén’s monocular scope, Holmgren had developed an entirely new and revolutionary binocular operating microscope. In his initial description of the uses of the operating microscope in the temporal bone, Holmgren enthusiastically presaged its benefit in ear surgery, stating that the advantages of using the microscope for radical operations on otitis, “. . . are indeed so obvious that no operator, who has had experience of the lens will give it up when doing this operation.”115 Holmgren’s words are prescient indeed, as any current otologic, neurotologic, skull base surgeon or neurosurgeon will attest! Additionally, Holmgren

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Figure I-45. Gunnar Holmgren, Nylén’s chief at the University Otolaryngology Clinic in Stockholm, who significantly improved the operating microscope. (From Shambaugh GE: Surgery of the Ear. Philadelphia, WB Saunders, 1967, with permission.)

Figure I-47. Walter Dandy (1886–1946). (Courtesy of the Alan Mason Chesney Medical Archives, Johns Hopkins University.)

Walter Dandy employed what he termed, “. . . a little circular cutting file, viz., one driven by a little electro-motor of the type which is often used by dentists, armed with the very smallest drills obtainable, which are sufficiently small to make it possible that even very delicate bone operations can be carried out in the utmost safety under the guidance of the eye.”116 This was perhaps the first application of the drill for aural surgery and has to be regarded as a seminal event in the history of neurotology and skull base surgery.

Figure I-46. Gunnar Holmgren is shown using binocular operative microscope, from his 1922 monograph, “Operations on the temporal bone carried out with the help of the lens and the microscope.” (From Holmgren G: Operations on the temporal bone carried out with the help of the lens and the microscope. Acta Otolaryngol 4:383–393, 1922.)

At approximately the same time Nylén and Holmgren were introducing the operating microscope to aural surgery, one of Cushing’s protégé’s was carrying on the transformation of neurosurgery started by his mentor. Walter Dandy (1886–1946) (Fig. I-47), perhaps Cushing’s most accomplished student, is clearly responsible for ushering in the next great leap in neurotologic, neurosurgical, and skull base surgery. Passing up a Rhodes Scholarship to enter Johns Hopkins Medical School, Dandy would go on to redefine the specialty of neurosurgery. After graduating medical school, he was appointed by Halsted to surgery, and spent his first year in the Hunterian Labs where Cushing was carrying out his physiologic experiments. There the two giants developed a contentious relationship almost from the start. At one point, Dandy accused Cushing (apparently with some justification) of not being, “. . . a real scientist.”117 It is no surprise, therefore, that when Cushing left Johns Hopkins to take over the new neurosurgical department at Brigham Hospital in Boston in 1912, Dandy was not asked to join the team. Furthermore, the animosity did not entirely dissolve after Cushing’s departure; according to Greenblatt, “. . . Cushing often remained jealously suspicious of anything that issued . . .” from Dandy’s work at Hopkins.108 If great minds truly do clash, then the squabbles between Cushing and Dandy should come as no surprise. For as much as Cushing transformed the landscape of neurologic surgery, Dandy would nearly rival his teacher’s accomplishments while at Johns Hopkins. Perhaps Dandy’s greatest accomplishment came while he was still in his training years. In 1918 he reported on ventriculography by

The History of Neurotology and Skull Base Surgery

the injection of air into the cerebral ventricles.118 The effect on the field of neurosurgery was enormous, for it allowed the direct localization and size estimation of brain tumors for the first time. According to Horrax, “It brought immediately into the operable field at least one third more brain tumors than could be diagnosed and localized previously by the most refined neurological methods.”72 One year later he introduced pneumoencephalography. Dandy’s influence upon neurotology and skull base surgery was equally profound. In 1917 he reported on the first successful total excision of an acoustic neuroma.119,120 Whereas Cushing had advocated leaving the capsule intact to minimize surrounding brain injury, bleeding, and facial paralysis, Dandy recommended total excision (Fig. I-48). This departure from his former teacher’s doctrine reportedly left Cushing infuriated.117,121 Reports extending into the 1940s followed Dandy’s subsequent practice of the suboccipital approach for complete acoustic neuroma resection.122 Dandy’s influence on neurotology and skull base surgery would not end with his achievements in vestibular schwannoma resection. As discussed later on, his influence on the treatment of Ménière’s disease was equally important. However, to better understand the import of these advances, it is necessary to understand the advances that were simultaneously occurring in the vestibular sciences in the early part of the 20th century.

Advances in Vestibular Science in the Early 20th Century Even with the rapidly accumulating data on the structure and function of the vestibular apparatus, at the turn of the

Figure I-48. Dandy’s technique of tumor excision, from his monograph, “Results of removal of acoustic tumors by the unilateral approach,” published in 1941. (From Dandy WE: Results of removal of acoustic rumors by the unilateral approach. Arch Surg 42:1026–1033, 1941.)

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century, knowledge of Ménière’s disease had progressed little since Ménière’s original description nearly 40 years earlier. Many vertiginous disorders were still confusingly grouped together, and therapy was based on empiricism and anecdotal reports. For example, Crockett in 1903 attempted to remove the stapes in two patients with Ménière’s disease, which lead to complete deafness. A year later Lake opened the semicircular canals in a Ménière’s patient and instilled an antiseptic solution.123,124 This lack of a rational approach to Ménière’s disease was in part due to the poor state of vestibular diagnosis. This would be radically changed by the eminent physician-scientist Robert Bárány (1876–1936) (Fig. I-49). Barany fundamentally advanced our understanding of vestibular physiology during the first part of the century. Bárány initially trained under Adam Politzer. Working at the University of Vienna, Barany introduced into the clinical exam caloric testing, rotational testing, galvanic testing, and the air-fistula test.46 He correlated various forms of nystagmus with vestibular pathologies and explored the relationship between the semicircular canals and the central nervous system. His new methods of examination enabled the clinician to differentiate between eighth nerve tumors, vestibular neuronitis, and other forms of nystagmus. Much of this work was outlined in his classic work, “Untersuchengen über den vom Vestibularapparat des Ohres reflektorisch ausgelosten rhythmischen Nystagmus und seine Begleiterscheinungen,” published in volume 40 of the Monatschrift für Ohrenheilkund.46,125 For his achievements, Bárány received, among numerous other international awards, the Nobel Prize in medicine 1915. Tragically, due to professional jealousy and religious prejudice, he was accused by his

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Figure I-49. Robert Bárány. (From Pappas DG: Bárány’s History of Vestibular Physiology: Translation and Commentary. Ann Otol Rhinol Laryngol 93:1–16, 1984.)

Figure I-50. Georges Portmann, a pioneer in surgery of the endolymphatic sac for Ménière’s disease. (From Shambaugh GE: Surgery of the Ear. Philadelphia, WB Saunders, 1967, with permission.)

colleagues in Vienna of plagiarism. He was eventually inducted into the Austrian army during World War I. He learned of his award of the Nobel Prize while a Russian prisoner in 1915. The Swedish Red-Cross had to exchange him for a high-ranking Russian officer so he could deliver his Nobel lecture. He thereafter shunned his former Viennese colleagues, spending the remainder of his professional life at the University of Uppsala in Sweden.46

According to Portmann himself, “I was pleased that I had dared to carry out the first operation on the inner ear to decompress the membranous labyrinth by opening the endolymphatic sac in an attempt to relieve vertigo and preserve, not destroy, hearing.”127 It was considered the first successful operation for Ménière’s disease. Although endolymphatic sac decompression would not become popular in the United States for another 20 years, a new era in neurotology had begun.

Georges Portmann and the Endolymphatic Sac Bárány’s work inspired a generation of vestibular clinicians and scientists. Among those influenced by Bárány was Georges Portmann, from Bordeaux, France (Fig. I-50). Based on earlier work he performed in fish in the early 1920s and the belief that increased pressure within the endolymphatic sac produced Ménière’s syndrome, Portmann proposed a new method for treating the disease by opening the endolymphatic sac.126 He based his operation on: (1) other’s research in rabbits that demonstrated changes in endolymphatic sac pressure (including opening the sac) causing changes in limb tonus; (2) the analogy of Ménière’s disease with ocular glaucoma, termed aural glaucoma, as advanced by Knapp in 1871; and (3) Guild’s research 1 year previously demonstrating the endolymphatic sac as an organ of endolymphatic fluid filtration. Portmann proposed a transmastoid opening of the endolymphatic sac with a small knife to relieve the pressure from Ménière’s syndrome (Fig. I-51). The operation was first attempted on January 18, 1926, on a patient with Ménière’s disease and extremely severe vertigo. The patient reportedly had complete resolution of vertiginous symptoms.

Figure I-51. An illustration from Georges Portmann’s endolymphatic sac operation demonstrating his technique.

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Reemergence of the Operative Intervention for Ménière’s Disease in the 1930s and 1940s: Walter Dandy’s Vestibular Nerve Section Walter Dandy (1886–1946), though he stated that he initially began sectioning the eighth cranial nerve for patients with vertigo as early as 1912, started selectively sectioning the vestibular nerve beginning around 1930.128 By 1940, he published the results of the operation in over 400 patients with Ménière’s disease. Dandy was not the first to treat Ménière’s disease by dividing the VIIIth cranial nerve, as this honor probably belongs to R. H. Parry, who reported on such a case using a middle fossa approach in 1902.129 Undoubtedly, the primitive state of neurologic surgery at the time, the outcome of Parry’s reported case (complete facial nerve paralysis), and the report of two other deaths from similar attempts at relieving vertigo dissuaded others from trying this treatment for quite some time. By the time of Dandy’s report in 1941, however, the procedure was far safer. As Dandy stated, “Ménière’s disease can be permanently cured by division of the auditory nerve. This procedure carries almost no risk to life. Up to the present time, I have performed 401 operations, with 1 death—the 358th case—due to meningitis.”130 Dandy was a neurosurgeon by training, yet otolaryngologists and otologists were more and more involved in caring for patients with vertiginous disorders, particularly after scientific advances pinpointed the essential lesion to the labyrinth. Though, even at the time of his publication in 1941, Dandy was not convinced that the semicircular canals were the seat of the pathology in Ménière’s disease. In fact, Dandy pointedly stated that Hallpike and Cairns’ assertion that the pathology of Ménière’s lay in the semicircular canals was, “. . . by no means secure and I think is very doubtful.”130 Similarly, as for the dietary (low-salt) medical cures offered by Furstenberg and others, Dandy wrote, “I do believe them to be useless.”130 The evidence against Dandy’s point of view mounted, however, and Dandy’s method of intracranial division of the vestibular nerve became supplanted by other, less invasive procedures over the following decade.

Terence Cawthorne and the Rise of the Transmastoid Labyrinthectomy One of the principle reasons for the demise of vestibular nerve section was that otologists of the 1930s and 1940s encountered a number of difficulties when attempting to perform Dandy’s surgery, most obvious being the unfamiliarity of neurosurgical anatomy.131 As a result, a variety of otologic operations were tried during this time to relieve patients of the severe symptoms of Ménière’s disease, including injections of alcohol through the horizontal canal or stapes footplate, electrocoagulation of the horizontal canal, or simply opening the labyrinth and suctioning the contents.132 However, it was the British otologist Terence Cawthorne’s (Fig. I-52) method—the transmastoid labyrinthectomy—that eventually became the new standard for treating Ménière’s disease in the 1940s and 1950s. Sir Terence Cawthorne (1902–1970) was universally acknowledged as one of the greatest ear surgeons in the

Figure I-52. Sir Terence Cawthorne, a pioneering surgeon who helped popularize the transmastoid labyrinthectomy and was instrumental in applying the operating microscope to aural surgery. (From Shambaugh GE: Surgery of the Ear. Philadelphia, WB Saunders, 1967, with permission.)

mid-1900s.133 While serving on the staff of the National Hospital for Nervous Diseases and the Metropolitan Hospital in England, he began intensively studying labyrinthine vertigo. In 1943, Cawthorne introduced a transmastoid labyrinthectomy as a means of destroying the labyrinth and curing the symptoms of Ménière’s disease.134 The transmastoid labyrinthectomy was certainly not a new operation when Cawthorne reintroduced it in the 1940s. The earliest known reports of labyrinthectomy for treating balance disorders date to 1904, with reports by both Lake and Milligan.124,135,136 Following these reports, the labyrinthectomy became the more popular treatment over vestibular nerve section for vertigo because it was felt to be a safer operation.136 However, the labyrinthectomy failed to gain widespread acceptance for treatment of vertiginous disorders among neurosurgeons, who still favored the vestibular nerve section and its potential for hearing preservation. Dandy’s work and widely published results on vestibular nerve section subsequently dominated the medical community, and Dandy’s technique gradually won favor during the 1920s and 1930s. When Cawthorne’s repopularized the labyrinthectomy in the 1940s, however, the appeal to the otolaryngologic community was immediate. The mastoid operation was one that all otolaryngologists were quite familiar with already. As amply noted in this historical review, the mastoidectomy had become a widely accepted treatment for suppurative diseases of the ear and chronic otitis media since the 1860s. By the 1940s, all otolaryngology training programs included the mastoidectomy as a basic part of resident training, practiced essentially as it is today, with the exception of the types of instruments used. Modifying

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the mastoid operation to include a labyrinthectomy was a simple step, and the transmastoid labyrinthectomy quickly became the preferred method for treating patients with Ménière’s disease, surpassing the vestibular nerve section championed by Dandy. With the subsequent rise of the operating microscope in the 1960s, this debate between the superiority of the labyrinthectomy versus the vestibular nerve section would again rage within the surgical community, and in some circles, is still being debated.

Neurotologic Surgery Advances in the 1930s and 1940s: Maurice Sourdille, Julius Lempert, and the Fenestration Operation Pioneering efforts to restore hearing to patients with otosclerosis has undeniably benefited the development of neurotology and skull base surgery. For the operation to succeed required improvements in both aural operative technique and surgical microscopy, advances that were ultimately incorporated into neurotologic and skull base surgery. During the 1940s, two figures stand prominent in the development of an effective surgical treatment for otosclerosis: Maurice Sourdille (1885–1961) (Fig. I-53) and Julius Lempert. Though the lesser known of the two men, Maurice Sourdille’s influence on the surgical treatment of otosclerosis is perhaps nearly as important. After studying at the University of Paris in 1911, he eventually became a pupil of Lermoyez, one of the most prominent otolaryngologists in France at that time. It was under Lermoyez’s tutelage that

Figure I-53. Maurice Sourdille (1885–1961), a pioneering French surgeon for otosclerosis. Sourdille developed the three-stage fenestration operation that would later become the basis for Lempert’s famed fenestration operation. (From Shambaugh GE: Surgery of the Ear. Philadelphia, WB Saunders, 1967, with permission.)

Sourdille developed his passion for hearing preservation surgery.137 Following World War I, Sourdille traveled to Sweden where he studied with Holmgren and Bárány. There he witnessed firsthand the spectacular, though often shortlived, labyrinthine fenestration results with the microscope that Holmgren was achieving on patients with otosclerosis. The high incidence of deafness eventually led Bárány and Holmgren to abandon the procedure. However, Sourdille recognized that the two principle drawbacks of Holmgren’s operation were closure of the fistula and the risk of infection. After experiments in the cadaver, Sourdille developed a three-stage procedure. He decided that the horizontal canal was the most accessible, and he closed the fistula with a thin cutaneous flap from the external auditory canal, which came to be known as “Sourdille’s flap.”137 Not only were his hearing results superior, but the auditory improvement lasted. After Sourdille presented his results in 1929 to the French Academy of Medicine, word quickly spread throughout Europe and the Americas, leading both otologists and patients from around the world to seek out Sourdille. He eventually came to North America in 1937, lecturing in several cities about his new, improved technique. Ultimately, however, Sourdille’s technique would lose favor to one devised by an American sitting in the audience of one of these lectures. As Shambaugh later recollected, Julius Lempert was present in the audience at the New York Academy of Medicine, where Sourdille was speaking at the invitation of Edmund Fowler.138 Afterward, Lempert reportedly invited Sourdille to dinner where he obtained further details of the new procedure. It would be a meeting that Sourdille would later regret. Julius Lempert (1890–1968) (Fig. I-54) was truly one of the groundbreaking neurotologists of the 20th century and has been considered by some to be the father of modern otology.139 According to Terence Cawthorne, Lempert, “. . . lead the renaissance of otologic surgery and of otology as a science, at the very moment that antibiotics began to remove acute mastoid infections and their dread complications from the surgeon’s scalpel to the family doctor’s prescription pad.”140 His charm and charisma were legendary. He developed the endaural approach to ear surgery141 and popularized the drill in otologic surgery, as used by Holmgren before him. According to Glasscock, his exposure of the carotid artery during temporal bone surgery in 1938 was one of the seminal events of skull base surgery development.139 However, it was at Sourdille’s lecture in New York that Lempert would conceive of his legendary method for the fenestration operation that would make him famous. He altered Sourdille’s technique into a single-stage procedure, applied his endaural approach, and used a dental burr to expose the horizontal semicircular canal. However, in his subsequent descriptions of the technique, Lempert failed to cite Sourdille’s prior work.137 This appears not to be the first time that Lempert failed to cite prior work that may have influenced him. In Lempert’s original description of the endaural approach to the mastoid, he failed to cite Joachim Heermann, the German physician who had first described the procedure.138 Regardless of the controversy surrounding the primacy of the procedure, Lempert’s one-stage fenestration operation

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bear on the classification of glomus tumors, previously termed a variety of confusing names, such as hemangioendothelioma. Over the years, Dr. Rosenwasser built up an impressive series of cases of glomus tumors and is widely considered the father of glomus jugulare surgery while he was on faculty at Columbia University in New York. Dr. Rosenwasser was later elected as president of the American Otological Society in 1966.144 Advances in the understanding and treatment of glomus jugulare tumors began with Rosenwasser’s report.145 The classic clinical finding of a glomus tumor of the middle ear, a reddish blush against the drum, known colloquially as Brown’s sign, was named after Lester A. Brown in a report of his findings in six patients in 1953.146 However, it wasn’t until the 1960s with the introduction of polytomography and retrograde jugulography, a rational classification scheme proposed by Alford and Guilford, and innovative skull base approaches that were developed during this time that diagnosis and treatment of glomus jugulare tumors really began to accelerate.139

Neurotologic Surgical Advances in the 1950s Figure I-54. Julius Lempert, the highly influential surgeon who popularized the fenestration operation for otosclerosis, and performed pioneering neurotologic and skull base surgery. (From Shambaugh GE: Surgery of the Ear. Philadelphia, WB Saunders, 1967, with permission.)

rapidly took hold and revolutionized otologic surgery in the United States. Surgeons and patients from all over the world soon flocked to Lempert’s private office in New York, while Sourdille slipped into relative obscurity. Sadly, when Lempert’s operation was ultimately supplanted by the stapes mobilization procedure, and later the stapedectomy, it would be Lempert who would refuse to change, ultimately slipping into obscurity himself.

Glomus Jugulare Tumors— Harry Rosenwasser There is no doubt that glomus tumors have played a pivotal role in the development of neurotology and skull base surgery. The innovative infratemporal fossa skull base approaches that have been developed and refined over the years have their origins in surgery for glomus tumors. As has been noted by Schuknecht, perhaps the first complete description of a glomus body tumor was in 1937 in the Dutch literature by J. Lubbers.142 However, it was in 1941 when Stacy Guild was credited with the first description of a glomus jugulare tumor in the English literature.143 It was just a year later when Harry Rosenwasser, a surgeon at The Mount Sinai Hospital in New York City operated on a patient with a vascular mass protruding from his ear and extending into the mastoid (though not reported until 1945).144 In this report, Rosenwasser credited Guild with the first report of a glomus tumor. It was most likely Rosenwasser and Guild’s lack of access to the Dutch literature that led to the historical confusion on primacy of the description of glomus tumors. Following these initial reports, however, a new understanding was brought to

Surgical advances in neurotology in the 1950s are principally remembered for three advances: the stapedectomy operation, the modern tympanoplasty, and the development of a microscope that would revolutionize surgery. Of the three, the development of the microscope is the most important, since it directly enabled the other two advances. After Nylén’s, and subsequently Holmgren’s, description of the operating microscope, its adaptation by the general otologic community was slow. George Shambaugh Jr. was the first to apply the binocular microscope to Lempert’s one-stage fenestration operation in the 1940s. With the assistance of the operating microscope, as well as the first use of continuous irrigation to help wash away bone dust, Shambaugh was able to demonstrate significantly better surgical results, highlighting the utility of the microscope during ear surgery.147 During the same period, Cawthorne in London was popularizing the microscope for transmastoid labyrinthectomy and for operations on the facial nerve, Tullio began applying the microscope to mastoid surgery, and Simpson-Hall began using the microscope for Sourdille’s earlier fenestration operation in Europe.112 Despite these reports, however, there was still some general resistance to the use of the “otomicroscope” for several reasons. First, there were cost issues; these microscopes were custom built and quite expensive. Second, Lempert preferred the loupes for ear surgery along with a headlamp, probably because of the microscope’s limitations, and his technique dictated much of what was done in operating rooms of the United States during the 1940s.148 Last, and perhaps most important, were the microscope’s technical limitations—each of the previously mentioned surgeons, and many others, had their own, unique microscope design, which were slightly modified and improved versions of the original operating microscopes of Holmgren and Nylén, and which incorporated better working distances, maneuverability, and lighting.113

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Figure I-55. The Zeiss OpMi-1 binocular dissecting microscope, also known as the Opton microscope. This scope would revolutionize neurotologic and skull base surgery through its ease of use and widespread availability. (From Mudry A: The History of the Microscope for Use in Ear Surgery. Am J Otol 21(6):877–886, with permission.)

Then in 1951, the Zeiss company, under the direction of Hans Littmann, produced the OpMi-1 binocular dissecting microscope (Fig. I-55), also known as the Zeiss-Opton, which simultaneously incorporated many of the advances that had occurred over the previous decade.113 This device would revolutionize microsurgery. Of particular importance, the microscope included illumination that entered the

operative field through the same objective as the operating surgeon was viewing. It also incorporated variable magnification from 6× to 40×, an adequate working distance of ≈20 cm using a 200- or 250-mm lens, which was just about ideal for ear surgery.113 In many ways, the Zeiss-Opton can be considered the “Model T” of operating microscopes. It wasn’t the first, but it was adaptable, it was affordable, and it was durable, all of which led to its enduring success. The microscope was presented for the first time at the fifth medical congress in Amsterdam in 1951 and was commercially produced from 1953 onward.149 Today, many of these scopes are still working as well as they did when they were introduced in the 1950s, and nearly every otologist, neurotologist, neurosurgeon, and skull base surgeon over the age of 40 can claim at least part of his or her training to the Zeiss OpMi-1. Most of the development of Zeiss’s OpMi-1 was done in collaboration with Hörst Wullstein and Fritz Zöllner during the development of their revolutionary technique of tympanoplasty, or what they termed plastic surgery of the sound conducting apparatus.150 According to Wullstein, as translated by Mudry, “In the era of surgical dissection, microsurgery brought a new dimension into surgery far less reachable by conventional methods. This can only be compared with the radical change that occurred in medicine with the introduction of antisepsis, asepsis and anesthesia.”148 With Zöllner and Wullstein’s landmark work on surgery for chronic ear disease, the utility of the microscope became obvious and was quickly adapted for nearly every type of otologic surgery. Rosen developed the stapes mobilization procedure,151 while Shambaugh, Derlacki, Heermann, and House simultaneously advanced and independently adapted it toward stapes surgery, along with specially designed instruments for use under the microscope (Fig. I-56).152–154 These instruments are all still routinely used during otologic and neurotologic surgery, and homage is paid every time a surgeon asks their scrub nurse for an instrument such as the “Rosen knife.”

Figure I-56. Some of the pioneering aural surgeons of the 1950s. George E. Shambaugh, Jr. (left), was instrumental in applying the operating microscope to otosclerosis surgery, along with Dr.’s House (right), Rosen, Derlacki, and Heermann. John Shea (center) pioneered the modern stapedectomy operation.

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Perhaps the most important adaptation of the microscope, however, was by John Shea, who used it to develop the stapedectomy procedure.155 The success of this operation influenced a generation of ear surgeons and made them facile with the operating microscope. According to Glasscock, “. . . it was Shea who made it a practical, everyday instrument for performing otologic procedures.”139 In fact, this widespread acceptance of the microscope during routine otologic surgery, as pioneered by surgeons such as Shea, Cawthorne, and Shambaughand Rosen, directly lead to the birth of an independent subspecialty: neurotology and skull base surgery.

William House and the Birth of Modern Neurotology and Skull Base Surgery Today the operating microscope is the indispensable tool of the neurosurgical, neurotologic, and skull base surgeon. However, this was not the case in the late 1950s and early 1960s. While the operating microscope was beginning to permeate otologic surgery, neurosurgery was still performed by essentially the same techniques championed by Dandy and Cushing. History has taught us that most scientific paradigm shifts are introduced from outside the establishment, and often in the face of tremendous resistance.156 When the operating microscope was first introduced into neurosurgery by an outsider—an otologist—such fierce antagonism was similarly met. From the moment William House (Fig. I-57) applied the operating microscope to acoustic neuroma resection, he faced an uphill battle. That his prescience and perseverance led to his ultimate triumph over the neurosurgical establishment of the day has earned him a revered spot in the pantheon of great ear surgeons. The 1960s were a time of tremendous social change. It saw the birth of the free-speech movement, a countercultural revolution, and an entire generation questioning the values and morays of their parents and society at large. Otology and neurosurgery were not spared the changes happening in the broader social context. It was perhaps the social trends of the day that enabled surgeons such as House to openly question and challenge the way surgery was performed, particularly by another field such as neurosurgery. After completion of his residency, William House joined his brother Howard in a private otology practice in the flourishing Los Angeles of the 1950s. William House soon developed an interest in the treatment of diseases of the inner ear. It was House’s interest in sensorineural hearing loss from otosclerosis and the possibility of restoring hearing by drilling out the internal auditory canal that ultimately led him to attempt a middle fossa approach.157 After a series of experiments on cadavers in his local morgue, he attempted the middle fossa approach using the operative microscope, along with the neurosurgeon Kurze on a patient with cochlear otosclerosis.158,159 The patient did not regain hearing, nor did the two subsequent patients on whom the operation was attempted. According to House, when he presented the operative approach at a symposium, he was publicly ridiculed not only for the results, but for the approach itself.157 It was several years subsequent to this that House revived the translabyrinthine approach to the cerebellopontine

Figure I-57. William House, the “father” of modern skull base surgery. (From House W: Monograph: Transtemporal bone microsurgical removal of acoustic neuromas. Arch Otolaryngol 80:597–756, 1964, with permission.)

angle for resection of vestibular schwannomas. House, along with William Hitselburger, thus introduced the operating microscope and otologic surgical technique to neurosurgery.160 The operative approach was immediately recognized for its importance within the otolaryngologic community. George Shambaugh Jr. wrote in the foreword to House’s highly influential 1964 monograph that his work was, “. . . destined to become a second milestone in the surgical approaches through the temporal bone made possible and practical by microsurgical temporal bone techniques.”161 In fact, the first milestone that Shambaugh was referring to was Cushing’s work nearly 50 years prior. Shambaugh also noted in his foreword the not so subtle manner in which House patterned his monograph exactly as Cushing laid out his classic work in Tumors of the Nervous Acusticus in 1917.110 Despite the enthusiastic reception of the work within otolaryngology, the opposition that House and Hitselburger faced from the neurosurgical community, which had traditionally cared for these tumors, was fierce.139,157 The squabble at House’s own institution would ultimately be mirrored across the country on numerous other hospital staffs as similar turf wars would play themselves out between neurosurgeons and otologists. However, soon the advantages of House and Hitselberger’s microscopic technique became obvious, and the microscope quickly spread to other fields, including neurosurgery itself. Both otology and neurosurgery gradually came to realize that by combining their individual expertise toward the resection of vestibular schwannomas, the ultimate benefactor was the patient. Once the acoustic neuroma obstacle had been cleared, collaboration on resection of other skull base tumors soon followed. Thus, one can argue convincingly

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that once the reconciliation between neurosurgery and otology over acoustic neuromas had occurred in the late 1960s and early 1970s, the field of skull base surgery was born. House’s influence on neurotology was profound. He went on to develop additional, expanded approaches to the skull base, including the extended middle fossa and transcochlear approaches. His pioneering work on cochlear implants was far ahead of its time and again initially met with great opposition from within otology’s own elite establishment.162 Clearly, one of House’s laudatory attributes as a person is his perseverance in the face of misdirected opposition. In each case, he appears to have won, convincingly. As noted by Glasscock, “Had William F. House not had such a strong personality, had he not been so determined, then neurootology would not exist as we know it today.”139

Electrical Stimulation of the Auditory Nerve—The Birth of Cochlear Implants The 1960s were notable for another milestone in neurotology, the birth of the cochlear implant. As the first true prosthetic device that enables the restoration of a lost sense, the cochlear implant surely has to be ranked as one of the greatest achievements of medical science. Fittingly, cochlear implants arose out of uncoordinated international efforts, replete with individuals who persisted in their work despite fierce criticism within the academic and medical communities. Attempts to electrically stimulate the ear date as early as 1790, when Alexander Volta, professor of natural philosophy at the University of Pavia, was experimenting with the relatively new phenomenon of electricity. He inserted a metal rod into each of his ears, connected a 50-volt battery between them, and heard a noise similar to the boiling of a viscous liquid.163 In the mid-18th century, two prominent otolaryngologists introduced the idea of electrical stimulation to medicine by advocating it for the diagnosis and treatment of many ear diseases. This short-lived field of “electro-otiatrics” was abandoned by the start of the 20th century, however, and remained dormant for the following 30 years.164,165 The idea that sound could be artificially created through electrical stimulation of the ear was resurrected by two events in the early 20th century. In 1925 radio engineers discovered that sound could be produced by stimulating electrodes in the near vicinity of the ear, and in 1930 Weaver and Bray discovered a phenomenon known as the “cochlear microphonic,” an electrical potential arising from the cochlea as a result of acoustic stimulation.166 Shortly before World War II, a group of scientists at MIT, the prominent psychophysicist S. S. Stevens, and a group of Soviet scientists, began independently investigating the concept of electrical stimulation of the eighth nerve.167–169 Each of these groups tried to stimulate the cochlea from within the middle ear to create sound. With only primitive electronics such as vacuum tubes, however, this proved to be too great a technical feat. Each group encountered difficulty with the dynamic range of their devices and couldn’t create sound without causing pain or stimulating the facial nerve. However, their early, rigorous scientific endeavors were instrumental in setting the stage for successful stimulation of the eighth nerve within the following two decades.

Djourno and Eyries published their first data on direct stimulation of the cochlear nerve in a totally deaf person in 1957. During a reoperation for facial paralysis and deafness in a 50-year-old man, an electrode was placed into the region of the cochlear nerve stump and a current was passed. The patient heard sounds like “crickets” or a “roulette wheel.”170,171 The researchers never followed up their results, however, and their work remained obscure for a number of years. In 1961 William House and James Doyle designed a few implantable cochlear-stimulating devices based on the work of the scientists at MIT and in the Soviet Union and tested them in human patients. Due to poor construction and the toxic nature of the implant material, however, the devices had to be removed after 3 weeks. Despite this setback and the use of a nonphysiologic stimulating current, House and Doyle’s initial results indicated that patients could perceive the rhythm of speech and music and were aware of a variety of environmental sounds.172 The technical difficulties they encountered, however, discouraged them from continuing further with cochlear implants for a number of years. The most widely acclaimed implantation in the 1960s occurred under the direction of Blair Simmons at Stanford University.173 He placed an implant in the cochlea of a terminally ill, congenitally deaf patient and showed that the patient could perceive sound. Ironically, because the patient could not understand speech, Simmons concluded in his landmark paper that, “. . . the chances are small indeed that electrical stimulation of the auditory nerve can ever provide a uniquely useful means of communication.” A colleague of Simmons, Robin Michelson, would ultimately leave Simmons to begin his own program at the University of California San Francisco. In 1973 the First International Conference on Cochlear Implants was held at the University of California San Francisco. By this time, House had preformed a total of 22 implants, Michelson and his colleagues had done seven with some published results, and Simmons had done two. Additional cochlear implant development programs were well underway in Melbourne, Australia, and Innsbrück, Austria, each making landmark strides on their own. However, Merle Lawrence summed up the prevailing attitudes of a large segment of the medical and scientific community when he implied at the conference assembly that there is no way, “. . . of the number of channels or electrode points . . .” by means of which one can get tonotopic or specific frequency stimulation by attempting to stimulate first order neuron dendrites in the cochlea, and all that would be produced would be “noise.”174 Harold Schuknecht, another conference participant, was more direct when he flatly stated at the conference’s conclusion, “. . . I will admit that we need a new operation in otology but I am afraid this is not it.”174 Much of the criticism of the implants at this point centered on the belief that it was immoral to proceed in humans until sufficient animal work had been done, combined with the prevailing belief that the device itself would simply never work because of the extensive and irreversible neural damage already present in deaf individuals. Beyond these concerns, extravagant claims surfacing in the public, including testimonials about “. . . hearing the chirping of mockingbirds once again (and) enjoying symphony

The History of Neurotology and Skull Base Surgery

music . . .” further alienated the scientific community and made research in cochlear implants a pariah of audiologic research.175 However, a pivotal year for the advancement of the cochlear implant came in 1977, when the National Institutes of Health began an independent, multicenter study of patients with cochlear implant devices. Led by Dr. Bilger at the University of Pittsburgh, the study concluded that the device was a definite aid in communication.176 Bilger, who was skeptical of cochlear implants, was actually converted to a modest supporter by the results of his own report: “It . . . (the report) . . . put to rest some of the wilder claims about the benefits of . . . implants and it substantiated that for some individuals there were benefits in lip reading, environmental awareness and voice modulation control.”175 What is more important, the study provided substantial scientific evidence for the benefits of cochlear implantation and gave credibility to the emerging technology.

The Creation of the American Neurotologic Society By the mid-1960s, the multitude of advances in the hearing, vestibular, and neurosciences, as well as in otologic and skull base surgery were stirring the restive members of the American Academy of Ophthalmology and Otolaryngology. There was a concept of “neurotology” as an independent subspecialty that was slowly growing and gaining consensus. As later recalled by Marcus,177 the growing array of diagnostic tests and surgical approaches, as well as advances in the basic understanding of the inner ear and central nervous system led Nicholas Torok and Richard Marcus to form “the Neurotology group,” in 1965. The goals of the group were twofold: (1) to exchange and disseminate information about the physiology, pathology, and clinical management of the sensorineural systems of audition and equilibrium; and (2) to stimulate education and basic and clinical research relating to these systems. In 1974, the group changed its name to the American Neurotologic Association.177 With its formation, neurotology can thus be said to have “officially” begun.

CONCLUSION In many ways, this current textbook, Neurotology, is the triumph of the goals of the “Neurotology group,” that originally formed in 1965. However, in so many more ways, neurotology and skull base surgery are the continuation of a tradition of the pioneering spirit of the clinician, the surgeon, and the scientist, often wrapped up in the same individual, dating back to the Renaissance and beyond. The past 25 years, though not covered by this historical review, has seen the emergence of revolutionary forms of technology, such as computed tomography and magnetic resonance imaging, each of which have had no less of a revolutionary effect on our specialty. It is without doubt that future generations will write on our own time as a new kind of renaissance; not one of art and anatomy, but one of genetics, neuroscience, computers, and biotechnology. It is precisely the appreciation of our historic origins that enables each of us to revel in our specialty’s own great achievements.

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Eighty years ago, Sir Charles Ballance, the pioneering skull base surgeon, eloquently acknowledged what each of us owes to our teachers and predecessors, and his sentiments remain relevant today as we look forward to the next millennium: “Every man is a debtor to his profession. A vast field of our art and science still remains unmapped and unexplored. I trust that succeeding generations of surgeons . . . will devote time to research work. Research adds zest and satisfaction to life, and gives the promise of that thrill of delight which accompanies the first perception, the slow unfolding of some new truth or principle. Thus may we surgeons rightly forge new weapons against disease and death” (Sir Charles Ballance, 1922).12

It is only through such dedication to clinical and surgical advances and basic neurotologic research that tomorrow’s leaders, as great and revolutionary as those in our historical past will emerge, and neurotologic and skull base history will continue to advance.

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76. Flexner S, Thomas FJ: William Henry Welch and the Heroic Age of American Medicine. New York, Dover, 1941. 77. Bowman AK: Sir William Macewan: A Chapter in the History of Surgery. London, William Hodge, 1942. 78. Tan TC, Black PM: Sir Victor Horsley (1857-1916): Pioneer of neurological surgery. Neurosurgery 50:607–611, discussion 11–12, 2002. 79. Cushing H: Neurological surgeons: With the report of one case. Arch Neurol Psychiat 10:381–390, 1923. 80. Bennett AH, Godlee RJ: Case of cerebral tumour. The surgical treatment. Trans R Med Chir Soc Lond 68:243–275, 1885. 81. Stone JL: Sir Charles Ballance: Pioneer British neurological surgeon. Neurosurgery 44:610–631, discussion 31–32, 1999. 82. Anonymous. Sir Charles Ballance: Obituary. Lancet 1:450–452, 1936. 83. Ballance C: On the removal of pyemic thrombi from the lateral sinus. Trans Med Soc Lond 13:345–370, 1890. 84. Ballance C: (1)Epithelial grafting of the mastoid, (2)gunshot wound of the temporal bone, (3)Radiogram of suspected auditory nerve tumor. Proc R Soc Med 14:1–2; 16–18, 1920. 85. Ballance C: Cerebellar abscess secondary to ear disease: A case successfully treated by operation. St Thomas Hosp Rep 23: 133–219, 1896. 86. Dandy WE: An operation for the total removal of cerebellopontile (acoustic) tumors. Surg Gynecol Obstet 41:129–148, 1925. 87. House H, House W: Historical review and problem of acoustic neuroma. Arch Otolaryngol 80:601–604, 1964. 88. Ballance CA: A case of division of the auditory nerve for painful tinnitus. Lancet 2:1070–1073, 1908. 89. Shah SB, Jackler RK: Facial nerve surgery in the 19th and early 20th centuries: The evolution from crossover anastomosis to direct nerve repair. Am J Otol 19:236–245, 1998. 90. Duel AB: History and development of the surgical treatment of facial palsy. Surg Gynecol Obstet 56:382–390, 1933. 91. Ballance C, Duel AB: The operative treatment of facial palsy. Ann Otolarynol 15:1–70, 1932. 92. Touma JB: Prosper Meniere: A Glimpse at His Personality and Time from His Introduction of Kramer’s Book, “Diseases of the Ear.” Am J Otol 7:305–308, 1986. 93. Kramer W: Traite des Maladies de l’orielle. Translated by P. Meniere. Paris, Cellot et Hubert, 1848. 94. Chalat NI: Who was Prosper Meniere and why am I still so dizzy? Am J Otolaryngol 1:52–56, 1979. 95. Meniere P: Revue hebdomadaire. Academie de medicine: Congestions cerebrales apoplectiformes: discussion: MM. Bouillaud, Piorry, Tardieu, Durand-Fradel. Gaz Med Paris, sx3, Jan. 26;16, 1861. 96. Williams HL: Ménière’s Disease. Springfield, IL, Charles C Thomas, 1952, pp 3–16. 97. Camus M, Creed RS: The Physiology of the Vestibular Apparatus. Oxford, Clarendon Press, 1930, pp 5–9. 98. Boettcher A: Über den aqueductus vestibuli bei Katsen und Menschen. Arch Anat Physiol 36:372–380, 1869. 99. Hasse S: Die Lymphbahnen des inneren Ohres. Anat Studien Bd 1:765, 1873. 100. Schindler RA: The ultrastructure of the endolymphatic sac in man. Laryngoscope 90:1–39, 1980. 101. Knapp H: A clinical analysis of the inflammatory affections of the inner ear. Arch Ophthalmol 2:204–283, 1871. 102. Hoogland GA: Some historical remarks on acoustic neuroma. Adv Otorhinolaryngol 34:3–7, 1984. 103. Sandifort E: De Duro Quodam Corpusculo Nervo Auditorio Adhaerente. Observationes Anatomico-Pathologicae. Leiden, Lugduni Batavorum, 1777, pp 116–120. 104. McBurney C, Starr MA: A contribution to cerebral surgery: Diagnosis, localization and operations for removal of three tumors of the brain: With some comments upon the surgical treatment of brain tumors. Am J Med Sci 55:361–387, 1893.

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105. Ballance C: Some Points in Surgery of the Brain and Its Membranes. London, Macmillan, 1904, p 276. 106. Jackler RK: Acoustic Neuroma (Vestibular Schwannoma). In Jackler RK, Brackman DE (eds.): Neurotology. St Louis, Mosby, 1994, pp 729–785. 107. Laws ER Jr: Neurosurgery’s man of the century: Harvey Cushing—The man and his legacy. Neurosurgery 45:977–982, 1999. 108. Greenblatt SH, Smith DC: The emergence of Cushing’s leadership: 1901-1920. In Greenblatt SH (ed.): A History of Neurological Surgery. Park Ridge, IL, The American Association of Neurological Surgeons, 1997, pp 167–190. 109. Olivecrona H: Notes on the history of acoustic tumor operations. In Hamberger C-A, Wersall J (eds.): Disorders of the Skull Base Region; Proceedings of the Tenth Nobel Symposium. Stockholm, John Wiley, 1968. 110. Cushing H: Tumors of the Nervus Acusticus and the Syndrome of the Cerebello-Pontine Angle. Philadelphia, WB Saunders, 1917. 111. Maior Lion: Exper. Nachweis d. Endolymfbewegung. Pflügers Arch 187:1–3, 1921. 112. Dohlman GF: Carl Olaf Nylén and the birth of the otomicroscope and microsurgery. Arch Otolaryngol 90:161–165, 1969. 113. Nylén CO: The microscope in aural surgery, its first use and later development. Acta Otolaryngol (Stockh) 116(Suppl):226–240, 1954. 114. Nylén CO: An Oto-microscope. Acta Otolaryngol 5:414–417, 1923. 115. Holmgren G: Operations on the temporal bone carried out with the help of the lens and the microscope. Acta Otolaryngol 4:383–393, 1922. 116. Holmgren G: Some experiences in the surgery of otosclerosis. Acta Otolaryngol 5:460–466, 1923. 117. Flamm E: New observations on the Dandy-Cushing controversy. Neurosurgery 35:737–740, 1994. 118. Dandy WE: Ventriculography following the injection of air into the cerebral ventricles. Ann Surg 68:5, 1918. 119. Dandy WE: An operation for the total extirpation of tumors in the cerebello-pontine angle: A preliminary report. Johns Hopkins Med Bull 33:344–345, 1922. 120. Dandy WE: Exhibition of cases. Johns Hopkins Med Bull 28:96, 1917. 121. Fox WL: The Cushing-Dandy controversy. Surg Neurol 3:61–66, 1975. 122. Dandy WE: Results of removal of acoustic rumors by the unilateral approach. Arch Surg 42:1026–1033, 1941. 123. Crockett EA: Removal of the stapes for the relief of vertigo. Ann Otol Rhinol Laryngol 12:67, 1903. 124. Lake R: Removal of semicircular canals in a case of unilateral aural vertigo. Lancet 1:421, 1904. 125. Barany R: Untersuchengen über den vom Vestibularapparat des Ohres reflektorisch ausgelosten rhythmischen Nystagmus und seine Begleiterscheinungen. Berlin, C Coblenz, 1906. 126. Portmann G: The saccus endolymphaticus and an operation for draining the same for the relief of vertigo. Arch Otolaryngol 6:309–317, 1927. 127. Portmann G: The old and new in Ménière’s disease—Over 60 years in retrospect and a look to the future. Otolaryngol Clin North Am 13:567–575, 1980. 128. Dandy W: Effects on hearing after subtotal section of the cochlear branch of the auditory nerve. Bull Johns Hopkins Hosp 55:240–243, 1934. 129. Parry RH: A case of tinnitus and vertigo treated by division of the auditory nerve. J Laryngol Rhinol Otol 19:402–406, 1904. 130. Dandy W: The surgical treatment of Ménière’s disease. Surg Gynecol Obstet 72, 1941. 131. Bordley JE, Brookhouser PE: The history of otology. In Bradford LJ, Hardy WG (eds.): Hearing and Hearing Impairment. New York, Grune & Stratton, 1970, pp 3–14.

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132. Lustig LR, Lalwani AK: The history of Ménière’s disease. Clin Otolaryngol Clin North Am 30(6):917–945, 1997. 133. Weir N, Weir S, Stephens D: Who was who and what did they do? A bibliography of contributors of otolaryngology from Great Britain and Ireland. J Laryngol Otol 101:23–87, 1987. 134. Cawthorne TE: The treatment of Ménière’s disease. J Laryngol Otol 58:363–371, 1943. 135. Milligan W. Ménière’s disease, a clinical and experimental inquiry. J Laryngol Rhinol Otol 19:440, 1904. 136. Jackler RK, Whinney D: A century of eighth nerve surgery. Otol Neurotol 22:401–416, 2001. 137. Portmann M: Historical vignette: Prof Maurice Sourdille. Arch Otolaryngol 84:128–132, 1966. 138. Shambaugh GE: Julius Lempert and the fenestration operation. Am J Otol 16:247–252, 1955. 139. Glasscock ME. The history of neuro-otology; A personal perspective. Otolaryngol Clin North Am 35:227–238, 2002. 140. Cawthorne T: Julius Lempert: A personal appreciation. Arch Otolaryngol 90:28–49, 1969. 141. Lempert J: A simple subcortical mastoidectomy. Arch Otolaryngol 7:201–286, 1929. 142. Schuknecht H: To the editor. Am J Otol 15:568–569, 1994. 143. Guild S: A hitherto unrecognized structure: The glomus jugulare in man. Anat Rec 79:28, 1941. 144. Rosenwasser H: Glomus jugulare tumors. I. Historical background. Arch Otolaryngol 88:1–40, 1968. 145. Karas DE, Kwartler JA: Glomus tumors: A fifty-year historical perspective. Am J Otol 14:495–500, 1993. 146. Brown LA: Glomus jugulare tumors of the middle ear: Clinical aspects. Laryngoscope 63:281–292, 1953. 147. Derlacki EL, House HP, Shea JJ Jr: George E. Shambaugh, Jr, MD. A pioneer of American otomicrosurgery. Arch Otolaryngol Head Neck Surg 122:596–599, 1996. 148. Mudry A: The History of the Microscope for Use in Ear Surgery. Am J Otol 21:877–886, 2000. 149. Kriss TC, Kriss VM: History of the operating microscope: from magnifying glass to microneurosurgery. Neurosurgery 42: 899–907; discussion 908, 1998. 150. Zöllner F: The principles of plastic surgery of the sound-conducting apparatus. J Laryngol Otol 69:637–652, 1955. 151. Rosen S: Mobilization of the stapes to restore hearing in otosclerosis. New York J Med 53:2650, 1953. 152. Shambaugh GE. the surgical treatment of deafness. Illinois Med J 81:104, 1954. 153. Derlacki EL: Chisel techniques for stapes mobilization. Arch Otolaryngol 71:271, 1960. 154. Heermann H: Mobilisierung des steigbugels durch Ausmeisseln und eiwartzverlagern der fussplatte. Z Laryngol Rhinol Otol Grenzgebiete 35:415, 1956. 155. Shea JJ: Fenestration of the oval window. Ann Otol Rhinol Laryngol 67:932, 1958. 156. Kuhn T: The Structure of Scientific Revolutions. Chicago, University of Chicago Press, 1962.

157. House W: Foreword. In Salvinelli F, De la Cruz A (eds.): Otoneurosurgery and Lateral Skull Base Surgery. Philadelphia, WB Saunders, 1996, pp xiii–xv. 158. Kurze T, Doyle JB: Extradural intracranial (middle fossa) approach to the internal auditory canal. J Neurosurg 19:1033, 1962. 159. House WF: Surgical exposure of the internal auditory canal and its contents through the middle cranial fossa. Laryngoscope 71:1363–1385, 1961. 160. House W: Evolution of the transtemporal bone removal of acoustic tumors. Arch Otolaryngol 80:731–742, 1964. 161. House W: Monograph: Transtemporal bone microsurgical removal of acoustic neuromas. Arch Otolaryngol 80:597–756, 1964. 162. Doyle JH, Doyle JB, Turnball FM: Electrical stimulation of the eighth cranial nerve. Arch Otolaryngol 80:388–391, 1964. 163. Volta A: On the electricity excited by the mere contact of conducting substances of different kinds. Trans Roy Soc Phil 90:403–431, 1800. 164. Neftel WB: Galvano-Therapeutics. New York, Appleton, 1871. 165. Shah SB, Chung JH, Jackler RK: Lodestones, quackery, and science: Electrical stimulation of the ear before cochlear implants. Am J Otol 18:665–670, 1997. 166. Wever EG, Bray CW: The Nature of the Acoustic Response: The Relation Between Sound Frequency and Frequency of Impulses in the Auditory Nerve. J Exp Psychol 13:373–387, 1930. 167. Stevens SS, Jones RC: The mechanism of hearing by electrical stimulation. J Acoust Soc Am 10:261–269, 1939. 168. Simmons B: Electrical stimulation of the auditory nerve in man. Arch Otolaryngol 84:2–54, 1966. 169. Andreef AM, Gersuni GV, Volokhov AA: Electrical stimulation of the hearing organ. J Pysiol USSR 17, 1934. 170. Eisen MGR: Djourno and Eyries and the first stim of the VIIIth nerve. Otol Neurotol, in press. 171. Djourno A, Eyries C: Prothese auditive par excitation electieque a distance du nerf sensoriel a l’aide d’un bobinage inclus a demeure. Presse Med 35:14–17, 1957. 172. Doyle JH, Doyle JB, Turnball FM: Electrical stimulation of the eighth cranial nerve. Arch Otolaryngol 80:388–391, 1964. 173. Simmons FB: Electrical stimulation of acoustic nerve and inferior colliculus: Results in man. Arch Otolaryngol 79:559–567, 1964. 174. Lawrence M: In Merzenich MM, Schinder RK, Sooy FA (eds.): Proceedings of the First International Conference on Electrical Stimulation of the Acoustic Nerve as a Treatment for Profound Sensorineural Deafness in Man. University of California, San Francisco, 1973. 175. Simmons B: In Schindler RA, Merzenich MM (eds.): Cochlear Implants. New York, Raven Press, 1985. 176. Bilger RC, Black FO, Hopkinson NT, Myers EN: Evaluation of subjects presently fitted with implanted auditory prostheses. Ann Otol Rhinol Laryngol (Suppl) 38:3–10, 1977. 177. Marcus RE: History of the American Neurotologic Society. Otolaryngol Head Neck Surg 104:1–4, 1991. 178. Paget S: Sir Victor Horsley. New York, Harcourt, 1920. 179. Shambaugh GE: Surgery of the Ear. Philadelphia, WB Saunders, 1967.

1

Outline Brainstem Topography Generation of Evoked Potentials Information Processing in the Brainstem Cochlear Nuclei Superior Olivary Complex Lemniscal Nuclei

Chapter

The Human Brainstem Auditory System

Inferior Colliculus Descending Pathways Effects of Hearing Loss Conclusions

T

his chapter looks at the human brainstem auditory system from several standpoints relevant for the clinician. First, it examines the unique topography of the human central auditory pathway. Next, it considers how brainstem structures act as generators of evoked auditory potentials, information that may be useful in distinguishing peripheral and central pathology. It then considers the manner in which information from the cochlea is analyzed and altered as it passes through brainstem centers. Finally, it reviews what is currently known about the type and degree of central degenerative change that occurs subsequent to hearing loss.

BRAINSTEM TOPOGRAPHY An overview of the brainstem auditory pathway in longitudinal section, based on serially sectioned human brainstems,1 is presented in Figure 1-1. As shown in this figure, the brainstem auditory pathway begins at the pontomedullary junction, at the point where the cochlear nerve enters the brainstem and terminates in the cochlear nuclei. The cochlear nuclear complex consists of two components, a dorsal nucleus and a ventral nucleus. The dorsal cochlear nucleus is a flattened structure that curves around the inferior cerebellar peduncle on the dorsolateral surface of the brainstem. The ventral nucleus is a compact structure that extends laterally along the caudal edge of the middle cerebellar peduncle. The cochlear nerve enters the center of the ventral cochlear nucleus, and its axons radiate to innervate both the dorsal and ventral nuclei. The pathway carrying most of the ascending auditory information to higher centers originates in the ventral nucleus, and its axons leave the nucleus as the trapezoid body, a broad pathway that crosses the brainstem. Within the brainstem, the superior olivary complex lies a short distance medial and rostral to the cochlear nuclei. The medial olivary

Jean K. Moore, PhD

nucleus is a very prominent laminar nucleus, while the lateral olivary nucleus is a small compact cell group. Periolivary cells ring the medial and lateral nuclei and form a column of cells extending almost a centimeter rostrally through the brainstem. At the point where the pons is no longer covered laterally by the middle cerebellar peduncle, the auditory pathway swings laterally to become a flattened, superficial band of axons, the lateral lemniscus. A few clusters of small cells scattered throughout the lemniscus are vestiges of the lower lemniscal nuclei. The dorsal lemniscal nucleus is a distinct cell group that gives rise to the dorsal commissure of the lateral lemniscus. The lateral lemniscus terminates in the inferior colliculus, a large and irregularly spherical nucleus that is connected to the contralateral colliculus through the collicular commissure. Previous comparisons of the human and cat brainstem1 have shown that their auditory centers are approximately the same size, but because of the overall size of the human brainstem, human auditory centers are strung out along a considerably longer pathway. An accurate measurement of the length of the human brainstem auditory pathway has been obtained from a computer reconstruction based on a series of digitized histologic sections.2 The reconstruction shows that the distance the axon of a neuron in the human ventral cochlear nucleus travels to reach the ipsilateral superior olivary complex is approximately 10 mm; to reach the contralateral superior olivary complex is about 25 mm; to reach the upper level of the contralateral lateral lemniscus is about 40 mm; and to reach the center of the contralateral inferior colliculus is roughly 45 mm. Thus a response in the human brainstem to a transient stimulus will consist of waves of action potentials passing along myelinated axons for a total distance of up to 4.5 cm. In the cat, by comparison, the total distance from the center of the cochlear nuclei to the center of the contralateral inferior colliculus is less than 2 cm. 45

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Figure 1-1. Overview of the brainstem auditory pathway as seen in longitudinal section. Spatial relationships and dimensions are based on reconstructions from serially sectioned human brainstems. Auditory nuclei (solid outlines) are labeled in the lower half of the figure and tracts (dotted outlines) are labeled in the upper half. AS, acoustic stria; BIC, brachium of inferior colliculus; CIC, commissure of inferior colliculus; DCLL, dorsal commissure of lateral lemniscus; DCN, dorsal cochlear nucleus; DNLL, dorsal nucleus of lateral lemniscus; IC, inferior colliculus; LSO, lateral superior olivary nucleus; MCP, middle cerebellar peduncle; MSO, medial superior olivary nucleus; PO periolivary region; TB, trapezoid body; VCN, ventral cochlear nucleus; VNLL, ventral nucleus of lateral lemniscus; VIIIc, cochlear nerve. (Modified from Moore JK: The human auditory brainstem as a generator of auditory evoked potentials. Hear Res 19:33–43, 1987.).

GENERATION OF EVOKED POTENTIALS Evoked auditory brainstem responses (EABR) are generally regarded as reflecting synchronized discharges in groups of axons. However, it is difficult to apply the results of animal investigations when attempting to identify the generators of potentials evoked from the human brainstem because the human cochlear nerve and brainstem pathways are much longer than those in other species. More relevant information can be obtained from studies done in human subjects. In contrast to lower mammals, in which only a single wave is generated by the cochlear nerve, there is evidence that the human cochlear nerve generates the two earliest potentials of the EABR, waves I and II. Intrasurgical recordings, made with a wire electrode placed directly on the auditory nerve,3,4 concluded that wave I is generated within the cochlea, presumably by activation of the peripheral nerve processes contacting cochlear hair cells. Wave II was localized to the cochlear nerve at the level of the internal auditory meatus. Similarly, dipole localization studies5 concluded that wave II is generated as the wave of action potentials following a click stimulus crosses the conduction boundary between the temporal bone and the intradural space. This interpretation is supported by clinical findings in a case of Gaucher’s disease with marked brainstem gliosis,6 in which EABR

waves I and II were present but all subsequent waves were absent. When intrasurgical recordings were made directly from the surface of the human brainstem,3,7 they indicated that waves III, IV, and V are generated by brainstem structures. A wave coinciding with scalp-recorded wave III was seen when electrodes were placed over the cochlear nuclei. Both these recordings and human dipole studies5 concluded that wave III is generated by a volley of action potentials in axons emerging from the cochlear nuclei in the trapezoid body. Similar conclusions have been reached on the basis of tumors or demyelinating lesions in the lower pons that affect or eliminate wave III.8 Because they occur later, waves IV and V presumably reflect activity at a higher brainstem level. This assumption is confirmed by intrasurgical electrodes placed on the dorsal surface of the pons that recorded potentials corresponding to scalp-recorded waves IV and V.7 In an attempt to locate the point of generation of these two waves more precisely, the length of the human brainstem pathway was correlated with the latencies of waves IV and V to derive axonal conduction velocity.2 The most reasonable conduction velocity, one closely matching the known conduction velocity of eighth nerve axons, was obtained by assuming that waves IV and V were generated at the level of the superior olivary complex contralateral to the stimulated ear, presumably by the bend in the axonal pathway occurring at that point (see Fig. 1-1). The idea that waves IV and V are generated at the level of the olivary complex, rather than higher in the brainstem, is supported by the fact that both waves are intact after destructive lesions of the inferior colliculus.9,10 The brainstem auditory system is known to consist of separate pathways running in parallel.11 On the one hand, many axons leave the cochlear nuclei and run without interruption to the contralateral inferior colliculus.12 As they traverse the trapezoid body and lateral lemniscus, these axons do not encounter any synaptic junction. Alternatively, some pathways to the inferior colliculus synapse in the intermediate brainstem nuclei, such as the medial and lateral olivary nuclei and the periolivary cell groups.12 It has been suggested that the closely spaced waves IV and V reflect activity in parallel asynaptic and monosynaptic pathways. Passing though a single synaptic junction would delay the wave of action potentials by approximately 0.7 msec, which is, in fact, the interval separating waves IV and V. Additional support for the idea that waves IV and V are generated by parallel pathways comes from EABRs recorded during placement of an auditory brainstem implant device on the cochlear nuclei.13 Because tumor removal interrupts the continuity of the eighth nerve, the peripheral generators of the EABR are missing and the electrical stimulus acts directly on cochlear nucleus neurons. This direct activation of axons leaving the cochlear nuclei bypasses cochlear mechanics, the synapses at the level of the hair cells, and the synapses in the cochlear nuclei, all of which normally precede wave III. In these recordings, peaks are recognizable that correspond in time to waves III, IV, and V of the acoustically evoked ABR. When the stimulus rate is increased from 100/sec to 200/sec, the peak corresponding to wave IV is unaffected, but the peak corresponding to wave

The Human Brainstem Auditory System

V shows rapid attenuation. This implies that the two peaks are generated by different pathways, rather than by sequential structures in a single pathway, and that wave V is rate-sensitive because its generator contains a synaptic junction.

INFORMATION PROCESSING IN THE BRAINSTEM Cochlear Nuclei The activity of the cochlea is carried as a single representation in the auditory nerve. Upon entering the nerve root in the center of the ventral cochlear nucleus, its axons bifurcate to form ascending and descending branches. In humans, as in other species, fascicles of ascending branches of the cochlear nerve fill the anterior half of the ventral nucleus, and similar fascicles of descending branches penetrate the posterior part of the nucleus and then continue into the dorsal nucleus.14 The ventral nucleus is very densely innervated, but in the dorsal nucleus synaptic terminals are much more sparsely scattered. The tonotopic sequence of axons in the auditory nerve identified in the monkey15 is identical to that of other mammalian species, with high-frequency information carried by fibers bifurcating in the tip of the nerve root, and an orderly sequence of progressively lower frequencies extending down to axons bifurcating at the base of the nerve root. Frequency information should therefore be represented in the human ventral cochlear nucleus as stacked sheets of eighth nerve axons, with the highest frequency input in the most dorsal sheets and lowest frequency input in the most ventral. In the human dorsal cochlear nucleus, changes in the cytoarchitecture have altered the direction of axons such that the cochleotopic planes run parallel to the surface of the nucleus.14 Neurons in the cochlear nuclei do not simply relay pitch information to higher auditory centers. Instead, the nuclei are a point of transformation of the pattern of activity carried in the auditory nerve. Each individual auditory nerve axon, as it runs through the nuclei, passes through areas of different cell types.1,14 Distinct types of synapses are formed on each class of neuron, with the synapses varying from expanded calyces surrounding the cell body to scattered small boutons located mainly on dendrites.16 As a result, the transformation of impulses across the synapse results in a distinctive pattern of activity in each postsynaptic cell group. An additional factor in the transformation of the pattern of information originally carried by the cochlear nerve is the presence of many synaptic terminals containing the inhibitory transmitters γ-aminobutyric acid (GABA) and glycine. Several types of inhibitory systems have been described in nonprimate mammals, but two systems are particularly well developed in the baboon17 and, by analogy, in humans. The first system is a very precise, tonotopically specific system projecting from the dorsal nucleus to the ventral nucleus. The origin of this system is a population of glycine- and GABA-positive cells in the central dorsal cochlear nucleus that are characterized by dendritic arbors flattened in the isofrequency planes of the nucleus. Their

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axons form tightly bundled fascicles penetrating the central area of the ventral nucleus. Studies in mouse slice preparations have shown that these dorsal nucleus cells project to bands of neurons in the ventral nucleus that are innervated by the same subset of auditory nerve axons.18 Thus, this system appears to provide extremely frequency-specific inhibition with one synaptic delay to neurons in the ventral nucleus. The point-to-point nature of these dorsal-to-ventral nucleus connections stands in contrast to a much more widespread projection pattern of commissural axons. The commissural projection arises from relatively large glycinepositive cells scattered throughout the cochlear nuclei. Their large-diameter axons come together to form a distinct bundle, the commissural stria, and form a plexus of axons in the contralateral nuclei.19 Within the contralateral cochlear complex, commissural axons branch widely and distribute their inhibitory terminal very broadly.20 This glycine-positive commissural projection is undoubtedly responsible for the short-latency crossed inhibition shown in recordings in the cat21 and presumably plays a role in the balance of level of activity of the cochlear nuclei on the two sides of the brainstem. It is apparent that by the time auditory information has passed through its first central synapse in the cochlear nuclei, it has been acted on by modulatory influences. First, a recoding of the pattern of activity in the auditory nerve occurs during the interaction of the presynaptic axons and the postsynaptic neuron. Second, there is an interplay of that excitatory activity with intrinsic inhibitory systems. These factors combine to ensure that a unique pattern of activity is carried in each of the pathways leaving the cochlear nuclei.

Superior Olivary Complex One basis for complexity in brainstem information processing is the fact that the cochlea, unlike the retina or body surface, does not directly encode the spatial locus of a stimulus. Instead, the spatial dimension of a sound stimulus must be recreated by the central auditory system. Behavioral studies in cats have implicated the superior olivary complex in this process. Animals with lesions at or above the level of the superior olivary complex are unable to locate a sound source in the spatial field contralateral to the lesion, while lesions below the level of the olivary complex cause more diffuse deficits.22 A very similar deficit has been seen in a human subject with an extensive midline pontine lesion that eliminated crossed input to the superior olivary complex on both sides.23 The subject could detect frequency and amplitude modulation and had no general deficit in detection of auditory temporal information, but was unable to determine, by sound alone, the location and direction of motion of objects in the environment, such as ringing telephones and passing trains. Collectively, these findings imply that the central representation of auditory space is first organized at the level of the superior olivary complex and that the process of organization occurs similarly in humans and other mammals. Physiologic studies carried out in animals have long indicated that time and intensity cues to spatial location are analyzed separately in the superior olivary complex,

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and dipole studies carried out in human subjects24 suggest that the same is true in humans. The human dipole studies involved recordings of the binaural interaction component of the EABR, which is obtained by subtracting the response to a binaural stimulus from the algebraic sum of the right and left ear monaural responses to the same stimulus. The reduction in total activity in the binaural response is presumed to reflect the fact that the binaural response involves convergence of activity from the right and left ears on some subset of brainstem auditory neurons that process information from both ears. When the binaural interaction component was determined for a variety of interaural time and intensity differences, the dipoles for interaural time versus intensity differences had slightly different locations in the brainstem, suggesting that time and intensity cues are processed by two separate structures. The system that uses interaural time differences has long been believed to be the medial olivary nucleus. This nucleus is a laminar structure, with long primary dendrites extending medially and laterally from a central column of cell bodies. The laterally directed dendrites are innervated by the ventral cochlear nucleus on the same side of the brainstem, and the medially directed dendrites are innervated by the nucleus on the contralateral side.12 Thus, each neuron receives frequency-matched input from both ears. The discharge rate of cells in the medial nucleus is influenced by interaural time differences, including phase disparities, and shows phase-locking to both monaural and binaural stimuli.25,26 These response properties allow the neurons to create a map of interaural time differences along the rostrocaudal axis of the nucleus. Because time disparities are most useful for low-frequency sound, and phase cues are unambiguous only below 1500 Hz, the medial nucleus is biased toward low-frequency information, with most of its neurons having best frequencies of less than 3 to 4 kHz.27 Given that the human range of audible frequencies is quite low by general mammalian standards, it is not surprising that the human medial olivary nucleus is twice as large as that of the cat and several times larger than those of most other species.28 Because large head size increases the range of frequencies that can be used for interaural phase difference cues, both human head size and low-frequency hearing range may account for the prominence of the medial olivary nucleus in our binaural hearing system. Stimulus intensity cues are generally believed to be processed by the lateral olivary nucleus. Single unit recordings have shown that lateral nucleus neurons respond to interaural intensity differences and also to monaural amplitude fluctuations.29,30 Because intensity cues can be used across a broad range of frequencies, the mammalian lateral olivary nucleus has an orderly representation of best frequencies spanning the entire audible range.27 The nucleus is large in carnivores that are sensitive to frequencies from 20 Hz to 40 kHz and is extremely large in echolocating species, such as bats and porpoises, whose range extends above 100 kHz.28 Possibly because our range of usable frequencies is restricted to those at the low end of the mammalian spectrum, the human lateral nucleus is a relatively small nucleus, much smaller than that of the cat and similar in absolute size to the nucleus in rodents and insectivores.28

The medial and lateral olivary nuclei are surrounded by a separate component of the olivary complex, the periolivary region. Human periolivary cells are roughly grouped into medial, lateral, and dorsal periolivary nuclei. A unique feature of the human periolivary system is a rostral column of cells that extends up to 8 to 10 mm through the pons. Periolivary neurons are a heterogeneous population that forms ascending and descending projections to a number of diverse targets. The hypertrophied rostral cell group is composed of a type of periolivary neuron that, in the cat, forms a projection to the inferior colliculus31 and thus may represent the main ascending pathway from the periolivary region to the midbrain. Other periolivary neurons form descending pathways and are discussed in the section on the descending auditory system.

Lemniscal Nuclei In most species, the lower part of the lemniscus contains two sizable nuclei, the ventral and intermediate lemniscal nuclei. These nuclei are prominent in the cat and are extremely large in echolocators such as the porpoise and bat, suggesting that they are related to some aspect of high-frequency acoustic processing. In humans, these nuclei are represented only by cell clusters scattered along the course of the lateral lemniscus.1 Thus the comparative development of the lower lemniscal nuclei across mammals suggests that their reduction in the human brainstem, like that of the lateral olivary nucleus, is related to our comparatively low-frequency range of hearing. In contrast, the dorsal lemniscal nucleus is a prominent cell group, very similar in size and morphology to the corresponding nucleus in the cat.1 In mammals, afferent input to the dorsal nucleus comes mainly from the medial and lateral superior olivary nuclei,32 meaning that its input is related primarily to spatial localization. The dorsal nucleus projects directly to the adjacent inferior colliculus and through its commissure to the dorsal lemniscal nucleus and inferior colliculus on the opposite side.33 Because the dorsal nucleus consists mainly of neurons that use GABA as a neurotransmitter,34 this symmetrical and reciprocal projection is inhibitory and must influence the level of activity in the inferior colliculus bilaterally. It is likely that the dorsal lemniscal nucleus plays a role in the balance of ipsilateral and contralateral activity related to spatial mapping in the inferior colliculus.

Inferior Colliculus Essentially all the axons in the lateral lemniscus terminate in the inferior colliculus, with greatest density in its central nucleus. Thus the central nucleus receives overlapping input from the dorsal and ventral cochlear nuclei, the medial and lateral olivary nuclei, periolivary cell groups, and the lemniscal nuclei, particularly the dorsal lemniscal nucleus. The overlap of the ascending projections to the central nucleus does not occur in a random manner, but rather in an organized fashion related to the laminar organization of the nucleus. As axons enter the central nucleus, they form bands running from ventrolateral to dorsomedial. These axonal bands run parallel to cellular planes formed by neurons with flattened, disc-shaped dendritic fields, producing

The Human Brainstem Auditory System

a laminar architecture of alternating bands of axons and flattened cells. Studies of evoked activity and 2-deoxyglucose labeling in primates have shown that the laminae represent frequency-specific planes of the central nucleus.35,36 The tonotopic planes are curved and tipped at about 20 to 30 degrees from the horizontal, with a regular progression of best frequencies from low dorsally to high ventrally. Some projections, such as those from the ventral cochlear nucleus and the lateral olivary nucleus, span the entire tonotopic spectrum, while the medial olivary nucleus is a major source of afferents to the low-frequency region of the central nucleus. Tonotopy is not the only organizing principle within the inferior colliculus. Recordings in the cat show that neurons in the central nucleus respond to simulations of natural combinations of interaural time and intensity differences and to spectral cues indicating location of a sound source.37 Most cells are sensitive to stimulus location along the horizontal azimuth, and about half of the neurons tested are sensitive to elevation. This suggests that at the level of the colliculus, pathways representing spatial localization, that is, those from the medial and lateral olivary nuclei and dorsal lemniscal nucleus, are integrated into a single spatial map. Overall, it seems safe to assume that multiple parameters of auditory stimuli, including frequency spectrum, loudness, time patterning, and spatial location, are correlated within the central nucleus to produce an integrated neural representation of the stimulus. Information from the central nucleus of the colliculus is passed on to the forebrain by axons that form the brachium of the inferior colliculus. Brachial axons continue forward on the surface of the brainstem, lateral to the superior colliculus, to reach the medial geniculate complex of the thalamus. This ascending pathway from the inferior colliculus is the route for essentially all information ultimately reaching the thalamic and cortical levels. However, the inferior colliculus is also the source of descending auditory pathways, which are discussed in the following section. One descending projection ultimately reaches the acousticomotor centers involved in head and eye orientation to sound. A second descending system is the purely auditory pathway to lower brainstem auditory centers and, through the olivocochlear projection, to the cochlea itself. In sum, it appears that the inferior colliculus is a point of convergence for a series of parallel brainstem pathways, but also a point of divergence from which integrated auditory information is sent up to auditory cortex, back down the brainstem through feedback pathways, and to centers concerned with motor responses to sound stimuli.

Descending Pathways The central nucleus of the inferior colliculus is surrounded by a relatively large pericentral zone. The rostral half of this zone is notable for being an area of multisensory convergence. This region has been called the external cortex and is also termed the intercollicular area because it forms a bridge, anatomically and functionally, between the inferior and superior colliculi. In addition to auditory input from the central nucleus of the colliculus, it receives visual input via the optic tract38 and somatosensory input from the spinal trigeminal nucleus and the dorsal column

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nuclei.39 Electrophysiologic studies of the external cortex show that many cells are influenced by both auditory and somatosensory stimuli, and most have relatively nonspecific response fields, reflecting broad frequency ranges and large areas of the body.40 An organized map of auditory space has been demonstrated in this region,41 and behavioral studies have shown that lesions here cause deficits in the ability to orient to sound.22 Neurons in the intercollicular area project to the deep layers of the superior colliculus, where the auditory map is aligned with the map of visual space. In turn, output from the multimodal neurons in the deep layers of the superior colliculus plays a major role in control of the motor nuclei for head and eye turning. Thus the external cortex of the inferior colliculus is the beginning of a process of integration of auditory input with visual and somatosensory information, leading to creation of a multisensory spatial map and, ultimately, direction of head and eye position by that map. The caudal half of the pericentral region of the inferior colliculus is often called the dorsal cortex because it is a multilayered structure, with neurons segregated into several layers and cells becoming progressively larger in the deeper layers. This area is a way station for relaying cortical influence to the brainstem. Many of the axons descending from cortex bypass the thalamus and travel to the inferior colliculus, where they end in the dorsal cortex.42,43 Efferent axons from the dorsal cortex project down to the level of the superior olivary complex, where they terminate exclusively in the periolivary region.44 The periolivary cells that receive these projections form the olivocochlear pathway that travels in the vestibular nerve to reach the cochlea. Recent work has provided a clearer picture of the human olivocochlear system. Immunostaining for choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine, has been used to identify olivocochlear neurons in the human brainstem45 and efferent terminals on hair cells in the human cochlea.46 In addition, immunostaining has made it possible to identify two subdivisions of the human efferent system. One division, the medial olivocochlear system, is known to form synaptic terminals contacting outer hair cells, and occasionally, their afferent fibers. This subsystem appears as a population of large multipolar cells, scattered throughout the periolivary region, that are immunopositive only for ChAT. The other subdivision, the lateral olivocochlear system, forms synaptic terminals contacting afferent fibers from inner hair cells and, in some cases, inner hair cell somata. These are predominantly small oval cells, located in or near the lateral olivary nucleus. They colocalize a variety of neuropeptides with the cholinergic enzymes and can be visualized by their reactivity for both ChAT and calcitonin gene-related peptide (CGRP). The most significant difference between the human olivocochlear system and that of other mammalian species is the relative size of the two subdivisions. In mammals generally, the lateral efferent component is consistently the largest portion of the olivocochlear system, making up approximately 75% of the system in the cat and monkey, 85% to 90% in rodents, and 90% to 100% in bats. In contrast, the human lateral olivocochlear system makes up at most one-third to one-half of the total number of efferent axons. Despite anatomic differences, the behavioral influence of the human olivocochlear system

50

ANATOMY, PHYSIOLOGY, AND PATHOLOGY

can be demonstrated in subjects in whom vestibular neurectomy has disrupted the efferent projection to the cochlea. These subjects have no detectable change in hearing in quiet surroundings, but in the presence of noise, there is increased subjective loudness and worsened intensity discrimination in the deafferented ear.47

EFFECTS OF HEARING LOSS Prosthetic stimulation, provided at the level of the ear, the cochlea, or the brainstem, requires some structural foundation in the central auditory system to process the input. Thus one question to be considered is the possibility of degenerative change in brainstem auditory centers subsequent to hearing loss. Some insight into this question can be obtained from investigations of changes in the human brainstem subsequent to adult-onset, bilateral profound hearing loss.48,49 The subjects of these investigations were temporal bone/brainstem donors with well-documented clinical histories, including cause of deafness, age of onset, duration of deafness, and hearing assessments. Postmortem examination of the temporal bones provided histopathologic evaluation and counts of the number of surviving cochlear ganglion cells. In the brainstems of these profoundly deaf subjects, neuronal size was measured by digitizing the cross-sectional area of cells in the cochlear nuclei, superior olivary complex, and inferior colliculus. A reduction in neuronal size was observed in all of the subjects. The change was primarily a reduction in the volume of cell cytoplasm, with little change in size of the cell nucleus, and it was accompanied by marked reduction in cell staining. Because protein production occurs in the cytoplasmic compartment of cells, smaller size reflects a lesser volume of the subcellular machinery needed to support this activity. Reduction in stainable cytoplasmic Nissl substance (rough endoplasmic reticulum, RNA) also reflects lower levels of protein synthetic activity. One consistent observation was that, in any given subject, all of the auditory centers were affected equally, that is, the same degree of size reduction and pallor was seen in neurons of the cochlear nucleus, which are directly innervated by the cochlear nerve, and in the higher brainstem nuclei. This indicates that the factors that produce cellular degeneration in the central nervous system operate across several synaptic levels of the central pathway. The size of central auditory neurons in these profoundly deaf subjects varied from near normal to only 50% of normal, despite the fact that all of the subjects ultimately experienced the same degree of hearing loss. One potential factor in the differential central degeneration appeared to be duration of deafness. Not surprisingly, the best preservation of central neurons was seen in a case in which onset was sudden and the duration of deafness was only 1 year. The excellent survival of central auditory neurons in this case could be explained by the fact that this subject had maintained a near normal population of ganglion cells, since cochlear nerve axons are generally believed to have a tonic effect on the central auditory system. Degenerative change was consistently greater in the subjects who had died 7 to 30 years after the onset of deafness and whose populations of cochlear ganglion cells were reduced to less

than one-third of normal. However, there are indications that ganglion cell survival is not the only factor in central neuronal survival, and that causal factors play a prominent role in determining the degree of central degenerative change. On the one hand, excellent preservation of central neurons was seen in a patient with neurofibromatosis type 2, in whom tumor removal 7 and 10 years prior to death had disrupted the eighth nerves, thus reducing the population of cochlear ganglion cells acting on the brainstem to effectively zero. In addition, among the subjects with reduced populations of ganglion cells, neuronal degenerative change was significantly greater in those with deafness due to bacterial meningitis or adult-onset cochleosaccular degeneration (Scheibe’s degeneration). Additionally, there was some evidence for a direct effect of genetic mutation on the central nervous system, as one subject with Scheibe’s degeneration showed changes in other eighth nerve-related brainstem nuclei.50

CONCLUSIONS Information from the ear undergoes significant reorganization as it passes through the brainstem, with an interplay of excitation and inhibition, and changing patterns of activity in successive populations of neurons. The present protocol for placement of the auditory brainstem implant adjacent to cochlear nuclei takes advantage of the ability of brainstem centers to process and modify the artificial electrical stimuli. If it becomes technically feasible to implant electrode arrays higher in the auditory pathway, consideration will have to be given to the issue of sacrificing the brainstem’s contribution to stimulus resolution and perception. However, it is also true that much of the complexity of stimulus processing in the brainstem relates to recreation of the auditory spatial field, a factor that will not be significant in use of a central prosthetic device. Thus, at the present time, optimal device placement is still an open question. It is clear that profound deafness ultimately causes degenerative changes within the auditory pathway, but these changes did not appear to occur immediately after hearing loss and complete loss of central neurons was never observed. The pronounced central degeneration in subjects with genetically and meningitis-induced deafness suggests that cause of deafness is at least as important as severity and duration of hearing loss. Thus etiology may provide at least a partial explanation of differences in performance among those who have suffered hearing loss. The fact that profound loss of auditory input over decades did not appear to cause complete degeneration of the central auditory structures gives reason for optimism and allows for an expectation that even the most severely affected cases will maintain a population of neurons potentially responsive to stimulation from a prosthetic device.

REFERENCES 1. Moore JK: The human auditory brainstem: A comparative view. Hear Res 29:1–32, 1987. 2. Moore JK, Ponton CW, Eggermont JJ, et al: Perinatal maturation of the ABR: Changes in path length and conduction velocity. Ear Hear 17:411–418, 1996.

The Human Brainstem Auditory System

3. Moller AR, Janetta PJ: Auditory evoked potentials recorded intracranially from the brainstem in man. Exp Neurol 78:144–157, 1982. 4. Martin WH, Pratt H, Schwegler JW: The origin of the human auditory brain-stem response wave II. Electroencephalogr Clin Neurophysiol 96:357–370, 1995. 5. Scherg M, von Cramon D: A new interpretation of the generators of BAEP waves I-V: Results of spatio-temporal dipole modeling. Electroencephalogr Clin Neurophysiol 62:290–299, 1985. 6. Kaga K, Ono M, Yokomaru K, et al: Brainstem pathology of infantile Gaucher’s disease with only wave I and II of auditory brainstem response. J Laryngol Otol 112:1069–1073, 1998. 7. Hashimoto I, Ishiyama Y, Yoshimoto T: Brainstem auditory evoked potentials recorded directly from human brainstem and thalamus. Brain 104:841–859, 1981. 8. Levine RA, Gardner JC, Fullerton BC, et al: Effects of multiple sclerosis brainstem lesions on sound lateralization and brainstem auditory evoked potentials. Hear Res 68:73–88, 1993. 9. Durrant JD, Martin WH, Hirsch B, Schwegler J: 3CLT ABR analyses in a human subject with unilateral extirpation of the inferior colliculus. Hear Res 72:99–107, 1994. 10. Vitte E, Tankere F, Bernat I, et al: Midbrain deafness with normal brainstem auditory evoked potentials. Neurology 58:970–973, 2002. 11. Ponton CW, Moore JK, Eggermont JJ: Auditory brain stem response generation by parallel pathways: Differential maturation of axonal conduction time and synaptic transmission. Ear Hear 17:402–410, 1996. 12. Strominger NL, Nelson LR, Dougherty WJ: Second order auditory pathways in the chimpanzee. J Comp Neurol 15:349–365, 1977. 13. Waring MD: Refractory properties of auditory brain-stem responses evoked by electrical stimulation of human cochlear nucleus: evidence of neural generators. Electroencephalogr Clin Neurophysiol 108:331–344, 1998. 14. Moore JK, Osen KK: The cochlear nuclei in man. Am J Anat 154:393–418, 1979. 15. Moskowitz N, Liu J-C: Central projections of the spiral ganglion of the squirrel monkey. J Comp Neurol 144:335–344, 1972. 16. Adams JC: Neuronal morphology in the human cochlear nucleus. Arch Otolaryngol Head Nech Surg 112:1253–1261, 1986. 17. Moore JK, Osen KK, Storm-Mathisen J, Ottersen OP: GABA and glycine in the baboon cochlear nuclei: An immunocytochemical colocalization study with reference to interspecies variation in inhibitory systems. J Comp Neurol 369:497–519, 1996. 18. Wickesberg RE, Oertel D: Tonotopic projection from the dorsal to the anteroventral cochlear nucleus of mice. J Comp Neurol 268:389–399, 1988. 19. Wenthold RJ: Evidence for a glycinergic pathway connecting the two cochlear nuclei: An immunocytochemical and retrograde transport study. Brain Res 415:183–187, 1987. 20. Cant NB, Gaston KC: Pathways connecting the right and left cochlear nuclei. J Comp Neurol 212:313–326, 1982. 21. Mast TE: Binaural interaction and contralateral inhibition in dorsal cochlear nucleus of the chinchilla. J Neurophysiol 33:108–115, 1970. 22. Thompson GC, Masterton RB: Brainstem auditory pathways involved in reflexive head orientation to sound. J Neurophysiol 541:1183–1202, 1978. 23. Griffiths TD, Bates D, Rees A, et al: Sound movement detection deficit due to a brainstem lesion. J Neurol Neurosurg Psychiatry 62:522–526, 1997. 24. Pratt H, Polyakov A, Kontorovich L: Evidence for separate processing in the human brainstem of interaural intensity and temporal disparities for sound lateralization. Hear Res 108:1–8, 1997. 25. Yin TCT, Chan JC: Interaural time sensitivity in medial superior olive of cat. J Neurophysiol 645:465–488, 1990. 26. Spitzer MW, Semple MN: Neurons sensitive to interaural phase disparity in gerbil superior olive: Diverse monaural and temporal response properties. J Neurophysiol 73:1668–1690, 1995.

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27. Guinan JJ Jr, Norris BE, Guinan SS: Single auditory units in the superior olivary complex. II. Location of unit categories and tonotopic organization. Int J Neurosci 4:147–166, 1972. 28. Moore JK: Organization of the human superior olivary complex. Microsc Res Tech 51:403–412, 2000. 29. Caird D, Klinke R: Processing of binaural stimuli by cat superior olivary complex neurons. Exp Brain Res 52:385–399, 1983. 30. Joris PX, Yin TC: Envelope coding in the lateral superior olive. III. Comparison with afferent pathways. J Neurophysiol 79:253–269, 1998. 31. Adams JC: Cytology of periolivary cells and the organization of their projections in the cat. J Comp Neurol 10:275–289, 1983. 32. Glendenning KK, Brunso-Bechtold JK, Thompson GC, Masterton RB: Ascending auditory afferents to the nuclei of the lateral lemniscus. J Comp Neurol 197:673–703, 1981. 33. Kudo M: Projections of the nuclei of the lateral lemniscus in the cat: An autoradiographic study. Brain Res 221:57–69, 1981. 34. Saint Marie RL, Shneiderman A, Stanforth DA: Patterns of gammaaminobutyric acid and glycine immunoreactivities reflect structural and functional differences of the cat lateral lemniscal nuclei. J Comp Neurol 389:264–276, 1997. 35. FitzPatrick KA: Cellular architecture and topographic organization of the inferior colliculus of the squirrel monkey. J Comp Neurol 164:185–207, 1975. 36. Webster WR, Servière J, Crewther D, Crewther S: Iso-frequency 2DG contours in the inferior colliculus of the awake monkey. Exp Brain Res 56:425–437, 1984. 37. Delgutte B, Joris PX, Litovsky RY, Yin TC: Receptive fields and binaural interactions for virtual-space stimuli in the cat inferior colliculus. J Neurophysiol 81:2833–2851, 1999. 38. Itaya SK, Van Hoesen GW: Retinal innervation of the inferior colliculus in rat and monkey. Brain Res 233:45–52, 1982. 39. Wiberg M, Westman J, Blomqvist A: Somatosensory projection to the mesencephalon: An anatomical study in the monkey. J Comp Neurol 264:92–117, 1987. 40. Aitkin LM, Kenyon CE, Philpott P: The representation of the auditory and somatosensory systems in the external nucleus of the cat inferior colliculus. J Comp Neurol 196:25–40, 1981. 41. Binns KE, Grant S, Withington DJ, Keating MJ: A topographic representation of auditory space in the external nucleus of the inferior colliculus of the guinea pig. Brain Res 589:321–342, 1992. 42. Fitzpatrick KA, Imig TJ: Projections of auditory cortex upon the thalamus and midbrain in the owl monkey. J Comp Neurol 177:537–555, 1978. 43. Luethke LE, Krubitzer LA, Kaas JH: Connections of primary auditory cortex in the New World monkey, Saguinus. J Comp Neurol 285:487–513, 1989. 44. Moore RY, Goldberg JM: Projections of the inferior colliculus in the monkey. Exp Neurol 14:429–438, 1966. 45. Moore JK, Simmons DD, Guan Y-L: The human olivocochlear system: Organization and development. Audiol Neurootol 4:311–325, 1999. 46. Schrott-Fischer AL, Egg G, Kong W-J, Renard N, Eybalin M: Immunocytochemical detection of choline acetyltransferase in the human organ of Corti. Hear Res 78:149–157, 1994. 47. Zeng F-G, Martino KM, Linthicum FH, Soli SD: Auditory perception in vestibular neurectomy subjects. Hear Res 142:102–112, 2000. 48. Moore JK, Niparko JK, Miller MR, Linthicum FH Jr: Effect of profound hearing loss on a central auditory nucleus. Am J Otol 15:588–595, 1994. 49. Moore JK, Niparko JK, Perazzo LM, et al: Effect of adult-onset deafness on the human central auditory system. Ann Otol Rhinol Laryngol 106:385–390, 1997. 50. Lalwani AK, Linthicum FH, Wilcox ER, et al: A five-generation family with late-onset progressive hereditary hearing impairment due to cochleosaccular degeneration. Audiol Neurootol 2:139–154, 1997.

Chapter

2 Aage R. Møller, PhD

Physiology of the Ear and the Auditory Nervous System Outline Introduction The Ear Sound Conduction to the Cochlea Frequency Analysis in the Auditory System The Cochlea as a Frequency Analyzer Representation of Frequency in the Auditory Nerve Basis for Frequency Discrimination in the Auditory System: Temporal or Place Representation? The Auditory Nervous System

INTRODUCTION Many of the disorders confronting the neurotologist are related to the auditory nervous system. Therefore, neurotologists need to comprehend the physiologic processes that occur in the ear as well as those arising from the auditory nervous system. Initially, understanding of the processing that occurs in the ear and the auditory nervous system was mainly limited to academic interest. Now the development of cochlear and brainstem implants has made understanding of the function of the processing that occurs in the ear and the auditory nervous system of direct clinical importance. Therefore the function of both the ear and the central auditory system will be covered here. The representation of the frequency of sounds in the auditory nervous system is of particular importance and it is discussed separately in this chapter. The physiologic processes involved in coding and transformation of complex sounds are important because most natural sounds not only have a broad spectrum but a more or less rapidly varying frequency or spectral composition. The intensity of natural sounds such as speech sounds also varies more or less rapidly. Having an understanding of how sounds such as pure tones are processed by the auditory system is not sufficient to understanding how complex sounds such as speech sounds are processed by the ear and the various nuclei of the auditory system. During recent years much information has been gained about processing in more central parts of the auditory system, and the importance of parallel processing and stream segregation has become evident. It has also become evident that neural plasticity is important for the functioning of the auditory 52

Classical Ascending Auditory Pathways Cochlear Nucleus Superior Olivary Complex and Binaural Hearing Inferior Colliculus Medial Geniculate Body Auditory Cortex Nonclassical Ascending Pathways Efferent System Olivocochlear Bundle Centrifugal Pathways to the Cochlear Nucleus and Higher Centers Neural Plasticity

Higher-Order Processing Parallel Processing and Stream Segregation Connections to Other Nonauditory Parts of the Brain Evoked Potentials Generated by the Ear and the Auditory Nervous System The Ear Electrocochleographic Potentials Evoked Potentials from the Auditory Nervous System Brainstem Auditory Evoked Potentials Acoustic Middle Ear Reflex

system. Understanding the role of the nonclassical auditory pathways has progressed over the years, and the importance of connections from the auditory pathways to nonauditory parts of the brain have been explored. Studies in animals that have provided important information about the way the auditory nervous system codes and transforms complex sounds will also be discussed in this chapter. Current knowledge about the function of the auditory nervous system is based primarily on recordings made from single nerve fibers and cells in animals. Because it is not technically feasible to record from single nerve cells or nerve fibers in the human auditory system, it is important to know how results obtained from animal experiments can be applied to understanding the human auditory system. Recording of evoked potentials, either from electrodes placed on the scalp or from electrodes placed intracranially in patients undergoing neurosurgical operations, has been the most common method of studying the physiology of the human auditory system. Such studies have contributed to understanding the pathophysiology of disorders that affect the ear and the auditory nervous system. Auditory evoked potentials are used in the diagnosis of pathologies of the human ear and auditory nervous system and also in intraoperative monitoring. Interpretation of evoked potential tests such as brainstem auditory evoked potentials (BAEP, also known as AEP or ABR) requires neurotologists to understand how neural activity in the auditory nerve and auditory nuclei and fiber tracts is reflected in the BAEP, as well as how changes in function are reflected in these potentials and what those changes mean in terms of pathologic processes. In many applications of the BAEP, it is important to know the neural generators

Physiology of the Ear and the Auditory Nervous System

of the different components of these potentials. This chapter describes the generation of sound-evoked electrical activity in the ear, the auditory nerve, and the various auditory nuclei of the ascending auditory pathway. The transformation of these near-field potentials into far-field potentials that can be recorded from electrodes placed on the scalp is also discussed. The neural generators of the BAEP are described on the basis of auditory evoked potentials that were recorded from humans. Auditory evoked potentials recorded from animals are different from those recorded from humans because of anatomic differences. The neural generators of the human BAEP can therefore not be directly deduced from studies of animals. More recently, magnetoencephalography (magnetic evoked potentials, MEP), a measure of the magnetic field that is created by electrical currents in the central nervous system (CNS), has come into use for studies of the response to sensory simulation. Functional imaging methods such as functional MRI (fMRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) are other means of detecting activation of neural structures due to sound stimulation for research purposes and are beginning to find clinical applications. These methods all measure small changes in blood flow and the use of such methods are based on the assumption that increased neural activity is associated with increased blood flow. However, this assumption has been challenged. This chapter describes the basic functions of the ear and the auditory nervous system. The role of the cochlea as a frequency analyzer and the representation of frequency in the nervous systems are discussed, followed by a discussion of neural processing of complex sounds. Contemporary knowledge and understanding of higher-order processing in the auditory nervous system is described as assessed using different experimental methods in studies of animals as well as in a few studies in humans. Parallel processing and stream segregation are described, and their importance in central processing of auditory information is discussed. The role of neural plasticity in the normal function of the auditory system and as a cause of symptoms of pathologies is discussed. The anatomy and physiology of the acoustic middle ear reflex is examined in view of its importance in neurotologic diagnoses.

THE EAR The following description of the function of the ear is divided into that of the sound conductive apparatus and that of the cochlea. The description of the function of the cochlea focuses on its ability to separate sounds according to their frequency (frequency analysis).

Sound Conduction to the Cochlea The ear canal and the middle ear conduct sound to the cochlea, where the sensory cells are located. The ear canal and the acoustic effects of the head as an obstacle in a sound field modify the sound that reaches the cochlea. The ear canal acts as a resonator that is tuned to a frequency of approximately 3 kHz depending on the length of the canal (average 2.8 kHz).1 The sound pressure at the

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entrance of the ear canal is different from that measurable without the person being present because the head acts as an obstacle that disturbs a free sound field. When sound reaches an observer from a source that is located in front of the observer, the sound pressure at the entrance of the ear canal is higher than it would be in that place if the person were not present. Together with the effect of the resonance in the ear canal, the total gain is approximately 15 dB in the frequency range between 2 and 5 kHz.2,3 The sound pressure at the entrance of the ear canal depends on the direction to the sound source. Therefore, the sound pressure at the two ears is different except when sound reaches the observer from directly in front of or behind the observer. The difference depends on the frequency of the sounds. There is also a difference in the arrival time of sounds at the two ears that is a direct function of the azimuth. The arrival time difference together with the difference between the sound pressure at the two ears are the physical bases for directional hearing. Sounds that reach the tympanic membrane set it into motion, and this motion is conducted to the fluid of the cochlea by the three ossicles of the middle ear. The middle ear functions as an impedance transformer, which improves the transmission of sound to the cochlear fluid. This improvement in transmission is mainly the result of the large ratio between the area of the tympanic membrane and that of the stapes footplate.2,4 The improvement of sound transmission varies with its frequency. The increase is between 25 and 30 dB. This also means that the middle ear causes a large difference between the amount of sound that reaches the two windows of the cochlea. This difference between the force at the two windows sets the fluid in the cochlea into motion. The improvements of sound transmission to the cochlea by the action of the middle ear compared with a situation when an equal amount of sound reaches both windows is thus much greater than the aforementioned 25 to 30 dB; patients without the middle ear can experience hearing impairment on the order of 50 dB.2 Various pathologies can affect the function of the middle ear.2,4 For example, the sound transmission through the middle ear changes (decreases) when the air pressure in the middle ear cavity is different from the ambient pressure.2,5 Transmission of sound is also decreased when fluid in the middle ear covers the tympanic membrane or parts of it.2 Tympanometry, which involves measuring the ear’s acoustic impedance (or admittance or compliance) while the air pressure in the sealed ear canal is varied, can determine the pressure in the middle ear cavity noninvasively.2,5 Disorders such as otosclerosis impair hearing by adding stiffness to the middle ear. A perforation of the tympanic membrane impairs hearing by allowing sound to enter into the middle ear cavity and by impairing the function of the tympanic membrane.2,6 Two small muscles that are attached to the ossicles can affect sound transmission through the middle ear. One, the tensor tympani, is innervated by the trigeminal nerve and pulls the tympanic membrane inward when it contracts, thus causing the tympanic membrane to be stretched and thereby attenuating sound transmission for low-frequency sounds. The other muscle, the stapedius muscle, is attached to the stapes and pulls the stapes in a direction

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perpendicular to its normal motion in response to sound. The stapedius muscle is innervated by the facial nerve, and its contraction also decreases the middle ear’s ability to conduct low-frequency sounds. In humans the stapedius muscle contracts as an acoustic reflex in response to a strong sound. (See the section on Acoustic Middle Ear Reflex near the end of this chapter.) Contraction of the stapedius and the tensor tympani muscles increases the ear’s acoustic impedance.2,5,7 The contractions of the stapedius muscle can therefore be recorded by measuring changes in the ear’s acoustic impedance. This technique is noninvasive. Unlike a contraction of the tensor tympani muscle, which causes the tympanic membrane to move inward, a contraction of the stapedius muscle does not cause any noticeable movement of the tympanic membrane.2,7

Frequency Analysis in the Auditory System The cochlea separates sounds according to their frequency (or spectrum*) before the sounds are converted into a neural code by the inner hair cells. The frequency selectivity of auditory nerve fibers and cells in the nuclei throughout the ascending auditory pathways including those of the auditory cerebral cortex is based on the frequency selectivity of the cochlea. However, that frequency selectivity is transformed in various ways as the information ascends in the auditory nervous system. Much of our knowledge about the function of the frequency analysis in the cochlea has been achieved by studies of the responses from single auditory nerve fibers but valuable information has also been obtained by recordings from single hair cells and from measurements of the vibration of the basilar membrane.

decreases until the wave motion becomes extinct. The distance that the wave travels before it reaches its peak amplitude is a direct function of the frequency of the sound that has initiated the motion. Thus, the vibration amplitude of the basilar membrane in response to lowfrequency sounds is highest near the apex of the cochlea, while high-frequency sounds give rise to maximal vibration of regions of the basilar membrane at the base of the cochlea. Each point of the basilar membrane vibrates with the greatest amplitude for a certain frequency, and each point can be regarded as possessing frequency selectivity, that is, being tuned to a certain frequency (Fig. 2-1). A frequency scale can be laid out along the basilar membrane with respect to the highest vibration amplitude, low frequencies at the apex and high frequencies at the base of the cochlea. This also means that the basilar membrane separates sounds according to their spectral contents, and the different spectral components of a complex sound are separated along the basilar membrane. Once technologic advances made it possible to measure the vibration amplitude of the basilar membrane in living animals at sound intensities within or just above that of normal sounds,10 and later down to threshold values11–13 (see Fig. 2-1), it became evident that the motion of the basilar membrane was nonlinear. Its frequency selectivity depended on the sound intensity. The vibration of the basilar membrane activates sensory cells (inner and outer hair cells) that are located along the basilar membrane. The hair cells are therefore activated according to the frequency (spectrum) of sounds. The outer hair cells are morphologically similar to inner hair cells, but they have a purely mechanical function in that they act as “motors” that amplify the motion of the basilar

The Cochlea as a Frequency Analyzer Studies of the frequency selectivity of the ear were pioneered by von Békésy between 1928 and 1942 (see von Békésy 19608), who examined this feature in human cadaver ears. This work provided the first experimental evidence that the cochlea performs a frequency analysis on incoming sounds and that the type of motion of the basilar membrane is a traveling wave. Theoretical studies of the hydromechanical properties of the cochlea have been important in providing the basis for experimental studies and for providing explanations of the findings in animal studies. (For a review of the frequency selective properties of the cochlea, see a recent book by Jozef Zwislocki.9) The basilar membrane is set into motion by the cochlear fluid. That motion is a traveling wave because of the properties of the basilar membrane and the interaction between the basilar membrane and the fluid in the cochlea. The traveling wave is initiated at the base of the cochlea and progresses toward the apex. As it travels along the basilar membrane, its amplitude first increases and then, once the wave has traveled a certain distance, its amplitude rapidly *Frequency and spectrum of sounds are sometimes used synonymously but the word frequency should only be used to describe the properties of simple sounds such as pure tones or trains of impulses, while the properties of complex sounds should be described by their spectrum which represents the distribution of energy as a function of the frequency.

Figure 2-1. Basilar membrane vibration amplitude as a function of frequency for different sound levels in a guinea pig. (Adapted from Johnstone BM, Patuzzi R, Yates GK: Basilar membrane measurements and the traveling wave. Hear Res 22:147–153, 1986.)

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membrane for sounds of low intensities.14 This amplification, which adds approximately 50 dB to the sensitivity of the ear gradually decreases with increasing sound intensity, thereby compressing the intensity range of sounds. The transduction mechanism of the inner hair cells provides additional amplitude compression. Amplitude compression is important because of the limited dynamic range of neural coding in auditory nerve fibers. Representation of Frequency in the Auditory Nerve The frequency (or spectrum) of sounds is represented in two ways in the auditory nerve. One way, the place representation, is a result of the frequency selectivity of the basilar membrane, and the other, the temporal representation, is by the temporal pattern of the discharges of single auditory nerve fibers. The basis for the temporal representation of sounds is that the vibration of the basilar membrane is reflected in the time pattern of the discharges in auditory nerve fibers. Thus, a pure tone causes the basilar membrane to vibrate with a frequency of the tone and this vibration is reflected in the excitation of inner hair cells and subsequently in the temporal pattern of the discharges of auditory nerve fibers. This phenomenon, known as phase-locking, has been experimentally confirmed, at least for sounds of relatively low frequencies. Place Representation of Frequency in the Auditory Nerve Individual inner hair cells are activated according to the frequency of sounds that reach the ear, and therefore nerve fibers of the auditory nerve that innervate these hair cells also become activated according to the frequency of sounds. Each nerve fiber consequently responds best to a certain frequency of a pure tone. The response of an individual nerve to tones decreases as the frequency of a tone is changed up or down from the frequency to which the fiber responds best. Recordings from single auditory nerve fibers by means of microelectrodes in response to pure tones have confirmed that assumption. The discharge rate of a single auditory nerve fiber increases above its normal spontaneous rate when the stimulus sound’s frequency and intensity are within a certain range15–17 (Fig. 2-2). A curve that envelops the area of response shows the thresholds of a single auditory nerve fiber for tones of different frequencies. Such curves are known as tuning curves or frequency threshold curves (FTCs). The frequency at which the threshold is lowest is known as the nerve fiber’s best frequency, or the nerve fiber’s characteristic frequency (CF). It corresponds to the frequency of the tone that produces the highest vibration amplitude on the basilar membrane. When FTCs are obtained from representative samples of auditory nerve fibers, a family of such tuning curves is obtained, and the CFs of the individual nerve fibers cover the entire range of frequencies audible to the particular animal from which the recordings were obtained15–17 (Fig. 2-3). The vibration amplitude of the basilar membrane for sounds at physiologic levels is extremely small, and only recently has it become possible to study the vibration of the basilar membrane down to the threshold of hearing. Ten to 20 years ago, the techniques for obtaining basilar membrane tuning curves by measuring the vibration

Figure 2-2. Frequency response area of a single auditory nerve fiber in a guinea pig. A continuous tone, the frequency of which was varied, was used as stimulus. The different rows of nerve impulses are the responses to this tone when its intensity was varied in 5-dB steps. (Adapted from Evans EF: The frequency response and other properties of single fibers in the guinea pig cochlear nerve. J Physiol 226:263–287, 1972.)

amplitude of the basilar membrane in human cadaver ears or in the ears of anesthetized experimental animals used very high sound levels. The need to use high-intensity stimuli resulted in selectivity curves that were much broader than the FTCs of single auditory nerve fibers. Thus a discrepancy arose in measurements of tuning acuity of the basilar membrane and single auditory nerve fibers. This discrepancy gave rise to several hypotheses about what kind of “spectral sharpening” could be occurring in the neural transduction process.18

Figure 2-3. Family of frequency tuning curves obtained by recording from a number of auditory nerve fibers. (Adapted from Kiang NYS, Watanabe T, Thomas EC, Clark L: Discharge Patterns of Single Fibers in the Cat’s Auditory Nerve. Cambridge, MA, MIT Press, 1965.)

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Studies of the frequency selectivity of auditory nerve fibers using noise as stimuli in connection with cross-spectral analysis of the discharge rates of single auditory nerve fibers in animals showed evidence that the basilar membrane is nonlinear from threshold values of sound intensities to above physiologic sound levels.19,20 These studies showing that the frequency selectivity of the auditory periphery broadened when the intensity of the sound was increased were confirmed by studies of the motion of the basilar membrane.11–13 The obtained FTCs19,20 were narrower near the threshold of hearing, and their width increased when the sound level increased. In addition, the frequency to which a certain nerve fiber is tuned shifts downward when the sound intensity increases2,19,20 (Fig. 2-4). Earlier, it was shown that the location of maximal generation of cochlear microphonics (CM) along the basilar membrane shifts with the intensity of the stimulus sound.21 These results were confirmed when the frequency selectivity of the cochlea in living animals were studied, using methods that allowed measurements of the vibration of the basilar membrane near the threshold of hearing11,13 (see Fig. 2-1). Similar results were obtained in anesthetized cats13 and guinea pigs.11,12 It also became evident that the mechanical tuning curves of the basilar membrane in living animals were nearly identical to the FTCs obtained by measuring the responses from single auditory nerve fibers12,13 (Fig. 2-5). There was no longer a need of

Figure 2-4. Tuning properties of a single auditory nerve fiber in a rat estimated from the responses of a single auditory nerve fiber to pseudorandom noise of different intensities (given in dB SPL). (Adapted from Møller AR: Frequency selectivity of phase-locking of complex sound in the auditory nerve of the rat. Hear Res 11:267–284, 1983.)

Figure 2-5. Frequency selectivity of the basilar membrane (Thick line: isovelocity; thin line: isodisplacement) determined at sound levels near the threshold of hearing, compared with a FTC (dashed line) of the auditory nerve. Both measurements were done in anesthetized guinea pigs. (Adapted from Sellick PM, Patuzzi R, Johnstone BM: Modulation of responses of spiral ganglion cells in the guinea pig cochlea to low frequency sound. Hear Res 7:199–221, 1982.)

a “second” filter that sharpened the selectivity of the basilar membrane. The results of these studies radically changed the view of the function of the ear as a frequency analyzer. A similar fundamental change in our understanding of the frequency analyzing function of the ear was caused by the discovery of the role of the outer hair cells. The explanation for this nonlinearity of the basilar membrane response was provided when it was shown that the outer hair cells act as “motors” that provide the energy necessary to compensate for frictional losses of the basilar membrane motion.14 The action of the outer hair cells is thus responsible for the high degrees of sensitivity and frequency selectivity of the basilar membrane that is present at low stimulus intensities. Loss of outer hair cells results in a hearing loss of 50 to 60 dB and a degradation in cochlear frequency selectivity.2 The discovery of the function of the outer hair cells also explained the results of earlier studies of the responses from single auditory nerve fibers that showed that the frequency selectivity of the cochlea is vulnerable and depends on metabolic activity.18 Evans showed that depriving the cochlea of oxygen results in a broadening of the tuning curves18 (Fig. 2-6). At the time these studies were published the results were interpreted to indicate the existence of a neural mechanism (“second filter”) that sharpened the frequency selectivity of the basilar membrane. These studies were performed using simple sounds as stimuli, mostly pure tones. Other aspects of coding of sounds in the auditory nerve become apparent when more complex sounds are used. The tuning curves shown in Figures 2-2 and 2-3 were obtained by probing with a single tone, the frequency and intensity of which was changed, to

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It has been shown recently that two-tone inhibition is not mediated through synaptic transmission but rather it is a result of the nonlinearity in the micromechanics of the cochlea,23 and is thus another manifestation of cochlear nonlinearities. This is one reason why many investigators prefer to call this phenomenon two-tone suppression rather than two-tone inhibition. Temporal Representation of Frequency in the Auditory Nerve

Figure 2-6. Effect of anoxia on the frequency threshold curves of a single auditory nerve fiber in a guinea pig. (Adapted from Evans EF: Normal and abnormal functioning of the cochlear nerve. Symp Zool Soc Lond 37:133–165, 1975.)

determine the least intensity necessary to produce a noticeable increase in firing rate. When two tones are presented, one constant tone at the fibers CF and the other a tone with varying intensity and frequency, it is found that the discharges evoked by the constant tone decrease when the variable tone is within a specific intensity and frequency range. Figure 2-7 shows examples of such interaction in which the response area, obtained using a single tone, is shown together with the areas of intensity and frequency in which a second tone decreased the discharge rate of the response evoked by the first tone (cross hatched in Fig. 2-7).22 Note that there are two such inhibitory areas, one on each side of the response area of the fiber depicted in Figure 2-7. This is typical for auditory nerve fibers, and this two-tone inhibition has been studied extensively.22

Figure 2-7. Inhibitory areas of a typical auditory nerve fiber (cross hatched) in a cat together with the frequency threshold curve (filled circles). The inhibitory areas were determined by presenting a constant tone (CTCF ) together with a tone, the frequency and intensity of which were varied to determine the threshold of a small decrease in the neural activity evoked by the constant tone (CTCF ). (Adapted from Sachs MB, Kiang NYS: Two-tone inhibition in auditory nerve fibers. J Acoust Soc Am 43:1120–1128, 1968.)

The discharges of single nerve fibers are phase-locked to the waveforms of sounds within their response areas24 (Fig. 2-8). Such phase-locking can be demonstrated at least for frequencies below 4 to 5 kHz.19,20,25 This is assumed to be the basis for the temporal hypothesis for frequency discrimination in the auditory system, which was originally known as the volley theory.26 Phase-locking to the waveform of a sound means that the neural discharges in single auditory nerve fibers have a higher probability of appearing at a certain phase of the sound than at other phases of the sound. Phase-locking was first shown to occur in fibers of the auditory nerve for pure tones,27 but later it was shown to occur also for more complex sounds such as those that consist of more than one sinusoid28 (Fig. 2-9), including broadband sounds such as vowels29 and broadband noise.19,20

Figure 2-8. Phase-locking of discharges in a single guinea pig auditory nerve fiber to a low-frequency tone (300 Hz), near threshold. (Adapted from Arthur RM, Pleiffer RR, Suga N: Properties of “two tone inhibition” in primary auditory neurons. J Physiol 212:593–609, 1971.)

Figure 2-9. Period histograms of discharges in a single auditory nerve fiber of a squirrel monkey to stimulation with two tones of different frequencies that were locked together with a frequency ratio of 3:4 and an amplitude ratio of 10 dB. The different histograms represent the responses to this sound when the intensity was varied over a 50-dB range. (Modified from Rose JE, Hind JE, Anderson DJ, Brugge JF: Some effects of stimulus intensity on response of auditory fibers in the squirrel monkey. J Neurophysiol 34:685–699, 1971.)

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Basis for Frequency Discrimination in the Auditory System: Temporal or Place Representation? The frequency of a sound can be determined equally well from its spectrum as from its temporal pattern. Therefore, auditory frequency discrimination can either be based on the place of maximal vibration along the basilar membrane (place hypothesis), or the coding of the temporal pattern of sounds in the discharge pattern of auditory nerve fibers (temporal hypothesis), or a combination of both. The question of the importance of place versus temporal representation for frequency discrimination was of purely academic interest before cochlear implants were introduced. Since then it has become of great practical and clinical significance for the design and use of cochlear implants.2,30,31 The place principle of coding the frequency of a sound was favored for many years as an explanation for the ability to discriminate frequency. Recently evidence has accumulated that indicates temporal coding may play a more important role in the coding of frequency or spectral components of sounds than was believed earlier. The finding that the frequency to which a fiber in the auditory nerve is tuned changes with the intensity of the sound19,20 (see Fig. 2-4) indicates that frequency maps in higher centers of the ascending auditory pathway, including the auditory cortex, would change with the intensity of a sound because such maps are based on cochlear frequency tuning. This generates doubt that the place principle alone is responsible for the neural coding that is the basis for discrimination of the frequency of a pure tone or for discrimination of complex sounds such as speech sounds on the basis of their frequency.30 It has been evident for a long time that the selectivity of the basilar membrane is not sufficiently acute to explain the power of human frequency discrimination but it was assumed that some (unknown) neural mechanisms would sharpen the selectivity so that it would be sufficiently acute to explain the ability to discriminate small differences in frequency of sounds. The fact that the frequency to which a point on the basilar membrane is tuned depends on the intensity of the sounds demonstrates that basilar membrane tuning,2,10,11,13,19–21 and thus the place principle, is not sufficiently robust to explain common psychoacoustic findings that frequency discrimination depends little on sound intensity.32 This is a strong indication that mitigates against the place hypothesis as a basis for auditory frequency discrimination. Increasing evidence has accumulated during this time regarding the importance of the temporal code for discrimination of complex sounds such as speech sounds. Frequency discrimination is important for discrimination of speech sounds. However, it has been shown that the temporal representation of vowel sounds in the discharge pattern of single auditory nerve fibers is more robust29 than place representation of vowel spectra.33 A major obstacle for the temporal hypothesis has been the belief that synaptic transmission involved temporal uncertainties (synaptic jitter) that would impair the precision of temporal coding of frequency. That obstacle, however, does not exist because many neurons that receive hundreds and indeed thousands of synaptic inputs from

the auditory nerve function as spatial averagers that not only preserve the precision of temporal coding but in fact can improve the temporal precision of neural coding.34,35 Some neurons in the cochlear nucleus respond with greater temporal precision than that of auditory nerve fibers.36,37 That temporal information is preserved in synaptic transmission is also evident from the fact that directional hearing depends on the detection of very small time intervals between the arrival time at the two ears. That temporal information must be preserved until it can be decoded, presumably in the medial superior olivary nucleus. Psychoacoustic studies have shown that human observers can discriminate azimuths with an accuracy of a few degrees, corresponding to less than 10 μsec (microseconds). This means that temporal coding must be preserved with that level of precision through at least two synapses (cochlear nucleus and medial superior olivary nucleus) in addition to that of the hair cells. Other studies have shown that phase-locking in the auditory nerve can be demonstrated for frequencies of at least up to 5 kHz,19,20 and it probably exists for much higher frequencies.38 The great importance of temporal coding of complex sounds also explains the success of cochlear implants, which provide excellent timing of sounds but only coarse place representation of sound spectra.31 Another indication of the importance of the temporal code for frequency discrimination is the fact that disorders of the auditory nerve impair speech discrimination more than does a hearing loss of cochlear origin with the same threshold shift. Disorders of the auditory nerve are likely to cause desynchronization of neural activity, thus impairing the temporal code of frequency. Recently, the term auditory neuropathy has been used to describe such disorders. In summary, it seems that the ability of the cochlea to separate sounds according to their frequency may be less important for frequency discrimination than was previously assumed. Instead the importance of the cochlea’s frequency selectivity may rather be to separate the sound spectrum of complex sounds such as speech sounds into narrow “slices” to facilitate temporal coding of sounds.31

THE AUDITORY NERVOUS SYSTEM The ascending auditory nervous system is anatomically organized so that it can perform hierarchical and parallel processing of auditory information. Two different ascending pathways have been identified: the classical pathways (also known as the lemniscal or the specific pathways) and the nonclassical pathway (extralemniscal, or nonspecific pathways).2,35,39–42 The anatomy and the function of the classical pathways are better known than that of the nonclassical.

Classical Ascending Auditory Pathways The classical auditory ascending pathways are more complex than the ascending pathways of other sensory systems.2,35,40 All auditory information is interrupted by synaptic transmission in each of the three main relay nuclei: the cochlear nucleus (CN), the central nucleus of the inferior colliculus (ICC), and the ventral portion of the

Physiology of the Ear and the Auditory Nervous System

medial geniculate body (vMGB) (Fig. 2-10). The fiber tract of the lateral lemniscus (LL) crosses the midline while connecting the CN with the ICC. The brachium of the IC (BIC) connects the ICC with the vMGB, which projects to the primary (and secondary) auditory cerebral cortices (AI, AAF, PAF). Other nuclei, such as those of the superior olivary complex (SOC), the dorsal and ventral nuclei of the lateral lemniscus (DNLL and VNLL) interrupt some ascending information (see Fig. 2-10).

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All these nuclei have complex internal networks of neurons that process auditory information, although the FTCs of neurons in the cochlear nucleus, the nuclei of the superior olivary complex, and the nucleus of the inferior colliculus are rather similar to those of fibers of the auditory nerve16 (Fig. 2-11). Whereas the representation of the frequencies of simple sounds such as pure tones seems consistent throughout the ascending auditory nervous system, auditory information about complex sounds undergoes

AAF

AI

Cortex PAF

AII

Dorsel thalamus

D M

Ventral thalamus

OV V

DC ICC

B

A

Inferior ICX calliculus

LL

Figure 2-10. Schematic drawing of the ascending auditory pathways. A, Anatomic locations and connections from the auditory nerve to the MGB. AN, auditory nerve; CN, cochlear nucleus; SOC, superior olivary complex; LL, lateral lemniscus; NLL, nuclei of the lateral lemniscus; ICC, central nucleus of the inferior colliculus; BIC, brachium of the inferior colliculus; MGB, medial geniculate body. (Adapted from Møller AR: Sensory Systems: Anatomy and Physiology. Amsterdam, Academic Press, 2001). B, Connections from the central nucleus of the inferior colliculus (ICC ) to the ventral portion of the MGB and their connections to auditory cortical radiations. Most of the connections have reciprocal descending connections; only one of which are shown (between AI and the MGB). AAF, anterior auditory field; AI, primary auditory cortical area; D dorsal division; DC, dorsal cortex of the inferior colliculus; ICC, central nucleus of the inferior colliculus; ICX, external nucleus of the inferior colliculus; M, medial (or magnocellular) division of MGB; OV, ovoid part of the MGB; PAF, posterior auditory field; V, ventral division (Adapted from Møller AR: Sensory Systems: Anatomy and Physiology. Amsterdam, Academic Press, 2001.)

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A

in the ascending auditory pathway to tone bursts indicate that successive transformation of information occurs as it ascends in the ascending auditory pathways. Although the ascending auditory pathways are mainly crossed, there are connections between the CN and the ipsilateral ICC and there are ample connections between nuclei on the two sides (see Fig. 2-10). The information from the two ears reaches the same neurons in the nuclei of the SOC and in the ICC and that is assumed to be the basis for the ability to discriminate the direction to a sound source and perception of auditory space43 (directional hearing). The superior colliculus (SC), which receives auditory input from the ICC, is important for perception of auditory space. Cochlear Nucleus

B

C

When the auditory nerve enters the cochlear nucleus each fiber bifurcates and one branch terminates on neurons in the anterior ventral cochlear nucleus (AVCN). The other branch bifurcates again, and one branch terminates on neurons in the posterior ventral cochlear nucleus (PVCN), and the other branch terminates in the dorsal nucleus of the cochlear nucleus (DCN). This means that each fiber of the auditory nerve innervates each of the three main divisions of the cochlear nucleus, thus enabling information that is carried in each of the fibers of the auditory nerve to be processed (in parallel) in three different populations of neurons. This represents the beginning of parallel processing that is abundant in the ascending auditory nervous system. Tonotopic organization is clearly evident in the cochlear nucleus44 (Fig. 2-12), and each of the three main subdivisions of the cochlear nucleus has its own frequency map. At first glance the responses of single nerve cells of all divisions of the cochlear nucleus possess frequency selectivity similar to that of single auditory nerve fibers (see Fig. 2-11), but some neurons in the CN have tuning curves of different shapes, and some neurons’ FTCs have more than one peak.2,18,44 Response areas of cells in the cochlear nucleus to a tone, the frequency of which is changed, become narrower when the frequency of the tone is changed rapidly, compared with those obtained in response to tones with slowly varying

D Figure 2-11. Tuning curves obtained from the auditory nerve (A), dorsal cochlear nucleus (B), trapezoidal body (C), and inferior colliculus (D). Solid lines in D show average human hearing threshold. (Adapted from Katsuki Y, Sumi T, Uchiyama H, Watanabe T: Electric responses of auditory neurons in cat to sound stimulation. J Neurophysiol 21:569–588, 1958.)

considerable transformation and reorganization as it passes through the various nuclei of the ascending auditory pathways, as can be demonstrated by recording the response to complex sounds such as sounds the frequencies or intensities of which vary at different rates. The response patterns of the auditory nerve fibers and of cells of the various nuclei

Figure 2-12. Tonotopical organization in the cat cochlear nucleus. Pv, posterior ventral; Av, anterior ventral; Dc, dorsal cochlear nucleus. (Adapted from Rose JE, Galambos R, Hughes JR: Microelectrode studies of the cochlear nuclei in the cat. Bull Johns Hopkins Hosp 104:211–251, 1959.)

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frequency45 (Fig. 2-13), and more nerve impulses are delivered when the frequency of the stimulus tone is close to the cell’s CF. When the frequency of the stimulus tone is changed above a certain rate, the response again broadens. Similar changes have not been demonstrated in the responses of auditory nerve fibers, and the above mentioned features of cells in the cochlear nucleus therefore are taken as an indication of some of the transformations that occurs in the responses of cells in auditory nuclei. Other signs of processing of information in the cochlear nucleus are the differences in the response to tone burst between cells in the cochlear nucleus compared with auditory nerve fibers. Although the shape of post-stimulus time histograms of the responses of all single auditory nerve fibers to tone bursts are similar, showing a rapid increase in discharge after a brief latency and then a slight gradual decrease in the discharge rate (Fig. 2-14A), the shape of post-stimulus time histograms of the responses of different neurons in the cochlear nucleus varies and at least four different types of response patterns have been identified2,17,46–49 (Fig. 2-14B). Post-stimulus time histograms of the response to tone bursts have been used to classify neurons in the cochlear nucleus but other differences could be used for classification of neurons in the CN. One such feature relates to the responses to small changes in the amplitude of sounds. The discharge rate of neurons in the cochlear nucleus in response to tones, the amplitudes of which are varied sinusoidally (sinusoidally amplitude-modulated tones), becomes modulated with the same frequency as that used to modulate the stimulus tones,2,25,50 and different neurons respond to such sounds in distinctly different ways.47,48,51–53 A plot showing the degree of modulation of the discharge rate as a function of the modulation frequency is known as the modulation transfer function (MTF). The discharge rates of neurons in the cochlear nucleus are modulated to the greatest extent for modulation

Figure 2-13. Histograms of the responses recorded from a single nerve cell in the cochlear nucleus of a rat to tones, the frequencies of which were changed at two different rates. A, At 10 sec for a complete path. B, At 156 ms for a complete path. C, D, Histograms showing the same data on an expanded time/frequency scale. The change in the frequency of the stimulus tones is shown below. (Adapted from Møller AR: Coding of sounds with rapidly varying spectrum in the cochlear nucleus. J Acoust Soc Am 55: 631–640, 1974.)

Figure 2-14. A, PST histograms of responses to tone bursts of different intensities recorded from a single auditory nerve fiber in a cat. (Adapted from Kiang NYS, Watanabe T, Thomas EC, Clark LF: Discharge Patterns of Single Fibers in the Cat’s Auditory Nerve. Cambridge, MA, MIT Press, 1965.) B, PST histograms of responses of cells in the cochlear nucleus to tone bursts. Each histogram represents one class of units. (Adapted from Pfeiffer RR: Classification of response patterns of spike discharges for units in the cochlear nucleus: Tone-burst stimulation. Exp Brain Res 1:220–235, 1966.)

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frequencies in the range of 50 to 150 Hz,47,48,54,55 (Fig. 2-15) while MTF of auditory nerve fibers have cut-off frequencies of approximately 1 kHz.25 Neurons in the cochlear nucleus thus selectively modulate the frequency of a tone (or noise) as well as the frequency of a tone stimulus. At the “best” modulation frequency, the discharges of neurons in the cochlear nucleus may be modulated nearly 100% when the amplitude of the sound is modulated by only a few decibels.2,36,49,50,54 The response of cells in the cochlear nucleus is also different from that of auditory nerve fibers in that cells in the CN respond better to the modulation waveform than do auditory nerve fibers.47,48,54,55 Although the vast majority of nerve cells in the cochlear nucleus receive input from only the ipsilateral ear, some neurons respond to contralateral sounds,56–58 either by increasing their discharge rate (excitatory) or by decreasing it (inhibitory). Sound-driven activity from the ipsilateral ear can also, in a few nerve cells, be inhibited by delivering sound, in a specific frequency range, to the opposite ear. Superior Olivary Complex and Binaural Hearing The superior olivary complex (SOC) (see Fig. 2-10) consists of a series of nuclei scattered in the brainstem. The anatomic organization of the SOC in humans versus that in small animals is the most different of all the ascending auditory nuclei of the brainstem.59 The possible physiologic effects of these differences are difficult to assess, but caution should be exercised when drawing conclusions from the results of studies in animals about the function of the various groups of neurons in the SOCs of humans.

The SOC is usually regarded as the most peripheral level at which the ascending auditory pathway crosses from one side to the other. However, there are also connections between the two cochlear nuclei, as mentioned earlier. When hearing acuity is nearly equal in both ears, the direction of a sound can be determined with great accuracy and, perhaps more importantly in humans, binaural hearing helps to discriminate sound on the basis of the location of its source in space. When listening to speech in an environment with more than one speaker, or in a noisy environment, binaural hearing improves the ability to distinguish one speaker from another. The use of binaural hearing for this purpose is known as the “cocktail party phenomenon.” The ability to discriminate from which direction a sound is coming is based on the difference in arrival time and intensity of the sound that reaches both ears. When a sound is located directly in front of the head, or exactly behind the head, the sound will arrive at both ears at precisely the same time. When a sound comes from any other direction, it will arrive at each ear at different times because of the different distance between each ear and the sound source. The value of this time difference is a direct function of the azimuth to the sound source (and the propagation velocity of the sound), which is constant. Jeffress60 presented a hypothesis that describes how interaural time differences can be detected by a neural circuit that consists of coincidence detectors and variable delay lines. Experimental evidence has been presented that such a circuit exists in the medial superior olivary (MSO) nucleus of the SOC.61 It has been shown in animal experiments that neurons in the MSO nucleus act as coincidence detectors and only respond when excited from both ears simultaneously. These coincidence detectors receive their input from cochlear nucleus cells through axons of different lengths. These axons act as delay lines with different delays, which enables the coincidence detectors to respond to sounds that arrive at the two ears with different intervals. A population of neurons with such an array of coincidence detectors with their delay lines of different length could cover the range of interaural delays that correspond to azimuths of 180 degrees (approximately 0.65 msec). In addition to the interaural time difference, interaural intensity differences that are a function of the azimuth are used as a physical basis for directional hearing. However, intensity differences between the sound at one ear and that at the other ear has a more complex relationship to the azimuth than the interaural time differences and is highly dependent on the spectrum of the sound. Neurons in the SOC may be sensitive to interaural intensity differences but that property of binaural hearing is primarily processed by neurons in the inferior colliculus. Inferior Colliculus

Figure 2-15. Modulation transfer functions obtained in a single auditory nerve fiber (thin line) and a cell in the cochlear nucleus (heavy line) of a rat. (Adapted from Møller AR: Dynamic properties of primary auditory fibers compared with cells in the cochlear nucleus. Acta Physiol Scand 98:157–167, 1976.)

The IC is the midbrain nuclei of the ascending auditory pathways (see Fig. 2-10). On anatomic grounds, the IC can be divided into the central nucleus (ICC), the external nucleus (ICX), and the dorsal cortex (DC).41,62 The neurons of the ICC are the midbrain relay nucleus of the classical ascending auditory pathways.63 The cells of the ICC receive auditory input via the lateral lemniscus,64 mainly from the

Physiology of the Ear and the Auditory Nervous System

contralateral ear, but significant input also comes from the ipsilateral ear through the nuclei of the lateral lemniscus. The ICX and DC belong to the nonclassical auditory pathways, and these nuclei receive their auditory input mainly from neurons in the ICC. It is generally assumed that all auditory information is interrupted by synaptic contacts in neurons of the ICC. However, considerable differences may exist among species, and there are indications that in the chimpanzee some cochlear nuclear axons may bypass the IC.41 Similar findings have been made more recently showing connections between neurons in the DCN and the medial division of the MGB.65 Also, neurons in the central nucleus of the IC are tonotopically organized,41,66 similar to more peripheral nuclei. Neurons in the central nucleus of the IC exhibit frequency selectivity similar to that of neurons in the auditory nerve and the cochlear nucleus, but again the variations in the widths and shapes of the tuning curves of these neurons are greater than that of neurons of more caudally located nuclei41,67 (Fig. 2-16).

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Some neurons of the ICC respond with a sustained discharge when stimulated with continuous sounds or tone bursts, whereas others respond only to the onset or the offset of tone bursts.41 In this connection, keep in mind that the response pattern may be affected by the level and type of anesthesia used. Responses in unanesthetized animals tend to have more complex patterns than those from anesthetized animals. This is true also for more peripheral levels of the auditory system. Although responses from the auditory nerve and the ventral portion of the cochlear nucleus are generally assumed not to be affected by anesthesia, a noticeable effect of anesthesia on the dorsal cochlear nucleus has also been demonstrated.68 Many neurons in the central nucleus of the IC respond in a nonmonotonic fashion, which means that the discharge rate first increases when the stimulus level is increased from threshold levels and then, at a certain stimulus intensity, the rate begins to decrease, reaching very low values at the highest stimulus levels.41 Studies have shown that development of a normal response pattern of the neurons in the ICC depends on

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Figure 2-16. Four different types of tuning curves found in the inferior colliculus. CF, characteristic frequency. (Adapted from Ehret G, Romand R: The Central Auditory Pathway. New York, Oxford University Press, 1997; after Ehret G, Merzenich MM: Complex sound analysis (frequency resolution, filtering and spectral integration) by single units of the inferior colliculus in the cat. Brain Res Rev 13:139–163, 1988.)

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prior sound stimulation, especially in young animals.41,69 When 2-day-old gerbils underwent ablation of the cochlea on one side, responsiveness of the ipsilateral ICC was greatly enhanced 6 months after birth compared with the response in normal animals. Apparently, sound deprivation caused reorganization of the ascending auditory pathways. Deprivation of sound70 and hearing loss due to auditory overstimulation (in adult cats) have been shown to result in a decrease in temporal integration of the IC.71 This change may reflect hypersensitivity of the IC to sound. Experimental evidence for involvements of the ICC in directional hearing have been presented, and neurons in the ICC have been shown to specifically respond to differences between the ears in the intensity of a sound.72 The physical properties of the head provide the interaural intensity differences that are related to the azimuth of a sound source. The modification of the spectrum of sounds by the physical properties of the head also contribute to the perception of space (stereophonic sound).43 Almost all neurons in the ICC respond to contralateral sound stimulation, whereas fewer than 40% of the neurons are excited by ipsilateral sound stimulation.41 There are several anatomic bases for binaural interaction in the auditory midbrain. One is the commissure of the IC, which is a large fiber bundle that connects the two ICCs. The lateral lemniscus and the ICC are also connected via the DNLL and VNLL. The commissure of Probst connects one of the dorsal nuclei of the lateral lemniscus with the corresponding nucleus on the other side as well as the contralateral ICC. Directional information from the auditory system is integrated with that from the visual system in the SC to achieve a perception of space.73,74 Some neurons in the SC thus respond to sound, although this nucleus does not function as a relay nucleus for auditory stimuli.41 The IC is a reflex center that passes on auditory information to motor systems, for example, to the spinal cord and to the SC, which activates the extraocular muscles. The IC is not involved in the acoustic middle ear reflex.75 Medial Geniculate Body The medial geniculate body (MGB) is the thalamic relay nucleus of the auditory pathway. On anatomical grounds, the MGB in the cat has been divided into ventral, dorsal, and medial divisions,76 and physiologic studies have shown that the response patterns of neurons in these three divisions are different. The ventral MGB (vMGB) belongs to the classical ascending auditory pathways, and the dorsal and medial portions of the MGB belong to the nonclassical pathways. All information from the ICC is conducted to the vMGB through the brachium of the IC (BIC), where all information is interrupted by synaptic connections before it reaches the cerebral cortex. The neurons in the vMGB are sharply tuned, and they project to the primary auditory cortex.77 There is a considerable projection from the auditory cortex to the vMGB78,79 as well. No known connections exist between the vMGB of the two sides. Auditory Cortex The primary auditory cortex (AI) receives its input from the vMGB.77,80 Other auditory cortical areas are the anterior

and posterior auditory fields (AAF and PAF), which receive input from the AI. Neurons in the AI on one side connect to neurons in similar areas on the other side through the corpus callosum.81,82 Single nerve cells in the AI cortical area respond to sounds in a more stereotypical fashion than do neurons in the more caudally located nuclei of the ascending auditory pathway, but cortical neurons have more complex frequency tuning than that of cells in the nuclei at more caudal levels of the ascending auditory pathways.83 Nerve cells in the primary auditory cortex usually respond to stimulation of both ears, and they are distinctly sensitive to the time interval between stimulation of the two ears.83,84 Responses of the nerve cells of the auditory cortex to pure tones indicate that these nerve cells are organized according to the frequency to which they are tuned. Cells in the AI and the AAF cortex respond well to amplitude-modulated sounds, but the range of modulation frequencies is much lower than that of neurons at more peripheral levels.85,86 Animal experiments in which sounds have been applied to both ears have shown that cortical neurons are organized in bands where neurons respond with excitation from the contralateral and ipsilateral ear (EE). These bands alternate with bands where neurons are excited from the contralateral ear but inhibited from the ipsilateral ear (EI).87 Also, recent animal experiments have revealed a high degree of neural plasticity of cortical neurons caused by deprivation88 and prior stimulation with various kinds of sounds.86 The auditory cortex in humans is located deep in the lateral fissure of the temporal lobe, in the superior temporal gyrus (Heschel’s gyrus)77,83 (Brodmann’s area 41), and it is therefore not easily accessible for studies using physiologic methods. Only a few studies of the physiology of the human auditory cortex have been published. Penfield and Rasmussen89 showed that electrical stimulation of the primary auditory cortex in their patients who were operated on under local anesthesia evoked a sensation of simple sounds, such as buzzing. Celesia,90 in recording evoked potentials from the exposed auditory cortex in patients undergoing neurosurgical operations, has shown that sounds are represented bilaterally in the human cortex. These somewhat contradictory findings call into question the level that should be assigned to the primary auditory cortex. Is the cortex the end point in the auditory system, the point at which we actually perceive and interpret natural sounds, such as speech sounds, to which we are normally exposed? When viewed in one way, the primary auditory cortex may be regarded as just another stage of the ascending auditory pathway where considerable information processing occurs, as indicated by the response patterns of single cortical neurons being more complex than that of neurons in the lCC and the vMGB. The primary auditory cortex may thus be just another common pathway in the ascending auditory pathway leading toward higher brain centers (association cortices) where complex sounds such as speech and music are interpreted. For the neurotologist, the answer to the questions may not be very important because lesions rarely occur on the auditory cortex, and modern imaging techniques, such as CT and MRI can delineate most lesions that affect the auditory cortex. Before these techniques were available,

Physiology of the Ear and the Auditory Nervous System

low-redundancy speech was used in tests designed to identify the location, and perhaps the nature, of lesions in this part of the auditory nervous system.91,92

Nonclassical Ascending Pathways The main anatomic differences between the classical and the nonclassical ascending auditory pathways are that the nonclassical pathways are interrupted by synaptic contacts with neurons in the medial and dorsal part of the MGB whereas the classical pathways use the ventral portion of the MGB (Fig. 2-17). Neurons in the dorsal and medial MGB project to secondary cortices and association cortices,41,93 and those in the ventral part project to primary auditory cortex (AI). There is a direct connection from neurons in the dorsal and medial MGB to the lateral nucleus of the amygdala.94 This connection provides a fast route through which little processed information can reach the amygdala. Another important difference between the classical and nonclassical auditory systems is

Figure 2-17. Schematic drawing of the ascending nonclassical auditory pathways. Connections from the central nucleus of the inferior colliculus (ICC) to the external nucleus of the inferior colliculus (ICX ) and the dorsal cortex of the inferior colliculus (DC) and connections from these nuclei to other structures. Efferent input from the cerebral cortex and connections to the DC and ICX from the somatosensory system (dorsal column nuclei) and from the opposite IC are not shown (for more details see Fig. 9-1). AAF, anterior auditory field; AI, primary auditory cortex; AII, secondary auditory cortex; D, dorsal division; M, medial division; OV, ovoid part of the MGB; PAF, posterior auditory field; SAG, sagulum; V, ventral division. (Adapted from Møller AR: Sensory Systems: Anatomy and Physiology. Amsterdam, Academic Press, 2003.)

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that the nonclassical auditory pathways receive input from other sensory systems, most noticeably the somatosensory system.39,41,63,95–97 For example, some neurons in the cochlear nucleus receive input from the somatosensory system (dorsal column nuclei and trigeminal nuclei)95,96,98 (for a more detailed description of the nonclassical pathways see Chapter 9, and Møller, 2003.35). Some neurons in the ICX receive input from the somatosensory system (mainly cutaneous tactile), and approximately 10% of the neurons in the ICX receive both somatosensory and auditory input.41,63 The main auditory input to the DC and ICX is from the ICC, but some evidence indicates that auditory input may also arise from the auditory cortex.41 Animal studies have confirmed that somatosensory input can interact with the responses to auditory input from neurons in the ICX and DC41 and evoked responses from the surface of the IC.99 Interaction between sensory modalities has been demonstrated at several levels of sensory pathways.100 The tonotopic organization seems to be less prominent in the ICX and DC compared with that in the ICC. These neurons are broadly tuned and sometimes difficult to excite with the simple stimuli that are usually employed in such experiments.93 The neurons in the ICX and DC are more sensitive to the effects of anesthesia than neurons in the ICC, which may explain some of the differences in the results reported by different investigators. Also, the anatomic border between the ICC and the ICX and DC is diffuse, which means that some neurons from which recordings were made may have been assigned to the incorrect nucleus. An expression of interaction between the auditory system and the somatosensory system has been demonstrated in humans by observing the effect of somatosensory stimulation on the loudness of sounds.101,102 Using that technique, it was found that electrical stimulation of the median nerve could affect the perception of loudness in young children but the effect decreased with age and only a few individuals older than 18 years of age experience any change in the perception of such sounds as a result of electrical stimulation of the median nerve102 (see Chapter 9). Median nerve stimulation can alter the perception of tinnitus in some patients with severe tinnitus, a fact taken as an indication of an abnormal involvement of the nonclassical auditory system in these patients.101 Evidence that somatosensory stimulation can alter the perception of sounds in humans with some forms of severe tinnitus has been confirmed by other investigators (see Chapter 9). On the basis of the diverse functions of the nonclassical auditory system some investigators distinguish between two different nonclassical auditory systems: a diffuse system and a polysensory system.103

Efferent System The auditory pathways include abundant descending systems. Traditionally, the efferent pathways have been described as separate systems, and two main efferent systems have been identified: one the olivocochlear bundle that terminates in the ear and one that terminates in various nuclei of the ascending auditory system. However, it

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may be more appropriate to regard the descending systems as being reciprocal pathways to the ascending pathways, because most of the neurons that receive ascending input also send descending fibers to the same nuclei from which they receive ascending input (and often also other nuclei of the auditory pathways). Olivocochlear Bundle The olivocochlear bundles consist of the crossed olivocochlear bundle (COCB) that originates in the medial superior olivary nucleus (MSO)104,105 and the uncrossed olivocochlear bundle (UOCB) that originates in the lateral superior olivary complex (LSO). The COCB fibers mainly terminate on outer hair cells, whereas the UOCB fibers mainly terminate on axons of inner hair cells. The efferent fibers have sharp frequency tuning and about the same sensitivity as auditory nerve fibers.106 Early animal experiments have shown that activation of the COCB results in a decrease of stimulus-driven neural activity in fibers of the auditory nerve,107,108 but more recently it has become evident that neural activity in these fibers can also affect the mechanical properties of the cochlea. This effect is mediated by the termination of efferent fibers on the cell bodies of outer hair cells and is a consequence of the fact that the outer hair cells are an integral part of the mechanical system of the cochlea.14 This means the medium that transmits the stimulus to the receptors (inner hair cells) is controlled from the CNS.109,110 Neural activity in the COCB can be elicited by (contralateral) sound stimulation. The mechanical properties of the cochlea can therefore be affected by contralateral sound stimulation, which can be detected by recording otoacoustic emissions from the ear.111,112 The functional importance of the OCB is not yet understood, but some studies indicate that its stimulation reduces masking in auditory nerve fibers.113 Other behavioral studies, performed in patients who had undergone vestibular nerve section in the cerebello pontine angle that included section of the OCB, show no measurable deficits as a result of the neurotomy. Several psychoacoustic tests on such patients have not revealed any specific effects of severing the OCB except a better ability to detect signals at unexpected frequencies, and that was interpreted as an impaired ability to focus attentions in the frequency domain.114 It has been reported that the OCB offers protection against noise-induced hearing loss.115 It is difficult to believe that such an effect should be the primary function of this system because noise-induced hearing loss was probably not a factor that influenced an animal’s survival during evolution. Centrifugal Pathways to the Cochlear Nucleus and Higher Centers The descending systems of the central auditory pathways are abundant.78,116 The number of fibers that connect cortical cells with cells in the MGB is several times larger than that of the fibers that ascend from the MGB to the auditory cortex.117 The cells of the auditory cortex also send connections to the ICC.78,116 There is also an abundant

descending system from the ICC to neurons in the dorsal cochlear nucleus bilaterally.118 Generally, little is known about the physiology of the descending auditory systems. It has been shown that electrical stimulation of the auditory cortex affects soundactivated responses of the cochlear nucleus.119 More recently it was shown that inactivation of cortical cells caused a change in the frequency to which neurons in the MGB as well as the ICC were tuned.120

Neural Plasticity Neural plasticity is usually regarded as a process that cause changes in the nervous system in response to altered demands or which shifts function from one region of the CNS to another after injuries. Neural plasticity is assumed to involve establishment of new connections or elimination of connections (synapses and axons or dendrites) or by changes in synaptic efficacy. Morphological changes can be altered as a result of the firing pattern of neurons121 and that is the basis for activity induced plasticity. Recent studies have shown that neural plasticity is much more extensive than earlier assumed and it is not always beneficial to the organism. For example, neural plasticity can cause symptoms and signs of disorders such as pain and tinnitus.122,123 Studies of the auditory cortex have shown that extensive alterations in processing may occur as a result of deprivation of input or exposure to specific kinds of sounds.88,124–127 The nucleus basalis128 (an acetylcholine pathway) is important for many functions such as memory, arousal, and facilitation of neural plasticity of the auditory cortex that are caused by prior sound stimulation.129 The functional changes in the response of neurons in the AI cortex caused by prior sound stimulation are facilitated by electrical stimulation of the nucleus basalis as well as by application of acetylcholine to the cortex.129 These changes involve the tuning of cortical neurons and of their response to temporal information.86,129

Higher-Order Processing The primary auditory cortex may be regarded as one of the final common pathways to higher CNS centers. Connections from the primary auditory cortices (AI) reach secondary auditory cortices such as the anterior (AAF) and posterior auditory fields (PAF) and from there, auditory information can reach larger regions of association cortices. Neurons in the auditory AI cortex respond only to sound, but some neurons in secondary cortices respond to other sensory modalities. Such multimodal responses are common in neurons in the association cortices, where information from different sensory modalities is integrated. Parallel Processing and Stream Segregation Considerable processing of auditory information occurs in the association cortices, and there is evidence that the same information is processed in different populations of neurons (parallel processing) and that different types of information is processed in different populations of

Physiology of the Ear and the Auditory Nervous System

neurons (stream segregation). Although parallel processing is prominent throughout the ascending auditory pathways beginning in the cochlear nucleus, stream segregation seems to be mainly present in the cerebral cortex. Stream segregation has been studied to the greatest extent in the visual system, where it has been demonstrated that spatial information (“where”) and object information (“what”) is processed in two different regions of associations cortices (dorsal and ventral regions, respectively).130 Although the basis for parallel processing is obvious from the anatomy of the auditory systems, stream segregation has only been demonstrated in the auditory system relatively recently.131–134 One form of stream segregation in the auditory system is based on projections of two different kinds of information from the vMGB to the supertemporal plane in addition to the more commonly known projection to the AI area.131 Neurons in another cortical region, the caudomedial cortical area, receive input indirectly from the vMGB via AI, and many of these neurons respond to the spatial location of a complex sound, whereas neurons in the lateral surface of the superior temporal gyrus respond best to complex sounds such as species-specific communication sounds. Auditory stream segregation has been demonstrated in monkeys,131,133 where it has been shown that certain populations of neurons respond to complex sounds, whereas others preferentially respond to pure tones.134 Little is known about stream segregation of auditory information in association cortices.

Connections to Other Nonauditory Parts of the Brain Similar to other sensory systems, the auditory system has ample connections to parts of the brain that are not usually associated with sensory functions.35 Connections between the auditory system and motor systems are evident from such phenomena as the startle response and the acoustic middle ear reflex. There are also connections to speech motor centers from the auditory system. Connections from the auditory system to structures of the limbic system are important under normal conditions and in pathologies of the auditory system such as severe tinnitus123 (see Chapter 9). It is especially true of nuclei of the amygdala, which are important to the auditory system.35,94 Auditory information can reach the nuclei of the amygdala through mainly two routes. One route involves the primary auditory cerebral cortex, secondary cortices, and association cortices, which connect to the lateral nucleus of the amygdala.135 That route is known as the “high route,”94 and it carries highly processed information. The other route known as the “low route,”94 is shorter and faster and consists of direct connections to the lateral nucleus of the amygdala from the dorsal and medial parts of the MGB. The low route thus carries information from the nonclassical auditory pathway while the high route carries information from the classical auditory pathways. This information is likely to be subjected to modulation by other sensory input and intrinsic information from different parts of the CNS. The low route carries information that is little processed and less affected by other (intrinsic of extrinsic) neural activity.

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The lateral nucleus of the amygdala connects to the basolateral group of nuclei, which in turn connect to the central nucleus of the amygdala. That nucleus connects to many parts of the brain, such as the hippocampus and various endocrine centers.35,94 It also connects to the nucleus basalis, which is important for neural plasticity94 and controlling arousal. The nonclassical pathways that provide input to the amygdala through the low route may not be active in adults, but there are indications that it is active in young children102 and in some patients with tinnitus101 (see Chapter 9). The fast path between the dorsal and medial auditory thalamus and the amygdala may explain why sounds can evoke emotional reactions and why tinnitus can evoke fear and phonophobia and cause other affective symptoms such as depression.35,136

EVOKED POTENTIALS GENERATED BY THE EAR AND THE AUDITORY NERVOUS SYSTEM Evoked potentials from the ear and the auditory nervous system are important diagnostic tools. They have provided some insight in the differences between the human auditory system and that of the animals commonly used in studies of the function of the auditory system.

The Ear Several different types of evoked potentials can be recorded from the cochlea and its vicinity in response to sound. The earliest of such potentials is the cochlear microphonic (CM), which, as the name indicates, is a potential that has the same waveform as the sound. When recorded from the round window membrane, the CM potential is assumed to be generated by outer hair cells.137 Neural activity in the auditory nerve gives rise to evoked potentials (action potentials, APs) that can be recorded from the round window. When recorded from animals, these potentials are known as CM, summating potentials (SP), and AP (Fig. 2-18), and when recorded from the promontorium of the cochlea in humans they are known as electrocochleographic (ECoG) potentials (Fig. 2-19). When recorded from the round window in small animals, the AP consists of two negative peaks, the first generated in the cochlea by neural transduction processes and the second generated by the cochlear nucleus138 and conducted to the recording site by electronic conduction. Whereas the CM can best be visualized in response to continuous pure tones of low frequency, the AP is best visualized in response to a transient sound. This potential is a slow potential that follows the envelope of a sound and, like the CM, it is generated by hair cells.137 The SP is best visualized in response to tone bursts. The polarity of the SP can be either negative or positive, depending on the condition of the cochlea and the way the SP is recorded.139 By choosing a tone burst stimuli of a not-too-high frequency, all three potentials can be visualized in the same recording2 (see Fig. 2-18).

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Evoked Potentials from the Auditory Nervous System

Figure 2-18. Recording from the round window of a rat showing cochlear microphonic (CM ) and action potentials (AP ) (N1N2). The stimulus was a 5-kHz tone burst. The summating potential (SP ) is represented by the baseline shift during the tone burst. The sound is shown at the bottom of the graph. (Adapted from Møller AR: Auditory Physiology. New York, Academic Press, 1983.)

Auditory evoked potentials that are generated in the auditory nervous systems can be recorded from electrodes placed on the scalp. Three main types of auditory evoked potentials have been identified. The most commonly used type for neurotologic diagnosis is the evoked potentials that appear during the first 10 msec after a transient sound. These potentials are known as the brainstem auditory evoked potentials (BAEP). Potentials that appear in the time window of 0 to 80 msec (or 10 to 100 msec) after a stimulus are known as the middle latency responses (MLR), and those potentials that occur at longer latencies (50 to 500 msec or 50 to 1000 msec) are known as eventrelated potentials (ERP). Other auditory evoked potentials are the frequency-following response (FFR)143 and various kinds of myogenic potentials144 that can be recorded from electrodes placed on the scalp. These potentials, including the MLR and the ERP, have little importance in neurotologic diagnosis, and their generators are not known in any detail. We will therefore limit the discussions to the BAEP.

Electrocochleographic Potentials

Brainstem Auditory Evoked Potentials

The neural components of the ECoG potentials recorded in humans are different from the APs recorded in small animals in that the AP consists of two distinct peaks and the neural component of the ECoG normally consists of one peak140,141 (see Fig. 2-19). The reason for this difference between the response in humans and that in small animals is that potentials generated in the cochlear nucleus in small animals are conducted effectively to the recording site (the cochlea) due to the small distance between the cochlea and the cochlear nucleus. In humans, potentials that are generated in the cochlear nucleus are attenuated because of the much longer distance from the recording site (the cochlear capsule) to the cochlear nucleus (the length of the auditory nerve in small animals is 5 to 8 mm, whereas in humans it is 25 mm.142 The SP can also be identified in the ECoG recordings. ECoG potentials are often elicited by click sounds, which provide distinct AP components but less distinct CM and SP responses. If the purpose of recording ECoG is to obtain CM and SP responses, it is advantageous to use tone bursts as stimuli.2

These potentials are generated by the auditory nerve and the fiber tracts and nuclei of the ascending auditory pathway of the brainstem. Recorded in the conventional way, differentially between electrodes that are placed on the vertex (Cz) and on the mastoid (or earlobe) on the side that is being stimulated, the BAEPs are characterized by five to seven vertex-positive peaks.145 The first five peaks of the BAEP are relatively constant (although peak IV may at times be difficult to identify), but the peaks beyond peak V are variable. Some investigators prefer to display the BAEP with the vertex-positive peaks pointing upward; others show them pointing downward. The common way of displaying neuroelectric potentials is with the negative potential of the active electrode giving a downward deflection (Fig. 2-20). Only the vertex-positive peaks are labeled (with Roman numerals), whereas both positive and negative peaks of other evoked potentials are usually labeled. The spectral filtering used in connection with recording BAEP alters its waveform depending on the settings of the filters and the kinds of filters. Different investigators use a different degree of filtering, which is one reason the waveforms of the BAEP shown by different investigators often differ. The BAEP is of interest in neurotologic diagnosis because these potentials reflect the successive activation of the fiber tracts and nuclei of the ascending auditory pathway that is located in the brainstem (see Møller, 20002). The BAEP is an effective diagnostic tool for disorders that affect the auditory nerve, such as vestibular schwanomas.146,147 Together with recordings of the acoustic middle ear reflex and speech discrimination tests, these tests are very effective in diagnosing vestibular schwanomas.147 BAEP is also an effective test of vascular irritation of the auditory nerve, such as may occur in patients with tinnitus148 and in patients with a particular form of vestibular disorder (disabling positional vertigo, DPV)149 and inflammatory processes that affect the

Figure 2-19. Typical electrocochleographic (ECoG) recording from the promontorium of an individual with normal hearing in response to click stimuli (arrow). (Adapted from Eggermont JJ: Electrocochleography. In Keidel WD, Neff WD [eds.]: Handbook of Sensory Physiology, vol 3, chap 15, New York, Springer Verlag, 1976.)

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Figure 2-20. BAEP obtained in an individual with normal hearing. A, Vertexpositive peaks shown as upward deflections. B, Vertex-positive peaks shown as downward deflections. C, BAEP after filtering.

auditory nerve. A prerequisite for the use of BAEPs in differential diagnosis in neurotology is a determination of which neural structures generate the different components of these potentials. In the following section, the sources of these potentials are discussed. Neural Generators of Brainstem Auditory Evoked Potentials Earlier studies of the neural generators of the BAEP used information from animal research to identify the sources of BAEP peaks, but the differences between the small animals used in such studies and humans made it difficult to draw conclusions about the neural generators of the human BAEP on the basis of animal studies. The animals commonly used for auditory research only have four distinct peaks in their BAEP compared with the five in humans.150 Intracranial recordings from the auditory nerve in patients undergoing neurosurgical operations revealed that the auditory nerve is the generator of the first two peaks (I and II) in humans,151–153 whereas in animals only peak I is generated by the auditory nerve and peak II is generated by the cochlear nucleus.150,154 The explanation for these differences is that the human auditory nerve is much longer than that of the animals commonly used in studies of the auditory system. The auditory nerve in humans is approximately 2.5 cm long,142,155 and it is only 0.8 cm in the cat. Even the monkey has a much shorter auditory nerve than humans.154 This difference in length of the eighth cranial nerve in humans and the animals used in studies of the auditory system is partly the result of humans having larger heads than these animals and partly the result of the much larger subarachnoidal space of the

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cerebellopontine angle in humans compared with animals, including nonhuman primates. Other studies that used intracranial recordings of evoked potentials from different structures that belong to the ascending auditory pathway have revealed that peak III of the BAEP is mainly generated by the cochlear nucleus.156 However, it must be emphasized that the neural generators of peaks III, IV, and V are more complex than those of peaks I and II. Peaks I and II only have contributions from the auditory nerve. Although the (ipsilateral) cochlear nucleus is the main contributor to peak III, peak III also may have contributions from the auditory nerve, and possibly from the cochlear nucleus, on the opposite side. Little is known about the generator of peak IV, but studies in patients undergoing neurosurgical operations indicate that the source of peak IV is located near the midline157 and that the SOC is most likely an important contributor to peak IV.152 The anatomy of the SOC is complex, with nuclei scattered throughout a large region of the brainstem, and there are many interconnections between the two sides of the SOC. The fact that the appearance of peak IV is not as constant as the other peaks of the BAEP makes it difficult to determine the exact anatomical location of the generators of this peak. It was assumed earlier that peak V was generated by the IC but the results of intracranial recordings in patients undergoing neurosurgical operations have indicated that the sharp (vertex-positive) portion of the peak is generated by the lateral lemniscus where it terminates in the IC.157–159 The slow (vertex-negative) deflection that follows the sharp part of peak V (SN10)160 most likely represents dendritic potentials from the IC.161 Animal experiments, however, indicate that the IC does not produce any noticeable far-field potentials,154 despite the fact that a very clear (slow) response can be obtained by recording directly from the nucleus both in animals154 and in humans.158,159 The failure of the IC to produce any noticeable far-field potentials is assumed to be related to nearly random organization of the dendrites of the cells of the IC, which causes the electrical field produced by the nuclei to decrease rapidly with distance from the nucleus (known as a closed field).162 However, the SN10 of some individuals is very large, suggesting a large individual variation of the anatomy of the IC. The fact that only vertex-positive peaks of the BAEP are labeled has diverted the interest from the vertex-negative peaks. Most studies of the neural generators of the BAEP have focused on the vertex-positive peaks despite the fact that the negative peaks may have distinct generators,157 as does the vertex-positive peaks, and these vertex-negative peaks may be of diagnostic value. Figure 2-21 shows a simplified summary of the neural generators of the BAEP in humans.163 The generation of evoked potentials from the nervous system is often represented by dipoles. The amplitude of the recorded potentials depends on the orientation of such (fictive) dipoles in relation to a line through the two recording electrodes. The greatest amplitude is obtained when the orientation of the dipoles is parallel to the line between the recording electrodes, and small potentials are recorded when the orientation of a dipole is perpendicular

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ACOUSTIC MIDDLE EAR REFLEX

Figure 2-21. Neural generators of the human BAEP. DCN, dorsal division of the cochlear nucleus; LL, lateral lemniscus; MG, medial geniculate body; SO, superior olivary complex; VCN, ventral division of the cochlear nucleus. (Adapted from Møller AR, Jannetta PJ: Simultaneous surface and direct brainstem recordings of brainstem auditory evoked potentials (BAEP ) in man. In Cracco RQ, Bodis-Wollner I [eds.]: Evoked Potentials, chap 20, New York, Alan R Liss, 1986.)

to a line through the recording electrodes. The dipoles of the generators of peak I and II are nearly horizontal, whereas the source of peak V is nearly vertical and the orientation of the dipole of peak III is approximately 30 degrees from the horizontal plane.164 This means that the conventional electrode placement (between the mastoid and the vertex) is not ideal for recording peak I, II, and V but nearly ideal for recording peak III. This is the reason that some investigators have chosen to record BAEP in two channels, with one pair of electrodes placed at the ear lobe and the other pair placed at the vertex and the neck. The placement of the earlobe electrodes is ideal for recording peak I and II and will also record peak III. The other pair of electrodes are in an ideal position to record peak V and will also record peak III. Individual differences in the auditory nervous system are considerable, which makes the amplitude and the latency of the different components of the BAEP vary among individuals. The effectiveness of different electrode placements also varies from one individual to another.

The acoustic middle ear reflex causes the middle ear muscles to contract in response to a strong sound. Testing of the acoustic middle ear reflex is of value in neurotologic diagnosis because its reflex arc involves the ear and parts of the ascending auditory nervous system up to the nuclei of the SOC. Also the reflex’s efferent limb involves the facial motonucleus and the most central portion of the facial nerve. Disorders of the auditory nerve affect the response of the acoustic middle ear reflex, and, in particular, the growth of the reflex response with increasing stimulus intensity is grossly impaired in many disorders of the auditory nerve, such as vestibular schwannomas and vascular compression. The contraction of the middle ear muscles can be recorded noninvasively by recording changes in the ear’s acoustic impedance.2 Contraction of the stapedius muscle reduces sound transmission in the middle ear and, therefore, the reflex acts to keep input to the cochlea nearly constant for sounds that exceed the threshold of the reflex. The acoustic middle ear reflex acts to suppress steady-state sounds of slowly varying intensity, whereas transmission of sounds with fast changes in intensity are not affected.2,165 An intact middle ear reflex has been shown to be important in protecting against hearing damage from noise exposure.166 The neural pathway (reflex arc) of the stapedius reflex has been studied in detail in the rabbit by lesion techniques.75 The reflex arc for the stapedius muscle involves the cochlea, the auditory nerve, the ventral cochlear nucleus, and the trapezoidal body. There are connections to the ipsilateral and contralateral facial motonuclei via interneurons in the medial superior olive2 (Fig. 2-22). Direct connections also exist between the ventral cochlear nucleus and the facial motonucleus. In addition, numerous indirect pathways exist, but little is known about these. The inferior colliculus does not seem to be involved in the acoustic middle ear reflex.75 The population of neurons in the facial motonucleus involved in the acoustic reflex is located at the edge of the facial motonucleus anatomically adjacent to the SOC.167 In humans, activation of the acoustic middle ear reflex causes contractions of only the stapedius muscle. In the animals commonly used in auditory research, the tensor tympani muscle is also involved, although it has a somewhat higher threshold than the stapedius muscle. The reflex arc for the acoustic tensor tympani reflex that is active in animals involves the cochlea, the auditory nerve, the ventral cochlear nucleus, the superior olivary complex, and the motonucleus of the fifth cranial nerve.75 In humans, the tensor tympani can be made to contract by stimulating the skin around the eye, for instance by an air

Figure 2-22. Reflex arc of the acoustic stapedius reflex. N VIII, Auditory nerve; N VII, facial nerve; VCN, ventral cochlear nucleus; SO, superior olive; n VII, facial motonucleus. (Adapted from Møller AR: Auditory Physiology. New York, Academic Press, 1983.)

Physiology of the Ear and the Auditory Nervous System

puff.168 This response is not an acoustic reflex, but a trigeminal reflex similar to the blink reflex. When only one ear is stimulated, the reflex response is bilateral. In humans, ipsilateral stimulation elicits a stronger contraction than the same level of contralateral stimulation, and the threshold for ipsilateral activation is slightly lower than it is for contralateral activation.169 Bilateral stimulation is about 3 dB more effective than ipsilateral stimulation (Fig. 2-23). The threshold of the middle ear reflex for contralateral stimulation is about 85 dB above hearing threshold in the frequency range of 500 to 4000 Hz.2,170 The strength of the stapedius muscle contraction increases with increasing stimulus intensity.165,169 A lowfrequency continuous tone or noise elicits a sustained contraction of the stapedius muscle, but the reflex adapts after a few seconds when elicited by tones of frequencies higher than about 1500 Hz. (For more detail about the physiology of the acoustic middle ear reflex, see Møller, 20002.) Because the branch of the facial nerve that innervates the stapedius muscle exits the main trunk of the facial nerve at a point between the brainstem and the stylomastoid foramen, testing for the middle ear reflex response can help determine the anatomic location of injury to the facial nerve. When the facial nerve regenerates from a central location, the acoustic middle ear reflex response returns before contractions of the facial muscles. This means that the acoustic middle ear reflex test is a predictor of facial recovery in patients with facial palsy such as Bell’s palsy. Return of the acoustic middle ear reflex

Figure 2-23. Response of the acoustic middle ear reflex, recorded as changes in the ear’s acoustic impedance, to 500-ms tone bursts (1450 Hz) at different intensities. Recordings were made in both ears while the stimulus tone was applied to one or both ears. Solid lines show the response to ipsilateral stimulation, and dashed lines show the response to contralateral stimulation (when both ears were stimulated, the solid line is from the right ear). (Adapted from Møller AR: The acoustic reflex in man. J Acoust Soc Am 34:1524–1534, 1962.)

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response means that the facial nerve is in the process of regenerating, and although no facial muscle activity is yet present, this return of the reflex is a good indication that facial function will also return. The ipsilateral response returns sooner than the contralateral response and should therefore be used as a test of regeneration of the facial nerve.

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123. Møller AR: Symptoms and signs caused by neural plasticity. Neurol Res 23:565–572, 2001. 124. Kaas JH: Plasticity of sensory and motor maps in adult mammals. Ann Rev Neurosci 14:137–167, 1991. 125. Merzenich MM, Recanzone G, Jenkins WM, et al: Cortical representational plasticity. In Rakic P, Singer W (eds.): Neurobiology of Neocortex. New York, Wiley, 1988, pp 41–67. 126. Schwaber MK: Neuroplasticity of the adult primate auditory cortex following cochlear hearing loss. Am J Otol 14:252–258, 1993. 127. Irvine DR, Rajan R: Injury-induced reorganization of frequency maps in adult auditory cortex: The role of unmasking of normallyinhibited inputs. Acta Otolaryng (Stockh) 532:39–45, 1997. 128. Weinberger NM: Learning-induced physiological memory in adult primary auditory cortex: Receptive field plasticity, model, and mechanisms. Audiol Neuro-Otol 3:145–167, 1998. 129. Kilgard MP, Merzenich MM: Cortical map reorganization enabled by nucleus basalis activity. Science 279:1714–1718, 1998. 130. Ungeleider LG, Mishkin M: Analysis of visual behavior. In Ingle DJ, Goodale MA, Mansfield RJW (eds.): Analysis of Visual Behavior. Cambridge, MA, MIT Press, 1982. 131. Rauschecker JP, Tian B: Mechanisms and streams for processing of “what” and “where” in auditory cortex. Proc Nat Acad Sci U S A 97:11800–11806, 2000. 132. Kaas JH, Hackett TA: Subdivisions of auditory cortex and processing streams in primates. Proc Nat Acad Sci U S A 97:11793–11799, 2000. 133. Romanski LM, Tian B, Fritz J, et al: Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex. Nat Neurosci 2:1131–1136, 1999. 134. Tian B, Reser D, Durham A, et al: Functional specialization in rhesus monkey auditory cortex. Science 292:290–293, 2001. 135. McDonald AJ: Cortical pathways to the mammalian amygdala. Progr Neurobiol 55:257–332, 1998. 136. Møller AR: Similarities between severe tinnitus and chronic pain. J Am Acad Audiol 11:115–124, 2000. 137. Dallos P: The Auditory Periphery: Biophysics and Physiology. New York, Academic Press, 1973. 138. Møller AR: On the origin of the compound action potentials (N1N2) of the cochlea of the rat. Exp Neurol 80:633–644, 1983. 139. Ferraro JA, Ruth RA: Clinical electrocochleography. Hear J 38:51–55, 1985. 140. Coats AC: Human auditory nerve action potentials and brainstem evoked responses-latency-intensity functions in detection of cochlear and retrocochlear pathology. Arch Otolaryngol 104: 709–717, 1978. 141. Eggermont J: Electrocochleography. In Keidel W, Neff W (eds.): Handbook of Sensory Physiology, vol 3. New York, Springer Verlag, 1976, pp 625–705. 142. Lang J: Facial and vestibulocochlear nerve, topographic anatomy and variations. In Samii M, Jannetta P (eds.): The Cranial Nerves. New York, Springer Verlag, 1981, pp 363–377. 143. Moushegian G, Rupert AL, Stillman RD: Evaluation of frequency following potentials in man: Masking and clinical studies. Electroenceph Clin Neurophysiol 45:711–718, 1978. 144. Douek EE, Ashcroft PB, Humphries KN: The clinical value of the postauricular myogenic (crossed acoustic) response in neuro-otology. In Stephens SDG (ed.): Disorders of Auditory Function II. London, Academic Press, 1976, pp 139–144. 145. Jewett DL, Williston JS: Auditory evoked far fields averaged from scalp of humans. Brain 94:681–696, 1971. 146. Selters WA, Brackmann DE: Acoustic tumor detection with brainstem electric response audiometry. Arch Otolaryngol 103:181–187, 1977. 147. Godey B, Morandi X, Beust L, et al: Sensitivity of auditory brainstem response in acoustic neuroma screening. Acta Otolaryngol (Stockh) 118:501–504, 1998.

148. Møller MB, Møller AR, Jannetta PJ, Jho HD: Vascular decompression surgery for severe tinnitus: Selection criteria and results. Laryngoscope 103:421–427, 1993. 149. Møller MB, Møller AR, Jannetta PJ, Jho HD, et al: Microvascular decompression of the eighth nerve in patients with disabling positional vertigo: Selection criteria and operative results in 207 patients. Acta Neurochirur 125:75–82, 1993. 150. Buchwald J, Huang C: Far field acoustic response: Origins in the cat. Science 189:382–384, 1975. 151. Hashimoto I, Ishiyama Y, Yoshimoto T, Nemoto S: Brainstem auditory evoked potentials recorded directly from human brain stem and thalamus. Brain 104:841–859, 1981. 152. Møller AR, Jannetta PJ: Compound action potentials recorded intracranially from the auditory nerve in man. Exp Neurol 74:862–874, 1981. 153. Martin WH, Pratt H, Schwegler JW: The origin of the human auditory brainstem response wave II. Electroenceph Clin Neurophysiol 96:357–370, 1995. 154. Møller AR, Burgess JE: Neural generators of the brain stem auditory evoked potentials (BAEPs) in the rhesus monkey. Electroenceph Clin Neurophysiol 65:361–372, 1986. 155. Lang J: Clinical Anatomy of the Head. New York, Springer Verlag, 1983. 156. Møller AR, Jannetta PJ: Auditory evoked potentials recorded from the cochlear nucleus and its vicinity in man. J Neurosurg 59:1013–1018, 1983. 157. Møller AR, Jho HD, Yokota M, Jannetta PJ: Contribution from crossed and uncrossed brainstem structures to the brainstem auditory evoked potentials (BAEP): A study in human. Laryngoscope 105:596–605, 1995. 158. Hashimoto I: Auditory evoked potentials from the humans midbrain: Slow brain stem responses. Electroenceph Clin Neurophysiol 53:652–657, 1982. 159. Møller AR, Jannetta PJ: Evoked potentials from the inferior colliculus in man. Electroenceph Clin Neurophysiol 53:612–620, 1982. 160. Davis H, Hirsh SK: A slow brain stem response for low-frequency audiometry. Audiology 18:441–465, 1979. 161. Møller AR, Jannetta PJ: Interpretation of brainstem auditory evoked potentials: Results from intracranial recordings in humans. Scand Audiol (Stockh) 12:125–133, 1983. 162. Lorente de No R: Analysis of the distribution of action currents of nerve in volume conductors. Studies of the Rockefeller Institute for Medical Research 132:384–482, 1947. 163. Møller AR, Jannetta PJ: Simultaneous surface and direct brainstem recordings of brainstem auditory evoked potentials (BAEP) in man. In Cracco RQ, Bodis-Wollner I (eds.): Evoked Potentials. New York, Alan R. Liss, 1986, pp 227–234. 164. Scherg M, von Cramon D: A new interpretation of the generators of BAEP waves I V: Results of a spatio temporal dipole. Electroenceph Clin Neurophysiol 62:290–299, 1985. 165. Møller AR: The acoustic reflex in man. J Acoust Soc Am 34:1524–1534, 1962. 166. Zakrisson JE, Borg E, Diamant H, Møller AR: Auditory fatigue in patients with stapedius muscle paralysis. Acta Otolaryngol (Stockh) 79:228–232, 1975. 167. Joseph MP, Guinan JJ, Fullerton BC, et al: Number and distribution of stapedius motoneurons in cats. J Comp Neurol 232:43–54, 1985. 168. Klockhoff I, Anderson H: Recording of the stapedius reflex elicited by cutaneous stimulation. Acta Otolaryngol (Stockh) 50:451–454, 1959. 169. Møller AR: Bilateral contraction of the tympanic muscles in man, examined by measuring acoustic impedance-change. Ann Otol Rhinol Laryngol 70:735–753, 1961. 170. Møller AR: The sensitivity of contraction of the tympanic muscles in man. Ann Otol Rhinol Laryngol 71:86–95, 1962.

3

Outline Peripheral Anatomy Vestibular Nerve Vestibular Nuclei Central Termination of the Vestibular Nerve Efferent Projections of Vestibular Nuclei

Chapter

Anatomy of the Central Vestibular System

Vestibulocerebellar Connections Commissural Projections Vestibulospinal Projections Vestibulo-Ocular Projections Efferent Vestibular Pathway Vestibuloreticular Projections

Other Afferent Projections to the Vestibular Nuclei Spinal Vestibular Projections Vestibulocerebellar Projections Higher Central Vestibular Centers Cortical Vestibular Projection

T

he vestibular system is one of the oldest central nervous system reflex pathways, both phylogenetically and ontogenetically. It performs a basic stabilizing function in all species, although in higher animal forms it is especially developed to provide orientation for posture and locomotion on land, sea, and air. The reflexes to eye muscles and trunk and limb muscles are developed to meet the needs of these animal forms. Although the primary function of the maintenance of body orientation in space is accomplished by intricate vestibular system reflexes acting on the body, limb, and extraocular muscles, other modalities interact with the vestibular system to accomplish equilibrium. These are vision, proprioception, and cerebellar function. The discussion here focuses primarily on the vestibular system because most of the disorders encountered clinically affect the peripheral and less often the central nervous portions of the pathway. The neurotologist, however, should be aware of other contributing sensory systems, not only because they may occasionally be responsible for balance disorders but also because of their role in recovery from a vestibular lesion induced by either pathology or therapy.

PERIPHERAL ANATOMY Mammals have two types of vestibular sense organ, crista ampullaris and macula utriculi and sacculi, which are contained in the endolymph-filled membranous labyrinth surrounded by perilymph in the bony labyrinth. The different chemical compositions of endolymph and perilymph1 are responsible for vastly different bioelectric potentials that are essential for the normal function of these sense organs.2 Crista ampullaris is the sense organ of the semicircular canal and is located in the enlarged portion (ampulla) of the membranous semicircular canal, which is positioned to represent a plane in space. The crista is a ridge of neurosensory epithelium that is covered by a gelatinous cupula composed of mucopolysaccharides. The cupula extends

Richard R. Gacek, MD, FACS

from the surface of the sense organ to the ampullary roof and serves as an elastic partition that can be deformed by endolymph movement created by the stimulus of angular acceleration or deceleration. This cupular deflection causes a deflection of the rigid stereocilia, which protrude from the sensory cells, resulting in an electrical response in the vestibular nerve fibers. The macula of the utricle or the saccule is a saucer-shaped arrangement of neurosensory cells that lies beneath a mesh-like otoconial membrane that contains calcium carbonate crystals (otoliths) with a specific gravity of 2.71. Displacement of the otoconial blanket by linear acceleration and deceleration or gravity causes deflection of the hair cell cilia in this sense organ and a subsequent neural discharge. Two types of cell populate the sensory epithelium of the mammalian vestibular labyrinth.3 These are called type I and type II hair cells4,5 (Fig. 3-1). Type I hair cells are phylogenetically newer, are flask shaped, and are engulfed by a large calyx-like terminal, which is supplied by large-caliber vestibular dendrites. Small vesiculated nerve terminals also make contact with the nerve terminal or the dendrite.6 A single large dendrite typically innervates one or two type I hair cells and rarely may innervate three hair cells. Type II hair cells are cylindrical and directly contacted by small bouton-type terminals belonging to small-caliber vestibular dendrites. Vesiculated bouton terminals also contact the cell surface of the type II hair cells. Small afferent fibers branch and innervate a large number of type II hair cells over a larger area of the vestibular sensory epithelium. Therefore, each large nerve fiber receives input from a restricted area of the sense organ, but each small fiber is associated with more extensive regions of the neuroepithelium. Both types of hair cell have a characteristic arrangement of cilia protruding from the cuticular (superior) plate. Each cell has a single kinocilium located at one edge of a large number (100 to 200) of stereocilia (see Fig. 3-1). This special arrangement of the kinocilium and stereocilia determines the electrical response that occurs from ciliary deflection.7,8 Deflection of the cilia toward the kinocilium decreases the 75

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Location of type I hair cells differs in the two types of sense organ.10 Type I hair cells are predominant at the top of the crista and type II cells are more common along the slopes. Macular type I hair cells seem to be more prevalent near the striola line, although they may be distributed among the type II cells in the remaining areas of the macula.11,12

VESTIBULAR NERVE

Figure 3-1. The two types of mammalian vestibular hair cell and their innervation.

potential difference that exists between endolymph and the sensory cell (approximately 120 mmol), causing intracellular depolarization and an increase in the frequency of the action potentials in vestibular nerve fibers. Conversely, deflection of the cilia away from the kinocilium results in intracellular hyperpolarization and a decrease in the vestibular nerve action potentials. Since most vestibular neurons have a resting neural discharge, an opportunity exists to either increase or decrease the neural activity. Type I and type II hair cell distribution in the vestibular sense organs is characteristic for the type of sense organ.9 In the crista ampullaris all hair cells are similarly oriented so that the kinocilium is on the same side of the stereocilia. In the crista of the lateral canal the kinocilium is located closest to the utricle, whereas in the vertical canals the kinocilium is located away from the utricular end of the membranous canal (Fig. 3-2). In the macula of the utricle and saccule the hair cell orientation is 180 degrees opposite in the two halves of the macula. In the utricular macula the hair cell polarization is directed toward a line that more or less bisects the macula (striola line). In the saccular macula the polarization of hair cells is away from the striola line. This arrangement of hair cells in each macula makes it possible for opposite effects to occur in hair cells of each half of the macula in response to a given stimulus. In the crista, the movement of endolymph in a particular canal can produce either a decrease or an increase in the neural resting potentials. When angular acceleration occurs in a particular plane, the coplanar canals from each labyrinth are stimulated in opposite directions, producing excitation in one canal and inhibition in the other. The two canals are complementary. The lateral canals of each labyrinth are coplanar; the anterior and posterior canals of one labyrinth are complementary to the posterior and anterior canals of the contralateral labyrinth.

The vestibular nerve that supplies the five vestibular sense organs in each labyrinth is composed of bipolar neurons with myelinated peripheral and central processes.13,14 The ganglion cells of these bipolar neurons are located in Scarpa’s ganglion surrounded by cerebrospinal fluid in the internal auditory canal (Fig. 3-3). The human vestibular nerve is composed of approximately 18,000 neurons,15 and the monkey has a similar number. The cat has 12,000 nerve fibers, the guinea pig and chinchilla, each about 7000.16 In the cat the myelinated fiber composition ranges from 1 to 10 μm with the majority being between 2 and 4 μm. Richter and Spoendlin17 found that the ganglion cells of Scarpa’s ganglion in the cat measured from 25 to 47 μm in diameter. In these mammalian species the sense organs of the semicircular canals and the utricle receive an approximately equal number of nerve fibers, whereas the saccular nerve contains a lower number. For example, in the monkey and the human, each of the three ampullary nerves and the utricular nerve has approximately 3500 nerve fibers. The saccular nerve has slightly fewer than 3000 nerve fibers. These first-order vestibular neurons terminate in all four major vestibular nuclei and in three minor nuclei. The dendrites of the neurons supplying the cristae of the three semicircular canals are located in both the inferior and the superior vestibular divisions but their axons are located in the rostral half of the vestibular nerve as it enters the brainstem (see Fig. 3-3). The neurons supplying both the utricular and saccular maculae occupy the caudal half of the vestibular nerve before entering the brainstem. The differential localization of the canal and macular fibers predicts a different termination within the vestibular nuclei. The canal neurons terminate in the superior and medial vestibular nuclei primarily, although the macular input

Figure 3-2. Schematic summary of the polarization of hair cell cilia in the vestibular sense organs.

Anatomy of the Central Vestibular System

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Vestibular nerve fibers are spontaneously active so as to allow bidirectional change depending on the deflection of hair cell cilia in the periphery. Generally, the discharge rates range from 10 or fewer spikes per second to more than 100 spikes per second.22 A small but undetermined number of neural units are silent unless provoked. The mean firing rates in the nerve supplying the cristae are somewhat higher than those supplying the maculae (the crista is 90 spikes per second and the macula is 60 spikes per second). Although a major input to the vestibular nuclei is from the labyrinth, several other afferent inputs influence the activity in these nuclei and their reflex actions via several efferent projections. A description of the major vestibular nuclei and several minor cell groups precedes a discussion of these afferent and efferent projections.

VESTIBULAR NUCLEI

Figure 3-3. The peripheral course of first-order vestibular neurons in a right ear. SG, Scarpa’s ganglion; OCB, efferent cochlear bundle. The darkened area shows location of large fiber group in the superior vestibular division.

concerns the lateral, medial, and descending vestibular nuclei.18,19 Vestibular neurons display a wider spectrum of fiber size than the cochlear nerve.16 In the cat the vestibular neurons range from 1 to 10 μm in diameter, and the cochlear nerve ranges from 1 to 8 μm. Similarly, the monkey vestibular nerve fiber range is from 1 to 9 μm, whereas the cochlear nerve is 1 to 8 μm. In the monkey most of the fibers in both the nerves are from 3 to 4 μm in diameter, whereas in the cat the cochlear nerve has a majority of fibers in the 3- to 4-μm range, while the majority of cat vestibular nerve fibers are 2 to 4 μm. In this population of vestibular nerve fibers, one can differentiate a small population of large neurons and a larger population of small neurons18 (see Fig. 3-3). These two types of vestibular neuron are associated with a different peripheral input, with the large fibers innervating the type I hair cells and the small fibers the type II hair cells. A group of intermediate-sized fibers has a dimorphic form of innervation that combines both type I and type II hair cells. The differential localization of these fibers in the ampullary nerve, where large fibers predominate in the center and smaller ones at the periphery, reflects the peripheral terminus of these fibers. The large fibers have been shown to have an irregular discharge pattern and the small fibers a regular discharge pattern,20,21 further strengthening the concept of differential units within the vestibular nerve supplying a different hair cell terminus and exhibiting different activity patterns and probably central terminations. The significance of these two major types of functional units is not known.

The first-order vestibular neurons terminate in all four major vestibular nuclei (Fig. 3-4) and in three minor ones. The main vestibular nuclei are the superior, lateral, medial, and descending nuclei.23 The superior vestibular nucleus lies in the rostral portion of the fourth ventricle and is bordered by the brachium conjunctivum superiorly, the restiform body laterally, the fourth ventricle medially, and various neural structures coursing across the brainstem ventrally; these are the facial nerve root, the descending trigeminal root, and the rostral end of the lateral vestibular nucleus, which undercuts the caudal end of the superior nucleus. The superior vestibular nucleus is comprised of medium-sized neurons, which tend to have a high concentration in the central portions

Figure 3-4. Summary of the central termination of the vestibular neurons that supply the cristae ampullares.

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Figure 3-5. Photomicrograph of a transverse section through the superior vestibular nucleus showing the distribution of large, medium, and small cells (cresyl violet stain). RB, restiform body; BC, brachium conjunctivum; IV, fourth ventricle; V, vestibular nerve root.

of the nucleus, while small neurons predominate laterally and medially (Fig. 3-5). The medium-sized cells are multipolar or pear shaped. Clusters of larger multipolar cells, which are dispersed among the medium-sized cells, are present in the central portion of the nucleus. The dendrites of the cells in the superior nucleus radiate in different directions. Some dendrites are directed medially and ventral laterally. In the peripheral region of the nucleus, dendrites are arranged tangential to the nuclear border. By and large the dendritic trees of these neurons remain within the confines of the nucleus, but in the ventral region some dendrites may extend into the adjacent reticular formation. The larger neurons in the central portion of the nucleus are strung out in a ventral lateral to dorsal medial direction and separated by bundles of nerve fibers representing the incoming vestibular nerve. The large and medium-sized neurons are primarily those that represent vestibulo-ocular projections and vestibulocerebellar projections. The small neurons represent commissural neurons.24 The peripheral input to the superior vestibular nucleus is entirely from the semicircular canals, while the efferent projections are vestibulo-ocular, vestibulocerebellar, and commissural. The lateral vestibular nucleus is located immediately caudal to the superior vestibular nucleus and its rostral end undercuts the caudal end of the superior vestibular nucleus. It is bordered laterally by the restiform body, superiorly by the cerebellar nuclei, medially by the dorsal acoustic stria, which separates it from the medial vestibular nucleus, and caudally by the rostral ends of the medial and descending vestibular nuclei. The lateral vestibular nucleus is characterized by large, multipolar neurons and numerous smaller cells, which are concentrated in two subdivisions, a larger dorsocaudal division and a smaller rostroventral division (Fig. 3-6). This division represents a separation of the two groups of large neurons, which receive different primary inputs. The ventral division of the lateral vestibular nucleus receives input from the labyrinth, primarily those fibers inputting from the utricular macula. The primary vestibular fibers enter the nucleus from a lateral aspect and are seen to radiate in a fanlike pattern within the limits of the nucleus. A prominent

Figure 3-6. Transverse section through the dorsal (DL) and ventral (VL) divisions of lateral vestibular nucleus and the rostral extension of medial nucleus (M). RB, restiform body; DAS, dorsal acoustic stria; V, descending trigeminal root; VII, facial nerve genu; VI, abducens nucleus.

projection of myelinated fibers enters the nucleus from a dorsal aspect to supply the dorsal division. These represent cerebellar vestibular afferents. However, collateral branches from the descending rami of canal neurons also terminate in cells of the ventral division. The dorsal division of the lateral nucleus receives its primary input from the cerebellar cortex, particularly from the hemisphere, flocculus, and paraflocculus. The primary output of the large multipolar neurons of the lateral nucleus is in a descending direction to the anterior horn cells of the spinal cord. These neurons form the lateral vestibulospinal tract. The medial vestibular nucleus is the longest rostracaudally of the major vestibular nuclei and has a main body that extends from the caudal end of the lateral vestibular nucleus caudal to the facial nerve nucleus, where it tapers to its caudal end. The medial border of the nucleus is formed by the floor of the fourth ventricle; laterally, it interfaces with the descending vestibular nucleus. The medial vestibular nucleus has a narrow rostral extension that extends medial to the dorsal acoustic stria and blends in with the caudal portion of the superior vestibular nucleus (see Figs. 3-6 and 3-7). The cells of the medial

Figure 3-7. Transverse section through the caudal part of the lateral nucleus and the midportion of medial (M) nucleus. The group Y nucleus is also seen at this level.

Anatomy of the Central Vestibular System

Figure 3-8. High-power photomicrograph of the medial nucleus showing the large vestibulo-ocular neurons (to abducens nucleus) and smaller commissural neurons.

vestibular nucleus are large, medium, and small with most of the small neurons located in the rostral extension (Fig. 3-8), whereas in the wider caudal section or body of the medial nucleus, large and medium-sized cells predominate (see Fig. 3-7). The large and medium cells in the body of the medial vestibular nucleus represent the primary terminus of first-order neurons terminating by way of the descending rami of incoming nerve fibers. These neurons represent input from the semicircular canals, the utricle, and to a smaller extent, the saccule. These neurons project contralaterally as the vestibulo-ocular pathway, and in a descending fashion down the medial longitudinal fasciculus as the medial vestibulospinal tract. A small number of neurons in the medial vestibular nucleus also project rostrally in the lateral tegmental field as a separate vestibulo-ocular pathway (ascending tract of Deiters), which terminates in the ipsilateral portion of the oculomotor nucleus that serves the medial rectus eye muscle.25 The larger neurons in the rostral extension of the medial vestibular nucleus represent vestibulo-ocular neurons projecting to the ipsilateral and contralateral abducens nuclei (see Fig. 3-8). The small neurons throughout the rostral as well as the body of the medial vestibular nucleus provide the commissural projections of this nucleus. The descending (spinal) vestibular nucleus parallels and is lateral to the body of the medial vestibular nucleus extending from the caudal end of the lateral vestibular nucleus and bordered laterally by the restiform body (Fig. 3-9). This nucleus contains large and medium neurons, which are interspersed among longitudinally coursing fiber bundles representing the descending rami of firstorder vestibular neurons as well as cerebello-vestibular projections. The primary output of the descending nucleus is in a descending direction over the medial vestibulospinal tracts. A commissural component is present comparable to those of the medial and superior vestibular nuclei. Several minor cell groups are associated with the vestibular nuclei.23 The group Y nucleus is comprised of

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densely packed, small, spindle-shaped neurons that are interspersed between the restiform body and the lateral vestibular nucleus and capped by the fasciculus angularis26 (see Fig. 3-7). It extends laterally toward the dorsal cochlear nucleus. A subdivision of this nucleus (infracerebellar) lies dorsal to the fasciculus angularis and contains large and medium-sized multipolar and pear-shaped neurons. The small neurons of the group Y nucleus represent commissural projections to the contralateral group Y and superior vestibular nuclei24 (Fig. 3-10B). The larger neurons in the infracerebellar nucleus, which project ipsilaterally to the oculomotor and trochlear nuclei, represent vestibuloocular neurons (Fig. 3-10A). Because both divisions of the group Y receive input from the saccular nerve,18 they activate commissural as well as vestibulo-ocular reflexes initiated by saccular input.27 The interstitial nucleus of the vestibular nerve (NIV) is a fusiform nucleus with some strands of cells embedded in the entering vestibular root fibers as it courses over the descending trigeminal root (Fig. 3-11). The cells are medium sized and elongated parallel to the vestibular root fibers. Occasionally large cells derived from the lateral nucleus are found in this nucleus. This nucleus has two divisions, rostral and caudal, which receive collateral input from the neurons projecting from the semicircular canals (see Fig. 3-4). The rostral division receives the input from the canals of the superior vestibular division (lateral and anterior), while the caudal receives those of the posterior canal.18 The efferent projection of the NIV is not precisely known, although it has been observed to label when horseradish peroxidase (HRP) is injected into the contralateral vestibular nuclei, which suggests a commissural connection.24 The group L nucleus is a small subset of medium-sized lateral vestibular nucleus multipolar neurons that lies between the lateral vestibular nucleus and the restiform body (see Figs. 3-6 and 3-7). These cells have abundant branching dendrites, which are oriented parallel to the fibers of the restiform body. It is considered part of the lateral nucleus and sends fibers to spinal cord levels.23 Because it is regarded as part of the lateral nucleus, the afferent input to this minor nucleus is from the utricular nerve.

Figure 3-9. Transverse section through the caudal portions of the medial (M) and descending (D) vestibular nuclei.

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A

and the restiform body. It contains small cells with short branching dendrites that are confined to the territory of the group. Although it has been considered part of the descending vestibular nucleus, lesions of the eighth nerve do not produce degeneration in this group, although there is abundant degeneration in the descending nucleus. Therefore it does not receive primary input from the periphery. However, group X does receive a heavy influx of spinal afferent ascending fibers as well as a projection from the contralateral descending vestibular nucleus. These cerebellar and spinal projections qualify it as part of the vestibular nuclear complex. Group Z is a small collection of cells near the nucleus gracilis just beneath the dorsal surface of the medulla. It is dorsal to the caudal end of the descending vestibular nucleus and group G. It contains medium-sized cells, which are oval, and it has unbranched dendrites that do not extend beyond its nuclear borders. This group does not receive primary vestibular fibers but does receive spinal afferents. Therefore it is similar to group X in this regard. Other small-cell groups have been mentioned in the literature regarding the vestibular nuclear complex, but their efferent and afferent projections are unknown and they do not appear to be important for vestibular function.

Central Termination of the Vestibular Nerve

B Figure 3-10. The two components of group Y nucleus are shown by retrograde labeling techniques. A, Infracerebellar division to the oculomotor nucleus. B, Commissural neurons of group Y.

Group F is a collection of closely packed relatively large cells near the descending vestibular nucleus. Ventrolaterally, it is related to the spinal trigeminal tract and nucleus, and the cells have short, richly branched dendrites that do not extend far from the cell bodies. This group does not receive primary vestibular fibers but does send fibers to the cerebellum and therefore is considered a part of the vestibular nucleus complex. The group does receive input from the cerebellum by way of the hook bundle. Group X is another very discrete small-cell group that is located lateral to the caudal end of the descending nucleus

The first-order neurons from the cristae bifurcate on entering the brainstem and then terminate in all regions of the superior vestibular nucleus by way of an ascending ramus and the rostral portion of the medial vestibular nucleus by way of a descending ramus.13,14,18 Collateral branches are given off both the descending and ascending branches, providing additional rich termination in the rostral extension of the medial nucleus and ventral division of the lateral nucleus (see Fig. 3-4). Collaterals also supply terminal fibers to the medial portion of the superior nucleus. The incoming axons of the vestibular neurons also terminate in the interstitial nucleus of the vestibular nerve by way of short collaterals. The ascending ramus after terminating in the superior nucleus proceeds through the brachium conjunctivum to the vestibular portion of the cerebellum (the nodulus, uvula, flocculus, and paraflocculus). A differential localization of ascending rami and termination exists for superior and lateral canal input compared with the posterior canal input in the superior vestibular nucleus.18,19 The posterior canal input terminates more caudally and centrally in the superior nucleus, while the cristae of the superior division terminate rostrally and laterally. The superior and lateral canal afferents terminate by short collaterals in the rostral division of the NIV, while the posterior canal afferents similarly terminate in the caudal division of the NIV. Descending vestibular nerve rami of the superior and lateral canal rami are more ventrally located than those belonging to posterior canal fibers. The termination of these two groups in the medial nucleus remains ventrodorsal. These canal afferents all converge in the medial vestibular nucleus with the utricular and saccular macular fibers. Input from the utricular macula is primarily to the ventral division of the lateral vestibular nucleus and to the medial and descending vestibular nuclei (Fig. 3-12). The input

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Figure 3-11. This section through the vestibular nerve root shows the interstitial nucleus of the vestibular nerve (NIV). S, superior vestibular nucleus; CN, cochlear nucleus; V, descending trigeminal root.

from the saccule is also to the ventral division of the lateral vestibular nucleus and the medial nucleus. However, the saccule has a unique input to the group Y nucleus, which differentiates it from utricular fibers. Neither utricular nor saccular macular fibers terminate primarily in the cerebellum, but they do project to the vestibular cerebellum by way of second-order neurons in the medial and descending nucleus and possibly the reticular formation. Four physiological types of second-order vestibular neurons have been described in the major vestibular nuclei. Type I neurons are the most numerous; they make

up approximately 90% of the active second-order neurons. Type I neurons are those that respond in the same directional pattern as first-order afferents. The next most common are the type II neurons, which exhibit an opposite response pattern to that seen in the first-order neurons providing input. Types III and IV are extremely uncommon and show both increased and decreased activity during rotations in both directions. The majority of type I and type II secondorder neurons are located in the rostral portion of the medial vestibular nucleus and the superior nucleus, where the primary input of canals is concentrated.

EFFERENT PROJECTIONS OF VESTIBULAR NUCLEI The primary efferent projections of the vestibular nuclei for purposes of the initiation of vestibular reflexes are vestibulocerebellar, commissural (vestibulovestibular), vestibulospinal, vestibulo-ocular, vestibuloreticular, and the efferent pathway to the end organs (Figs. 3-13, 3-14, and 3-15). The vestibulocerebellar and commissural neurons are special in that they can be regarded as efferent projections of the nuclei that in turn modify or influence the activity of the vestibular nuclei. They do not directly bring about the activation of a peripheral muscle group, which stabilizes the body; instead, they modify the activity in the vestibular nuclei.

Vestibulocerebellar Connections

Figure 3-12. Summary of the central termination of the vestibular neurons that supply the otolith sense organs.

The vestibulocerebellar connection is a very prominent projection between the vestibular nuclei and the cerebellum that emphasizes the relationship between these two centers. All four major vestibular nuclei, and in particular the medial and descending nuclei, contain second-order neurons that project abundantly to the anterior and posterior lobes

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Figure 3-15. Summary of the projections of the saccular macula. IFC, infracerebellar nucleus; LVST, lateral vestibulospinal tract; MVST, medial vestibulospinal tract; MLF, medial longitudinal fasciculus. Figure 3-13. Line drawing summary of the reflex projections of the cristae ampullares. ND, nucleus of Dankschewitz; INC, interstitial nucleus of Cajal; VO, vestibulo-ocular; VV, commissural; VS, vestibulospinal; MLF, medial longitudinal fasciculus.

of the vermis and to the vestibulocerebellum.28 The vestibulocerebellar projections can be primary or secondary. Primary vestibulocerebellar fibers represent the continuation of vestibular nerve axons that terminate in the vestibular nuclei and then continue on to the vestibulocerebellum.29

(MLF)

Figure 3-14. Summary of the reflex projections of the utricular macula. MVST, medial vestibulospinal tract; LVST, lateral vestibulospinal tract; MLF, medial longitudinal fasciculus.

Primary vestibulocerebellar fibers have been described in both submammalian and mammalian animal forms to terminate in the flocculus and nodulus of the cerebellum ipsilaterally. This is a heavily ipsilateral pathway, which includes the paraflocculus and the caudal folia of the uvula. The bundles of primary vestibulocerebellar fibers have been grouped into three types: medial, intermediate, and lateral. The medial group of fibers passes dorsally through the medial aspect of the superior nucleus through the fastigial nucleus and then curves ventrally to enter the nucleus. Some fibers emerge at the ventral aspect of the nucleus and enter the nodulus and uvula. The lateral group of primary vestibulocerebellar fibers takes a dorsal and lateral direction to loop around the restiform body from medial to lateral and merge in the lateral aspect of this structure to supply the flocculus and paraflocculus. The smallest intermediate group of fibers passes through the rostral part of the interpositus cerebellar nucleus, where it terminates in the cortex of the flocculus. Therefore primary vestibulocerebellar fibers terminate in an extensive region of the cerebellum consisting of the uvula, ventroparaflocculus, dorsoparaflocculus, the lateral dentate nucleus, and the flocculonodular lobe. Retrograde degeneration studies have indicated that the origin of secondary vestibulocerebellar fibers is primarily in the caudal vestibular nuclei (the descending and medial nuclei as well as group X) and that they terminate in regions similar to that of the primary vestibulocerebellar fibers.30 Since this group of fibers originates primarily from the caudal vestibular nuclei, it probably is more closely related to vestibulospinal activity in the cerebellum. The labyrinth, particularly the semicircular canals, projects directly to the vestibular part of the cerebellum by way of first-order afferents. Second-order neurons in the caudal vestibular nuclei, especially those receiving input from the maculae, also form projections to the cerebellum. In a reciprocal way, the

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vestibulocerebellar projections terminate in all four major vestibular nuclei with the major part of this activity representing Purkinje cells in both the vestibulocerebellar cortex and the vermis. The effect of this projection is primarily inhibitory and modifies vestibular nuclear activity. Details of this projection are presented in a later section.

Commissural Projections Commissural projections are also quite prominent and concern primarily the superior and medial vestibular nuclei with a weaker connection between the descending nuclei and the projection between the group Y nuclei24 (Fig. 3-16). The superior vestibular nucleus represents a large part of the commissural pathway and uses the commissure of the superior nuclei, which courses beneath the floor of the fourth ventricle and terminates in the entire nucleus.31 Some fibers pass around the lateral border of the superior nucleus to end caudally in the lateral portion of the lateral nucleus. Some fibers may terminate more caudally in the descending and medial nuclei. The commissural projections between the caudal vestibular nuclei in particular take a much more ventral course through the brainstem to cross the midline before arching upward to terminate in the medial and descending nuclei of the contralateral side. The commissural projections are provided by the small neurons in these nuclei, which are more numerous than the larger neurons that give rise to vestibulo-ocular projections (Fig. 3-17). The effect of commissural activity is largely inhibitory and because it involves primarily the superior, descending, and medial vestibular nuclei, this activity is provoked mainly by input from the semicircular canals. It is thought that commissural inhibition initiated by canal activity may potentiate the inhibition of the contralateral complementary canal, therefore representing an effective mechanism for differential activity in complementary or coplanar canals. The primary mechanism for this differential coplanar canal activity is afforded by the opposite polarization of hair cells in the cristae. Because the maculae have an opposite polarization of the hair cells in the two halves of the sense organs, commissural projections may not be necessary to produce a differential effect from activation of this sense organ.

Vestibulospinal Projections Vestibulospinal reflexes constitute one of the most important reflex activities of the vestibular system. These projections

Figure 3-16. Summary of the commissural projections of the vestibular nuclei.

Figure 3-17. Retrograde label demonstrating the commissural neuron population of the medial vestibular nucleus. See Figure 3-8.

are divided into lateral (LVST) and medial vestibular spinal tracts (MVST) (see Figs. 3-13, 3-14, and 3-15). The LVST is an ipsilateral projection originating from the neurons of the lateral vestibular nucleus.32 The fibers of the LVST proceed ventrally and somewhat medially after leaving the vestibular nuclei and then turn in a caudal direction, where they are located dorsal medial to the nucleus of the facial nerve and dorsal lateral to the inferior olive and lateral to the hypoglossal nerve. On leaving the medulla, the fibers continue into the spinal cord where they are found largely in the ventral half of the lateral funiculus, while other fibers pass in the lateral part of the ventral funiculus.33 Fibers terminate in the anterior horn cells of the spinal gray matter terminating in lamina VIII and lamina VII. A few fibers terminate in lamina IX, which contains alpha as well as gamma motoneurons. Physiologic studies indicate that the vestibulospinal fibers exert a monosynaptic excitatory influence on extensor motoneurons, but a polysynaptic pathway through internuncial neurons in laminae VII and VIII is also possible. Brodal’s studies32,34,35 have shown that the large and medium cells of the lateral vestibular nucleus giving rise to the lateral vestibulospinal tract are somatotopically organized so that the most rostral ventral cells project to the cervical cord, while those in the most caudal and dorsal division terminate in the lumbosacral cord. The origin of the tract to the thoracic cord is located in the intermediate zone of Deiters nucleus. The dorsal division of the lateral vestibular nucleus has a close relation to the cerebellum, where it receives direct Purkinje cell input. The activity of the LVST is excitatory to the extensor muscles of the limbs, but it inhibits the flexor muscles by local neuronal circuits. The lateral vestibular nucleus is also activated by input from proprioceptive impulses in the somatosensory system (joints, muscle tendons, etc.), which

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arrive by way of the spinovestibular tracts. The peripheral input to the ventral portion of the lateral vestibular nucleus is from all the sense organs, but particularly from the maculae of the utricle and saccule. Therefore, the LVST to the upper levels of the spinal cord, that is the cervical and thoracic levels, are tightly connected to the otolith organs. The MVST is not as extensive as the LVST and projects bilaterally over the medial longitudinal fasciculi to the cervical and upper thoracic cord levels36 (see Figs. 3-13, 3-14, and 3-15). The medial vestibulospinal tract course is along the medium raphe, where it terminates on the anterior horn gray matter in laminae VIII and VII. The pathway is bilateral and some of the fibers, especially those coming from the medial vestibular nucleus, dichotomize and send a branch ascending in the medial longitudinal fasciculus as well as a descending ramus, which forms the MVST.32 The MVST originates from the medial, lateral, and descending vestibular nuclei and performs both excitatory and inhibitory functions. Its peripheral input is from the canals and to a lesser extent the utricle. The vestibulospinal tracts arising from the caudal levels of the vestibular nuclei are activated primarily by gravity receptors (utricle, saccule). However, there is also a pathway for cervical muscle activation from canal input by way of connections to the caudal vestibular nuclei.

Vestibulo-Ocular Projections In mammals, a very prominent vestibular reflex associated with the labyrinth function is the vestibulo-ocular reflex.14 The vestibulo-ocular second-order neurons are located in the superior and medial vestibular nuclei, the ventral

Figure 3-18. Summary of the vestibulo-ocular neuronal network serving horizontal eye movements. MR, medial rectus subgroup of III nucleus; ATD, ascending tract of Deiters; MLF, medial longitudinal fasciculus; NPH, nucleus prepositus hypoglossi.

portion of the lateral vestibular nucleus, and in the infracerebellar division of the group Y nucleus. There is evidence that some first-order vestibular neurons projecting from the utricle also connect directly to the ipsilateral abducens nucleus.37 The efferent projection pathways of these vestibular neurons are the medial longitudinal fasciculus (MLF), the ascending tract of Deiters, reticular formation, and the brachium conjunctivum. The vestibulo-ocular projections that are responsible for horizontal eye movement differ from those that elicit vertical or oblique eye movements. The medial and lateral rectus muscle groups innervated by the oculomotor and abducens nuclei are responsible for horizontal eye movements (Fig. 3-18), while the superior and inferior recti and superior and inferior oblique muscles are responsible for oblique and rotatory eye movements. These muscles are innervated by the oculomotor and trochlear nuclei (Fig. 3-19). The cranial nerve nuclei serving the extraocular muscles are three, four, and six. The third or oculomotor nucleus is the most complex and is located in the floor of the midbrain and near the aqueduct of Sylvius. This nucleus serves the innervation of four eye muscles, the medial and inferior recti, the inferior oblique, and the superior rectus. The organization of this nucleus, demonstrated by retrograde axonal tracers, indicates that the nucleus comprises rostracaudally oriented cell columns, which are contained in two halves of the nucleus38 (Fig. 20A and B). In the rostral half of the nucleus, the main subnuclei are those innervating the medial rectus and the inferior rectus, with the medial rectus being located dorsally while the inferior rectus is immediately ventral. In the caudal division of the oculomotor nucleus the subnucleus for the superior rectus is located medially, while the subnucleus for the inferior oblique, the smallest of all of the subnuclei, is located just lateral to that for the superior rectus. All of the subnuclei except for that supplying the superior rectus provide ipsilateral innervation to the respective eye muscle. The superior

Figure 3-19. Summary of the vestibulo-ocular neuronal network for vertical and rotatory eye movements. BC, brachium conjunctivum; IFC, infracerebellar nucleus; MLF, medial longitudinal fasciculus; NPH, nucleus prepositus hypoglossi.

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A

B Figure 3-20. A, B, The oculomotor nucleus showing the arrangement of the motor neuron pools of the extraocular muscles. MR, medial rectus; IR, inferior rectus; SR, superior rectus; IO, inferior oblique.

rectus subnucleus supplies the contralateral eye muscle. Additional oculomotor neurons are located outside the confines of the nucleus in between the muscle bundles of the MLF and also in the reticular formation ventral to the MLF. These neurons belong to the subgroup that supplies the inferior rectus muscle.38 The trochlear nucleus is the smallest of the extraocular nuclei, is located immediately caudal to the oculomotor nucleus, and is a spherical nucleus that indents the dorsal surface of the MLF. The majority (approximately 90%) of neurons in the trochlear nucleus innervate the contralateral superior oblique muscle; approximately 10% innervate the ipsilateral superior oblique muscle.38 The sixth cranial nerve or abducens nucleus is located in the brainstem (medulla oblongata) immediately ventral to the genu of the facial nerve root. The multipolar neurons in this nucleus are larger than those in the other two cranial nerve nuclei, are compactly arranged, and primarily innervate the ipsilateral lateral rectus muscle. Approximately 50% to 65% of neurons project into the abducens nerve to the lateral rectus muscle. The remaining 25% to 50% are small fusiform neurons, which project contralaterally by way of the MLF to the medial rectus subgroup of the oculomotor nucleus (Fig. 3-21).39,40 The vestibulo-ocular neurons supplying vertical and oblique eye muscle neurons arise primarily from the superior nucleus and rostral portions of the medial nucleus.41,42 The superior nucleus projects ipsilaterally and the medial nucleus contralaterally via the MLF to the trochlear nucleus and subgroups of the oculomotor nucleus.41–44 The ipsilateral vestibulo-ocular pathway rising from the superior nucleus is inhibitory while the contralateral projection from the medial nucleus is excitatory. Neurons in the dorsal portion of the superior nucleus are driven by the anterior canal and project by way of the brachium

Figure 3-21. Horizontal section through the abducens nucleus showing labeled interneurons that project to the medial rectus subgroup of IIIN. MLF, medial longitudinal fasciculus; 7, facial nerve.

conjunctivum to reach the third and fourth nuclei.45 Large cells in the infracerebellar division of group Y nucleus also project to the fourth nucleus and some subgroups of the third nucleus. Since the saccule projects to this nucleus, group Y provides a pathway for vertical eye movements from saccular input.29 The vestibulo-ocular projections providing horizontal eye movements are provided by the lateral rectus and medial rectus subgroups (see Fig. 3-18). The second-order neurons projecting to the ipsilateral and contralateral abducens nuclei are located in the medial vestibular nucleus, particularly in its most rostral portion.37,46 Excitation is provided to the ipsilateral abducens nucleus and inhibition to the contralateral abducens nucleus to provide synchronized eye movement. Interneurons in the abducens nucleus project contralaterally through the MLF to the medial rectus subgroup, thereby providing a tight connection from the ipsilateral lateral rectus and contralateral medial rectus motor neurons. Some neurons in the medial vestibular nucleus, together with those in the ventral portion of the lateral nucleus, give rise to the ascending tract of Deiters, which projects outside of the MLF to the ipsilateral medial rectus subgroup to provide it with an excitatory input. This neuronal network provides projections to the abducens and medial rectus neurons that can be activated by both utricular and canal afferents. In addition to these more traditional pathways, vestibulo-ocular projections can occur through the reticular formation. However, anatomic verification of such connections is lacking.

Efferent Vestibular Pathway An efferent vestibular pathway projecting from the brainstem to the vestibular sense organs has been known for more than 40 years.47,48 The small cells of origin of this pathway

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Figure 3-22. Summary of the efferent vestibular pathway (solid line). Efferent cochlear pathway shown as stippled bundle.

are located lateral to the abducens nuclei and provide each labyrinth with a bilateral and approximately equal projection from the groups of neurons in the efferent vestibular nucleus49 (Fig. 3-22). Although the number of efferent neurons is considerably smaller than the afferent (approximately 400 to 500 efferent neurons in the cat), the peripheral innervation of sensory epithelium by way of vesiculated terminals is rich because of a complex branching pattern in each efferent neuron. The efferent vestibular neurons travel with the efferent cochlear bundle in the vestibular nerve and reach the peripheral sense organs scattered among afferent fibers in the individual vestibular nerve branches. Both of these efferent systems are associated with high levels of acetyl cholinesterase, which can be used in histochemical preparations to differentiate them from afferent fibers.50 These nerve fibers terminate as small vesiculated endings on both type I and type II hair cells in all vestibular sense organs (see Fig. 3-1). However, their mode of termination on the two types of hair cell varies. The efferent terminals contact the calyx type terminal on type I hair cells, while they make direct contact with the hair cell membrane of type II hair cells. It is therefore possible that activation of the efferent component produces different physiologic effects at the sensory epithelium level. Both excitation and inhibition51–53 of the vestibular nerve response have been demonstrated following excitation of the efferent vestibular pathway. However, inhibition has been the predominant effect demonstrated and may provide a mechanism by which self-stimulation of the vestibular system can be prevented or at least controlled. It may also be possible that either excitation or inhibition can be used to modulate the resting activity in individual vestibular neurons, thereby modifying the range over which they can be altered by peripheral end organ excitation.52

Vestibuloreticular Projections Connections between the vestibular nuclei and the reticular formation have been sparsely studied, but the major segment

of our information on this pathway comes from studies of the Brodal group, who made discrete lesions in the vestibular nuclei and studied axonal degeneration emanating from the lesion.31 These lesions were isolated to the nuclei so that fairly reliable conclusions could be made regarding their termination. These studies indicate that the superior and lateral vestibular nuclei form the major projections from the vestibular nuclei to the reticular formation. A few primary vestibular fibers, which project into the lateral reticular formation for a short distance, have been reported.18,34 The termination of these first-order fibers has not been determined. The reticular formation projection from the superior vestibular nucleus splits off from a large group of fibers coursing medially in the superior nucleus. These medially directed fibers are those projecting into the MLF as well as commissural fibers to the contralateral superior nucleus. The fibers destined for the reticular formation split off ventrally to terminate in the contralateral nuclei reticularis pontis caudalis and oralis, and a large number turn ventrally to end throughout the contralateral nucleus reticularis tegmenti pontis. Some fibers do not cross the midline but ascend and terminate in the ipsilateral nucleus reticularis pontis caudalis and the nucleus reticularis giganto cellularis. Some of the commissural fibers of superior vestibular nucleus continue into the descending and medial nuclei and also give off terminal branches to the rostral part of the nuclei reticularis giganto cellularis and parvi cellularis. After lesions in the lateral vestibular nucleus, fibers pass through the ventral part of the superior nucleus and course ventrally to the ipsilateral nucleus reticularis pontis caudalis. However, the majority of fibers passing to the reticular formation leave the lateral nucleus and pass ventromedially toward the midline and terminate in the contralateral nucleus reticularis pontis caudalis. The evidence thus accumulated indicates that the lateral and superior nuclei are associated with the reticular formation nuclei that project to the cerebellum. These are the lateral reticular nucleus and nucleus reticularis tegmenti pontis. In turn, the lateral and superior nuclei receive abundant fibers from the cerebellum and are, therefore, interrelated in a circuit through the cerebellum, reticular formation, and vestibular nuclei. Those regions of the reticular formation that give rise to fiber connections of the spinal cord receive projections from the superior, lateral, and descending vestibular nuclei, that is, nuclei that have also a close relationship to spinal cord mechanisms.

OTHER AFFERENT PROJECTIONS TO THE VESTIBULAR NUCLEI In addition to the vestibular nerve input, there are two major afferent projections to the vestibular nuclei, as discussed in the following sections.

Spinal Vestibular Projections Direct spinal vestibular fibers are distributed only to the portions of the vestibular nuclei that do not receive primary vestibular afferents.54 Degeneration studies have

Anatomy of the Central Vestibular System

indicated that the spinal vestibular projection (which is modest compared to the descending vestibulospinal projection) originates from the lumbar and sacral portions of the cord. The projection is entirely ipsilateral and ascends in the dorsal portion of the lateral funiculus. Its termination is in the caudal vestibular nuclei, that is, the descending and medial nuclei, with a small portion also in the dorsal caudal portion of the lateral nucleus. The minor cell groups X and Z also receive input from the spinal vestibular pathway.55

Vestibulocerebellar Projections Input to the vestibular nuclei from the cerebellum forms the largest complement of afferent fibers in the system. This projection may be divided into a projection from the vestibular portion of the cerebellar cortex and the other from the spinal cerebellar cortex.56 The cerebellovestibular projection originates from the cortex of that portion of the cerebellum supplied by the projection from the primary vestibular neurons and the uvula and paraflocculus. A portion of the lateral cerebellar nucleus is also included. This projection is entirely ipsilateral, with a projection from the flocculus that supplies the superior and medial nuclei and a second bundle, which is more lateral than the first, that gives off fibers to all four vestibular nuclei and group F. The terminations in the vestibular nuclei occupy discrete portions of the nuclei. The paraflocculus does not have a projection in the vestibular nuclei. The nodulus projection terminates in the peripheral portion of the superior nucleus, the caudal and medial portions of the medial nucleus, and the ventral caudal portion of the descending nucleus as well as group F and group X. The uvula projects to the peripheral portion of the superior nucleus, to the caudal portion of the descending nucleus, and to group X. As mentioned earlier, the projection of the different portions of the vestibulocerebellum are to rather discrete portions of the vestibular nuclei, which suggests that there are some functional differences between the lobules of cortex in the vestibulocerebellum. The projection from the spinal portion of the cerebellum (vermis) to the vestibular nuclei is generally considered the termination of spinal afferents to the cerebellum.57 This projection is further broken down into a direct projection from the spinal cerebellum to the vestibular nuclei and an indirect projection, which relays in the fastigial nucleus. The direct spinal vestibular projection terminates primarily in the dorsal rostral portion of the descending nucleus and the dorsal portion of the lateral nucleus. The experiments of Walberg and Jansen57 demonstrated that the projection from the vermis of the anterior lobe to Deiters nucleus is somatopically arranged with the fore limb portion projecting to the rostral dorsal portion of the lateral nucleus and the hind limb to the caudal dorsal portion. The indirect projection from the spinal portion of the cerebellum relays through the fastigial nucleus.58,59 The first link in this pathway, that is, the cerebellar fastigial projection, is organized so that the vermal cortex projects to the fastigial nucleus, the intermediate portion of the cerebellar cortex to the nucleus interpositus, and the lateral hemispheres onto the lateral or dentate nucleus. This

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organization is also demonstrated in the projection of the vermal cortex to the fastigial nucleus.60 The fore and hind limbs of the vermis, that is, the lobules 1 through 5, project to the rostral end of the fastigial nucleus with the fore limb located behind the hind limb terminus in the fastigial nucleus. The caudal, vermal lobules (VIII and IX) terminate in the caudal portion of the fastigial nucleus, with the fore limb being located rostral to the hind limb. The fastigiovestibular projection forms the final link in this pathway, which is an ipsilateral projection from the rostral half of the nucleus that relays the projection from the anterior vermis, which then terminates in the peripheral portions of the superior nucleus, the dorsal half of the lateral nucleus, and the dorsomedial portion of the descending nucleus and medial nuclei. The crossed or contralateral fastigiovestibular projections form the final link in the projection from the caudal vermal cortex. These fibers terminate in the peripheral portion of the superior nucleus, the ventral portion of the medial ventral half of the lateral nucleus, the ventral lateral portion of the descending nucleus, and groups F and X. These two projections terminate in different portions of the major vestibular nuclei, and this is particularly well demonstrated in the dorsal division of the lateral nucleus where the ipsilateral cortical fastigial vestibular projection terminates ipsilaterally and the posterior or caudal vermal projection terminates in the contralateral lateral vestibular nucleus.

HIGHER CENTRAL VESTIBULAR CENTERS Nuclei concerned with higher projections of the vestibular pathway exist both in the midbrain and in the thalamus and cortex. In the midbrain the two nuclei that receive the most rostral termination of the vestibulo-ocular projections from the major vestibular nuclei are the interstitial nucleus of Cajal (INC)61 and the nucleus of Dankschewitz (ND) (see Fig. 3-13). These nuclei are adjacent to the MLF in the mesencephalon and have been little studied over the years. However, recent physiologic as well as anatomic retrograde tracing techniques have revealed some of their connections. Both nuclei consist of small cells, fairly compactly arranged in nuclei that have indistinct borders. More is known about the functions and connections of the INC.62,63 These studies have demonstrated that the INC projects to the oculomotor nucleus and to several other centers in the midbrain and the thalamus. In addition to projections from the major vestibular nuclei by way of the MLF, the INC receives input from the group Y nucleus. The majority of functional studies have indicated that this nucleus is concerned with the neural integration of vertical eye movements in response to vestibular stimulation. By way of its aforementioned projections, this rather unique function can be understood. The ND is somewhat less studied physiologically, but the anatomic connections have demonstrated that it receives projections from the frontal eye field as well as the thalamus.64 It projects to both the anterior and posterior lobes of the cerebellum by way of the accessory olivary nucleus. Some studies have suggested that projections from group Y nucleus as well as some of the major vestibular nuclei

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provide input to the ND. A proposed functional pathway from the ND is one that conveys information for eye movement from the frontal eye fields in the cortex to the cerebellum for ultimate projection to the oculomotor nuclei.

region of the thalamus.71 Demonstration of this linkage in the ascending pathway will require careful use of intraaxonal tracers.

REFERENCES

CORTICAL VESTIBULAR PROJECTION The existence of a cortical representation of the vestibular system has been suggested by many and is based particularly on two observations: (1) the demonstration by Walzl and Mountcastle65 of evoked potentials in the cerebral cortex between the auditory area and the somatic sensory area following stimulation of the labyrinth in the laboratory animal, and (2) the demonstration by Penfield66 in experiments on humans where direct stimulation of the temporal lobe cortex often elicited sensations of vertigo and dizziness. The two animal models that have been used to demonstrate this sensory representation are the cat and the monkey. Walzl and Mountcastle65 demonstrated in the cat by the evoked potential method under barbiturate anesthesia that the area of evoked potentials was located in the anterior sylvian sulcus posterior to the face zone of the somatosensory field anterior to the auditory cortex. The projection was bilateral but strongly contralateral.67 Mickle and Ades68 found an overlap of the vestibular representation with the somatic afferents. The location of the cortical area in the cat left some doubt as to whether the projection was more associated with the auditory cortex in the temporal lobe or with the somatosensory portion of the parietal lobe. In the rhesus monkey the primary cortical vestibular projection has been demonstrated in the postcentral gyrus at the lower end of the intraparietal sulcus, near the face level of the first somatosensory field.69 In Brodmann’s classification this is area 2 but because of differences in the cytoarchitecture and the different senses represented in somatic area 2, it has been called area 2V. Neurons in area 2V respond strongly to caloric and galvanic stimulation of the labyrinth. The physiology of the neurons in this area is left for a different discussion. Suffice it to say that the physiologic demonstration has been confirmed repeatedly. Anatomic demonstration of this projection with the newer axonal tracers has not been produced. The location of the vestibular sensory area in humans has been speculated to be located in the anterior portion of the interparietal sulcus, which would correlate with the location of 2V in the monkey and the cat. This speculation about this location has been based on direct stimulation experiments.66 A second vestibular cortical projection area designated in area 3 may represent the projection from the somatosensory arm field.70 Therefore this portion of the projection probably represents a projection from the somatic afferents involved in balance. These projections would appear to integrate labyrinthine and somatic proprioceptive signals in order to provide the subject with an awareness of body orientation. The pathway by which vestibular signals reach the cortex is not well known. It is suggested that a pathway may take place through the thalamus, particularly the ventral posterior

1. Smith CA, Lowry OH, Wu ML: The electrolytes of the labyrinthine fluids. Laryngoscope 64:141–153, 1954. 2. Fernández C: Biochemistry of labyrinthine fluids. Arch Otolaryngol 86:222–233, 1967. 3. Engström H, Wersäll J: Structure and innervation of the inner ear sensory epithelia. Int Rev Cytol 7:535–585, 1958. 4. Engström H: The innervation of the vestibular sensory cells. Acta Otolaryngol Suppl 163:30–40, 1961. 5. Engström H, Ades HW, Hawkins JE: The vestibular sensory cells and their innervation. In Szentágothai J (ed.): Symposia bioligica Hungarica vol 5. Modern Trends in Neuromorphology. Budapest, Adakémiai Kiado, 1965. 6. Smith CA, Rasmussen GL: Nerve endings in the maculae and cristae of the chinchilla vestibule, with a special reference to the efferents. In Graybiel A (ed): Third Symposium on the Role of the Vestibular Organs in Space Exploration. Washington, DC, US Government Printing Office, 1967. 7. Lowenstein OE, Wersäll J: A functional interpretation of the electronmicroscopic structure of the sensory hairs in the cristae of the elasmobranch Raja clavata in terms of directional sensitivity. Nature (Lond) 184:1807–1810, 1954. 8. Wersäll J, Flock A, Lundquist PG: Structural basis for directional sensitivity in cochlear and vestibular sensory receptors. Cold Spring Harbor Symp Quant Biol 30:115–132, 1965. 9. Spoendlin HH: Ultrastructural studies of the labyrinth in squirrel monkeys. In Graybiel A (ed): Symposium on the Role of the Vestibular Organs in the Exploration of Space. Washington, DC, US Government Printing Office, 1965. 10. Wersäll J: Studies on the structure and innervation of the sensory epithelium of the cristae ampullares in the guinea pig: A light and electronmicroscopic investigation. Acta Otolaryngol Suppl 126: 1–85, 1956. 11. Lindeman HH: Studies on the morphology of the sensory regions of the vestibular apparatus. Ergeb Anat Entw Gesch 42:1–113, 1970. 12. Lindeman HH: Anatomy of the otolith organs. Adv Otorhinolaryngol 20:405–433, 1973. 13. Lorente de Nó R: Anatomy of the eighth nerve. Laryngoscope 43:1–38, 1933. 14. Lorente de Nó R: Vestibuloocular reflex arc. Arch Neurol Psychiat (Chic) 30:245–291, 1933. 15. Rasmussen AT: Studies of the eighth cranial nerve of man. Laryngoscope 50:67–83, 1940. 16. Gacek RR, Rasmussen GL: Fiber analysis of the statoacoustic nerve of guinea pig, cat, and monkey. Anat Rec 139:455–463, 1961. 17. Richter E, Spoendlin H: Scarpa’s ganglion in the cat. Acta Otolaryngol 92:423–431, 1981. 18. Gacek RR: The course and central termination of the first-order neurons supplying vestibular end organs in the cat. Acta Otolaryngol 254:1–66, 1969. 19. Stein BM, Carpenter MB: Central projections of portions of the vestibular ganglia innervating specific parts of the labyrinth in the Rhesus monkey. Amer J Anat 120:281–318, 1967. 20. Goldberg JM, Fernández C: Physiology of peripheral neurons innervating semi-circular canals of the squirrel monkey. I. Resting discharge and response to constant angular accelerations. J Neurophysiol 34:635–660, 1971. 21. Walsh BT, Miller JB, Gacek RR, Kiang NYS: Spontaneous activity in the eighth cranial nerve of the cat. Int J Neurosci 3:221–236, 1972.

Anatomy of the Central Vestibular System

22. Goldberg JM, Fernández C: Responses of peripheral vestibular neurons to angular and linear accelerations in the squirrel monkey. Acta Otolaryngol 30:101–110, 1975. 23. Brodal A, Pompeiano O: The vestibular nuclei in the cat. J Anat (Lond) 91:438–454, 1957. 24. Gacek RR: Location of commissural neurons in the vestibular nuclei of the cat. Exp Neurol 59:479–491, 1978. 25. Gacek RR: Anatomical demonstration of the vestibulo-ocular projections in the cat. Acta Otolaryngol 293:1–63, 1971. 26. Fuse G: Die innere abteilung des Kleinhirnstiels (Meynert, IAK) and der Deiterssche kern. Arb Hirnanat Inst Zurich 6:29–267, 1912. 27. Hwang JC, Poon WF: An electrophysiological study of the sacculoocular pathways in cats. Jap J Physiol 25:241–251, 1975. 28. Kotchabhakdi N, Walberg F: Cerebellar afferent projections from the vestibular nuclei in the cat: An experimental study with the method of retrograde axonal transport of horseradish peroxidase. Exp Brain Res 31:591–604, 1978. 29. Brodal A, Hoivik B: Site and mode of termination of primary vestibulocerebellar fibres in the cat. An experimental study with silver impregnation methods. Arch Ital Biol 102:1–21, 1964. 30. Brodal A, Torvik A: Über den ursprung der sekundären vestibulocerebellaren fasern bei der katze. Eine experimentell-anatomische studie. Arch Psychiat Nervenkr 195:550–567, 1957. 31. Ladpli R, Brodal A: Experimental studies of commissural and reticular formation projections from the vestibular nuclei in the cat. Brain Res 8:65–96, 1968. 32. Pompeaino I, Brodal A: The origin of vestibulospinal fibers in the cat. An experimental-anatomical study, with comments on the descending medial longitudinal fasciculus. Arch Ital Biol 95: 166–195, 1957. 33. Nyberg-Hansen R, Mascitti I: Sites and mode of termination of fibers of the vestibulo-spinal tract in the cat. An experimental study with silver impregnation methods. J Comp Neurol 122:369–387, 1964. 34. Brodal A, Pompeiano O, Walberg F: The vestibular nuclei and their connections. In Ramsay Henderson trust lectures. Edinburgh and London, Oliver & Boyd, 1962. 35. Pompeiano I, Brodal A: Spino-vestibular fibers in the cat: An experimental study. J Comp Neurol 108:353–382, 1957. 36. Nyberg-Hansen R: Origin and termination of fibers from the vestibular nuclei descending in the medial longitudinal fasciculus. An experimental study with silver impregnation methods in the cat. J Comp Neurol 122:355–367, 1964. 37. Gacek RR: Location of abducens afferent neurons in the cat. Exp Neurol 64:342–353, 1979. 38. Gacek RR: Localization of neurons supplying the extraocular muscles in the kitten using horseradish peroxidase. Exp Neurol 44:381–403, 1974. 39. Spencer RF, Sterling P: An electron microscopic study of motoneurons and interneurons in the cat abducens nucleus identified by retrograde intra axonal transport of horseradish peroxidase. J Comp Neurol 176:65–86, 1977. 40. Steiger HJ, Büttner-Ennever JA: Relationship between motor neurons and interneurons in the abducens nucleus: A double retrograde tracer study in the cat. Brain Res 148:181–188, 1978. 41. Gacek RR: Location of brain stem neurons projecting to the oculomotor nucleus in the cat. Exp Neurol 57:725–749, 1977. 42. Graybiel AM, Hartwieg EA: Some afferent connections of the oculomotor complex in the cat: An experimental study with tracer techniques. Brain Res 81:543–551, 1974. 43. Tarlov E: Organization of vestibulo-oculomotor connections in the cat. Brain Res 20:159–179, 1970. 44. Gacek RR: Location of trochlear vestibulo-ocular neurons in the cat. Exp Neurol 66:692–706, 1979. 45. Yamamoto M, Shimoyana I, Highstein S: Vestibular nucleus neurons relaying excitation from the anterior canal to the oculomotor nucleus. Brain Res 148:31–42, 1978.

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46. Maciewicz RJ, Eagen K, Kaneko CRS, Highstein SM: Vestibular and medullary afferents to the abducens nucleus in the cat. Brain Res 123:229–240, 1977. 47. Gacek RR: Efferent component of the vestibular nerve. In Rasmussen GL, Windle W (eds.): Neural Mechanisms of the Auditory and Vestibular Systems. Springfield, Ill, Charles C Thomas, 1960. 48. Gacek RR. The vestibular efferent pathway. In Wolfson RI (ed.): Vestibular System and Its Disease. Philadelphia, University of Pennsylvania Press, 1966. 49. Gacek RR, Lyon M: The localization of vestibular efferent neurons in kitten using horseradish peroxidase. Acta Otolaryngol 77:92–101, 1974. 50. Gacek RR, Nomura Y, Balogh K: Acetylcholinesterase activity in the efferent fibers of the statoacoustic nerve Acta Otolaryngol 59:541–553, 1965. 51. Dieringer N, Blanks RHI, Precht W: Cat efferent vestibular system: Weak suppression of primary afferent activity. Neurosci Lett 5:285–290, 1977. 52. Goldberg JM, Fernández C: Efferent vestibular system in the squirrel monkey [abstract]. Neurosci Abstr 3:543, 1977. 53. Sala O: The efferent vestibular system: Electrophysiological research. Act Otolaryngol Suppl 197:1–34, 1965. 54. Brodal A, Angaut P: The termination of spinovestibular fibres in the cat. Brain Res 5:494–500, 1967. 55. Sadjapour K, Brodal A: The vestibular nuclei in man. A morphological study in the light of experimental findings in the cat. J Hirnforsch 10:299–323, 1968. 56. Angaut P, Brodal A: The projection of the “vestibulocerebellum” onto the vestibular nuclei in the cat. Arch Ital Biol 105:441–479, 1967. 57. Walberg F, Jansen J: Cerebellar corticovestibular fibers in the cat. Exp Neurol 3:32–52, 1961. 58. Jansen J, Brodal A: Experimental studies on the intrinsic fibers of the cerebellum. II. The cortico-nuclear projection. J Comp Neurol 73:267–321, 1940. 59. Jansen J, Brodal A: Experimental studies on the intrinsic fibers of the cerebellum. III. The corticonuclear projection in the rabbit and the monkey. Norske Vid-Akad Avh I Math-Nat KI 3:1–50, 1942. 60. Rossum J van: Corticonuclear and corticovestibular projections of the cerebellum. An experimental investigation of the anterior lobe, the simple lobule and the caudal vermis in the rabbit [thesis]. Assen, Van Gotcum, 1969. 61. Cajal SR: Histologie du Système Nerveux de l’Homme et des Vertébrés. Paris, Maloine, 1909–1911. 62. Fukushima-Kudo J, Fukushima K, Tashiro K: Rigidity and dorsiflexion of the neck in progressive supranuclear palsy and the interstitial nucleus of Cajal. J Neurol Neurosurg Psychiatry 50(9): 1197–203, 1987. 63. Labandeira-Garcia JL, Guerra-Seijas MJ, Labandeira-Garcia JA: Oculomotor nucleus afferents from the interstitial nucleus of Cajal and the region surrounding the fasciculus retroflexus in the rabbit. Neurosci Lett 101(1):11–16, 1989. 64. Rutherford JG, Zuk-Harper A, Gwyn DG: A comparison of the distribution of the cerebellar and cortical connections of the nucleus of Darkschewitsch (ND) in the cat: A study using anterograde and retrograde HRP tracing techniques. Anat Embryol (Berl) 180(5):485–496, 1989. 65. Walzl EM, Mountcastle VB: Projection of vestibular nerve to cerebral cortex of cat. Amer J Physiol 159:595, 1949. 66. Penfield W, Jasper HH: Epilepsy and the functional anatomy of the brain. London 1954. 67. Kornhuber HH, DA Fonseca JS: Optovestibular integration in the cats cortex: A study of sensory convergence on cortical neurons. In Bender MB (ed.): The oculomotor system. New York, L Hoeber, 1964. 68. Mickle WA, Ades HW: A composite sensory projection area in the cerebral cortex of the cat. Amer J Physiol 170:682–689, 1952.

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69. Fredrickson JM, Figge U, Scheid P, Kornhuber HH: Vestibular nerve projection to the cerebral cortex of the rhesus monkey. Exp Brain Res 2:318–327, 1966. 70. Kornhuber HH, Fredrickson JM, Figge U: Die korti-cale projektion der vestibulären afferenz beim rhesusaffen. Pflügers Arch Physiol 283:20, 1965.

71. Stanton GB, Tanaka D Jr, Sakai ST, Weeks OT: Thalamic afferents to cytoarchitectonic subdivisions of area 6 on the anterior sigmoid gyrus of the dog: A retrograde and anterograde tracing study. J Comp Neurol 252(4):446–467, 1986.

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Outline Development of the Labyrinth Labyrinth Fluid Spaces Hair Cells Vestibular Sensory Organs Semicircular Canals Hydrodynamics Human Semicircular Canal Afferent Neurons Otolith Organs Adequate Stimulus Macula Afferents Vestibular Efferents Vestibulo-Ocular Reflex VOR Pathways Horizontal Canal VOR Anterior Canal VOR Posterior Canal VOR Otolith VOR Spinal Influences

Chapter

Physiology of the Vestibular System

Cerebellar Loop Signal Transformation Central VOR Neurons Burst-Tonic Cells Second-Order Vestibular Neurons Burst Neurons Pause Cells Tonic Cells Commissural Connections Neuron Activity During Nystagmus Intermediary Neurons Motoneurons Visual Vestibular Interaction VOR Neurons Nystagmus Quantification of Human Vestibulovisual Interaction Adaptive VOR Plasticity

T

he purpose of this chapter is to provide the neurotologist an overview of vestibular neurophysiology. A truly comprehensive review is not possible within the constraints of this chapter nor is it desirable. An attempt has been made to refer to review articles as much as possible so that the interested reader can find additional information if desired. Such reviews are cited at the beginning of each section where possible. The most important general text is the book by Wilson and Melvill Jones.1 More detailed references to the older literature can be found in the handbook edited by Kornhuber.2 Finally, an excellent overview of the vestibulo-ocular reflex and its associated pathologies can be found in Leigh and Zee.3 The material in this chapter concentrates on areas of clinical relevance. Thus more emphasis is placed on peripheral and vestibulo-ocular physiology. Undoubtedly, the importance of the vestibular system on spinal, cortical, cerebellar, and autonomic physiology will increase as our knowledge of these systems increases.

DEVELOPMENT OF THE LABYRINTH The labyrinth is derived from the skin during early embryogenesis. Lateral ectoderm, destined to become the inner ear (placode), invaginates to form an otic pit, which

Eye-Head Coordination Habituation Compensation for Loss of Labyrinth Function Vestibulospinal System Vestibulocollic Reflex Tonic Labyrinth and Neck Reflexes Falling Pathways Lateral Vestibulospinal Tract Medial Vestibulospinal Tract Caudal Vestibulospinal Tract Projection to Forebrain Motion Sickness

Dietrich W. F. Schwarz, MD, PhD R. David Tomlinson, PhD

eventually buds off to become the otic cyst, representing the primordial endolymphatic space lined by ectodermal epithelium. The labyrinth and its sense organs (semicircular canals, utricle, saccule, and cochlea) develop from the otic cyst by further growth and differentiation. The physician must realize that the endolymphatic space corresponds originally to the exterior environment of the organism. The original vertebrate hair cell probably evolved in aquatic animals before the evolution of terrestrial vertebrates. Its function was, as it is now in many species, to monitor water currents relative to the body surface. The apical portions of the hair cell, equipped with stereocilia and kinocilia, were exposed to the water, whereas the basolateral cell membrane was contacted by extracellular fluid. Because of the differences in ionic concentration between the exterior water, the intracellular milieu, and the extracellular space, continuous ionic currents existed. Deflection of the cilia could alter those currents. The ionic concentration in the exterior water was subject to changes that must have affected transducer sensitivity. It was therefore an advantage to generate a separate endolymphatic space by encapsulation of the inner ear space so that the ionic composition could be controlled. Another advantage was that the physical forces deflecting the cilia could be selected very precisely by the evolution of accessory structures such as the semicircular canal system, the otolithic 91

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system, and vibration-sensitive structures (cochlea, papilla basilaries, and so forth).

LABYRINTH FLUID SPACES If ear development is considered from a teleologic perspective, much of the mystery surrounding the unique extracellular space within the membranous labyrinth vanishes. Because the original hair cell had to operate with any ion species available in the exterior water, the receptor current through the apical end of the hair cell had to be carried by a variety of cations. Contrary to widespread belief, regular extracellular fluid (perilymph) can mediate the mechanoelectric transduction as long as the hair cell remains vital. Because the predominant extracellular (and perilymphatic) ion is sodium, a constant Na+ current would have to flow through the hair cell. As a result, the Na+ and K+ electrogenic pumps in the hair cell membrane would be rapidly overburdened, and the cell would die. This problem does not exist for the second most common cation, K+. Thus having the K+ concentrated at the apical end of the hair cell and the Na+ removed from this location is advantageous. The dark cell is specialized for this task. Dark cells are strategically located on the slopes of the semicircular canal cristae and close to the utricular maculae as well as in the stria vascularis of the cochlea. Labeled Na+ and K+ have been demonstrated to move through these cells in a direction opposite to their gradients.4 The basal portion of these cells, directed toward the basement membrane and capillaries, is characterized by extensive indentations, which serve to increase the surface area. Dark cells contain an unusual concentration of mitochondria, testifying to high metabolic activity. Their apical cell membrane bears villi much as other secretory cells. Quite possibly, other cells surrounding the hair cells are also responsible for the high K+ concentration in the endolymph. Because the ionic concentrations within the mammalian endolymph and hair cell intracellular space are similar, little ionic gradient is available to drive a K+ receptor current. The existence of a positive electric charge within the endolymphatic space, with respect to the perilymph, compensates for this deficit. A corresponding potential is to be found in the cochlea and is known as the endolymphatic potential. In the vestibular labyrinth, this potential appears to be concentrated over the relatively small patches of sensory epithelium (cristae ampullares, otolithic maculae). The positive potential increases when a recording electrode is moved from the endolymph into either the cupula or the otolithic membrane and is greatest just above the apical surface of the hair cells. In areas far from these sites, the endolymphatic potential becomes small. The regional differences in this potential illustrate clearly that the high K+ concentration in the endolymph and the positive endolymphatic potential are independent of one another. This point has been proven experimentally in the cochlea where a positive charge over the stria vascularis can be recorded after removal of all K+ from the endolymphatic space.5 Both the positive endolymphatic potential and the high extracellular K+ concentration at the apical surface of the hair cell appear to be fundamental for the hair cell transducer function. In lateral line organs with

limited access to seawater, a K+-rich milieu is maintained, and even the cupula of the toad (Xenopus laevis), which is exposed to freshwater, contains an enriched K+ concentration and carries a positive charge.6 It represents a driving force supporting the K+ current through the hair cell. The intensity of this current is modulated by deflection of the stereocilia.

HAIR CELLS The two hair cell (HC) types found in the human labyrinth are illustrated in Figure 4-1A. The phylogenetically original type II HCs (right) have cylindrical shapes and are contacted by afferent dendritic nerve terminal boutons as well as efferent axon boutons. Type I HCs (left) are more recent and are concentrated in the central portions of the sensory epithelia, that is, on the cristae crests and within the striolae of the maculae. They are flask-shaped, and a calyx-shaped dendritic afferent terminal surrounds most of their basolateral membrane. Thus efferent terminals can only contact the neural calyx membrane of type I HCs, not the cell membrane itself. The “hairs” of these cells, the cilia, extend from the apical surface and greatly increase the membrane surface area. Vestibular hair cells typically have 40 to 200 stereocilia and one kinocilium. The kinocilium is located at the end of the stereocilia bundle (Figs. 4-1A and C). Thus the hair cell is morphologically polarized. Deflection of the cilia bundle toward the kinocilium depolarizes the cell membrane and leads to afferent nerve fiber activation, whereas deflection in the opposite direction has the opposite effect (Fig. 4-1B). Thus a functional polarization exists as well. Cilia deflection is effective only along this polarization axis. At other angles of deflection, the response amplitude, measured as either membrane potential, receptor current, or spike rate change in the afferent neuron, drops off according to a cosine function (Figs. 4-1C, D, and E). As the name implies, the kinocilium is capable of active motion. As with other mobile cilia, it is equipped with the typical nine-plus-two axoneme of microtubules that distinguishes mobile cilia in the respiratory tract, sperm cells, and elsewhere. Mammalian vestibular hair cell kinocilia are longer than the longest stereocilia and extend into the gelatinous substance of the cupula or otolithic membrane, thus mediating displacement of these structures relative to the epithelial surface. The kinocilium tip is typically bulb-shaped and connected to the longest stereocilia by fine filaments. The kinocilium appears to store free calcium ions, perhaps to safeguard receptor current changes when stereocilia are deflected. Transducer function of the HC appears to depend critically on stereocilia deflections. Their displacement toward the kinocilium causes the resting membrane current through the apical membrane to increase, presumably by opening membrane ion channels. Stereocilia are arrayed with the longer ones standing at the excitatory pole adjacent to the kinocilium, their length gradually decreasing toward the inhibitory pole. This length gradient may be important for transduction. With a diameter of 0.2 μm, they are slightly thinner than the kinocilium (0.25 μm). In contradiction to the classic belief, stereocilia are stiff,

Physiology of the Vestibular System

A

B

C

D

E

Figure 4-1. Hair cells and their mechanoelectric transduction. A, Schematic drawing of type 1 and type 2 hair cells. B, Plot of receptor potential or receptor current (y axis) against cilia deflection (x axis). Excitatory deflection causes much greater response than inhibitory deflection. C, Schematic top view of one hair cell. Viewing direction indicated by arrow in A. The + and − arrows represent excitatory and inhibitory deflections, respectively. Arrows labeled 30, 60, and 90 degrees indicate deflections yielding corresponding response amplitudes in D. Relative size of receptor potential for various angles of deflection (top) for same deflection amplitude (bottom). E, Receptor potential amplitudes drop with deviation of deflection direction from polarization vector according to cosine function.

the result of a skeleton of actin filaments. The actin filaments penetrate into the cuticular plate just below the stereocilia (see Fig. 4-1A). When the stereocilia are deflected, they do not bend but rather lean over like sticks, moving the cuticular plate with them.7 Stereocilia are stiff enough to exhibit resonant oscillations, the preferred frequency being a function of the cilia length.8 Although this characteristic serves as an auditory tuning mechanism in some reptilian ears,9,10 it also underlies the need to dampen such oscillations within the mammalian vestibular apparatus by

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coupling the stereocilia mechanically to the gelatinous superstructure (e.g., the cupula) via the kinocilium. Such mechanical coupling would not be necessary to induce stereocilia deflection; viscous endolymph drag would suffice to transfer cupula or otolithic membrane movement to the cilia. Frog saccular HC membranes have been shown to be tuned electrically.11,12 Their resting membrane potential oscillates by a few millivolts at a frequency between 0 and 100 Hz. Mechanical stimuli of the same frequency produce maximum receptor potentials, indicating a resonance. This preferred frequency can be shifted up and down, respectively, by depolarizing and hyperpolarizing the cell membrane. Because efferent volleys cause hyperpolarization in the HCs, their activity could shift maximum receptor sensitivity from high frequencies to lower frequencies. The stereocilia bundle apparently can be induced to move in response to an electrical polarization stimulus. Also, chemicals that normally cause muscle contraction alter the deflection response to a natural stimulus.13 Interestingly, myosin has been located within and close to the cuticular plate, and striated bands resembling actinmyosin complexes in skeletal muscle have been observed around the cuticular plate.14 Active mobility of the stereocilia bundle might be responsible for adaptation. The response to cilia deflection dies down after 10 to 100 msec, thus guaranteeing sensitivity to new stimuli even if the full response range was saturated initially during a head movement. Both adaptation rate and cilia mobility change with Ca2+ concentration in the endolymph. The cilia deflection required for a maximal response is quite small; displacement of stereocilia tips by about 1 μm, leading to a deflection angle of some 3 to 6 degrees is sufficient. At threshold, the displacement only needs to be about 4 × 10−3 degrees. Such cilia movement would be below the dimensions of many protein molecules. Thus, not surprisingly, a classic threshold (an energy step required for activation) cannot be defined in the vestibular system. The HC response is induced by a conductivity change for cations at the apical cell membrane. The term apical is particularly appropriate in this context, because the maximal receptor current change has been measured at the location of the stereocilia tips. The current itself is normally carried by K+ because of its high concentration in the endolymph, but Li+, Na+, Rb+, Cs+, NH4+, and to a lesser extent Ca++, as well as tetramethylammonium, acetylcholine, choline, and other cations can also contribute. Apparently charge carrier molecules must not exceed the molecular diameter of 0.6 nm to be passed through the ionic channels. Opening of the membrane channels in response to cilia deflection depends on small amounts of Ca2+ in the endolymph, and at this location calcium can be replaced by strontium (Sr2+) and blocked by magnesium, cobalt, and barium (Mg2+, Co2+, Ba2+ ) ions and other compounds. Other systems have shown that one ionic channel accounts for a conductance of about 50 ps. A measured peak conductance of some 2 to 5 ns at the stereocilia tips would imply the existence of about one channel per stereocilium. The maximal response current is about 200 pA, leading to a maximal depolarization of some 5 to 20 mV. Thus the

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typical HC membrane resting potential of about −60 mV is decreased to at most −40 mV. Stereocilia deflection in the opposite inhibitory direction yields a maximal polarization change of about one-fifth the excitatory response, that is, a hyperpolarization to about −64 mV. The HC therefore is a rectifying transducer, dramatically overemphasizing the excitatory response (see Fig. 4-1B). Note, however, that this asymmetry in the excitatory and inhibitory responses is much larger than that seen in the afferent nerve. The membrane resistance is voltagedependent: the input resistance of some 200 to 300 MΩ drops to about 6 MΩ after depolarization to −50 mV or less. This reflects an increased K+ conductance. Similarly, Ca2+ conductance is voltage-controlled at the basolateral membrane of the HC. Depolarization results in Ca2+ influx toward the synaptic region of the HC, which is necessary to induce fusion of synaptic vesicles with the cell membrane and trigger release of the synaptic transmitter. Synaptic activity thus depends on the receptor current. A constant apical K+ current provides for synaptically mediated resting activity in the primary vestibular neuron. Modulation of the receptor current, through membrane conductance changes, induces synaptic modulation of the resting discharge rate. Thus the transduction theory Davis proposed many years ago has been supported by the rigorous studies in the laboratories of Flock, Hudspeth, and others.7,15–17 In this theory, the high potential between the endolymph and the HC was considered to be a battery driving a current through the ciliated apical membrane, which acted like a variable potentiometer capable of controlling the receptor current and potential.

VESTIBULAR SENSORY ORGANS Semicircular Canals The three coplanar (complementary) canal pairs act reciprocally.1 Because these canal pairs are connected via the brainstem commissures, the reciprocal arrangement is the basis for functional symmetry, compensating for the asymmetrical responses of the individual canals. All HCs in one canal are activated by rotation in the same direction: toward the ipsilateral side for the lateral canal, during forward and ipsilateral bending of the head for the anterior canal, and during backward and ipsilateral head flexions for the posterior canal. Thus the three coplanar canal pairs are both lateral canals and each of the two ipsilateral anterior and contralateral posterior canal pairs. The term coplanar indicates only that the two canals in each pair are approximately parallel. Both horizontal canal planes are inclined to each other by about 20 degrees, and in humans the anteroposterior canal planes deviate by about 24 degrees. This implies that rotation in any canal plane will cause some stimulation of all canals. Horizontal canal planes do not coincide with the stereotactic horizontal plane but are tilted backward by about 25 degrees. Thus a patient’s head must be raised by that amount during caloric stimulation to position the lateral canal vertically. The canal position, however, is kept approximately horizontal during normal behavior.

Hydrodynamics The canal responses exhibit two time constants, the short time constant T1 reflects the time taken for the cupula to deflect when stimulated with a step of head velocity while the long time constant T2 describes the time taken by the cupula to return to its rest position. The long cupular time constant T2 is of diagnostic significance in Bárány’s classic rotation test, in which a velocity step is applied, usually from 0 degrees/sec to some value between 10 and 100 degrees/sec (Fig. 4-2). The cupula deflects almost instantly (because the Tl time constant is so short) and then reverts back to its rest position with a time constant of T2. Postrotatory cupular deflections in the opposite direction follow an identical time course. In addition, T2 dominates the caloric test; however, diagnostic determination of T2 cannot be recommended using caloric stimuli since the time course of temperature conduction is highly variable and unknown for each patient. Although the time constant of the cupula, T2, lies in the range of 5 to 10 sec, the time constant of the nystagmus that follows step changes in head velocity is much longer. Postrotatory nystagmus, in normal subjects, exhibits a time constant of 18 to 30 sec, or approximately three times that of the cupula. This difference is the result of brainstem and cerebellar circuits that act to perseverate the activity generated by the afferent nerve. The precise topography of these circuits (sometimes called the velocity storage system) is not yet fully understood, but they are known to be related to the optokinetic system. Unilateral peripheral vestibular lesions result in a reduction of the nystagmus time constant to a value close to that of the cupula for rotations toward the side of the lesion. Finally, the time constant of postrotatory nystagmus is increased to values well above normal following lesions involving the cerebellar nodulus. These issues are dealt with in more detail later.

Human Semicircular Canal The canal time constant T1 depends heavily on the narrow canal diameter. About one-quarter of the semicircular canal circumference is occupied by the membranous utricle, which has a much larger diameter. For this portion, the viscous drag becomes negligible. The greater utricular volume would probably also increase the moment of inertia because of the greater endolymph mass. Thus the real canal time constant T1 is probably greater than the calculated one, but it should still only be a few milliseconds.

Figure 4-2. Cupular displacement induced by velocity step. Cupula is deflected immediately with short time constant and returns to midposition with long time constant (top) during step in rotation velocity (bottom).

Physiology of the Vestibular System

Perilymph fluid dynamics probably do not play an important role in vestibular function. Because blood vessels and trabeculae in the perilymphatic space are highly variable, as is the volume of that space, protecting the HCs from this undoubtedly real fluid movement would be advantageous. Nonetheless, experiments by Rabbitt and Damiano18 have demonstrated that semicircular canal dynamics are more complex than would be expected from the old torsion pendulum model and as a result canals remain able to respond at high frequencies even after plugging. However, these responses are only significant at frequencies above those involved in normal human head movements and thus are of little clinical significance. The considerations discussed here explain the semicircular canal’s function as an angular accelerometer. During the years many researchers discussed the possibility that the canals might also be sensitive to linear forces. Guedry kindled interest in this possibility when he observed that there is a maintained compensatory nystagmus generated when the subject is placed horizontally and rotated about his or her longitudinal axis (“barbecue spit” nystagmus19). In this situation the labyrinth is exposed to a constantly changing gravity vector. This nystagmus is now known to be generated by the combined action of many otolithic afferents. No conclusive evidence for canal sensitivity to linear accelerations exists under normal circumstances, although almost everyone has experienced linear canal sensitivity under slightly unusual circumstances. Positional alcohol nystagmus and vertigo is caused by slow alcohol diffusion into the endolymph, starting at the well-vascularized crista-cupula region. The cupula density is thought to be decreased as a result, becoming sensitive to changing gravity vectors. Heavy water, resulting in the opposite density change, has been shown to cause nystagmus and vertigo in the opposite direction. An appropriate cocktail of alcohol and heavy water can prevent nystagmus and vertigo, as well as the alcohol-induced nausea, which can be interpreted as being related to motion sickness.20 Another example of linear canal sensitivity is benign paroxysmal positional nystagmus. Otolith debris is believed to fall through the endolymph and cause currents much like a stone falling through water will. These currents would activate the HC for the time required for the debris to reach the bottom of the canal. Any series of head movements that moved the debris out of the canal lumen would alleviate the problem. The best known canal response to linear acceleration occurs during caloric stimulation. The amplitude and direction of caloric stimulation of the lateral canal should change according to a cosine function when the canal is tilted away from the proper vertical position. This is clinically important because it implies that misalignment of the head by 10 to 20 degrees should have very little effect on the nystagmus amplitude (1.5% to 6%). The caloric stimulus is also known to exert a small direct temperature effect on the sensory epithelium such that cooling causes a direct decrease in afferent firing, whereas warming has the opposite effect. This will result in a slightly faster nystagmus slow phase than would be predicted based on the convection currents alone.

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Afferent Neurons A clear concept of primary neuron activity is fundamental to both clinical diagnostic studies and physiologic theory. All primary vestibular neurons are active at rest.21 This spontaneous activity ranges from about 10 to 200 spikes per second with a mean of around 90. This resting discharge rate is probably caused by the resting receptor current already described and is a prerequisite for bidirectional sensitivity. Canal rotation in the excitatory direction leads to an increased firing rate, and rotation in the opposite direction simply results in a spike rate reduction without the need for any synaptic inhibition. The spontaneous rate also eliminates the need for a definable threshold. Stimulus detection depends not so much on a minimal spike rate modulation amplitude as on the signal-to-noise ratio. This ratio is severely limited by the binary nature of pulse rate coding for stimulus intensity in a single neuron, but is enormously improved by averaging over the entire neuron population. Thus very sensitive vestibular transducers must be equipped with many neurons. Since the two classes of HCs are defined mainly by their innervation pattern, it is not surprising that two classes of primary afferents have been found: regular and irregular neurons. In general, regular units, with narrow ranges of interspike intervals, have thin axons with low conduction velocities, and they innervate predominantly the slopes of the cristae where mainly type II HCs are found. Conversely, irregular firing patterns are associated with thick axons having high conduction velocities. These axons innervate predominantly the crest of the cristae where mainly type I HCs are found. This functional classification is not as distinct as the morphologic HC classification. Experiments have determined three different morphologic categories of afferent axons based on the synaptic contacts that they make with the HCs: calyx, bouton, and dimorphic. Calyx-ending axons only synapse on type I HCs and are only found on the crests of the cristae; they have relatively low sensitivity but are irregular in their discharge pattern. Bouton-ending axons are only found in the periphery of the sensory epithelium innervating type II HCs; they exhibit regular firing patterns and are also rather low in sensitivity. Finally, axons with dimorphic endings innervate both type I and type II HCs and are found in all parts of the cristae. They exhibit a clear relationship between their degree of regularity and their sensitivity, with low-sensitivity units exhibiting regular firing patterns and vice versa. Regular and irregular neurons differ in their responses to rotatory stimuli. In general, the more regular the neuron’s firing rate, the more accurately it will encode angular head velocity in its firing pattern. If a rotatory stimulus of long duration is applied (Figs. 4-3A and B), then regular neuron spike rates encode angular velocity quite accurately (Figs. 4-3C and D), although the excitatory response is greater than its inhibitory counterpart. In contrast, the spike rate of irregular neurons peaks earlier and adapts exponentially with an adaptive time constant of about 30 sec, which is reminiscent of the HC adaptation already discussed. This adaptive behavior accounts for the apparent inhibition after termination of

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Semicircular canal afferents can also respond to audio frequencies if a direct mechanical or acoustic stimulus vibrates the cupula with sufficient force. In keeping with the resonant behavior of stereocilia alluded to previously, a regular tuning curve can be assembled that has a characteristic frequency of about 7 kHz in pigeons. If this stimulus is presented to one ear only, the animal will turn its head as if the ipsilateral canal were excited (Tullio effect).

Otolith Organs

Figure 4-3. Relationship of head rotation stimulus (A and B) to cupular deflection. (C) and primary canal afferent signals (D and E). A, Rotatory head ¨ C, Cupular deflection velocity (Q ). B, Rotatory head acceleration (Q). following slow time constant. D, Response of regular neuron (firing rate versus time). E, Response of an irregular neuron. RD, resting discharge; Sp/sec, spikes per second; °/sec, degrees per second.

excitation (undershoot) and the overshooting rebound following an inhibitory stimulus (Fig. 4-3E). The rapid rise time of the response in Figure 4-3E reflects a lead element,22 which is best studied using the Bode plots of Figure 4-4. The gain curve (Fig. 4-4A) for irregular neurons follows the theoretical mechanical fluid movement reasonably well at low frequencies. At higher frequencies, above 1 Hz, however, a dramatic gain increase occurs. The phase behavior of irregular neurons is characterized by a consistent lead throughout the frequency range, with an enormous difference between the fluid movement and the neuron firing rate evident in the higher frequency range (Fig. 4-4B). Although much more limited, a similar difference for high-frequency phase and gain is seen in regular neurons. As mentioned previously, irregular neurons tend to be more sensitive than regular neurons. In the middle frequency range where gain is nearly constant, the average sensitivity of nonadapting regular neurons is about 1.8 spikes per second per degree/sec, whereas the corresponding value for highly adapting irregular neurons is 2.5. Efferent innervation is unlikely to play a role in this difference because semicircular canal neuron behavior is virtually unchanged when anesthetized and alert animals are compared.

Figure 4-4. Relationship between canal dynamics (solid line) and response encoded in regular (dotted line) and irregular (dashed line) neurons. A, Gains (discharge rates per velocity). B, Phases.

Figure 4-5 illustrates a schematic view of the orientation of the otolithic maculae relative to the horizontal stereotactic plane. The horizontal portion of the utricular macula is tilted backward and downward by 25 to 30 degrees and laterally upward by about 10 degrees, just as in the horizontal semicircular canals. Since normal head position tilts the stereotactic plane by about 25 degrees with the chin downward, evidently both of these structures are normally held in the plane of their maximum sensitivity. A small anterior portion of the utricular macula is bent upward, so that maximum differential sensitivity would be obtained while the subject is in the supine or prone position. The saccular macula is oriented almost at right angles to both utricular portions, with its lower end deflected laterally by about 18 degrees. Its maximal horizontal sensitivity would occur while lying on one ear. Also shown in Figure 4-5 are the HC orientation vectors for the saccular macula (A) and the utricular macula (C). Although probably not physiologically significant, HC orientation vectors (and thus kinocilia) are always directed away from the striola in the saccule and toward the striola in the utricle. More importantly, both maculae contain HC orientation vectors in all directions. The striolae in both maculae are the central areas containing a greater density of smaller calcite otoliths on the otolithic membrane than on more peripheral areas. They are equipped with more type I HCs and are innervated by thicker axons, conducting spikes at greater velocities.

Adequate Stimulus The calcite crystals constituting the otoconia (statoconia) have a specific gravity of about 2.7 and are moving in endolymph with a specific gravity of about 1. Their greater inertia causes their relative displacement in a direction opposite to an imposed linear acceleration. The amplitude and

Figure 4-5. Position of utricular and saccular maculae relative to stereotactic horizontal plane. Deflection angles are given in A and B, and hair cell polarization vectors are summarized by arrows in A and C.

Physiology of the Vestibular System

dynamic characteristics of such relative otolith movement depend on the complex viscoelastic properties of the gelatinous otolithic membrane, which are not well enough understood for simple analytical treatment such as that applied earlier to the semicircular canal system. Direct measurements have shown, however, that the otolithic layer moves by about 30 μm/g (1 g is the linear acceleration exerted by gravity); threshold movements would be about 0.15 μm. This would translate into stereocilia deflections of the same small amplitudes discussed earlier for the semicircular canals. Otoconia movement is linear over an amplitude range of 1 g and saturates at higher acceleration values. In addition, the movement is damped so that the membrane does not oscillate after the application of an acceleration transient, although transient responses are brisk.

Macula Afferents Gravitational acceleration is always acting on the otolithic maculae; therefore attempts to define resting discharges for afferent neurons are not as easy as in the semicircular canal system.21 Only shearing forces acting at an angle to the stereocilia are effective, not compression forces acting along the axis of the cilia. Thus background activity can be defined as the firing rate that occurs when the HC is perfectly horizontal. Since afferent axons collateralize to innervate several HCs, and since HCs have different polarization vectors, an average resting position has to be defined for each afferent fiber. This can be achieved in three-dimensional space through direct measurements. For example, the vector component in the pitch plane for one utricular afferent can be extracted from Figure 4-6, in which discharge frequency is plotted against head position while the head is slowly rotated about the interaural axis. The pitch vector component for this fiber points toward the occiput, because gravity pull causes maximum firing in that direction. The roll vector component can then be measured in the same fashion and the two measurements combined to yield a complete representation of the polarization vector. The neuronal polarization vector directions measured in this manner correspond approximately to the HC vectors illustrated in Figures 4-5A and C; on average they are oriented horizontally in the utricular macula and vertically in the saccular macula. The fiber’s resting rate can then be measured when the gravity vector is oriented at right angles to the polarization vector. Referring to Figure 4-6, the fiber’s greatest sensitivity to positional

Figure 4-6. Static response to various positions in sagittal plane of utricular neuron. (See text.)

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change is clearly close to this resting position, whereas minimal sensitivity occurs at positions of either maximal or minimal firing rates. As in the canal system, macular units can be classified by their resting activity into regular, intermediate, and irregular groups. Irregular neurons tend to have thicker and faster conducting axons, lower average spike rates, and greater sensitivity. They are concentrated in the striolar region, whereas regular fibers tend to innervate more peripheral macular portions. Figure 4-7A illustrates that irregular units exhibit far greater adaptation with greater poststimulatory rebounds to extended acceleratory stimuli than do regular neurons. Thus regular neurons appear to signal steady head position, whereas irregular units better encode head position changes. This difference is quantified further in the Bode plots of Figure 4-7B, in which gains are almost independent of frequency for regular neurons, which represents faithful encoding of head position. For irregular units, however, gains are seen to increase with frequency, indicating a relative overemphasis on rapid acceleration changes. Figure 4-7A illustrates again the rectifying property of hair cell transducers, which leads to greater excitatory rather than inhibitory responses. As in the canal system, a consequence of this would be a net excitation during vibratory stimuli.

Figure 4-7. Tilt response of otolith neurons. A, Spike rate versus time plot illustrates differing adaptation for regular and irregular neurons. B, Gains (spike rate/acceleration) for regular and irregular neurons during oscillatory tilting.

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Vestibular Efferents Labyrinthine HCs are innervated not only by the postsynaptic afferent dendrites, but also by presynaptic terminals that contact the HC membrane in type II HCs and the calyx of the afferent ending at type I HCs. These terminals contain spherical vesicles, much as has been described in cholinergic terminals elsewhere in the body, and are derived from a small, distinct axon bundle within the vestibular nerve that is strongly cholinesterase-positive.23 Cells of origin for the efferent bundle do not appear to degenerate following transection of the vestibular nerve and therefore have only been discovered since the development of retrograde tracer techniques. Most efferent cell bodies in mammals are clustered in a small group, termed group E, which is dorsolateral to the nucleus of the abducens nerve and adjacent to the genu of the facial nerve.24 In birds25 and lower vertebrates, the efferent cells are scattered in the caudal pontine reticular nucleus, where some of these cells are also found in rodents.26 Only a few hundred of these cells exist, distributing their axons to some 20,000 HCs in the periphery. Thus many collaterals issue from each efferent cell, and each cell innervates several semicircular canals or otolithic maculae (or both), with some cells even innervating both labyrinths.27 This implies that the efferents cannot exercise a direction-specific control function. Because of the extensive efferent collateralization, electrical stimuli of one ampullary nerve can produce trans-synaptic responses in other subdivisions of the vestibular nerve. These responses are simply axon reflexes and do not indicate peripheral interconnections between various labyrinthine sensors. It has been suggested that if the efferent system is activated in anticipation of movement, then it could be used to switch the vestibular system from a postural mode to a volitional mode by inhibiting units that could be saturated by large head movements and activating units that have large dynamic ranges. Although many theories exist, the exact function of the efferent system remains elusive.

VESTIBULO-OCULAR REFLEX No brain function is as well understood and as thoroughly studied as the vestibulo-ocular reflex (VOR).1,28–30 There are several reasons for this: 1. Detailed knowledge is available about the input from the vestibular labyrinth and the signals required to drive the eye. 2. Input and output are linked by only one brainstem neuron. 3. Signal transformation within the brain are well understood. In contrast to many reflexes used in clinical diagnostic studies, the VOR’s purpose is understood completely. Thus VOR analysis is a particularly useful diagnostic tool, directly assessing the patient’s functional capacity. The VOR’s purpose is to stabilize images on the retina during head movements. The reader can immediately verify how critically important this reflex is by attempting to read this text while shaking the book through a small angle

a few times per second. Reading will become impossible because the visual tracking reflexes are far too slow to guarantee satisfactory visual stability when the visual target is moving at such frequencies. If, however, the book is kept still and the head is gently shaken, reading is easy because now the relative movements between the visual target and the head are compensated for by the VOR, which drives the eyes at the same velocity as the head but in the opposite direction. It is possible, however, to exceed the dynamic performance of even the VOR by vigorous head shaking, thus causing the print to blur. The dynamics of the human VOR have been studied in some detail. Recent experiments have demonstrated that human subjects are able to generate vestibular eye movements that compensate for the head movements up to 350 degrees/sec. For velocities higher than this, the gain (eye velocity/head velocity) is seen to decrease and the maximum eye velocities observed were about 500 degrees/ sec. Since the entire reflex pathway only requires a total of three neurons, it is not surprising that the latency (the time from the beginning of a head movement to the onset of the eye movement) is very short. Although there has been some disagreement as to the actual value, most authors now believe the latency of the human VOR to be 10 to 12 msec.

VOR PATHWAYS Strictly speaking, the VOR is defined as any compensatory eye movement resulting from stimulation of labyrinthine receptors by a head movement. It is more practical, however, to consider such eye movements as a combination of several separate reflexes that can be studied in isolation and that are transmitted via separate brainstem pathways. These reflex pathways are labeled according to their site of origin within the labyrinth.

Horizontal Canal VOR The horizontal canal VOR, which only compensates for horizontal head rotation, should not be confused with the horizontal VOR, which must also compensate for lateral linear motion of the head and is mediated by otolithic receptors. To avoid confusion, the canal-based VOR has recently been renamed the angular VOR, or aVOR, to distinguish it from the otolith-mediated linear VOR. Electric stimulation of one horizontal canal nerve causes a pure horizontal deviation of both eyes toward the contralateral side, which is mediated via the three-neuron reflex arc summarized in Figure 4-8. The excitation from the horizontal canal afferents is fed through excitatory interneurons in the vestibular nuclei to the contralateral abducens nucleus, resulting in excitation of lateral rectus (LR) muscle motor units. A second group of excitatory vestibular interneurons sends its axons up through the ascending tract of Deiters (ATD) to terminate on ipsilateral medial rectus (MR) muscle motor units in the oculomotor nucleus. Although the ipsilateral MR and contralateral LR muscles contract simultaneously, the corresponding vestibular nucleus (VN) neurons do not send axon collaterals to both motoneuron groups. Strict separation of these pathways permits separate regulation of muscle

Physiology of the Vestibular System

Figure 4-8. Direct neuron connections of horizontal VOR. Arrows in eye indicate direction of evoked eye movement. IS, Interstitial nucleus of vestibular nerve; S, L, D, and M, superior, lateral, descending, and medial vestibular nuclei, respectively; PH, nucleus prepositus hypoglossi; III, ocular motor nucleus; VI, abducens nucleus.

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Although second-order VOR neurons in the vestibular nuclei transmit signals to great functional specificity, their axons do not terminate exclusively around extraocular motoneurons. For the horizontal VOR, detailed knowledge is available on the axon collateralization of these neurons.32–35 The excitatory axons terminating in the contralateral abducens nucleus have two main collaterals, which ascend and descend in the MLF to issue side collaterals toward the prepositus hypoglossi (PH) nucleus and certain portions of the reticular formation. The descending collaterals travel down to at least the second cervical segment of the spinal cord and thus represent part of the medial vestibulospinal tract. Some of these neurons send further collaterals into the contralateral medial vestibular nucleus, where they excite local interneurons (type II) capable of inhibiting horizontal VOR transmitting neurons. Inhibitory VN neurons terminating in the ipsilateral abducens nucleus issue only caudally directed collaterals traveling in the MLF. Both inhibitory and excitatory VOR-mediating neurons send recurrent collaterals back into the VN, which might be partly responsible for the integration process discussed in the following sections.

Anterior Canal VOR contraction to combine vergence movements with the VOR while fixating targets at various distances. These connections suggest that the VOR gain to the separate horizontal eye muscles might be adjusted by vergence signals within the vestibular nuclei. These excitatory VN cells are scattered around the border between the medial, lateral, and descending vestibular nuclei, which casts some doubt on the functional significance of these cytoarchitectonic borders. Because the eyes are always moved in a push-pull fashion, the antagonist eye muscles are relaxed simultaneously by two separate inhibitory pathways. Inhibitory interneurons excited by the lateral canal nerve project directly to the ipsilateral abducens nucleus and thus cause a relaxation of the ipsilateral LR. The inhibitory pathway to the contralateral MR involves one more neuron (a four neuron reflex arc). The lateral canal nerve contacts an excitatory VN interneuron, activating in turn an inhibitory interneuron in the superior vestibular nucleus, which sends its axon through the contralateral medial longitudinal fasciculus (MLF) to inhibit contralateral MR motor units. Again, inhibitory pathways to both eyes are kept strictly separate, presumably to allow for the influence of vergence during the horizontal VOR. Both motor nuclei involved in the horizontal VOR are interconnected by internuclear neurons. Such cells constitute about 50% of the abducens nucleus neuron population and act somewhat like surrogate MR motoneurons as they convey the signals destined for LR motoneurons to the MR motoneurons on the opposite side. Their axons ascend in the MLF and it is the interruption of these axons that results in the MR paresis seen in internuclear ophthalmoplegia. Internuclear neurons within and around the oculomotor nucleus31 are excited by axon collaterals from MR motoneurons and project back to the abducens nucleus of the other side. A few of these fibers appear to be directed to the ipsilateral abducens nucleus.

Electrical stimulation of the anterior canal nerve results in a conjugate upward deviation of both eyes along with counterrolling such that the upper poles of both eyes move toward the contralateral side (i.e., the ipsilateral eye intorts and the contralateral eye extorts) (Fig. 4-9). When the eye is at primary position, elevation is more pronounced in the ipsilateral eye, whereas counterrolling is more pronounced in the contralateral eye. Both elevation and counterrolling are produced by a contraction of the ipsilateral superior rectus (SR) and the contralateral inferior oblique (IO) muscles. In contrast, the antagonists of these muscles, the ipsilateral inferior rectus (IR) and contralateral superior oblique (SO) muscles, are relaxed by inhibition of their motoneurons in the ipsilateral trochlear nucleus and the

Figure 4-9. Anterior canal VOR connections. Symbols and abbreviations as in Figure 4-8.

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IR subdivision of the ipsilateral oculomotor nucleus. The inhibition is mediated by one class of interneurons on the superior VN, innervating both of these motoneuron pools via axon collaterals.35 The contraction of the ipsilateral SR and the contralateral IO is mediated by one type of excitatory VN interneuron, also located in the superior VN, which innervates both motoneuron pools within the contralateral oculomotor nucleus. Remember that the SR and SO muscles have their motoneurons located contralaterally in the brainstem, whereas all other extraocular muscles are innervated ipsilaterally, thus the innervation of the vertically acting extraocular muscles is arranged so that the muscles that cause intorsion of the eye have their motoneurons located on the contralateral side of the brainstem, while muscles that cause extorsion are innervated ipsilaterally. The wiring diagram for the anterior canal VOR is simpler than that for the horizontal canal VOR because there are only two classes of VN cells involved as can be seen in Figure 4-9.

Posterior Canal VOR Electrical stimulation of the posterior canal nerve (Fig. 4-10) causes counterrolling in the same direction as does ipsilateral anterior canal stimulation. The rotatory component is stronger in the ipsilateral eye and the additional downward deviation is more apparent in the opposite eye. These movements are caused by contraction of the ipsilateral SO and contralateral IR. The corresponding motoneuron pools receive excitatory input from a single class of VN neurons located in the medial vestibular nucleus, which sends axon collaterals to both the trochlear nucleus and the IR subdivision of the oculomotor nucleus, both on the contralateral side. These axons travel up and down the MLF to contact cells in a variety of other areas including the pretectal areas, the interstitial nucleus of Cajal, the nucleus of the facial nerve, and neuron groups in the reticular formation around the abducens nucleus. In addition, axon collaterals

are seen to ramify within the medial and lateral vestibular nuclei and in the PH nucleus.36 Most of these cells send a prominent axon branch down into the spinal cord, although excitatory secondary vestibular neurons without such vestibulospinal connections also exist. The antagonist muscles are relaxed by inhibition of their motoneurons in the ipsilateral oculomotor nucleus. This inhibition is mediated by inhibitory neurons located in the superior VN that form synaptic contacts with both SR and IO motoneurons. The SR motoneurons then send their axons across the midline to innervate the contralateral eye. These inhibitory vestibular neurons form less extensive collateralizations outside of the oculomotor complex and only appear to contact reticular formation neurons close to the midline. The final ascending axons appear to project beyond the midbrain to some higher centers. Excitatory VN cells in all of the canal VOR pathways exhibit extensive collateralization within their target ocular motor nuclei, with each second-order axon contacting some 90% of the motoneurons in its specific target nucleus. This results in a signal-averaging process that lends credibility to the approach of using a single quantitative equation to describe the signal carried by that cell group. Figures 4-9 and 4-10 clearly show that all vertical canals participate in the vertical VOR as well as in the counterrolling torsion reflex (tVOR). The discrete connection of certain eye muscles with specified canals in the schemes already described must not be viewed as a complete description of the canal-based VOR (aVOR). Rather, the antagonist muscle pairs connected with each canal can only be regarded as the prime movers, since all extraocular muscles are always involved in all vertical eye movements. The reasons for this are as follows: 1. Canal pairs are not exactly coplanar, thus during any head movement more than two canals are stimulated. 2. About 40% of the secondary vestibulo-ocular neurons receive afferents from two canal pairs and 16% of them from all three canal pairs.37 3. The eye muscle pulling directions are not perfectly orthogonal to the canal activation axes. 4. The actions of the vertically acting extraocular muscles are dependent on the eye position; for example, the relative amounts of elevation and intorsion produced by contraction of the superior rectus vary with the position of the eye in the orbit. These multiple input neurons are thought to regulate eye movements in intermediate planes.

Otolith VOR

Figure 4-10. Posterior canal VOR connections. Symbols and abbreviations as in Figure 4-8. PrT, Pretectum; IC, interstitial nucleus of Cajal; IV, trochlear nucleus; VII, facial nucleus.

For many years, it was widely believed that the otoliths did not contribute significantly to the VOR because experiments with linear translation as a stimulus failed to demonstrate substantial compensatory eye movements. The reason for this is a geometric one. When a target at visual infinity (in practice it need only be a few meters away) is viewed, then the eye movement required to keep the target on the fovea is negligible. If, however, a near target is viewed, then the required tVOR gain for clear vision becomes much greater; indeed, the required gain is a function of target distance (Fig. 4-11A). Thus if tVOR

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Figure 4-12. If the head moves toward (or away from) a target that is in line with the right eye, the required compensatory eye movement is a rotation of the left eye but no rotation of the right eye. Thus the IVOR gain must be a function of both the target distance and the position of the eye in the head.

Figure 4-11. A, When the head is displaced laterally through a distance X, the required compensatory eye movement, θ, can be calculated from the formula θ = arctan (X/D ) where D is the distance to the target; thus when the target is moved close to the head, from T2 to T 1 in this instance, the required eye rotation increases. B, If a subject views a target at the position T, which is located closer to the head than the axis of rotation R, then the eye movement required to compensate for a rotation through an angle A is B + C. Note that the eye movement required is in the same direction as the head rotation; thus if the head rotates to the right, the eyes must also rotate to the right. In this situation, the aVOR and the IVOR act in opposite directions and the IVOR must dominate if clear vision is to be maintained.

gain is measured during linear acceleration while viewing a near target, the gain is found to be very significant and, in addition, has been found to be a function of the vergence angle of the eyes.38,39 In fact, if a target is closer to one eye than it is to the other, and this is often the case, then the tVOR varies in the two eyes, as it should. Indeed, the gain, and even the direction of movement, of the eyes during the tVOR needs to be a function of both eye position and vergence angle (Fig. 4-12). For example, if the head is moved in the nasal-occipital direction toward a target that is in line with one eye, then the required tVOR should produce no movement in the eye in line with the target, but an adduction of the other eye (see Fig. 4-12). This is, indeed, just what is observed.40,41 Many second-order canal neurons also receive input from the otoliths.42 The latency of the three-neuron arc on which the aVOR is based has been measured and found to

be about 12 msec. The latency of the tVOR is similar. This discovery of the tVOR is of potential clinical relevance because it offers a means of testing otolith function. Since the axis of rotation of the eyes is in front of the axis of rotation of the head, translation of the eyes occurs with all normal head rotations and thus the tVOR is used when the head moves while viewing a near target. Horizontal linear head translations are sensed mainly by the utricular maculae, whereas the vertical head translations activate the saccular maculae. Detailed examination of the pathways from the otolithic maculae to the eye muscles is much more difficult than it is for the canals, since the macular nerves carry information about all conceivable directions of movement. Thus stimulation of these nerves produces eye movements of no functional significance. For example, stimulation of the whole utricular nerve causes torsional movements of the eyes with intorsion of the ipsilateral eye and extorsion of the contralateral eye. In addition, the ipsilateral eye elevates and adducts while the contralateral eye depresses and abducts. If small areas of the utricular macula are stimulated, more discrete contractions, apparently of a single eye muscle in each eye, can be achieved. Similarly, stimulation of the superior saccular area produces upward movement, and stimulation of the lower area causes downward movement.

Spinal Influences The diagrams summarizing the semicircular canal VOR pathways (Figs. 4-8, 4-9, and 4-10) suggest that vestibuloocular neurons are the source of at least part of the medial vestibulospinal tract. This is largely true for excitatory second-order cells, whereas the inhibitory neurons tend to be kept separate for ocular and spinal function. Generally, vestibulo-ocular neurons use γ-aminobutyric acid (GABA) as a transmitter substance (blocked by picrotoxin), whereas vestibulospinal neurons tend to be glycinergic (blocked by strychnine). Spinal cervical proprioceptive afferents in turn can influence the activity of second-order vestibulo-ocular neurons, which implies that the normally weak neck-to-eye

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reflex is at least partly funneled through VOR pathways. It is presumably through this pathway that the effects of neck injury on balance and eye movements are mediated. The corresponding afferent pathways are not as well understood. Injection of anterograde tracers into the upper two spinal ganglia revealed a scanty projection system into the caudal portions of the descending and medial vestibular nuclei as well as into the intercalated (Staderini) nucleus, which is a caudal extension of the PH nucleus (D. W. F. Schwarz and I. E. Schwarz, unpublished observations). None of these areas receives primary vestibular afferents, nor do they contain secondary VOR neurons. The neck proprioceptive afferent influence on the VOR thus must be polysynaptic.

CEREBELLAR LOOP Primary vestibular axon collaterals terminate in the caudal vermis of the cerebellum on granule cell (GC) dendrites within the granular layer of the cortex (Fig. 4-13). In addition, axon collaterals convey the same information to the fastigial nucleus. Rather surprisingly, the flocculus, a portion of the cerebellum that projects directly to the VN, does not appear to receive as many direct inputs from the vestibular nerve. GC axons, the parallel fibers, excite Purkinje cells (PCs), which are the only output of the cerebellar cortex. These PCs send inhibitory GABAergic axons into the VN, which terminate on VOR neurons. Part of the GC excitation within this loop is derived from VN neurons rather than primaries. This is particularly true of the flocculus, which receives a substantial input from the VN. Such vestibulocerebellar inhibition is available for all coplanar semicircular canal pairs but not for all secondary VOR neurons. For the horizontal canal system, only the VN cells terminating in the ipsilateral abducens nucleus are so inhibited; in the vertical canal system only secondary cells connected to the anterior semicircular canals have this inhibitory control, not those responding monosynaptically to posterior canal stimulation. For each canal-specific eye movement plane, a special microzone of the floccular cortex is responsible for this direct inhibition. As indicated in Figure 4-13, the cerebellar loop is closed at the ocular output side. Retinal slip signals carried via the accessory optic tract and relayed in the nuclei of the optic tract are carried to these same cerebellar PCs via their second afferent type, the climbing fibers (CFs). All cerebellar CFs originate in the inferior olivary nucleus.

Figure 4-13. Schematic diagram of visual and cerebellar influence on VOR. VN, Vestibular nucleus; GC, granule cells; PF, parallel fibers; PC, Purkinje cells; CF, climbing fibers; RF, reticular formation; IO, inferior olivary nucleus; AOT, accessory optic tract; NAOT, nuclei of accessory optic tract.

Activity of the CFs is thought to be able to modulate the efficacy of the parallel fiber-PC synapse, and this type of modulation is thought to be responsible for the adjustment of motor signals during trained movement coordination.43

SIGNAL TRANSFORMATION If the VOR input and output signals are known, the signal processing that must take place within the brain can be deduced. The semicircular canal input has already been discussed and has been well characterized by a number of investigators.44–46 The output elements are the ocular motoneurons and their associated muscle fibers. The extraocular muscles are very discretely innervated with a ratio of motoneurons to muscle fibers of nearly 1:1. Although several types of muscle fibers can be identified both histologically and functionally, all the motoneurons behave in much the same fashion. Some of the motoneurons have low recruitment thresholds (i.e., they are recruited into the active pool when the eye is still far in the off direction of the muscle), and these units tend to have low velocity sensitivity as well, resulting in a behavior that is more tonic in nature. Others have high thresholds and tend to have higher velocity sensitivity and thus might be described as being more phasic in their firing patterns. In spite of these differences, all motoneurons are involved in all types of eye movements. Even those with the lowest thresholds show some phasic behavior, and those with the highest thresholds exhibit tonic firing during fixation if the eye is deviated far enough. Thus they all exhibit both phasic and tonic firing patterns and so can be classified as burst-tonic (BT) cells. The ocular motor apparatus (often called the plant if the motoneurons are included) is simpler than that for skeletal joints for a number of reasons. First, the forces resisting muscle contraction are almost totally due to the viscous drag and elastic tension within the eye muscles, with a small contribution from the other orbital contents. Thus the system does not have to deal with variable and unpredictable external loads. Second, the eye muscles insert tangentially to the globe and “peal off ” as the eye rotates. Thus their insertion angles, and corresponding mechanical advantage, are essentially constant. The result is that over most of its operating range, the eye represents a completely predictable load. Given the mechanical simplicity of the system, it is not surprising that the behavior of the motoneurons can be described with substantial accuracy by means of simple linear equations. Furthermore, since all the motoneurons behave in much the same fashion, we can write down a general equation that will apply for all motoneurons with the only modification necessary being an adjustment of a few parameter values in order to specify the behavior of any particular cell. If average values for the parameters are measured, a general equation that describes the behavior of the whole pool can be deduced. The neuron discharge rate (Rm) has been shown to be a function of both eye position and velocity. Therefore the equation needs to have parameters related to these two variables along with a description of the eye position at which the neuron is recruited into the active pool. If we define E as

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eye position, Et as recruitment threshold, and E′ as eye velocity, then experiments have found that the required equation is Rm = k(E − Et ) + rE′

(4-1)

If the eye were to be passively displaced (by pulling on it when the patient is anesthetized), this equation predicts that the eye should return to its rest position with an exponential time course exhibiting a time constant of r/k. Recordings from awake trained monkeys have demonstrated the average values of the measured parameters. Et is about −25 degrees (i.e., the average motoneuron begins firing when the eye is still deviated 25 degrees into the field of the antagonist muscle). k is approximately 4.0; and r is about 0.95. Thus Equation 4-1 becomes Rm = 100 + 4E + 0.95E′ which means that the average motoneuron is firing at about 100 spikes per second when the eye is aimed straight ahead. Thus the eye muscles exhibit a remarkable amount of cocontraction. As the fixation position of the eye moves in the pulling direction of the muscle, the motoneuron firing rate will on average increase by 4 spikes per second for each degree of rotation. In addition, the firing rate will increase further if the eye is moving (rather than fixating a stationary target). This phasic increase will generate an additional 0.95 spikes per second for each degree per second of eye velocity. Finally, the time constant of the system should be 0.95/4 or about 240 msec, a value close to what has been measured under deep anesthesia. Equation 4-1 demonstrates that the oculomotor neurons exhibit both an eye position and an eye velocityrelated discharge. The signal coming from the semicircular canals is only related to head velocity. Its amplitude and direction can be adjusted in the VN so that it is appropriate to drive the eyes, that is, to supply the eye velocity command to the oculomotor neurons, but the eye positionrelated part of the signal still needs to be generated in some fashion. Because, in the mathematical sense, position can be derived from velocity through the process of integration, it has been deduced that a neural integrator must exist that generates the eye position signal by integrating the eye velocity signal. This turns out to be true for all eye movements, not just the VOR; a controller (for saccades or quick phases, for example) generates an eye velocity command, which is sent to both the integrator and to the motoneurons. The integrator output is then also sent to the motoneurons so that they receive the correct mixture of eye position and velocity inputs (Fig. 4-14). Experiments have strongly suggested that there is a single integrator for all types of eye movements. This integrator was originally thought to be located between the VN and the motoneurons (see Fig. 4-14A), because in anesthetized animals the VN neurons carried a head velocity signal just like the afferents. However, with the advent of singleneuron recordings in awake animals, the discovery was made that secondary VOR neurons already possessed an eye position signal, and so the situation must be closer to that illustrated in Figure 4-14B. The exact location of the integrator is still not clear. Lesions of the cerebellum greatly degrade integrator function, but do not eliminate it. Recently, lesions involving the VN and PH in primates

Figure 4-14. A, Convergence of the vestibular velocity and integrated position signals on ocular motoneurons as originally proposed by Skavenski and Robinson. B, Corrected version of the same diagram. Note that a portion of the eye position signal is already present on the secondary vestibular neurons. OMN, Ocular motoneurons; VN, vestibular nuclear neurons: INT, integrator.

have succeeded in completely eliminating integrator function. Whether the integrator is located in PH or in VN is still not completely clear, and the most likely explanation for the experimental data is that they involve interconnections among VN, PH, and the cerebellum. Note, however, that one integrator is not sufficient; instead, separate integrators are required for each eye movement direction (up, down, left, and right). Because the integrator is required to maintain the eye in eccentric positions, lesions that affect its performance (most commonly lesions of the posterior cerebellum) will result in an inability to hold eccentric gaze. The nystagmus that results has been termed gaze paretic nystagmus.

CENTRAL VOR NEURONS Figure 4-15 illustrates the oculomotor neuron firing that would result from an idealized VOR eye movement caused by a rapid head rotation while viewing a stationary target. The motoneuron discharge rate following the termination of the movement shows a step increase relative to that before the onset of the movement that reflects the new eye position (as manifested by the kE term in Equation 4-1). During the actual movement, the rE′ results in a further eye velocity-related increase in the discharge rate. Thus the BT activity is manifest as a pulse-step of activity in the spike rate versus time plot of Figure 4-15B, a terminology Robinson46 introduced to describe similar events during saccadic eye movements. During a movement of this type, the burst would result from semicircular canal activity while the step would be the result of the integrator output.

Burst-Tonic Cells Qualitatively, the same signal as that found on the motoneurons has been found in the vestibular nuclei, the PH nucleus, the paramedial pontine reticular formation (PPRF), the interstitial nucleus of Cajal, and the mesencephalic reticular formation. The function of these cells is unclear; they may be premotor cells, they may subserve

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Figure 4-15. Neuronal pulse-step response of a burst-tonic (BT) cell during idealized VOR eye movement. A, Head and eye position. B, Spike rate versus time, indicating combination of pulse (B, burstlike spike activity, bottom) and S, step (tonic rate increase, bottom).

an efference copy function, or they may be involved in oculomotor control in some other fashion. Since many of the BT cells in the vestibular nuclei project into the MLF,39 it seems likely that at least this subgroup may provide some drive to the motoneurons. BT neurons carry both eye velocity and eye position signals. Although the eye position signal is generally independent of the oculomotor system moving the eyes (saccades, VOR, smooth pursuit, etc.), the amount of eye velocity modulation is often not.

Second-Order Vestibular Neurons The neurons in the vestibular nucleus are diverse and are named based on the types of signals they convey. These cells include (1) position-vestibular-pause (PVP) neurons, (2) burst-tonic (BT) cells, (3) eye-head velocity (EHV) neurons, (4) floccular target neurons (FTN) (although these may be the same as EHV), (5) vestibular-only (VO) cells, and (6) vestibular pause cells.39,47–54 The firing rate of PVP cells is proportional to angular head velocity and eye position when the head is stationary and ceases during a saccade. It is thought to be the second neuron in the threeneuron arc of the angular VOR.39,53 Evidence for this comes from the finding that PVP cells involved in generating horizontal eye movements project directly to the contralateral abducens nuclei and that afferents have been shown to monosynaptically activate PVP cells.34,53 PVPs also can make inhibitory connection to the ipsilateral abducens (11% of the population53). There are also PVPs that make monosynaptic connections to the oculomotor (third) nucleus and participate in vertical eye movements.39,55 Eye and head velocity signals converging onto PVP cells act synergistically, since eye position sensitivity is in the opposite direction to head velocity sensitivity.51,53 This is true for both type I and type II PVPs, where type I indicates an increase in the firing rate in response to ipsilateral head velocity and contralateral eye velocity and type II is just the opposite. In general, the sensitivity of PVP

neurons to eye movements is measured by having an animal pursue a target. Similarly, the head velocity sensitivity of these cells can be measured by recording during VOR cancellation (looking at a target that rotates with the body). It is then common practice to use these sensitivity values to predict the behavior of PVPs. However, this form of linear analysis has not yet been validated. Indeed, it has been known for many years that linear summation of signals poorly predicts their behavior during stable gaze.39 The EHV cells, in contrast to the PVP, fire for eye and head movement in the same direction. Contralateral EHVs increase their firing rate in response to contralateral eye and head velocity,51,53 while ipsilateral EHV have opposite characteristics.56 It is believed that these cells are a subset of FTNs.51,55,57 Like the EHVs, FTNs also encode eye velocity, eye position, and head velocity although their eye velocity signal can be contralateral or ipsilaterally directed.58-61 VO neurons fire during translation and rotation of the head and have no eye position on them.39,53,54,62 Their behavior is perplexing and their exact role unknown. Recently it was shown that VO neurons decrease their sensitivity to head motion during head-on-body movement and combined eye-head gaze shifts,62 leading to the hypothesis that efference copy of the neck motor command suppresses the activity of these cells. These neurons, especially those in the LVN, MVN, and IVN (but not in the SVN) project to the spinal cord via the lateral vestibulospinal tracts (LVST), the medial VST (MVST), and the caudal VST (CVST).63,64 In addition, these cells project to the rostral fastigial nucleus in the rhesus monkey where most of the neurons also exhibit a combined canal and otolith input.65 Indeed, the rostral fastigial nucleus receives extensive input from the vestibular nucleus66 and minor input from vestibular afferents, making the cerebellum the most likely target of these vestibular neurons. The exact function of these cells is unknown although there do exist some hypotheses. For example, they could be a part of a preprocessing circuit for the VOR,54 or more likely they contribute to vestibulospinal reflexes as suggested by their projections to the fastigial nucleus.67 VO neurons are ideal for the study of convergence of rotational and translational signals. Given that natural head movements are composed of a combination of translation and rotation,68 then elucidating the types of interactions between these signals is paramount for the understanding of vestibular reflexes. Both these stimuli have been introduced simultaneously by using eccentric rotation (rotation around an axis removed from the interaural line).30,69,70 Linear techniques have been applied to PVP, FTN, and VO cells in order to calculate the sensitivity of the various individual signals converging onto them. Experiments using the previously mentioned method calculated the translational sensitivity of the VO cell by subtracting the linearly calculated rotational contribution to the firing rate. Specifically, an animal would be rotated on-axis (about an axis centered on the interaural line so that no translational acceleration exists) while the response of a neuron is being recorded. Given the rotational attributes, such as velocity or acceleration, the sensitivity of the cell to the stimulus can then be easily calculated. Then, the animal is shifted off-axis, so that eccentric rotation can be

Physiology of the Vestibular System

applied introducing a tangential acceleration. Note that the rotational stimulus does not change during the eccentric condition since the semicircular canals continue to sense the same rotational acceleration. The total forces during this condition do change though, as tangential and centripetal accelerations, which are dependent on the distance of the head from the axis of rotation are introduced. Given that the rotational sensitivity has been calculated, then the rotational contribution to the response of the cell during eccentric rotation was removed, leaving behind a residual signal. Since translational accelerations represented the additional stimuli during eccentric rotation, then the additional signals recorded (the residual) were assumed to be otolith in origin. This methodology makes the bold assumption that the interaction between the rotational and translational contribution to the firing rate is linear. No proof of linear behavior exists in the vestibular nucleus although there may be linear interaction between vestibulo-ocular reflexes. Sargent and Paige,71 by studying the VOR during eccentric rotation, have suggested that signals from different end organs sum linearly. The assumption of linearity in the vestibular nucleus was necessary since it was the only way to obtain an estimate of the otolith sensitivity. Assuming linearity, the otolith response was obtained by subtracting on-axis responses from eccentric responses.51,72,73 This method has been applied to cells in the vestibular nucleus with and without eye position sensitivity. The head velocity command is forwarded to the motoneurons by secondary vestibular neurons that behave in a manner similar to vestibular primaries during head movements, but exhibit firing patterns related to other eye movements (saccades, smooth pursuit, and optokinetic nystagmus) as well. Experiments have shown that FTNs exhibit large changes in firing behavior when the VOR gain is changed as a result of wearing magnifying or minifying lenses, while PVP change very little. As a result, many experimenters currently believe that the VOR is based on two parallel pathways: a PVP pathway that is relatively fixed, and an FTN pathway that is highly modifiable. It is likely that the FTN pathway is largely responsible for the compensation that occurs following unilateral peripheral lesions.

Burst Neurons Burst neurons are found in the pontine reticular formation near the abducens nucleus (horizontal “on” directions) and in the mesencephalic reticular formation near the midline and anterior to the oculomotor nucleus (vertical “on” directions). These neurons fire an intense burst of spikes beginning just before the onset of saccades and quick phases but are otherwise silent. They supply the saccadic pulse to the motoneurons. Several types of burst neurons exist. Discharges of short-lead burst neurons start 4 to 16 msec before the onset of the saccade. They can be further subdivided into inhibitory burst neurons (IBNs) and excitatory burst neurons (EBNs). For the horizontal system the IBNs are located just caudal and deep to the abducens nucleus, and the EBNs are located in reticular formation just rostral to the abducens nucleus. The vertical burst neurons are located in a nucleus in the mesencephalic reticular formation called the

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rostral interstitial nucleus of the MLF (riMLF). Consider the horizontal system as an example: The short-lead IBNs are inhibitory to contralateral abducens motoneurons, and the EBNs are excitatory to the ipsilateral abducens. Thus these two neuron pools are responsible for the bursts and pauses seen in the motoneurons during saccades and quick phases. During light sleep, burst neurons are seen to fire irregularly even though no saccades are occurring. If the animal is rotated under these conditions, burst neurons fire in phase with head velocity and thus must receive a vestibular input. Although the function of this vestibular input is unknown, it may be related to the problem of eye-head coordination, which is treated later. Since the burst neurons are responsible for the premotor drive signal during all saccades and quick phases, it is not surprising that lesions in medial reticular regions can result in slow or absent saccades.

Pause Cells Although many cells have been demonstrated to pause during saccades, there is one discrete group for which experimental data suggest a functional role. These cells are found close to the midline anterior to the abducens nucleus. They exhibit a regular firing rate except that they pause during all nystagmus quick phases and saccades. They have been shown to be monosynaptically inhibitory to the EBNs74 and IBNs.75 They are believed to function as part of a latch circuit that prevents neural noise from causing random saccades. Thus they must be inhibited in order to initiate a quick phase or saccade. Furthermore, stimulation of the pause neuron area results in the complete inhibition of all saccades and quick phases for the duration of the stimulus.

Tonic Cells The PPRF and PH nucleus also contain cells that encode only eye position by their firing. These cells have been termed tonic cells and are thought to represent the output of the neural integrator. Other cells behave in a manner similar to tonic cells except they have a weak eye velocity signal as well and thus may represent an intermediate step in the integration process.

COMMISSURAL CONNECTIONS Virtually all type I (excited by ipsilateral head rotation) VN neurons involved in the VOR send axon collaterals into a commissural system that connects both VN complexes (Fig. 4-16). BT cells monosynaptically excite type II (excited by contralateral head rotation) cells of the opposite side, which in turn inhibit BT cells there. In addition, type II neurons are monosynaptically inhibited by contralateral IBNs and BT cells excited by ipsilateral EBNs. A proposal has been made that the positive feedback loop that results from the connections between the BT neurons and the type II neurons might be subject to gain control and time constant modulation via the burst neurons. Galiana and Outerbridge76 have suggested that the commissural system functions as a type of oculomotor integrator. Unfortunately, although of theoretical interest,

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Figure 4-16. Neuron types mediating VOR from horizontal canal to contralateral abducens nerve and commissures. VP, Vestibular pause cell; BT, burst-tonic cell; TVP, tonic vestibular pause cell; PC, Purkinje cell; 2, type 2 cell; VI, abducens motoneuron; EB, excitatory burst cell; IB, inhibitory burst cell; P, pause cell: LR, lateral rectus muscle; F, neuronal filters. Dotted lines indicate hypothetic connections.

few data exist to support this view, especially since recent lesion studies have implicated the VN and the PH complex in the integration process. Certain statements concerning the commissures, however, can be made. Since many type I neurons are connected to the opposite canal via type II neurons, these type I neurons receive two complementary signals during head rotation. Specifically, they are excited by the ipsilateral canal and simultaneously they are disinhibited by the contralateral canal. Thus when one canal is lesioned, the head velocity sensitivity of type I neurons drops to approximately onehalf of its normal level (due to the loss of contralateral disinhibition). As a result, following a unilateral peripheral lesion, the brain needs to compensate for both the unequal activity in the VN on the two sides (resulting in spontaneous nystagmus) and the reduced sensitivity, which results in a subnormal VOR gain.

NEURON ACTIVITY DURING NYSTAGMUS Intermediary Neurons Because of the fact that the canals are arranged in complementary pairs, the two vestibular nuclei fire reciprocally during rotation and its resulting nystagmus.77 Thus the firing rate increases in the ipsilateral (relative to the rotation direction) type I neurons and a parallel decrease results in the contralateral type I cells. The various different cell types found in the VN exhibit characteristic behavior during nystagmus. During a slow phase directed toward the contralateral side (which occurs with ipsilateral rotation), VP cells maintain a steady discharge rate proportional to slow-phase, or head, velocity (Fig. 4-17A). The reciprocal pattern of concerted cell firing during excitatory (contralateral) quick phases and inhibitory (ipsilateral) movements is exemplified in Figures 4-17A to D. The behavior of all of the different cell types during nystagmus is simply what

Figure 4-17. Firing behavior of various VOR-mediating neurons during nystagmus. A, Excitatory slow phase. Eye position (top); discharge rates of burst tonic (BT), type 2, and vestibular pause (VP) cells (bottom). B, Excitatory quick phase. Eye position (top); discharge rates of BT, type 2, and VP cells (bottom). C, Inhibitory slow phase. Eye position (top); discharge rate of TVP (tonic vestibular pause) cells (bottom). D, Inhibitory quick phase. Eye position (top); firing rates of TVP cells and inhibitory burst (IB) cells (bottom).

would be predicted based on their activity during saccades, periods of fixation, and sinusoidal rotation.

Motoneurons Activation during both excitatory quick and slow phases in all extraocular motoneurons is caused by a combination of EPSPs (excitatory postsynaptic potentials) and a simultaneous release from synaptic inhibition (disinhibition). The opposite situation occurs during slow and quick phases in the inhibitory direction. In this case, there is a drop in motoneuron firing rate caused by a combination of IPSPs (inhibitory postsynaptic potentials) and disfacilitation. A notable exception to this is medial rectus motoneurons, which do not exhibit IPSPs during nystagmus.

VISUAL VESTIBULAR INTERACTION The primary function of the VOR is to stabilize images on the retina during head movements. There are three other eye movement systems with which the VOR must interact.78,79 The optokinetic system (OK) stabilizes images whenever the entire visual world (or at least a large part of it) moves. The smooth pursuit system (SP) functions to stabilize images of smoothly moving foveal targets (e.g., a bird flying through the air). The saccadic system is used to move a target from the peripheral retina onto the fovea. The first two of these, the OK and SP systems, are discussed here. Interactions between the saccadic system and the VOR are considered later in the section on Eye-Head Coordination. Both of these visual following mechanisms are very sluggish relative to the VOR since they require

Physiology of the Vestibular System

substantial processing of visual information and the visual system is slow. Due to the nature of the semicircular canals, the information that they supply concerning head velocity is only accurate at frequencies above 0.1 Hz. But what happens if the rotation frequency is below this value, as it might well be if one were, for example, running around a curved track? The answer is simply that the vestibular estimate of angular head velocity would become inaccurate (as the cupula moved back to its rest position), the compensatory eye movements would abate, and the seen world would become hopelessly blurred. The brain deals with this problem by using information from the visual system to supply it with the required data about low-frequency movements. Indeed, when the seen world moves, the brain assumes that since the world cannot move, it must be the body that is moving. This is the cause of a series of illusions called vection. Circular vection is the illusion of self-rotation that results from rotation of the visual surroundings (as when one is inside an optokinetic drum), and linear vection is the illusion that results when the visual world appears to move linearly. Most people have experienced linear vection at some time in their lives. If you are sitting in a train looking out the window while the train is in a station and the neighboring train begins to move, you feel as if you are moving instead.

VOR Neurons The inability to distinguish between self-motion and environmental motion can be explained by the behavior of second-order vestibular neurons. All VN neurons with canal input can also be activated by an OK stimulus in the appropriate plane. For example, a horizontal type I neuron will be excited by rotation of the visual field (an OK drum) to the contralateral side in the horizontal plane. Note that when the drum rotates contralaterally, the movement of the drum relative to the observer is the same as it would be if the drum were stationary and the observer rotated ipsilaterally. The function of this OK input to VN neurons is to compensate for the poor low-frequency behavior of the canals and to cause the neurons in VN to behave appropriately (Fig. 4-18). If a velocity step is used in darkness, the cell typically reaches its peak firing rate very quickly (Fig. 4-18A), but then returns to its background level with a time constant of about 25 sec (see Fig. 4-18B). The reason that the observed time constant is 25 sec instead of the cupular time constant is rather complex and is not fully understood. However, both Robinson46 and Raphan and colleagues80 have suggested ways in which this might be accomplished. Robinson uses a positive feedback loop and Raphan uses a velocity storage integrator (separate from the previously mentioned oculomotor integrator). Which of these two theories turns out to be correct (if either) remains to be seen, but the effect in either case is to increase the time constant to about three times that of the cupula. If an OK drum is now rotated around the stationary animal, the firing rate of the VN neurons is seen to build slowly with this same 25-sec time constant (see Fig. 4-18C). Thus, when the vestibular and OK responses are combined, as would happen if the animal were rotated in the

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Figure 4-18. Response of VN neurons (A to D) and nystagmus slow-phase velocity (E to H) to prolonged rotatory stimulation at constant velocity. A, Stimulus velocity ramp for B, C, and D. B, VN neuron discharge rate versus time during rotation in dark (solid line) or rotation while fixating on target moving with monkey (dashed line). C, Neuron response to optokinetic stimulation (drum rotating around monkey). D, Neuron firing rate during rotation in light. E, Stimulus velocity profile for F to H. F, Nystagmus slow-phase velocities during rotation in dark G, Slow-phase velocities of optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN). Dashed line indicates contribution by OK and smooth pursuit (SP) system, respectively. H, Slow-phase nystagmus velocities during rotation in light. Note that firing rate in D represents sum of rates in B and C and that nystagmus slow-phase velocity in H is obtained by adding SP velocities of F and OK portion of G.

light inside a stationary drum, the resulting neuron firing precisely mimics the actual rotation velocity profile. (Obviously the desired effect as the cell now accurately reflects the required eye movement command.) The OK signal is derived from specialized retinal ganglion cells with large receptive fields covering much of the retinal periphery. Their firing rates encode the velocity with which the visual field is moving (often called retinal slip velocity) in specific directions. The axons of these cells constitute the accessory optic tract (AOT), which terminates in the nuclei of the accessory optic tract (NAOT) in the midbrain. From there the signal is fed to the vestibular nuclei and vestibulocerebellum via the pontine reticular formation. Thus the vestibular nuclei generate an estimate of head velocity based on both vestibular and visual information. The vestibular information is used during highfrequency movements, whereas the visual information is used during low-frequency movements.

Nystagmus The responses of secondary VN neurons (see Figs. 4-18A-D) are reflected in the corresponding nystagmus slow-phase velocities (see Figs. 4-18E-H). Vestibular

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rotatory and postrotatory nystagmus time constants are identical to the neuronal time constants (see Figs. 4-18B and F), and the combined vestibular and OK responses generate a faithful replica of the stimulus in the nystagmus slow-phase velocity profiles when the rotation occurs in the light (see Fig. 4-18H). The optokinetic response, however, is complicated by the fact that both the OK and SP systems contribute to the overall visual response (see Fig. 4-18G). We can see in Figure 4-18G that an initial rapid rise in slow-phase eye velocity occurs followed by a slow increase until finally eye velocity matches drum velocity. The pattern shown here is commonly seen in nonhuman primates. Human subjects, however, exhibit a slightly different pattern in that there is not normally a slowly increasing part to the response. Instead, eye velocity jumps immediately to drum velocity and then stays there. Other experiments have demonstrated that during the course of the maintained response, the SP system is generating almost all of the nystagmus immediately after the start of the stimulus, but this contribution subsequently drops as the OK system increases its contribution (the slowly increasing part of the monkey response in Fig. 4-18G). When the lights are then switched off, the SP component decreases very rapidly to zero. As a result, the residual nystagmus after the lights are extinguished starts at a lower velocity (due to the lack of any SP component) and is a result of the OK system. It is termed optokineticafter-nystagmus (OKAN). This OKAN declines with a time constant of about 25 sec, approximately the same as that of postrotatory nystagmus, and its initial value reflects the contribution of the OK system immediately prior to turning out the lights. Thus, the fact that both the SP and OK systems contribute to optokinetic nystagmus (OKN), whereas OKAN is driven only by the OK system, means that only measurements of OKAN reflect OK systems behavior. Indeed, OKN could theoretically be normal even with a completely nonexistent OK system; the nystagmus would be purely a result of smooth pursuit of the moving stripes. OKAN has some function in the diagnostic assessment of vestibular function.81 Although its usefulness is limited by the fact that it exhibits considerable test-to-test and subjectto-subject variability. OKAN is lost following bilateral labyrinthectomy, and after loss of only one labyrinth, it is stronger toward the intact side. Again, following unilateral lesions, the time constant of OKAN is reduced when the slow phase is directed toward the intact side as is the time constant of the VOR. Together with the second-order neuron data (see Fig. 4-18C), all of these observations suggest that some form of neural velocity storage mechanism is shared by both the OKN and VOR pathways. This is believed to be the same mechanism that prolongs the time constant of the vestibular system from that of the cupula to that seen during postrotatory nystagmus. In animals with laterally positioned eyes and no fovea (e.g., the rabbit), there is no SP system. Thus, during OK stimulation, the velocity of the slow phases of the nystagmus does not exhibit a sudden initial jump as it does in primates. Instead, the velocity is seen to build slowly until it reaches drum velocity. Up to about 60 degrees/sec the OKN system exhibits a gain of about 0.8. (Gain here is defined as eye velocity

divided by drum velocity.) For drum velocities greater than this value, the gain begins to decrease until the system saturates for drum velocities in excess of 120 degrees/sec, and further increases in stimulus velocity result in lower, rather than higher, eye velocities. Horizontal vestibular nystagmus can be driven by either the horizontal canals, or, under exceptional circumstances, by the otoliths (during barbecue spit rotation, for example). During normal rotations, the horizontal canal activity contributes to the nystagmus in the following two ways: 1. Modulation of firing rates in the primary afferents caused by cupular deflection is responsible for rotatory and postrotatory vestibular nystagmus; the slow-phase velocities quickly approach head velocity and then decay with a time constant of about 20 sec. 2. The background activity in the lateral canal fibers is essential for normal function of the velocity storage mechanism in the VOR and OKN pathways. Thus the slow decay in OKN after the drum lights are extinguished, OKAN, is present if the canal’s mechanical responsiveness is eliminated by canal plugging, but disappears if the lateral canal nerve is cut. If a subject is tilted and then rotated about the new tilted axis, which might be earth horizontal (barbecue spit nystagmus82) or merely at some intermediate angle (off vertical axis rotation [OVAR]),19 the resulting nystagmus endures for the duration of the stimulus and does not decay as it does when the rotation axis is vertical. If the lateral canals are plugged, the enduring nystagmus is still present but disappears when the utricular nerve is sectioned. If, however, the lateral canal nerve is sectioned and the utricular nerve is left intact, the nystagmus cannot be elicited. Thus, although this type of nystagmus seems to be driven by the otoliths, it requires a certain amount of activity in the lateral canal nerve. The most reasonable explanation for these findings is that the otolith information responsible for generating OVAR nystagmus is fed through the velocity storage system, which depends on lateral canal nerve activity to function. Thus if OVAR nystagmus is elicited clinically with any kind of rotating chair (which, of course, must be able to be tilted) then the responses can be used to check lateral canal, otolith, and velocity storage system functions. The velocity storage mechanism can be discharged, or “dumped,” by changes in head orientation. For example, if, during postrotatory nystagmus, the head is suddenly pitched forward, the nystagmus decay time constant suddenly drops from the normal value of 20 sec to that of the cupula (about 6 sec). Thus this procedure greatly reduces the duration of the postrotatory response. This is believed to be caused by a sudden tilt-induced discharge of the activity in the velocity storage circuits and is often termed dumping. This dumping is dependent on the integrity of the cerebellar nodulus. Thus patients with lesions involving the nodulus do not dump their postrotatory nystagmus when they tilt their heads. A similar simple diagnostic avenue exists for the vertical canals. If horizontal rotation is maintained about the normal vertical axis, then the nystagmus will also be maintained provided the head is pitched (nose up and down)

Physiology of the Vestibular System

periodically.80 In this situation, information about the rotation is available because the anterior and posterior canals are alternately excited and inhibited during the pitching as their planes are being moved away from the null (vertical) position. The brain apparently derives the true axis of rotation from the combined and constantly changing activity of all six canals. Again this information seems to make use of the velocity storage system since it survives lateral canal plugging but not lateral canal nerve section. Utricular nerve section has no effect in this case. Curiously, periodic roll movements (ear up and down) do not result in maintained nystagmus. As interesting as these observations are, they cannot be used for clinical testing in the way that OVAR can since pitch head movements during horizontal rotation rapidly provoke nausea in most subjects. An interesting asymmetry exists for vertical nystagmus.83 Although velocity storage for upward slow phases exists, when slow phases are directed downward, little or no velocity storage seems to occur. Thus if a subject is rotated while lying on his or her side with the vertical rotation axis passing through both ears, then the rotatory and postrotatory nystagmus will be markedly different in duration, reflecting the different up and down time constants. In this situation, the time constant for downward nystagmus (upward slow phases) has been found to be about 30 sec, whereas that for upward nystagmus (downward slow phases) is only about 7 sec, which is not surprising because the OK and vestibular system share the same velocity storage system. Downward OKN is prominent but upward OKN is minimal or even absent. Furthermore, otolithic input appears to be able to suppress the unidirectional vertical velocity storage system. When vertical OKN is evoked with the subject seated in the normal upright position, minimal OKAN occurs in both up and down directions. The up and down asymmetry can be restored, however, if the otolithic maculae are destroyed.84 Finally, nystagmus behaves as if it wants its direction to be horizontal (perpendicular to the gravity vector). Thus if one attempts to induce horizontal (relative to the head) OKN while the subject is lying on his or her side (note that this means that the OK drum must also be on its side so that the stripes move horizontally with respect to the head), the resulting nystagmus beats not purely in the direction of the drum rotation but instead develops a vertical (with respect to the head, horizontal with respect to the gravity vector) component. Thus the otoliths are even able to modulate the direction of visually induced OKN, not just its time constant. When the normal gravitational effect on otolithic input is reduced under the microgravity conditions that occur during space flight, the prominence of velocity storage for upward movements results in a constant bias and an accompanying circular vection, which may account for some of the disorientation and space sickness that occurs. Pigeons in zero gravity fly in a vertical backward circle attempting to compensate for this illusion. A practical consequence of these observations is that a short and updown symmetric time constant for vertical OKAN will be indicative of a lesion affecting the otoliths. A similar bias occurs in the horizontal system following unilateral horizontal canal lesions. The lesion, because of

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its effect on the velocity storage system, results in a decrease in the time constant of the nystagmus directed toward the lesioned side. Thus vigorous head shaking will charge the intact velocity storage system but not the lesioned one. This will result in a bias that will in turn cause a brief period of nystagmus after the head shaking stops. This head shaking nystagmus will beat away from the side of the lesion and its existence can be used as a simple test for unilateral lesions.

Quantification of Human Vestibulovisual Interaction Eye-tracking reflexes are important for stabilization of the visual environment during head movements. If a person is oscillated on a rotating chair strong enough to cover the VOR frequency range of up to 6 Hz, then perfect compensation requires a gain (eye velocity/head velocity) of 1 (Fig. 4-19A) and a phase shift of 180 degrees (the eyes and head must move in opposite directions).85 The ideal gain is only observed when the subject is fixating a stationary

Figure 4-19. Visual vestibular interaction measured with random and sinusoidal stimulation on high-torque hydraulic rotating chair. A, VOR gains (eye velocity/head velocity) in subject watching and earth-fixed target in the light. B, Gains with random stimuli in dark. Arrows indicate corrective action by visual tracking necessary to obtain the fully compensatory gains in A. C, Comparison of gains during fixation of target moving with subject (VOR suppression) and smooth-pursuit (SP) gains. Solid lines, Random stimuli; dashed lines, sinusoidal stimuli.

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target.86 When visual fixation is excluded by conducting the test in the dark or in a visually unstructured but illuminated environment, the VOR gain drops with decreasing stimulus frequency, indicating that at low frequencies the VOR alone is not adequate to generate accurate compensatory eye movements. Clearly, visual tracking mechanisms must make greater contributions at lower frequencies. This lowfrequency compensation is accomplished mainly by the OK system. Indeed, since the optokinetic signal is fed through the vestibular nuclei, it is often useful to think of the OK system as part of the VOR even though its input does not come from the labyrinth. Many people believe that canal function can be measured reliably by rotating the patients in darkness so as to exclude visual input. This, however, is incorrect, since imaginary visual tracking in total darkness can have large effects on VOR gain.87 At high frequencies (>2.5 Hz) the VOR gain rises with increasing frequency to values greater than 1, just as the gain of the primary afferents rises at high frequencies. This increase, however, is observed only when a randomized, unpredictable stimulus is employed. When predictable waveforms are used or during active high-frequency head shaking,88 the gain remains close to the ideal value of 1, presumably because of the contribution of predictive motor programs. Indeed, if a subject rapidly shakes his or her head while viewing a distant target, the target appears to move in the opposite direction to the head movement, thus indicating that the VOR gain must be slightly less than 1 under these conditions. Because high-frequency gains during unpredictable rotations are reduced to the appropriate value of unity as long as the test is performed in light, visual tracking mechanisms must be able to make small contributions even at these high frequencies. Under these conditions, retinal slip velocities appear to remain low enough for the pursuit system to largely overcome them. Thus at high frequencies, visual tracking mechanisms have the opposite effect on VOR gain when compared with low frequencies (see Fig. 4-19B). The level of visual acuity during head shaking is a sensitive measure of VOR function since even small deviations from a gain of 1 will result in visual blurring. This fact is of substantial clinical importance because it means that if a patient’s head is taken in the hands and gently shaken through a few degrees in an unpredictable fashion while the patient attempts to read a Snellen chart, then VOR deficiencies are easily uncovered. Normal people do not lose more than two lines (relative to their score with the head still), and a loss of more than this can be viewed as a sign of vestibular dysfunction. Although this test does not yield information about the site of the lesion, it requires no equipment, is more sensitive than the caloric test, and can quickly alert the clinician to a potential problem. When fixating a visual target that is moving with the head during random rotation, the subject is attempting to suppress the VOR, and consequently VOR gain is reduced at low frequencies although no suppression is seen at high frequencies. The mechanism responsible for VOR suppression, or cancellation as it is often called, is unclear. It was initially believed to be a function of the SP system because cancellation and pursuit exhibit similar frequency response curves and show parallel decreases in performance

following lesions of the cerebellum. Recently, however, this view has been called into question. Tomlinson and Robinson39,89 demonstrated that the behavior of many cells in the VN was inconsistent with the notion that the pursuit was used to cancel the VOR. In addition, Lisberger90 and Cullen and colleagues91 have both demonstrated that under certain circumstances the cancellation system has a much shorter latency than smooth pursuit (<30 msec versus 100 msec). Thus the current view is that two separate mechanisms cooperate to cancel the VOR, a short latency system that is probably independent of visual feedback and thus may be viewed as parametric in nature, and a second, longer latency system that probably corresponds to smooth pursuit. Finally, there are now reports of patients who exhibit different degrees of deficit in their SP and cancellation systems.92 Given this information, it would seem that clinical testing should involve tests of both SP and VOR cancellation since the two systems may exhibit differential deficits.

ADAPTIVE VOR PLASTICITY A disadvantage of the very short latency of the VOR (about 12 msec) is that there is no time for visual feedback control. (Note, however, that increasing the latency of the reflex would destroy its usefulness because visual blurring would occur during head movements.) The eyes need to move too quickly for the long transneuronal delays in the retina and central visual pathways to supply adequate visual slip information. Since such feedback does not exist, the VOR is an open-loop system and VOR eye velocity (E′) will depend only on the concurrent head velocity (H′), with its size depending only on the value of the parameter k in the following equation: E′ = k × H′

(4-2)

The parameter k represents the efficacy of the signal transduction. It can be adjusted over a slow time course if gaze is not sufficiently stable during head movements.93,94 Thus the VOR, lacking closed-loop feedback control, represents an open-loop system that is subject to parametric control, that is, the value of k can be adjusted. There is an obvious necessity for such parametric control. It is unlikely that synaptic efficacy would remain constant throughout a lifetime without some means of periodic adjustment. In addition, both the degree of ocular mobility and the efficiency of the mechanoelectric transduction in the labyrinth are likely to vary due to disease or aging. Common eyeglasses will change visual distances by about 3% per diopter and thus will require a parallel change in VOR gain (for example, 2 × lenses cause objects to apparently move twice as much as the head moves and thus require a VOR gain of 2.0). This required recalibration of VOR gain partly explains the disorientation associated with a new prescription. Spectacle wearers can easily confirm these facts by fixating a stationary target while shaking their heads and the repeating the procedure after removing their glasses. If they are myopic, the target will appear to move in the direction of the head

Physiology of the Vestibular System

movement; if they are hyperopic, the apparent motion will be in the opposite direction. Of course, this only works for people who have rather large corrections, because small inaccuracies (a few percent) in VOR gain cannot be detected. These gain changes are referred to as parametric adjustments (the parameter k is being changed) and are maintained for long periods of time. Because of the general applicability of such control to a wide range of brain functions, this phenomenon has been extensively studied in a variety of laboratories.43,93–96 Since visual acuity is maintained provided the retinal image does not drift at a velocity greater than a few degrees per second, the VOR gain is normally kept within 3% of unity,97 at least in subjects with normal vision. If retinal image slip increases during head movements, the VOR gain will slowly change so as to minimize the slip. Thus if a subject wears telescopic goggles with a magnification factor of 2, the VOR gain will slowly change during a period of days until it approaches this value. Similarly, if 0.5 × goggles are worn, the VOR gain will drop to about one-half of its normal value. Such gain changes only occur in the plane in which slip occurs. Indeed, the VOR can even be “twisted” if vertical slip is induced during horizontal head movements. The result is that, after adaptation, horizontal head movements will produce oblique eye movements. Experiments by Lisberger and colleagues96,98 have demonstrated that the modified VOR has a different latency than the unmodified VOR. Thus when a sudden head movement is made, the eyes always follow the same trajectory for the initial short period of 12 msec; however, the eye trajectories obtained at different VOR gains depart from one another about 19 msec after movement onset. Thus it would appear that the three-neuron arc always has the same gain (and a latency of about 12 msec), but other modifiable pathways act to change the VOR gain and have an additional latency of 7 msec. The variable gain mechanism is thought to involve modifiable synapses. Since VOR gain plasticity does not survive cerebellar lesions, this was initially thought to be the site of the modifiable synapse. This assumption is now less certain. Demer and Robinson95 demonstrated that if the climbing fibers (CF) carrying retinal slip information from the inferior olive to the cerebellum were reversibly lesioned with lidocaine, then the VOR gain immediately changed to a default value that was essentially independent of the state of adaptation of the VOR. These experiments imply that the cerebellum may be necessary for plastic modification of the VOR, but it is not sufficient; some other structures must also be involved. When the lesion is rostral to the inferior olive so that visual input from the NAOT (see Fig. 4-13) for the CF is eliminated but their spontaneous firing rate is maintained, the VOR gain is maintained at its adapted value but subsequent modification becomes impossible. Thus the CF-cerebellum circuit seems to be necessary to maintain gain changes that are established outside of the cerebellum and to establish new gains. Indeed, Paige and Sargent99 have demonstrated that elderly patients with poor cerebellar function exhibit reduced ability to modify their VOR gain. Since such patients would also exhibit reduced ability to compensate for unilateral vestibular lesions, testing the ability of a

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patient to modify VOR gain in response to reversing prisms might be of diagnostic value. The adaptive process normally requires both visual and vestibular inputs because the gain remains at its adapted level if the animal is kept in the dark (no visual input) or has its head immobilized (no vestibular input). However, if a subject is rotated in darkness for several hours while attempting to fixate an imaginary target that is also moving, the VOR gain drops. This had been attributed to VOR plasticity. A number of factors appear to contribute to parametric modification of VOR gain. If the gain is followed over a period of weeks in animals fitted with telescopic lenses or reversing prisms (which require a reversal of the VOR), the gain change is seen to exhibit two time constants; there is an initial rapid change in gain with a time constant of about 10 h, followed by a slower change with a time constant of about 1 week. Thus it seems likely that at least two mechanisms are involved. The latency data of Lisberger have demonstrated that the plastic change in VOR gain is not accomplished through a simple change in the three-neuron arc. Other evidence also supports this conclusion. If the VOR is adapted during prolonged rotation at a single frequency, then although the gain change is seen at all frequencies, it is greatest at the frequency of the adapting stimulus.100,101 Frequency-specific adaptation has been cited to explain the well-known habituation of figure skaters to high rotational velocities, as opposed to that of sailors to low-frequency movements of their ships. However, habituation is most likely a different phenomenon from plastic gain changes. In addition, predictive mechanisms seem also to play a role because greater adaptation is seen if the testing is done with predictable sinusoidal stimuli rather than randomized stimulation profiles.102 Finally, adaptation is more complete when gains are measured in the light and with active head movements than with passive rotation in darkness. Animals without previous visual experience (reared in complete darkness) cannot adjust their gain at all, although the VOR and its cancellation by visual fixation of a target moving with the head are intact in these animals.103 Gain adaptation is possible in animals reared under stroboscopic illumination, although visual motion processing by the visual cortex and superior colliculus is absent in these animals. This suggests that the accessory optic system must supply the critical visual input as it does for the optokinetic system. The location of the modifiable synapses still remains elusive in spite of repeated efforts by many laboratories.

EYE-HEAD COORDINATION During normal behavior, targets located more than 20 degrees from the line of sight are acquired with a stereotyped combined eye and head movement called a gaze saccade (Fig. 4-20A). In this situation, gaze is defined as the direction of the visual axis and is therefore the sum of eye-in-head plus head-in-space. The actual movement can be broken down into two parts: the saccade, during which gaze is moving, and the terminal head movement, during

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which the eye is already on the target and is maintained there by the VOR as the head continues to rotate. The head movement takes longer to execute than the eye saccade because of the greater mass of the head and its slower dynamics. At the end of the movement, the head will be nearly aligned with the target and thus the eye will be near the center of the orbit (at its primary, or straight ahead, position). This normal pattern is altered in predictable fashion if the VOR gain has been adapted to a new value. If the VOR gain has been increased by wearing 2 × lenses (see Fig. 4-20B), the compensatory rollback of the eyes is too great, necessitating a series of corrective saccades. If, on the other hand, the VOR gain is too low, the compensatory rollback is inadequate and again a corrective saccade is required (see Fig. 4-20C). This latter pattern is also seen if the VOR gain has been reduced by labyrinthine disease. Following bilateral labyrinthectomy, the compensatory rollback is initially lost, but later recovers due to increases in the cervico-ocular (neck-to-eye) reflex and the use of predictive eye movements, presumably driven by the motor program responsible for moving the head. The mechanism for adjusting the amplitude of the eye saccade to compensate for variable head contributions has recently been the focus of renewed interest. It has previously been proposed that the saccadic command was summed linearly with the VOR. Thus, if a 40-degree saccade were called for, the saccadic system would program a 40-degrees saccade and if the head moved during the saccade, the VOR would effectively subtract the head contribution. This simple view is now known to be incorrect. Instead, VOR gain is substantially reduced during large saccades, allowing the head to contribute to the

change in gaze position. Accuracy is maintained, however, by the fact that the saccadic system programs the saccade in gaze (eye-in-space) rather than eye (eye-in-head) coordinates.104–107 Thus the saccadic system must use information from the labyrinth to tell it how much the head moved during the course of the saccade. Disorders of this system could theoretically result in patients with normal saccades with their heads still, normal VOR, and abnormal gaze saccades. Such patients might find quick head movements disorienting because the eyes would not be on target after the rapid head movement of a gaze saccade. Whether such a possibility might account for complaints of disorientation during rapid head movements in certain patients with normal vestibular and oculomotor examination results is unknown at present.

HABITUATION In the previous section, the term adaptation was used to describe the adjustment of the VOR to altered conditions (e.g., 2 × spectacles) with the purpose of optimizing the reflex performance. In contrast, the term habituation is applied to describe the gradual decline of the response to a normal stimulus. These definitions are not identical to those used in classical sensory physiology in which adaptation is normally used to describe response decline during a stimulus, whereas habituation is used to indicate the response attenuation that occurs with repeated stimulus presentations. Habituation of vestibular nystagmus is diagnostically important because nystagmus slow-phase velocity, frequency, and duration are often used to quantify the VOR. These parameters are attenuated whenever the stimulus is repeated frequently.108,109 This phenomenon contributes to the great variability seen in the bithermal, bilateral caloric, or postrotatory nystagmus responses. If slow sinusoidal rotation is applied for a long time, such as 1 h, habituation will not only cause the gain of the VOR to be reduced, but in addition, its time constant will shorten. Thus the central pathways involved in habituation probably include the velocity storage mechanism. It is not surprising that OK stimuli can habituate vestibular nystagmus if both stimuli result in the same sensation of rotation. The converse is also true: Habituation of the VOR can cause a parallel habituation of OKAN. Indeed, the stimulus responses of all central VOR neurons exhibit the same time constant change as seen in the nystagmus response. Less habituation occurs in response to continued sinusoidal rotation than in response to repeated constant velocity rotations, presumably because a sinusoidal rotation is a more natural stimulus than a constant velocity rotation.

COMPENSATION FOR LOSS OF LABYRINTH FUNCTION

Figure 4-20. Head-eye coordination. Solid line, Gaze curve; dashed line, eye movement; dotted line, head movement. A, Normal subject. B, Subject after plastic VOR adaptation to 2 × telescopic goggles. C, Subject after plastic adaptation to 0.5 × goggles.

Unilateral labyrinthectomy or sectioning of the vestibular nerve causes vertigo and several motor symptoms including the following: 1. The head and body tilt toward the side of the lesion. This tendency may be so strong that an animal such

Physiology of the Vestibular System

as a rat can induce active rolling about its longitudinal axis until it is exhausted. 2. Spontaneous nystagmus toward the contralateral side. 3. Reduced VOR gain for rotations toward the ipsilateral side. 4. Circular locomotion toward the ipsilateral side. Immediately following the lesion, VOR gain is reduced for rotations in both directions with the greatest reduction for high-velocity rotations directed toward the side of the lesion. A reduction in the time constant to about 6 sec and a brisk spontaneous nystagmus are also seen. This decrease in time constant results in the phase shift during low-frequency rotations that is commonly seen during rotation testing of patients with unilateral lesions. Over time, these symptoms are alleviated.110–112 The spontaneous nystagmus is greatly reduced within a few days. This nystagmus results from an inequality between the firing rates in the two vestibular nuclei, creating a sense of rotation toward the side contralateral to the lesion. The recovery from spontaneous nystagmus has been demonstrated to not require vision, but does depend on the integrity of the cerebellum. The recovery of VOR gain is much slower and has been demonstrated to require several months. Gain recovery, however, is never complete, particularly for high rotational velocities where the gain exhibits a permanent reduction, particularly for rotations toward the side of the lesion.38,110 Since this gain reduction is much more modest when low-velocity stimuli are used (<100 degrees/sec), it is often not seen during conventional rotational testing. Paige38 evaluated the performance of the VOR in patients following unilateral vestibular ablation surgery by using a range of different stimulus velocities, up to 300 degrees/sec. Although he only followed the patients for 4 months following the surgery, he found that performance approached normal values when using a 0.25Hz stimulus and a peak velocity of 50 degrees/sec. However, when the peak velocity was increased to 300 degrees/sec, the patient gains were less than half of those recorded in normal controls. In addition, a large gain asymmetry was present during high-velocity stimuli that was not present at lower velocities. Although substantial improvement in function was seen over the 4-month period when low-velocity stimuli were used, very little recovery was seen with high-velocity stimuli. He concluded from his studies that high-velocity stimuli were more likely than other more conventional methods to identify and lateralize even subtle vestibulopathy. Halmagyi and his coworkers113 have demonstrated that sudden impulsive movements of the head (accelerations of >2000 degrees/sec) are accompanied by a very marked and permanent VOR gain reduction when the movement is directed toward the side of the lesion. This same group114 has also demonstrated that unilateral lesions result in marked ocular torsion, presumably due to asymmetric otolith input, but this sign disappears with time. Although some improvement is seen in VOR gain following unilateral lesions, this improvement is dependent on retinal slip occurring during activation of the reflex. Thus, although elimination of vision does not disrupt the resolution of the spontaneous nystagmus, it does prevent improvement in VOR gain. Although the evidence is not conclusive at this time, prevention of retinal slip during head movements, which can be accomplished either by

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preventing vision or preventing head movements, seems to result in a reduction in the amount of recovery that eventually occurs. This result argues strongly in favor of mobilizing patients as quickly as possible following unilateral lesions because the recovery process will be delayed if they do not move their heads. This may in turn result in a reduction in the degree of recovery ultimately achieved. If the second labyrinth is lesioned following compensation for the first labyrinthectomy, a mirror image of the original symptoms is observed (Bechterew’s phenomenon). For example, the head is tilted toward the side of the second lesion and a spontaneous nystagmus develops that beats toward the side of the first lesion. This, of course, is the result of the compensation for the first lesion. In the course of the compensation for the original lesion, the background activity in the two vestibular nuclei was equalized. The second lesion now results in a depression of activity levels in the ipsilateral nucleus and the resulting inequality results in the new symptoms. This is a demonstration of the fact that it is not an inequality between the firing in the two vestibular nerves that is important, but rather an inequality between the two nuclei. Although some researchers originally believed that denervation hypersensitivity of VN neurons on the side of the lesion accounted for the compensation for unilateral vestibular loss, this explanation seems unlikely. Following unilateral lesions, both the excitatory and inhibitory commissural connections originating on the intact side and terminating on the VN cells on the lesioned side have been shown to exhibit an enhanced synaptic connectivity, with the resulting postsynaptic potentials having lower thresholds, faster rise times, and higher amplitudes. Also, electron microscopic evidence has shown new synapse formation in the denervated VNs.115,116 Transection of the commissural system between the two VN prevents compensation and the development of Bechterew symptoms. Nonetheless, the commissural system alone is clearly insufficient for the compensatory process because compensation can be prevented by cerebellar lesions. In addition, cerebellar lesions in animals that have compensated for a previous unilateral loss result in the reappearance of symptoms for which no compensation is possible. Thus care must be taken when contemplating a surgical solution for unstable peripheral lesions (e.g., Ménière’s disease). If the patient has compromised cerebellar function, compensation for labyrinth destruction will not occur and the symptoms may get worse instead of better. Although the commissural system and the cerebellum seem to be particularly important for recovery from unilateral lesions, other brain systems must contribute as well. Furthermore, since different symptoms seem to resolve with different time courses, different pathways must be involved, at least to some extent. Sensory experience during active locomotion undoubtedly plays an important role.117 Such compensation largely depends on information from the intact labyrinth. For example, compensation for the head tilt is accomplished much faster when the gravitational force is enhanced in a centrifuge. Even the remnants of the VN on the side of the lesion may contribute because dendrites regrow into the periphery118 and the deafferented nerve develops background activity.119

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If a critical role of the vestibular commissural system in the compensation process is accepted, it should not be surprising that commissurotomy causes an immediate and complete decompensation; that is, all primary symptoms reappear. Varying degrees of decompensation, however, are also seen after many other CNS lesions, including spinal cord transection, hemispherectomy, bilateral fastigial nucleus lesions, inferior olive lesions, and cerebellectomy. Lesions of the lateral reticular nucleus decompensate the skeletal motor symptoms more than the oculomotor effects. All of these structures have connections with the vestibular nuclei and therefore can influence the dynamics of the commissural loops. Galiana, Flohr, and Melvill Jones120 assume that this is also possible by much more general changes in brain activity, such as that induced by certain drugs.121 For example, general depressants, such as barbiturates and chlorpromazine, retard the compensation process, and a decompensation is seen after administration of ether, alcohol, and muscimol (a GABA agonist). Indeed, even moderate doses of barbiturates can produce nystagmus in some people, which may be the result of decompensation of minor peripheral inequalities. The physician must realize that drugs, especially alcohol, can cause symptoms associated with long-past pathologic events for which complete compensation has occurred. The central cholinergic system plays an important role in compensation. Cholinesterase inhibitors such as physostigmine, paraoxon (E600), parathion (E605), and diisopropyl fluorophosphate (DFP, or isoflurophate), when applied systemically, can cause an immediate dose-dependent decompensation. This is also seen after use of cholinomimetics, such as nicotine, muscarine, and oxotremorine. This decompensation occurs at much lower dosages if the drugs are applied into the cisterna magna, suggesting localized effects in the brainstem. Cholinolytics, such as atropine and scopolamine, have a direct antagonistic effect and can cause overcompensation, such as spontaneous nystagmus and head tilt to the wrong side. When cholinergic drugs are repeatedly given to animals during the compensation process, the repeated periods of decompensation result in increased error signals, causing the compensation process to occur with an accelerated time course. Similarly, when a unilateral lesion is produced not in one but in several successive subtotal surgical procedures, the presence of repeated new symptoms induces an accelerated and more complete final compensation.

VESTIBULOSPINAL SYSTEM In addition to the VOR, the vestibular sensory input provides the drive to a series of reflex systems capable of affecting almost all of the skeletal muscles that contribute to the stability of the body with respect to gravity.1,122 Obviously, direction of the gravity vector with respect to the otolithic maculae changes with head position. In addition, the net vector sensed by the otoliths will be a function of both the head position (with respect to gravity) and any linear accelerations that the head is undergoing. It is equally obvious that the reflex changes in muscle force necessary for the maintenance of any particular body posture will differ if the whole body moves relative to what is required when only the head moves. For example, tilting

the head to one side (in the roll plane) requires a different postural adjustment in order to maintain an upright posture than does a tilt of the whole body. Since the vestibular labyrinth is located in the head, it is unable to distinguish between tilting of the body and tilting of the head. Given this situation, it is not surprising that the vestibular nuclei require information from other sensory systems than the labyrinth in order to make the appropriate postural adjustments. The two most important sensory systems contributing to the resolution of this problem are the visual system, which provides information concerning the relationship of the body to the visual surround, and the somatosensory system (particularly proprioceptors), which provide information about the postural state of the body. Continuing with the same example cited previously, if information from neck proprioceptors, signaling head-on-body position, is combined with information from the otoliths, signaling head-in-space position, then the relationship of the body to the gravity vector can be calculated. The major function of the vestibulospinal reflexes is to keep the head and body stable in space. This task is far more complex than the oculomotor analogue, the VOR, for two main reasons: 1. Vestibulospinal reflexes act on many joints and the required muscle tension at any joint must depend on the forces acting on other relevant joints (including forces external to the body, such as weights carried in the hands). Thus an analytic treatment of the VOR action on any single joint is an extremely complex task. 2. Although labyrinthine head stabilization reflexes serve to prevent head movement, the head must move to induce these reflexes. This head movement becomes the error signal of a negative feedback control system, perhaps best illustrated by the vestibulocollic reflex (VCR).

VESTIBULOCOLLIC REFLEX If a subject is suddenly and unexpectedly rotated with the head free to move, the head tends to maintain its original position in space. This is partly the result of the inertia of the head itself and partly due to an active head rotation, opposite to the rotation of the body, driven by information from the semicircular canals. Because of the greater mass of the head, this reflex is slower than the VOR. When subjects are rotated at constant velocity in darkness, they may execute head and eye nystagmus in the same direction without necessarily being aware of either. In this situation, saccadic repositioning of the eyes and head occurs almost simultaneously and the VCR and VOR both contribute to the overall gaze stabilization. Rotatory head perturbations in the vertical plane will result in a head tilt and will therefore activate both the otolithic maculae and both semicircular canals. In this situation, the canal input is primarily responsible for the high-frequency component of the VCR, bringing the head back quickly, while the maculae are more important for lowfrequency corrections and thus maintain the long-term head position with respect to gravity. When all the semicircular

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canals are inactivated by plugging and the otolith organs are left intact, the VCR still operates, although only in the lower frequency range. Cats with plugged canals can still hold their heads erect, albeit with increased sway. After complete labyrinthectomy, however, head position in darkness appears to be largely uncontrolled. Direct electrical stimulation of the peripheral nerve branches has demonstrated directional specificity in the VCR, as would be expected. For example, stimulation of the right lateral canal nerve causes head rotation to the left. Similarly, stimulation of both anterior canal nerves results in an upward pitch of the head (elevation of the chin); bilateral posterior canal nerve stimulation results in a downward pitch; and stimulation of both vertical canal nerves on the same side results in a head tilt toward the opposite side. Thus the induced head movement always occurs in the plane of the canal(s) stimulated, in a direction opposite to that which would produce an activation of the stimulated canal. When one canal becomes inactivated, the error signal necessary to correct head deviation in its plane will become greater (since only one side is functional), resulting in greater head instability in that plane. This principle is illustrated when the swimming behaviors of lampreys and eels are compared. Lampreys, lacking horizontal canals, execute horizontal sinusoidal head movements, whereas eels, with lateral canals, proceed with their heads along a straight line.

TONIC LABYRINTH AND NECK REFLEXES When higher motor control is removed by decerebration in animals or functional decerebration during brain disease in humans, several positional reflexes become apparent that cannot normally be elicited. If the body is turned about the neck joints while the head is maintained stable in space so as to result in neck bending but no change in vestibular input, the tonic neck reflexes can be demonstrated (Fig. 4-21, N reflex pattern). For example, if the neck is bent toward one side, a reflex flexion of the ipsilateral limbs results, as well as an extension of the contralateral limbs. Thus the tonic neck reflexes tend to compensate for surface support tilt when the head is kept in the upright position with respect to gravity. The patterns of flexion and extension are changed with different directions of neck flexion so as to compensate for all directions of tilt. For example, when the neck is flexed upward in a labyrinthectomized animal, the hind limbs flex and the forelimbs extend, with the opposite occurring for downward neck flexion. If neck afferent input is prevented by the use of a cast (thus preventing the neck from bending) or deafferentation of the upper cervical segments, the tonic labyrinth reflexes can be demonstrated. These reflexes again function to stabilize body position on a tilting platform (see Fig. 4-21, L reflex pattern). Note that the tonic labyrinth reflexes act in exactly the opposite direction to the tonic neck reflexes, resulting in limb extension on the side toward which the head is tilted and flexion on the contralateral side. Because the two reflexes induce opposite effects, if the head is simply tilted to one side without

Figure 4-21. Tonic neck and labyrinth reflexes and dynamic labyrinth reflex. N, Reflex pattern caused by neck flexion; L, labyrinthine reflexes causing mirror image of neck reflexes; N + L, neck and labyrinth reflexes cancel each other. Bottom, Quick, dynamic linear acceleration causing ipsilateral limb extension and contralateral flexion.

any movement of the body, the two effects cancel and no reflex change in limb position results (see Fig. 4-21, N + L reflex pattern). This is of course precisely what is necessary because there is no danger of loss of balance in this situation. Thus these two reflex systems cooperate to produce always the correct change in body support musculature for any change in head and body position. The maintained limb position of the tonic labyrinthine reflexes is derived from the otolithic maculae. More rapid stabilization adjustments in the same directions depend on canal input. For example, if all of the semicircular canals of a cat are inactivated by plugging, the animal is still able to compensate for slow platform tilts, but is thrown off balance by rapid tilts that would be easily handled by the normal animal. Following complete labyrinthectomy, however, both slow and rapid tilts result in loss of balance. The effect of rapid linear translation on the limbs appears to be quite different from that of the tonic labyrinthine reflexes. For example, rapid linear translation to the left of a mobile platform results in ipsilateral (left) limb extension and contralateral flexion, the exact opposite to that induced by the tonic reflexes generated by the same direction of utricular hair cell deflection (see Fig. 4-21). Mayne123 and Nashner124 have therefore proposed that tonic gravitational reflex actions are processed separately from dynamic linear signals within the CNS. Nonetheless, the complexity of these systems is such that considerable confusion still

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remains as to the functional responses of the body to tilts and translations, and even the relative importance of the vestibular input, compared with visual and proprioceptive cues, remains unclear.

inputs to the vestibular nuclei for the generation of vestibulospinal and oculomotor reflexes.

PATHWAYS FALLING If a cat is falling, it will always right itself during the fall so that it lands on its feet regardless of the original body position. If the apparent gravity vector is inclined for a long time, as demonstrated by driving a car round and round on a circular track (the centrifugal acceleration results in an apparent change in the gravity vector orientation), then the motor system slowly changes its responses to the new vector orientation. Thus when the cat fell after reentering a straight stretch of road, the animal aligned its head and body with the previously tilted gravity vector. Otolithic effects on skeletal muscles, however, can be very rapid. Electromyography (EMG) has revealed that four peaks occur in the extensor activation when a subject is falling. The first two peaks occur prior to landing and are the result of labyrinthine reflexes. The second two peaks occur just after landing and are the result of the segmental myotatic (stretch) reflex and the so-called functional long-loop reflexes, respectively. The earliest component, which occurs about 75 msec after the start of the fall in the human gastrocnemius muscle (the latency is a little shorter in more proximal muscles), probably reflects saccular activity, which is still present after canal plugging but is eliminated by labyrinthectomy. Its amplitude is directly proportional to the acceleration and does not habituate. This earliest activity safeguards the body against the impact associated with unexpected short falls. If the fall distance is too short for the reflex to act (about 5 cm), landing is much less comfortable than for greater heights. When the falling distance is greater, the second EMG burst can also be seen. Its timing depends on the falling distance and its amplitude can be altered by visual cues and experience. This burst has been suggested to be a preprogrammed preparation for landing, although the fact that it is influenced by visual cues may mean that it is at least partly visual in origin. Muscle activity during vertical falls is subject to visual suppression. If the entire visual field moves with the head, the second EMG burst is greatly attenuated, whereas little amplitude change is seen in the first component. Conversely, if the visual field moves upward as the subject falls downward, an amplitude increase can be seen, but only if downward acceleration is reduced below the normal value of 9.8 m/sec2 so that the saturation limit of the OK system is not exceeded. Thus this experiment provides further evidence that the second EMG burst depends on visual input. After labyrinthectomy, visual cues contribute to the recovery of the early muscle response during the first two to three postoperative weeks. This visual influence is more evident on the side of the lesion after a unilateral labyrinthectomy, which suggests that the corresponding modulation occurs at the source of the vestibulospinal pathways. All of this evidence serves to point out the importance of visual

Four pathways are available to mediate vestibulospinal reflex activity:1 the lateral vestibulospinal tract, the medial vestibulospinal tract, the caudal vestibulospinal tract, and the vestibuloreticulospinal tract.

Lateral Vestibulospinal Tract Figure 4-22 summarizes the organization of the lateral vestibulospinal tract (LVST). It originates from both large and small neurons in the lateral vestibulospinal nucleus (Deiters’ nucleus), sending axons through the ipsilateral anterior funiculus into the gray matter of the cord and, to a lesser extent, directly to the motoneurons. LVST cells with shorter axons terminating in the cervical cord are located ventrorostrally in the nucleus, whereas those with longer axons terminating at lumbar levels are located more dorsocaudally. From a functional point of view, this apparent somatotopic arrangement is not strict since caudally directed axons give off many collaterals at more rostral levels. Stimulation of Deiters’ nucleus increases extensor tone via both mono- and polysynaptic excitation of alpha and gamma motoneurons. All monosynaptic PSPs are excitatory, and no IPSPs, either mono- or polysynaptic, are seen in neck muscle motoneurons. However, polysynaptic IPSPs have been recorded in motoneurons supplying the antagonists of the antigravity muscles in the limbs. The polysynaptic effects are mediated by interneurons located in the spinal gray matter. The LVST reflex connections

Figure 4-22. Lateral vestibulospinal tract.

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can be gated by other motor areas. For example, when Deiters’ nucleus is electrically stimulated during different phases of the step cycle in the decerebrate cat, a facilitation of gastrocnemius muscle activity can be seen only during the extension phase and not during flexion. Thus these reflexes can be modulated according to the circumstances. Not all LVST neurons receive monosynaptic labyrinthine input because vestibular afferents are concentrated in the ventral portion of the nucleus. As the antigravity function of this system would predict, most vestibular input arises from the otolithic maculae, including the saccular macula. Neurons whose axons project exclusively to the cervical segments tend to exhibit an alpha response to tilting (excitation when the ipsilateral eye is tilted down and inhibition for tilts in the opposite direction). Cells with axons directed to the lower spinal segments more frequently exhibit a gamma response pattern (excitation for tilts to both sides). Tilt-sensitive neurons do not receive commissural inhibition from the contralateral side, although the less common canal driven LVST neurons do. An indirect input to Deiters’ nucleus travels via the fastigial nucleus of the cerebellum, as well as through the posterior vermis and anterior lobe of the cerebellar cortex. Deiters’ nucleus could be considered a cerebellospinal relay rather than a strictly vestibular structure since most LVST neurons receive cerebellar input, and many neurons, particularly in the dorsal half of the nucleus, do not exhibit monosynaptic inputs from the vestibular nerve. Deiters’ cells receive somatic sensory input via the spinocerebellar tracts as well as through the mossy fiber (MF) inputs derived from the reticular system and the climbing fiber (CF) system originating in the inferior olive. All this somatic sensory input does not appear to be somatopically organized, and modalities include muscle afferents and other proprioceptive and skin afferents. Deiters’ cells excited by somatosensory input are generally inhibited via the MF or CF cerebellar loop (or both) (see Fig. 4-22) since all Purkinje cells (PC), which terminate on Deiters’ neurons or elsewhere are inhibitory. Removal of the anterior lobe of the cerebellar cortex, which projects to Deiters’ nucleus, results in increased extensor tonus and opisthotonos, which disappears after ipsilateral labyrinthectomy. In the intact cat, Deiters’ cells often respond to tilt in a phasic fashion, that is, only during the tilting movement. However, after cerebellectomy these neurons exhibit the typical static response seen in otolithic afferents. Many Deiters’ neurons are strongly modulated when a cat walks on a treadmill, with activation coinciding with the stance phase. After cerebellectomy, the spontaneous firing rate of the cells is seen to increase but the modulation during locomotion is lost.

Medial Vestibulospinal Tract The medial vestibulospinal tract (MVST) descends bilaterally in the MLF and terminates mainly in the cervical spinal cord, with its most caudally directed afferents terminating in thoracic segments. Cells of origin are located within the same VN area that contains VOR neurons, that is, a region around the borderline between the medial, descending, and lateral vestibular nuclei. Examination

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of the collateralization patterns for VOR neurons (see Figs. 4-8 and 4-10) reveals that some cells in this area belong to both the VOR and the MVST systems. In contrast to the LVST, the MVST contains many inhibitory fibers that mediate monosynaptic IPSPs in many neck motoneurons. These IPSPs can be blocked by strychnine, indicating that the transmitter is glycine rather than GABA. Excitatory MVST fibers, however, also make monosynaptic contacts with cervical motoneurons. Polysynaptic excitation and inhibition mediated via this tract are also seen. Most MVST neurons are second-order vestibular cells, which are monosynaptically activated by semicircular canal afferents. Characteristically, type 1 or type 2 canal responses are rare; however, many vestibulospinal neurons exhibit type 3 response patterns (excitation with rotations in both directions). Evidence also suggests utricular input. MVST neurons with canal input receive commissural inhibitory connections, just as VOR neurons do. Although only a few MVST neurons do not receive direct labyrinthine input, even those are driven by vestibular stimuli via interneurons. MVST neurons in Deiters’ nucleus are subject to cerebellar control, but the functional relationship between the vestibulocerebellum and MVST neurons is not well understood. Nonetheless, it is known that fastigial nucleus neurons can excite type 1 MVST neurons bilaterally. Fredrickson, Kornhuber, and Schwarz125 observed a strong somatosensory input to the VN region containing MVST neurons. This input did not appear to be organized somatotopically since the neurons were typically activated by a coordinated joint movement pattern involving several proximal joints. In keeping with the MVST action, the strongest input was derived from the neck. MVST cells can also be influenced by stimulation of the rostral brainstem, particularly the interstitial nucleus of Cajal.

Caudal Vestibulospinal Tract The caudal vestibulospinal tract is a newly discovered pathway originating from the most caudal aspects of the medial and descending vestibular nuclei and projecting as far down as the lumbar spinal cord. Its functional significance is still unknown. However, the most caudal portions of the descending and medial vestibular nuclei, as well as the intercalated (Staderini’s) nucleus, receive direct input from peripheral cervical nerves (D. W. F. Schwarz and I. E. Schwarz, unpublished observations). Proprioceptive afferents from the most rostral cervical segments are known to play an important role in the maintenance of balance. In cats, denervation of the first two segments, or merely severing cervical muscle tendons at their insertion, causes a severe imbalance with a marked hind limb ataxia.126 Thus it seems very likely that information from neck proprioceptors is combined with all the other inputs concerned with movement sensation within the central vestibular system. Some vestibulospinal neurons with canal input also respond to a comparable neck flexion.127 Movement of the body with respect to the fixed (in space) head can even induce a sensation of rotation if the movement is slow.128 At higher velocities, trunk movement is perceived. Clinical neurotologists are familiar with the fact that neck injury

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can cause severe vertigo, and even nystagmus, without any indication of vascular impairment. Thus the preponderance of evidence certainly indicates that the vestibular nuclei utilize information from a variety of sources in order to estimate the movements of the body.

PROJECTION TO FOREBRAIN The vestibular organs are represented in the cerebral cortex as other senses are, but the projection differs from other sensory systems.125,129 To date, no cortical area has been found to be specifically and exclusively dedicated to vestibular input; rather, vestibular signals appear to blend into the representation of other senses. Early evoked potential studies, as well as cortical stimulation in alert human subjects, had suggested the existence of at least one specific vestibular cortical field in the parietal lobe. Subsequent single-unit investigations, however, have revealed that vestibular responses can be found over wide areas of the somatic parietal fields (areas 3a, 2, and 5). This input is derived from thalamic cells located in the ventral posterior complex (ventroposterolateral nucleus [VPL], its oral portion [VPLo], and the ventroposteroinferior nucleus [VPI]), which in turn receive axon terminals from the contralateral lateral and medial vestibular nuclei. It is not clear how much of this sensory convergence is simply the consequence of the convergence already present in the VN. It is known, however, that thalamic neurons transmitting vestibular information to the parietal lobe also carry somatic sensory signals, usually from proximal joints and muscles. Because all secondary vestibular neurons with canal input also receive visual information from the OK system, this signal must also be present. Thus the vestibular system is unique among sensory systems because its estimates of head angular velocity are based on information from a variety of sources including the labyrinth, the retina, and joint and muscle proprioceptors. The visual cortex also appears to receive vestibular input. Researchers have shown that the orientation of certain visual cortical receptive fields can be changed by otolithic stimulation. Reinis and colleagues130 also showed that semicircular canals stimulated with heavy water can influence visual cortical background firing rates as well as the size of complex visual cortical receptive fields. The superior temporal gyrus has been suspected to contain a specific vestibular projection field ever since Penfield evoked sensations of rotation and imbalance from this general area by electrical stimulation in human subjects. However, no confirmation of this finding using neurophysiologic methods has been made. One might reasonably postulate that no specific vestibular cortical area should exist, since no specific and detailed vestibular sensations exist. What is sensed is always movement of the body, whether the stimulus affects the somatosensory system, the visual system, or the vestibular system. The illusion of rotation, circular vection, created by causing the entire seen world to rotate, is in no way different from the sensation of rotation induced by a rotatory stimulus acting on the labyrinth. As a result, going through life without ever being aware of the vestibular sense organs is quite possible.

Vestibular input is certainly necessary for spatial orientation. Children or rats without functional labyrinths cannot remember a path through which they have been passively transported. Such egocentric orientation capability appears to be mediated via a pathway through the VN, the magnocellular medial geniculate body, and the caudal caudate nucleus.131 As a result, rats with caudate lesions cannot find their way back to a location from which they have been passively transported.

MOTION SICKNESS Clinically, the most important vestibular sensations are dizziness and vertigo associated with autonomic reactions such as sweating, salivating, and vomiting.132 This syndrome can be elicited by a variety of different peripheral and central vestibular lesions and is undoubtedly related to motion sickness. A prerequisite for motion sickness is labyrinthine input that conflicts with a central representation of a stable world. After bilateral labyrinthectomy, motion sickness does not occur; however, an OK stimulus can evoke the syndrome in healthy subjects. The visual stimulus needs to be a smooth retinal image slip, since motion sickness caused by visual direction reversal (produced by wearing spectacles fitted with reversing prisms) does not occur under conditions of stroboscopic illumination. Visual fixation on a steady-reference horizon can be used effectively to prevent sea and car sickness.132 Conversely, car sickness is exacerbated by attempting to read in a moving vehicle. For the past 40 years, researchers believed that motion sickness depended on activity in the vestibulocerebellum and on secretion of a humoral mediator to the emetic trigger zone in the area postrema. Cats, however, are still susceptible to motion sickness after posterior cerebellectomy134 or ablation of the area postrema. If the aqueductus cerebri (sylvian aqueduct) is blocked, and thus the flow of the putative humoral mediator from the third ventricle to chemoreceptors further caudally, motion sickness apparently does not occur.135 If the emetogenic compound is secreted into the third ventricle, it must be derived from very caudal structures lining its wall, since motion sickness can be evoked in decerebrate animals. Conceivably, not one but a variety of natural brain chemicals can mediate the emetic response. Interestingly, a number of external poisons (pilocarpine, lobeline, L-dopa, and apomorphine) will no longer cause emesis after bilateral labyrinthectomy.136 These somewhat conflicting findings show that a coherent physiologic framework for those vestibular sensations that bring many patients to their physicians is not yet available.

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74. Curthoys IS, Markham CH, Furuya N: Direct projection of pause neurons to nystagmus-related excitatory burst neurons in the cat pontine reticular formation. Exp Neurol 83:414, 1984. 75. Furuya N, Markham CH: Direct inhibitory synaptic linkage of pause neurons with burst inhibitory neurons. Brain Res 245:139, 1982. 76. Galiana HL, Outerbridge JS: A bilateral model for central neural pathways in vestibuloocular reflex. J Neurophysiol 51:210, 1984. 77. Shimazu H: Neuronal organization of the premotor system controlling horizontal conjugate eye movements and vestibular nystagmus. In Desmedt JE (ed.): Motor Control Mechanisms in Health and Disease. New York, Raven Press, 1983. 78. Henn V, Cohen B, Young LR: Visual-vestibular interaction in motion perception and the generation of nystagmus. Neurosci Res Prog Bull 18:458, 1980. 79. Raphan T, Cohen B: Brainstem mechanisms for rapid and slow eye movements. Ann Rev Physiol 40:527, 1978. 80. Raphan T, et al: Nystagmus generated by sinusoidal pitch while rotating. Brain Res 276:165, 1983. 81. Zasorin NL, et al: Influence of vestibulo-ocular reflex gain on human optokinetic responses. Exp Brain Res 51:271, 1983. 82. Wall C, Black FO: The modulation component of nystagmus during earth horizontal rotation: relationship with gaze angle. Acta Otolaryngol (Stockh) 97:193, 1984. 83. Matsuo V, Cohen B: Vertical optokinetic nystagmus and vestibular nystagmus in the monkey: Up-down asymmetry and effects of gravity. Exp Brain Res 53:197, 1984. 84. Igarashi M, et al: Effect of macular ablation on vertical optokinetic nystagmus in the squirrel monkey. ORL J Otorhinolaryngol Relat Spec 40:312, 1978. 85. Schwarz DWF: Clinically relevant physiology of the vestibuloocular reflex. J Otolaryngol 5:425, 1976. 86. Hyden D, Istl YE, Schwarz DWF: Human visuovestibular interaction as a basis for quantitative clinical diagnosis. Acta Otolaryngol (Stockh) 94:53, 1982. 87. Barr CC, Schultheis LW, Robinson DA: Voluntary, nonvisual control of the human vestibulo-ocular reflex. Acta Otolaryngol (Stockh) 81:365, 1976. 88. Tomlinson RD, Saunders GE, Schwarz DWF: Analysis of human vestibulo-ocular reflex during active head movements. Acta Otolaryngol (Stockh) 90:184,1980. 89. Tomlinson RD, Robinson DA: Is the vestibulo-ocular reflex cancelled by smooth pursuit? In Fuchs AF, Becker W (eds.): Progress in Ooculomotor Research, New York, Elsevier/ North-Holland, 1981. 90. Lisberger SG: Visual tracking in monkeys: Evidence for shortlatency suppression of the vestibuloocular reflex. J Neurophysiol 63:676, 1990. 91. Cullen KE, Belton T, McCrea RA: A non-visual mechanism for voluntary cancellation of the vestibulo-ocular reflex. Exp Brain Res 83:237, 1991. 92. Chambers BR, Gresty MA: The relationship between disordered pursuit and vestibulo-ocular reflex suppression. J Neurol Neurosurg Psychiat 1983. 93. Melvill Jones G, Mandl G: Neurobionomics of adaptive plasticity: Integrating sensorimotor function with environmental demands. In Desmedt JE (ed.): Motor Control Mechanisms in Health and Disease. New York, Raven Press, 1983. 94. Miles FA, Lisberger SG: Plasticity in the vestibuloocular reflex: a new hypothesis. Ann Rev Neurosci 4:273, 1981. 95. Demer JL, Robinson DA: Effects of reversible lesions and stimulation of olivocerebellar system on vestibuloocular reflex plasticity. J Neurophysiol 47:1084, 1982. 96. Lisberger SG, Miles FA, Zee DS: Signals used to compute errors in monkey vestibuloocular reflex: Possible role of flocculus. J Neurophysiol 52:1140, 1984. 97. Collewijn H, Martin AJ, Steinman RM: Compensatory eye movements during active and passive head movements: Fast adaptation to changes in visual magnification. J Physiol 340:259, 1983.

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98. Lisberger SG: The latency of pathways containing the site of motor learning in the monkey vestibulo-ocular reflex. Science 225:74, 1984. 99. Paige GD, Sargent EW: Visually-induced adaptive plasticity in the human vestibulo-ocular reflex. Exp Brain Res 84:25, 1991. 100. Godaux E, Halleux J, Gobert C: Adaptive change of the vestibuloocular reflex in the cat: The effects of long-term frequency-selective procedure. Exp Brain Res 49:28, 1983. 101. Lisberger SG, Miles FA, Optican LM: Frequency selective adaptation: Evidence for channels in the vestibulo-ocular reflex? J Neurosci 3:1234, 1983. 102. Istl-Lenz YE, Hyden D, Schwarz DWF: Response of human vestibulo-ocular reflex following long-term 2 × magnified visual input. Exp Brain Res 191:1, 1985. 103. Harris LR, Cynader M: Modification of the balance and gain of the vestibulo-ocular reflex in the cat. Exp Brain Res 44:57, 1981. 104. Laurutis VP, Robinson DA: The vestibulo-ocular reflex during human saccadic eye movements. J Physiol 373:209, 1986. 105. Pelisson D, Prablanc C: Vestibuao-ocular reflex (VOR) induced by passive head rotation and goal-directed saccadic eye movements do not simply add in man. Brain Res 380:397, 1986. 106. Tomlinson RD: Combined eye-head gaze shifts in the primate. III. the mechanisms underlying the compensation for mechanical perturbations of the head. J Neurophysiol 64:1873, 1990. 107. Tomlinson RD, Bahra PS: Combined eye-head gaze shifts in the primate. 11. interactions between saccades and the vestibuloocular reflex. J Neurophysiol 56:1558, 1986. 108. Collins WE: Arousal and vestibular habituation. In Kornhuber HH (ed.): Handbook of Sensory Pphysiology, VIA, Vestibular System, Part II, Psychophysics, Applied Aspects, and General Interpretations. New York, 1974, Springer Verlag. 109. Henn V, Waespe W: Visual-vestibular interactions: neurophysiological investigations in the monkey. Fortschr Zool 28:261, 1983. 110. Fetter M, Zee DS, Proctor LR: Effect of lack of vision and of occipital lobectomy upon recovery from unilateral labyrinthectomy in rhesus monkey. J Neurophysiol 59:394, 1988. 111. Flohr H: Concepts of vestibular compensation. In Flohr H, Precht W (eds.): Lesion-Induced Neuronal Plasticity in Sensorimotor Systems, Berlin, Springer Verlag, 1981. 112. Schaefer KP, Meyer DL: Compensation of vestibular lesions. In Kornhuber HH (ed.): Handbook of Sensory Physiology. VI. Vestibular System. Part II. Psychophysics, Applied Aspects, and General Interpretations. New York, Springer Verlag, 1974. 113. Halmagyi GM, et al: The human horizontal vestibuloocular reflex in response to high-acceleration stimulation before and after unilateral vestibular neurectomy. Exp Brain Res 81:479, 1990. 114. Curthoys IS, Dai MJ, Halmagyi GM: Human ocular torsional position before and after unilateral vestibular neurectomy. Exp Brain Res 85:218, 1991. 115. Korte GE, Friedrich VL: The fine structure of the feline superior vestibular nucleus: Identification and synaptology of the primary vestibular afferents. Brain Res 176:3, 1979. 116. Schwarz DWF, Schwarz IE, Fredrickson JM: Fine structure of the medial and descending vestibular nuclei in normal rat and after unilateral transsection of the vestibular nerve. Acta Otolaryngol (Stockh) 84:80, 1977.

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117. Bles W, De Jong JMBV, DeWit G: Somatosensory compensation for loss of labyrinthine function. Acta Otolaryngol (Stockh) 97:213, 1984. 118. Fermin CD, Igarashi M: Dendritic growth following labyrinthectomy in the squirrel monkey. Acta Otolaryngol (Stockh) 97:203, 1984. 119. Jensen DW: Survival of function in deafferented vestibular nerve. Brain Res 273:175, 1983. 120. Galiana HL, Flohr H, Melvill Jones G: A reevaluation of intervestibular nuclear coupling: its role in vestibular compensation. J Neurophysiol 51:242, 1984. 121. Bienhold H, Abeln W, Flohr H: Drug effects on vestibular compensation. In Flohr H, Precht W (eds.): Lesion-Induced Neuronal Plasticity in Sensorimotor Systems. Berlin, Springer Verlag, 1981. 122. Roberts TDM: Neurophysiology of Postural Mechanisms, 2nd ed. London, Butterworth Publishers, 1978. 123. Mayne R: A systems concept of the vestibular organs. In Kornhuber HH (ed.): Handbook of Sensory Physiology, VI, Vestibular System, Part 11. Psychophysics, Applied Aspects, and General Interpretations. New York, Springer Verlag, 1974. 124. Nashner LM: Analysis of movement control in man using the moveable platform. In Desmedt JE (ed.): Motor Control Mechanisms in Health and Disease. New York, Raven Press, 1983. 125. Fredrickson JM, Kornhuber HH, Schwarz DWF: Cortical projections of the vestibular nerve. In Kornhuber HH (ed.): Handbook of Sensory Physiology, VI/I, Vestibular System, Part I, Basic Mechanisms. New York, Springer Verlag, 1974. 126. Deecke L, Schwarz DWF, Fredrickson JM: Hindlimb ataxia following section of neck muscles in cat. Naturwissenschaften 68:432, 1981. 127. Kasper J, Thoden U: Effects of natural neck afferent stimulation on vestibulo-spinal neurons in the decerebrate cat. Exp Brain Res 44:401, 1981. 128. Thoden U, Doerr M, Leopold HC: Motion perception of head or trunk modulates cervico-ocular reflex (COR). Acta Otolaryngol (Stockh) 96:9, 1983. 129. Schwarz DWF, Fredrickson JM: The clinical significance of vestibular projection to the parietal lobe: A review. Can J Otolaryngol 3:381, 1974. 130. Reinis S, et al: Effects of deuterium oxide and galvanic vestibular stimulation on visual cortical cell function. J Neurophysiol 51:481, 1984. 131. Abrahams L, Potegal M, Miller S: Evidence for caudate nucleus involvement in an egocentric spatial task: return from passive transport. Physiol Psychol 11(1):11, 1983. 132. Reason JT, Brand JJ: Motion sickness. New York, 1975, Academic Press. 133. Probst TH, et al: Visuelle Praevention der Bewegungskrankheit im Auto. Arch Psychiat Nervenkr 231:409, 1982. 134. Miller AD, Wilson VJ: Vestibular-induced vomiting after vestibulocerebellar lesions. Brain Behav Evol 23:26, 1983. 135. Crampton GH, Daunton NG: Evidence for a motion sickness agent in cerebrospinal fluid. Brain Behav Evol 23:36, 1983. 136. Money KE, Cheung BS: Another function of the inner ear: facilitation of the emetic response to poisons. Aviat Space Environ Med 54:208, 1983.

Chapter

5 Anand N. Mhatre, PhD Anil K. Lalwani, MD

Molecular Genetics in Neurotology Outline Introduction Inherited Disorders and Their Inheritance Patterns Autosomal-Recessive Inheritance Autosomal-Dominant Inheritance X-Linked Inheritance Variations on Mendelian Principles Linkage and Recombination Mitochondrial Inheritance X Chromosome Inactivation Genomic Imprinting Trinucleotide Repeat Expansion Multifactorial Inheritance

INTRODUCTION Applications of the molecular genetic techniques toward hereditary hearing loss (HHL) have led to the identification and characterization of a large number of “deafness genes,” encoding a wide variety of protein products with differing biologic roles. Each of these “deafness genes” represents a genetic tool or a probe for deciphering the molecular pathophysiology of hearing loss precipitated by the mutant allele and thus contributing toward our understanding of the molecular circuitry responsible for hearing. The immediate clinical impact of these discoveries includes the development and deployment of genetic tests for molecular diagnosis of hearing loss in the general population, thus affecting their care and management. The long-term clinical impact includes the development and application of gene-based therapy that can correct certain forms of inherited and acquired hearing loss. The objective of this brief review is to inform the neurotologist of the progress in hearing research, its impact upon our understanding of hearing loss, and its application to current and future clinical practice. The review begins with a brief overview of Mendelian genetics, illustrated through analysis of inherited disorders and their inheritance patterns. This is followed by a review of molecular genetic analysis and genetic epidemiology of nonsyndromic hereditary hearing loss. Genetics and genetic analysis of vestibular schwannomas and glomus tumors are also described. Finally, the review 122

Genetics and Genetic Epidemiology of Nonsyndromic Hereditary Hearing Loss Connexin 26 Pendrin Myosins Molecular Genetics of Vestibular Schwannomas and Glomus Tumors Neurofibromatosis Type 1 Neurofibromatosis Type 2 Familial Paragangliomas Genetic Mapping of the PGL Loci and Identification of the PGL1 Gene PGL2, PGL3, and PGL4

Parent-Specific Transmission and Loss of Heterozygosity Intracochlear Transgene Expression and Its Potential Therapeutic Application Animal Models and Gene Transfer Vectors Intracochlear Gene Delivery Modalities Preclinical Applications Risks and Limitations Summary

provides a critical assessment of the intracochlear gene transfer studies that are directed toward treatment of hearing loss.

INHERITED DISORDERS AND THEIR INHERITANCE PATTERNS Roughly half of the observed severe hearing loss seen in childhood has been attributed to genetic factors. Approximately one in every 1000 children is born with a severe hearing loss with the estimated prevalence of genetic hearing loss around 1 in 2000.1 Of these cases, approximately 75% exhibit an inheritance pattern that is consistent with an autosomal-recessive trait, 23% exhibit autosomal-dominant inheritance, 2% appear to be X-linked, and less than 1% are caused by deleterious mutations in the mitochondrial genome.

Autosomal-Recessive Inheritance An autosomal-recessive trait is characterized by having two unaffected parents who are heterozygous carriers for mutant forms of the gene in question but in whom the phenotypic expression of the mutant allele is masked by the normal allele. These heterozygous parents (A/a) can each generate two types of gamete, one carrying the mutant copy of the gene (a) and the other having a normal copy of the gene (A). Of the four possible combinations of

Molecular Genetics in Neurotology

these two gamete types from each parent, only the offspring that inherits both mutant copies (a/a) will exhibit the trait. Of the three remaining possibilities, all will have a normal hearing phenotype but two of the three will be heterozygous carriers of the mutant form of the gene, similar to the carrier parents. Although relatively uncommon, it is permissible for more distant relatives such as first or second cousins to marry and have children. This practice, known as consanguineous mating, greatly increases the potential to produce a child affected by a recessive disorder. Figure 5-1 illustrates the inheritance pattern of an autosomal-recessive trait in offsprings of consanguineous mating in a pedigree spanning several generations. A consanguineous mating of first cousins can generate a risk of 1 in 64 for having a child affected with an autosomal-recessive disorder from unaffected parents with a common grandparent. With approximately 1 in 2000 children born having a genetic form of hearing loss and 75% of these due to autosomal-recessive inheritance, a generalized risk of having such an affected child is on the order of 1 in 2700 for any two unaffected parents. Thus the increased risk that a consanguineous mating will produce a child with autosomal-recessive hearing loss is 1:64 divided by the frequency of autosomal-recessive hearing loss in the general population (random mating) 1:2700. This represents a 42-fold increase over the odds of two unrelated individuals giving rise to a child with autosomalrecessive hearing loss. Autosomal-recessive deafness is extremely heterogeneous, as inferred from frequent examples of families where both parents are deaf while their children have normal hearing. Thus, the generalized risk of having such an affected child is a simplification based on an assumption of a single causative locus and consequently an overestimate. It is possible that individuals with a mutant phenotype whose

Figure 5-1. A pedigree pattern illustrating transmission of autosomalrecessive trait. The affected individuals (shaded) have parents who are first cousins as well as carriers of the recessive trait. The double horizontal line between the parents of the affected children indicates that this is a consanguineous mating between first cousins. When the recessive allele is rare, it is more likely to become homozygous through inheritance from a common ancestor than from parents who are completely unrelated.

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expression is consistent with autosomal-recessive inheritance in fact possess mutations in two distinct genes that are in trans to each other. Such noncomplementary double heterozygotes, or digenic individuals, have been identified in retinitis pigmentosa within several families in which mutations in unlinked photoreceptor-specific genes ROM1 and peripherin/RDS were identified.2 Only the double heterozygotes were observed to develop retinitis pigmentosa. These cases represent the first example of digenic inheritance in human disease. Potential double heterozygotes have also been identified in nonsyndromic hearing loss within the Ashkenazi Jewish population. The affected individuals possess a common mutation 167delT in the GJB2 gene in trans to a major deletion spanning the GJB3 gene, thus suggesting digenic mode of inheritance.3 However, the effect of the deletion upon transcription of the adjacent GJB2 gene remains to be determined. If the deletion adversely affects transcription of GJB2, then the deletion effectively represents another example of recessive mutation.

Autosomal-Dominant Inheritance For autosomal-dominant disorders, the transmission of a rare allele of a gene by a single heterozygous parent is sufficient to generate an affected child. A heterozygous parent can produce two types of gamete. One gamete will carry the mutant form of the gene of interest, and the other the normal form. Each of these gametes then has an equal chance of being used in the formation of a zygote. Thus, the chance that an offspring of an autosomaldominant affected parent will itself be affected is 50%. Equal numbers of affected males and females are expected for an autosomal-dominant trait and roughly half of the offspring of an affected individual will be affected. If male-to-male transmission of the trait is observed, the possibility that the trait is X-linked can be eliminated. Figure 5-2A illustrates the inheritance pattern of an autosomal-dominant trait with complete penetrance. Thus all carriers of the disease allele express the disease trait. Autosomal-dominant traits often exhibit incomplete penetrance and variable expressivity. Variable expressivity refers to the differences in the observed effects of a given allele in related and unrelated individuals. Incomplete penetrance is an extreme form of variable expressivity and is characterized by the absence of expression in persons known to carry the mutant allele. Variation in the age of onset for symptoms associated with a genetic disorder is common for traits that are not expressed at birth or prenatally. Variation in age of onset is often treated as incomplete penetrance in linkage analysis. An example of this variation in the age of onset is seen in a single, large pedigree from Costa Rica, affected by nonsyndromic autosomaldominant hearing loss. In that nine-generation pedigree all affected individuals have one affected parent, a hallmark of autosomal-dominant disorders with high penetrance. Also the ratio of affected males to affected females approaches unity and male-to-male transmission of the hearing loss phenotype is observed, thus ruling out X-linked inheritance. All affected offsprings developed bilateral sensorineural hearing loss greater than 80 dB by their mid-thirties to early forties and had normal intelligence

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A

B Figure 5-2. A, A pedigree pattern illustrating transmission of autosomaldominant trait (shaded). The autosomal-dominant trait is transmitted from the affected parent to the offsprings, who have 50% probability of inheriting the disease allele. All carriers of the mutant gene express the disease trait, indicating complete penetrance of the mutant allele. B, A pedigree pattern illustrating transmission of autosomal-dominant trait with incomplete penetrance. Not all carriers of the mutant gene are affected, indicating incomplete penetrance of the mutant allele.

and fertility. Thus, the penetrance of the mutant allele was shown to be complete in older individuals. However, the age of onset of the hearing loss was variable. All affected individuals were born with normal hearing followed by degeneration of their hearing ability beginning between the ages of 6 to 16 years and continuing into their third decade of life, when the rate of hearing loss plateaus. The initial linkage analysis of this family excluded children younger than 16 years to avoid problems of misdiagnosing carriers of the mutant allele who had not yet expressed the phenotype. The gene for this nonsyndromic hearing loss was mapped to chromosome 5q31 by genetic linkage analysis and the locus was identified as DFNA1, denoting mapping of the first nonsyndromic deafness gene with autosomal-dominant mode of inheritance.4 The DFNA1 gene was subsequently determined to be diaphanous (DIAPH1) several years later through the identification of a splice-site mutation, leading to a frameshift in the DIAPH1 mRNA in only the affected members of the

Costa Rican family.5 This “deafness gene” is a member of the formin gene family, expressed in multiple tissues, including brain, heart, placenta, lung, kidney, pancreas, liver, and skeletal muscle and involved in cytokinesis and establishment of cell polarity. If the mutant phenotype is always expressed in individuals who carry the disease allele, then its penetrance is said to be complete; otherwise, it is incomplete. Where penetrance of the affected gene is complete, or 100%, then the pattern of its inheritance may be discerned relatively straightforwardly. Complete penetrance of the dominant allele will result in expression of the disease phenotype in all carriers of that allele without skipping generations. However, with incomplete penetrance of the affected gene, the inheritance pattern of the affected trait becomes relatively harder to discern; that is, one cannot easily distinguish between dominant inheritance with reduced penetrance and more complicated modes of inheritance. If the penetrance of an allele is very low, the parents of the affected child may not initially recognize the existence of similarly affected relatives who are distantly related. Figure 5-2B illustrates a pedigree expressing transmission of autosomaldominant trait with incomplete penetrance. Note that not all carriers of the disease allele are affected. The presence of low-penetrance-dominant alleles causing the phenotype to be transmitted through unaffected carriers cannot be ruled out without a thorough pedigree analysis that includes the ancestors and relatives of the affected individual. The gene may fail to express itself for a variety of reasons. The most common rationale put forth to explain reduced penetrance is the effect of genetic background. Factors such as genetic redundancy, presence of more than one gene for the performance of a given function, and modifiers affect variety of genes. Incomplete penetrance can also be seen in traits that are inherited in an autosomal-recessive, X-linked recessive, and X-linked dominant manner. Variable expression of different aspects of syndromes, including hearing loss, is common. Some aspects may be expressed in a range from mild to severe, or different combinations of associated symptoms may be expressed in different individuals carrying the same mutation within a single pedigree. An example of variable expressivity is seen in families transmitting autosomal-dominant branchiooto-renal (BOR) syndrome. For BOR syndrome, aplasia or stenosis of the lacrimal duct is reported in approximately 10% of cases; diagnosed structural anomalies of the renal system occurs in 12% to 20% of cases; branchial cysts or fistulas are present in approximately 60% of cases; anomalies of the inner ear occur in 30% to 60% of reported cases; and hearing loss is found in approximately 75% of reported cases. Of the hearing loss seen in BOR syndrome cases, 50% is mixed, 30% is conductive, and 20% is sensorineural loss. All three forms of hearing loss have been seen in affected members of the same family. In several individuals the type of hearing loss appears to differ between the two ears. Positional cloning approach led to the identification of EYA1 as the disease gene responsible for the BOR syndrome and has been shown to be the human homologue of the Drosophila eyes absent gene (EYA).6 Analysis of its murine orthologue, EYA1, suggests a role in the development of the inner ear and the kidney. The range of variation observed in dominant disorders is generally wider than in recessive disorders. A major

Molecular Genetics in Neurotology

contributing factor to the variation observed in the dominant disorders is the presence of a functional product from the wild-type allele. Variable regional concentration of the functional product may lead to the variable phenotype in the affected individuals. The wide range of phenotypic expression of the syndrome may also reflect the epistatic effects of different genetic backgrounds in the affected individuals; that is, different alleles for other genes interact with the major causative gene or genes. Additionally, variable expression may be influenced by environmental exposures and random stochastic events, which occur during development. The ability of a single mutant allele to express its aberrant phenotype, despite the presence of a normal allele, as observed in transmission of dominant disease traits, can occur via several mechanisms. These in turn depend on the nature of the protein encoded by the gene and the nature of the pathogenic mutation. If the mutant protein is involved in transcriptional regulation or functions that are sensitive to its quantity, then its dysfunction would reduce the available product by a half. This pathologic reduction in total amount of the active product is referred to as haploinsufficiency. For example, PAX3 is considered to encode a transcription factor and its haploinsufficiency resulting from a mutant allele is postulated to cause the expression of the disease phenotype, the dominantly transmitted type I Waardenburg’s syndrome. Another group of genes that can cause expression of the disease phenotype are those that encode structural proteins or membrane proteins that physically interact to yield functional product. Mutations within genes that encode collagens or connexins represent examples of such dominantly inherited disorders.7,8 However, not all mutations in genes whose products are part of an oligomeric assembly are dominant. For example, both dominant and recessive forms of a disease can result from different mutations of the same gene. This has been demonstrated for autosomal-dominant and -recessive forms of Stickler’s syndrome, a syndromic sensorineural deafness that results from different mutations within COL11A2 gene.

X-Linked Inheritance In humans, females have 22 pairs of autosomes and a pair of X chromosomes (46,XX); males have 22 autosomes, 1 X chromosome, and 1 Y chromosome (46,XY). Accordingly, males always receive their Y chromosome from their father and their X chromosome from their mother, and females receive one of their X chromosomes from each parent. Because males have one copy of the X chromosome, they are hemizygous for genes on the X chromosome and the X chromosome is active in all their nucleated cells. In general, only one of the two X chromosomes carried by a female is active in any one cell, while the other is rendered inactive by a natural process known as lyonization. This random inactivation process makes all females, who are heterozygous for X-linked traits, mosaic at the tissue level, resulting in variable expression of the mutant gene. Diseases that are rarely expressed clinically in heterozygous females are called X-linked recessive. In female tissues, various proportions of cells may exist in which one or the other of two alleles for an X-linked locus is expressed. Occasionally, a carrier female manifests some symptoms of an X-linked-recessive disorder due to this mosaicism if she

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Figure 5-3. A pedigree pattern illustrating transmission of an X-linked recessive trait (shaded). The affected males inherit the X-linked recessive disease allele from their unaffected carrier mother. The X-linked trait is characterized by absence of male-to-male transmission; all daughters of the affected male are heterozygous or carriers for the disease allele.

by chance has an abundance of cells with the mutant allele being expressed. Transmission of an X-linked-recessive trait in a pedigree is illustrated in Figure 5-3. The X-linked diseases were some of the first welldocumented genetic disorders in humans because of their unique inheritance patterns. Hemophilia A is one the most well known X-linked human diseases resulting from deficiency in a blood-clotting factor, factor VIII, encoded by its gene located on the X chromosome. While comprising only approximately 2% of cases, X-linked transmission of alleles involved in inherited hearing loss is significant. Examples of such disorders include Norrie’s syndrome, X-linked congenital sensorineural hearing loss, and X-linked high-frequency sensorineural hearing loss. In pedigrees exhibiting X-linked-recessive traits, many more males are affected than females because males have only one X chromosome. Thus, a recessive allele for hearing loss is not masked in males. Females have two X chromosomes, allowing the masking of a recessive allele on one X chromosome by a normal allele of the gene on their other X chromosome. Females who express a true X-linked-recessive trait have inherited a mutant form of the gene from both parents. Approximately half of the sons are affected and half are unaffected when a female carrier of an X-linkedrecessive gene has children with a normal male. No affected offspring will result from the mating of a male affected by an X-linked-recessive disorder with a homozygous normal female; however, all of his daughters will be carriers. The absence of father-to-son transmission is a unique characteristic of all X-linked traits because males always receive their X chromosome from their mother. DFN3 represents one of the most frequent forms of X-linked deafness. Affected males have conductive hearing loss (as a result of stapes fixation) and progressive sensorineural deafness. The DFN3 gene has been cloned and is referred to as POU3F4, a member of a multigene family that encodes nuclear transcription factors.9 POU3F4 represents the first cloned gene whose mutant allele was identified in individuals with nonsyndromic deafness.

Variations on Mendelian Principles Mendel established the two fundamental principles of genetics: segregation of genes and their independent

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assortment. These principles refer to processes that occur in the formation of germ cells known as meiosis. Segregation refers to separation of homologous genes, representing the paternal and the maternal contribution to the individual’s genotype, into two separate daughter cells. Thus, the diploid genome is reduced to the haploid state in the germ cells. The principle of independent assortment states that segregation of one gene occurs independent of other genes. These principles have served well for analysis and understanding of inheritance of traits through a single locus. However, a number of variations on these principles do exist, some of which have already been stated implicitly. These variations and their underlying principles have increased our understanding of genetic etiology of disease.

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4

Figure 5-4. A pedigree pattern illustrating mitochondrial inheritance of the disease trait (shaded). The disease trait is transmitted maternally, through its mitochondrial genome, to both male and female offsprings.

Linkage and Recombination Not all genes assort independently of each other. Thomas Hunt Morgan initially identified this variation on the Mendelian principle in fruit flies through analysis of transmission of selected traits. Experiments showed inheritance of a specific pair of alleles in a combination not present in the parental phenotype. This new combination of alleles was considered to result from crossover and exchange of genetic material between two homologous chromosomes, known as homologous recombination, yielding the new combination of alleles not present in the original parental chromosomes. Analysis of recombination frequencies between two traits considered to be controlled by genes residing on the same linkage group (i.e., the same chromosome) provided two essential concepts that led to the development of the genetic map: Genes are arranged in a linear order and the frequency with which two alleles are inherited together is a function of the relative physical distance from each other. Thus, the closer the two genes, the greater the chance that they will remain linked post meiosis. The relative chromosomal positions of genes may be readily mapped through the application of these principles of linkage and recombination to generate genetic maps. The genetic distance between two linked genes as measured through frequency of recombinants between the two alleles is measured in centimorgans (cM). These two loci are one cM apart on the genetic map if there is a 1% chance of a recombination between them in meiosis. Thus, genes that are far apart on a chromosome will assort in an apparent independent manner and genes that are close will tend to remain linked post meiosis. Applying the principles of genetic linkage, Morgan and his colleagues were able to order more than several hundred genes in D. melanogaster via recombination analysis by the year 1922. Mitochondrial Inheritance Not all genes are inherited equally from both parents. The extranuclear genome is inherited solely through the mother. Male mitochondria are not contributed to newly formed zygotes. This inheritance pattern, illustrated in Figure 5-4, gives rise to pedigrees in which all the children of an affected mother may be affected and none of the children of an affected father will be affected. In practice, the expression of mitochondrially inherited disorders is often variable and may be incompletely penetrant. This

observation is possibly due in part to the fact that a population of mitochondria, which can itself be genetically heterogeneous, is actually transmitted by the mother. If all of the mitochondria transmitted by the mother are of the same genotype, it is called homoplasmia; if there are genetic differences between them, it is call heteroplasmia. Despite its small size relative to the nuclear genome, 1:200,000, mutations of the mitochondrial genome are a significant contributor to human disease. This is in part due to the 10-fold higher mutation rate that is associated with the replication of mitochondrial genome relative to the nuclear genome and that it consists of proportionately far less noncoding sequence. To date there are 326 syndromes, disorders, and peculiar phenotypes associated with mutations in the mitochondrial genome.10 Twenty-one of these disorders have some involvement with sensorineural hearing loss, which indicates that the requirement for a healthy population of mitochondria is very important to the cells involved in normal hearing.11–14 One of the most striking examples of a mitochondrially inherited trait whose expression is environmentally affected is the hearing loss caused by hypersensitivity to aminoglycosides.12 Hypersensitivity to aminoglycosides phenotype is the result of a single base transition of A to G at position 1555 in the mitochondrial 12S rRNA. This mutation causes a portion of the 12S rRNA transcript structure to closely resemble the binding site of aminoglycosides to bacterial rRNA. When an aminoglycoside such as streptomycin is administered to patients who carry this mutation, it binds to the mutant 12S rRNA and prevents it from functioning in the translation of mitochondrially transcribed genes. This results in the loss of mitochondria that may lead to cell death or loss of their normal function. Screening for this mutation before initiation of aminoglycoside therapy may reduce the incidence of ototoxicity. X Chromosome Inactivation The chromosome can be identified in nondividing cells of females (within the interphase nuclei) as a darkly staining mass called the Barr body attached to nuclear membrane. The Barr body represents the X chromosome that has been inactivated and thus appears as a condensed mass (heterochromatization). This X-chromosome inactivation in females is also known as lyonization, named after

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Mary Lyon, who first offered an explanation for its presence in females. Thus, lyonization represents a dosage compensation mechanism to correct for differences in sex chromosome constitution between sexes and targeted toward the X chromosome. This mechanism ensures that genes located on the X chromosome are not expressed in proportion to the number of X chromosomes but equivalent to a single X chromosome that is present in both male and female cells. Thus, both the male and female cells are balanced with respect to the expression of their X-linked genes. Consequence of X inactivation in females and hemizygous expression of X-linked genes in males as it relates to inheritance patterns of familial Mendelian disorders is discussed under the heading X-Linked Inheritance.

I

Genomic Imprinting

III

Some genetic disease occur more often if inherited from the fathers than from mothers or vice versa. This occurrence is considered to result from “genomic imprinting.”15 This phenomenon runs counter to the teachings of Mendelian genetics, which emphasize equal contribution from paternal and maternal genes, with the obvious exception of genes on the sex chromosomes. Thus, in certain instances, despite the presence of both the paternal and maternal alleles, only one parental allele is expressed. This differential expression of the parental alleles is detected in certain disease states when inheritance of that disorder depends on the sex of the parent that transmits the mutant gene. The gene-specific imprinting, as with the X-chromosome inactivation, is presumed to be the consequence of reversible “epigenetic” modification of the parental allele during gametogenesis, leading to its differential expression. The precise mechanism of imprinting and its evolutionary significance remain unknown. Imprinting is considered to be established prior to or during gametogenesis and is known to persist stably throughout somatic cell divisions. Hypermethylation of the imprinted gene represents one possible mechanism. This process involves the covalent addition of a methyl group to the C5 position of the cytosine ring. The role of methylation for mediating the imprinting process is supported by the observations that all of the imprinted sequences that have been analyzed are methylated. It is possible that methylation of the imprinted gene is secondary to a prior imprinting step and its role may be stabilizer of the imprinted signal. The gene-encoding IGF-II, a potent growth factor and a mitogen, was the first identified example of an autosomalimprinted gene.16,17 The expression of IGF-II was shown to be restricted to its paternal allele, the maternally derived allele was transcriptionally silent. Several other imprinted loci or genes have been identified in humans based on inheritance patterns of familial disorders that are consistent with imprinting phenomenon. These include the PraderWilli syndrome, where the affected gene is maternally imprinted, and the Angelman syndrome, where the affected gene is paternally imprinted. A pedigree transmitting a maternally imprinted disease gene is illustrated in Figure 5-5. An example of genomic imprinting at the level of a specific gene has also been identified in familial cases of nonchromaffin paragangliomas, benign tumors of the paraganglionic cells. Although benign, their enlargement can cause deafness and facial palsy. Familial cases of

Figure 5-5. A pedigree pattern illustrating transmission of autosomaldominant trait (shaded) that is genomically imprinted. A pedigree demonstrating a maternally imprinted autosomal-dominant transmission of a disease allele. Individuals are affected only if they receive the mutant allele through paternal and not maternal transmission. Furthermore, the affected carrier male who has received the mutant allele through maternal inheritance can then transmit the allele.

2

2

3

2

II

1

3

4

5

4

6

7

8

9

5

6

7

8

2

paragangliomas (glomus tumors) have shown an autosomaldominant inheritance with genomic imprinting of the maternal allele. Thus, the transmission of the disease occurs via the affected paternal allele and not the maternal allele.18,19 The genetic basis of the head and neck paragangliomas and the observed parent-specific transmission pattern are discussed in greater detail in a later section. Trinucleotide Repeat Expansion Another type of deviation from Mendelian genetics has been identified through analysis in six neurologic disorders that are characterized by increased severity or an earlier onset of the disease in successive generations. This phenomenon, unique to these disorders, is termed anticipation. These include the fragile X syndrome (FRAXA), spinal and bulbar muscular atrophy (SBMA), Huntington’s disease (HD), and muscular dystrophy (MD). Analysis of mutation in the affected individuals has revealed a pathologic expansion of a region of DNA, known as trinucleotide repeats, beyond the normal range observed in the unaffected, within genes linked to disorders characterized by anticipation. A progressive increase in the size of these trinucleotide repeats is correlated with the increased severity and/or age of onset of the disease. The mechanism of pathophysiology caused by this dominantly inherited pathologic mutation remains relatively unknown. In patients affected by fragile X syndrome, the syndrome can be transmitted not only by heterozygous female carriers but also by unaffected (hemizygous) males. The “carrier males” possess expanded repeat numbers of 60 to 230, relative to normal controls who express an average repeat number of 29. The unaffected paternal carriers of X-linked disorders or the phenomenon of anticipation associated with trinucleotide repeat expansion could not have been predicted from principles of Mendelian genetics.

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Multifactorial Inheritance An expression of a phenotype whose outcome is determined by a single gene is termed a Mendelian trait. Its pattern of transmission within a pedigree can be readily discerned in most cases, as described in previous sections. On the other hand, most common human diseases and traits show irregular inheritance patterns. These traits are considered to be determined from action of multiple genes and nongenetic factors. A phenotype that is an outcome of both genetic and environmental factors is called a multifactorial, or complex, trait. The low proportion of Mendelian traits relative to number of multifactorial traits in humans is better illustrated by considering the proportion of total number of Mendelian traits known, approximately 6,000 according to McKusiak,20 to the total number of genes that are estimated to exist, approximately 30,000. It should be emphasized that classification of Mendelian traits as being determined by single genes is an oversimplification. As more Mendelian disorders are identified and their phenotypes investigated, the phenotypic variability and complexity of each Mendelian trait is becoming increasingly clear and concomitantly its distinction from complex or multifactorial trait is becoming increasingly blurred. Phenotype variability or variable expression seen in a single gene disorder such as Waardenburg’s syndrome may reflect interaction of that major gene, such as PAX3, with “modifier” genes. Identification of these modifier genes has important implications for understanding and treatment of the Mendelian disorders with variable expressivity. One of the clearest examples of interaction of other genes and their products (termed epistatic effects) or nongenetic factors during development of a particular Mendelian phenotype is provided by the large variation of the clinical phenotype observed in individuals with an identical mutation in a given gene. A classical example of a single mutant allele yielding a varying phenotype is the hemoglobin βS mutation that results in substitution of valine or glutamine at position six of the β-globin chain. In the homozygous state, this mutation usually causes sickle cell anemia of varying clinical severity. The identity of the modifying genetic factors that interact to yield the variable clinical severity in sickle cell anemia remain as yet undetermined. Such phenotypic heterogeneity despite the identity of mutation has been described in number of disorders including Waardenburg’s syndrome (WS), cystic fibrosis, phenylketonuria (PKU), Duchenne’s muscular dystrophy (DMD), retinitis pigmentosa (RP), and Marfan syndrome, as well as XY gonadal dysgenesis ( XYGD). Thus, mutation analysis alone is insufficient in predicting the clinical phenotype of the affected individual. Conversely, the phenotypic outcomes do not depend on the nature of mutations only. As seen in the examples cited, the primary structural change in the DNA sequence can result in spectrum of consequences depending on the individual’s genotype or genetic background. This can range from complete blocking of the pathway to complete compensation of the defect, depending on interactions with other genes and their products and their relative influence for the specific process or the role that is mediated by the mutant gene. The relatively irregular mode of inheritance that characterizes a multifactorial trait is presumed to result from

interaction of multiple genes (polygenic).21 This interaction is apparently distinct from that presumed for Mendelian traits. But this distinction may be at a quantitative rather than qualitative level. For example, instead of a predominant influence or effect of one gene upon expression of the phenotype, the multifactorial trait is characterized by a number of genes with equivalent influence or effect. The genetic component of multifactorial traits is referred to by terms such as increased risk, predisposition, and susceptibility. Because of their complexity, the factors that contribute to the multifactorial traits are poorly defined. Several wellstudied diseases that are classified as multifactorial include cardiovascular conditions, diabetes, and distinct behavioral disorders. Influence of nongenetic factors, such as environmental agents and stochastic processes during developmental outcome of variety of traits, is also clearly illustrated in the studies of identical twins.

GENETICS AND GENETIC EPIDEMIOLOGY OF NONSYNDROMIC HEREDITARY HEARING LOSS Hearing loss is the most common form of sensory loss in humans. Nearly 10% of the U.S. population, or 30 million Americans, have significant auditory dysfunction. For some, the hearing loss is present at the beginning of life. The prevalence of permanent, moderate to severe sensorineural hearing loss (SNHL) is estimated to be between 1 and 3 per 1000 live births.1 Historically, infectious disorders such as otitis media, maternal rubella infections, and bacterial meningitis, as well as environmental factors such as intrauterine teratogenic exposure and ototoxic insult were the dominant causes of congenital and acquired hearing losses. The introduction of antibiotics and vaccines and the increasing awareness of teratogens has led to a decline in hearing loss resulting from infectious and environmental agents. Currently, more than half of childhood hearing loss is thought to be hereditary.22 Genetic analysis of hereditary hearing loss has benefited significantly from the development of critical resources and techniques. The development of a high-resolution map of the human genome characterized by closely spaced genetic markers (1 centimorgan or 1 megabase separation) and the application of the polymerase chain amplification (PCR) technique for rapid characterization of these genetic markers (genotyping) has enabled the localization and identification of genes responsible for variety of inherited disorders in humans. This genetic approach has also been applied toward determining the genetic basis of syndromic and nonsyndromic hereditary hearing loss. In syndromic hearing loss, more than 100 genes have been identified since 1990, showing a large heterogeneity even within a single type of syndromic hearing loss [e.g., Usher syndrome type Ia-f with 6 different genetic loci (Table 5-1)]. In nonsyndromic hearing loss, as of January 2004, 51 autosomal-dominant, 39 autosomal-recessive, 8 X-linked, 1 modifier, and 2 mitochondrial loci have been mapped on the human genome. From these 101 mapped loci, 37 genes have been identified (Table 5-2).23 The 37 “deafness genes” that have been identified encode a variety of protein products that play different

Neurofibromatosis type II Norrie’s disease

Pendred’s syndrome

Stickler’s syndrome

Treacher Collins syndrome

Usher syndrome

PDS

STL1 STL2 STL3

TCOF1

USH1A USH1B

Leucine tRNA

Mitochondrial syndromes

Unknown MYO7A

TCOF1

COL2A1 COL11A2 COL11A1

SLC26A4

NF2 Norrin

Lysine tRNA Lysine tRNA Several

KVLQT1 KCNE1 (IsK)

DDP

DFN1, Mohr-Tranebjaerg syndrome Jervell and Lange-Nielsen syndrome

FGFR2

EYA1

COL4A5 COL4A3, COL4A4

Alport syndrome

Branchio-Oto-Renal syndrome Crouzon syndrome

Gene

Syndrome

ND

JLNS1 JLNS2

BOR

Locus

Development of critical neuroepithelium where auditory transduction takes place in hair cells of the cochlea

Nucleolar-cytoplasmic transport

Hydrophobic proteins containing the sulphate transporter signature Encoding of a structural protein Skeletal morphogenesis Formation of the human vitreous

Tumor suppression Neuroectodermal cell–cell interaction

Formation of basement membrane structures in the cochlea (immunolocalization to kidney glomerculus) Development of all components of the inner ear, from the emergence of the otic placode Formation of cell-surface binding sites for fibroblast growth factors Mitochondrial protein-import system (neurologic development) Formation of a delayed rectifier potassium channel in the inner ear

Function

TABLE 5-1. Genes and Loci for Syndromic Hearing Loss

Autosomal-dominant

Autosomal-dominant

Autosomal-recessive

Autosomal-dominant X-linked

Autosomal-recessive

X-linked

Autosomal-dominant

Autosomal-dominant

X-linked dominant Autosomal-recessive

Inheritance

Continued

Progressive myopia, vitreoretinal degeneration, premature joint degeneration with abnormal epiphyseal development, midface hypoplasia, irregularities of the vertebral bodies, cleft palate deformity, and variable sensorineural hearing loss Coloboma of the micrognathia, microtia, hypoplasia of the zygomatic arches, respect to the medial canthilower eyelid (the upper eyelid is involved in Goldenhar syndrome), hearing impairment and retinitis pigmentosa

Ocular symptoms, progressive sensorineural hearing loss, and mental disturbance Congenital deafness and thyroid goiter

Prolongation of the QT interval, torsade de pointe arrhythmias, sudden syncopal episodes, and severe-to-profound sensorineural hearing loss Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes, diabetes mellitus Myoclonic epilepsy and ragged red fibers Myoclonic epilepsy and ragged red fibers Kearns-Sayre syndrome, progressive external ophthalmoplegia

Branchial, otic, and renal anomalies

Focal thinning and thickening with eventual basement membrane splitting in the glomerulus

Clinical Features Associated in Development

Molecular Genetics in Neurotology 129

Formation of endothelin-signaling pathways Formation of endothelin-signaling pathways Encoding of a transcription factor

USH3

EDNRB EDN3 SOX10

USH3

SLUG

MITF

PAX3

Unknown

USH2B USH2C

Waardenburg’s syndrome

Two predicted transmembrane domains; function unknown Production of a protein that contains the paired domain structural motif and regulates the expression of other genes Production of a protein that is a homodimeric transcription factor expressed in adult skin and in embryonic retina, otic vesicle and hair follicles Zinc finger transcription factor

Unknown USH2A

USH1G USH2A Production of a tissue-specific extracellular matrix protein

Member of cadherin superfamily; putatively plays a role in lock-and-key molecular mechanism involved in synaptic sorting

Unknown PCDH15

Unknown Member of cadherin superfamily; involved in establishment of cell–cell contacts and organization of extracellular matrix

Function

USH1E USH1F

Gene USH1C CDH23

Syndrome

USH1C USH1D

Locus

TABLE 5-1. Genes and Loci for Syndromic Hearing Loss—cont’d

Autosomal-recessive Autosomal-recessive Autosomal-recessive

Autosomal-dominant

Autosomal-dominant

Autosomal-recessive

Inheritance

Dystopia canthorum, pigmentary abnormalities of hair, iris, and skin, sensorineural deafness

Hearing impairment and retinitis pigmentosa

Clinical Features Associated in Development

130 ANATOMY, PHYSIOLOGY, AND PATHOLOGY

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131

TABLE 5-2. Genes and Loci for Nonsyndromic Hearing Loss Locus

Gene

Biological Role

Inheritance

DFNB1 DFNB1 DFNB2 DFNB3 DFNB4 DFNB6 DFNB7/DFNB11 DFNB8/DFNB10 DFNB9 DFNB12 DFNB16 DFNB18 DFNB21

GJB2 (CX26) GJB6 (CX30) MYO7A MYO15 SLC26A4 TMIE TMC1 TMPRSS3 OTOF CDH23 STRC USH1C TECTA

Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive

DFNB22

OTOA

DFNB23 DFNB29 DFNB30 DFNB31 DFNB37

DFNA5

PCDH15 CLDN14 MYO3A WHRN MYO6 PRES (Prestin) DIAPH1 GJB3 (CX31) KCNQ4 GJB2 (CX26) GJB6 (CX30) DFNA5

DFNA6/DFNA14

WFS1

DFNA8/12

TECTA

DFNA9

COCH

DFNA10 DFNA11 DFNA13 DFNA15

EYA4 MYO7A COL11A2 POU4F3

DFNA17 DFNA20/26 DFNA22 DFNA28 DFNA36 DFNA48

MYH9 ACTG1 MYO6 TFCP2L3 TMC1 MYO1A CRYM POU3F4

A gap junction protein that forms intercellular channels A gap junction protein that forms intercellular channels Moves different macromolecular structures relative to actin filaments Organizes actin in hair cells Encodes highly hydrophobic proteins containing the sulphate transporter signature Transmembrane inner ear expressed gene Transmembrane protein expressed in cochlear hair cells and vestibular end organs Transmembrane serine protease Involved in trafficking of membrane vesicles Cadherin superfamily Protein stereocilin associated with stereocilia on mechanosensitive hair cells Unknown Includes an aminoterminal hydrophobic signal sequence for translocation across the membrane and a carboxyterminal hydrophobic region characteristic of precursors of glycosylphosphatidylinositol-linked membrane-bound proteins A glycosylphosphatidylinositol-anchored protein with weak homology to megakaryocyte potentiating factor/mesothelin precursor Morphogenesis and cohesion of stereocilia bundle Protein component of tight junctions between cells Class III myosin with hybrid motor-signaling function PDZ domain molecule involved in stereocilia elongation A molecular motor involved in intracellular vesicle and organelle transport A motor protein of the outer hair cell Involved in cytokinesis and establishment of cell polarity Gap junction protein that forms intercellular channels Forms potassium channel A gap junction protein that forms intercellular channels A gap junction protein that forms intercellular channels Unknown; related to a gene that is upregulated in estrogen-receptor-negative breast carcinomas Protein with nine putative transmembrane domains and putative role in protein sorting or trafficking Includes an aminoterminal hydrophobic signal sequence for translocation across the membrane and a carboxyterminal hydrophobic region characteristic of precursors of glycosylphosphatidylinositol-linked membrane-bound proteins Involved in hemostasis, complement system, immune system, and extracellular matrix assembly Member of the vertebrate EYA family of transcriptional activators Moves different macromolecular structures relative to actin filaments Collagen protein Serves as a critical developmental regulator for the determination of cellular phenotypes Conventional heavy chain nonmuscle myosin An actin molecule, a major component of the cytoskeletal system of nonmuscle cells Unconventional myosin Transcription factor cellular promoter 2-like 3 Transmembrane cochlear-expressed protein Unconventional myosin A thyroid hormone-binding protein (THBP) Serves as a critical developmental regulator for the determination of cellular phenotypes

DFNA1 DFNA2 DFNA3

DFN3

roles in cellular physiology (Table 5-3). These protein products include the following: cytoskeletal proteins important in maintaining cellular structure, division, and intracellular transport; transcription factors that regulate the expression of other genes; ion channels important in transport of sodium, potassium, chloride, and iodine; developmental genes that regulate morphogenesis; and proteins involved in intercellular communications such as gap junctions and tight junctions. Genetic analysis of hearing loss has profoundly altered conventional notions of the relationships between genes, mutations, and the corresponding disease phenotype. Numerous examples illustrate that distinct mutations within

Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant Autosomal-dominant X-linked

a single gene have a differing effect upon the encoded protein, thus affecting the mode of inheritance and/or the clinical phenotype associated with the disease gene. Thus, mutation of the gene-encoding myosin VIIA can cause either dominant or recessive forms of nonsyndromic deafness.24,25 This phenomenon has also been documented for connexin 26: Different mutations of CX26 are associated with dominant and recessive mode of transmission.8,26 The dominant or recessive mode of inheritance for a specific mutation is considered to reflect the disruptive effect of the mutant protein upon functional integrity of the multimeric assemblies formed by the individual subunits. Syndromic and nonsyndromic deafness associated with mutations of

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TABLE 5-3. Gene Transfer Vectors Vector

Genome

Insert Size

Site

Efficiency

Cell Division

Expression

Advantages

Disadvantages

AAV

ssDNA

4.5 kB

Genome

Variable

Not required

Permanent

Retrovirus

RNA

6–7 kB

Genome

Low

Required

Permanent

Adenovirus

dsDNA

7.5 kB

Episome

Moderate

Not required

Transient

Herpesvirus Plasmid

dsDNA RNA/DNA

10–100 kB Unlimited

Episome Episome

Moderate Very low

Not required Not required

Transient Transient

Liposome

RNA/DNA

Unlimited

Episome

Very low

Not required

Transient

No human disease Suited for neoplastic cells Ease of production Neural tropism Safe, easy production Safe, easy production

Difficult to produce Insertional mutagenesis Inflammatory response Human disease Low transfection Low transfection

myosin VIIA, an intracellular motor protein, represents an excellent example of differing clinical phenotypes due to mutations in a single gene. Similarly, mutant alleles of pendrin, encoding a solute transporter, can cause either Pendred’s syndrome or isolated (nonsyndromic) large vestibular aqueduct. The patient’s genetic background is a critical factor in determining the clinical phenotype that results from a specific mutation. The genetic background represents other genes that interact with the mutated gene via its protein products. These genes are known as modifier genes and their interactions can determine the clinical severity of the disease trait predicated by the mutant allele. For example, affected individuals within a family carrying an identical mutation in PAX3 gene, associated with Waardenburg’s syndrome type I, can display a clinical phenotype of varying severity, corroborating the important contribution of differing genotypes in determining the phenotype.27 Several of the genes whose mutant alleles have been causally linked to nonsyndromic deafness are especially important in clinical otology on the basis of their prevalence or their associated histopathology. These include geneencoding connexins, PDS, and the myosins. Each of these is discussed here.

Connexin 26 Connexin 26 is a member of a family of proteins that are involved in the formation of gap junctions. Connexins are transmembrane proteins that form channels to allow transport of ions or small molecules between adjacent cells. Each connexin subunit contains three intracellular domains and two extracellular domains, crossing the plasma membrane four times. The second intracellular domain (IC2) contains the cytoplasmic loop. The other two intracellular domains consist of the N terminus and C terminus. Six connexin subunits join to form a connexon. A pair of connexons, one in each adjacent cell, comes together to form an intercellular channel. The connexin gene family plays an important role in normal hearing; mutations in several members of the family are associated with hearing loss. To date, mutations in five members of the connexin gene family—CX26, CX30, CX31, CX32, and CX4—have been implicated in hearing loss.28 Among them, mutations of CX26 are the most common and represent a major cause of inherited and sporadic nonsyndromic deafness.29–31 Specifically, CX26 mutations

are responsible for both recessive (DFNB1) and dominant (DFNA3) forms of HHL.8,26 Several studies have demonstrated prevalence of CX26 mutations in 50% of individuals with recessive deafness with a carrier rate as high as 4%.32,33 Given the large genetic heterogeneity of HHL, evidenced by the 93 distinct loci that have been mapped, the predominance of a single gene’s being responsible for the majority of the hearing loss in the general population is a surprising outcome with significant implications for screening and clinical management. Studies investigating physiologic role of CX26 in the cochlea suggest that it serves as the structural basis for recycling of potassium ions back to the endolymph of the cochlear duct after stimulation of the sensory hair cells.34 Dysfunction of CX26 is believed to affect homeostasis of potassium ions in the cochlear duct, thus affecting mechanotransduction and resulting in hearing loss. Currently, more than 60 mutations have been identified.28 Two single base pair deletions account for nearly half of all mutations in this gene: 35delG and 167delT.32,33 The 35delG mutation has been found to be common in several populations, accounting for up to 70% of CX26 mutant alleles in families from the United Kingdom, France, Italy, Spain, Tunisia, Lebanon, Israel, Australia, Greece, United States, and New Zealand, as well as up to 40% of sporadic cases of congenital deafness in these countries. The 35delG mutation leads to frameshift and early termination of the nascent protein and a nonfunctional intracellular domain in the protein. Alternatively, this mutation may lead to an unstable RNA, leading to its early degradation or absence of its translation into protein. Clinically, homozygous patients with the 35delG mutation show a variable phenotype, ranging from mild to profound hearing loss. However, most patients with homozygous 35delG mutation show a severe to profound phenotype. The differences in the worldwide populations are also reflected in the varying prevalence of the common CX26 mutant alleles. Thus, although common in most populations, the 35delG mutation is much less frequent in the Japanese populations in which 235delC is the prevalent CX26 mutation.35,36 Likewise, in the Ashkenazi Jewish population, the 167delT mutation has been found to be more common than the 35delG mutation with a carrier rate of 4%.33 The high frequency of mutant CX26 alleles associated with recessive forms of hearing loss, presence of a single coding exon of a relatively small size, and predominance of two mutations collectively represent attributes of an ideal

Molecular Genetics in Neurotology

gene for mutation screening. Correspondingly, screening for the two common CX26 mutations is now available at numerous medical centers and laboratories; however, its role in the diagnosis and management hearing loss in children needs to be determined. We have recently screened 154 individuals with SNHL for mutations in CX26 by DNA sequencing and identified 34 patients with mutations for an overall incidence of 22% in the study population.37 Of all CX26 mutations, the 35delG mutation accounted for 26%. The 35delG mutation was present in a homozygous state in only 4 individuals (each of the two chromosomes harbored the 35delG mutation) and heterozygous in 6 individuals (only one chromosome had the 35delG mutation). Herein lies the fundamental problem with screening for only 35delG: only 4 of 34 individuals (12%) with CX26 mutations, or 154 individuals in total (3%), had homozygous mutation that would be required to clearly implicate CX26 as the causative gene. The identification of a single copy of 35delG mutation does not implicate this gene in deafness and may simply reflect the high carrier rate in the population. In this case, the rate of identifying the cause of childhood SNHL by genetic testing is significantly less than that of radiologic imaging. Therefore, genetic testing for 35delG and 167delT mutation only, without sequencing the entire CX26 gene, is inadequate.

Pendrin Mutations of the SLC26A4 ( PDS) gene are the pathogenic cause of isolated large vestibular aqueduct, the most common radiologic abnormality associated with childhood deafness, as well as Pendred’s syndrome. The SLC26A4 ( PDS) gene on chromosome 7q31 consists of 21 exons and encodes an 86 kDa polypeptide known as pendrin that is expressed in the kidney, thyroid gland, and cochlea.38 Comparative sequence analysis indicated that this gene is a member of a gene family that is involved in sulfate transport. However, functional studies have shown this transmembrane protein to be an energy- and sodium-independent transporter of iodide and chloride ions, primarily.39 In the mouse inner ear, pendrin localizes to the endolymphatic duct and sac, distinct areas in the utricle and saccule, and the external sulcus region within the cochlea, implicating a possible role in endolymph resorption and/or homeostasis. However, the specific substrate and the biological role of Pendrin in the inner ear remain undetermined. It has been estimated that mutations of SLC26A4 may be responsible for as much as 10% of HHL and thus represents the most common cause of syndromic HHL.40,41 Two frequent missense mutations of SLC26A4, L236P (707 T to C), and T416P (1246 A to C) were initially identified40; subsequently, a third common mutation, E384G (1151 A to G) has also been identified. Although the gene is too large for screening by direct sequencing, identification of common mutations opens the opportunity for screening for these isolated mutations. Goiter that is associated with Pendred’s syndrome results from the reduced ability of the thyroid gland to organify iodine into the thyroid hormone.42 However, goiter is not considered to be a specific marker of the Pendred syndrome due to its variable expression and phenocopies. The hearing loss is usually congenital and profound. However, there are reports of a milder or progressive hearing loss. Investigation of the role of pendrin in

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hearing and its dysfunction has led to the generation of knockout mice carrying null allele of SLC26A4.43 These knockout mice (Slc26a4–/Slc26a4–) have both auditory and vestibular dysfunction. However, goiter or other abnormalities of thyroid function are absent. SLC26A4 mutations are also responsible for nonsyndromic hearing loss associated with the large vestibular aqueduct. Isolated presence of a large vestibular aqueduct (LVA) is one of the most common forms of inner ear anomalies. Genetic studies of families with LVA disorder identified a recessive nonsyndromic locus, DFNB4 that also mapped to the same region as the PDS gene. This led to the evaluation of PDS gene and the subsequent identification of seven PDS mutations responsible for LVA with nonsyndromic HHL.44 Like Pendred’s syndrome, different mutations, V480D, V653A, I490L, and G497S, have been found to be commonly associated with LVA. In review of our experience at the University of California–San Francisco, LVA was the most common imaging abnormality detected in children with nonsyndromic SNHL.45 At least 40% of children with LVA will develop profound SNHL. Patients with LVA are at risk for progressive hearing loss after minor head trauma. Identifying this anomaly influences parent counseling with respect to the dangers of incidental head trauma. In summary, the spectrum of PDS mutations and the wide range of phenotypic manifestations show that pendrin is an important but only one participant in ear structural development and in the normal functioning of the inner ear and thyroid. Screening for mutations may play an important role in the diagnosis and management of a child as well as siblings with hearing loss.

Myosins The importance of myosins in inner ear function is widely recognized by the growing list of unconventional (nonclass II) myosin-heavy-chain genes pathogenically linked to HHL. These disease genes encode the heavy chains of myosin IA, IIIA, VI, VIIA, and XV. Myosin VIIA was the first of the unconventional myosins that was causally linked to hereditary hearing loss in both rodents and humans. Mutations in the gene-encoding myosin VIIA are responsible for mouse shaker 1, human Usher syndrome type 1, human nonsyndromic hearing loss DFNB2 and DFNA11. Shaker 1 mice are deaf and have vestibular defects. Mice that are homozygous for mutant shaker 1 allele display progressively disorganized stereocilia. Myosin XV is the largest of all myosin-heavy chains, having a molecular weight of 395 kDa. Mutations in myosin XV have been pathogenically linked to DFNB3 in humans and the shaker 2 phenotype in mice. Myosin VI was initially identified as the deafness gene in a mouse model of inherited hearing loss; the cochlear and vestibular neurosensory epithelium in this mouse model, known as Snell’s waltzer, degenerates soon after birth. A mutant allele of myosin VI is considered to be responsible for the DFNA22, the human nonsyndromic, form of hereditary hearing loss. Mutant alleles of myosin IA and IIIA have also been recently identified as responsible for DFNA48 and DFNB30, respectively. Expression of these unconventional myosins is not limited to the cells and tissues of the inner ear. Yet, the expression of their dysfunction is largely restricted to hearing loss. The unconventional myosins are distributed throughout

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the mechanosensory hair cells. Moreover, histopathology of mouse models of myosin XV dysfunction has been valuable for understanding the consequences of myosin dysfunction upon the sensory hair cells. Myosin VI is localized in the actin-rich cuticular plate and in the rootlet actin filaments that descend from stereocilia into the cuticular plate, suggesting a role in stabilizing the basal attachment of stereocilia.46,47 Myosin VIIA is localized in the stereocilia and cell body of hair cells.47 Postulated roles for myosin VIIA include maintaining stereocilia integrity and membrane trafficking in the inner hair cells. Histopathology of the inner ears of mouse models of myosin XV dysfunction revealed significantly shortened stereocilia in the sensory hair cells, demonstrating the importance of myosin XV in the maintenance of hair cell structure and thereby its function. A mutation in a conventional or class II myosin, MYH9, resulting in nonsyndromic has also been described. The class II myosins, broadly expressed in skeletal, cardiac, and smooth muscles as well as nonmuscle tissues, consist of a pair of heavy chains, a pair of light chains, and a pair of regulatory light chains.48 The N-terminal motor domain is the most highly conserved region of the myosin heavy chain and contains the ATP and actin binding sites. The apparent molecular weight of the class II myosin heavy chain is 200 kDa. The myosin that mediates skeletal muscle contraction, also known as the sarcomeric myosin, represents the most well characterized representative of class II myosin family. Cardiac and smooth muscle cells also express isoforms of class II myosin, distinct from the sarcomeric myosin that mediate contraction in these muscle cells. Mutation in MYH9, a conventional nonmuscle myosin, was described in an American family with autosomaldominant nonsyndromic hereditary hearing loss (DFNA17) associated with cochleosaccular degeneration.49,50 The affected members of the DFNA17 family exhibit progressive, postlingual onset of hearing loss, a pattern that is observed in the majority of nonsyndromic autosomal-dominant HHL. The cosegregation of the mutant MYH9 with nonsyndromic hearing loss illustrates a biologically significant role for MYH9 in hearing and an organ-specific pathology associated with the mutant allele. Two other myosin genes have been predicted to have an important role in hearing. Myosin V is an abundant protein of afferent nerve fibers that innervate both inner and outer hair cells.51 Myosin Iß has been implicated as an effector of adaptation of the hair cell transduction apparatus.52 The diverse classes and subtypes of myosins whose dysfunction can result in hearing loss is not surprising given the varying forms of actin filament systems in the inner ear.53

MOLECULAR GENETICS OF VESTIBULAR SCHWANNOMAS AND GLOMUS TUMORS Neurofibromatosis Type 1 Neurofibromatosis 1 (NF1), also known as von Recklinghausen’s disease, is one of the most common Mendelian diseases that affects the nervous system. NF1 is characterized by autosomal-dominant inheritance with complete penetrance but extremely variable expression. The most common tumor

seen in NF1 is the neurofibroma and the second most common tumor is the optic pathway glioma. The diverse phenotype associated with NF1 is the consequence of mutations within a single gene located on chromosome 17q11.2, which was identified in 1990 through positional cloning and designated NF1.54–56 The gene spans 350 kilobases of genomic DNA, contains 60 exons, and encodes a large cytoplasmic protein product known as neurofibromin, a member of a family of proteins known for their GTPase activation.56 Mutations of NF1 have been identified throughout the gene. Most studies have not found an obvious relationship between particular NF1 mutations and resulting clinical manifestations in a patient. However, attempts at genotypephenotype correlation in NF1 are confounded by the effect of age, which increases the frequency of disease manifestations and the likelihood of serious complications in all patients. In addition, there is no consensus regarding how to define NF1 severity. While some mutations recur in different families, no true “hotspots” have been found in NF1. The most frequently recurring alteration is a nonsense mutation in exon 31 (R1947X), which accounts for 1% to 2% of NF1 mutations identified. The wide variability of the NF1 phenotype, even in individuals with the same NF1 gene mutation, suggests a contribution of other protein products in determining the clinical manifestations. Screening of individuals with a hereditary form of NF1 has linked them to the single NF1 locus at 17q11.2. This finding negates genetic heterogeneity of NF1 or mutations at more than one locus/gene responsible for the tumor phenotype. Due to absence of locus or genetic heterogeneity of NF1, frequency of mutant NF1 genes can directly be inferred from the incidence of the disease at birth, estimated to be 1 in 2500. Thus, the mutant gene frequency is approximately 1 in 5000, or half of the estimated prevalence of NF1 at birth. It is estimated that about half of all NF1 patients represent new mutations since a positive family history is confirmed in half of all NF1 cases and penetrance is presumed to be complete. Thus, the rate of new NF1 mutations is estimated to be as high as 1 per 10,000 gametes, representing one of the highest single-locus mutation rates known in humans. Interestingly, more than 80% of new mutations are considered to be of paternal origin. However, the predominance of paternal mutations in NF1 has not yielded a significant correlation between risk of sporadic NF1 and paternal age. The loss-of-function results suggest that neurofibromin acts as a tumor suppressor. The proposed tumor suppressor function is supported by the findings of somatic “second hit” mutations of the NF1 gene in benign and malignant tumors from NF1 patients carrying a germline mutation of the NF1 gene. Although, neurofibromin is expressed in number of neuronal cell types as well as in the gonadal tissue and the white blood cells, histopathologic and molecular analysis of the NF1-associated tumors has shown that the neoplastic cell of origin in the neurofibromas is the Schwann cell.57,58 The molecular factors that contribute to the loss of regulatory control in the Schwann cell with the mutant NF1 allele remain to be determined. The physiologic role of neurofibromin has been investigated though analysis of mouse models deficient in NF1 and drosophila NF1 mutants. These studies indicate that defects in neurofibromin function affect diverse signaling pathways in different cell types.59

Molecular Genetics in Neurotology

Neurofibromatosis Type 2 Neurofibromatosis 2 (NF2) is characterized by autosomaldominant inheritance that predisposes the carriers to nervous system tumors in their second and third decades of life. The hallmark central nervous system tumor in NF2 is the schwannoma, which affects the eighth cranial nerve and results in bilateral vestibular schwannoma (VS), also referred to as acoustic neuroma. Continued growth of the vestibular schwannomas leads to deafness and balance problems. In addition to the eighth cranial nerve, schwannomas can occur on other cranial or peripheral nerves throughout the body. Ninety percent of patients with NF2 also have ocular abnormalities, causing blurred or loss of vision. Patients with NF2 who have bilateral vestibular schwannomas represent 2% to 4% of all occurrences of vestibular schwannomas, which in turn represent approximately 8% of intracranial tumors. The majority of vestibular schwannomas are sporadic and unilateral, presenting in the fifth decade. The incidence of NF2 is estimated to be between 1:33,000 and 1:50,000,60 or approximately 10-fold less than the frequency of NF1. In approximately 50% of cases, there is no family history and these patients are considered to carry new germline mutations.61 The genetic differentiation of NF1 and NF2 as distinct disease entities did not occur until 1987. Molecular genetic analysis of these disorders localized the disease gene for NF1 near the proximal long arm of chromosome 17. At the same time, the gene responsible for NF2 was localized to chromosome 22.62 In 1993, the NF2 gene, designated merlin or schwannomin, was isolated by two groups working independently.63,64 The NF2 gene is spread over approximately 100 kB on chromosome 22q12.2 and contains 17 exons. The coding sequence of the messenger RNA is 1785 base pairs in length and encodes a protein of 595 amino acids. Comparative sequence analysis has led to classification of merlin as a member of the protein 4.1 subfamily, which includes ezrin, radixin, and moesin (ERM proteins). These proteins are involved in linking cytoskeletal components with the plasma membrane and are located in actin-rich surface projections such as microvilli. Like other ERM proteins, merlin binds to actin and is associated with actin cytoskeleton. However, a distinct role of merlin relative to the ERM proteins is emphasized by its unique subcellular distribution in the peripheral nerve Schwann cells. The NF2 gene has been hypothesized to function as a growth regulator or a tumor suppressor. Support for this role is derived from studies demonstrating germline mutations in the NF2 gene in patients with NF2 and biallelic inactivation of NF2 in NF2-associated tumors, including schwannomas, ependymomas, and meningiomas. Support for the tumor-suppressing role of NF2 is derived from in vitro studies that include the demonstration of growth suppression as a consequence of NF2 gene expression in merlin-deficient meningiomas and schwannoma cells. Expression of NF2 mutant allele encoding dysfunctional merlin had no effect on growth in these cell lines. The predilection for tumor growth in the superior vestibular branch of the eighth cranial nerve remains to be determined, as does its suppressing-suppressing role, which is expressed predominantly within the Schwann cells. Dissection of the potential mechanism of action of Merlin is also being

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addressed through development of transgenic mouse models. Mice homozygous for the NF2 null allele die during early embryonic development as a consequence of their inability to induce mesoderm formation.65 Mice that are heterozygous for the NF2 null allele are viable but develop malignant sarcomas, tumors that are not seen in humans affected with NF2. To be able to assess the biologic effect of the loss of merlin within the glial cells, a conditional knock-out was generated where merlin expression was specifically interrupted in the Schwann cells. These conditional knock-outs developed schwannomas that histologically resemble human schwannomas.66 Thus, the conditional knock-outs support the hypothesis that the loss of merlin is sufficient for the onset of schwannomas. To date more than 200 mutations of the NF2 gene have been identified, including single-base substitutions, insertions, and deletions. Most mutations lead to truncation of the C-terminal end of the protein as only 13 missense mutations have been identified. Ruttledge and colleagues67 have found that mutations in the NF2 gene that result in protein truncation are associated with a more severe clinical presentation of NF2 and missense and splice-site mutations are associated with a milder form of the disease.64 Similarly, Parry and colleagues68 have reported that retinal abnormalities were associated with the more disruptive protein truncation mutations of the NF2 gene.68 Both studies showed intrafamilial variability of phenotypic expression. The more severe phenotype in patients with mutations that result in protein truncation may be due to the dominant negative effect of the mutant protein, negating the biologic function of the protein product of the wild-type allele. Mutations involving the NF2 gene have also been observed in 22% to 59% of patients with sporadic vestibular schwannomas. Included in this group are individuals with de novo germline mutations as well as those with somatic mutations that are detected in the DNA of their tumor tissue. The large fraction of the sporadic cases of NF2 who are negative for NF2 mutation suggests a non-NF2 etiology. However, no evidence exists that substantiates or contests genetic homogeneity of NF2. To date, only mutation in the NF2 gene has been identified as the causal event in schwannoma formation. Defects of the NF2 gene have also been detected in other malignancies including meningiomas, malignant mesotheliomas, melanoma, and breast carcinoma. These findings suggest that the NF2 gene may also be the critical tumor suppressor in these sporadic tumors. The precise mechanism by which merlin regulates cellular proliferation within the cell types that are tumor-prone (i.e., Schwann cells) remains to be determined. The identification of the gene responsible for NF2 has significantly advanced our understanding of the molecular pathology as well as factors responsible for the clinical heterogeneity among patients with NF2. Understanding of the function of merlin may lead to the development of novel therapies that may eventually alleviate the suffering associated with NF2.

Familial Paragangliomas Paragangliomas (PGLs) are rare tumors of the paraganglia, an assembly of neuroendocrine tissues and small organs

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distributed throughout the body. The tumors are identified within two major sites, the carotid body of the head and neck and the adrenal medulla. The carotid body is the largest of all paraganglia and is considered to function as an oxygen sensor. Genetic analysis of hereditary paraganglioma has served to disclose its molecular etiology and provided an insight into its underlying pathophysiology. Currently, three genes have been identified whose mutant alleles have been pathogenically linked to hereditary paraganglioma. All of these genes encode distinct subunits of a hetero-oligomeric protein known as the mitochondrial complex II. This heteromeric protein consisting of four separate subunits is a component of the mitochondrial ETC and the Krebs cycle. Dysfunction of the mitochondrial complex II is considered to result in malfunction of the oxygen-sensory apparatus and thus activate the pathophysiologic pathway that leads to the development of paragangliomas. Identification of the disease genes and the protein that they encode has enabled us to address and understand some of the questions and paradoxes raised by genetic analysis of familial PGL. Genetic Mapping of the PGL Loci and Identification of the PGL1 Gene Unraveling the genetic basis of the hereditary PGL followed a well-established pathway for finding disease genes,69,70 which begins with the identification of affected families and determination of the mode of inheritance of the disorder. This is followed by two-point linkage analysis to localize the disease gene to a chromosomal locus. The resolution of the locus may vary from 1 to 12 centiMorgans in genetic distance or equivalent to 1 to 12 megabase pairs. Localization and resolution of the disease locus sets the stage for the end game. Identifying the disease gene within the linked locus can be the most challenging stage of the genetic study of the affected family. The difficulty of this task is demonstrated by the presence of several hundred genes that can potentially occupy the linked locus, many of which remain to be cloned and characterized. Further compounding the difficulty of the task is that the pathogenic sequence alteration can be as subtle as a single-base pair change within a gene whose sequence length can span several thousand nucleotides. A sequence alteration in the candidate gene affecting the coding sequence or splice signals can then be considered pathogenic if it is shown to cosegregate with or be inherited by the affected and not the unaffected in a family that is under study. Genetic linkage analysis of a large Dutch family with hereditary PGL mapped the disease locus to the short arm of chromosome 11, 11q22–q23 in 1991.18 This disease locus, designated PGL1, was further resolved to approximately 11 megabase region at 11q23.71 This finding was later confirmed in several North American families and the critical region was further resolved to a 2-megabase interval through the presence of informative individuals displaying a recombination event in the linked locus and the use of new polymorphic markers.72 Both the Dutch and the North American families that mapped to the PGL1 locus were shown to carry an identical haplotype, or set of markers, indicating that these apparently unrelated families likely carried an identical mutation that had occurred in a distant ancestor.

Following genetic mapping, the disease locus was then physically mapped to identify the set of genes present. Thus, the linked locus defined by genetic recombination events is isolated in overlapping large- and small-capacity cloning vectors. Physical mapping of the overlapping clones, or the contig, includes determining their size in base pairs and localization of various polymorphic markers such as short sequence repeat polymorphisms (SSRPs) and nonpolymorphic markers such as sequence tag sites (STSs), anonymous sequences that serve as landmarks and expressed sequence tags (ESTs), short sequences that are identified from cDNA libraries. The physical map facilitates subdivision of the contig and thus aids in the identification of candidate genes spanning the cloned region. This strategy of physically mapping the linked locus is also referred to as positional cloning.69 Physical mapping of the PGL1 identified a minimum of 10 distinct genes within the linked locus. Based on their physical locations, all of these genes are considered positional candidates for PGL1. Screening of all of these genes for a pathogenic mutation would have represented a monumental, labor-intensive task. A critical factor in hunting for disease genes is to determine which of the positional candidates might have a role in the etiology of the disease on the basis of function. Although intuitive, this principle is very difficult to apply since histopathologic analysis of the disorder does not by itself enable determination of the underlying molecular pathophysiology. Under these circumstances, the gene hunter must be highly resourceful in searching for parallel cases that may provide clues concerning the molecular etiology of the disease under study. Identification of the PGL1 gene represents an excellent illustration of this principal. Baysal and colleagues72 focused their search on a single candidate gene on the basis of an insight derived from study of the histopathology of the PGL and its similarity to carotid body tumors found in people living at high altitudes.73 In these tumors, the observed hyperplasia of the carotid body chemoreceptor cells was inferred to be the result of their sustained stimulation by chronic hypoxia. The observed link between hypoxic stress and carotid body tumors and the physiologic role of the carotid body in oxygen sensing led to the hypotheses that chronic stress upon the oxygen-sensory apparatus or a mutation in its molecular components causing its malfunction can both serve to trigger its hyperplasia. Supporting evidence for this hypothesis included enlargement of carotid body in rats exposed to hypoxic conditions.73 Thus, the 10 candidate genes were evaluated on basis of their potential role in oxygen sensing and signaling. The candidate gene selected encoded SDHD, a small subunit of cytochrome b in the mitochondrial complex II, one of the five protein assemblies or complexes that form the electron transport chain. Through its production of reactive oxygen molecules, the electron transport chain was considered to play a pivotal role in the signaling and detection of oxygen tension. The gene encoding SDHD consists of 4 exons and yields 159 amino acid polypeptides. Screening of the families with hereditary PGL identified various mutations of the SDHD gene that segregated with the disease.74 These mutations were subtle alterations of the gene sequence, affecting post-transcriptional processing of

Molecular Genetics in Neurotology

the transcript or the amino acid sequence of the primary polypeptide. None of the pathogenic sequence alterations were detected in more than 100 normal individuals. The predisposition of the PGL due to inheritance of a single mutant allele is consistent with the predicated role of the SDHD as a tumor-suppressor gene that is subjected to “two-hit inactivation.” The classification of PGL1 as a tumor suppressor was initially based on the observation that the genome of the tumor cells from affected individuals did not reveal the expected heterozygosity for a genetic marker at their PGL1 locus.75 This loss of heterozygosity (LOH) was inferred to be due to deletion or other mutational event within the normal allele that renders the cell either hemizygous (one deleterious allele and one deleted allele) or homozygous for the deleterious allele. The occurrence of somatic mutation leading to LOH can cause complete inactivation of SDHD within the cell type. This cell type carrying the two “hits” will no longer possess regulatory growth control due to loss of both alleles encoding SDHD as a consequence of germline and somatic mutations and will no longer behave normally. Thus, the “second hit” catapults the cell on the biologic pathway toward hyperplastic and neoplastic proliferation. The “two-hit” paradigm has also been used to explain the occurrence of certain sporadic tumors. Unlike the inherited predisposition to the tumors, the sporadic tumors are considered to be caused by two independent somatic mutations inactivating the two wild-type alleles of the tumor-suppressor genes. This proposed mechanism is consistent with the relatively rare occurrence of sporadic tumors and has been validated by genetic analysis of sporadic cases of NF1 and retinoblastoma.76,77 The sporadic occurrence of paragangliomas without family history is also observed. Genetic studies have yet to determine if mutation of the SDHD gene also accounts for sporadic cases of paragangliomas. PGL2, PGL3, and PGL4 Given that SDHD is a subunit of a the mitochondrial respiratory chain complex II, it was inferred that mutation in the other subunits can also cause dysfunction of the complex II and the onset of neoplasia. This hypothesis has been validated for two of the three subunits, SDHC and SDHB, through identification of mutations in their genes that are causally linked to hereditary PGL.78,79 SDHC located on chromosome 1q21 was found to be within the PGL3 locus that was mapped using a German PGL family. Mutation analysis of SDHC, consisting of six exons and yielding a polypeptide of 169 amino acids, identified the pathogenic sequence alteration in the affected German family. Unlike the mapping studies that were used for selecting SDHD and SDHC for mutation screening, mutations in SDHB, consisting of eight exons and yielding a polypeptide of 280 amino acids, were identified in small families in which linkage analysis was not possible due to their limited numbers. Linkage analysis in an extended Dutch family has also linked a distinct locus on chromosome 11q13 cosegregating with familial PGL.80 However, the responsible gene within this locus, designated PGL2, remains to be identified. Mutations of SDHB, SDHC, and SDHD linked to the head and neck tumors localized to the carotid body have

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also been associated with paragangliomas in the adrenal medulla, conventionally referred to as phaeochromocytomas.81,82 Although, they differ in their anatomic location, innervation, and specific function, both the paraganglia of the head and neck region and the adrenal medulla are linked by their common embryologic origin, their similar morphology, and their general role in responding to acute alterations in the surrounding environment. Thus, it is not surprising that specific mutations of SDHB and SDHD result in familial forms of head and neck paraganglioma as well as phaeochromocytoma.79 However, in general, mutations of these three subunits are linked with either the head and neck paraganglioma or the phaeochromocytoma. Pathogenic mutations have also been identified in SDHA. However, germline mutations in this subunit of complex II do not result in paragangliomas. The clinical phenotype characterized by mutations in SDHA result in optic atrophy, ataxia, myopathy, and Leigh syndrome.83 The dissimilar clinical phenotype suggests a distinct role for the SDHA subunit and its apparent separation from the task of oxygen sensing and signaling that is linked to SDHB, SDHC, and SDHD. The mechanism of this dichotomy remains to be determined. Identification of several of the genes underlying hereditary PGL has led investigators to assess their prevalence among both familial and sporadic cases of PGL in which the affected individuals have no family history of this tumor. These studies have been carried out using population samples in the United States84 and in the Netherlands.85 Germline mutations in SDHD, SDHB, and SDHC have been identified in the majority of patients with positive family history. Amongst these three candidate genes, mutations of SDHD are most common. Molecular epidemiologic studies of hereditary head and neck paragangliomas (HNPs) in the Dutch population has identified two common mutations of SDHD, D92Y and L139P. These are considered to be founder mutations; that is, the affected individuals who are positive for this mutation are linked through their common ancestry. In contrast to the Dutch population, the common SDHD mutation in the U.S. sample is P81L. However, this particular site is considered to be a mutational hotspot and hence not all individuals carrying P81L are considered to share common ancestry. The presence of SDHB mutations among the affected with positive family history is considerably lower than that of SDHD, accounting for up to 20% of the sample population. No mutations of SDHC were identified. Up to 30% of the familial HNP samples in the U.S. study were negative for mutations in the candidate genes. Contribution of noncomplex II genes, including the PGL2 gene, toward etiology of familial HNP represents a valid explanation for this outcome. In the absence of positive family history, the association of complex II gene mutations is significantly less. The Dutch study identified founder mutations of SDHD in the germline of 36% of the affected while the U.S. study identified germline mutations of SDHD or SDHB in 8% of nonfamilial samples. The presence of germline mutations of the complex II genes in the apparently sporadic PGL cases may be explained by variable penetrance or imprinting of the mutant allele or an occurrence of a de novo mutation. Both of these alternatives attempt to account for the

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absence of positive family history despite the presence of a germline mutations associated with familial PGL. These alternatives may be verified through genetic analysis of family members of the affected individual. Mutation screens of the candidate genes in the DNA from sporadic tumors did not detect mutated alleles of the complex II genes that were not present in the germline, thus eliminating the contribution of somatic mutation. Parent-Specific Transmission and Loss of Heterozygosity Hereditary PGL has generally been observed to follow the autosomal-dominant inheritance pattern. However, a variation on this pattern is observed for families with mutation in the SDHD. In these families, the disease phenotype is transmitted only through the fathers; the mothers do not transmit the disease.86 The sex-specific transmission pattern is an example of the phenomenon referred to as genomic imprinting. The mechanism of imprinting remains unknown but its effect is to silence the expression of the imprinted allele. The SDHD mutations have provided an excellent case study for assessing and deciphering the molecular basis of parent-specific gene expression pattern. Analysis of SDHD expression in various tissues has shown expression of both the maternal and the paternal alleles.74 These results argue against a widespread silencing of the maternal allele but do not exclude imprinting of SDHD limited to the paraganglionic tissue. The inference of maternal imprinting specifically within the paraganglion is at odds with the observation of preferential deletion of the maternal SDHD allele in the tumor DNA, as determined through LOH analysis.75 This leads one to question the mechanism of maternal imprinting that is put forward to explain the observed parent-specific (paternal) transmission of PGL. Thus, if the onset of tumor is believed to be initiated by inactivation of the normal allele through somatic mutation in accordance with the two-hit pattern of tumor initiation, then the mechanism is yet unknown by which the children of an affected mother carrying one mutant SDHD allele are refractory to developing tumors, since they already have one inactive copy in their germline. This paradox remains to be resolved. There is no evidence for parent-specific disease transmission in families with SDHC and SDHB mutations.

INTRACOCHLEAR TRANSGENE EXPRESSION AND ITS POTENTIAL THERAPEUTIC APPLICATION Concurrent with the enlarging list of deafness genes is a steady progress in the development of intracochlear gene transfer technology. The simple and powerful objective of this technology is to introduce a “therapeutic gene” (e.g., a normal version of the defective gene) into appropriate target cells of the affected individual. Expression of the exogenous therapeutic gene would then alter the target cell and the clinical phenotype. In the absence of effective conventional therapy for most types of hearing disorders

and the rapid advances in therapeutic applications of gene transfer in various diseases, including cancer, intracochlear gene therapy represents a promising treatment modality that is under development. Much of the experimental data to date addresses the utility of various gene transfer vectors for expression of marker genes within the cochlea and the vestibular end organs. These studies have demonstrated that the transgene can be expressed in the inner ear and that the transfer vector and the mode of its delivery represent the critical determinants of tissue or cell specificity and duration of the transgene expression.87 Despite the promising advances, much work remains to be carried out before application of intracochlear gene transfer can be clinically applied to specific forms of hearing loss.

Animals Models and Gene Transfer Vectors Preliminary studies in intracochlear gene transfer used the guinea pig as the animal model because of the relatively large size of its cochlea compared to mice and rat and the ease of surgical manipulation in this species. Subsequent studies have shifted their focus to using a mouse as the model organism. The mouse genome is the most extensively characterized of all mammalian model organisms. The intrinsic value of the mouse as a model organism in hearing research is the availability of a number of mutant mice with inherited hearing loss.88 These mutant mice have been well characterized and the genetic basis of their hearing loss identified. In addition, a number of transgenic mice have been generated to assess the effect of specific candidate genes whose mutant alleles have been linked to nonsyndromic and syndromic hearing loss.89 Both the mutant and the transgenic mice represent excellent animal models to assess the utility and efficacy of intracochlear gene therapy. Both viral and nonviral vectors have been used to transfer and express genes in the inner ear of animal models. A major advantage of nonviral vectors is the lack of immunogenic components. However, the nonviral vectors are still in a developmental state and in competition with viral vectors, which have the advantage of having developed through evolution. Thus, individual virions represent a highly efficient means of introducing the viral genome into the nuclei of target cells followed by the use of the cellular machinery to express the viral genes. These viral agents have been adapted for the purpose of gene transfer by altering their genome so that they can no longer replicate within the transduced cell and lead to cellular lysis. These replication-defective viruses are engineered to function solely to introduce the desired gene into the nuclei of target cells. Viral vectors have been developed from both DNA (e.g., adeno, adeno-associated, and herpes) and RNA (e.g., retro and influenza) viruses. Feasibility of intracochlear gene therapy was initially demonstrated through intracochlear transgene expression using the guinea pig as an animal model.90 A viral vector derived from the adeno-associated virus (AAV ) capable of transducing nondividing cells and considered to be safer than other viral vectors, in view of its nonimmunogenicity

Molecular Genetics in Neurotology

and nonpathogenicity, was used to deliver a marker transgene to the cochlea via steady-state infusion using an osmotic minipump. Based on expression of the marker transgene encoding a bacterial enzyme β-galactosidase, AAV vector was found to transduce the spiral limbus, spiral ligament, spiral ganglion, and the organ of Corti. The marker gene expression was shown to be present up to 24 weeks after osmotic minipump mediated infusion of the AAV-βgal.90 Subsequent studies investigating intracochlear gene transfer have characterized a variety of vectors for their efficacy and safety as well as their mode of introduction into the cochlea. The adenoviral (Ad) vector represents one of the wellcharacterized vectors used for intracochlear gene transfer. The attributes of adenoviral vector for gene transfer include its capacity to carry large transgenes (8 kB) and that it can be generated at high titer and can transduce both dividing and nondividing cells. However, the Ad vector has been reported to elicit a strong immune response, thus contravening its attributes.91 A lentiviral vector, based on the human immunodeficiency virus (HIV ), can integrate into the chromosome of both dividing and nondividing or mitotically quiescent cells, leading to a potentially stable, long-term expression of a transgene spliced into the viral vector. Thus, the postmitotic cochlear neuroepithelia and the spiral ganglion neurons represent suitable targets for a stable long-term transgene expression via lentivirusmediated gene transfer. Infusion of the lentiviral vector carrying a marker transgene into a guinea pig cochlea has revealed a highly restricted fluorescence pattern limited to the periphery of the perilymphatic space.92 Transduction of spiral ganglion neuron (SGN) and glial cells by lentivirus in vitro but not in vivo suggests limited dissemination of the viral vector from the perilymphatic space. Restricted transduction of cell types confined to the periphery of the perilymphatic space by the lentivirus is ideal for stable production of gene products secreted into the perilymph. In addition to viral vectors, cationic lipid vesicles, or liposomes, have also been used for intracochlear gene transfer. The liposomes coupled to the transgene integrated within a plasmic vector bind to the plasma membrane of the target cells, releasing the DNA into the cytoplasm, where it is eventually incorporated into the host genome. Liposome vectors are nonimmunogenic and easy to produce. Furthermore, the DNA introduced into the host cell is incorporated by recombination, so there is little risk of insertional mutagenesis. The drawback of liposome vectors

is a low transfection rate compared with other vectors. The feasibility of inner ear gene transfer with liposome vectors has been demonstrated by several in vivo studies.93 The attributes of the gene transfer vectors that have been used in intracochlear gene transfer are summarized in Table 5-3. These parameters provide a guide for assessing suitability of a given vector for a specific objective. Thus, if a transgene expression is required for a short period only, then an adeno-associated or adenoviral vector may be suitable. However, if sustained gene expression is required that replaces a nonfunctional mutant gene product, then a retroviral vector will be more suitable because the transgene carried by the retroviral vector will be stably integrated into the genome. The cochlear expression of the transgenes mediated by the transfer vectors described in Table 5-3 is summarized in Table 5-4. The different cell types and tissues transduced by these expression vectors likely reflect the unique property of individual transfer vectors, each being similarly introduced within the cochlear perilymph and carrying marker genes driven by strong viral promoters. The variability in the transgene expression pattern is likely a consequence of number of factors including the size of the viral particle, presence or absence of viral receptors, and mode of delivery. Inspection of the table allows some generalization about the ability of various viral vectors in transfecting cochlear tissues. The spiral ganglion cells, spiral ligament, and Reissner’s membrane were transfected by every virus tested. On the other hand, only adenovirus demonstrated transgene expression within the stria vascularis. Immune response was present in the cochlea following transfection with adenovirus, HSV, and Vaccinia virus.

Intracochlear Gene Delivery Modalities Local gene transfer to the inner ear is feasible because of its relatively closed anatomy. However, developing a delivery method for genetic vectors to the inner ear without causing local destruction and concomitant hearing loss is a significant obstacle. The general strategy behind these delivery modalities is to introduce the transgene-carrying vector into the inner ear circulation, enabling its diffusion to the surrounding tissues. Most of the delivery methods introduce the gene transfer into the perilymphatic circulation. These methods include microinjection via the round window membrane (RWM), microinjection or miniosmotic pump infusion following cochleostomy, and

TABLE 5-4. Transfection of Cochlear Cells and Tissues by Viral Vectors Vector AAV Adenovirus Herpes virus Vaccinia Lentivirus Liposomes

Hair Cells

Supporting Cells

Auditory Neurons

+ + − + − +

+ + + + − +

+ + + + +

139

Stria Vascularis − + − − − −

Reissner’s Membrane

Spiral Ligament

Immune Response

+ + + + + +

+ + + + + +

− + + + − −

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diffusion across the RWM after local Gelfoam placement. Gene transfer vectors have also been introduced into the endolymphatic circulation through injection into endolymphatic sac94 or into the scala media following cochleostomy.95 Introduction of viral vector via infusion with a miniosmotic pump was characterized by evidence of trauma at the basal turn adjacent to the cochleostomy associated with an inflammatory response and connective tissue deposition. Carvalho and colleagues96 demonstrated preservation of preoperative ABR thresholds in the lower frequencies (1 to 2 kHz), mild postoperative elevation of thresholds (<10 dB) in the mid frequencies (4 to 8 kHz), and marked rise (>30 dB) in ABR thresholds at higher frequencies (>16 kHz) after miniosmotic pump infusion via a cochleostomy.96 However, in general, cochleostomy has been shown to cause histopathologic alterations (including localized surgical trauma and inflammation) and may lead to hearing loss. A much less traumatic alteration to cochleostomy is the direct microinjection through the RWM without causing permanent hearing loss or tissue destruction. Histologically, cochleae microinjected through the round window demonstrated intact cochlear cytoarchitecture and an absence of inflammatory response 2 weeks after microinjection. Further, microinjection through the round window membrane did not cause permanent hearing dysfunction.97 To avoid hearing loss associated with the direct manipulation of the cochlea, gene transfer vectors have also been delivered through the vestibular apparatus via canalostomy.98 This delivery modality yielded transgene expression mainly in the perilymphatic space with the preservation of cochlear function. The potential for surgical trauma, inflammation, and hearing loss associated with these infusion or microinjection techniques has led to the investigation of a less invasive delivery method. Jero and colleagues99 investigated the potential to deliver a variety of vectors across an intact RWM by loading vectors onto a Gelfoam patch that was placed in the round window niche. Adenovirus and liposome vectors, but not the AAV vector, effectively infected inner ear tissues, as evidenced by detection of reporter genes. Thus, diffusion across the RWM has been shown to be an effective, atraumatic, but vector-dependent method of delivery for gene transfer vectors.99 An effective test of the delivery modality as well as the transfer vector will have to await the generation of a mouse model with inherited hearing loss that can potentially be corrected with the introduction of a normal gene.

Preclinical Applications The preclinical applications for gene transfer in the inner ear have focused on protective effects of various neurotrophins and growth factors against ototoxic agents, including noise, aging, and aminoglycoside-based antibiotics. These neurotrophins and growth factors, including brain-derived neurotrophic factor (BDNF), neutroophin-3 (NT3), and glial cell line–derived neurotrophic factor (GDNF), have been expressed within the cochlea as transgenic products and have served to protect sensory hair cells and the primary auditory neurons against atrophy and degeneration.

Staecker and colleagues100 used a herpes simplex virus-1 (HSV-1) vector to deliver BDNF to the inner ear and assessed its protective effect against neomycin. The gene therapy group demonstrated a 94.7% salvage rate for SGNs, in contrast to a 64.3% loss of SGNs in control animals (without the BDNF transgene). Interestingly, BDNF expression was ubiquitous in inner ear tissues, but this was not the case for the reporter gene, β-galactosidase. This reporter gene was detected in only 50% of the cells, thus identifying the cells specifically transduced by the HSV-1 vector. This transduction rate was sufficient to affect cochleawide BDNF distribution and ensure 95% SGN survival. The authors speculate that SGNs must require only a small number of BDNF-producing cells to ensure the survival of the entire ganglion.100 Lalwani and colleagues used both in vitro and in vivo models to test the protective effect of AAV-mediated BDNF expression.101 They found a significant survival rate of SGN in cochlear explants transduced with AAV-BDNF and challenged with aminoglycoside relative to controls. Although direct expression of transgenic BDNF could not be recorded, the vector’s ability to salvage SGNs was tested against a gradient of known BDNF concentrations applied directly to the cochlear explants. They found that the vector system was able to achieve the same protective effects as 0.1 ng/mL of BDNF. However, this protective effect is subtherapeutic, as the most efficient dose was determined to be 50 ng/mL, a concentration of BDNF that results in almost total SGN protection. In the in vivo experiment, animals infused with AAV-BDNF with an osmotic minipump displayed enhanced SGN survival. The protection from AAV-BDNF therapy was region-specific; there was protection at the basal turn of the cochlea but not at the middle or apical turn. The authors propose that this regional selectivity is a pharmacokinetic phenomenon.101 Neurotrophin-3-mediated protection against cisplatininduced ototoxicity has been documented using an HSV-1 derived viral vector. Chen and colleagues102 established that efficacy of the vector in an in vitro study, where HSV1-mediated transfer of NT-3 (demonstrated by production of NT-3 mRNA proteins and by reporter gene expression) conferred increased survival to cochlear explants after cisplatin exposure.102 Bowers and colleagues103 confirmed these effects in an in vivo model, where HSV-1-mediated transfer of NT-3 to SGNs suppressed cisplatin-induced apoptosis and necrosis. The authors suggest that these findings may not only be useful to prevent cisplatin-related injury, but may also provide preventive treatment for hearing degeneration due to normal aging.103 Several studies have established the efficacy of an Ad vector carrying the GDNF gene (Ad.GDNF) to protect against a variety of ototoxic insults. When administered prior to aminoglycoside challenge, Ad.GDNF significantly protects cochlear104 and vestibular105 hair cells from cell death. Pretreatment with Ad.GDNF also provides significant protection against noise-induced trauma.106 Finally, Ad.GDNF enhances SGN survival when administered 4 to 7 days after ototoxic deafening with aminoglycosides.107 The studies described here have assessed the therapeutic efficacy of gene transfer against chemically or physically induced ototoxicity in animal models. The results of these studies are promising as preventive countermeasures

Molecular Genetics in Neurotology

in preservation of spiral ganglion neurons following loss of sensory hair cells. In addition, these results provide proof of the principle of therapeutic efficacy of gene therapy. However, correction or amelioration of hearing dysfunction in mouse models with hereditary hearing loss through the use of gene transfer technology remains to be addressed. Replacement or correction of a defective gene underlying inherited hearing loss that results in a significant change in the animal’s ability to hear will represent a defining test for the therapeutic application of intracochlear gene therapy.

SUMMARY

Risks and Limitations

REFERENCES

Major risk factors associated with the introduction of a gene transfer vector into the inner ear are twofold: damage to the cochlear structure and function as a consequence of delivery modality and the relative safety of the gene transfer vector. Delivery modalities that prevent damage to the cochlear structure or function are described in the section Intracochlear Gene Delivery. The safety of the gene transfer agent is determined by assessing its immunogenicity and toxicity. Unwanted dissemination of the therapeutic agent outside the target region also represents a risk factor. Using AAV as the gene therapy vector, Lalwani and colleagues91 observed transgene expression within the contralateral cochlea of the AAV-perfused animal, albeit much weaker than within the directly perfused cochlea. Subsequently, Stover and colleagues demonstrated transgene expression in the contralateral cochlea using adenovirus.108 Expression of the transgene away from the intended target site (i.e., within the contralateral cochlea) raises concern about the risks associated with dissemination of the virus from the target tissue. The appearance of the virus distant from the site of infection may be due to its hematogenous dissemination to near and distant tissues. However, this is unlikely due to the absence of the viral vector in near and distant tissues.109 Other possible explanations include migration of AAV via the bone marrow space of the temporal bone or via the cerebrospinal fluid (CSF) space to the contralateral ear.109 The perilymphatic space into which the virus is perfused is directly connected to the CSF via the cochlear aqueduct; transgene expression within the contralateral cochlear aqueduct has been demonstrated following introduction of the viral vector in the ipsilateral cochlea. Collectively, these results suggest possible routes for AAV dissemination from the infused cochlea via the cochlear aqueduct or by extension through the temporal bone marrow spaces. Subsequent investigations have shown that dissemination outside the target cochlea can largely be eliminated by using microinjection or round window application of a vector and avoiding the infusion technique. Although transgene expression within the inner ear has been well established, several limitations of the gene transfer vector are evident. These include cell-target specificity of the gene transfer agent and the sustained or regulated expression of the transgene by the transduced cell. These concerns are currently being addressed through the development of vectors that carry cell-specific receptors and the use of promoters from genes with cell-specific and cell-selective expression.

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Identification of deafness genes and the determination of their prevalence in the human population have had a significant impact on diagnosis and treatment of HHL. Thus, it is critical to practicing otologists and neurotologists to understand the principles of molecular genetics so that they may selectively apply the appropriate diagnostic tests and therapeutic interventions and judiciously interpret their results.

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66. Giovannini M, Robanus-Maandag E, van der Valk M, et al: Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev 14:1617–1630, 2000. 67. Ruttledge MH, Andermann AA, Phelan CM, et al: Type of mutation in the neurofibromatosis type 2 gene NF2 frequently determines severity of disease. Am J Hum Genet 59:331–342, 1996. 68. Parry DM, MacCollin MM, Kaiser-Kupfer MI, et al: Germ-line mutations in the neurofibromatosis 2 gene: Correlations with disease severity and retinal abnormalities. Am J Hum Genet 59:529–539, 1996. 69. Collins FS: Identifying human disease genes by positional cloning. Harvey Lect 86:149–164, 1990. 70. Collins FS: Positional cloning moves from perditional to traditional. Nat Genet 9:347–350, 1995. 71. Heutink P, van Schothorst EM, van der Mey AG, et al: Further localization of the gene for hereditary paragangliomas and evidence for linkage in unrelated families. Eur J Hum Genet 2:148–158, 1994. 72. Baysal BE, van Schothorst EM, Farr JE, et al: Repositioning the hereditary paraganglioma critical region on chromosome band 11q23. Hum Genet 104:219–225, 1999. 73. Arias-Stella J, Valcarcel J: Chief cell hyperplasia in the human carotid body at high altitudes: Physiologic and pathologic significance. Hum Pathol 7:361–373, 1976. 74. Baysal BE, Ferrell RE, Willett-Brozick JE, et al: Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287:848–851, 2000. 75. van Schothorst EM, Beekman M, Torremans P, et al: Paragangliomas of the head and neck region show complete loss of heterozygosity at 11q22-q23 in chief cells and the flow-sorted DNA aneuploid fraction. Hum Pathol 29:1045–1049, 1998. 76. Li Y, Bollag G, Clark R, et al: Somatic mutations in the neurofibromatosis 1 gene in human tumors. Cell 69:275–281, 1992. 77. Serra E, Puig S, Otero D, et al: Confirmation of a double-hit model for the NF1 gene in benign neurofibromas. Am J Hum Genet 61:512–519, 1997. 78. Niemann S, Muller U: Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat Genet 26:268–270, 2000. 79. Astuti D, Latif F, Dallol A, et al: Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet 69:49–54, 2001. 80. Mariman EC, van Beersum SE, Cremers CW, et al: Analysis of a second family with hereditary non-chromaffin paragangliomas locates the underlying gene at the proximal region of chromosome 11q. Hum Genet 91:357–361, 1993. 81. Astuti D, Douglas F, Lennard TW, et al: Germline SDHD mutation in familial pheochromocytoma. Lancet 357:1181–1182, 2001. 82. Neumann HP, Bausch B, McWhinney SR, et al: Germ-line mutations in nonsyndromic phaeochromocytoma. N Engl J Med 346:1459–1466, 2002. 83. Ackrell BA: Cytopathies involving mitochondrial omlex II. Mol Aspects Med 23:369–384. 84. Baysal BE, Willett-Brozick JE, Lawrence EC, et al: Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. J Med Genet 39:178–183, 2002. 85. Dannenberg H, Dinjens WN, Abbou M, et al: Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma. Clin Cancer Res 8:2061–2066, 2002. 86. van der Mey AG, Maaswinkel-Mooy PD, Cornelisse CJ, et al: Genomic imprinting in hereditary glomus tumors: Evidence for new genetic theory. Lancet 2:1291–1294, 1989. 87. Lalwani AK, Jero J, Mhatre AN: Developments in cochlear gene therapy. Adv Otorhinolaryngol 61:28–33, 2002.

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88. Avraham KB: Mouse models for deafness: Lessons for the human inner ear and hearing loss. Ear Hear 24:332–341, 2003. 89. Anagnostopoulos AV: A compendium of mouse knockouts with inner ear defects. Trends Genet 18:499, 2002. 90. Lalwani AK, Walsh BJ, Reilly PG, et al: Development of in vivo gene therapy for hearing disorders: Introduction of adeno-associated virus into the cochlea of the guinea pig. Gene Ther 3:588–592, 1996. 91. Staecker H, Li D, O’Malley BW Jr, et al: Gene expression in the mammalian cochlea: A study of multiple vector systems. Acta Otolaryngol 121:157–163, 2001. 92. Han JJ, Mhatre AN, Wareing M, et al: Transgene expression in the guinea pig cochlea mediated by a lentivirus-derived gene transfer vector. Hum Gene Ther 10:1867–1873, 1999. 93. Wareing M, Mhatre AN, Pettis R, et al: Cationic liposome mediated transgene expression in the guinea pig cochlea. Hear Res 128:61–69, 1999. 94. Yamasoba T, Yagi M, Roessler BJ, et al: Inner ear transgene expression after adenoviral vector inoculation in the endolymphatic sac. Hum Gene Ther 10:769–774, 1999. 95. Ishimoto S, Kawamoto K, Kanzaki S, Raphael Y: Gene transfer into supporting cells of the organ of Corti. Hear Res 173:187–197, 2002. 96. Carvalho GJ, Lalwani AK: The effect of cochleostomy and intracochlear infusion on auditory brain stem response threshold in the guinea pig. Am J Otol 20:87–90, 1999. 97. Kho ST, Pettis RM, Mhatre AN, Lalwani AK: Cochlear microinjection and its effects upon auditory function in the guinea pig. Eur Arch Otorhinolaryngol 257(9):469–472, 2000. 98. Kawamoto K, Kanzaki S, Yagi M, et al: Gene-based therapy for inner ear disease. Noise Health 3:37–47, 2001. 99. Jero J, Mhatre AN, Tseng CJ, et al: Cochlear gene delivery through an intact round window membrane in mouse. Hum Gene Ther 12:539–548, 2001. 100. Staecker H, Gabaizadeh R, Federoff H, Van De Water TR: Brainderived neurotrophic factor gene therapy prevents spiral ganglion degeneration after hair cell loss. Otolaryngol Head Neck Surg 119:7–13, 1998. 101. Lalwani AK, Han JJ, Castelein CM, et al: In vitro and in vivo assessment of the ability of adeno-associated virus-brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult. Laryngoscope 112:1325–1334, 2002. 102. Chen X, Frisina RD, Bowers WJ, et al: HSV amplicon-mediated neurotrophin-3 expression protects murine spiral ganglion neurons from cisplatin-induced damage. Mol Ther 3:958–963, 2001. 103. Bowers WJ, Chen X, Guo H, et al: Neurotrophin-3 transduction attenuates cisplatin spiral ganglion neuron ototoxicity in the cochlea. Mol Ther 6:12–18, 2002. 104. Yagi M, Magal E, Sheng Z, et al: Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor. Hum Gene Ther 10:813–823, 1999. 105. Suzuki M, Yagi M, Brown JN, et al: Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity. Gene Ther 7:1046–1054, 2000. 106. Yamasoba T, Schacht J, Shoji F, Miller JM: Attenuation of cochlear damage from noise trauma by an iron chelator, a free radical scavenger and glial cell line-derived neurotrophic factor in vivo. Brain Res 815:317–325, 1999. 107. Yagi M, Kanzaki S, Kawamoto K, et al: Spiral ganglion neurons are protected from degeneration by GDNF gene therapy. J Assoc Res Otolaryngol 1:315–325, 2000. 108. Stover T, Yagi M, Raphael Y: Transduction of the contralateral ear after adenovirus-mediated cochlear gene transfer. Gene Ther 7:377–383, 2000. 109. Kho ST, Pettis RM, Mhatre AN, Lalwani AK: Safety of adenoassociated virus as cochlear gene transfer vector: analysis of distant spread beyond injected cochleae. Mol Ther 2:368–373, 2000.

Chapter

6 A. Julianna Gulya, MD, FACS

Pathologic Correlates in Neurotology Outline Vestibular Schwannomas (Acoustic Neuromas) Neurofibromatosis Meningiomas Glomus Tumors Metastatic Tumors Auditory Implants Pacchionian Bodies

I

mplicit in the title of this chapter is the concept that its scope does not encompass an in-depth examination of the pathology and biology of the myriad of disorders encountered in neurotologic practice. Such information should be sought in the chapters focusing on the particular pathologic process of interest. Instead, this chapter concentrates on the intradural pathologic correlates to neurotologic symptomatology, as well as the pathologic features of neurotologic entities that have implications in the medical and surgical treatment of the patient.

VESTIBULAR SCHWANNOMAS (ACOUSTIC NEUROMAS) Vestibular schwannomas give rise to symptoms such as sensorineural hearing loss (SNHL), tinnitus, disequilibrium, and other neurologic symptomatology through the direct effects of the tumor, namely, compression and destruction of neural structures,1–3 as well as by indirect effects. Studies of the pathology of the vestibular schwannoma can be divided into two groups: those that use the tumor or nerve specimen obtained at the time of surgery and those that make use of the temporal bone specimens harvested at the time of the patient’s death. Tumor-nerve specimens obtained at the time of surgery allow for electron microscopic and immunohistochemical studies, which in turn facilitate the analysis of the tumor-nerve interface with respect to both the cochlear and vestibular nerves, as well as analysis of neural integrity. Neely and colleagues4–6 have presented detailed studies of three small vestibular schwannomas completely resected by the translabyrinthine approach. Considering nerve VIII as a unit, they4 identified two types of tumor interface simultaneously coexisting in the same tumor at different locations; the first constituted a distinct separation of the tumor and the nerve, whereas the other was described as a 144

Facial Nerve Patterns of Degeneration Internal Carotid Artery Serpentine Aneurysms Vascular Loops Dural Arteriovenous Malformations Jugular Bulb

direct cellular continuity of the two, without any intervening capsule or margin. Even immunohistochemical studies7,8 have been unable to discern a distinct tumor-nerve interface in some instances. In subsequent studies, Neely and Hough5 focused on cochlear nerve involvement with small schwannomas. In the evaluation of a superior vestibular nerve schwannoma, a separation of the tumor from the cochlear nerve was maintained throughout its length. With schwannomas of inferior vestibular nerve origin, however, Neely and Hough5 found that the cochlear nerve, initially separate from the tumor, rotated about and progressively became more tightly applied to and incorporated within the tumor as evaluation progressed laterally. Cochlear nerve fiber incorporation progressed, with loss of expected fiber orientation, until no identifiable cochlear nerve fiber aggregates remained. Paradoxically, the superior vestibular nerve schwannoma, which had the greater number of cochlear nerve fibers, was associated with poorer hearing than the inferior vestibular nerve schwannoma. Ylikoski and associates,9 based on a similar study encompassing larger, predominantly inferior vestibular nervederived tumors, described three stages of tumor growth (Fig. 6-1). In stage I, the tumor only invades its nerve of origin and displaces the facial nerve and the remainder of the eighth cranial nerve. In the second stage, the tumor invades the adjacent cochlear nerve and compresses both the superior vestibular nerve and the facial nerve, while the third stage involves tumor invasion of all components of the eighth cranial nerve and extensive compression of the facial nerve. They10 also found a gradual transition from tumor to cochlear nerve, with no correlation between the number of preserved fibers and auditory function as measured by standard clinical audiologic techniques. Because auditory function fails to reflect the remaining cochlear nerve fiber population,11 it has been suggested that a cochlear nerve “conduction block” exists, stemming

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Figure 6-1. A, Internal auditory canal relationships of an inferior vestibular nerve schwannoma at stage I. All nerves remain discretely identifiable, although there may be some displacement of the superior vestibular nerve and the cochlear nerve. B, In stage II, the inferior vestibular nerve schwannoma has invaded the cochlear nerve. Both the cochlear and superior vestibular nerves are flattened, but the facial nerve remains intact. C, In stage III, the entirety of the eighth cranial nerve is involved with tumor. The facial nerve is flattened but not invaded. T, Transverse crest; SV, superior vestibular nerve; IV, inferior vestibular nerve; C, cochlear nerve; F, facial nerve. (From Ylikoski J, et al: Eighth nerve in acoustic neuromas, special reference to superior vestibular nerve function and histopathology. Arch Otolaryngol 104:532–537, 1978. Copyright 1978, American Medical Association.)

from a tumor pressure effect.10 Ylikoski12 and Neely and Hough6 have presented histologic evidence supportive of the conduction block idea with the demonstration of “onion bulbs”—concentric layers of Schwann cell processes among which are interspersed an increased number of collagen fibers. The onion bulbs are thought to result from repetitive demyelination and remyelination, and are manifested in a marked decrease in the conduction velocity of the affected fiber. These pathologic correlates have at least theoretic implications in the concept of total tumor removal with attempt at hearing preservation. First, the degree of cochlear nerve involvement with the tumor is not reflected by auditory function, although the auditory brainstem response (ABR)13 may be able to prognosticate to some extent the likelihood of successful hearing preservation. Second, the lack of a clear interface between cochlear nerve and tumor implies that in some proportion of cases, tumor inevitably will be left behind in the hearing preservation attempt.14 One factor playing a role in the lack of a clear interface between the cochlear nerve and the vestibular schwannoma may relate to the infiltrative tendency of the vestibular schwannoma, but it may also derive from the fact that in 25% of normal eighth nerves15 no cleavage plane is evident between the cochlear and vestibular components in the cerebellopontine angle, with vestibular fibers imperceptibly blending into the substance of the cochlear component.16 Practically speaking, such microscopic remnants do not inevitably give rise to tumor recurrences,17–19 but they do, particularly in the younger patient, represent a source of concern. Clearly, restricting histologic evaluation to merely the internal auditory canal (IAC) components disregards consideration of the effect of various end organ changes evidenced in the temporal bones of individuals with vestibular schwannomas. Although direct invasion of 20–23 and

origin from24–26 labyrinthine structures are not rare occurrences, vascular, biochemical, and perhaps viscosity changes indirectly stemming from a vestibular schwannoma appear to be more important in peripheral dysfunction. DeMoura and associates21,27 conducted detailed clinicopathologic studies of 11 vestibular schwannomas. Loss of cochlear neurons most severe in the basal turn was the most frequently observed finding; basal hair cell loss also was seen but to a lesser degree. Cochlear neuronal loss out of proportion to hair cell loss manifests with loss of speech discrimination out of proportion to pure tone thresholds in neural presbycusis28 and perhaps in vestibular schwannomas as well. Suga and Lindsay22 reviewed the temporal bone pathology of three cases of vestibular schwannoma with a particular interest in validating the concept that impairment of blood supply to the inner ear was the cause of the manifested alterations. In the animal model, Perlman and associates29 showed that temporary occlusion of the labyrinthine artery was associated with a predominant loss of cochlear neurons, atrophy of the spiral ligament, variable hair cell loss in the organ of Corti, and little effect on the tectorial membrane. In contrast, permanent obstruction of the labyrinthine artery30 precipitated a cascade of events, from hair cell changes and supporting structure degeneration to the end stages of fibrosis and ossification. Venous obstruction (vein at the cochlear aqueduct)31 results in scattered hemorrhages, progressive outer hair cell loss, severe strial atrophy, mild spiral ligament atrophy, and no tectorial membrane alterations. Since the main venous drainage of the human inner ear is by the vein of the cochlear aqueduct and the vein of the vestibular aqueduct, and the arterial supply is provided by the arteries in the IAC, notably the labyrinthine artery, Suga and Lindsay22 reasoned that vestibular schwannomas should disrupt

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arterial supply to the inner ear to a greater extent than venous drainage; moreover, the obstruction should be chronic and partial. Using the nontumor ear as a reference, they22 attributed degeneration of nerve fibers, ganglion cells, the stria vascularis, and the tectorial membrane; fibrosis and ossification of a semicircular canal; and relatively good preservation of sensory cells seen in the tumor to the presence of the vestibular schwannoma. They22 believed that their constellation of findings, particularly the good preservation of sensory cells in the presence of extensive degeneration of the nerve fibers, ganglion cells, and stria, reflected partial vascular obstruction of the IAC blood supply by the vestibular schwannoma. Johnsson and colleagues32 used the surface preparation method to study the putative vascular alterations related to a vestibular schwannoma by comparing the normal and tumor-associated inner ears. Although they found fewer red blood cells in the vessels of the tumor-affected ear than the normal ear, an observation confounded by the patient’s death some 2 weeks after surgery for tumor removal, they did not find any excessive capillary atrophy or devascularization, as they had noted in association with presbycusis. Thus the role of ischemia in precipitating end-organ dysfunction remains debatable. Changes in the biochemistry of the inner ear may underlie some of the peripheral manifestations of the vestibular schwannoma. Eosinophilic staining of inner fluids reflects their increased protein content,3,21,33 which may be 5 to 15 times normal.34 Using immunoelectrophoresis, immunodiffusion, and disc electrophoresis, Silverstein34 and Palva and associates35 found that the increased protein levels in perilymph represent an accumulation of blood serum proteins and not those from cerebrospinal fluid (CSF). Schuknecht3 proposed that “biochemical alterations in the inner ear fluids are responsible, in part at least, for the hearing losses showing flat audiometric patterns and loudness recruitment” (similar to metabolic presbycusis). Johnsson and associates32 theorized that the increased protein content of the inner ear fluids leads to an increase in their viscosity and hence cochlear dysfunction based on altered hydrodynamics. No concrete evidence supporting either of these theories can be found, yet how rapidly such abnormalities are corrected, if ever, subsequent to tumor treatment would seem of practical importance in the maintenance or improvement of hearing. Hearing loss is a frequent occurrence after tumor removal, even in the majority of instances in which preservation is attempted. Vascular disruption, spasm, and frank injury to the cochlear nerve are most commonly implicated, but the idea of a “conduction block” is perhaps worthy of consideration as well. Sekiya and Møller36 used the canine model to study the effect of surgical manipulations (e.g., retraction), thought to be analogous to those performed in acoustic recess tumor removal, on the cochlear nerve. Light and electron microscopic studies were correlated to alterations in the recorded compound action potential (CAP). With reversible changes in the CAP, such as latency, they found microhemorrhages within the cochlear nerve; abrupt amplitude decrease in the CAP was associated with near avulsion of the Obersteiner-Redlich (OR) zone (the glial-Schwann cell sheath junction).36 The OR zone in particular seems to be

prone to injury, even if distant from the area of compression by retraction, and Sekiya and Møller36 believe the transition from the fragile glia of the central portion to the collagen-reinforced Schwann sheath of the peripheral portion of the cochlear nerve, in combination with the significantly greater vascularity of the peripheral portion, explains the predilection of this region for injury. Kveton and associates37 suggest that the spontaneous improvement in hearing experienced by four patients several months after suboccipital/transmeatal acoustic neuroma removal may be due to a reversible nerve conduction block phenomenon at the OR zone. Alternatively, Fukaya and associates38 concluded that “occlusion of perforating arteries . . . caused lateral brain stem infarction around the entry zone of nerves VII and VIII,” which triggered the transient, low-frequency (retrocochlear) SNHL they found in 14 of nearly 1000 patients undergoing microvascular decompression for hemifacial spasm. They38 based their conclusion on (1) the association of Horner’s syndrome or bulbar palsy in more than one-third of the patients with low-frequency SNHL, (2) audiometric findings, especially ABR and electrocochleographic (ECoG), suggestive of brainstem pathology, and (3) surgical records uniformly describing “extremely short perforating arteries surrounding the entry zone of nerves VII and VIII, so that they had to be stretched during surgery.” No pathologic study has been provided, but the observation seems to have some relevance to acoustic recess surgery in general.

NEUROFIBROMATOSIS Cytologically, the vestibular schwannomas of neurofibromatosis type 2 (NF2) are indistinguishable from unilateral schwannomas, but histopathologically there are some differences. The schwannomas seen in NF2 generally (1) are larger and more often multicentric; (2) are more frequently multilobular39; (3) more often infiltrate, rather than splay, the facial and cochlear nerves39,40,41 (Fig. 6-2); (4) are associated with more extensive bony erosion and enlargement of the IAC; and (5) tend to invade temporal bone air cells and marrow spaces.1,2,42 Such characteristics can render hearing conservation attempts more problematic. In addition, as emphasized by Linthicum and Brackmann,43 the multicentricity of the vestibular schwannomas of NF2, for example, simultaneous intracochlear or intralabyrinthine schwannomas distinct from the IAC tumor, may foil even the most skilled surgeon’s attempts at complete tumor removal, at least when the surgeon is using the standard translabyrinthine approach. Widening of the IACs, asymmetrical or symmetrical, usually betrays the presence of vestibular schwannomas. Rarely, however, in neurofibromatosis patients at least, ectasia of the dural sheath of the IAC may mimic a vestibular schwannoma both in terms of symptomatology and the finding of uni- or bilateral widening of the IACs.44–46 Pantopaque,45,46 air,44 and metrizamide44 cisternography have been used in the past to ascertain the absence of tumor, confirmed by several-year imaging follow-ups; now gadolinium-enhanced magnetic resonance imaging (MRI) is recommended for optimal evaluation.

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A

A

F

B Figure 6-5. A, This vertical section through the labyrinth shows meningioma tissue invading the fallopian canal (arrow). B, At a higher magnification, the meningioma can be seen abutting the facial nerve (F ). (From Nager GT, Heroy J, Hoeplinger M: Meningiomas invading the temporal bone with extension to the neck. Am J Otolaryngology 4:297–324, 1983.)

producing progressive hearing loss, headache, vertigo, tinnitus, otalgia, and facial paresis.47 Recurrent otitis media with otorrhea and the development of granulation tissue may be seen. In addition, the jugular foramen syndrome (usually Vernet’s) as well as cerebellar and brainstem involvement can be seen.47,51 The diagnosis of meningioma must be considered when dealing with a temporal bone, parapharyngeal space, or jugular foramen lesion. The rarity of the primary, purely intratympanic meningioma51 demands thorough imaging evaluation for an intracranial component. The difficulty in discerning normal from meningioma tissue requires wide surgical margins47,50; for example, as cited by Maniglia,51 if the site of dural attachment is coagulated rather than excised, the recurrence rate of intracranial tumor after removal is 19%. The need for long-term follow-up after apparent excision, commensurate with the slow growth rate of meningiomas, is evident.47 Recurrent symptomatology alone should not serve as the indicator for follow-up imaging; as reported by Leonetti and colleagues,52 of

B Figure 6-6. A, A meningioma has densely infiltrated the petrous apex, as seen in this vertical section (C ). B, Infiltration of the carotid canal with some compression of the internal carotid artery (arrow). (From Nager GT, Heroy J, Hoeplinger M: Meningiomas invading the temporal bone with extension to the neck. Am J Otolaryngology 4:297–324, 1983.)

55 sphenoid wing/parasellar meningiomas that were excised and recurred, one-third had no new symptoms referable to the recurrence and 42% had no new physical findings.

GLOMUS TUMORS The heritage of the chief cell of the paraganglioma and its implications in the biologic behavior of these tumors is reviewed elsewhere in this text; this section concentrates on the patterns of growth and extension of jugulotympanic and vagale tumors, which are relevant to the planning of surgical extirpation. Reminiscent of meningiomas, paragangliomas tend to expand within and traverse the temporal bone by means of preformed pathways that offer minimal resistance.53–55 The pneumatized air cell tracts of the temporal bone are the most important route of spread; for instance, by means of the peritubal air cells, glomus tumors can invade the petrous apex and involve the internal carotid artery, clivus, dorsum sella, and sphenoid sinus.53 Extension along the facial nerve can occur in the fallopian canal.53 The eustachian tube can

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TABLE 6-1. Classification of Neural Invasion by Jugulotympanic Paragangliomas Grade I Grade II Grade III Grade IV

Tumor is no closer than 1 mm to the perineurium Tumor is less than 1 mm from perineurium and involves epineurium Tumor infiltrates perineurium Tumor involves endoneurium

From Makek M, et al: Neural infiltration of glomus temporale tumors. Am J Otol 11:1–5, 1990.

A

B Figure 6-7. A, This vertical section through the skull base in the region of the jugular foramen shows extensive infiltration by a meningioma. C, Internal carotid artery; X, vagus nerve; J, jugular bulb. B, The meningioma encroaches on the vagus nerve (X ). (From Nager GT, Heroy J, Hoeplinger M: Meningiomas invading the temporal bone with extension to the neck. Am J Otolaryngology 4:297–324, 1983.)

serve as a conduit beyond the temporal bone to the nasopharynx.53 The lumens of the internal jugular vein and sigmoid sinus are likewise avenues for tumor extension beyond the temporal bone, extraordinarily as far as the atria.56 Spector and associates 57 warn that extension into the sigmoid sinus is evidence for posterior fossa involvement. The carotid sheath lends access to the neck, and the various foramina and sutures of the skull base also allow for tumor expansion with neural compression, especially the lower cranial nerves, and the hallmark erosion of the caroticojugular crest. Perforation of the tympanic membrane permits extension along the external auditory canal. The tumors tend to expand through multiple pathways simultaneously.53,57 Invasion of the labyrinth may occur along the nerves of the IAC.53,54 Paragangliomas tend to ramify within the bony labyrinth before causing complete bony destruction58; labyrinthine ossification is believed to reflect interference with the vascular supply of the end organs by the tumor.53 The ossicular chain, even with extensive tumor53 or with primary tympanicum tumors,59 remains relatively unscathed. Makek and colleagues60 have published a unique study of neural infiltration by jugulotympanic paragangliomas.

Of 83 cases scrutinized, 66 had some degree of cranial nerve infiltration involving, in descending order of frequency, the vagus, facial, spinal accessory, glossopharyngeal, and hypoglossal nerves. The mastoid segment was the most common area of involvement of the facial nerve. Preoperative physical findings of, and intraoperative confirmation of, neural infiltration were found with tumors of at least a C2 (Fisch classification) magnitude. Physical findings did not predict neural involvement reliably. Histopathologic examination permitted the creation of a classification system (Table 6-1) of the neural infiltration by paragangliomas following a sequence of the tumor approaching the nerve, contacting the epineurium, invading the perineurium along the perivascular spaces of the neural capillary supply (Fig. 6-8), and penetrating the endoneurium (Fig. 6-9). With grade I and grade II invasion, it is possible to dissect tumor away, leaving behind intact nerve; however, grade III and grade IV invasion require segmental nerve resection.60 Intracranial extension, according to Spector and colleagues,57 is most likely to occur within two “dangerous triangles”: the hypotympanic and the protympanic (Fig. 6-10). The hypotympanic triangle is delimited by the inferior petrosal sinus, the sigmoid sinus, and the internal jugular vein. Extension from the hypotympanic triangle may occur intraluminally in the great veins of the triangle, extraluminally along the carotid sheath into the neck, or along the cranial nerves at the base of the skull. The protympanic triangle is determined by the eustachian tube opening, the tensor tympani tendon, and the zygomatic root cells. Further growth may then progress along the

Figure 6-8. Paraganglioma contacts the perineurium of the facial nerve (stage II invasion). (From Makek M, et al: Neural infiltration of glomus temporale tumors, Am J Otol 11[1]:1–5, 1990.)

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Secondary involvement of the temporal bone by malignant processes is a problem of increasing magnitude, relating to improved chemotherapeutic regimens that allow for longer survival and the development of intracranial extension, as

well as the relative impenetrability of the CNS to many chemotherapeutic agents.62,63 Clinical recognition of metastatic temporal bone involvement in all probability lags the true incidence both because of the paucity of evoked symptoms63 and the rarity with which the temporal bone is surveyed as a matter of routine in patients with possible metastatic disease.64 In general, the distribution of temporal bone involvement depends on its avenue of access to the temporal bone.63 Modes of dissemination to the temporal bone include the following: hematogenous from a distant primary (carcinoma or sarcoma) or leukemia/lymphoma; direct extension from a primary extracranial tumor, for example, pharyngeal cancer; direct extension from a primary intracranial tumor, as discussed with meningiomas; and leptomeningeal spread, both by distant and intracranial primary tumors. Metastatic tumors most commonly gain access to the temporal bone by hematogenous spread.64 Breast, lung, kidney, prostate, and stomach carcinoma, in descending order of frequency, have been reported as metastasizing to the temporal bone.63 Deposition of tumor cells occurs predominantly in the petrous marrow (Fig. 6-11); the sluggish flow in the sinusoidal capillaries promotes filtering of the tumor cells from the circulation.64,65 Involvement of the petrous apex can be found nearly uniformly.63 Metastatic deposition within the air cell spaces of the temporal bone is also quite common and leads to tympanic cavity and facial nerve involvement.62 Invasion of the otic capsule is uncommon, reflecting its resistance to neoplastic invasion.64 Lymphomas and leukemias infiltrate the petrous apex almost without exception, subsequently following the submucosal plane of the mastoid air cells, the ossicles, the middle ear muscles and tendons, the eustachian tube, the IAC, and the subcutaneous tissues of the external auditory canal.62,66 Regional, extracranial neoplasms, most commonly pharyngeal carcinoma, extend directly into the temporal bone

Figure 6-10. The protympanic and hypotympanic triangles allow for central extension of paraganglioma. (From Spector GJ, et al: Panel discussion: Glomus jugulare tumors of the temporal bone. Patterns of invasion in the temporal bone. Laryngoscope 89:1628–1639, 1979.)

Figure 6-11. Breast adenocarcinoma metastatic to the right temporal bone. Tumor (arrows) occupies the petrous apex and the internal auditory canal, with partial destruction of the cochlear, vestibular, and facial nerves. Clinically, the patient had sudden right facial paresis, hearing loss, and vertigo, and examination documented a right profound SNHL and a right absent vestibular response. (Reprinted by permission of the publishers from Schuknecht HF: Pathology of the Ear. Cambridge, MA, Harvard University Press, Copyright © 1974 by the President and Fellows of Harvard College.)

Figure 6-9. Stage IV invasion: paraganglioma tissue involves the endoneurium of the facial nerve. (From Makek M, et al: Neural infiltration of glomus temporale tumors, Am J Otol 11[1]:1–5, 1990.)

lumen of the eustachian tube to the nasopharynx, within air cell tracts to the petrous apex, or along the IAC into the middle cranial fossa. Kinney61 found that intracranial extension most commonly involves the posterior cranial fossa, inferior and medial to the IAC. In a fashion similar to that occurring in meningiomas, paragangliomas extend predominantly along preformed pathways, and their complete extirpation mandates thorough preoperative imaging evaluation and wide-field exposure.

METASTATIC TUMORS

Pathologic Correlates in Neurotology

by many of the same preformed pathways discussed previously, particularly the eustachian tube, the carotid canal, the foramen lacerum, the foramen ovale, and the jugular foramen.63,64 Similarly, malignant intracranial tumors may secondarily involve the temporal bone by routes described in the discussion of meningiomas, paragangliomas, and vestibular schwannomas. Leptomeningeal extension, in which the malignant tumor cells diffusely proliferate in a lamellar manner along the pia-arachnoid of the brain and spinal cord, may develop both with distant primary neoplasms and primary intracranial tumors, especially medulloblastomas.62 Bilateral IAC invasion with disruption of the facial and cochleovestibular nerves is characteristic and may lead to transgression of the cribrose areas and membranous labyrinth.62 Symptomatic manifestations of metastatic temporal bone disease are conspicuous by their absence; Nelson and Hinojosa63 found that of 33 patients with metastatic temporal bone involvement, nearly 60% were asymptomatic, and that “diffuse metastases . . . were present in all cases . . . when the petrous apex was involved by the hematogenous route.” It is self-evident then that metastatic temporal bone invasion is a late development in the course of the disease, and that the diagnosis of the underlying primary tumor or metastatic disease will have been previously established.63 Schuknecht and associates64 emphasized hearing loss as a common early manifestation of hematogenous or directly extending metastatic tumors of the temporal bone, with conductive hearing loss reflecting eustachian tube dysfunction and secondary serous otitis media (Fig. 6-12); less frequently, ossicular destruction, mucosal invasion, and tympanic membrane infiltration precipitated the conductive hearing loss. SNHL is a manifestation of cochlear nerve compression or destruction, or cochlear invasion along the IAC. Rapidly progressive uni- or bilateral SNHL, especially if associated with uni- or bilateral facial paresis, vertigo, and widespread neurologic signs, is

Figure 6-12. A chondromyxosarcoma (C ) has destroyed the right petrous apex and has compressed and occluded both the internal carotid artery and the eustachian tube. Clinically, the patient experienced right serous otitis media and left hemiparesis. (Reprinted by permission of the publishers from Schuknecht HF: Pathology of the Ear. Cambridge, MA, Harvard University Press, Copyright 1974 by the President and Fellows of Harvard College.)

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suggestive of leptomeningeal temporal bone involvement; lumbar puncture is particularly helpful in establishing the diagnosis.62,67 Facial paralysis may be caused by metastatic tumor infiltrating and destroying the facial nerve,62,64 but may also reflect compression by tumor nodules.3 Chloromas are localized, green masses of leukemic cells, associated particularly with acute myeloblastic leukemia. Shanbrom and Finch68 have cited data indicating that of those patients with chloromas, approximately half will have temporal bone involvement. Leukemic infiltrations in general may precipitate recurrent otitis and acute symptomatology related to hemorrhage.62,68 Chloromas have been associated with compressive effects on both the facial and cochleovestibular nerves, tympanomastoiditis, otalgia, hearing loss, and vertigo. In general, the diagnosis of temporal bone metastasis is based on clinical suspicion confirmed by appropriate diagnostic imaging. Temporal bone biopsy may be helpful, although the metastatic lesions are often less well differentiated than the primary tumor, foiling attempts to determine the probable site of the primary.64

AUDITORY IMPLANTS Labyrinthitis ossificans (LO) and alterations in the cochlear nuclei are pathologic findings with relevance to neurotology, particularly in the consideration of cochlear implantation or auditory brainstem implant (ABI) placement. Suga and Lindsay69 defined LO as replacement of the fluid spaces of the inner ear by fibrous tissue and new bone. LO may develop as a consequence of severe inflammation, trauma, or vascular compromise of the inner ear.69–71 Specific entities associated with LO include labyrinthitis (bacterial or viral, tympanogenic or meningogenic), faradvanced otosclerosis, autoimmune inner ear disease, labyrinthine artery occlusion, and leukemia.70 The details of the rate of progression of LO are unknown,70 although Novak and associates72 suggest, on the basis of serial temporal bone computerized tomography (CT) scans, that intracochlear osteoneogenesis begins within the first 4 to 8 weeks following the acute phase of meningitis. Irrespective of cause, the basal scala tympani (Fig. 6-13) is the most likely site for cochlear LO; despite this relatively consistent finding, differing patterns of cochlear involvement with LO have been associated with different causes.70 Meningogenic labyrinthitis appears to be the most common cause of LO.70 In one series of children profoundly deafened by meningogenic labyrinthitis who subsequently underwent cochlear implantation,73 80% had some degree of cochlear ossification noted at the time of surgery. In 3 of 24 cases studied, Green and associates70 found ossification of the middle and apical cochlear turns which exceeded that found in the basal turn (Fig. 6-14). They hypothesized that the distribution of ossification reflected the spread of infection along the cochlear aqueduct and modiolus.70 Tympanogenic labyrinthitis tends to provoke new bone formation only in the scala tympani near the round window membrane, consistent with the round window membrane allowing inner ear access to a middle ear infection.70

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Figure 6-13. This cochlea shows new bone formation in the basal scalae of a gentleman who was profoundly deaf from meningitis (presumably meningococcal). (Reprinted by permission of the publishers from Schuknecht HF: Pathology of the Ear. Cambridge, MA, Harvard University Press, Copyright © 1974 by the President and Fellows of Harvard College.)

The cochlear ossification of otosclerosis characteristically is restricted to the basal-most 6 mm of the scala tympani.70 In general, total obliteration of the cochlear fluid spaces with new bone is rare (Fig. 6-15) and can be seen with both meningogenic and tympanogenic labyrinthitis.70 In addition, scala tympani occlusion with new bone tends to precede ossification of the scala vestibuli, and the scala media and vestibule are ossified only in the most severe cases.70 The predilection for ossification of the basal scala tympani after labyrinthitis mandates that the cochlear implant surgeon be prepared to perform the required cochlear “drill out.” The excessive LO of the middle and apical turns may explain the occasional inability to pass entirely a long intracochlear electrode.70 Because the scala vestibuli seem to be less affected by the ravages of LO, Steenerson and associates74 have proposed, and have apparently successively performed, insertion of the

Figure 6-14. Labyrinthitis ossificans predominantly in the apical portion of this cochlea of a patient who was profoundly deafened by meningitis (probably meningococcal). (Reprinted by permission of the publishers from Schuknecht HF: Pathology of the Ear. Cambridge, MA, Harvard University Press, Copyright © 1974 by the President and Fellows of Harvard College.)

Figure 6-15. Complete obliteration of the cochlea by labyrinthitis ossificans, as seen here in an 84-year-old patient who suffered a febrile illness (presumably meningococcal meningitis) at the age of 2 months, is unusual. (Reprinted by permission of the publishers from Schuknecht HF: Pathology of the Ear. Cambridge, MA, Harvard University Press, Copyright © 1974 by the President and Fellows of Harvard College.)

intracochlear electrode into the scalae vestibuli of two patients with scala tympani occlusion by LO. Alternatively, Balkany75 has described endoscopically guided laser eradication of LO for cochlear implantation. Extreme LO may require extensive coring out of the cochlear modiolus, as described by Gantz and associates.76 The degree of LO has implications in the survival of the cochlear neuronal population and their fibers, apparently the elements stimulated by the intracochlear electrode.77 Nadol and Hsu78 have shown that, even in those cochleae with severe occlusion by LO related to meningogenic labyrinthitis, “significant numbers” of spiral ganglion cells remained. More specifically, Linthicum and colleagues77 have reported that “as few as 3212 cells may produce a useful auditory sensation.” The ABI holds hope for those profoundly deafened individuals with loss of both cochlear nerves, as in NF2.79 Although still considered experimental at this time, it is reasonable to expand our database regarding the pathology of the cochlear nuclei to establish which diseases may allow for ABI placement and which might not. It is particularly important to know the status of the ventral cochlear nucleus (VCN), because the VCN has extraventricular surface exposure and hence is surgically accessible. It seems logical to assume that a viable population of cochlear nuclear neurons is key in the successful use of the ABI. Some data indicate that with aging loss of cochlear neurons takes place in both the VCN and the dorsal cochlear nucleus80,81 and that those with hyperbilirubinemia similarly suffer a depopulation of cochlear neurons in the VCN.81 In theory, these individuals might be expected to perform less well with the ABI.

PACCHIONIAN BODIES Pacchionian bodies, commonly referred to as arachnoid granulations,82 consist of multiple arachnoid villi (see the earlier section, Meningiomas) found in close relationship

Pathologic Correlates in Neurotology

to (i.e., projecting intraluminally) the major venous sinuses. The space within the villi contains loose arachnoid tissue48 and represents a continuation of the subarachnoid space82 (Fig. 6-16). Thus, the bodies are thought to function in the resorption of CSF into the intracranial venous system. Protrusion through the dura by the pacchionian bodies eventuates in bony resorption and the creation of depressions in adjacent bone, known as foveolae granulares,48 and may occur in relationship to the middle and posterior cranial fossa aspects of the temporal bone (Figs. 6-17 and 6-18). Ordinarily, surgical exposure of such granulations does not provoke CSF leakage.82 However, Gacek83 has provided evidence that pacchionian bodies, associated with bone erosion into the pneumatized air cell spaces of the mastoid, are pathologic correlates of spontaneous (nontraumatic) adult-onset fluid in the tympanomastoid compartment,84 which may manifest with CSF otorrhea/rhinorrhea, conductive hearing loss, meningitis with acute otitis media, or intracranial extension of chronic otitis media. The detection of bony-dural defects associated with pacchionian bodies requires scanning in both the axial and coronal planes, because either the middle cranial fossa or posterior cranial fossa plates may be involved, whereas CSF flow into the mastoid may be detected either by intrathecal metrizamide–enhanced CT scanning or MRI.83 The surgical exposure is dictated by the size of the defect(s) and the multiplicity of defects found.83,85 Small (<1 cm) isolated defects may be managed through a simple mastoidectomy, but multiple or large (>1 cm) defects generally require additional middle cranial fossa exposure. Whatever herniated brain tissue is encountered is nonfunctional and is resected.

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Figure 6-17. This horizontal section shows a pacchionian body impinging on the middle cranial fossa surface of a right temporal bone. (Reprinted by permission of the publishers from Schuknecht HF, Gulya AJ: Anatomy of the Temporal Bone with Surgical Implications. Philadelphia, Lea & Febiger, 1986.)

Schuknecht and Shinozaki-Hori86 presented clinicopathologic studies of 12 cases as illustrative of patterns of degeneration of the facial nerve associated with disorders at

various locations along its path from the pons through the mastoid. Two general conclusions they made are particularly germane to neurotology: (1) The facial nerve (both motor and sensory divisions) adapts well to space-occupying lesions in the IAC; in the fallopian canal both divisions are “highly prone” to pressure atrophy. (2) Destruction of any segment of the motor division results in distal atrophy. A lesion of the sensory division central to the geniculate ganglion results in atrophy central to the lesion, while a lesion distal to the geniculate ganglion results in distal atrophy. The details of four of the illustrative cases are sufficiently relevant to neurotology to warrant expanded discussion. An intra-axial lesion of the pons is exemplified by the case of a 4-year-old child who presented with a progressive (>2 weeks) facial paralysis and ipsilateral, profound SNHL. An autopsy, performed 9 months later when the patient died, disclosed a pontine astrocytoma. The motor

Figure 6-16. Arachnoid granulations consist of a peripheral layer of arachnoid cells and fibrous tissue surrounding a central core (C ) of loose arachnoid tissue. (Reprinted by permission of the publishers from Schuknecht HF, Gulya AJ: Anatomy of the Temporal Bone with Surgical Implications. Philadelphia, Lea & Febiger, 1986.)

Figure 6-18. A pacchionian body interdigitates with the bony septa of the posterior cranial fossa surface of the temporal bone. (Reprinted by permission of the publishers from Schuknecht HF, Gulya AJ: Anatomy of the Temporal Bone with Surgical Implications. Philadelphia, Lea & Febiger, 1986.)

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component of the left facial nerve (Fig. 6-19) was completely degenerated throughout, but the sensory division (nervus intermedius, greater superficial petrosal nerve, and the chorda tympani nerve) appeared normal. An intracanalicular vestibular schwannoma and a somewhat more extensive meningioma illustrate the consequences of facial nerve compression in the environs of the IAC. The vestibular schwannoma manifested with SNHL and tinnitus 18 years before the death of an 81-year-old man. Temporal bone histopathologic examination (Fig. 6-20) revealed a left intracanalicular vestibular schwannoma with flaring of the IAC and distortion, anterior displacement, and flattening of, but apparently no invasion of, the facial nerve. Both the motor and sensory divisions of the facial nerve were normal peripheral to the lesion. The meningioma developed in a 56-year-old woman who had a history of headaches, left otalgia, and left facial paralysis. Her death, at age 60, occurred 3 days after attempted removal of the petrous ridge and cerebellopontine angle (CPA) meningioma. Temporal bone histopathologic examination (Fig. 6-21) showed the tumor

A

B Figure 6-20. A, In this schematic, the vestibular schwannoma is depicted compressing neural structures in the internal auditory canal. B, The intracanalicular vestibular schwannoma (S) is seen flattening the facial nerve (arrow) in this horizontal section of a left temporal bone. (From Schuknecht HF, Shinozaki-Hori N: Patterns of degeneration of the facial nerve. Am J Otol 6(Suppl):47–54, 1985.)

A

B Figure 6-19. A, Summary diagram of the effect of an astrocytoma (glioblastoma) of the pons on the facial, cochlear, and vestibular nerves. B, This horizontal section through the vertical segment of the facial nerve demonstrates pale staining consistent with degeneration of the motor component (m). The chorda tympani nerve and sensory component are intact. (From Schuknecht HF, Shinozaki-Hori N: Patterns of degeneration of the facial nerve. Am J Otol 6(Suppl):47–54, 1985.)

to be invading the IAC and compressing the geniculate ganglion, the neuronal population of which remained within normal limits. The motor division of the facial nerve, in contrast, was completely degenerated, whereas the greater superficial petrosal nerve, chorda tympani nerve, and sensory bundle showed partial degeneration. Compression of the vertical segment of the facial nerve, the most common area of facial nerve involvement by paragangliomas,60 was also found in the left temporal bone of a 49-year-old woman who died 5 months after the development of a rapidly progressive left facial paralysis caused by diffuse carcinomatosis related to an undifferentiated carcinoma of the lung (Fig. 6-22).3 The facial nerve was found to be compressed at the superior aspect of its vertical segment. Medial to the metastatic nodule, the motor and sensory divisions were normal, but distally they showed severe degeneration. In treating the patient with facial nerve symptomatology, such as progressive paresis, the neurotologist must determine the area(s) of involvement of the facial nerve with clinical examination supplemented by medical imaging. Therapeutic deliberations are guided by an understanding of the pathologic consequences of lesions at various locations.

Pathologic Correlates in Neurotology

A

155

A

F

B Figure 6-21. A, A meningioma, in this diagram, extends along the internal auditory canal to the geniculate ganglion. B, Despite compression by the meningioma, there is no obvious loss of neurons in the geniculate ganglion. C, Complete degeneration of the motor component and partial degeneration of the sensory bundle of the facial nerve occurs. (From Schuknecht HF, Shinozaki-Hori N: Patterns of degeneration of the facial nerve. Am J Otol 6(Suppl):47–54, 1985.)

INTERNAL CAROTID ARTERY The internal carotid artery (ICA) serves as a landmark to the neurotologic skull base surgeon in much the same fashion as the facial nerve guides the contemporary otologist. Just as the normal anatomic relationships of the facial nerve, as well as their variations, are key data in surgical undertakings, similar knowledge regarding the ICA is critical. In addition, it is important to be cognizant of the possible alterations of the ICA with age when contemplating surgical interventions in the elderly. The details of the anatomic relationships of the ICA within the temporal bone and cranial cavity have been published elsewhere.82,87 For the neurotologic surgeon, it is particularly important to be aware of the ICA as it runs medial to the eustachian tube (Fig. 6-23) and anterolateral to the basal turn of the cochlea (Fig. 6-24). According to Leonetti and associates87 the mean distance of the ICA to the basal turn of the cochlea, measured at the level of the tensor tympani muscle, is 2.83 mm, with a range of 1.14 to 5.52 mm. The congenitally ectopic ICA is theorized to derive from an anomalous or anomalously persisting branch, fixing the

B Figure 6-22. A, The metastatic nodule compresses the facial nerve in its vertical segment. B, Both motor and sensory components of the facial nerve (F ) show the degenerative effects of compression by the tumor nodule (T ). (From Schuknecht HF, Shinozaki-Hori N: Patterns of degeneration of the facial nerve. Am J Otol 6(Suppl):47–54, 1985.)

ICA at the origin of the branch and deviating the ICA posterior and lateral to its usual course during the remainder of development.88 Fisch89 proposes alternatively that the aberrant vessel in the tympanic cavity represents the enlarged inferior tympanic and caroticotympanic arteries, which substitute for the “original atrophic” vessel. Despite the rarity of this anomaly, it is an element in the differential diagnosis of a jugulotympanic paraganglioma. A marked diminution in the tissues of the carotid canal can occur with aging; in extreme cases, the wall of the ICA is reduced to a mere intimal layer. Clearly, in such instances, skeletonization of the ICA would be fraught with the hazard of ICA rupture, or the ICA may be more susceptible to tumor invasion (Fig. 6-25). Arteriosclerotic plaques may also involve the ICA (Fig. 6-26), with the possibility of arterial manipulation sending a shower of obliterative emboli. MRA (magnetic resonance angiography) may prove invaluable in estimating arterial obliteration by plaques; it is less invasive than standard cranial arteriography. Aneurysmal dilatation of the ICA most commonly develops immediately proximal to the external carotid foramen,89 but traumatic aneurysms develop at the site of

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Figure 6-23. The internal carotid artery (C) lies medial to the eustachian tube (e). (Reprinted by permission of the publishers from Schuknecht HF, Gulya AJ: Anatomy of the temporal bone with surgical implications. Philadelphia, Lea & Febiger, 1986,)

injury, for example, the tympanic cavity with laceration during tympanostomy tube insertion.90 Extraordinarily, an intrapetrous carotid artery aneurysm can present with facial paralysis.91 Large (Fisch types C and D) paragangliomas generally involve the intratemporal ICA.89 No methodical study of invasion of the ICA akin to that published detailing facial nerve invasion by paragangliomas could be found, yet frank invasion of the ICA is thought to be unusual (Fig. 6-27). Perhaps the periosteum of the carotid canal presents a protective barrier: Inadvertent disruption of the ICA can occur with removal of invasive tumor, but more significant in paraganglioma surgery are the caroticotympanic arteries, which supply the anteromedial portion of the tumor and which can be avulsed in operative dissection at the level of the tympanic orifice of the eustachian tube.89 The lining matrices of congenital epidermoids and dermoid cysts generally can be peeled from the ICA.89

Figure 6-24. The basal turn of the cochlea (b) lies adjacent to the internal carotid artery (C). (Reprinted by permission of the publishers from Schuknecht HF, Gulya AJ: Anatomy of the Temporal Bone with Surgical Implications. Philadelphia, Lea & Febiger, 1986.)

Figure 6-25. With age, extreme thinning of the wall of the internal carotid artery may occur (compare with Fig. 6–23). (Reprinted by permission of the publishers from Schuknecht HF: Pathology of the Ear. Cambridge, MA, Harvard University Press, Copyright 1974 by the President and Fellows of Harvard College.)

SERPENTINE ANEURYSMS Massive ectasia and serpentine tortuosity of the vertebrobasilar system is most appropriately referred to as a serpentine aneurysm of the involved artery, although the term dolichoectasia is also used.92,93 The basilar artery is most commonly involved, but often the vertebral and internal carotid arteries are distorted as well.93 The typical patient is a man in his mid-60s with a history of hypertension and arteriosclerosis. Suggestive symptoms relate to compression of the pons, medulla, lower cranial nerves, and ventricular system, and/or embolism from mural thrombi.94 Atypically, the serpentine aneurysm may present with vertigo, with94–96 or without97,98 SNHL and tinnitus. Central facial nerve paralysis94 and facial numbness96 have also been reported.

Figure 6-26. An atherosclerotic plaque (a) partially occludes the lumen of the intratemporal internal carotid artery. (Reprinted by permission of the publishers from Schuknecht HF: Pathology of the Ear. Cambridge, MA, Harvard University Press, Copyright 1974 by the President and Fellows of Harvard College.)

Pathologic Correlates in Neurotology

Figure 6-27. A paraganglioma (glomus jugulare) has invaded the internal carotid artery (A) adventitia (arrow) as seen at the level of the petrous apex. (From Dayal VS, Hinojosa R, Amenta CA III: Surgical interferences from study of temporal bones with glomus jugulare tumor. Otolaryngol Head Neck Surg 102:690–697, 1990.)

Contrast-enhanced CT scanning or MRI can be diagnostic. MRA promises to be a minimally invasive manner in which to confirm the diagnosis; it can be substituted for a formal vertebral arteriography.

VASCULAR LOOPS The compression of neural structures by vascular loops, either within the IAC or at the nerve root entry zone has been implicated in the generation of symptoms such as tinnitus, vertigo, and SNHL, with “decompression” or nerve section offered as treatment.99–101 Mazzoni102 conducted a detailed study of the vascular relationships of the IAC. The 100 temporal bones used were harvested in such a fashion as to leave attached contiguous portions of the brainstem and cerebellum. He found an arterial loop, most commonly the anterior inferior cerebellar artery, within the IAC in 40% of his specimens (Fig. 6-28). In 27% of his specimens the loop was located at the porus; in the remaining 33% it was in the CPA. More recently, Reisser and Schuknecht103 attempted to correlate clinical symptomatology (unexplained audiovestibular symptoms) with the presence of an IAC loop. Although their method for harvesting temporal bone did not ensure uniform preservation of intact IAC/vascular relationships, in the 12.3% of 1327 temporal bones studied that did have these loops in the IAC, no correlation could be made between ante mortem symptoms and the presence of, or laterality of, the vascular loop.

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Figure 6-28. A loop of the anterior inferior cerebellar artery (arrows) indents the posterior aspect of, and enters, the internal auditory canal. (Reprinted by permission of the publishers from Schuknecht HF, Gulya AJ: Anatomy of the Temporal Bone with Surgical Implications. Philadelphia, Lea & Febiger, 1986.)

injury) has also been implicated.104 Pure DAVMs are dependent on a meningeal arterial supply and are limited to the dura, but the clinical presentation relates to the route of venous drainage.104 The occipital DAVM presents with pulsatile tinnitus and headache and may also provoke increased intracranial pressure, subarachnoid hemorrhage, and seizures.105 A characteristic bruit is heard loudest in the mastoid region and decreases with ipsilateral carotid artery compression. Treatment, either embolization or surgical excision, is offered according to the severity of the symptomatology.

JUGULAR BULB The jugular bulb is a landmark in neurotologic surgery, for example, leading to the cochlear aqueduct and the inferior margin of the IAC, and its variants, the high (enlarged) jugular bulb, the dehiscent jugular bulb, and the

DURAL ARTERIOVENOUS MALFORMATIONS Dural arteriovenous malformations (DAVMs) are rare lesions and even more rarely cause objective pulsatile tinnitus.94 They are usually considered to be congenital in origin, stemming from a disturbance in vascular development at 3 weeks’ gestation,94 but trauma (surgery or head

Figure 6-29. This high-riding jugular bulb (j ) also has areas of bony dehiscence. (Reprinted by permission of the publishers from Schuknecht HF, Gulya AJ: Anatomy of the Temporal Bone with Surgical Implications. Philadelphia, Lea & Febiger, 1986.)

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TABLE 6-2. Distinguishing Characteristics—High Jugular Bulb vs. Jugular Bulb Diverticulum Jugular Bulb Diverticulum

High Jugular Bulb Lateral/Anterior

Location

Medial/Posterior

Yes Otoscopy Conductive Uncommon

Tympanic cavity extension Diagnostic study Hearing loss Tinnitus

No No Yes?

Vertigo Ménière’s symptoms Expansion

No Radiology Sensorineural Continuous or intermittent Yes Yes Yes?

jugular diverticulum are entities of which the neurotologist should be aware in order to avert potential surgical misadventure. The high (enlarged) jugular bulb (Fig. 6-29) protrudes above the level of the tympanic annulus and may attain prodigious proportions (the so-called jugular megabulb).106,107 The high jugular bulb has been reported to occur in 3.5%108 to 7.0%109 of temporal bones studied, more commonly occurs on the right side, and arguably has been related to the degree of pneumatization of the peri- and infralabyrinthine regions.110,111 The high jugular bulb may be confused with a paraganglioma by the unwary clinician and serves primarily as a nuisance in both translabyrinthine and retrosigmoid tumor extirpation. The high jugular bulb has been incriminated in subjective pulsatile tinnitus112 with mixed reports of successful symptomatic control with surgical ligation of the internal jugular vein.106,113 The high jugular bulb may or may not have an intact bony covering, that is, be dehiscent. Clearly, in the latter situation, it is prone to inadvertent penetrating injury.114 An entity distinct from the high jugular bulb is the jugular bulb diverticulum.115 According to Jahrsdoerfer, Cail, and Cantrell115 the jugular diverticulum is a true venous anomaly and has some characteristic features that serve to distinguish it from a high jugular bulb (Table 6-2). Notably, the jugular diverticulum may erode into the IAC or obstruct the endolymphatic duct resulting in the “classical symptoms of Ménière’s disease.”115

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7. Hebbar GK, McKenna MJ, Linthicum FH Jr: Immunohistochemical localization of vimentin and S-100 antigen in small acoustic tumors and adjacent cochlear nerves. Am J Otol 11:310–313, 1990. 8. Marquet JFE, et al: The solitary schwannoma of the eighth cranial nerve. An immunohistochemical study of cochlear nerve-tumor interface. Arch Otolaryngol Head Neck Surg 116:1023–1025, 1990. 9. Ylikoski J, Palva T, Collan Y: Eighth nerve in acoustic neuromas. Special reference to superior vestibular nerve function and histopathology. Arch Otolaryngol 104:532–537, 1978. 10. Ylikoski J, et al: Cochlear nerve in neurilemomas. Audiology and histopathology. Arch Otlaryngol 104:679–684, 1978. 11. Neely JG: Hearing conservation surgery for acoustic tumors a clinical-pathologic correlative study. Am J Otol 6(Suppl):143–146, 1985. 12. Ylikoski J: Light and electron microscopic findings in a case of small acoustic schwannoma (associated with a schwannoma of the facial nerve). J Laryngol Otol 100:785–795, 1986. 13. Shelton C, et al: Acoustic tumor surgery. Prognostic factors in hearing conservation. Arch Otolaryngol Head Neck Surg 115: 1213–1216, 1989. 14. Neely JG: Is it possible to totally resect an acoustic tumor and conserve hearing? Otolaryngol Head Neck Surg 92:162–167, 1984. 15. Silverstein H, et al: Combined retrolab-retrosigmoid vestibular neurectomy. An evolution in approach. Am J Otol 10:166–169, 1989. 16. Silverstein H, et al: Cochlear and vestibular gross and histologic anatomy (as seen from postauricular approach). Otolaryngol Head Neck Surg 92:207–211, 1984. 17. Cohen NL, Ransohoff J: Hearing preservation-posterior fossa approach. Otolaryngol Head Neck Surg 92:176–183, 1984. 18. Rosenberg RA, Cohen NL, Ransohoff J: Long-term hearing preservation after acoustic neuroma surgery. Otolaryngol Head Neck Surg 97:270–274, 1987. 19. Shelton C, et al: Hearing preservation after acoustic tumor removal: Long-term results. Laryngoscope 100:115–119, 1990. 20. Amoils CP, Lanser MJ, Jackler RK: Acoustic neuroma presenting as a middle ear mass. Poster presentation at the 95th annual meeting of the American Academy of Otolaryngology-Head & Neck Surgery, Kansas City, MO, September 22, 1991. 21. DeMoura LFP, Hayden RC Jr, Conner GH: Further observations on acoustic neurinoma. Trans Am Acad Ophthal Otolaryngo 173:60–70, 1969. 22. Suga F, Lindsay JR: Inner ear degeneration in acoustic neurinoma. Ann Otol Rhinol Laryngol 85:343–358, 1976. 23. Tran Ba Huy P, et al: Acoustic schwannoma presenting as a tumor of the external auditory canal. Case report. Ann Otol Rhino Laryngol 96:415–418, 1987. 24. Babin RW, Harker LA: Intralabyrinthine acoustic neurinomas. Otolaryngol Head Neck Surg 88:455–461, 1980. 25. Huang T-S: Primary intralabyrinthine schwannoma. Ann Otol Rhinol Laryngol 95:190–192, 1986. 26. Sataloff RT, Roberts B-R, Feldman M: Intralabyrinthine schwannoma. Am J Otol 9:323–326,1988. 27. DeMoura LFP: Inner ear pathology in acoustic neurinoma. Arch Otolaryngol 85:125–133, 1967. 28. Schuknecht HF: Further observations on the pathology of presbycusis. Arch Otolaryngol 80:369–382, 1964. 29. Perlman HB, Kimura R, Fernandez C: Experiments on temporary obstruction of the internal auditory artery. Laryngoscope 69:591–613, 1959. 30. Kimura R, Perlman HB: Arterial obstruction of the labyrinth. Pan I. cochlear changes. Ann Otol Rhinol Laryngo167:5–24, 1958. 31. Kimura R, Perlman H: Extensive venous obstruction of the labyrinth. A. Cochlear changes. Ann Otol Rhinol Laryngol 65:332–350, 1956. 32. Johnsson L-G, Hawkins JE Jr, Rouse RC: Sensorineural and vascular changes in an ear with acoustic neurinoma. Am J Otolaryngol 5:49–59, 1984.

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33. Silverstein H, Schuknecht HE: Biochemical studies of inner ear fluid in man. Changes in otosclerosis, Ménière’s disease, and acoustic neuroma. Arch Otolaryngol 84:395–402, 1966. 34. Silverstein H: Inner ear fluid proteins in acoustic neuroma, Ménière’s disease and otosclerosis. Ann Otol Rhinol Laryngol 80:27–35, 1971. 35. Palva T, et al: Disc electrophoresis in acoustic neurinoma. Ann Otol Rhinol Laryngol 81:106–113, 1972. 36. Sekiya T, Molter AR: Cochlear nerve injuries caused by cerebellopontine angle manipulations. An electrophysiological and morphological study in dogs. J Neurosurg 67:244–249, 1987. 37. Kveton JF, et al: Cochlear nerve conduction block: An explanation for spontaneous hearing return after acoustic tumor surgery. Otolaryngol Head Neck Surg 100:594–601, 1989. 38. Fukaya T, Nomura Y, Fukushima T: Transient retrocochlear lowfrequency sensorineural hearing loss: A new clinical entity. Laryngoscope 101:643–647, 1991. 39. Martuza RL, Ojemann RG: Bilateral acoustic neuromas: Clinical aspects, pathogenesis, and treatment. Neurosurgery 10:1–12, 1982. 40. Eckermeier L, Pirsig W, Mueller D: Histopathology of 30 non-operated acoustic schwannomas. Arch Otorhinolaryngol 222:1–9, 1979. 41. Linthicum FH Jr: Unusual audiometric and histologic findings in bilateral acoustic neurinomas. Ann Otol Rhinol Laryngol 81: 433–437, 1972. 42. Flexon PB, et al: Bilateral acoustic neurofibromatosis (neurofibromatosis 2): A disorder distinct from von Recklinghausen’s neurofibromatosis (neurofibromatosis 1). Ann Otol Rhinol Laryngol 100:830–834, 1991. 43. Linthicum FH Jr, Brackmann DE: Bilateral acoustic tumors. A diagnostic and surgical challenge. Arch Otolaryngol 106:729–733, 1980. 44. Egelhoff JC, et al: Dural ectasia as a cause of widening of the internal auditory canals in neurofibromatosis. Pediatr Radiol 17:7–9, 1987. 45. Hill MC, Oh KS, Hodges FJ III: Internal auditory canal enlargement in neurofibromatosis without acoustic neuroma. Radiology 122:730, 1977. 46. Sarwar M, Swischuk LE: Bilateral internal auditory canal enlargement due to dural ectasia in neurofibromatosis. Am J Roentgenol 129:935–936, 1977. 47. Nager GT, Heroy J, Hoeplinger M: Meningiomas invading the temporal bone with extension to the neck. Am J Otolaryngol 4:297–324, 1983. 48. Nager GT, Masica DN: Meningiomas of the cerebellopontine angle and their relation to the temporal bone. Laryngoscope 80:863–895, 1970. 49. Guzowski J, et al: Meningiomas of the temporal bone. Laryngoscope 86:1141–1146, 1976. 50. Rietz DR, et al: Significance of apparent intratympanic meningiomas. Laryngoscope 93:1397–1404, 1983. 51. Maniglia AJ: Intra and extracranial meningiomas involving the temporal bone. Laryngoscope 88(Suppl 12):1–58, 1978. 52. Leonetti JP, et al: Meningiomas of the lateral skull base: neurotologic manifestations and patterns of recurrence. Otolaryngol Head Neck Surg 103:972–980, 1990. 53. Belal A Jr, Sanna M: Pathology as it relates to ear surgery. I. Surgery of glomus tumours. J Laryngol Otol 96:1079–1097, 1981. 54. Myers EN, et al: Glomus jugulare tumor—A radiographichistologic correlation. Laryngoscope 81:1838–1851, 1971. 55. Rosenwasser H: Monograph on glomus jugulare tumors. Arch Otolaryngol 88:3–40, 1968. 56. Winship T, Klopp CT, Jenkins WH: Glomus jugularis tumors. Cancer 1:441–448, 1948. 57. Spector GJ, et al: Panel discussion: glomus jugulare tumors of the temporal bone. Patterns of invasion in the temporal bone. Laryngoscope 89:1628–1639, 1979. 58. House WF, Glasscock ME III: Glomus tympanicum tumors. Arch Otolaryngol 87:550–554, 1968.

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59. O’Leary MJ, et al: Glomus tympanicum tumors: A clinical perspective. Laryngoscope 101:1038–1043, 1991. 60. Makek M, et al: Neural infiltration of glomus temporale tumors. Am J Otol 11:1–5, 1990. 61. Kinney SE: Glomus jugulare tumor surgery with intracranial extension. Otolaryngol Head Neck Surg 88:531–535, 1980. 62. Berlinger NT, et al: Patterns of involvement of the temporal bone in metastatic and systemic malignancy. Laryngoscope 90:619–627, 1980. 63. Nelson EG, Hinojosa R: Histopathology of metastatic temporal bone tumors. Arch Otolaryngol Head Neck Surg 117:189–193, 1991. 64. Schuknecht HF, Allam AF, Murakami Y: Pathology of secondary malignant tumors of the temporal bone. Ann Otol Rhinol Laryngol 77:5–22, 1968. 65. Proctor B, Lindsay JR: Tumors involving the petrous pyramid of the temporal bone. Arch Otolaryngol 46:180–194, 1947. 66. Adams GL, Paparella MM, El Fiky FM: Primary and metastatic tumors of the temporal bone. Laryngoscope 81:1273–1285, 1971. 67. Houck JR, Murphy K: Sudden bilateral profound hearing loss resulting from meningeal carcinomatosis. Otolaryngol Head Neck Surg 106:92–97, 1992. 68. Shanbrom E, Finch SC: The auditory manifestations of leukemia. Yale J Biol Med 31:144–156, 1958. 69. Suga F, Lindsay JR: Labyrinthitis ossificans. Ann Otol Rhinol Laryngol 86:17–29, 1977. 70. Green JD Jr, Marion MS, Hinojosa R: Labyrinthitis ossificans: Histopathologic consideration for cochlear implantation. Otolaryngol Head Neck Surg 104:320–326, 1991. 71. Nadol JB Jr: Histological considerations in implant patients. Arch Otolaryngol 110:160–163, 1984. 72. Novak MA, et al: Labyrinthine ossification after meningitis: Its implications for cochlear implantation. Otolaryngol Head Neck Surg 103:351–356, 1990. 73. Eisenberg LS, et al: Electrical stimulation of the auditory system in children deafened by meningitis. Otolaryngol Head Neck Surg 92:700–705, 1984. 74. Steenerson RL, Gary LB, Wynens MS: Scala vestibuli cochlear implantation for labyrinthine ossification. Am J Otol 11:360–363, 1990. 75. Balkany T: Endoscopy of the cochlea during cochlear implantation. Ann Otol Rhinol Laryngol 99:919–922, 1990. 76. Gantz BJ, McCabe BF, Tyler RS: Use of multichannel cochlear implants in obstructed and obliterated cochleas. Otolaryngol Head Neck Surg 98:72–81, 1988. 77. Linthicum FH Jr, et al: Cochlear implant histopathology. Am J Otol 12:245–311, 1991. 78. Nadol JB Jr, Hsu W: Histopathologic correlation of spiral ganglion cell count and new bone formation in the cochlea following meningogenic labyrinthitis and deafness. Ann Otol Rhinol Laryngol 100:712–716, 1991. 79. McElveen JT Jr, et al: Electrical stimulation of cochlear nucleus in man. Am J Otol 6(Suppl):88–91, 1985. 80. Arnesen AR: Presbyacusis—loss of neurons in the human cochlear nuclei. J Laryngol Otol 96:503–511, 1982. 81. Dublin WB: Central auditory pathology. Otolaryngol Head Neck Surg 95(Part 2):363–424, 1986. 82. Schuknecht HF, Gulya AJ: Anatomy of the temporal bone with surgical implications, Philadelphia, Lea & Febiger, 1986. 83. Gacek RR: Arachnoid granulation cerebrospinal fluid otorrhea. Ann Otol Rhinol Laryngol 99:854–862, 1990. 84. Schuknecht HF, Zaytoun GM, Moon CN Jr: Adult onset fluid in the tympanomastoid compartment. Arch Otolaryngol 108: 759–765, 1982. 85. Kemink JL, Graham MD, Kartush JM: Spontaneous encephalocele of the temporal bone. Arch Otolaryngol Head Neck Surg 112:558–561, 1986. 86. Schuknecht HF, Shinozaki-Hori N: Patterns of degeneration of the facial nerve. Am J Otol 6(Suppl):47–54, 1985.

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87. Leonetti JP, Smith PG, Linthicum FH: The petrous carotid artery: anatomic relationships in skull base surgery. Otolaryngol Head Neck Surg 102:3–12, 1990. 88. Steffen TN: Vascular anomalies of the middle ear. Laryngoscope 78:171–197, 1968. 89. Fisch U: Carotid lesions at the skull base. In Brackmann DE (ed.): Neurological Surgery of the Ear and Skull Base. New York, Raven Press, 1982. 90. Glasscock ME III, et al: Management of aneurysms of the petrous portion of the internal carotid artery by resection and primary anastomosis. Laryngoscope 93:1445–1453, 1983. 91. Brandt TW, Jenkins HA, Coker NJ: Facial paralysis as the initial presentation of an internal carotid artery aneurysm. Arch Otolaryngol Head Neck Surg 112:198–202, 1986. 92. Sacks JG, Lindenburg R: Dolichoectactic intracranial arteries. Symptomatology and pathogenesis of arterial elongation and distention. Johns Hopkins Med J 125:95–106, 1969. 93. Stehbens WE: The pathology of intracranial aneurysms and their complications. In Fox JL (ed.): Intracranial Aneurysms, vol 1. New York, Springer Verlag, 1983. 94. Gulya AJ, Kobrine AI, Davis DO: “Nonotologic” causes for otologic symptoms: Two unusual cases. Otolaryngol Head Neck Surg 95:615–620, 1986. 95. Campbell JB, Pearman K, Nahl SS: Basilar artery ectasia: a rare cause of sensorineural deafness. J Laryngol Otol 100:333–335, 1986. 96. Musiek FE, Geurkink NA, Spiegel P: Audiologic and other clinical findings in a case of basilar artery aneurysm. Arch Otolaryngol Head Neck Surg 113:772–776, 1987. 97. Benecke JE Jr, Hitselberger WE: Vertigo caused by basilar artery compression of the eighth nerve. Laryngoscope 98:807–809, 1988. 98. Smith BD, Cunningham D: Basilar artery aneurysm: A cause of vertigo. Otolaryngol Head Neck Surg 96:573–576, 1987. 99. Applebaum EL, Valvasorri G: Internal auditory canal vascular loops: Audiometric and vestibular system findings. Am J Otol 16(Suppl):110–113, 1985. 100. Jannetta PJ, Moller MB, Moller AR: Disabling positional vertigo. N Engl J Med 310:1700–1705, 1984.

101. McCabe BF, Harker LA: Vascular loop as a cause of vertigo. Ann Otol Rhinol Laryngol 92:542–543, 1983. 102. Mazzoni A: Internal auditory canal arterial relations at the porus acusticus. Ann Otol Rhinol Laryngol 78:797–814, 1969. 103. Reisser C, Schuknecht HF: The anterior inferior cerebellar artery in the internal auditory canal. Laryngoscope 101:761–766, 1991. 104. Nabors MW, et al: Delayed postoperative dural arteriovenous malformations. Report of two cases. J Neurosurg 66:768–772, 1987. 105. Jungreis CA: Imaging case study of the month: pulsatile tinnitus from a dural arteriovenous fistula. Ann Otol Rhinol Laryngol 100:951–953, 1991. 106. Buckwalter JA, et al: Pulsatile tinnitus arising from jugular megabulb deformity: A treatment rationale. Laryngoscope 93:1534–1539, 1983. 107. Mueller DP, Dolan KD: Imaging case study of the month. Enlarged jugular foramen. Ann Otol Rhinol Laryngol 97:326–327, 1988. 108. Subotic R: The high position of the jugular bulb. Acta Otolaryngol (Stockh) 87:340–344, 1979. 109. Overton SB, Ritter FN: A high placed jugular bulb in the middle ear: A clinical and temporal bone study. Laryngoscope 83:1986–1991, 1973. 110. Orr JB, Todd NW: Jugular bulb position and shape are unrelated to temporal bone pneumatization. Laryngoscope 98:136–138, 1988. 111. Wilbrand HF, Stahle J, Rask-Andersen H: Tomography in Ménière’s disease why and how. Morphological, clinical and radiographic aspects. Adv Otorhinolaryngol 24:71–93, 1978. 112. Adler JR, Ropper AH: Self-audible venous bruits and high jugular bulb. Arch Neurol 43:257–259, 1986. 113. Kennedy DW, EI-Sirsy HH, Nager GT: The jugular bulb in otologic surgery: Anatomic, clinical, and surgical considerations. Otolaryngol Head Neck Surg 94:6–15, 1986. 114. Smith B, Myer CM III, Towbin RB: X-ray study of the month. Dehiscent jugular bulb. Ann Otol Rhinol Laryngol 96:232–233, 1987. 115. Jahrsdoerfer RA, Cail WS, Cantrell RW: Endolymphatic duct obstruction from a jugular bulb diverticulum. Ann Otol Rhinol Laryngol 90:619–623, 1981.

7

Outline Types and Mechanisms of Hearing Loss Clinical Differentiation of Hearing Loss: Cochlear Versus Noncochlear Presentation of Cerebellopontine Angle Lesions Sudden or Fluctuating Hearing Loss Normal Hearing Progression of Hearing Loss Hearing Loss Secondary to Lesions Other Than Acoustic Neuroma Summary

H

earing loss and tinnitus, in their various manifestations, have historically been the hallmark of neurotologic disorders. This chapter examines the characteristics and incidence of hearing loss in neurotologic disease states. Much of the attention focuses on acoustic neuromas (AN) (or vestibular schwannomas), since they are generally the most common neoplasm seen in neurotology practices and also represent a prototype for hearing loss in neurotologic diagnosis. The association of hearing loss with AN has long been recognized. Harvey Cushing,1 in his classic 1917 monograph on AN, wrote: The chronology of symptoms in the foregoing series of cases makes it clear that the clinical diagnosis of an acoustic tumor can be made with reasonable assurance, only when auditory manifestations definitely precede the evidence of involvement of other structures in the cerebellopontile angle. This is characteristic of so large a percentage of the clinical histories that the exceptions . . . merely serve to make it more striking . . . The significance of this does not seem to have been heretofore sufficiently emphasized, nor was it appreciated when the study of these cases was first undertaken, and it must be confessed that in most of the clinical histories, the fact was hidden in a mass of symptomatic details, while in others it has only been brought to light by subsequent inquiries directed towards this particular matter. It would appear that patients rarely call attention to the premonitory auditory symptoms, which are either forgotten or are not associated with the subsequent and more incapacitating phenomena, and it is equally certain that the sequences apt to be slighted by the questioner.

The retrospective, frequent association of hearing loss with neurotologic problems has been noted many times throughout the succeeding 85 years; however, as noted even in very recent AN evaluations, the time between the onset of symptoms and first evaluation, or more importantly, between the onset of symptoms and diagnosis, has

Chapter

Hearing Loss in Neurotologic Diagnosis

Michael A. Novak, MD

continued to be years rather than weeks or months. As seen in this chapter, the incidence of auditory symptoms in retrocochlear disorders is so great that a high index of suspicion should be maintained for any unexplained auditory symptoms to encourage early evaluation and diagnosis of these disorders. At present, readily available, accurate audiologic and imaging techniques exist such that the delay between onset of symptoms and diagnosis can be shortened significantly if the awareness of patients and health care providers can be heightened. In this chapter, the types of hearing loss encountered in neurotologic diagnosis, the pathophysiology of these losses, and the incidence and exceptions are examined. As mentioned earlier, the primary focus is on AN diagnosis; other diagnostic entities will be mentioned to contrast with the AN presentation. Historically, since the first description of a definite AN seen at autopsy by Charles Bell2 in 1830, the recognition of hearing loss as a diagnostic indicator for AN has undergone a very slow evolution. Cruveilhier3 recognized the first complete clinical and pathologic description of AN, noting the primary deafness in 1835. Stevens4 (1879) noted the first case of a tumor of the auditory nerve that was diagnosed prior to death based on symptoms. In 1904, Stewart and Holmes5 described in the English literature a study of 40 cases of extracerebellar and intracerebellar tumors and drew a distinction between the two based on symptoms. As noted previously, Cushing’s book1 in 1917 still noted that the hearing loss of retrocochlear lesions was often recognized very late and lost in the midst of other symptoms because the tumors were diagnosed very late in their course. Gradual improvements in audiometry and imaging have led to earlier diagnosis of tumors. Therefore, especially in the last decade, the clinical picture has slowly changed. Tumors are now being found earlier, and the degree of hearing loss associated with AN is also changing. In 1992 163

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Tos, Thomsen, and Charabi6 examined tumors diagnosed in the period from 1983 to 1990 and compared them with tumors diagnosed from 1976 to 1983. In a stable population with centralized medical care, the incidence of tumors was 9.4 per million in the second 7-year period versus 7.8 tumors per million in the first 7 years. Fewer tumors were more than 4 cm in diameter in the second 7-year period, but the total number of medium-sized and large tumors was still the same. With the widespread use of gadoliniumenhanced magnetic resonance imaging (MRI) an increase has occurred in diagnosis of tumors in the 1- to 10-mm range. Associated with this earlier identification of tumors, the index of suspicion and criteria for work-up of hearing loss has slowly changed. Numerous authors have noted an increase in identification of tumors in the small to medium size range, and an associated increase in the number of patients with symmetrical or normal hearing, or minimal hearing loss at the time of diagnosis.

TYPES AND MECHANISMS OF HEARING LOSS Hearing losses are generally characterized as conductive or sensorineural losses. Sensorineural losses can be further subdivided into sensory or cochlear losses and neural or retrocochlear losses. With rare exception, neurotologic diseases cause a sensorineural type of hearing loss. Conductive losses are rarely seen, except for glomus jugulare tumors, neuromas of the facial nerve with extension into the middle ear, rare middle ear tumors, or cholesteatomas or cholesterol granulomas. This chapter focuses on the nonconductive or sensorineural losses. Sensory or cochlear losses resulting from peripheral hair cell damage typically manifest by decreased sensitivity to pure tones, the phenomenon of recruitment7,8 intact auditory brainstem responses (ABR), loss of otoacoustic emissions (OAEs), and relatively preserved speech discrimination until widespread hair cell damage has occurred.9 Neural or retrocochlear losses typically show decreased speech discrimination out of proportion to the relatively unaffected pure tones,9 auditory fatigue or tone decay,10 abnormal or absent ABR,11 and intact OAEs.12 As widespread hair cell damage occurs in cochlear losses, speech discrimination will deteriorate, but in neural losses, as increasing numbers of auditory nerve fibers are damaged, pure tone thresholds will elevate. Theoretically, retrocochlear lesions should produce the picture of a pure neural loss, but in reality they often appear to be cochlear in nature or to show elements of both types of hearing losses on objective, behavioral, or speech perception auditory testing.13 The exact cause of hearing loss in most neurotologic lesions is unknown; however, in tumors of the eighth nerve and cerebellopontine angle (CPA), a number of mechanisms have been theorized. Direct eighth nerve compression, stretching of the nerve, vascular compression or occlusion of the blood supply to the eighth nerve or blood supply to the cochlea, damage to the cochlear efferents, biochemical changes within the inner ear, and hemorrhage within the nerve or into the tumor all may have a place in the etiology of hearing loss. In other neurotologic entities, neurovascular compression of the eighth nerve near the

brainstem or direct lesions of the auditory nerve or central pathways may also be causes. Most ANs arise from one of the vestibular nerves at the junction of the proximal and distal nerves (also the junction of the oligodendroglia and Schwann cells), usually near the porus acusticus internus. They occasionally arise more distally in the internal auditory canal (IAC) in tumors that originate in the cochlear nerve.14 These slowgrowing lesions within the confines of the bony IAC will cause slow compression of the cochlear nerve. The hearing loss will reflect this compression of auditory nerve fibers. The rate and amount of hearing loss will vary depending on the rate of growth of the tumor, the plasticity of the nerve, the consistency of the tumor, the location within the IAC, and the amount of early expansion into the CPA. The pure tone loss may be seen quite late in the course of the tumor growth, because as Schuknecht and Woellner15 demonstrated, if the organ of Corti is intact, 75% of the auditory nerve fibers need to be destroyed before pure tone hearing is affected. This mechanism, more than most others, explains the typical, slowly progressive hearing loss of CPA tumors. This mechanism also partially explains the middle- and high-frequency hearing losses usually associated with eighth nerve tumors. Sando16 demonstrated anatomically that the high-frequency auditory nerve fibers from the basal turn of the cochlea are located inferiorly and laterally all the way from the spiral ganglion to the cochlear nuclei in the brainstem, whereas the middle and apical fibers twist about the axis from the spiral ganglion to the cochlear nuclei. The apical fibers actually make approximately 13/4 turns about the long axis before reaching the brainstem. Low-frequency apical fibers also are more centrally located within the nerve. These differences of position within the nerve may allow for earlier involvement of the high-frequency basal fibers and a variable involvement of the middle- and lowfrequency fibers from the middle and apical turns of the cochlea. In addition to direct tumor compression of the auditory nerve, Badie and colleagues17 proposed a theory of increased pressure in the IAC as a cause for tumorrelated hearing loss. They measured the intracanalicular pressure in 15 patients undergoing tumor resections. Intracanalicular pressure directly correlated with the amount of tumor in the IAC. There was a strong trend toward lower IAC pressure in patients with better preoperative hearing, but the differences did not reach statistical significance. Vascular compression as a cause of the hearing loss in AN has also been theorized. Since the anterior inferior cerebellar artery loops into the internal auditory meatus a variable distance, and the internal auditory artery arises from the loop of the anterior inferior cerebellar artery about 80% of the time,18 the blood supply to the cochlea should be at risk with expanding lesions of the IAC. The internal auditory artery divides into the cochlear-anterior vestibular and vestibulocochlear arteries within the internal auditory meatus, so lesions of the internal artery should result in vertigo or in very rapid deterioration of cochlear hair cell function, especially in the low frequencies since the cochlear apex blood supply is the most tenuous.13,19 These symptoms are not typically seen in AN. In fact, seldom is a cochlear pure tone hearing loss seen before

Hearing Loss in Neurotologic Diagnosis

decreased speech discrimination or neural type changes. Also, acute vascular compression should cause electrocochleographic changes identified by a decreased cochlear microphonic, which is not often seen.20 In an attempt to explain the different types of hearing losses seen in AN, Lehnhardt21 suggested a theory involving both myelin and axon compression damage. He theorized that early in the course of compression, the myelin damage might be the only lesion, allowing for tone decay and acoustic reflex decay without recruitment. Auditory brainstem evoked responses would also be delayed. This would be the typical picture of AN. Later on, as myelin and axon compression both become involved, the ABR would be delayed, still without recruitment. If the tumor compression changes, for instance, in cessation of tumor growth or recovery from intratumor hemorrhage, enough axons may remain to allow for adequate nerve conduction and remyelinization may occur. Therefore recruitment may be positive, the ABR may be positive, but tone decay may not occur. Lesions of the olivocochlear system or auditory efferents22 have also been implicated in early hearing losses with auditory distortion, but little pure tone threshold increase. Deficits of the efferent system will affect the outer hair cells of the cochlea, allowing for difficulty with speech understanding in noise and the subjective sensation of distortion while having little effect on the pure tone hearing thresholds. Outer hair cell function as evaluated by otoacoustic emissions should be reduced or absent in ears affected by cochlear hearing losses.12 Distortion product otoacoustic emissions (DPOAEs) should be normal in AN patients if the hearing thresholds are better than 45 to 50 dB HL and the loss is purely retrocochlear (neural compression), and DPOAEs should be abnormal in losses that have a cochlear (vascular or inner ear biochemical) component. Telischi12 reported on 97 patients with AN who underwent DPOAE testing. He found that from 37% to 57% of tumors were classified as having a cochlear loss pattern, and 41% to 59% had a retrocochlear pattern depending on the analysis method used. He concluded that the majority showed evidence of reduced outer hair cell function in at least one frequency. The effects on the OAEs did not reverse after tumor resection even when other behavioral and objective hearing measures improved, implying a nonreversible cochlear or efferent pathway damage. These findings are compatible with previous studies that have demonstrated biochemical and magnetic resonance image (MRI) changes in the ipsilateral cochlea of some AN patients. As early as 1950, Dix and Hallpike23 found changes in the characteristics of perilymph in AN patients. Other authors24,25confirmed these changes. Somers and coworkers26 reported on MRI studies in AN and meningiomas, and showed increased postoperative hearing preservation in ears with normal intralabyrinthine and lateral IAC fluid characteristics versus ears with hypointense perilymph and fundus cerebrospinal fluid (CSF) images. They theorized that an arterial vascular compromise in the IAC secondary to mechanical obstruction by the tumor leads to reversible and irreversible intracochlear changes. Some MRI changes returned to normal after tumor removal, but many times OAEs do not revert to normal, again suggesting possible

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reversible biochemical changes but permanent hair cell injury. Grabel and colleagues27 suggested that the chronic effect of high tumor volume within the infratentorial compartment may also play a role in AN hearing loss when they showed a strong positive correlation between maximum tumor volume and prolonged ABR interpeak latencies for waves III through V following stimulation of the nontumor side. This suggests tumor volume-generated distortion as an additional factor in tumors that extend into the CPA. Sekiya and colleagues28 demonstrated in dogs that gentle traction on the eighth nerve in the CPA could lead to hemorrhages within the nerve and secondary auditory deficits. This mechanism may help explain the hearing loss associated with other tumors within the CPA that cause nerve distortion without significant compression. It may also help explain the tinnitus and hearing loss that may accompany neurovascular compression of the eighth nerve in the CPA.29 Direct auditory nerve or brainstem auditory pathway lesions30 have also been associated with neurotologic hearing loss in cases of multiple sclerosis (MS). The hearing losses associated with neurotologic entities, and especially those of AN, most likely involve multiple mechanisms, any or all of which may be seen in any one lesion. The variety of mechanisms possible for the hearing loss of neurotologic lesions also helps explain the variety of hearing losses that may be seen.

CLINICAL DIFFERENTIATION OF HEARING LOSS: COCHLEAR VERSUS NONCOCHLEAR Until the past two decades, the literature reflected efforts to diagnose AN by the characteristics of the hearing loss it induces. As mentioned under the discussions of the different mechanisms of hearing loss, the loss from an AN or other CPA lesion was considered noncochlear or retrocochlear. The characteristics of a cochlear loss should reflect hair cell damage with an intact eighth nerve (i.e., recruitment, pure tone hearing loss with intact discrimination, evidence of hair cell damage, and the absence of auditory fatigue). A number of test batteries were developed, all with a high degree of false negativity. No one test, until the ABR, had a sufficiently high rate of diagnostic selectivity to stand on its own or to guide further radiologic evaluation. Now the role of the ABR, in the MRI era, is changing. The phenomenon of auditory fatigue has been used to try to differentiate cochlear versus retrocochlear losses. The stapedial reflex decay or its absence has also been used diagnostically for this purpose. Thomsen and coworkers31 noted positive stapedial reflex decay or an absence stapedial reflex in 78% of their 59-patient series in 1983. Kanzaki and colleagues32 found absent stapedial reflex, elevated threshold of the reflex, or positive decay in approximately 75% of their 132-patient series. The absence of the reflex or positive decay did not depend on tumor size. Moffat and coworkers33 identified only one of their 49

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SYMPTOMS OF NEUROTOLOGIC DISEASE

CPA tumor patients as having a normal stapedial reflex pattern. Hirsch and Anderson10 demonstrated 73 of 75 AN patients as having no stapedial reflexes or positive reflex decay, and Harner and Laws34 demonstrated 49 of 61 AN patients as having positive reflex decay or absent stapedial reflexes. Anderson and colleagues35 examined 17 patients with CPA tumors and hearing thresholds of less than 60 dB. Twelve of the tumors were ANs and five were not. Six patients had normal hearing. The stapedial reflex decay was positive in all 10 patients who attained reflex thresholds. Thomsen and coworkers31 further tried to differentiate between AN hearing losses and that due to other causes. They compared three groups of patients. The first group had AN verified at surgery, the second group was evaluated for an AN but found to be negative, and the third group was diagnosed with Ménière’s disease. In their comparison of the three groups, the AN patients had significantly worse hearing at high frequencies, significantly worse speech discrimination, significantly less recruitment, but no significant difference in stapedial reflex decay. They did find a significantly greater incidence of a progressive hearing loss as the first symptom of the disorder. Again, gross group distinctions were noted between AN patients and other types of sensorineural hearing losses, but on an individual basis, the cochlear versus noncochlear distinction is difficult to use as a diagnostic criterion. Beginning in the 1970s, diagnosis of neurotologic lesions by the identification of retrocochlear hearing loss began to take on a new picture with the advent of the ABR. Selters and Brackmann,36 House and Brackmann,37 and Clemis and McGee11 in the late 1970s began to demonstrate the high rate of abnormality of the ABR in AN patients. These authors demonstrated 92% to 98% sensitivity for absent or abnormal ABR in AN patients. Eggermont and colleagues20 suggested that the abnormal ABR was probably from abolition of the synchronized firing of nerve fibers rather than a prolongation of the nerve conduction velocities. This was especially true for the high-frequency fibers, which run around the outside of the auditory nerve, versus the middle and apical turn fibers, which are positioned more toward the middle of the nerve and possibly are less disturbed in the early stages of tumor growth. The responses from the middle and apical turns are longer in latency, due to the greater time needed for

the cochlear traveling wave to initiate the response. This would account for the reduced synchronization of firing of nerve fibers without necessarily a change in the hearing itself. Historically, the ABR has changed the evaluation of unilateral or asymmetrical sensorineural hearing losses, but the trend is toward finding more normal ABRs with the earlier identification of very small or intracanalicular lesions. In the past decade gadolinium-enhanced MRIs have become more widely available, and tumors smaller than 15 mm are more routinely identified. In tumors less than15 mm, and especially those that are intracanalicular, there may be insufficient neural compression to cause a retrocochlear hearing loss as defined by an abnormal ABR. Table 7-1 shows ABR results for several series of small ANs. ABR continues to show a consistent asynchronous, retrocochlear pattern in tumors >2 cm but, in intracanalicular tumors, a much greater percentage will show a normal (or cochlear) pattern. The ABR is not specific for AN. In the series of Laird and coworkers38 and of Granick and colleagues39 six out of six meningiomas of the posterior fossa that had an ABR were positive in each series. House and Brackmann37 also demonstrated that only about 75% of patients with CPA lesions that were not ANs had abnormal ABRS. Marangos and coworkers40 found 23.5% of meningiomas had a normal ABR. The diagnostic accuracy and sensitivity of the ABR is not matched by electrocochleography (ECoG). Eggermont and colleagues20 evaluated the use of ECoG in retrocochlear lesions. They found the slope of the action potential amplitude versus intensity function similar in range and dependent on the action potential threshold, as it was in Ménière’s disease. Narrowband ECoG analysis suggested the same number of viable neurons in AN patients as in normal or recruiting cochlear losses. They felt that for tumors with milder losses (those <60 dB) the loss may be more cochlear in origin, possibly a slow compression of the vascular supply with a secondary metabolic dysfunction accounted for the hearing loss in AN patients. As mentioned previously, even though DPOAEs logically should help differentiate cochlear from retrocochlear causes of hearing loss, in CPA lesions about half demonstrated both patterns so DPOAEs have therefore not been helpful as a diagnostic tool.

TABLE 7-1. Tumors with Normal Auditory Responses

Series

Year

Grabel et al.27* Levine48 Gordon75* Chandrasekhar73* Zappia76* Marangos40†

1991 1991 1995 1995 1997 2001

% Intracanalicular Tumors with Normal ABR 30 37 31 16.9 11

% Tumors <15 mm with Normal ABR

% Tumors >2 cm with Normal ABR ABR Latency & Morphology

15.5 41.7

*Normal ABR=Wave V interaural or interpeak I-V latency difference < 0.2 msec. † Normal ABR=Wave V interaural difference <0.3 msec or interpeak I-V difference < 0.2 msec. ‡ Tumor >25 mm.

3.3‡

Hearing Loss in Neurotologic Diagnosis

PRESENTATION OF CEREBELLOPONTINE ANGLE LESIONS

and Selesnick and colleagues43 have demonstrated shorter times from onset to diagnosis in intracanalicular and small tumors than in medium and large tumors. The signs and symptoms present at diagnosis are almost exclusively auditory, and only rarely are other neurologic symptoms found in the absence of auditory symptoms. Table 7-4 demonstrates the signs and symptoms at the time of diagnosis. The percentage of patients with hearing loss or tinnitus (or both) at the time of diagnosis is about 95% or greater in AN patients even in patients with small tumors; however, hearing loss or tinnitus was found in 60% of meningioma patients by Laird and coworkers38 and in 75% by Granick and colleagues.39 Unilateral tinnitus at diagnosis is identified in 56% to 85% of patients with AN. Again, in the meningioma series, tinnitus was identified in only 34% to 50% of patients at the time of diagnosis. The hearing loss identified is usually moderately severe, with typical pure tone averages (PTA) of 50 to 55 dB usually worse in the high frequencies. The percentage of patients with a PTA worse than 80 dB was 15% to 35%. A small correlation may exist between the degree of hearing loss and the amount of time symptoms have been present, but such a wide variation exists that generalization is difficult. Other auditory symptoms such as aural fullness are occasionally identified; however, aural fullness is rarely found in the absence of other auditory symptoms or signs. The symptoms of hearing loss or tinnitus are independent of tumor size, but there is a definite trend toward better hearing in tumors less than 1 cm. Atypical presentations, such as normal hearing and sudden or fluctuating hearing loss, are examined separately in a later section. Classically, the patient with an AN or other CPA tumor has been described as having a high-frequency sloping sensorineural hearing loss. Table 7-5 outlines the shape of the audiometric configuration in several large series of patients. The category of high tone loss is broken down in some cases to an abrupt loss, in which hearing shows a steep drop of at least 15 dB at frequencies greater than 2000 Hz, or a gradual high-frequency loss, in which the hearing threshold increases less than 15 dB per octave. The U-shaped configuration has the greatest hearing loss

In this section, the typical presentation of CPA tumors is examined. The focus, again, is on AN, since few differences exist in the presentation of hearing loss from other tumor types found in this area. Significant differences, when present, are identified in this section, and hearing losses related to other nontumor diagnostic entities are discussed in later sections. The typical picture or presentation of a CPA tumor, as can be imagined from gradual compression of a slowgrowing mass, is that of a very slowly progressive sensorineural hearing loss with speech discrimination much worse than would be expected for the given degree of pure tone hearing. As mentioned by Cushing,1 the hallmark of AN is auditory dysfunction with hearing loss or tinnitus. The incidence is so high that absence of these symptoms is striking. As seen in Table 7-2, a number of authors verify that the initial or presenting symptom is hearing loss with or without tinnitus in about 80% of patients. Tinnitus as the only presenting symptom is found in about 7% of patients, and hearing loss without tinnitus is identified in between 40% and 80%. The picture changes when examining initial or presenting symptoms versus symptoms present at the time of diagnosis for two reasons: one of which is the long delay between onset of symptoms and diagnosis, and the other is the proportion of patients with subjectively normal hearing, but identifiable audiometric abnormalities on examination. As seen in Table 7-3, the average number of years from onset of symptoms to diagnosis is about four. This has changed somewhat as diagnostic methods and awareness have improved; however, a long delay is still identified. Time from onset of symptoms to diagnosis is less than 1 year in only about 20% of patients. Delays of 7 to 10 years are not uncommon. In Table 7-3, the reports by Glasscock and coworkers41 and Hirsch and Anderson10 reflect diagnostic delays only in patients who have moderate hearing losses or better. All severe and profound losses have been excluded. This delay should decrease with the advent of the MRI. Using MRI, Kanzaki and colleagues42

TABLE 7-2. Initial or Presenting Symptoms of Acoustic Neuroma

Authors

Year

No. of Patients

Cushing1 Erickson et al.78 Ellis and Wright78 Hart and Davenport79 Thomsen et al.31 Thomsen and Tos58 Kanzaki et al.42 Levine et al. (>4 cm)80 Levine et al. (<4 cm)80 Selesnick et al.43 Dornhoffer et al.44* Chandrasekhar et al.73 Magdziarz et al.48

1917 1965 1974 1981 1983 1990 1991 1991 1991 1992 1994 1995 2000

30 129 214 20 59 300 132 19 8 136 70 197 369

*All tumors <2 cm.

No. with Hearing Loss Only (%) 45 (35) 90 (42) 14 (70) 47 (80) 245 (82) 79 (60)

167

No. with Tinnitus Only (%)

No. with Tinnitus, with or without Hearing Loss (%)

No. with Hearing Loss and/or Tinnitus (%)

15 (12) 8 (4)

25 (83) 80 (63) 160 (75)

4 (7) 22 (7)

51 (87) 267 (89)

Vertigo (%)

66 (50) 18 (95) 7 (88)

84 (67)

45 (36)

128 (65)

31 (16)

159 (81)

5 (26) 4 (50) 2 (3)

168

SYMPTOMS OF NEUROTOLOGIC DISEASE

TABLE 7-3. Duration of Symptoms from Onset to Diagnosis No. of Patients with Durations of Symptoms Authors

Year

No. of Patients

Years from Onset to Diagnosis

Erickson et al.77 Johnson45 Mathew et al.57 Hirsch and Anderson10† Glasscock et al.81 Glasscock et al.81 Glasscock et al.41‡ Thomsen and Tos58 Kanzaki et al42 Kanzaki et al.42 Selesnick et al.43

1965 1977 1978 1980 pre-1975 post-1975 1987 1990 1991 1991 1992

129 500 206 96 100 100 47 300 119 13 126

4.6 2 3.3 2.4 1.2 7.1§ 4.1|| 2.2|| 3.9

<6 mo.

7–12 mo.

1–3 yr.

>3 yr.

84 (17)

25 (5) 43 (21)* 11 (11)

202 (40) 60 (29) 20 (21)

188 (38) 103 (50) 39 (41)

26 (27)

67 (22)*

*Symptoms for 0-12 months. † All patients had pure tone average < 60 dB. ‡ All patients had pure tone average < 50 dB. § Average for patients with symptoms > 1 year. || 119 patients excluding those with intracanalicular tumors; 13 patients with only intracanalicular tumors.

at 2000 Hz. The peak configuration has the best hearing thresholds at 2000 Hz, with increasing losses at the low and high frequencies. As can be seen, the majority of losses are of the high-frequency nature with abrupt high tone losses a major proportion. If the abrupt and gradual highfrequency losses are combined, they account for anywhere from 32% to 68% of the configurations, with the majority between 50% and 60%. However, large minorities of configurations are flat or U-shaped. The percentages vary from 16% to 47%, with most lying in the 20% to 30% range. Ten to 25% of patients have severe to profound hearing losses, with PTA greater than 80 dB at the time of their initial audiogram. Low tone losses are very uncommon. Other configurations of audiograms can be found, but were too few to be classified into one of the characteristic shapes. Generally, no typical shape is found for any one type of tumor; however, Kanzaki and colleagues32 and Dornhoffer and coworkers44 noted that 20% to 22% of

small and intracanalicular tumors had a U-shaped audiometric configuration. The degree of hearing loss and speech discrimination deficits varies widely, but historically patients have had moderate to severe pure tone losses with poor speech discrimination scores (SDS) on presentation. Table 7-6 outlines the findings from several large series of tumor patients with audiometric examinations. In AN, anywhere from 3% to 22% of patients have three frequency PTA (500, 1000, and 2000 Hz) thresholds better than 20 to 25 dB, and 16% to 45% of patients have PTA worse than 70 dB. The figures of Kanzaki and colleagues32 include a PTA for five frequencies from 250 to 4000 Hz. Their category of 18% of patients in the better hearing group comprises patients with PTA between 0 to 30 dB. This group roughly corresponds to the other groups, because the hearing at 4000 Hz is characteristically considerably worse than that in the nontumor ear in AN patients. Of note is the series

TABLE 7-4. Signs and Symptoms at the Time of Diagnosis of Acoustic Neuroma or Meningioma Authors

Year

No. of Patients

No. with Tinnitus (%)

Erickson et al.77 Ellis and Wright78 Clemis and Mastricola82 Johnson44 Mathew et al.57 Harner and Laws34 Thomsen and Tos83 Moffat et al.33 Kanzaki et al.32 Selesnick et al.43 Laird et al.†38 Granick et al.†39 Dornhoffer et al.‡44 Chandrasekhar et al.73 Magdziarz et al.48

1965 1974 1976 1977 1978 1983 1988 1989 1991 1992 1985 1985 1994 1995 2000

129 214 121 500 206 131 300 66 132 126 20 32 70 197 369

1 %*

*Tinnitus without hearing loss. † All tumors were posterior fossa meningiomas. ‡ All tumors <2 cm. PTA, pure tone average; SRT, speech reception threshold.

135 (66) 92 (70) 112 (85) 71 (56) 10 (50) 11 (34) 45 (60) 157 (80) 290 (79)

No. with Hearing Loss and/or Tinnitus (%) 125 (98) 206 (96) 120 (99) 474 (95) 199 (97) 128 (98) 291 (97) 64 (97) 125 (95) 107 (85) 12 (60) 24 (75) 66 (95) 171 (87) 346 (97)

Mean PTA or SRT

50 dB 56 dB 52 dB 55 dB 46 dB 29.2

No. (%) with PTA or SRT >80 dB

Vertigo (%)

16 (13) 75 (15) 60 (29) 105 (35) 17 (25) 59 (45) 19 (15) 27 (39) 112 (57) 77 (21)

Hearing Loss in Neurotologic Diagnosis

169

TABLE 7-5. Audiogram Shape for Acoustic Neuroma Patients

Authors

Year

No. of Patients

Clemis, Mastricola82 Johnson45 Hirsch, Anderson10 Thomsen et al.31 Brunás et al.84 Glasscock et al.41 Moffat et al.33 Kanzaki et al.32 Dornhoffer et al.44|| Saunders et al.51¶

1976 1977 1980 1983 1984 1987 1989 1991 1994 1995

121 500 69 59 141 47§ 66 132 70 92

Abrupt High Tone Loss No. (%) 91 (75)* 282 (66)†‡ 39 (57) 35 (59) 21 (18) † 25 (53) 37 (56) ‡ 26 (20)

Gradual High Tone Loss

Low Tone Loss

No. (%) of Patients With: PeakFlat Loss U-Shaped Shaped

15 (12) 39 (9) 5 (7) 57 (50) 16 (12) 50 (71) 48 (52)

1 (1)

55 (13) 6 (9) 7 (12) 17 (15) 22 (47) 9 (14) 34 (26) 3 (4) 17 (18)

49 (12) 9 (13) 2 (4) 12 (11)

PTA >80 dB 16 (13) 75 (15)

10 (15)

1 (2) 7 (5) 13 (19) 18 (20)

15 (25) 27 (19) 17 (25) 15 (11) 9 (10)

*Combines abrupt high tone and flat losses. † Based on patients with recordable audiograms (%). ‡ Combines abrupt and gradual high tone losses. § All patients had PTA <50 dB. || All tumors <2 cm. ¶ Patients with sudden hearing loss only. PTA, pure tone average.

of meningioma patients. Laird and colleagues38 identified 8 of 15 patients, or 53%, as having a PTA of 0 to 20 dB. Granick and coworkers39 identified 6, or 26%, of their group with a PTA of 0 to 20 dB. As mentioned earlier, characteristically, speech discrimination for the eighth nerve tumor patients is quite poor. Table 7-6 also lists the SDS for several large series of subjects with eighth nerve lesions. The mean SDS is very poor, with the best being from the series of meningioma patients of Laird and colleagues.38 For an SDS greater than 90%, the Kanzaki series32 found 13% of patients in that category, and Harner and Laws34 found 9 of 117 patients, whereas, in the Dornhoffer series of subjects with small tumors,44 37% had normal discrimination and the mean speech score was 82%. Speech discrimination greater than 80% was found in 24% of subjects in the series by Kanzaki and colleagues,32 18% of Harner and Law’s,34 and in 30% in the series by Selesnick and coworkers.43 In the older series by Johnson,45 only 24% of patients

had a SDS better than 60%. Again, the meningioma patients experienced less effect on their speech discrimination than the AN patients. Laird and colleagues38 found that 40% of meningioma patients had discrimination better than 90%, 47% had discrimination better than 80%, and 60% of their patients had discrimination better than 60%. Historically, no correlation has been found between the degree of hearing loss or speech discrimination deficit and tumor size.13,46 Beginning in the MRI era, however, a trend is developing toward better hearing thresholds and SDS in patients with very small tumors. Selesnick and coworkers43 found that patients with tumors less than 1 cm in diameter had average pure tone loss of 40 dB, and 50% of those patients had a SDS of greater than 81%, and the series of less than 2-cm tumors of Dornhoffer44 found 37% with normal speech discrimination. In patients with medium and large-sized tumors, the average speech reception threshold was 47 and 58 dB, respectively, and only 25% of patients with medium or large tumors had a SDS better

TABLE 7-6. Degree of Hearing and Discrimination Loss in Patients with Acoustic Neuromas or Meningiomas No. (%) with PTA or SRT Author

Year

No. with Audiogram

Johnson45 Josey85 Harner and Laws34 Thomsen et al.58 Kanzaki et al.32 Selesnick et al.43 Laird et al.38‡ Granick et al.39‡ Dornhoffer et al.44§

1977 1980 1983 1990 1991 1992 1985 1985 1994

500 52 117 300 132 130 15 23 70

*PTA >56 dB. † 5 frequency PTA for 0.25-4 kHz <30 dB. ‡ All tumors were posterior fossa meningiomas. § All tumors <2 cm. SRT, speech reception threshold; PTA, pure tone average.

0–20

0–25

20/25–45

11 (21) 14 (12)

15 (29)*

No. (%) with Speech Discrimination ≥90%

≥80%

≥60%

Mean Discrimination

120 (24) 9 (3)

22 (18)

56% 8%

17 (13)

32 (24) 39 (30) 7 (47)

37% 53% 76%

48 (16) 24 (18)†

29 (22) 8 (53) 6 (26) 4 (6)

11 (9)

3 (20)

6 (40) 26 (37)

9 (60)

82%

170

SYMPTOMS OF NEUROTOLOGIC DISEASE

than 81%. As is seen in the discussion of CPA tumor patients with normal hearing,47–49 a poor correlation occurs between normal hearing and tumor size, though a definite trend exists toward better hearing in intracanalicular tumors. The very poor SDS for the tumors in general supports a hearing loss mechanism of neural compression. Thomsen and colleagues31 discussed the concept that discrimination at high presentation levels is primarily an inner hair cell function, and 95% of the fibers in the auditory nerve originate in the inner hair cells. Therefore, the neural compression would inhibit inner hair cell function with the resultant poor discrimination, especially at increasing presentation levels.

Sudden or Fluctuating Hearing Loss Though not common, space-occupying lesions of the CPA and IAC can present as a sudden hearing loss or as a sudden exacerbation of an existing hearing loss. Table 7-7 summarizes the incidence of sudden hearing loss in a number of large series of patients with AN and other CPA tumors. As can be seen, about 10% (4% to 26%) of patients with AN present with a sudden hearing loss. In those manuscripts that specified the sudden hearing loss as a presenting symptom, the incidence is 7% to 14%, with an exacerbation of an existing loss occurring in 7% or 8%. A number of the other series did not differentiate specifically, and in fact Selesnick and colleagues43 combined both types of sudden loss for the incidence of 26%. The large series by Pensak and coworkers50 described 77 patients (69 had AN and 7 had meningiomas) who complained of a sudden hearing loss. Of the 77, 25 patients had a PTA for the frequencies from 500 to 4000 Hz of better than 35 dB, and of these 25 patients, 11 had an SDS of better than 88%. Two additional patients of the 77 had an SDS better than 88%, even though their PTA fell between 35 and 60 dB. Twelve of the 77 patients had a PTA worse than 60 dB. They described a configuration of the audiogram as a high tone loss in 60%, a flat loss in 19%, a U-shaped (trough)

loss in 15%, and a low tone loss in 6%. The degree of hearing loss did not correlate with tumor size. Saunders and colleagues51 also showed a very low incidence of low-frequency losses especially compared with sudden hearing losses not secondary to tumors. Pensak and coworkers50 suggested the possibility of a vascular occlusion with degeneration of the organ of Corti, although the findings are too inconsistent to adequately differentiate the vascular occlusion effect from rapid eighth nerve compression due to hemorrhage in a tumor. In the series by Ogawa and colleagues,52 29 patients, or 22%, had a sudden hearing loss or exacerbation of an existing loss. They felt that the characteristics of AN with sudden hearing loss differed from other AN presentations in several ways: (1) smaller tumor, (2) shorter duration after onset, (3) lower incidence of dizziness or other neurologic symptoms, (4) a trough-type audiogram configuration, and (5) a higher incidence of a normal caloric response on electronystagmography. A higher incidence of the subjective symptom of aural fullness was also noted. Of note, of their 14 patients with intracanalicular tumors, 5, or 36%, had a sudden hearing loss. They questioned a vascular cause and supported a cause from nerve compression, due to the high incidence of midfrequency losses and the low incidence of dizziness. Berg and colleagues53 identified 13 of 133 patients with a sudden sensorineural hearing loss, 4 of whom recovered some auditory function. In evaluating their series of sudden hearing loss patients, no clinical distinction was noted between sudden hearing loss caused by tumors and that caused by other disease states, other than a positive ABR test. Saunders and coworkers51 felt that associated symptoms of pain, facial paresthesias, or unilateral tinnitus preceding the sudden hearing loss might suggest a tumor. Hallberg54 and Shaia and colleagues55 found a 0.6% and 0.8%, respectively, incidence of AN in a large series investigating sudden sensorineural hearing loss from any cause. Saunders and coworkers51 studied only patients with sudden hearing losses who had MRIs, and found an incidence of tumors of 2.7%. Again, the distinction between hearing loss caused by vascular disease or neural compression is blurred. Certainly,

TABLE 7-7. Cerebellopontine Angle Tumors Presenting as Sudden Hearing Loss

Author

Year

No. of Patients

Higgs86 Ellis and Wright78 Mathew et al.57 Hirsch and Anderson10 Thomsen et al.31 Pensak et al.50 Berg et al.51 Kanzaki 87 Thomsen and Tos83 Ogawa et al.52† Selesnick et al.43 Chandrasekhar et al.73 Saunders et al.51 Aslan et al.88 Magdziarz et al.48

1973 1974 1978 1980 1983 1985 1986 1986 1988 1991 1992 1995 1995 1997 2000

44 214 206 96 59 506 133 90 300 132 136 197 1204 192 369

*Initial symptom was sudden hearing loss. † Also Kanzaki.

No. with Sudden Hearing Loss or Sudden Change in Existing Loss (%) 4 (9) 11 (5) 9 (4) 7 (7) 5 (8)* 77 (15) 17 (13) 12 (13)* 21 (7)* 19 (14)* 33 (26) 26 (13) 79 (5) 14 (7.3) 38 (10.3)

No. with Sudden Change in Existing Loss (%)

No. with Recovery or Fluctuation (%)

Time From Onset to Diagnosis (mo.)

39.8 4/17 (23) 6 (7) 10 (8)

41.3

6/14 (43)

Hearing Loss in Neurotologic Diagnosis

aspects of both are involved in sudden hearing loss, but so are aspects that mitigate against one or the other causes, suggesting a combination of mechanisms in the majority of these losses. It is interesting that, even with a sudden change in hearing, the delay between onset of symptoms and diagnosis is more than 3 years on average. The series by Pensak and colleagues50 had an average time of 39.8 months between onset of symptoms to diagnosis, and the series by Ogawa and coworkers56 and the one by Kanzaki and colleagues42 had an average time of 41.3 months. In some cases, the patients had presented themselves for evaluation, but a diagnosis of AN was not made until much later. In the Saunders and colleagues51 series, patients who were not diagnosed in the 6 months after onset of hearing loss often went more than 2 years before diagnosis.

Normal Hearing Patients with CPA tumors can present with normal hearing. This fact has been recognized for some time, but has become more significant in the current climate of early identification and hearing preservation surgery for these tumors. Table 7-8 represents the summation of a number of series on patients with AN and other CPA tumors that have presented with normal hearing. The definition of normal hearing varies with the different series. As can be seen, the number of patients with a PTA or speech reception threshold less than 20 or 25 dB varies from 3% to 22%; however, when patients with an SDS greater than or equal to 90% are included, the number with normal PTA or speech reception threshold and normal speech discrimination is only 4% to 12%. The majority of series demonstrate about a 5% to 7% incidence of truly normal hearing. Generally, there was little correlation of normal hearing and tumor size. The decrease in SDS in AN patients is again seen to be out of proportion to the pure tone findings. As seen in the series of Mathew and colleagues,57 Selesnick and coworkers,43 and Beck and colleagues,47 possibly only about onefourth of the patients with a normal PTA also have normal

171

speech discrimination. This finding is not generalized throughout all series, but the majority of authors report a decrease in the number of patients with normal discrimination versus the number with normal PTA. Several series used 4000 Hz in their PTA, which seems to be a significant differentiating factor between normal and abnormal hearing. The hearing loss at 4000 Hz is often a marker for unilateral losses in cases of AN, whereas a PTA, based only on 500, 1000, and 2000 Hz, may misidentify patients, calling them normal when they would otherwise fit the category of a someone with a unilateral sensorineural loss. Two series24,58 looked at hearing loss at 4000 Hz. In the series by Beck and colleagues,47 of 21 patients with normal hearing, the pure tone thresholds at 4000 Hz averaged 35 dB on the ear with the tumor and averaged 14 dB on the tumor-free ear; while in the series of Selesnick and colleagues,43 85% of patients had an asymmetry of greater than 15 dB between the two ears at 4000 Hz. Interestingly, in the series that reported the symptom of subjective hearing loss, most showed a very high percentage of patients reporting a subjective hearing loss, even though the audiometric examination was normal. Anywhere from 20% to 70% of the patients with normal audiometric examinations had a subjective hearing loss, 40% to 70% had tinnitus, and 16% to 66% demonstrated dizziness. In the series by Beck and colleagues,47 only 1 patient out of 408 was truly asymptomatic at the time of diagnosis. Magdziarz and coworkers48 reported an incidence of 2.7% with completely normal hearing (PTA <20 dB, discrimination >90%, and interaural differences <10 dB at any frequency), but again at least 40% of that group had subjective hearing loss or tinnitus (and 70% had an abnormal ABR). Therefore even the patient with a normal audiometric examination frequently had objective or subjective symptoms that were otologic in nature. When adding the objective and subjective symptoms, only the very rare patient is truly asymptomatic on presentation, though this will probably change with the common use of MRI for other intracranial diagnoses. The other patient who can be considered to have normal hearing is the one with binaurally symmetrical hearing,

TABLE 7-8. Acoustic Neuroma Patients Presenting with Normal Hearing Number of Patients With (%): Author

Year

No. of Patients

Johnson45 Mathew et al.57 Harner and Laws34 Beck et al.47 Roland et al.46 Thomsen and Tos58 Ogawa et al.49 Selesnick et al.43 Dornhoffer et al.44§ Magdziarz et al.48

1977 1978 1983 1986 1987 1990 1991 1992 1994 2000

500 118 117 408 614 300 132 130 70 369

PTA or SRT <20 dB

Normal PTA & SDS ≥90%

Binaural Symmetry

Number of Patients With (%): Subjective Hearing Loss

Tinnitus

Dizziness

Positive ABR

5 (1) 8 (1)

13 (62) 16 (42)

9 (43) 24 (63)

14 (66) 6 (16)

8/9 (89) 31/33 (94)

10 (8) 9 (7) 6 (8)

7 (70)

7 (70)

3 (30)

9 (90) 33/35 (94)

2 (20)

4 (40)

4 (40)

26 (5) 24 (20)* 14 (12)* 21 (5)* 30 (5) 9 (3) 10 (8)† 29 (22)

8 (7) 14 (12) 5 (1) 31 (5) 6 (5)‡ 5 (4) 4 (6) 10 (2.7)

*PTA 0.5-2 kHz <25 dB. † PTA 0.5-4 kHz <25 dB. ‡ SDS ≥80%. § All tumors <2 cm. PTA, pure tone average; SRT, speech reception threshold; SDS, speech discrimination score.

7 (70)

172

SYMPTOMS OF NEUROTOLOGIC DISEASE

regardless of the hearing level of the tumor ear. Most of these patients are normal, and this rate is from 1% to 8%, with the average being about 5% to 7%. Normal hearing on presentation is more common in patients with noneighth nerve tumors. Hirsch and Anderson10 reported that of their 97 patients with hearing thresholds of 60 dB or better, 28 had hearing that was within normal limits with respect to age and sex. They did not specify objective audiometric criteria. In their series of 97, 22 did not have an AN. There were six meningiomas, six gliomas or astrocytomas, four cholesteatomas, two neuromas not of eighth nerve origin, and several other spaceoccupying lesions. In the 75 AN patients, 17, or 23%, met their criteria for normal hearing with respect to sex and age, whereas 50%, or 11 of the 22 non-AN patients, were classified as normal. There is no good correlation between tumor size and the occurrence of normal hearing46–49 though a trend exists toward patients with intracanalicular tumors having a higher likelihood of normal hearing.44 Patients with normal hearing usually are younger48 and have a much shorter length of time between onset of symptoms and diagnosis. Thomsen and Tos59 found a positive correlation between severity of hearing loss and the duration of symptoms. The patients in most of the normal-hearing series have had a shorter average time between presentation and diagnosis than AN patients in general. This is certainly logical when studying an entity known for producing gradually progressive hearing loss, and possibly the patient presenting with normal hearing may not represent as much a difference in tumor type or consistency, as it does the amount of time for the tumor effects to take place. As a diagnostic indicator, the ABR has a high incidence of positive findings, even in patients with normal hearing. In the series in Table 7-8, from 70% to 94% of the patients were identified by a positive (abnormal) ABR. The patient with the small tumor with normal hearing, however, seems to be the one in whom the ABR may be negative. In the series of Selesnick and colleagues43 2 patients out of 35 had a normal ABR, both had normal hearing, and both had tumors less than 1 cm in diameter. Magdziarz and coworkers48 found three of nine patients with normal hearing had a normal ABR. Marangos and colleagues40 studied 50 (of 261) AN patients and 4 (of 17) meningioma patients who had a normal ABR and found 20% of the AN group had normal hearing (PTA) and 18% had binaurally symmetrical hearing. Twenty-five percent of the patients in the meningioma group had a normal PTA, and 50% had binaural symmetry. Again, in the consideration of mechanisms of hearing loss in patients with CPA and IAC tumors, those with objectively normal hearing, but subjective complaints of hearing loss and tinnitus, and frequently an abnormal ABR support the concept of slow nerve compression coupled with the fact that 75% of the auditory nerve fibers can be damaged without a change in pure tone hearing.15

Progression of Hearing Loss Four studies31,56,60,61 have examined the progression of hearing loss in AN patients. Nedzelski61 followed 28 elderly patients with AN who chose no surgical treatment.

Eight of the 28 had serviceable hearing at the beginning of the follow-up. The average deterioration of the PTA was 6 dB/year. The mean annual growth rate of the tumors in the same series was 0.22 cm/year, with the median annual growth rate of 0.1 cm/year. The range was 0.05 to 0.69 cm/year. Thomsen and colleagues31 had 19 of 59 patients with AN who had an audiogram 1 to 10 years prior to their most recent audiogram. The average time was 4.2 years between audiometric examinations. The mean deterioration of the PTA, 500 through 2000 Hz, was 9 dB/year. The average deterioration at 1000 Hz was 9.9 dB/year, and the average deterioration at 125 Hz was 6.1 dB/year. The range was from 10 dB over 6 years to 60 dB in 1 year. They found no relationship between age or tumor size in the progress of the hearing loss. Massick and coworkers60 followed 21 patients with a small (<19 mm, mean diameter 7.8 mm) AN for least 2 years (mean of 3.8 years). Tumor growth by volumetric analysis occurred in 66%, 24% showed no growth, and 10% receded. Changes in audiometric function were classified by the American Academy of Otolaryngology-Head and Neck Surgery 1995 guidelines. They demonstrated a significantly different mean deterioration of PTA and SDS depending on the initial hearing. Seventy-five percent of the patients in the best hearing group (class A) remained in the best group throughout the study. Whereas 50% of the group with class B hearing deteriorated to class D (nonserviceable), and those initially with class D hearing showed the largest drop in PTA and SDS. They demonstrated a significant correlation between tumor volume growth and changes in PTA and SDS, with the rate of change dependent on the initial hearing status. There was no difference between the groups in initial tumor location or size. Interestingly, one patient had a regression in tumor size and an improvement in audiometric function. Ogawa and colleagues56 examined the progression of hearing loss in 42 patients who could be tested for at least 6 months before surgery. They used a five-frequency PTA from 250 to 4000 Hz and identified three separate groups: (1) 5 of the 42, or 12%, recovered at least 11 dB during the period, (2) 28 of the 42, or 66%, showed less than a 10 dB change, and (3) a third group, 9 patients, or 21%, showed deterioration greater than 10 dB during the follow-up. The length of time from onset of symptoms to the first visit was 49 months in the unchanged group, 28 months in the recovery group, and 8 months in the deterioration group. The rate of change for all patients averaged −1.1 dB/month, with a rate of +5.7 dB/month in the recovery group, −0.3 dB/month in the unchanged group, and −8.2 dB/month in the deterioration group. The deterioration group on average had the smallest tumor size. In fact, all patients with tumors greater than 3 cm were in the unchanged group. Overall, the hearing loss in 88% of the patients was either unchanged or had deteriorated (20% deteriorated). The average deterioration of −1.1 dB/month for the entire group equals 13 dB/year. The probability and rate of progression of tumor growth and hearing loss are important considerations when determining the timing of hearing preservation surgery, the selection of nonsurgical treatment, or the treatment of bilateral AN.

Hearing Loss in Neurotologic Diagnosis

HEARING LOSS SECONDARY TO LESIONS OTHER THAN ACOUSTIC NEUROMA Two series of patients with posterior fossa meningiomas were examined. Granick and colleagues39 and Laird and coworkers38 examined 32 and 20 patients, respectively, with meningiomas of the CPA. As can be seen in Tables 7-4 and 7-6, the incidence of tinnitus and hearing loss is somewhat lower than in AN patients, with only 60% to 75% of patients showing one or the other auditory symptoms at the time of diagnosis, compared with 95% or more of patients with AN. The patients with meningioma also showed a higher percentage with hearing loss less than 20 dB and discrimination greater than 80% than did AN patients; otherwise, the configuration of the loss and appearance audiometrically is identical with that for patients with AN. Marangos and colleagues40 demonstrated a higher incidence of normal hearing, binaural symmetry, and normal ABR in patients with meningiomas than those with AN. In glomus jugulare tumors, the hearing loss can be either sensorineural or conductive. As described by Alford and Guilford62 and Brammer and coworkers63 more than 90% of patients with glomus tumors present with hearing loss. In one series,62 25 patients were examined; 13 had infralabyrinthine tumors and 12 had glomus tympanicum tumors. All the patients in this series with sensorineural hearing loss had infralabyrinthine tumors. Only one of the patients with infralabyrinthine tumors had normal hearing, but the ABR was positive in this case. MS is also a cause of retrocochlear hearing loss. Cure and colleagues64 examined 167 patients with hearing loss or tinnitus who had undergone MRI. Fourteen of the 167 patients had multifocal white matter disease as the only positive finding. Of the 14, 4 had unrecognized, clinically probable MS that was previously unsuspected. In 9 of the 14, the demyelinating disease was the probable cause of the auditory symptoms due to the identification of lesions in the auditory pathways. The lesions in the auditory pathways in MS are usually in the brainstem, where the MRI may be relatively insensitive because the lesions may be microscopic or too small to be demonstrated by the imaging. Bauch and coworkers58 examined 255 patients with suspected retrocochlear hearing loss. Twenty-six of them had surgically confirmed AN, and 6 were felt to have a retrocochlear hearing loss secondary to MS. The ABR was positive in four of the six MS patients. Hearing loss is not a common presenting symptom of MS. Mustillo65 noted that only 7% of their series of patients had hearing loss as a presenting symptom of MS. A number of authors11,30,66,67 noted that while the hearing loss as a presenting symptom is not common, a large percentage of patients with MS have objective findings of auditory pathway dysfunction. Jerger and colleagues66 found a 95% prevalence of auditory abnormalities by acoustic reflex testing, speech audiometry, or ABR testing. In 62 patients with definite MS, the acoustic reflex was abnormal in 71%, speech audiometry was abnormal in 55%, and the ABR was abnormal in 52%. No typical pattern of hearing loss is seen in MS. The loss can be unilateral or bilateral, sudden, progressive, temporary, or permanent. The loss usually presents itself within the first 4 years after the onset of MS

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and most often within the first year after the onset of neurologic symptoms.68 Franklin and coworkers69 and Furman and colleagues30 identified sudden hearing loss as a presenting symptom of MS. Another possible cause of retrocochlear hearing loss is neurovascular compression of the eighth nerve in the CPA. Meyerhoff and Mickey29 described two patients who had undergone microvascular decompression of the cochlear nerve to treat incapacitating tinnitus. They had normal neurologic and psychological examinations, the MRI test was normal, both had unilateral high-frequency sensorineural hearing losses with retrocochlear findings, and no other cause was identified. Both patients underwent decompression of the cochlear nerve, one from an offending posterior-inferior cerebellar artery and the other from an anterior-inferior cerebellar artery. Both obtained symptomatic relief, and improvement was reported in the highfrequency sensorineural losses. These finding correlate with those of Sekiya and colleagues,28 who demonstrated that traction on the eighth nerve in dogs might lead to secondary auditory deficits. A variety of other CPA pathologies have been associated with hearing loss. Patients with schwannomas of the facial nerve70 in the CPA are known to present with hearing loss that can be conductive, sensorineural, or mixed. Patients with petrous apex cholesteatomas and cholesterol granulomas typically present with either sensorineural or mixed losses.71 Lipomas72 are rare but are also associated with hearing loss in at least two thirds of the cases. As a general rule, these other lesions in the CPA cause a hearing loss that is indistinguishable from AN.

SUMMARY The typical presentation of a CPA lesion is a slowly progressive, unilateral, sensorineural hearing loss with tinnitus and poor speech discrimination. However, a number of authors have clearly demonstrated that the hearing loss of neurotologic disorders can be of any configuration, with any type of presentation, including that similar to a sudden sensorineural cochlear loss. The mechanism of the hearing loss, whether it is direct compression of the auditory nerve, compression of the vascular supply to the cochlea, or a combination of many factors, is not clearly understood. Very likely, it is a combination, varying with the specific site and lesion involved. The typical picture may also be changing, as demonstrated by several authors.6,27,42,43,48,59,73–75 More tumors are being picked up in the less than 1-cm range, and more tumor patients are being seen with normal or near-normal hearing than previously noted. The presentation in patients with neurotologic lesions, and those with AN in particular, almost always includes auditory symptoms. Even in the face of objectively normal hearing, subjective complaints of hearing loss or tinnitus frequently occur. The long delay between onset of symptoms and diagnosis continues, and as noted in the series of Selesnick and colleagues,43 the average time from hearing loss onset to diagnosis was still 3.9 years in 1992. This delay, of course, may partially be due to the patient not presenting for evaluation, but also is due to physicians and audiologists not pursuing the

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evaluation of symptoms far enough. If neurotologic lesions are to be diagnosed as early as possible, allowing for the best treatment results, the general rule of completely working up any unilateral sensorineural hearing loss or tinnitus without an obvious cause is still recommended.

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24. O’Connor F, Luxon L, Shortman RC, et al: Electrophoretic separation and identification of perilymph proteins in cases of acoustic neuroma. Acta Otolaryngol 93:195–200, 1982. 25. Schuknecht H: Pathology of acoustic schwannoma. In Schuknecht HF (ed.): Pathology of the Ear. Cambridge, Harvard University Press, 1976. 26. Somers T, Casselman J, Ceulaer G, et al: Prognostic value of magnetic resonance imaging findings in hearing preservation surgery for vestibular schwannoma. Otol Neurotol 22(1):87–94, 2001. 27. Grabel JC, Zappulla RA, Ryder J, et al: Brain-stem auditory evoked responses in 56 patients with acoustic neurinoma. J Neurosurg 74:749–753, 1991. 28. Sekiya T, Moller AR, Janetta PJ: Pathophysiological mechanisms of intraoperative and postoperative hearing deficits in cerebellopontine angle surgery: An experimental study. Acta Neurochin (Wien) 81:142–151, 1986. 29. Meyerhoff WL, Mickey BE: Vascular decompression of the cochlear nerve in tinnitus sufferers. Laryngoscope 98:602–604, 1988. 30. Furman JMR, Durrant JD, Hirsch WL: Eighth nerve signs in a case of multiple sclerosis. Am J Otol 10:376–381, 1989. 31. Thomsen J, Terkildsen K, Tos M: Acoustic neuromas. Am J Otol 5(1):20–33, 1983. 32. Kanzaki J, et al: Audiological findings in acoustic neuroma. Acta Otolaryngol (Stockh) Suppl 487:125–132, 1991. 33. Moffat DA, Hardy DG, Baguley DM: Strategy and benefits of acoustic neuroma searching. J Laryngol Otol 103:51–59, 1989. 34. Harner SG, Laws ER: Clinical findings in patients with acoustic neuroma. Mayo Clin Proc 58:721–728, 1983. 35. Anderson H, Barr B, Wedenberg E: Early diagnosis of VIIIth nerve turnouts by acoustic reflex tests. Acta Otolaryngol 263:232–237, 1970. 36. Selters WA, Brackmann DE: Acoustic tumor detection with brain stem electric response audiometry. Arch Otolaryngol 103:181–187, 1977. 37. House JW, Brackmann DE: Brainstem audiometry in neurotologic diagnosis. Arch Otolaryngol 105:305–309, 1979. 38. Laird FJ, Harner SG, Laws ER, Reese DF: Meningiomas of the cerebellopontine angle. Otolaryngol Head Neck Surg 93(2):163–169, 1985. 39. Granick MS, et al: Cerebellopontine angle meningiomas: clinical manifestations and diagnosis. Ann Otol Rhinol Laryngol 94:34–38, 1995. 40. Marangos N, Maier W, Merz R, Laszig R: Brainstem response in cerebellopontine angle tumors. Otol Neurotol 22(1):95–99, 2001. 41. Glasscock ME, McKennan KX, Levine SC: Acoustic neuroma surgery: The results of hearing conservation surgery. Laryngoscope 97:785–789, 1987. 42. Kanzaki J, Ogawa K, Ikeda S: Changes in clinical features of acoustic neuroma. Acta Otolaryngol (Stockh) Suppl 487:120–124, 1991. 43. Selesnick SH, Jackler RK, Pitts LH: Clinical presentation of acoustic neuromas in the MRI era. Laryngoscope. 103:431–436, 1993. 44. Dornhoffer JL, Helms J, Hoehmann DH: Presentation and diagnosis of small acoustic tumors. Otolaryngol Head Neck Surg 111(3):232–235, 1994. 45. Johnson EW: Auditory test results in 500 cases of acoustic neuroma. Arch Otolaryngol 103:152–158, 1977. 46. Roland PS, Glasscock ME, Bojrab DI, Josey AF: Normal hearing in patients with acoustic neuroma. S Med J 80(2)0:166–169, 1987. 47. Beck JB, Beatty CW, Harner SG, Ilstrup DM: Acoustic neuromas with normal pure tone hearing levels. Otolaryngol Head Neck Surg 94(1):96–103, 1986. 48. Magdziarz DD, Wiet RJ, Dinces EA, Adamiec LC: Normal audiologic presentations in patients with acoustic neuroma: An evaluation using strict audiologic parameters. Otolaryngol Head Neck Surg 122(2):157–162, 2000.

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49. Ogawa K, et al: Acoustic neuromas with normal hearing. Acta Otolaryngol (Stockh) Suppl 487:144–149, 1991. 50. Pensak ML, et al: Sudden hearing loss and cerebellopontine angle tumors. Laryngoscope 95:1188–1193, 1985. 51. Saunders JE, Luxford WM, Devgan KK, Fettierman BL: Sudden hearing loss in acoustic neuroma patients. Otolaryngol Head Neck Surg 113(1):23–31, 1995. 52. Ogawa K, et al: Acoustic neuromas presenting as sudden hearing loss. Acta Otolaryngol (Stockh) Suppl 487:138–143, 1991. 53. Berg HM, Cohen NL, Hammerschlag PE, Waltzman SB: Acoustic neuroma presenting as sudden hearing loss with recovery. Otolaryngol Head Neck Surg 94(1):15–22, 1986. 54. Hallberg OE: Sudden deafness of obscure origin. Laryngoscope 66(10):1237–1267, 1956. 55. Shaia FT, Sheehy JL: Sudden sensorineural hearing impairment: A report of 1220 cases. Laryngoscope 86:389–398, 1976. 56. Ogawa K, et al: Progression of hearing loss in acoustic neuromas. Acta Otolaryngol (Stockh) Suppl 487:133–137, 1991. 57. Mathew GD, et al: Symptoms, findings, and methods of diagnosis in patients with acoustic neuroma. Laryngoscope 88(12):1893–1903, 1978. 58. Bauch CD, Rose DE, Harner SG: Auditory brain stem response results from 255 patients with suspected retrocochlear involvement. Ear Hear 3(2):83–86, 1982. 59. Thomsen J, Tos M: Acoustic neuroma: clinical aspects, audiovestibular assessment, diagnostic delay, and growth rate. Am J Otol 11:(1)12–19, 1990. 60. Massick DD, Welling B, Dodson EE, et al: Tumor growth and audiometric change in vestibular Schwannomas managed conservatively. Laryngoscope 110:1843–1849, 2000. 61. Nedzelski JM, Schessel DA, Pfeiderer A: Conservative management of acoustic neuromas. Otolaryngol Clin North Am 25:691–705, 1992. 62. Alford B, Guilford F: A comprehensive study of tumors of the glomus jugulare. Laryngoscope 72:785–787, 1962. 63. Brammer RE, Graham MD, Kemink JL: Glomus tumors of the temporal bone: Contemporary evaluation and therapy. Otolaryngol Clin North Am 17(3):499–512, 1984. 64. Cure JK, et al: Auditory dysfunction caused by multiple sclerosis: Detection with MR imaging. AJNR 11:817–820, 1990. 65. Mustillo P: Auditory deficits in multiple sclerosis: A review. Audiology 23:145–164, 1984. 66. Jerger JJ, et al: Patterns of auditory abnormality in multiple sclerosis. Audiology 25:193–209, 1986. 67. Schweitzer VG, Shepard N: Sudden hearing loss: An uncommon manifestation of multiple sclerosis. Otolaryngol Head Neck Surg 100(4):327–332, 1989. 68. Daugherty WT, et al: Hearing loss in multiple sclerosis. Arch Neurol 40:33–35, 1986. 69. Franklin DJ, Coker NJ, Jenkins HA: Sudden sensorineural hearing loss as a presentation of multiple sclerosis. Arch Otolaryngol Head Neck Surg 115:41–43, 1989.

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70. Lee KS, Britton BH, Kelly DL: Schwannoma of the facial nerve in the cerebellopontine angle presenting with hearing loss. Surg Neurol 32:231–234, 1989. 71. Gianoli GJ, Amedee RG: Hearing results in surgery for primary apex lesions. Otolaryngol Head Neck Surg 111(3): 250–257, 1994. 72. Kitamura K, Futaki T, Miyoshi S: Fluctuating hearing loss in lipoma of the cerebellopontine angle. Otorhinolaryngol 52:335–339, 1990. 73. Chandrasekhar SS, Brackmann DE, Devgan KK: Utility of auditory brainstem response audiometry in diagnosis of acoustic neuromas. Am J Otol 16(1):63–67, 1995. 74. Friedman RA, Kesse BW, Slattery III WH, et al: Hearing preservation in patients with vestibular schwannomas with sudden sensorineural hearing loss. Otolaryngol Nead Neck Surg 125(5): 544–551, 2001. 75. Gordon ML, Cohen NL: Efficacy of auditory brainstem response as a screening test for small acoustic neuromas. Am J Otol 16(2):136–139, 1995. 76. Zappia JJ, O’Connor CA, Wiet RJ, Dinces EA: Rethinking the use of auditory brainstem response in acoustic neuroma screening. Laryngoscope 107:1388–1392, 1997. 77. Erickson LS, Sorenson GD, McGavran MH: A review of 140 acoustic neuromas. Laryngoscope 75:601–627, 1965. 78. Ellis PDM, Wright JLW: Acoustic neuroma: a plea for early diagnosis and treatment. J Laryngol Otol 88:1095–1110, 1974. 79. Hart RG, Davenport J: Diagnosis of acoustic neuroma. Neurosurgery 9(4):450–463, 1981. 80. Levine SC, Antonelli PJ, Le CT, Haines SJ: Relative value of diagnostic tests for small acoustic neuromas. Am J Otol 12(5):341–346, 1991. 81. Glasscock ME, Levine SC, McKennan K X: The changing characteristics of acoustic neuroma patients over the last 10 years. Laryngoscope 97:1164–1167, 1987. 82. Clemis JD, Mastricola PG: Special audiometric test battery in 121 proved acoustic tumors. Arch Otolaryngol 102:654–656, 1976. 83. Thomsen J, Tos M: Diagnostic strategies in search for acoustic neuromas. Acta Otolaryngol (Stockh) Suppl 452:16–25, 1988. 84. Brunàs RL, Ylikoski J, Morra B: Pure tone audiogram configurations in acoustic tumor patients. Rev Laryngol 105(2):113–116, 1984. 85. Josey AF, Jackson CG, Glasscock ME: Brainstem evoked response audiometry in confirmed eighth nerve tumors. Am J Otol 1(4):285–290, 1980. 86. Higgs WA: Sudden deafness as the presenting symptom of acoustic neuroma. Arch Otolaryngol 98:73–76, 1973. 87. Kanzaki J: Present state of early neurotological diagnosis of acoustic neuroma. Otorhinolaryngol 48:193–198, 1986. 88. Aslan A, Donato G, Balyan FR, et al: Clinical observations on coexistence of sudden hearing loss and vestibular schwannoma. Otolaryngol Head Neck Surg 117(6):580–582, 1997.

Chapter

8 John F. Kveton, MD

Symptoms of Vestibular Disease Outline Symptoms of Specific Vestibular Disorders The Labyrinth Vestibular Nerve Central Nervous System

Common Symptoms Vertigo Imbalance Dizziness Syncope

COMMON SYMPTOMS Symptoms of vestibular dysfunction are as variable as the disorders that produce them. This variation in symptoms for such a specific organ site as the labyrinth can be explained by the particular pathology of the process affecting the vestibular system and, as importantly, by the general physiologic recovery process that takes place after any insult to the system has occurred. An understanding of these compensatory mechanisms for vestibular injury in relation to the type of vestibular damage must be incorporated into the interview of patients presenting with vestibular symptoms. Certain vestibular disorders are episodic, with vestibular dysfunction punctuated by normal function, and other disorders produce acute, single-event injury to the vestibular system. In addition, chronic or progressive vestibular dysfunction can also occur. Vestibular dysfunction may be primary, with actual deterioration or damage to neural elements, or secondary, in which metabolic or other systemic changes produce reversible neural dysfunction. These types of vestibular dysfunction will have characteristic symptoms, depending on the stage in which these disorders present to the otologist. In any case, preliminary understanding of the process of vestibular compensation is the foundation for accurate interpretation of vestibular symptoms to arrive at a diagnosis (Table 8-1). Acute vestibular injury produces symptoms because the resting tone of the vestibular system is disrupted. The loss of tone produced by the damaged side allows for greater, uninhibited input from the normal side, producing vertigo

and vegetative symptoms. Symptoms can last for hours with prostration. For a period of hours to days the resting tone of the intact side is reduced through central effects, thus reducing the acute symptoms. At this point the whole vestibular system is functioning at a lower level and is not as sensitive to stimuli. Symptoms now are less severe, mainly involving mild vertigo on positional changes, lightheadedness, spatial disorientation, dysequilibrium, or unsteadiness. The duration of this stage of recovery depends on the severity of the vestibular injury and can last from days to months. The system compensates as the lesion progresses; the near constant feelings of lightheadedness and spatial disorientation disappear, and dysequilibrium and unsteadiness occur only with extreme changes in head position or loss of other sensory cues that affect balance. Symptoms become sporadic and eventually disappear in the course of weeks to months. For the majority of patients, this pattern of recovery is complete, with the disappearance of all symptoms. If the compensation process stalls or is interrupted at any stage, the patient may continue to have symptoms according to the stage of compensation the patient has reached. In fact, this disruption of complete compensation from vestibular dysfunction can be as debilitating as any recurrent, acute process and comprises a greater number of patient visits and treatment challenges than the acute, more easily identifiable process. Although past emphasis of vestibular diagnosis has focused on differentiating between peripheral and central vestibular lesions, it is the identification of the degree of compensation after vestibular dysfunction that is clinically

TABLE 8-1. Symptoms During Stages of Vestibular Compensation Initial Injury

Early (hours/days)

Mid (days/weeks)

Late (months)

Whirling vertigo Nausea, vomiting Prostration

Less severe vertigo Nausea Severe dysequilibrium, spatial disorientation

Positional vertigo Mild nausea Dysequilibrium; spatial disorientation

Rare positional vertigo Dysequilibrium Spatial disorientation

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more critical. Knowledge of the extent of compensation will determine treatment choices as much as knowledge of the location of the lesion. The particular symptoms of vestibular dysfunction can be reviewed in relation to these features.

Vertigo A sensation of motion without external stimuli broadly defines vertigo. Vertigo can be a symptom of either central or peripheral vestibular pathology, but its absence does not preclude the possibility of primary vestibular disease. The character and severity, onset, duration and frequency, and precipitating factors are all useful qualities of vertigo that must be determined. The severity of the vertigo usually depends on the abruptness of the process. Whirling or turning denotes an acute unilateral process, whereas swaying, rocking, staggering, weakness, or a swimming or wavy sensation is associated with a unilateral subacute or bilateral injury. Sudden onset of vertigo cannot differentiate peripheral from central lesions, but the duration of the vertigo can help to identify the source. Classic Ménière’s attacks have a sudden onset and duration of 1 to several hours. Acute toxic labyrinthitis produces a more persistent vertigo that seems to build for 24 to 48 hours before subsiding. Central vestibular disorders may produce sudden vertigo and more prolonged symptoms that last up to several weeks. When the duration of the vertigo is similar to peripheral disorders, central pathology can usually be differentiated by additional central nervous system (CNS) symptoms. Knowledge of precipitating factors can direct diagnosis in some peripheral lesions. Changes in head or body position suggest acute posterior canal dysfunction when symptoms resolve during a period of weeks to months or uncompensated unilateral peripheral disorders when symptoms are chronic. Stress is recognized to precipitate vertigo in Ménière’s disease. A prodromal viral illness is seen in vestibular neuritis, and prior consumption of foods, medications, or alcohol can also produce vertigo.

Imbalance Imbalance, unsteadiness, or dysequilibrium describes a loss of equilibrium on movement or in situations in which conflicting sensory cues arise (mainly visual). These symptoms represent the normal pattern of compensation after an acute vestibular lesion and can last weeks to months depending on the severity of the injury (see Table 8-1). Persistent symptoms reflect either poor compensation after an acute vestibular loss or gradual, continuous loss of vestibular function. The symptoms worsen with fatigue or in darkness. Acoustic neuromas or other space-occupying lesions in the posterior fossa are the most common causes of gradual deterioration of vestibular dysfunction. A bilateral symmetrical loss of vestibular function builds to a maximum intensity of dysequilibrium for days. Vertigo at times precedes the progressive symptoms relating to station and gait. Young healthy patients stagger in early stages of bilateral loss, and the elderly may require a walker. The greatest improvement in station and gait occurs within 6 weeks. Within 6 months the young patient walks with a wide-based gait, but still feels imbalance on bending or other rapid changes in head or body position.

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Dizziness Any vague sensations of discomfort in the head can be described as dizziness. Other descriptors include lightheadedness, wooziness, or disorientation. This is the most common symptom that the patient describes on initial consultation with the otologist. Spatial disorientation is the best term to describe these symptoms as they relate to vestibular dysfunction. These symptoms must be sought out in the history since they are difficult for the patient to describe. Spatial disorientation is the prime indicator of poor vestibular compensation and includes head-eye dyscoordination and postural dysfunction. Most patients with poor vestibular compensation are visually dependent, so that either loss of visual cues or conflicting or ambiguous sensory cues enhance the symptoms (supermarket syndrome). Head-eye dyscoordination occurs in bilateral vestibular loss or cerebellar dysfunction. In less severe conditions only active head movements produce dyscoordination, whereas in severe cases with high-frequency range vestibular loss, the visual field cannot be stabilized with passive whole-body movement (oscillopsia). Postural dysfunction occurs in bilateral vestibular loss and demonstrates itself as postural disorientation or abnormal postural motor responses to movement. It is exemplified by the development of a wide-based gait and loss of hip strategy for postural control in patients with bilateral vestibular lesions.

Syncope Episodic loss of consciousness is a rare presentation of vestibular dysfunction because either the function of both cerebral hemispheres or the brainstem reticular formation must be compromised to produce the symptom. Sudden onset without prodromal features; focal sensory or motor phenomena; and olfactory, gustatory, or other hallucinations indicates seizure activity. Syncope as the cause for loss of consciousness is explained on a vascular basis. Diffuse CNS dysfunction produced by reduced cerebral blood flow is indicated by progressive lightheadedness, faintness, or dimming of vision. The causes for hypoperfusion are generally cardiac (Table 8-2). More rarely, ischemia of the posterior cerebral circulation produces syncope. In such cases vertigo may be associated

TABLE 8-2. Causes for Hypoperfusion Valvular stenosis (aortic, pulmonic, mitral) Mitral valve prolapse Hypertrophic cardiomyopathy Left atrial myxoma or thrombus Constrictive pericarditis Cardiac tamponade Atrial flutter/fibrillation Paroxysmal atrial tachycardia Sinus bradycardia Sinus arrest Second- or third-degree heart block Sick sinus syndrome Pacemaker failure or malfunction Ventricular tachycardia Ventricular fibrillation Drug toxicity

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with other symptoms such as diplopia, dysphagia, dysarthria, occipital headaches, and other motor or sensory symptoms.

SYMPTOMS OF SPECIFIC VESTIBULAR DISORDERS Although not completely reliable, specific vestibular symptoms generally do relate to particular areas of the vestibular apparatus. The labyrinth and vestibular nerve are considered the peripheral vestibular system, whereas the brainstem is the site of central vestibular pathology. Although somewhat artificial, it is helpful to group vestibular disorders according to the location of the dysfunction to arrive at a better understanding of the symptoms associated with each region.

The Labyrinth Peripheral disease is the most common cause for vestibular dysfunction. Symptoms are most severe and are associated with vegetative symptoms. In the acute stages of the disease, symptoms are self-limiting, with periods of normal function interspersed between symptomatic events. Symptoms become more chronic and usually less severe when the disease causes permanent neural damage. In many cases the symptoms of the vestibular disorders are on a continuum, and the diagnoses must be considered on such a dynamic disease continuum rather than a simply static condition. Acute labyrinthitis is the most common form of episodic vestibular dysfunction. The cause of this condition is usually viral, but can also be bacterial. A previously asymptomatic patient experiences an acute onset of whirling vertigo that builds over 1 hour to severe prostration with nausea, vomiting, pallor, diaphoresis, and a complete inability to function in the upright position. Symptoms can last from 12 to 36 hours. The patient is bedridden for 1 to 3 days. The vertigo gradually resolves with brief, symptoms recurring with head movement or perceived rapid movements. Sudden movement or bending may produce staggering or falling. Driving is difficult. Within 5 to 10 days the patient resumes near-normal activity. Recovery is agedependent, with little or no residual symptoms present by 2 to 3 months. Most cases of acute labyrinthitis of viral origin do not demonstrate auditory symptoms. When auditory symptoms are associated, a more definitive diagnosis may be possible. Deafness and vestibular loss is associated with 4% to 10% of measles infections and is mainly bilateral. Mumps, on the other hand, is usually associated with a unilateral hearing loss of varying degrees. Infectious mononucleosis, although rare, should be considered in teenagers, and cytomegalic inclusion disease can produce severe auditory and vestibular dysfunction in infants. The diagnosis of herpes zoster as the cause of acute labyrinthitis can be made in the presence of facial paralysis and a vesicular eruption in and around the external auditory canal. Herpes zoster is associated with varying degrees of hearing loss as well. Either acute or chronic bacterial infections may produce vestibular dysfunction. Acute labyrinthitis may be caused by penetration of bacterial toxins through the round window membrane during acute otitis media. At times the hearing

loss associated with the infection may be sensorineural, indicating that permanent labyrinthine damage has occurred. Chronic otitis media can also cause transitory or progressive vestibular symptoms relating to the stage of the infection. Benign paroxysmal positional vertigo (BPPV ) is a benign, self-limiting form of vestibular dysfunction that can be diagnosed accurately through history. Known as postural vertigo, positional vertigo, and cupulolithiasis, this condition produces sudden attacks of brief vertigo through head movement. Attacks can be induced by rolling in bed or turning the head from one side to the other, but not both sides. Extending the head to look up, turning the head, or looking down precipitates the symptoms. The vertigo is associated with an intense feeling of dysequilibrium, but patients rarely lose motor control and fall. Mild nausea can occur during or immediately after an attack. Vomiting after the positional change is rare. Vertigo will subside when the provocative position is maintained, but patients do not retain this position because of the often intensely disagreeable feeling encountered on assumption of the provocative position. BPPV classically persists for several weeks with complete resolution of vertigo. It is not unusual for patients to have a recurrence of symptoms months to years later. On rare occasions, positional vertigo persists. In such cases a complete vestibular test battery should be performed to identify a more significant vestibular pathology as the source of the symptoms. The accepted, although unproven, explanation for BPPV stems from the deposition of inorganic deposits on the cupula of the posterior semicircular canal. Schuknecht has demonstrated basophilic deposits in the cupula of the posterior canal in two patients, loosening of otoconia from the otolithic membrane in cats after section of the anterior vestibular artery, and the production of pure rotatory nystagmus by stimulation of the posterior canal in isolation to support the theory of cupulolithiasis. Loss of otoconia from the macula through linear acceleration and impact decelerations has been identified by several authors. Symptoms of BPPV are recognized to occur spontaneously or following labyrinthine concussion, otitis media, otologic surgery, or occlusion of the anterior vestibular artery. Endolymphatic hydrops produces vestibular dysfunction associated with auditory symptoms of fullness, tinnitus, and hearing loss. A change in one or several of these auditory symptoms often precedes the vestibular symptoms. Vertigo is sudden and is not precipitated by physical exertion or movement. Emotional stress and fatigue can precipitate or enhance an attack and can extend the symptomatic time period by either initiating repeated attacks of vertigo or prolonging recovery from an attack. Vertigo varies in severity and duration, although the classic attack lasts up to several hours. Patients most commonly describe severe whirling vertigo with nausea, vomiting, and prostration, but symptoms may be as mild as swaying, to-and-fro eye movements, or dysequilibrium. Vestibular symptoms can totally disappear within hours. In severe cases or the middle to late stages of the disease, however, patients may experience unsteadiness or spatial disorientation for hours to days afterward. The frequency of the vertigo attacks is partly dependent on the stage and severity of the disease. Patients may experience isolated attacks punctuated by months to years of symptom-free existence. Other patients

Symptoms of Vestibular Disease

experience attacks in series, for weeks to months, between extended periods of remission. Decreasing intervals between attacks or increasingly severe episodes of vertigo reflect progression of the disease. In addition, the appearance of chronic vestibular symptoms such as positional vertigo, dysequilibrium, and spatial disorientation indicate that permanent vestibular dysfunction has occurred. Rarely, in advanced stages of the disease, patients may experience abrupt falling attacks (otolithic crisis of Tumarkin). The high degree of variability of vestibular dysfunction in endolymphatic hydrops is reflected even more by reviewing subclasses of the disorder. Ménière’s disease is the classic form of endolymphatic hydrops, composed of unilateral sensorineural hearing loss, tinnitus, aural fullness, and episodic vertigo. The severity of this condition varies greatly from patient to patient, and symptoms within the patient can change from episode to episode as well. Loudness recruitment and intolerance and acoustic distortion are common auditory symptoms, as is hearing loss. Little correlation exists between the auditory and vestibular symptoms. Hearing loss characteristically fluctuates, with primarily low-tone sensorineural hearing loss being identified first. Hearing loss progresses to a flat severe loss in most cases, with total hearing loss rarely occurring. Classic auditory (cochlear Ménière’s) or vestibular (vestibular Ménière’s) symptoms alone constitute atypical forms of this disorder. Other variations in auditory and vestibular symptoms of endolymphatic hydrops have been identified. Delayed endolymphatic hydrops can occur in patients with unilateral congenital deafness. Vestibular symptoms usually begin abruptly in the mid-20s. Episodic, severe, whirling vertigo lasting minutes occurs frequently, often several times a day. Vertigo can be aggravated by positional changes or perceived visual motion. Nausea can be a predominant feature, and vertigo and prostration are less common. Tinnitus and aural fullness may be appreciated in the ear as well. Posttraumatic endolymphatic hydrops can develop months to years after traumatic injury to the labyrinth. The symptoms can range from a classic Ménière’s disease picture to isolated episodes of fullness associated with vestibular symptoms. Some type of auditory symptom is present in this condition. Vertigo is generally episodic but less severe than the classic Ménière’s attack. Whirling vertigo, swaying, and severe dysequilibrium are all described. The attack may be more prolonged than the classic syndrome. Vegetative symptoms are often less severe, with an annoying sensation of nausea lingering in many patients. This sensation sometimes is unrelated to noticeable vestibular symptoms. Drop attacks are slightly more frequent in post-traumatic patients than in classic Ménière’s disease. Vestibular symptoms similar to endolymphatic hydrops have been recognized on a limited basis in otosclerosis. Aural fullness is associated with the acute vertigo attacks, which are less severe than classic Ménière’s disease. Other patients with otosclerosis complain of positional vertigo or episodic dysequilibrium. Vestibular symptoms associated with perilymph fistula are at times indistinguishable from those of endolymphatic hydrops. An abrupt onset of whirling vertigo with vegetative symptoms after straining, exertion, or head trauma may be the initial symptoms. The vertigo can last several hours, with the usual vestibular compensation occurring if the fistula closes. In cases of persistent perilymph fistula,

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vestibular symptoms occur in approximately 80% of patients and can vary from recurrent, episodic vertigo to positional vertigo, dysequilibrium, spatial disorientation, motion intolerance, or a combination of these. The symptoms are generally episodic and can often be related to exertion or straining. Dysequilibrium occurs in almost all cases. Spatial disorientation is more common than vertigo, which occurs in about 75% of patients. Nausea is a more prominent feature than vomiting, which occurs in less than half of patients. Auditory symptoms are the sole presenting symptom of perilymph fistula in less than 10% of patients. Hearing loss, tinnitus, aural fullness, and hyperacusis occur alone or in combination in more than 80% of perilymph fistula patients with vertigo. Fistulization of the bony labyrinth produces a variety of vestibular and auditory symptoms. Symptoms of the superior canal dehiscence syndrome are more specific than those of a perilymph fistula. This unusual condition must be considered when vertigo or oscillopsia is evoked by loud sounds or activities that change middle ear or intracranial pressure. Patients often develop chronic dysequilibrium, hyperacusis, and gaze-evoked tinnitus, but hearing is normal. Fistulization of a semicircular canal, usually the lateral canal, occurs in 7% to 14% of patients with cholesteatoma. Vertigo often occurs suddenly and is associated with hearing loss. Sudden vertigo with deafness and a history of chronic ear disease should alert the otologist to the diagnosis of a labyrinthine fistula. Traumatic head injury, especially if the temporal bone is involved, can produce either immediate or delayed symptoms of vestibular dysfunction. Positional vertigo commonly occurs after any head injury. Labyrinthine concussion can be associated with any head injury and produces mild unsteadiness or lightheadedness, especially on changes in head position. An associated high-frequency sensorineural hearing loss may be present. The vestibular symptoms generally resolve during a period of several months. Cupulolithiasis can be caused by head injury. Temporal bone fractures are associated with more severe injury to the labyrinth. Abrupt onset of severe vertigo with nausea and vomiting indicates that a transverse temporal bone fracture has occurred. Total hearing loss is also noted. Because many patients with severe head injury are comatose, labyrinthine injury may be identified in various stages of vestibular compensation. Often the patient describes dysequilibrium as the first symptom once ambulation has begun. Mild unsteadiness may persist for 3 to 6 months, with the patient falling to the involved side. Labyrinthine concussion in the opposite ear may muddy the picture. Longitudinal temporal bone fractures are more common and produce less severe vestibular symptoms. Unless a perilymphatic fistula has occurred because of ossicular chain damage (which is common), severe vertigo is rare. Symptoms of labyrinthine concussion are more likely, with vertigo or dysequilibrium noted on movement or changes in head position. Sudden, severe, incapacitating vertigo with roaring tinnitus and total hearing loss (labyrinthine apoplexy) usually suggests labyrinthine hemorrhage. Vertigo slowly resolves during a period of 3 to 4 weeks with slow vestibular compensation. The presentation of the symptoms can lead to a fairly close presumption of the type of vascular injury that has occurred. Symptoms that began in the early morning or shortly after

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arising reflect a thrombotic phenomenon, but vertigo appearing after exertion or a hypertensive crisis suggests vascular rupture. The possibility of perilymphatic fistula must also be entertained with the exertional history. Other causes of labyrinthine hemorrhage include leukemic infiltrates and hemorrhage and sickle cell crisis with thrombosis. Metabolic derangements may produce vestibular symptoms primarily or interfere with the compensatory mechanisms of a preexisting vestibular dysfunction. Elevated serum lipids, diabetes mellitus, hypothyroidism, and allergy may produce the spectrum of vestibular symptoms. Vertigo is usually not as severe and not associated with such severe vegetative symptoms as cases of unilateral loss of vestibular function. Symptoms appear more constant than episodic. Dysequilibrium and spatial disorientation are common and can be almost continuous. Auditory symptoms are unusual in these conditions. The aminoglycoside class of antibiotics is well recognized as a cause for vestibular damage. Streptomycin, gentamicin, tobramycin, amikacin, and viomycin are primarily vestibulotoxic. In general, symptoms of ototoxicity include a progressive unsteadiness followed by ataxia, anorexia, nausea, and occasional vomiting. Acute vertigo is an unusual presentation of ototoxicity. Ataxia commonly persists to a mild degree afterward. If total ablation of vestibular function has occurred, the patient will complain of oscillopsia. Intravenous erythromycin or minocycyline not uncommonly causes mild, transient vertigo with or without hearing loss. These symptoms are often reversible with cessation of therapy. Acute vestibular dysfunction, usually associated with severe hearing loss or deafness, can be seen in collagen vascular diseases, which include rheumatoid arthritis, polyarteritis nodosa, temporal arteritis, nonsyphilitic interstitial keratitis, dermatomyositis, scleroderma, disseminated lupus erythematosus, Wegener’s granulomatosis, rheumatic fever, and relapsing polychondritis. Sudden, severe vertigo with roaring tinnitus and total hearing loss (labyrinthine apoplexy) can be a result of an acute hemorrhage often seen in Wegener’s granulomatosis. These symptoms usually occur later in the disease along with granulomatous involvement of the upper respiratory tract, maxillary swelling, saddle nose deformity, proptosis, and palatal ulcerations. By this stage most patients also demonstrate pulmonary and renal involvement. The other connective tissue disorders produce similar acute symptoms that often can be improved with corticosteroid therapy. Nonsyphilitic interstitial keratitis (Cogan’s syndrome) occurs in young adults and usually begins with auditory and ocular symptoms. Sudden onset of vertigo with nausea, vomiting, and tinnitus can occur with rapid onset of deafness. The disease is often bilateral and pathologically resembles endolymphatic hydrops. Temporal arteritis occurs in the elderly and is associated with temporal headache, scalp tenderness, and fever in addition to inner ear symptoms. Relapsing polychondritis produces systemic symptoms such as joint pains, cough, fever, malaise, and fatigue in addition to intermittent hyperemia and swelling of the auricles or nasal septum and eye findings 2 to 3 years prior to the onset of acute vestibular symptoms. Spirochetal disorders can produce vestibular symptoms that resemble the range found in endolymphatic hydrops.

Both acquired and congenital syphilis predominantly demonstrate hearing loss and often acute vestibular dysfunction. Congenital syphilis may present symptoms that are similar to classic Ménière’s disease. Lyme disease is a similarly complex spirochetal disorder that presents with a myriad of systemic symptoms. Patients with the disorder can present with acute vertigo, nausea, vomiting, malaise, and fluctuating hearing loss. Such patients have symptoms similar to those for syphilitic dysfunction with otic involvement. A common helpful diagnostic feature in these patients is a positive Tullio’s sign. Both disorders may produce vestibular symptoms by otic capsule or leptomeningeal involvement.

Vestibular Nerve Certain disorders affect the vestibular nerve alone and produce symptoms that reflect the same variety of symptoms as disorders that primarily involve the labyrinth. Vestibular neuritis (vestibular neuronitis, vestibular paralysis, or epidemic vertigo) produces sudden severe vertigo with nausea and vomiting. Vertigo often begins at night and the duration of severe vertigo is longer than a classic Ménière’s attack. There is no hearing loss. Vertigo subsides over days, and the length of time for vestibular compensation is variable, with dysequilibrium subsiding within 6 months. Persistence of symptoms suggests other diagnoses, including multiple sclerosis, acoustic neuroma, and vascular occlusion of the posterior fossa circulation. Vestibular symptoms are uncommon as the presenting symptom of an acoustic neuroma, despite the fact that the tumor originates on the vestibular nerve. This partly may be due to the slow-growing nature of the tumor so that an episode of vertigo years prior may be forgotten. Sudden vertigo with nausea and vomiting, similar to vestibular neuritis, is reported to occur in 5% to 19% of patients. This presenting symptom mainly occurs in patients with small tumors. Compensation can be complete with no residual symptoms. Dysequilibrium or unsteadiness is a more common symptom later in the course of acoustic neuroma. Patients may note the symptoms on rapid motion of the head or body only or as a constant state. Constant symptoms are associated with increasing tumor size, with impingement on the cerebellum and brainstem occurring in addition to encroachment on the vestibular nerves. Vascular compression of the eighth nerve (cochleovestibular nerve compression syndrome) remains a controversial diagnosis, because it is mainly a diagnosis of exclusion. This diagnosis is made by magnetic resonance imaging or aircontrast computed tomographic scan identification of a vessel impinging on the eighth nerve. Vestibular symptoms have ranged from acute vertigo with vegetative symptoms to positional vertigo to continuous motion intolerance and dysequilibrium. Motion intolerance is the most common feature, and this symptom worsens as the day progresses. Patients often demonstrate mid- or high-frequency sensorineural hearing loss and tinnitus. The precise pathogenic mechanism remains in question.

Central Nervous System Classically, the differentiation between central and peripheral causes of vertigo has been made by the duration of

Symptoms of Vestibular Disease

vertigo attacks, that is, episodic or constant. Although constant vertigo is definitely associated with a central cause, many central processes produce episodic vertigo, especially in the early stages. Careful attention to other symptoms referable to CNS dysfunction are important in diagnosing these disorders. Multiple sclerosis can present with transient episodes of vertigo, blurred vision, focal weakness, numbness, tingling, or limb unsteadiness. Dysequilibrium is a more common presenting symptom than acute vertigo, although severe acute vertigo with vegetative symptoms has been known to occur. Because the symptoms are transient early in the disease, mild vertigo or dysequilibrium may be confused with mild vestibular neuritis or acute, mild labyrinthitis. Sudden sensorineural hearing loss can occur, with some recovery of auditory function occurring in many patients. Episodic vertigo may be a symptom of temporal lobe or complex partial seizures. The symptoms vary, but they are stereotypical for the individual. The average length of the seizure is 1 to 3 minutes and includes epigastric sensations along with affective, cognitive, and sensory symptoms. Coordinated involuntary motor activity (automatisms) occur in the orobuccolingual region and other areas of the head and neck in most patients. Acute vertigo may be part of the aura associated with a classic migraine headache. This is usually a throbbing, unilateral hemicranial pain that occurs after vertigo. Visual alterations (hemianopic field defects, scotomas and scintillations, photophobia), nausea, and vomiting are common. Less commonly, diarrhea, light-headedness, fainting, and fluid retention can be present. Vestibular symptoms may also occur during the headache-free interval (migraine equivalent). Severe whirling vertigo may last from minutes to hours and is often associated with nausea and vomiting. In severe cases hearing loss and tinnitus may accompany the vertigo. Vertigo may occur several times a year or on a more frequent basis. Occasionally, near-constant dysequilibrium and unsteadiness may occur. Other neurologic symptoms such as slurred speech, leg weakness, or diplopia and a history of migraine are important diagnostic features. Vascular disorders are the most common cause of central vestibular dysfunction and present with the entire spectrum of vestibular symptoms. Vertebrobasilar ischemia, a result of arteriosclerosis, generally occurs in the older age group. Spontaneous, short episodes of vertigo occur and recur frequently. Such attacks may be precipitated by head movement. With increasing hypoxia, facial numbness or tingling, slurred speech, and other sensory disturbances may occur. Thrombosis of the internal auditory artery (labyrinthine apoplexy), usually a branch of the anterior inferior cerebellar artery, produces severe, sudden vertigo, roaring tinnitus, and total hearing loss. Acute vertigo, nausea, and vomiting, along with dysphagia, hoarseness, Horner’s syndrome, limb ataxia, sensory impairment over the face, and loss of touch and position in the limbs is evidence of a lateral medullary infarct ( Wallenberg’s syndrome). Patients note lateral pulsion to the side of the lesion. Hearing loss is generally not associated. Residual symptoms

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are common, and their extent depends on the degree of the infarct. Cerebellar infarction may present with similar symptoms. Severe unsteadiness or ataxia combined with ophthalmoplegia and confusion compose the classic triad of Wernicke’s encephalopathy. This disorder, most common in alcoholics, is the result of thiamine deficiency with involvement of the brainstem and cerebellum. The vestibular symptoms can often be reversed over weeks to months with administration of thiamine. Vestibular symptoms often occur after cervical injury. Patients may experience brief episodes of vertigo, especially on positional changes, or may complain of dysequilibrium. Labyrinthine concussion may be coincident and therefore complicate the patient’s symptoms. In the absence of positive findings on the vestibular test battery, the source for the vestibular symptoms must relate to the interaction of the neck proprioceptors with the vestibular nuclei. This cervical vertigo is usually self-limited and usually responds to physical therapy to reduce the neck spasms associated with the injury.

BIBLIOGRAPHY Alpers BJ: Vertigo: Its neurological features. Trans Am Acad Ophthalmol Otolaryngol 46:38–54, 1941. Ballenger JJ: Diseases of the Nose, Throat, Ear, Head, and Neck. Philadelphia, Lea & Febiger, 1977. Black FO, et al: Surgical management of perilymph fistulas. Arch Otolaryngol Head Neck Surg 117:641–648, 1991. Drachman DA, Hart CW: Dizziness as a symptom of vestibular disease. Neurology 22:323–334, 1973. Harker LA, Rassekh C: Episodic vertigo in basilar artery migraine. Otolaryngol Head Neck Surg 96:239–250, 1987. Harker LA, Rassekh C: Migraine equivalent as a cause of episodic vertigo. Laryngoscope 98:160–164, 1988. Igarashi M: Vestibular compensation: An overview. Acta Otolaryngol (Stockh) 406:78–82, 1984. McCabe BF: Vestibular physiology: Its clinical application in understanding the dizzy patient. In Paparella M (ed.): Otolaryngology, vol 1. Philadelphia, WB Saunders, 1980. McNally WJ, Stuart EA: Vertigo from the standpoint of the otolaryngologist. Trans Am Acad Ophthalmol Otolaryngol 46:33–37, 1941. Minor LB: Superior canal dehiscence syndrome. Am J Otol 21:9–19, 2000. Paparella MM, Chasin WD: Otosclerosis and vertigo. J Laryngol Otol 80:511–519, 1966. Paparella MM, Sugiura S: The pathology of suppurative labyrinthitis. Ann Otol Rhinol Laryngol 76:554–586, 1967. Schuknecht HF: Pathology of the Ear. Cambridge, MA, Harvard University Press, 1974. Schwaber MK: Cochleovestibular nerve compression syndrome. I. Clinical analysis and audiovestibular test findings. Laryngoscope 102: 1020–1029, 1992. Selesnick SH, Jackler RK: Clinical manifestations and audiologic diagnosis of acoustic neuromas. Otolaryngol Clin N Am 25:521–552, 1992. Seltzer S, McCabe BF: Perilymph fistula: The Iowa experience. Laryngoscope 94:37–49, 1986. Sidorov JE, et al: Metabolic abnormalities and vertigo. Arch Intern Med 147:197–203, 1987. Simon RP, Aminoff MJ, Greenberg DA: Clinical Neurology. East Norwalk, CT, Appleton & Lange, 1989.

Chapter

9 Aage R. Møller, PhD

R

Tinnitus Outline Nature of Subjective Tinnitus Quantification of Tinnitus Pathogenesis of Subjective Tinnitus Pathophysiology of Subjective Tinnitus Location of the Anatomic Abnormality that Causes Tinnitus Abnormalities that Cause Tinnitus Cochlear Injuries as a Cause of Tinnitus Tinnitus Caused by Injuries to the Auditory Nervous System Tinnitus Generated by Functional Changes in Auditory Brainstem Nuclei Tinnitus and Neural Pathways Activated by Sound Similarities between Severe Tinnitus and Other Phantom Sensations Interaction with Tinnitus from Other Sensory Systems Tinnitus and Affective Disorders Treatment of Tinnitus Masking Tinnitus Retraining Electrical Stimulation Medical Treatment Surgical Treatment

ecent developments in the treatment of certain types of tinnitus have increased the interest of neurotologists in the differential diagnosis of this disorder and its management. These developments have also encouraged research directed at the identification of the cause of tinnitus, and attempts have been made to determine the anatomic location of the physiologic abnormalities that cause specific types of tinnitus. There are essentially two types of tinnitus. One type, known as objective tinnitus, is a result of sounds that are generated in the body. The second type, subjective tinnitus, can be heard only by the individual experiencing the tinnitus. Objective tinnitus, which is rare, may be caused by vascular anomalies that facilitate turbulent blood flow in the region of the ear. This type of tinnitus represents a normal perception of the sound, possibly conducted to the cochlea by bony tissue, that results from such turbulent flow. Such tinnitus may be pulsatile in nature, with the frequency of the pulsations being the same as the individual’s heart rate. Pulsatile tinnitus may occur in association with arteriovenous malformations, glomus tumors, or aneurysms. Objective tinnitus may also present as a clicking sound in association with, for example, temporomandibular joint disorders or as a result of spontaneous contractions of middle ear muscles or palatal myoclonus.1 A patulous 182

eustachian tube may cause tinnitus by transmitting sound from the nasopharynx to the middle ear cavity. Because objective tinnitus is not a result of abnormal function of the auditory system but is caused by a physical sound generated in the body and sensed in the normal way, this type of tinnitus can usually also be heard by an observer when proper auscultation techniques are used. We will not discuss further this particular type of tinnitus, which presumably is processed by the auditory system in a way similar to the way any other sound is processed. (For details about objective tinnitus, see Schleuning1 and Andersen and Meyerhoff 2). Subjective tinnitus is characterized by an individual’s perception of a sound in the absence of any physical sound, and of course this sound cannot be heard by an observer. Subjective tinnitus is more common than objective tinnitus and reflects an abnormality of the ear or the auditory nervous system. Subjective tinnitus is similar to paresthesia of the somatosensory system, but many forms of tinnitus have even greater similarities with central neuropathic pain.3 The visual, olfactory, and gustatory sensory systems are rarely affected by phenomena similar to tinnitus. Most adults have occasionally experienced low-intensity tinnitus or a more constant type of tinnitus that can easily be masked by another sound. Tinnitus of this nature is

Tinnitus

normally benign and it does not require any medical attention, but patients with that kind of tinnitus may benefit from appropriate neurotologic examination to ensure that tinnitus is not due to a treatable condition, such as a vestibular schwannoma. However, when subjective tinnitus is so intense that it interferes noticeably with a person’s daily life, it must be of concern to the neurotologist. The pathophysiology and subjective nature of that kind of tinnitus has many similarities with neuropathic (central) pain,3 including that of being a formidable challenge to the physician. It may be associated with a history of exposure to noise, vestibular schwannomas, or with Ménière’s disease, but often no cause can be identified. In this chapter, the nature, pathogenesis, and pathophysiology of different forms of subjective tinnitus are discussed and the literature regarding the treatment of tinnitus is reviewed.

NATURE OF SUBJECTIVE TINNITUS Subjective tinnitus may be perceived as coming from one ear only, from both ears with different or nearly equal intensity, or from inside the head. (Often when tinnitus in one ear has reached an incapacitating level, it is also perceived to be in the other ear.) Tinnitus may be constant or may vary in severity from time to time, without any apparent cause for the variation. Conversely, variations in intensity may be related to external events such as exposure to loud sounds, ingestion of certain drugs or food, or to changes in the patient’s stress level or physical activities. Considerable individual differences exist in the intensity and regularity of tinnitus, and the effects that subjective tinnitus have on everyday life are related to these factors. The benign tinnitus that most people occasionally experience may appear as a weak pure tone, a ringing sound, or a soft hissing sound. Most patients with tinnitus find it difficult to describe how their tinnitus sounds. The intensity and character of the type of tinnitus that is incapacitating may be likened to a shrill chirping sound, similar to that made by crickets, or to a roaring noise like that made by a jet engine at close proximity. Severe tinnitus is often associated with hypersensitivity to sound and an exaggerated perception of loudness (hyperacusis). (Individuals with Williams syndrome, infantile hypercalcemia, have a high incidence of hyperacusis4,5). Patients with severe tinnitus may perceive some sounds as distorted, and some of these patients experience a sensation similar to pain from sound, which they often describe as being more troublesome than the tinnitus itself. In some patients, strong impulsive sounds can cause their tinnitus to increase, and that increase may be maintained long after the sounds that caused the increase in the tinnitus have disappeared. Tinnitus is often associated with affective disorders such as depression, and some sounds can elicit fear in some individuals with pain (phonophobia).3,6

QUANTIFICATION OF TINNITUS Several methods have been devised to quantify the intensity and character of tinnitus. Matching and masking have

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been used to quantify the nature and loudness of tinnitus, but the correspondence is typically poor between the results of masking and matching studies and the degree of annoyance the tinnitus causes in different patients. Studies agree that masking and matching tests show very low estimates of sound intensities even by patients who experience severe annoyance from the tinnitus.7,8 For example, one study estimated the loudness of tinnitus by matching the loudness of a sound presented to the ear without tinnitus (or the lesser affected ear) and found that 75% of the patients matched their tinnitus to sounds that were at a 10-dB sensation level (SL) or less. In fact, in about half of the patients tested, the loudness of the sounds to which they matched their tinnitus was only a 5-dB SL. Vernon9 reported that only 1 of the 513 patients he tested had tinnitus that the individual matched to a high-intensity (70-dB SL) sound. Estimating tinnitus loudness by matching the tinnitus to a sound presented to the same ear rather than the opposite ear yielded slightly higher values (23.9 versus 6.6 dB, averaged in nine subjects),10 but even these higher values seem low compared with the degree of annoyance reportedly caused by tinnitus. These studies thus show that masking does not have the same effect on tinnitus as it would if the sound sensation were caused by a physical sound. This discrepancy between the results of loudness matching and the degree of annoyance reported by patients with has led to speculation that the methods used to estimate loudness were invalid, that loudness recruitment somehow affected the results, or that the level of annoyance caused by tinnitus is not directly related to its perceived loudness.9 Some investigators have interpreted these findings to indicate that emotional factors play a role in the way patients perceive their tinnitus.8,9,11,12 It seems more likely, however, that the neural code generating the tinnitus is different from the one generated by physical sounds. The neural activity that causes the tinnitus is either generated by neurons of the ascending auditory pathways independent of input from the periphery of the auditory system, or it may be generated by neural structures that are not normally activated by sounds. This latter possibility may explain why the results of matching studies seem to underestimate the loudness of the tinnitus and thus its severity. Therefore a classification system based on the patients’ own estimate of the severity of the tinnitus8 seems to be more valuable than one based on matching or masking studies. The proposed classification defines three degrees of severity: slight, moderate, or severe. Slight is used to describe tinnitus that is not constant and usually bothers the patient only in a quiet environment; moderate describes tinnitus that is more intense and constantly present and bothers the patient when he or she tries to concentrate; it also disturbs sleep. Tinnitus that elicits serious complaints from the patient, interferes greatly with the patient’s ability to concentrate, and inhibits sleep is classified as severe. The classification of severe is used for incapacitating tinnitus. The present diagnostic methods, such as various forms of imagining techniques, cannot identify the morphologic and functional abnormalities that cause tinnitus, thus making differential diagnosis of tinnitus a challenge for the physician. Although it may be helpful to determine

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whether tinnitus is pulsatile and the pulsations are synchronous with the patient’s heartbeat, it is of little importance to know the nature of the sound perceived, such as whether the tinnitus resembles a high-frequency or lowfrequency sound, because no relationship has been established between these factors and the anatomic location of the abnormality causing the tinnitus. Considerable similarities occur between severe tinnitus and pain,3,13 especially central neuropathic pain. Both severe tinnitus and neuropathic pain occur in the absence of objective signs, and the perception of both tinnitus and pain vary as a result of circumstances. Both symptoms are difficult to describe, and different individuals may describe symptoms differently. Patients with chronic neuropathic pain typically experience normal stimulation of the skin to be painful (allodynia*), and such patients may also have an exaggerated sensation from acute somatic pain (hyperpathia†). In a similar way many patients with severe tinnitus often perceive normal sounds as stronger than normal (hyperacusis), and sounds that normally do not elicit any unpleasant sensations may be perceived as unpleasant or even painful. Many individuals with severe tinnitus perceive strong sounds as being extremely unpleasant and even painful, thus experiencing a phenomenon similar to hyperpathia. Individuals with neuropathic central pain often experience increasingly painful sensations from somatic stimulation repeated at short intervals. This phenomenon, known as the “wind-up” phenomenon13,15,16 often occurs together with severe pain and is described as a worsening of pain sensations from repeated stimulation with the same stimulus. Many individuals with severe tinnitus have analogous sensations from sounds that are repeated. Exposure to strong sounds may cause a patient’s tinnitus to increase for a long time after the sound has ended. As in many patients with severe neuropathic pain, no treatable cause can be found in many patients with severe tinnitus. When it has been determined that the tinnitus is not caused by a treatable illness, the objective of treatment is to eliminate or alleviate the symptoms.

PATHOGENESIS OF SUBJECTIVE TINNITUS The cause of subjective tinnitus is unknown in most patients and not related to a specific disorder. The cause of the tinnitus in most cases eludes identification by currently available diagnostic modalities. Some conditions, however, are well known to cause subjective tinnitus, including noise exposure, particularly exposure to impulsive noise; many pharmacologic agents; and some pathologic conditions, such as vestibular schwannoma, vascular compression of the auditory nerve, and arteriovenous malformations. Subjective tinnitus is one of the three symptoms that define Ménière’s disease. Otosclerosis may also be associated with tinnitus, specifically the cochlear type. *The term allodynia is usually defined to mean the pain elicited by stimuli that ordinarily are innocuous.14 † The word hyperpathia is used to describe an explosive increase in reaction to pain when a painful stimulus exceeds a certain threshold, with a continuing sensation of pain after the stimulation has ceased.14

Noise-induced tinnitus is perhaps the most common type of tinnitus, but tinnitus is not always associated with noise-induced hearing loss. The most severe noiseinduced tinnitus is caused by impulsive noise. Tinnitus caused by noise is worse immediately after exposure to noise and then gradually decreases after the end of the exposure. Hearing loss that affects high frequencies and occurs gradually through the process of aging (presbycusis) is sometimes accompanied by tinnitus. The first symptom of a vestibular schwannoma is almost always tinnitus, and such tinnitus frequently persists after the tumor has been removed even when the patient’s hearing has been successfully preserved during tumor removal. In fact, tinnitus may even be worse postoperatively, probably as a result of intraoperative injury to the auditory nerve as a result of surgical manipulation.17 Surgical manipulations of the intracranial portion of the eighth nerve in other types of operations such as microvascular decompression (MVD) to relieve hemifacial spasm (HFS), trigeminal neuralgia (TGN), or disabling positional vertigo (DPV) can cause tinnitus in addition to hearing loss. Recently it has been recognized that vascular compression of the intracranial portion of the auditory portion of the eighth cranial nerve can cause tinnitus. Tinnitus due to this cause may be alleviated by moving the blood vessel off the eighth nerve.18–20 Many pharmacologic agents can induce tinnitus.21 Two of the best known of these agents are aspirin (acetylsalicylate) and aminoglycoside antibiotics. Other drugs that can cause hearing loss and induce tinnitus as well are loop diuretics (furosemide, ethacrynic acid), quinine, indomethacin, aminoglycoside antibiotics, and cisplatin.21,22 Carbamazepine, tetracycline, antipsychotic drugs, lithium, tricyclic antidepressants, monoamine oxidase inhibitors, antihistamines, beta-adrenergic receptor blockers, local anesthetics, and steroids (to name only a few) are other drugs that can induce tinnitus, although they have not been associated with hearing loss. Caffeine and alcohol can also cause tinnitus. Tinnitus caused by pharmacologic agents is usually (but not always) reversible by cessation of administration of the offending agents. (For more details about drugs that induce tinnitus, see Simpson and Davies21). Little is known about the mechanism by which any of these agents produce tinnitus.

PATHOPHYSIOLOGY OF SUBJECTIVE TINNITUS As for other diseases, we want to know (1) the anatomic location of the abnormality that causes the symptoms (tinnitus, hyperacusis, and affective symptoms such as phonophobia and depression), and (2) the nature of the abnormalities (morphologic or functional).

Location of the Anatomic Abnormality that Causes Tinnitus Because the patient with subjective tinnitus often refers to sensation as being “in the ear,” it has generally been assumed that the anatomic location of the physiological abnormality causing the tinnitus is in the ear. Therefore,

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tinnitus has often been associated with pathologic processes involving the ear, and many studies of the pathophysiology of tinnitus have focused on the ear as the location of the physiological abnormality that causes the symptoms. Subsequent studies have found evidence that the anatomic location of the generation of the abnormal neural activity that causes tinnitus is not always the ear. Severe tinnitus is probably most often caused by functional abnormalities in the auditory nervous system such as those induced by neural plasticity. Severe tinnitus can probably also be caused by morphologic changes in the auditory nerve and, rarely, in the nuclei of the ascending auditory pathways. Tinnitus is often associated with other symptoms such as hyperacusis and phonophobia, the anatomic location of which may be the same as or different from the place where the neural activity engendering the tinnitus arises.

Abnormalities that Cause Tinnitus Some forms of tinnitus may be caused directly by abnormalities in the ear. Studies in animals have shown that direct electric current passed through the cochlea can change the spontaneous activity in single auditory nerve fibers. Studies of tinnitus have shown that electric current passed through the cochlea (positive current applied to the round window) can reduce the tinnitus in some patients,23,24 supporting the hypothesis that tinnitus is associated with the function of the cochlea and possibly with increased spontaneous activity in auditory nerve fibers. Tinnitus, at least in some patients, may also be caused by abnormalities in the function of the auditory nerve or more rostral structures of the ascending auditory pathways. Studies in animals have shown that functional changes may occur in auditory nuclei as a result of pathology of the auditory periphery.25,26 Such electrical anomalies in specific nuclei of the ascending auditory pathway may develop over time as an expression of neural plasticity evoked by abnormal input or lack of input from the auditory periphery. These anomalies may be in the form of reorganization of the nuclei, which may result in hyperactivity. Changes in brainstem nuclei caused by abnormal input (or absence of input) usually take time to reverse after cessation of the abnormal input, or the changes may in fact be irreversible. Abnormalities of central nuclei may rarely also develop as a result of a disease process or injury to a nucleus.

Cochlear Injuries as a Cause of Tinnitus Injury to the cochlea from disease processes such as Ménière’s disease, noise exposure, or administration of ototoxic drugs can cause verifiable morphologic changes in the sensory epithelium in the cochlea. The fact that these morphologic changes are related to hearing loss has led to the assumption that the tinnitus often accompanying such changes is caused by similar pathologic cochlear changes as those causing the hearing loss. However, animal studies have shown that hearing loss can also cause changes (hyperactivity of neurons) in nuclei of the ascending

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auditory pathways.25,26 These central changes may explain how cochlear injuries cause tinnitus. Conflicting results have been found in studies of the spontaneous activity of single auditory nerve fibers in animals that were treated with pharmacologic agents, such as salicylate and aminoglycoside antibiotics, known to induce tinnitus in humans.27,28 Some investigators27,29,30 found that salicylate and administered acutely to experimental animals caused an increase in the spontaneous discharge rates of single auditory nerve fibers, and other investigators have reported decreased spontaneous activity after administration of kanamycin, an ototoxic antibiotic that may cause hearing loss and tinnitus.28 Other experiments revealed reduced spontaneous activity in animals after exposure to sounds that caused hearing loss (and presumably tinnitus)31–33 and in animals that have experienced other forms of acute injury to the cochlea.34 These conflicting results regarding the relationship between changes in the spontaneous activity of auditory nerve fibers and tinnitus indicate that tinnitus is not related directly to the discharge rate of auditory nerve fibers. Other properties of auditory nerve activity such as phase-locking of the activity in many nerve fibers or the time pattern of the discharge may be more closely related to tinnitus than the discharge rate.35,36 In summary, there is little support for tinnitus being caused by increased activity of auditory nerve fibers due to injuries of the cochlea. Rather, considerable evidence points to deprivation of input to the auditory nerve as causing hyperactivity in more central auditory structures, and it seems likely that such hyperactivity may be responsible for some forms of tinnitus and hyperacusis. This is similar to some forms of central neuropathic pain.3,6

Tinnitus Caused by Injuries to the Auditory Nervous System Injuries of various kinds to the auditory nerve are very likely the cause of tinnitus. Tinnitus from injury of the auditory nerve is commonly caused by vestibular schwannoma, which almost always has tinnitus as its first symptom, indicating that tinnitus can be triggered by injury, irritation, or compression of the intracranial portion of the auditory nerve. This does not necessarily mean that the neural activity producing the tinnitus is generated in the auditory nerve, but the tinnitus can also result from functional changes in more rostral portions of the auditory nervous system, induced by abnormal or decreased neural activity in the auditory nerve through the expression of neural plasticity. Deprivation of input is a strong promoter of neural plasticity, which can bring about reorganization of neural circuits as well as hyperactivity and hypersensitivity (see Møller and Rollins13). It is also known that close contact between the auditory nerve and a blood vessel can induce tinnitus,18,19 but studies of patients undergoing MVD to relieve incapacitating tinnitus who had surgically verified vascular contact (vascular compression) of their auditory nerve did not demonstrate any noticeable abnormalities in the function of the nerve.37 Compound action potentials (CAPs) recorded directly from the exposed intracranial portion of the eighth nerve were not noticeably different from those

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recorded from patients who had similar hearing loss but no tinnitus, and who were operated on to relieve vascular compression of other cranial nerves.37 The latencies of peak III of the brainstem auditory evoked potentials (BAEP, AEP, or ABR) were not statistically different in these two groups of patients either.37 Since approximately 40% of patients who undergo MVD to treat tinnitus are cured or their tinnitus is considerably relieved after the procedure,37 it seems highly likely that the tinnitus in these patients was indeed caused by the effect of vascular compression of the eighth nerve. Because of the absence of statistically significant abnormalities in responses from the auditory nerve and the cochlear nucleus (peak III of the BA EP), we concluded that the anatomic location of the physiological abnormality that generated the tinnitus in these patients must have been rostral to the structures from which we recorded and most likely induced by reorganization of neural structures through expression of neural plasticity.6,38 Another hypothesis suggests that tinnitus may result from a pathologic correlation between the neural activity in individual auditory nerve fibers.35,39 Such correlations may be caused by abnormal communication between auditory nerve fibers or hair cells.35 When no sound is present, the time pattern of the spontaneous neural activity in auditory nerve fibers is assumed to be uncorrelated. Sounds elicit neural activity that is phase-locked to the waveform of a sound, and the neural discharges in such nerve fibers will become correlated. Such correlation may be important for detecting the presence of sounds.35,36 Abnormal correlation of neural activity in many nerve fibers that is not a result of sounds in the ear may therefore cause tinnitus.35,39 The time pattern of spontaneous activity in single auditory nerve fibers in animals receiving salicylate has been found to be abnormal.29 The fact that salicylate can induce tinnitus in humans supports the hypothesis that tinnitus is associated with an abnormal time pattern of spontaneous firing of auditory nerve fibers. It is known from other systems that nuclei may be hyperactive because of novel stimulation or deprivation. For example, some evidence suggests that the cause of spasm in hemifacial spasm40,41 is an example of hyperactivity resulting from abnormal input to the facial motonucleus. The changes in the facial motonucleus has been likened to the “kindling” phenomenon*.40 The fact that tinnitus cannot be masked in the same way as an external sound also supports the assumption that tinnitus is not usually associated with the same type of auditory nerve activity evoked by sound. Individual variability in the efficacy of masking (i.e., sometimes contralateral masking is effective) and the phenomenon of residual masking support the hypothesis that tinnitus is not associated with the type of neural activity evoked by sounds.44 There are thus indications that abnormal correlation between activity in many auditory nerve fibers, abnormal time pattern of firings of those fibers, or reduced activity *The kindling phenomenon was first described by Goddard,42 who noted that animals (rats) whose amygdala nuclei were electrically stimulated periodically over weeks developed seizures in response to the stimulation.43

may cause changes in the function of neurons in more central nuclei of the ascending auditory pathways.

Tinnitus Generated by Functional Changes in Auditory Brainstem Nuclei Studies in animals and patients with tinnitus have indicated that subjective tinnitus is unlikely to be directly caused by neural activity in the auditory nerve. It seems more probable that higher auditory centers are involved and that tinnitus may be caused by a complex interplay between the auditory periphery (ear and auditory nerve) and more rostral structures of the ascending auditory pathway in the brainstem. It is likely that abnormal input or lack of input from the ear can, over time, cause reorganization of central auditory structures in such a way that they become hyperactive. Animal experiments have shown that deafferentation (cochlear removal) can produce increased metabolic activity in auditory nuclei,45 or changes in temporal integration in the inferior colliculus (IC),26 which is another sign of hyperactivity. In other animal experiments strong sound stimulation has been shown to trigger hyperactivity in the IC and to alter temporal integration.46 If hyperactivity caused by reorganization of auditory nuclei becomes established, it may produce abnormal neural activity for some time after normalization of the peripheral anomaly that caused the reorganization. This may explain why the expected effect of MVD of the auditory nerve in patients with tinnitus is often delayed.18 Intracranial recordings from patients undergoing MVD operations for incapacitating tinnitus have shown that the latency of peak V in the click-evoked BAEP was slightly shorter (but statistically significant) than that obtained in patients with matched hearing loss and no tinnitus47 who underwent MVD operations for other cranial nerve disorders such as TGN. The shorter latency of peak V may be a sign of hyperactivity of auditory nuclei. Also other studies indicate that the IC is involved in tinnitus.48 The pathophysiology of severe of tinnitus may have similarities with that of other disorders produced by vascular compression of a cranial nerve, such as HFS and TGN.40,41,49 Recent intraoperative studies of patients undergoing MVD to relieve HFS have shown that the signs of physiological abnormalities in patients with HFS are not caused by the vascular compression of the facial nerve itself (or rather vascular contact with the facial nerve), but instead are a result of hyperactivity of the facial motonucleus induced by abnormal neural activity in the facial motonucleus from the irritation caused by the vascular contact with the nerve.40,41 There are also indications that the pain of TGN, which can be cured with a high degree of success (80% to 85%) by MVD of the trigeminal nerve, is a result of abnormalities in the trigeminal sensory nucleus.20,50,51 Other similarities exist between incapacitating tinnitus and disorders such as TGN and HFS. For example, patients with incapacitating tinnitus usually have, at most, moderate degrees of hearing loss similar to patients with HFS, who have little or no detectable facial weakness, and patients with TGN, who have little loss of sensation in the

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face, despite excruciating pain or involuntary muscle contractions that may involve the entire face. Vascular compression (or rather irritation) of cranial nerves is common in asymptomatic individuals with tinnitus and other hyperactive disorders such as HFS, TGN, and glossopharyngeal neuralgia (GPN) that can be cured by MVD of cranial nerves.49,52 Therefore, vascular compression of cranial nerves is not a sufficient condition for manifestation of pathology in these disorders, but since these disorders can be cured effectively by MVD, the vascular contact must be regarded as a necessary condition.41,49 The disorder that perhaps has the greatest similarity with some forms of severe tinnitus is central neuropathic pain. Tonndorf was one of the first to publish a possible analogy53 between tinnitus and pain. His proposal suggested a similarity with the Melzack-Wall gating hypothesis for pain.54 This hypothesis postulates that input from A-fibers normally suppresses neural transmission in C-fibers, which conduct pain. More recently it has been hypothesized that some forms of tinnitus have similarities with neuropathic pain.3,13 Such pain is assumed to be a result of functional changes in the central nervous system (CNS) that are caused by the expression of neural plasticity. That pain may be caused by reorganization of the nervous system induced by expression of neural plasticity has been known for a long time.55,56 These changes may be associated with hyperactivity, hypersensitivity, and altered temporal integration. (Temporal integration means that the response to a stimulus is affected by previous stimulation, which is mostly a property of the CNS.) Animal experiments have shown that normally the behavioral threshold of the response to electrical stimulation of auditory nuclei decreases exponentially with the number of impulses presented, but after impairment of hearing the threshold became lower and the threshold did not decrease with an increasing number of impulses, thus altering temporal integration.25,26 These changes are similar to those of the somatosensory system present in patients with neuropathic pain of central origin.57 In individuals without chronic pain, the threshold of pain to electrical stimulation of the skin decreases exponentially as a function of the repetition rate of the stimulation, but in individuals with chronic pain, the pain threshold is much lower and nearly independent of the stimulus rate, indicating that both the threshold and temporal integration of painful stimuli are altered in individuals with chronic pain.57 The “wind-up” phenomenon15,16 in pain is also an expression of abnormal temporal integration. A change in temporal integration is just one sign of involvement of neural plasticity that may occur in some forms of severe tinnitus. Rerouting of information is another change that may be induced by neural plasticity and may be involved in chronic severe pain. How changes in the organization of the CNS may cause different forms of tinnitus is, however, not known in detail.

Tinnitus and Neural Pathways Activated by Sound Tinnitus is often associated with hyperacusis, phonophobia, and emotional reactions not normally associated

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with sounds. This means that tinnitus is either caused by activation of neural circuits that are not normally activated by sounds or by neural circuits that are normally activated by sounds but altered (reorganized). The subcortical classical auditory pathways have no known input from other sensory systems, and the finding that tinnitus can be affected by somatosensory stimulation38,58,59 and by muscle activity60 and other forms of cross-modulation61 therefore indicates an abnormal involvement of neural circuits not normally activated by sound. Some neurons of the nonclassical auditory pathways6,62–65 (known as the polysensory pathway65) receive input from the somatosensory system.64,66–68 This makes it possible to test the hypothesis that the polysensory auditory pathway is involved in severe tinnitus. If the polysensory system is involved in tinnitus, stimulating the median nerve electrically would be expected to alter the perception of the tinnitus. Studies involving electrical stimulation of the median nerve at the wrist (that gave a strong tingling sensation but no pain) have shown indications that the nonclassical auditory pathways are involved in some forms of tinnitus. Such activation of the somatosensory system affected the tinnitus in 10 of 26 patients (6 experienced a decrease and 4 experienced an increase in the loudness).38 The input from the somatosensory system is excitatory in some neurons and inhibitory in others,64 which may explain why some individuals experienced an increase in the perception of their tinnitus while others experienced a decrease. The nonclassical system receives its auditory input from the traditional classical auditory system at the level of the IC64 to the external nucleus and the dorsal cortex of the IC. These nuclei project to the dorsal thalamus, which projects to association cortices and directly to the amygdala6,69 (Fig. 9-1) (see also Chapter 2). The existence of direct connections from the thalamic auditory nuclei to the amygdala may explain the affective components associated with some forms of tinnitus as well as the abnormal involvement of endocrine and sympathetic systems. The hypothesis of abnormal activation of the amygdala in some patients with severe tinnitus has been supported by studies using functional MRI.70 Little is known about the normal role of the nonclassical ascending auditory pathway but a recent study has shown evidence that the nonclassical auditory system is commonly involved in the perception of the loudness of sounds in children but rarely in adults.13 Abnormal activation of the nonclassical pathways may be caused by neural plasticity, resulting in functional reorganization of the nervous system. The efficacy of synapses that connect the classical pathways with the nonclassical pathways may increase as an expression of neural plasticity elicited by deprivation of input, as happens in the spinal cord after severance of dorsal roots,6,71 known as “unmasking of dormant synapses.” In the auditory system, this may occur at the midbrain level as well as probably at the pontine level of the auditory system. Deprivation of input to the auditory system may occur as a result of hearing loss (most patients with severe tinnitus have hearing loss).

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Figure 9-1. Schematic diagram showing connections from the classical and the nonclassical ascending auditory pathways to the nuclei of the amygdala. Some connections from the amygdala nuclei are also shown. AAF, Anterior auditory field; ABL, basolateral nucleus of the amygdala; ACE, central nucleus of the amygdala; AI, primary auditory cortex; AII, secondary auditory cortex; AL, lateral nucleus of the amygdala; DC, dorsal cortex of the inferior colliculus; ICC, central nucleus of the inferior colliculus; ICX, external nucleus of the inferior colliculus; MGB, medial geniculate body.

Similarities between Severe Tinnitus and Other Phantom Sensations Tinnitus has been likened to phantom perception,30 and it has been suggested that the prefrontal cortex is involved in tinnitus. Jastreboff has discussed the similarity between some forms of tinnitus and other phantom sensations.30 Out of that work grew a method for treating patients with tinnitus (see section on Tinnitus Retraining Method).

Interaction with Tinnitus from Other Sensory Systems Involvement of the nonclassical auditory system was indicated by the finding that stimulation of the somatosensory system could interact with the perception of tinnitus in some individuals with severe tinnitus.37 Subsequent studies have confirmed and extended these observations, and other forms of cross-modality interaction with tinnitus have been described.58,59,61 The relief of tinnitus by electrical stimulation of the skin behind the ears72 may act through stimulation of the somatosensory system (trigeminal system) rather than the cochlea. It has been shown recently that the auditory system (cochlear nucleus) receives connections from the trigeminal sensory ganglion.66–68 That the somatosensory system (dorsal column nuclei) provides input to the nonclassical parts of the midbrain auditory nuclei64 (see Chapter 2 and Møller6) may explain the relief of tinnitus by electrical stimulation of the somatosensory system.73,74

Several studies have shown that eye movements can affect tinnitus in some individuals58,59,61 as can contraction of other muscles75 in other individuals.

Tinnitus and Affective Disorders Tinnitus is often accompanied by affective symptoms such as depression and phonophobia. These symptoms may be related to involvement of the nonclassical auditory pathways, which use the dorsal and medial portion of the thalamic auditory nucleus (medial geniculate body, MGB).6 These nuclei provide direct input to the lateral nucleus of the amygdala and thereby channel “raw” auditory information to limbic structures6,69 (see also Chapter 2). The amygdala nuclei connect to many parts of the CNS (see Fig. 9-1). Involvement of the nonclassical auditory system in some individuals with severe tinnitus37 may therefore explain why tinnitus is often accompanied by affective disorders such as depression and why sound in such individuals many evoke fear (phonophobia) and hyperacusis.76 This hypothesis was supported by studies using functional MRI that show an abnormal activation of limbic structures in some forms of tinnitus.70 The direct route from the thalamic nucleus (dorsal and medial geniculate body) to limbic systems (the “low route”)69 may conduct auditory information to the amygdala in a pathway that it is little controlled by the CNS (see Fig. 9-1). The amygdala nuclei normally receive auditory input through a much longer route (the “high

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route”),69 where there are ample possibilities for processing the information before it reaches the amygdala, and the information may be modulated by input from higher CNS centers. That different hypotheses are considered regarding the anatomic location of the physiologic abnormalities that cause severe tinnitus may indicate that tinnitus has many different causes or, alternatively, a lack of knowledge about the disorder (or perhaps both). One fact seems evident: The pathophysiology of tinnitus is much more complex than previously assumed. We can only hope that these hypotheses will help to suggest experimental studies and guide the interpretation of the results of such studies so as to eventually identify the cause(s) of this (or these) disorder(s).

TREATMENT OF TINNITUS This section discusses treatments of tinnitus, hyperacusis, and other related disorders. Treatment is severely hampered by the insufficient knowledge about the mechanisms and the cause of tinnitus and the individual differences between the causes of tinnitus. Although a variety of treatments have been tried for alleviating tinnitus and many of these are effective for some patients, no treatment can alleviate tinnitus in all patients. One reason is that tinnitus is not one disorder but many with similar symptoms. Few possibilities exist for eliminating the cause of tinnitus. Most treatments for tinnitus are therefore directed at reducing the symptoms. The treatments currently in use are medical (pharmacologic), masking by sound retraining, and surgical.

Masking The annoyance caused by some forms of tinnitus can be decreased by masking77,78 and in some patients exposure to sound (masking) reduces the tinnitus for a longer or shorter period after termination of the noise exposure (residual masking).44,77 Many patients with mild to moderate levels of tinnitus experience a lessening of discomfort when hearing background sounds from a radio (or other soft sounds such as that produced by a fish tank filter motor). A hearing aid can often be of help to patients with severe tinnitus, maybe because it amplifies background sounds. However, some patients with severe tinnitus do not seem to benefit noticeably from such masking treatment, and in fact external sounds often make the tinnitus worse in some individuals.

Tinnitus Retraining The tinnitus retraining (TRT) program79,80 grew out of the assumption that tinnitus is a phantom sensation.30 It is now widely used for treatment of tinnitus and hyperacusis.81,82 The method makes use of a combination of counseling and exposure to moderately strong sounds. The beneficial effect of sound exposure depends on the sounds used; moderate sound levels seem to help some patients.80-82 The fact that tinnitus can be relieved by exposure to specific sound stimulation may be regarded as a method similar to that used to treat central neuropathic

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pain by electrical stimulation (transdermal electric nerve stimulation, TENS83,84). The outcome of TRT has been difficult to evaluate and the reported outcome of improvement of tinnitus and hyperacusis from long-term treatment (1 year or more) varies among investigators.81,82 The selection criterion is no doubt an important factor in obtaining good results. It has been claimed that counseling in itself is not new in being beneficial to patients with tinnitus.85

Electrical Stimulation Research has shown that direct electric current passed through the cochlea can reduce tinnitus in some patients.23,24,86 In these studies an electrode was placed on the round window or the promontorium, and when a positive current was passed through the cochlea, six of seven patients obtained relief.24 Such stimulation is assumed to be effective because electric current passing through the cochlea affects the hair cells so that the spontaneous activity in auditory nerve fibers decreases. It is also possible that the electric current affects the auditory nerve directly. Despite such positive effects from electrical stimulation of the ear, this method has not yet become widely used in the treatment of patients with tinnitus. The tinnitus of deaf people can be reduced by the electrical stimulation provided by a cochlear implant.11,87 This seems reasonable because cochlear implants represent a way of activating auditory nerve fibers and thereby reversing the deprivation of input to these nerve fibers caused by the cochlear injuries that resulted in the patient’s deafness. TENS trough electrodes placed on the skin near the ear has also been tried to treat severe tinnitus, but it seems to help only some patients.72,88,89 In some investigations about a third of the patients studied experience a prolonged relief from tinnitus after a few minutes of TENS. Such stimulation may have its effect by stimulating the trigeminal sensory system rather than the ear. Electrical stimulation applied to the skin of the hand has also been used in treatment of tinnitus.73,74

Medical Treatment Numerous drugs have been tried to manage tinnitus.21,90 The drugs most consistently able to alleviate tinnitus are local anesthetics, the most commonly used of which has been lidocaine (Lignocaine, Xylocaine, Procaine). It is still not known which one of the several actions of these drugs makes them effective in alleviating tinnitus. The effect of local anesthetic drugs such as Procaine and Lignocaine on peripheral nerves is assumed to be related to their blockage of sodium channels, but these drugs also have a considerable effect on the CNS. Lidocaine has been widely used, for example, to stop epileptic seizures.91 Studies using recordings of auditory evoked potentials showed that the later peaks of the BAEP are affected (prolongation of the interpeak latency of peaks I to V),92–94 indicating that lidocaine affects the central auditory nervous system and not the ear. These studies indicate that lidocaine affects tinnitus due to an action on the CNS and not on the ear.

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The consistent efficacy and sometimes dramatic effect of IV lidocaine have motivated a search for other oral drugs with similar and longer-lasting results. So far, the search has had little success. Tocainide, which is similar to lidocaine and can be administered orally,93,95 has proven beneficial to some patients with tinnitus, but only in dosages that were often associated with intolerable side effects. More recently Mexiletine, another drug similar to lidocaine, has also been tried with moderate success.96 Inspired by the success of lidocaine and recognizing lidocaine’s anticonvulsant effect, several investigators have tried various other anticonvulsant drugs such as carbamazepine and dilantin.97 Unfortunately, these drugs have also been found unacceptable or impractical for use in treating tinnitus.97 Because a patient with incapacitating tinnitus would most likely have to take a medication for the rest of his or her life, the side effects of the medication are an important consideration. The benzodiazepines hold some promise, especially because some of them (diazepam, alprazolam, and clonazepam)98 are documented as being effective and having few side effects in preliminary studies.98 These drugs may be effective because they enhance the effect of γ-aminobutyric acid (GABA) and because at least some forms of tinnitus may be caused by a reduction of inhibition in neurons in the ascending auditory pathway, in which GABA is the inhibitory neural transmitter.99 Animal experiments have shown that benzodiazepines (GABAA receptor agonists) can reduce signs of hyperactivity and restore temporal integration after prior exposure to loud noise in auditory midbrain nuclei (IC).100 Other pharmacologic agents having GABA or GABA-like effects, such as baclofen, (a GABAB receptor agonist), would seem to be good candidates for managing tinnitus, a hypothesis supported by studies in animals.100 However, clinical experience of baclofen in tinnitus treatment has not confirmed that hypothesis. Antidepressants such as the tricyclic drugs (e.g., Elavil) can sometimes be beneficial, but these drugs can also cause tinnitus or increase the tinnitus of patients who already have this disorder. Calcium channel blockers also have positive effects in some patients.

Surgical Treatment Surgical treatment of tinnitus has consisted of severing the auditory nerve, or microvascular decompression (MVD) or sympathectomy. Each of these treatments has had some success. MVD is a nondestructive surgical procedure to move a blood vessel off the intracranial portion of the auditory nerve.41,49,101–103 In the hands of surgeons with extensive experience of this type of procedure, MVD of the intracranial portion of the auditory nerve can provide a permanent cure for specific selected patients.18,19,41,49,101–103 For example, in a recent study18 in which 73 patients were operated on with the MVD technique, tinnitus was totally relieved or greatly improved in 40%. It is interesting to note that the patients who underwent MVD of the auditory nerve and obtained total relief from tinnitus also obtained relief from their hypersensitivity to sound,18 which indicates that the tinnitus and the hypersensitivity to sound in these

patients were most likely caused by the same or related mechanisms. The patients who obtained total relief or considerable improvement (40.3%) had endured their tinnitus for a much shorter time than those whose tinnitus did not improve (48.6%) (2.8 years vs. 7.1 years). This is in good agreement with the experience of MVD for TGN.104 Apfelbaum104 found that the average duration of symptoms of TGN for those who had excellent results following MVD was 70.9 months, whereas the average duration of symptoms for those who had recurrences of TGN following MVD was 109.4 months. This supports the hypothesis that severe tinnitus may, after a time, become less responsive to treatment; it may also indicate that treatment of patients with incapacitating tinnitus should not be postponed unnecessarily. More surprising was the finding that the success rate was much higher in women than in men (54.8% vs. 29.3%), despite similar selection criteria and intraoperative findings in men and women.18 Of 31 female patients who were operated on with the MVD procedure, 54.8% were either free from symptoms or markedly improved, but only 29.3% of the 41 male patients obtained similar results from the operation.18 Although the reason for the difference is unknown, it may indicate that many factors such as reproductive hormones may be involved. MVD is most effective in patients with unilateral tinnitus. In a study of 22 patients, 11 with unilateral and 11 with bilateral tinnitus, the outcome was favorable in 33% overall, but it was favorable in 63% of those 11 patients with unilateral tinnitus, but only 2 of the 11 patients with bilateral tinnitus improved (18%).105 In a recent study of 59 patients who were operated on by MVD, more than 75% improved (30 were free of tinnitus).106 In another study of 18 patients, 8 were free of tinnitus after MVD, and improvement of the tinnitus was achieved in 17 of 18.107 The anterior inferior cerebellar artery (AICA) is usually found to be in contact with the auditory nerve. Because the MVD procedure is similar for all of these disorders, it does not seem likely that these differences in the success of the surgical procedure are due to the procedure itself but rather the result of the criteria for selection of the patients to undergo the procedure. In summary, MVD of the auditory nerve in the hands of experienced surgeons is effective in treating severe tinnitus in carefully selected patients, but MVD also carries a substantial risk for making the tinnitus worse, and intraoperative monitoring of auditory nerve function is essential in reducing such risks.47 There is considerable evidence that severing the auditory portion of the eighth nerve can alleviate the tinnitus in many patients with Ménière’s disease,108 but the results are much less convincing in patients with tinnitus who do not have Ménière’s disease. Pulec109 reported complete relief from tinnitus in 67% of 91 patients with Ménière’s disease. In a more recent study, Pulec reported complete relief achieved in 101 of 151 patients with tinnitus.110 Others17,111 have obtained similar results. Relief or improvement in tinnitus was reported in 36% of patients with vertigo who had undergone retrolabyrinthine section of the vestibular portion of the eighth nerve and in 31% of patients who had undergone vestibular nerve section using a retrosigmoid approach.112

Tinnitus

This means that the results of auditory nerve section for tinnitus varies among investigators. The difference in the selection criteria used most likely contributes noticeably to this variation. Treating tinnitus by sectioning the eighth nerve seems to be more effective in patients whose tinnitus is caused by Ménière’s disease than in patients with tinnitus of another cause. It must be remembered that this is a destructive treatment limited to individuals who have no usable hearing in the ear with tinnitus, but good hearing in the ear that will not receive treatment. Some of the benefit of vestibular nerve section may result from sectioning of the cochlear efferent bundle, the fibers of which travel with the proximal portion of the vestibular nerve and therefore may also be severed when the vestibular nerve is cut. The efferent fibers have a suppressive effect on auditory nerve fibers when stimulated electrically, but their normal function is largely unknown (see Chapter 2). Sympathectomy has been used with some success in managing tinnitus113 as well as for pain.114 One study showed that stellate ganglion block in patients with Ménière’s disease has a beneficial effect on tinnitus, as much as a 56% relief rate115), whereas patients with causes of tinnitus other than Ménière’s disease benefited less (27% relief rate) from this procedure. Sympathectomy is seldom done now. A study of patients with otosclerosis who also had tinnitus found that 40% of the patients obtained relief following successful stapedectomy.116 Biofeedback has been shown helpful in treating tinnitus, as has various forms of psychotherapy. These topics, however, are outside the scope of this chapter, since these treatments do not seem to affect the tinnitus as such but rather the patient’s perception of it. In summary, many treatments have been tried for tinnitus, none of which has been shown effective in all patients. Some treatments have positive effects in some patients but not in others, supporting the hypothesis that tinnitus is not a single disorder but a group of disorders with different pathophysiology. It has generally been difficult to evaluate any treatment of tinnitus and the placebo effect is considerable, yet another similarity with pain. Some treatments that are effective in a limited group of patients have often been regarded as generally ineffective and have hence become disused, despite their effectiveness in some. The search for treatments of tinnitus should therefore not aim at a universal treatment but rather find diagnostic methods that can distinguish patients with different kinds of tinnitus and then find specific treatments for each such group.

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5. Borsel van J, Curfs LMG, Fryns JP: Hyperacusis in Williams syndrome: A sample survey study. Genet Couns 8:121–126, 1997. 6. Møller AR: Sensory Systems: Anatomy and Physiology. Amsterdam, Academic Press, 2003. 7. Fowler EP: The illusion of loudness of tinnitus—Its etiology and treatment. Ann Otol Laryngol 52:275–285, 1942. 8. Reed GF: An audiometric study of 200 cases of subjective tinnitus. Arch Otolaryngol 71:94–104, 1960. 9. Vernon J: The loudness of tinnitus. Hear Speech Action 44:17–19, 1976. 10. Goodwin PE, Johnson PM: The loudness of tinnitus. Acta Otolaryngol (Stockh) 90:353–359, 1980. 11. McKerrow WS, Schriener GE, Snyder RL, et al: Tinnitus suppression by cochlear implants. Ann Otol Rhinol Laryngol 100:552–558, 1991. 12. Hazell JWP: Measurement of tinnitus in humans. In Tinnitus (Ciba Foundation Symposium 85). London, Pitman Books, 1981. 13. Møller AR, Rollins P: The non-classical auditory system is active in children but not in adults. Neurosci Lett 319:41–44, 2002. 14. Anonymous: Pain terms: Current list with definitions and notes of usage. Pain Supp 3:215–221, 1986. 15. Woolf CJ, Thompson SWN: The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation: Implications for the treatment of post-injury pain hypersensitivity states. Pain 44:293–299, 1991. 16. Mendell LM: Modifiability of spinal synapses. Physiol Rev 64:260–324, 1984. 17. House JW, Brackmann DE: Tinnitus: Surgical treatment. In Tinnitus (Ciba Foundation Symposium 85). London, Pitman Books, 1981. 18. Møller MB, Møller AR, Jannetta PJ, Jho HD: Vascular decompression surgery for severe tinnitus: Selection criteria and results. Laryngoscope :421–427, 1993. 19. Kondo A, Ishikawa J, Yamasaki T, Konishi T: Microvascular decompression of cranial nerves, particularly of the seventh cranial nerve. Neurol Med Chir (Tokyo) 20:739–751, 1980. 20. Møller AR: Vascular compression of cranial nerves. I: History of the microvascular decompression operation. Neurol Res 20:727–731, 1998. 21. Simpson JJ, Davies E: Recent advances in the pharmacological treatment of tinnitus. Trends Pharmacol Sci 20:12–18, 1999. 22. Seligmann H, Podoshin L, Ben-David J, Fradis M, Goldsher MG: Drug-induced tinnitus and other hearing disorders. Drug Safety 14:98–212, 1996. 23. Aran J, Cazals I: Electrical suppression of tinnitus. In Tinnitus (Ciba Foundation Symposium 85). London, Pitman Books, 1981, pp 217–225. 24. Cazals Y, Negrevergne M, Aran JM: Electrical stimulation of the cochlea in man: Hearing induction and tinnitus suppression. J Am Audiol Soc 3:209–213, 1978. 25. Gerken GM, Saunders SS, Paul RE: Hypersensitivity to electrical stimulation of auditory nuclei follows hearing loss in cats. Hear Res 13:249–260, 1984. 26. Gerken GM, Solecki JM, Boettcher FA: Temporal integration of electrical stimulation of auditory nuclei in normal hearing and hearing-impaired cat. Hear Res 53:101–112, 1991. 27. Evans EF, Wilson JP, Borerwe TA: Animal models of tinnitus. In Tinnitus (Ciba Foundation Symposium 85). London, Pitman Books, 1981. 28. Kiang NYS, Moxon EC, Levine PA: Auditory-nerve activity in cats with normal and abnormal cochleas. In Wolstenholme GEW, Knight J (eds.): Sensorineural Hearing Loss. London, CIBA Foundation, 1970. 29. Evans EF, Borerwe TA: Ototoxic effects of salicylate on the responses of single cochlear nerve fibers and on cochlear potentials. Br J Audiol 16:101–108, 1982. 30. Jastreboff PJ: Phantom auditory perception (tinnitus): Mechanisms of generation and perception. Neurosci Res 8:221–254, 1990.

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31. Liberman MC, Kiang NYS: Acoustic trauma in cats. Acta Otolaryngol (Stockh) Suppl 358:1–63, 1978. 32. Salvi RJ: Central components of the temporary threshold shift. In Henderson D, Hamernik RP, Dnsanjh DS, Mills JH (eds.): Effect of Noise on Hearing. New York, Raven Press, 1976. 33. Salvi RJ, Ahroon WA: Tinnitus and neural activity. J Speech Hear Res 26:629–632, 1983. 34. Evans EF: Temporary sensorineural hearing losses and eighth nerve changes. In Henderson D, Hamernik RP, Dnsanjh DS, Mills JH (eds.): Effect of Noise on Hearing. New York, Raven Press, 1976. 35. Møller AR: Pathophysiology of tinnitus. Ann Otol Rhinol Laryngol 93:39–44, 1984. 36. Eggermont JJ: Between sound and perception: reviewing the search for a neural code. Hear Res 157:1–42, 2001. 37. Møller AR, Møller MB, Jannetta PJ, Jho HD: Compound action potentials recorded from the exposed eighth nerve in patients with intractable tinnitus. Laryngoscope 102:187–197, 1992. 38. Møller AR, Møller MB, Yokota M: Some forms of tinnitus may involve the extralemniscal auditory pathway. Laryngoscope 102:1165–1171, 1992. 39. Eggermont JJ: On the pathophysiology of tinnitus: A review and a peripheral model. Hear Res 48:111–124, 1990. 40. Møller AR, Jannetta PJ: On the origin of synkinesis in hemifacial spasm: Results of intracranial recordings. J Neurosurg 61:569–576, 1984. 41. Møller AR: Cranial nerve dysfunction syndromes: Pathophysiology of microvascular compression. In Barrow DL (ed.): Neurosurgical Topics, Book 13. Surgery of cranial nerves of the posterior fossa, Chapter 2. Park Ridge. IL, American Association of Neurological Surgeons, 1993, pp 105–129. 42. Goddard GV: Amygdaloid stimulation and learning in the rat. J Comp Physiol Psychol 58:23–30, 1964. 43. Wada JA: Kindling 2. New York, Raven Press, 1981. 44. Feldmann H: Homolateral and contralateral masking of tinnitus. Br J Laryngol Otol (Suppl) 4:60–70, 1981. 45. Sasaki CT, Kauer JS, Babitz L: Differential 14C 2-deoxyglucose uptake after deafferentation of the mammalian auditory pathway— A model for examining tinnitus. Brain Res 194:511–516, 1980. 46. Szczepaniak WS, Møller AR: Evidence of neuronal plasticity within the inferior colliculus after noise exposure: A study of evoked potentials in the rat. Electroencephalogr Clin Neurophysiol 100:158–164, 1996. 47. Møller AR: Intraoperative neurophysiologic monitoring. Luxembourg, Harwood Academic Publishers, 1995. 48. Melcher JR, Sigalovsky IS, Guinan JJ Jr, Levine RA: Lateralized tinnitus studied with functional magnetic resonance imaging: Abnormal inferior colliculus activation. J Neurophysiol 83: 1058–72, 2000. 49. Møller AR: Vascular compression of cranial nerves. II. Pathophysiology. Neurol Res 21:439–443, 1999. 50. Barker FG, Jannetta PJ, Bissonette DJ, et al: Microvascular decompression for hemifacial spasm. J Neurosurg 82:201–210, 1995. 51. Barker FG, Jannetta PJ, Bissonette DJ, et al.: The long-term outcome of microvascular decompression for trigeminal neuralgia. N Engl J Med 334:1077–1083, 1996. 52. Sunderland S: Microvascular relations and anomalies at the base of the brain. J Neurol Neurosurg Psychiatry 11:243–257, 1948. 53. Tonndorf J: The analogy between tinnitus and pain: A suggestion for a physiological basis of chronic tinnitus. Hear Res 28:271–275, 1987. 54. Melzack R, Wall PD: Pain mechanisms: A new theory. Science 150:971–979, 1965. 55. Price DD: Psychological and neural mechanisms of the affective dimension of pain. Science 288:1769–1772, 2000. 56. Devor M: Central changes mediating neuropathic pain. In R Dubner, G Gebhart and M Bond (eds.): Proceedings of the Fifth World Congress on Pain. Amsterdam, Elsevier, pp 114–128, 1988.

57. Møller AR, Pinkerton T: Temporal integration of pain from electrical stimulation of the skin. Neurol Res 19:481–488, 1997. 58. Cacace AT, Cousins JP, Parnes SM, et al: Cutaneous-evoked tinnitus. II: Review of neuroanatomical, physiological and functional imaging studies. Audiol Neuro-otol 4:258–268, 1999. 59. Cacace AT, Cousins JP, Parnes SM, et al: Cutaneous-evoked tinnitus. I: Phenomenology, psychophysics and functional imaging. Audiol Neuro-otol 4:247–257, 1999. 60. Pinchoff RJ, Burkard RF, Salvi RJ, et al: Modulation of tinnitus by voluntary jaw movements. Am J Otol 19:785–789, 1998. 61. Cacace AT, Lovely TJ, McFarland DJ, et al: Anomalous crossmodal plasticity following posterior fossa surgery: Some speculations on gaze-evoked tinnitus. Hear Res 81:22–32, 1994. 62. Webster DB, Popper AN, Fay RR: The mammalian auditory pathway: Neuroanatomy. In Fay RR, Popper AN (eds.): Springer Handbook on Auditory Research. New York, Springer Verlag, 1992. 63. Møller AR: Hearing: Its Physiology and Pathophysiology. San Diego, Academic Press, 2000. 64. Aitkin LM: The auditory midbrain, structure and function in the central auditory pathway. Clifton, NJ, Humana Press, 1986. 65. Ehret G, Romand R: The Central Auditory Pathway. New York, Oxford University Press, 1997. 66. Shore SE, Godfrey DA, Helfert RH, et al: Connections between the cochlear nuclei in guinea pig. Hear Res 62:16–26, 1992. 67. Shore SE, Vass Z, Wys NL, Altschuler RA: Trigeminal ganglion innervates the auditory brainstem. J Comp Neurol 419:271–285, 2000. 68. Vass Z, Shore SE, Nuttall AL, et al: Trigeminal ganglion innervation of the cochlea—A retrograde transport study. Neuroscience 79:605–615, 1997. 69. LeDoux JE: Brain mechanisms of emotion and emotional learning. Curr Opin Neurobiol 2:191–197, 1992. 70. Lockwood A, Salvi R, Coad M, et al: The functional neuroanatomy of tinnitus. Evidence for limbic system links and neural plasticity. Neurology 50:114–120, 1998. 71. Wall PD: The presence of ineffective synapses and circumstances which unmask them. Phil Trans Royal Soc (Lond.) 278:361–372, 1977. 72. Engelberg M, Bauer W: Transcutaneous electrical stimulation for tinnitus. Laryngoscope 95:1167–1173, 1985. 73. Rahko T, Kotti V: Tinnitus treatment by transcutaneous nerve stimulation (TNS). Acta Otolaryngol (Stockh) Suppl 529:88–89, 1997. 74. Kaada B, Hognestad S, Havstad J: Transcutaneous nerve stimulation (TNS) in tinnitus. Scand Audiol (Stockh) 18:211–217, 1989. 75. Levine RA: Somatic (craniocervical) tinnitus and the dorsal cochlear nucleus hypothesis. Am J Otolaryngol 20:351–362, 1999. 76. Møller AR: Pathophysiology of tinnitus. In Vernon JA, Møller AR (eds.): Mechanisms of Tinnitus. Boston, Allyn & Bacon, pp 207–217, 1995. 77. Coles RRA: Tinnitus and its management. In SDG Stephens and AG Kerr (eds.): Scott-Brown’s Otolaryngology. Smithfield, MA, Butterworth, 1987. 78. Pulec JL, Hodell SF, Anthony PFT: Tinnitus: Diagnosis and treatment. Ann Otol Rhinol Laryngol 87:821–833, 1978. 79. Jastreboff PJ, Hazell JWP: A neurophysiological approach to tinnitus: Clinical implications. Brit J Audiol 27:7–17, 1993. 80. Jastreboff PJ, Jastreboff MM: Tinnitus retraining therapy (TRT) as a method for treatment of tinnitus and hyperacusis patients. J Am Acad Audiol 11:162–177, 2000. 81. Kroener-Herwig B, Biesinger E, Gerhards F, et al: Retraining therapy for chronic tinnitus. A critical analysis of its status. Scand Audiol 29:67–78, 2000. 82. Bartnik G, Fabijanska A, Rogowski M: Effects of tinnitus retraining therapy (TRT) for patients with tinnitus and subjective hearing loss versus tinnitus only. Scand Audiol 52:206–208, 2001. 83. Willer JC: Relieving effect of TENS on painful muscle contraction produced by an impairment of reciprocal innervation: An electrophysiological analysis. Pain 32:271–274, 1988.

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84. Hansson P, Lundeberg T: Transcutaneous electrical nerve stimulation, vibration and acupuncture as pain-relieving measures. In Wall PD, Melzack R (eds.): Textbook of Pain, 4th ed. Hong Kong, Churchill Livingstone, pp 1341–1351, 1999. 85. Wilson PH, Henry JL, Andersson G, et al: A critical analysis of directive counselling as a component of tinnitus retraining therapy. Brit J Audiol 32:273–286, 1998. 86. Portmann M, Cazals Y, Negrevergne M, Aran JM: Temporary tinnitus suppression in many through electrical stimulation of the cochlea. Acta Otolaryngol. (Stockh) 87:249–299, 1979. 87. Sininger YS, Mobley JP, House W, Nielsen DW: Intra-cochlear electrical stimulation for tinnitus suppression in a patient with near-normal hearing. In Feldmann H (ed.): Proceedings of the III International Tinnitus Seminar. Karlsruhe, West Germany, Harsch Verlag, 1987. 88. Schulman A, Tonndorf J, Goldstein B: Electrical tinnitus control. Acta Otolaryngol (Stockh) 99:318–325, 1985. 89. Vernon JA, Fenwick JA: Attempts to suppress tinnitus with transcutaneous electrical stimulation. Otolaryngol Head Neck Surg 93:385–389, 1985. 90. Parnes SM: Current concepts in the clinical management of patients with tinnitus. Eur Arch Otorhinolaryngol 254:406–409, 1997. 91. Bernhard CG, Bohm E: On the central effects of Xylocaine with special reference to its influence on epileptic phenomena. Acta Physiol Scand 31(Suppl 114):5–6, 1954. 92. Javel E, Mouney DF, McGee J, Walsh EJ: Auditory brainstem responses during systemic infusion of lidocaine. Arch Otolaryngol 108:71–76, 1982. 93. Lenarz T: Treatment of tinnitus with lidocaine and tocainide. Scand Audiol (Stockh) 26:49–51, 1986. 94. Ruth RA, Gal TJ, DiFazio CA, Moscicki JC: Brain-stem auditoryevoked potentials during lidocaine infusion in humans. Arch Otolaryngol 111:779–802, 1985. 95. Emmett JR, Shea JJ: Treatment of tinnitus with tocainide hydrochloride. Otolaryngol Head Neck Surg 88:442–446, 1980. 96. Kay NJ: Oral chemotherapy in tinnitus. Brit J Audiol 15:123–124, 1981. 97. Goodey RJ: Drugs in the treatment of tinnitus. In Tinnitus (Ciba Foundation Symposium 85). London, Pitman Books Ltd, 1981. 98. Johnson RM, Brummett R, Schleuning A: Use of alprazolam for relief of tinnitus. Arch Otolaryngol Head Neck Surg 119:842–845, 1993. 99. Krnjevic K: Significance of GABA in brain function. In Tunnicliff G, Raess BU (eds.): GABA Mechanisms in Epilepsy. New York, Wiley Liss, 1991.

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100. Szczepaniak WS, Møller AR: Effects of (-)-baclofen, clonazepam, and diazepam on tone exposure-induced hyperexcitability of the inferior colliculus in the rat: Possible therapeutic implications for pharmacological management of tinnitus and hyperacusis. Hear Res 97:46–53, 1996. 101. Jannetta PJ: Neurovascular cross compression in patients with hyperactive dysfunction symptoms of the eighth cranial nerve. Surg Forum 26:467–469, 1975. 102. Møller MB, Møller AR: Vascular compression syndrome of the eighth nerve: Clinical correlations and surgical findings. In Arenberg IK, Smith DB (eds.): Neurologic Clinics: Diagnostic Neurotology and Otoneurology. Philadelphia, WB Saunders, pp 421–439, 1990. 103. Schwaber MK: Microvascular compression syndromes: Clinical features and audiovestibular findings. Laryngoscope 102: 1020–1029, 1992. 104. Apfelbaum R: Surgery for tic douloureux. Clin Neurosurg 31:357–368, 1984. 105. Vasama JP: Microvascular decompression of the cochlear nerve in patients with severe tinnitus. Preoperative findings and operative outcome in 22 patients. Neurol Res 20:242–248, 1998. 106. Ko Y, Park CW: Microvascular decompression for tinnitus. Stereotact Funct Neurosurg 68:266–269, 1997. 107. Okamura T, Kurokawa Y, Ikeda N, et al.: Microvascular decompression for cochlear symptoms. J Neurosurg 93:421–426, 2000. 108. Dandy WE: Surgical treatment of Ménière’s disease. Surg Gynecol Obstet 72:421–425, 1941. 109. Pulec JL: Tinnitus: Surgical therapy. Am J Otol 5:479–480, 1984. 110. Pulec JL: Cochlear section of intractable tinnitus. Ear Nose Throat J 74:469–476, 1995. 111. Hazell JWP: Tinnitus. In Ballantyne J, Groves J (eds.): ScottBrown’s Diseases of the Ear, Nose and Throat, 4th ed.: The Ear. London, Butterworth, 1979. 112. Glasscock MC, Thedinger BA, Cueva PA: An analysis of the retrolabyrinthine vs the retrosigmoid vestibular nerve section. Otolaryngol Head Neck Surg 104:88–95, 1991. 113. Passe EG: Sympathectomy in relation to Ménière’s disease, nerve deafness and tinnitus. A report of 110 cases. Proc R Soc Med 44:760–772, 1951. 114. Loh L, Nathan PW: Painful peripheral states and sympathetic blocks. J Neurol Neurosurg Psychiat 41:664–671, 1978. 115. Adlington P, Warrick J: Stellate ganglion block in the management of tinnitus. J Laryngol Otol 85:159–168, 1971. 116. Glasgold A, Altman F: The effect of stapes surgery on tinnitus in otosclerosis. Laryngoscope 76:1524–1532, 1966.

Chapter

10 John S. McDonald, DDS, MS, FACD

Otalgia Outline Pain Characteristics Anatomy Primary Otalgia Referred Otalgia Differential Diagnosis of Pain Referred to the Ear Acute Referred Otalgia Chronic Referred Otalgia Orofacial Pain

O

talgia, or pain perceived by the patient to be emanating from the ear, is a common otolaryngologic problem in all age groups and both sexes. In many cases it presents a vexing problem to the clinician. Although the source of the pathology may be the ear or temporal bone, in 50% or more of patients who complain of otalgia, the pain is referred from a source other than the ear.1 As with other complaints of pain in the head and neck, otalgia may be accompanied by protean symptoms, which may be described as aching, boring, sharp, throbbing, burning, itching, pressure-like, or the sensation of fullness. The severity of the pain may be disproportionate to the nature of its underlying cause; that is, an acute inflammatory process involving the external ear may present with pain of much greater severity than a primary neoplasm emanating from the pharynx but referring pain to the ear.

PAIN CHARACTERISTICS Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or is described in terms of such damage.2 Pain may be characterized in a variety of ways. The terms paresthesia and dysesthesia both imply an abnormal sensation, either spontaneous or evoked, with dysesthesia being used to denote an unpleasant abnormal sensation. Examples of dysesthetic pain include allodynia or a painful response to a stimulus that does not usually evoke pain, and hyperalgesia, which implies an increased response to a stimulus that would normally produce pain. Noxious stimulus or tissue damage activates nociceptors at the termination of myelinated A-delta and unmyelinated C-afferent nerve fibers in the skin, muscles, joints, fasciae, and other deep somatic structures. Cutaneous receptors may be activated by mechanical, thermal, chemical, or other algesic stimuli, and nociceptors in the deep somatic structures may be activated by disease, 194

Temporomandibular Disorders Atypical Facial Pain Neurologic Disorders Trigeminal Neuralgia Glossopharyngeal Neuralgia Postherpetic Neuralgia Vagal and Superior Laryngeal Neuralgia Headaches

Migraine Tension-Type Headache Cervicogenic Headache Cluster Headache Chronic Paroxysmal Hemicrania Traction and Inflammatory Headache Neoplastic Disease

inflammatory processes, contraction, ischemia, rapid distention, or other visceral stimuli. A prolonged increase in noxious input may make the nociceptors more responsive to noxious stimulation or nociceptors may begin to respond to stimuli that are normally innocuous. This process is called peripheral sensitization and may contribute to hyperalgesia and allodynia. Sensory innervation to the ear and periaural region is derived from cranial nerves V, VII, IX, and X as well as cervical nerves 2 and 3. Nociceptive impulses in the distribution of cranial nerves V, VII, IX, and X synapse with secondorder neurons in the part of the trigeminal brainstem sensory nuclear complex known as the subnucleus caudalis or the medullary dorsal born (MDH). Nociceptive pain impulses from cervical nerves 2 and 3 activate neurons in the spinal dorsal horn. It has also been pointed out3 that there is an unusually high degree of nociceptive convergence of the upper cervical nerves and the trigeminal system, providing overlap of peripheral C2 and C3 nociceptive fibers with the other cephalic nociceptive nerves—V, VII, IX, X, and XII. The three types of neurons in the MDH are lowthreshold mechanoreceptors (LTM), which respond only to nonnoxious stimuli; wide dynamic range (WDR) neurons, which respond to both noxious and nonnoxious stimuli; and high-threshold nociceptive-specific (NS) neurons, which respond exclusively to noxious stimuli. Central to the theme of referred pain to the ear is the concept of central convergence of primary afferent neurons at a single WDR or NS neuron in the MDH or spinal dorsal horn. A substantial number of the WDR and NS neurons show extensive convergence and can be excited by peripheral afferent inputs from skin, mucosa, visceral (laryngeal), temporomandibular joint (TMJ), jaw or tongue muscle, tooth pulp, and neck afferents, hence the spread and referral of pain.4 Pain referral depends not only on the convergent afferent input patterns of nociceptive neurons but also on the so-called neuroplasticity or central

Otalgia

sensitization (an increase in neuronal excitability) that may be generated in the neurons by these inputs as a result of injury or inflammation.5 Some of the afferent inputs to the nociceptive neurons may be “unmasked” as a result of this nociceptive input and become more effective in exciting these second-order neurons with the result that pain is perceived as coming from the tissue supplied by these afferents.5 Pain may also be characterized as either acute or chronic in nature. Acute pain has been defined as a complex constellation of unpleasant sensory, emotional, and mental experiences and certain autonomic (involuntary) responses and psychological and behavioral reactions provoked by tissue damage.2 Chronic pain has been defined as pain that persists a month beyond the usual course of an acute disease or a reasonable time for an injury to heal or that is associated with a chronic pathological process that causes continuous pain or the pain reoccurs at intervals for months or years.5 Acute pain may result from a variety of causes including trauma, infection, or neoplasm. Relatively speaking, acute pain conditions are usually readily diagnosed and have well-defined treatment parameters. As the causative condition is resolved, the resultant acute pain subsides usually leaving no disability. This is in contrast to the chronic pain patient who may demonstrate little or no pathology and when pathosis is present it is frequently disproportionate to the degree of discomfort experienced. Unlike acute pain, chronic pain does not tend to be a protective phenomenon and thus serves no useful purpose. The treatment of chronic pain tends to be less well defined and successful with rehabilitation rather than cure being a realistic goal. Compared to acute pain, chronic pain therapy tends to be protracted, frequently leaving the patient with some resultant limitation of function.

ANATOMY From an anatomical perspective cranial nerves (CNs) V, VII, IX, and X, cervical nerves 2 and 3 through the cervical plexus, and the caroticotympanic nerves derived from the carotid sympathetic plexus of the internal carotid artery provide afferent pathways for the transmission of sensory stimulation of the auricle, the external auditory canal, tympanic membrane, middle ear, and immediately adjacent areas. The auriculotemporal branch of the mandibular or third division of the fifth cranial nerve provides sensory innervation for the tragus, anterior, and superior aspects of the auricle and external auditory canal as well as the anterosuperior two-thirds of the lateral or external wall of the tympanic membrane. Located in the middle ear and in the eustachian tube, respectively, the tensor tympani and tensor palati muscles are derivatives of the mandibular or first branchial arch and are innervated by the third division of CN V. The masticatory muscles innervated by the third divisions of CN V receive innervation from both motor and sensory nerve fibers and there is no reason to assume that sensory innervation has been lost to the tensor tympani and tensor palati muscles merely because they have been “borrowed” by the ear through phylogenetic development. The majority of the sensory innervation of skeletal muscles is derived from thinly myelinated A-delta (group III) and unmyelinated C-afferent (group IV) fibers in muscle fascia,

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between muscle fibers, in the walls of blood vessels, and in tendons and many of these fibers act as muscle nociceptors (this is more certain for the C-afferent [group IV] units than for the A-delta [group III] fibers).6,7 Electromyographic studies of both the tensor tympani and stapedius muscles have demonstrated contraction of both muscles concomitantly with a number of complex movements including tight closure of the eyes, jaw opening and jaw clenching, swallowing, and speaking.8 It has been pointed out that tonic contractions of the tensor tympani muscle may be accompanied by otalgia, a sense of pressure and aural fullness, and tinnitus or other transient acoustic sensations.8 Hence the middle ear may not only be a site of referred pain but primary otalgia may arise from chronic contraction of the tensor tympani muscle along with, for instance, chronic contraction of the masseter muscle in cases of temperomandibular dysfunction worsened by bruxism. The question may then be: Is the middle ear pain primary or secondary in nature? The seventh CN supplies sensory innervation for a portion of the posterior and posterosuperior auricle, an adjacent portion of the external auditory canal and lateral aspect of the tympanic membrane, and a small area of skin in the postauricular area. CN VII also supplies innervation to the stapedius muscle in the middle ear. The ninth CN provides sensory innervation to part of the posterior portion of the external auditory canal and meatus, an adjacent portion of the lateral surface of the tympanic membrane, and the majority of the mastoid air cells and the eustachian tube.1 The middle ear including the medial aspect of the tympanic membrane receives its sensory innervation from the tympanic plexus, which is comprised of the tympanic branch of the glossopharyngeal nerve (Jacobson’s nerves) and the superior and inferior caroticotympanic branches of the sympathetic plexus surrounding the internal carotid artery. The auricular branch of the tenth CN (Arnold’s nerve) innervates a portion of the posterior wall and floor of the external auditory canal and the corresponding external surface of the tympanic membrane. The upper cervical nerves (C2, C3) also supply sensory innervation to the ear or periauricular structures. The posterior branch of the great auricular nerve supplies sensory innervation to the majority of the posterior portion of the auricle as well as a portion of the skin over the mastoid region, which also receives some overlapping communication with the lesser occipital nerve (C2) in the mastoid region. Although pain may be referred to the ear by means of any of the cranial or cervical nerves mentioned, the most common source of referred pain to the ear is through the fifth CN. For example, pain may be experienced in the external ear including part of the external auditory canal and the tympanic membrane by convergence of primary A-delta or C-afferent nociceptive fibers from the auriculotemporal branch of CN V3 with primary A-delta or C-nociceptive afferent trigeminal nerve fibers, most commonly other branches of CN V3, at WDR neurons in the medullary dorsal horn. It is also possible that pain may be referred to the middle ear or eustachian tube by convergence of primary afferent nociceptors from the tensor tympani and tensor palati muscles with other primary nociceptive afferents at WDR neurons in the medullary dorsal horn.

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It is likely then, as illustrated in the preceding example of pain sensed in the ear through the auriculotemporal branch of CN V, that convergence of primary nociceptive afferent fibers from CNs V, VII, IX, and X with WDR and possibly NS neurons in the medullary dorsal horn (trigeminal subnucleus caudalis) may be the means by which pain may be referred to the ear.4 It is also thought that pain referred to the preauricular region from C3 may be facilitated through overlap of C2 and C3 nociceptive fibers with afferent nociceptive fibers from cranial nerves V, VII, IX, and X.3

PRIMARY OTALGIA Otalgia, pain in the ear or earache, may be either primary in the ear (primary otalgia) or referred to the ear (secondary otalgia). As previously indicated, a patient with an earache has at least as good a chance that they have a normal ear with referral of pain to the ear from another site as they have of being diagnosed with primary ear disease. Because the practicing otolaryngologist and in particular the otologist should already have a good working knowledge of the differential diagnosis of primary otalgia, only a list is provided here: • • • • • • • • • • • • • •

Otitis externa (bacteria or fungal) Myringitis Cerumen impaction Foreign body in the ear canal Perichondritis or chondritis of the auricle Relapsing chondritis Carbuncle or furuncle Frostbite or burn of the auricle Trauma to the external canal Traumatic perforation of the tympanic membrane Hemotympanum Eustachian tube dysfunction Eustachian tube obstruction Otitis media and mastoiditis (may be confounded by) • Petrositis • Subperiosteal abscess • Extradural/subdural abscess • Venous sinus thrombus • Brain abscess • External canal, middle ear, or skull base neoplasms including metastatic disease In most cases primary causes of otalgia involving the external ear will be readily obvious, although potentially the most ominous, primary malignancy in the external canal may not be at all obvious in the early stage and may be overlooked. Conversely, however, the presence of mild erythema of the tympanic membrane or erythema and/or mild swelling of the external auditory canal should not preclude a thorough head and neck examination to rule out pathology that may refer to the ear. A classic example is the patient with temperomandibular (TMD or TMJ) pain with referral to the ear who may then rub the external ear canal with a finger or foreign object in attempts to alleviate their pain, resulting in the appearance of bacterial or fungal otitis externa.

REFERRED OTALGIA Differential Diagnosis of Pain Referred to the Ear Disorders that may produce referred pain to the ear can be either acute or chronic in their nature. For ease in differential diagnosis, disorders that present primarily as acute pain are discussed first followed by disorders that tend to become chronic or may present as a chronic pain condition on clinical examination. Table 10-1 lists the more frequently encountered “acute” disorders that may produce a feeling of pain in the ear, and Table 10-2 lists those disorders that are more typically chronic in nature that may refer pain to the ear.

Acute Referred Otalgia Orofacial pain disorders are arguably the most frequent cause of referred pain to the ear. The most common cause of acute pain in the orofacial region, which is innervated in the maxillary arch by CN V2 and in the mandibular arch by CN V3, is dental or periodontal in origin. This may include exposed dentin on root surfaces, pulpitis or pulpal necrosis with or without periapical pathosis or formation of an abscess, and either superficial or deep periodontal infections. TABLE 10-1. Acute Referred Otalgia: Common Causes by Region of Referral Orofacial Region Exposed root surfaces Pulpitis or pulpal necrosis Periapical infection Periodontal infection (superficial or deep) Unerupted or impacted teeth Traumatic occlusion Ill-fitting dental appliances Recent adjustment of arch wires (orthodontic therapy) Primary or recurrent herpetic infection Acute herpes zoster Recurrent aphthous stomatitis Mucocutaneous disorders (i.e., lichen planus) Geographic tongue Burning mouth or burning tongue Maxillary sinusitis Nasal infections Parotiditis

Pharynx Inflammatory disorder hypo-, oro-, nasopharynx Tonsillitis and peritonsillar abscess Post-tonsillectomy pain Eagle’s syndrome

Larynx and Esophagus Laryngitis Perichondritis or chondritis Arthritis of cricoarytenoid joint Hiatal hernia Infection or foreign body in esophagus

Other Sources Traction or inflammation involving cerebrovascular blood supply Thyroiditis Angina Aneurysm of great vessels

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Orofacial Pain (Chronic)

may originate from inflammatory processes in other visceral sources such as the thyroid gland and also from angina and aneurysms of the great vessels.

Temporomandibular disorders (TMD, TMJ); includes myofascial facial pain and intra-articular TMJ pain Atypical facial pain

Chronic Referred Otalgia

TABLE 10-2. Referred Otalgia, Typically Chronic Disorders

Neurologic Disorders Trigeminal neuralgia Glossopharyngeal neuralgia Postherpetic neuralgia Vagal and superior laryngeal neuralgia

Headaches Migraine headache Tension-type headache Cervicogenic headache Cluster headache Chronic paroxysmal hemicrania Traction and inflammatory headache (includes temporal arteritis)

Neoplastic Disease Carcinoma, sarcomas (including Hodgkin’s and non-Hodgkin’s lymphomas), and metastatic disease

Other dental factors such as unerupted or impacted teeth, traumatic occlusion, ill-fitting dental appliances, or even recently adjusted arch wires in a patient undergoing orthodontic therapy may also be causative factors. A variety of other painful oral inflammatory disorders may also refer to the ear including primary or recurrent herpetic gingivostomatitis, acute herpes zoster, recurrent aphthous stomatitis (primarily the major scarring form), mucocutaneous disorders such as erosive lichen planus, inflammatory lesions of the tongue such as geographic tongue and less well understood processes such as burning mouth syndrome. Other disorders of the orofacial region that may be referred to the ear along either the second or third divisions of CN V include maxillary sinusitis, nasal infections, and parotiditis caused by either infection or obstruction of Stensen’s duct by a stone. Some of the dural blood vessels are innervated by fibers from CN V3 (CN V1 provides the majority of the sensory trigeminal vascular innervation) and because pain is the only sensation that may be evoked by inflammatory or traction stimuli to the cerebral vascular blood supply, then disease in this area will nonselectively present as pain. Although temporomandibular dysfunction of intra- or extra-articular origin may be acute in nature, this is covered in the differential diagnosis of chronic disorders leading to otalgia. Disorders of the pharynx are also relatively common causes of referred pain to the ear with inflammatory disorders of the oro-, naso-, or hypopharynx, tonsillitis, peritonsillar abscesses, and post-tonsillectomy pain being common causes of referred otalgia. Also, Eagle’s syndrome caused by an elongated styloid process may present as referred pain to the ear and may classically be confused with or mimic glossopharyngeal neuralgia, which is discussed later in this chapter. Inflammatory disorders of the larynx and esophagus may be referred to the ear through the vagus nerve and include laryngitis, perichondritis, chondritis, arthritis of the cricoarytenoid joint, hiatal hernia and inflammation, and infection or foreign body in the esophagus. Referred otalgia

To many practitioners chronic pain remains an enigma from the standpoint of diagnosis and management. This is explained to a large extent by the fact that, of necessity, the emphasis in most training programs and hence in most practices centers on the diagnosis and management of “acute” pain conditions, resulting in attempts to treat individuals with chronic pain by therapies designed only for the short term. Even those patients with more chronic conditions such as malignancy tend to be treated with the acute pain model. The differential diagnosis of conditions that may produce chronic pain in the head and neck is a broad one and includes orofacial pain, neurologic disorders, headache, and pain due to cancer. The remainder of this section is a discussion of those chronic pain disorders that may present primarily or concomitantly with other diseases as referred otalgia. As a disclaimer, it should be mentioned that there are a variety of potential pitfalls in formulating a differential diagnosis for chronic head and neck pain. The first and potentially most significant pitfall is that chronic pain is usually viewed from an individual specialist’s perspective, which is frequently less than “global” in nature and may lead to diagnostic bias. The second is that, because the classification of these conditions is difficult, it tends to be based more on opinion than on an understanding of pathogenesis. This is further complicated by the fact that differential diagnosis always tends to be more straightforward in the literature than in the examining room where textbook distinctions are seldom as clear as anticipated.

OROFACIAL PAIN Temporomandibular Disorders Acute orofacial pain conditions as a cause of otalgia are described in an earlier section of this chapter. Chronic orofacial pain conditions include temporomandibular disorders (TMD, TMJ pain), atypical facial pain (AFP) and atypical odontalgia. Temporomandibular disorders present a complex problem from a standpoint of both diagnosis and management. The differential diagnosis of TMD includes nonarticular conditions mimicking TMD, extra-articular causes of jaw limitation, true pathology of the TMJs where the disorder in question begins primarily in the joint and remains limited to it, and finally myofascial pain dysfunction (MPD), which is far and away the most common cause of TMD and hence the most common cause of chronic referred pain from the orofacial region to the ear. At this point some explanation of the term MPD is warranted. Myofascial pain dysfunction has also been termed myofascial pain syndrome, musculoskeletal or muscle contraction pain, myofascitis, myofibrositis and myalgia. Myofascial pain is the most frequently encountered type of chronic facial, head, and neck pain and according to Laskin9 it accounts for as many as 90% of cases of TMJ pain. It has been characterized as a regional pain syndrome

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often with sudden onset and with trigger points causing locally referred pain.10 It has been defined as pain, tenderness, or other referred phenomena, with the dysfunction attributed to myofascial trigger points.11 The diagnosis of MPD is predicated on finding a trigger point. A myofascial trigger point is a hyperirritable spot in skeletal muscle that is associated with a hypersensitive palpable nodule in a taut band, which is painful on palpation and can give rise to characteristic referred pain, referred tenderness, motor dysfunction, and autonomic phenomena.12 Trigger points may be latent or active. An active trigger point will produce or reproduce a clinical pain complaint while latent trigger points, while tender to palpation and often causing motor dysfunction with stiffness and restricted range of motion, are pain free.13,14 Trigger points occur primarily in the deep midportion of the muscle and are best discovered by examining a muscle while it is relaxed, and being passively stretched by the examiner.10 The examiner first establishes the sensation of finger pressure by palpating a nonpainful area and then instructs the patient to respond when the pain or tenderness other than the pressure from finger palpation is noted. This is done by rolling the muscle transversely under the fingers. Usually a nodule or taut band will be felt. Many times a verbal response by the patient is unnecessary, as he or she may exhibit an involuntary “jump sign” when a tender trigger point is located. The concept of myofascial pain is discussed here not only with regard to TMD but also in later sections in conjunction with tension-type headache pain including cervicogenic headache of myofascial origin. Women are affected more frequently than men and although it may appear at virtually any age, myofascial pain appears to occur most commonly in the third, fourth, and fifth decades of life. Historically, the etiology of TMD was thought to be related to occlusal irregularities and dysfunctional occlusal contact.15 This misconception that occlusion was the primary etiologic factor in temporomandibular pain and dysfunction continues today to result in diagnostic errors, unnecessary irreversible dental treatments, and treatment failures. Over time, researchers and clinicians have looked beyond occlusal dysfunction to the musculature and the mechanics of joint function and dysfunction as the causative factors in TMD pain. TMD patients may present with pain, muscle tenderness, popping or clicking of the TMJ(s), limitation and/or deviation of jaw movement, and otologic manifestations. They may have jaw pain, frontal, frontotemporal or occipital headache pain, toothache, sinus pain, earache, pre- or postauricular pain, sore throat, dysphagia, a sense of an object in the throat, or periorbital pain. Both acute and chronic orofacial pain conditions (toothache, periodontal infection, TMD, etc.) frequently result in referred pain to the ear. This likely occurs as a result of the convergence of nociceptive pain impulses from the offending structure along primary afferent nerve fibers to WDR neurons in the medullary dorsal horn with thinly myelinated A-delta and unmyelinated C-afferent muscle nociceptors from the auriculotemporal branch of CN V3 innervating the external ear and possibly primary nociceptive afferents from the tensor tympani and tensor palati muscles.

Atypical Facial Pain The term atypical facial pain (AFP) is used as a moniker for persistent chronic facial or intraoral pain that does not fit into the diagnostic criteria for a specific orofacial pain disorder. It is usually a poorly defined, unilateral, deep, continuous, or nearly continuous aching, boring, or burning pain not limited to the distribution of the fifth or ninth cranial nerves which may actually spread over the area supplied by the cervical nerve roots. Although trigger zones are absent, attacks of atypical facial pain may be set off by mechanical stimulation including percussion or chewing. The majority of patients are women, with the most frequent age of occurrence being the fourth through sixth decades of life.16 The term atypical odontalgia has been used when the patient is convinced that their pain is emanating from a tooth or several adjacent teeth. Although its underlying mechanisms are unknown, potential etiologic factors may include trauma, hormonal factors (based largely on its strongly female prevalence), psychological factors, and local irritation.17 The action of these different factors may involve peripheral sensitization following the presence of chronic irritation or inflammatory stimuli or endodontic, surgical, or other traumatic events that may produce ectopic activity along a peripheral nerve. As alluded to earlier in this chapter, these peripheral changes may result in central sensitization, which appears to be a key mechanism in many of these idiopathic orofacial pain conditions. Sympathetic nervous system involvement may participate in the maintenance of the central sensitization. Loss of segmental inibition from deafferentation following nerve injury or impairment or loss of inhibitory interneurons may also be possible mechanisms. A neuropsychiatric assessment of patients with this disorder may show a significant number of them to have a specific psychiatric diagnosis as classified by DSM-IV criteria. In one study of 68 patients with AFP, 46 (68%) had a specific diagnosis by DSM-IV criteria covering a wide variety of disorders predominantly somatoform, affective, adjustment, or personality disorders.18 While AFP may be refractory to both medical and dental therapies, some patients may respond to antiepileptic medications such as gabapentin, topiramate, tiagapine, and others as well as tricyclic antidepressants and trazadone. Patients with AFP may experience referred otalgia or its diffuse nature may approximate the ear in the preauricular region.

NEUROLOGIC DISORDERS The categorization of neuralgias of the face, head, and neck can be both difficult and confusing. Although not usually considered a prime suspect in the differential diagnosis of referred otalgia, trigeminal neuralgia is included in this section not only because it is by far the most frequently occurring neuralgic condition in the head and neck but also because of the close proximity of occurrence of pain to the ear in some patients and the fact that it occasionally will refer pain to the ear. The etiology, pathogenesis, and management of trigeminal neuralgia has been studied far more than any of its other head and neck counterparts; hence the classic features of the CN neuralgias are briefly described in the discussion of trigeminal neuralgia.

Otalgia

Also included in this section are glossopharyngeal neuralgia, postherpetic neuralgia, and vagal and superior laryngeal neuralgia. The term atypical facial neuralgia is synonymous with AFP and is discussed in the previous section of this chapter. Also, because the vast majority of patients with occipital neuralgia have muscle contraction or tension-type headaches following the distribution of the occipital nerve, it is included in the discussion of muscle contraction headaches under the term cervicogenic headache.

Trigeminal Neuralgia Trigeminal neuralgia or tic douloureux is an episodic symptom complex characterized by agonizingly intense paroxysmal attacks of sharp, stabbing, burning, or electric shocklike pain confined to one side of the face in the trigeminal distribution. These attacks of pain, which may last from a few seconds to a few minutes, can be triggered by a light touch to the face including such light stimulus as a breeze or vibration. Trigger points are particularly common around the mouth and nose with pain often being exacerbated by simple acts such as taking food or fluids orally, which may result in severe weight loss and dehydration. Whereas light touch and vibration are the most effective triggering stimuli, pinching or pressing the trigger area is unlikely to provoke an attack.19 As previously mentioned, trigeminal neuralgia may occasionally be a source of referred pain to the ear and also may occur in close proximity to the ear. Physical examination is essentially unremarkable, with the absence of any detectable neurologic deficit or a subtle sensory deficit within the distribution of the trigeminal nerve. Although in the majority of cases no identifiable etiology for the trigeminal neuralgia is noted, in as many as 15% of patients there may be an underlying cause such as the presence of a benign or malignant neoplasm in the posterior fossa or multiple sclerosis which will present at a later point in the disease process.20 Hence, when considering the diagnosis of trigeminal neuralgia, a magnetic resonance imaging (MRI) study paying particular attention to the posterior fossa should be performed as a mass lesion in this area may cause symptoms typical of trigeminal neuralgia in the absence of other neurologic signs and symptoms.21 A broad range of other entities must be considered in the differential diagnosis of trigeminal neuralgia. These include a variety of dental causes of pulpal origin, including dental infection or cracked teeth; periodontal pathology; denture pain from pressure on the mental nerve; TMD, primarily myofascial pain; atypical facial pain including atypical odontalgia; glossopharyngeal neuralgia; postherpetic neuralgia; cluster headache; and chronic paroxysmal hemicrania and temporal arteritis. It is now believed that 80% to 90% of cases of trigeminal neuralgia result from specific abnormalities of trigeminal afferent neurons in the trigeminal root or ganglion resulting in hyperexcitable afferents that give rise to paroxysmal epsodes of pain as a result of synchronized after discharge activity.17,22 Both medical and surgical therapies have been used to treat trigeminal neuralgia. While trigeminal neuralgia is an excruciatingly painful and in some cases disabling, debilitating disorder, it should also be pointed out that in the absence of a malignant neoplasm as its primary cause,

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it is a nonfatal one and therefore the primary approach to treatment should be medical intervention with surgery being reserved for patients who become refractory to or unable to tolerate available medications. Various antineuralgic medications, the majority of which are anticonvulsants, are available for use singly or in combination and include baclofen (antispastic category), carbamazepine, oxcarbazepine, gabapentin, lamotrigine, topiramate, tiagapine, sodium valproate, clonazepam, and phenytoin. It is recommended that in view of its greater safety, baclofen should be the initial drug of choice in treating trigeminal neuralgia. In those cases where baclofen is ineffective or not tolerated, carbamazepine, oxcarbazepine, or gabapentin is the next drug of choice. In those patients who do not respond to therapy with either drug alone, the combination of baclofen and carbamazepine may be effective.23 It has also been reported that baclofen and phenytoin may be used in those patients who cannot take carbamazepine because baclofen and phenytoin have a synergistic action.23 The use of lamotrigine in combination with carbamazepine or phenytoin has been reported.24 In some cases tricyclic antidepressant and nonsteroidal anti inflammatory analgesic medications may be used in combination with antineuralgic drugs as mentioned above. The clinician will find that the right combination of medications often becomes very individualized from patient to patient and is often found by trial and error with the use of multiple medications being involved. Unfortunately some patients who have achieved good control of their symptoms over time may decide on their own to wean themselves from their medications with resultant return of their pain. It is the author’s experience that in many cases pain relief is not again achieved at the same combination and/or dosage of medication as the patient was previously taking. Nerve blockade with local anesthetic may be effective in breaking this new cycle of pain in combination with antineuralgic medications. In cases where adequate control of symptoms is not achieved or where medication is no longer effective, surgical intervention may then be indicated.

Glossopharyngeal Neuralgia Glossopharyngeal neuralgia is a relatively uncommon episodic symptom complex characterized by unilateral paroxysmal attacks of sharp, stabbing, burning, or electric shock–like pain that may be felt in the posterior tongue, tonsil, lateral pharyngeal wall, nasopharynx, and ear. The trigger zone is usually located in the lateral pharyngeal wall, tonsillar fossa, or in the area of the external ear posterior to the ramus of the mandible with pain referring outward from the trigger point. Episodes of pain may be provoked by stimulation of the trigger zone during the act of swallowing, yawning, or coughing. Some patients with glossopharyngeal neuralgia may experience bradycardia, syncope, and seizure with the attack of pain.25 As with trigeminal neuralgia, physical examination is essentially unremarkable, with the absence of any detectable neurologic deficit. When considering the diagnosis of glossopharyngeal neuralgia, care should be taken to rule out the presence of a carcinoma or other mass lesion in the oro-, hypo-, or nasopharynx or at the cerebellopontine angle.

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A useful technique in diagnosing true glossopharyngeal neuralgia is cocainization or blocking of the trigger point with a local anesthetic. The pathophysiology of glossopharyngeal neuralgia is thought to be the same as trigeminal neuralgia with involvement of the ninth instead of fifth cranial nerve. In some cases however, a specific cause for glossopharyngeal neuralgia can be found that, in addition to mass lesions, includes pharyngitis or tonsillitis, tonsillectomy, radiation therapy to the pharynx and an elongated styloid process. The treatment for glossopharyngeal neuralgia is the same as that for trigeminal neuralgia except in those cases where it is secondary to an elongated styloid process in which case relief may be effected by styloidectomy.

Postherpetic Neuralgia Following a primary infection with the varicella-zoster virus (VZV) the VZV lies dormant in trigeminal and dorsal root ganglia and may in later life reactivate to cause herpes zoster (shingles). It is theorized that following reactivation the virus transmigrates in a segmental fashion along spinal or cranial nerves, resulting in a localized painful vesicular eruption of the skin along the distribution of the involved nerve. Although the pain and vesicular eruption usually resolve within 2 to 3 weeks, pain in the form of postherpetic neuralgia may persist beyond resolution of these initial symptoms. Although pain may be referred to the ear from involvement of the cranial and cervical nerves and may mimic geniculate or nervus intermedius neuralgia, it is not uncommon for herpes zoster of the external ear to occur with referral of pain to the face, mastoid, and occipital regions as well as the neck. The primary goal in the treatment of acute herpes zoster is to palliate the patient’s pain and effect early resolution of the acute stage of the disease and prevent the development of postherpetic neuralgia. It is felt that in young healthy patients with acute herpes zoster, only symptomatic treatment is indicated.26 In patients more than 50 years of age, however, treatment for prevention of postherpetic neuralgia in addition to symptomatic relief is thought to be essential.26 The pain of postherpetic neuralgia is described as a persistent severe burning pain in the affected area and is often debilitating in its nature. In cases where the acute herpes zoster went untreated or was treated inadequately and the symptoms of postherpetic neuralgia are noted, initial early aggressive intervention is of the utmost importance. Although various treatment approaches have been taken in the management of acute herpes zoster, including the use of antiviral medication such as valacyclovir, corticosteroids, analgesics, antidepressants, or topical therapy, there is increasing evidence that an invasive approach including the use of sympathetic nerve blocks, somatic nerve blocks, and subcutaneous infiltration of combinations of local anesthetic and steroid alone or in combination with noninvasive therapies are indicated. Nonsteroidal anti-inflammatory analgesics may be useful in controlling the mild pain in an attack of acute herpes zoster, with opioid therapy being reserved for severe pain exacerbations. Tricyclic antidepressant medications such as amitriptyline, nortriptyline, doxepin, desipramine, or

imipramine may be used for both their potential pain relieving and sedative properties. Anxiolytic agents such as lorazepam, alprazolam, or diazepam may also be used on a short-term basis.26 Sympathetic nerve blocks may be performed as well as subcutaneous infiltrations in the areas of the vesicular eruption with a mixture of local anesthetic and steroid.26 Initial therapy for postherpetic neuralgia centers on the use of medications such as nonsteroidal anti-inflammatory analgesics and tricyclic antidepressants alone or in combination with phenothiazines such as fluphenazine. Gabapentin is regarded as first-line therapy. The use of other anticonvulsants as previously discussed for trigeminal neuralgia may be useful in the management of postherpetic neuralgia, especially where shooting or stabbing pain is experienced. As previously alluded to, time is of the essence in treating postherpetic neuralgia whose duration is of 6 months or less, because the likelihood of achieving satisfactory pain relief after this time is considerably diminished. Sympathetic blockade in the form of as series of stellate ganglion blocks should be performed by experienced personnel at the first sign of postherpetic neuralgia. Where persistent severe pain is present, sustained release opioids such as methadone and long-acting oral forms of morphine and oxycodone and the fentanyl skin patch may be helpful. Transcutaneous electrical nerve stimulation (TENS) may also be a useful adjunct.

Vagal and Superior Laryngeal Neuralgia Vagal and superior laryngeal neuralgia is an episodic symptom complex characterized by sudden severe attacks of brief lancinating electric shock–like pain in the side of the thyroid cartilage, pyriform sinus, and angle of the jaw; it rarely involves the ear. Attacks are precipitated by talking, swallowing, yawning, or coughing and usually occur in combination with glossopharyngeal neuralgia.27,28 Physical examination is essentially unremarkable with no neurologic deficit being noted within the distribution of the vagus nerve. As with the other cranial neuralgias, diagnosis is established by history and by identifying a trigger zone. Laryngeal topical anesthesia or blockade of the superior laryngeal nerves is said to stop the pain and is a useful diagnostic and prognostic procedure.29Also, as with the other CN neuralgias, pharmacologic therapy is indicated for the management of this disorder and is identical to that used for trigeminal neuralgia and glossopharyngeal neuralgia. Surgical management may be indicated if pharmacologic therapy is unsuccessful.

HEADACHES Despite attempts at clarification, the classification of headaches remains quite complex and often controversial, generally being based on the supposed pathophysiology. In 1988 the International Headache Society (IHS) published, on the basis of empirical findings, the first ever operational classification of headache.20 Those forms of headache that may present with referred pain to the ear will be discussed in this section.

Otalgia

Migraine Group 1 of the IHS classification of headaches comprises the various categories of migraine headache, most commonly migraine with and without aura (classic and common migraine). Migraine headaches with and without aura differ primarily in the presence or absence of premonitory transient focal neurologic symptoms known as the aura, the most common of which are visual disturbances, including the scintillating scotomata, also known as the fortification spectrum.30 The fortification spectrum is characterized by an area of blurred or cloudy vision, superimposed with bright zigzag lines often of various colors and usually in only one visual field, This phenomenon is so highly characteristic that it is said to be pathognomonic of migraine with aura.31 Somatosensory symptoms consisting of a feeling of “pins and needles” often beginning in the fingers of one hand and extending gradually up the arm, ultimately involving the ipsilateral side of the face particularly the nose and mouth, may also be seen.13,30 The headache phase of migraine headache with or without aura most commonly presents as unilateral pain in the head, which may initially be dull in nature evolving into a severe throbbing, boring pain that may spread to the contralateral side. Migraine headache is frequently accompanied by nausea, vomiting, diarrhea, photophobia, vertigo, tremors, excess perspiration, and chills.30 The diagnosis of “migraine” headache unfortunately is often used as a generic term to indicate a variety of chronic recurring headaches, including tension-type headache and headache for which no satisfactory cause can be found.

Tension-Type Headache The most common headache is the tension-type headache (Group 2 in the IHS classification), which has also been termed muscle contraction headache. It has been estimated that of all patients who seek medical care for their headaches, 80% suffer from tension-type headache.32 Tension-type headache may be either episodic or chronic. The criterion for chronic tension-type headache is that a headache must be present for at least 15 days a month during at least 6 months. Episodic or acute muscle contraction headache usually responds to analgesics available over the counter.29 Tension-type headache is usually characterized as a steady, nonpulsatile ache, which may be localized unilaterally or bilaterally to a single region in the head or may be generalized. It may occur in the frontotemporal region, occipital region, parietal region, or any combination of these sites, often with a feeling of tightness, drawing, or bandlike pressure. The pain of tension-type headache, especially that occurring in the temporal region unilaterally or bilaterally, may refer to the ear presenting as otalgia. The severity of the headache pain will vary from soreness to gnawing or a dull ache to a sharp, episodic, or continuous stabbing pain. Frequently, the patient will complain of a feeling of tightness or cramping in the neck or shoulder regions. Tension-type headache may begin as either unilateral or bilateral headache pain and may progress from a localized type of headache to a generalized headache pain frequently

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accompanied by photophobia, periorbital pain, lacrimation, tinnitus, vertigo, and, as previously mentioned, otalgia.

Cervicogenic Headache Although cervicogenic headache is a headache form that may derive its origin from one of several structures in the neck or back of the head including the nerves, ganglia, nerve roots, uncovertebral joints, intervertebral joints, discs, bone, periosteum, muscle, and ligaments, among other structures,33 experience would indicate that arguably the most common cause of this type of headache involves the cervical musculature in the occipital and suboccipital regions. As the term implies, cervicogenic headache originates in the neck with a referral pattern to the head, frequently the ophthalmic division of the trigeminal nerve presenting as retro-orbital and frontal headache pain. This is explained by the very close proximity of the cervical spinal and medullary dorsal horns with apparent convergence of some cervical nociceptive afferent fibers in the medullary dorsal horn.3 Through this pattern of convergence, pain may also be referred to the vertex along the midline, the periaural region, the pinna, and jaw. Although the pathogenesis of tension-type headache may vary from individual to individual, in the end the primary underlying cause is pain of myofascial origin. It may be difficult to differentiate a tension-type headache that includes occipital, parietal, or frontotemporal pain from TMD or cervicogenic headache of myofascial origin. All of these may present as frontotemporal, temporal, or occipital pain often with neck and shoulder tightness and all may be a source of referred pain to the ear or periaural region. Many patients with myofascial facial pain will relate a history of tension-type headache just as patients with tensiontype headaches will frequently mention facial pain. Another confounding issue is the frequent bias and lack of global perspective on the part of the examiner. The average physician may not take the time to examine the orofacial structures and musculature with the resulting diagnosis of tension-type headache, while the average dentist frequently may not examine beyond the orofacial region and make the diagnosis of TMD. Musculoskeletal examination of the patient with tension-type headache, TMD, or cervicogenic headache of myofascial origin will demonstrate nodular or bandlike tender muscle trigger points, which on finger palpation will produce the classic active trigger points reproducing the patient’s pain. The appropriate diagnosis should be made based on the primary region from which the pain complaint is found to emenate on clinical examination.

Cluster Headache Cluster headache falls under Group 3 of the IHS classification of headaches: cluster headache syndrome. The most portentous of the primary headache disorders, it has been known by a variety of appellations including erythroprosopalgia of Bing, ciliary neuralgia, migrainous neuralgia, erythromelalgia (Horton’s headache), histaminic cephalgia (Horton’s syndrome), lower half headache, Vidian neuralgia, Sluder’s neuralgia, sphenopalatine neuralgia, and hemicrania periodica neuralgiformis.34,35

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This type of headache is comprised of two major subtypes: episodic cluster headache and chronic cluster headache. Episodic cluster headache, the most common type, is said to account for 80% of all cases. In episodic cluster headache the patient experiences recurring clusters of headaches, which occur regularly and usually on a daily basis, alternating with periods of refractoriness or remission. The term chronic cluster headache is used when a remission has not occurred for 1 year.32 Cluster headache is described as a steady, excruciating, searing, stabbing, boring, or burning pain around the eye and frontotemporal region that occasionally may refer to the occipital region, the ipsilateral maxilla and mandible including the teeth, and the cheek extending into the neck on the affected side.36 The onset of the painful episode may be preceded by feeling a fullness or pressure in the area where the headache will occur. Unlike other primary headache disorders such as migraine and tension-type headache, which affect women more frequently than men, cluster headache predominantly affects31 men more than women by a ratio of up to 6:1. The differential diagnosis of cluster headache includes migraine headache, trigeminal neuralgia, temporal arteritis, pheochromocytoma, and Reader’s paratrigeminal syndrome.32

Chronic Paroxysmal Hemicrania Chronic paroxysmal hemicrania is a rare headache disorder thought to be a variant of cluster headache. It is similar to a cluster headache in character but differs from it in the fact that its attacks are more frequent and of shorter duration and it responds dramatically to indomethacin and partially to salicylates.37,38

Traction and Inflammatory Headache Traction and inflammatory headache is a broad category of headache pain, which crosses several sections of the IHS headache classification. It is caused by traction, stretching, compression, or inflammation of pain-sensitive structures in the skull or its components including the brain, meninges, arteries, veins, eyes, ears, teeth, nose, and paranasal sinuses. It denotes a nonspecific headache, which may be caused by mass lesions, hemorrhages, or inflammatory disease and includes inflammatory processes outside the skull such as temporal arteritis. Because branches of the trigeminal nerve, CN V1, and some CN V3 fibers supply the cerebrovascular innervation, pain may be referred to the ear by any event that produces traction on, or inflammation of, these vessels. Innervation of this blood supply is selectively nociceptive in its nature and hence pain is the only sensation that may be evoked. Temporal arteritis is included in the category of traction and inflammatory headache and is characterized as an intense, deep, persistent, throbbing, aching, burning pain, which may be accompanied by hyperalgesia of the scalp and extreme tenderness of the distended arteries. Patients with temporal arteritis may experience pain on mastication and may have referred pain to the teeth, ear, jaw, zygoma, and nuchal and occipital regions. The presenting complaint may be ocular symptoms with partial or complete loss of vision. Temporal arteritis should be considered in any

patient with deep, intense, throbbing pain in the temple, especially if there is accompanying loss of vision. The region should be palpated, looking for the presence of a distended throbbing temporal artery. The diagnosis is made by biopsy of the affected temporal artery; however, multiple biopsies may be necessary, as the histologic changes, essentially a giant cell arteritis, are patchy in their distribution. The erythrocyte sedimentation rate is almost invariably elevated. Claudication of the jaw is strongly suggestive of temporal arteritis and is characterized by pain as soon as chewing begins, as opposed to myofascial pain in which pain is usually noted on prolonged chewing.

NEOPLASTIC DISEASE As should be clear from the preceding sections, disorders included in the differential diagnosis of referred otalgia are many and varied and, as in the case of orofacial pain including TMD, quite common. Although many more cases of referred ear pain secondary to toothache, sinus infection, tonsillitis, TMD, and so on, are encountered than from neoplastic disease, this possibility should always be considered, especially in high-risk populations such as smokers. Even when the diagnosis seems obvious, a thorough head and neck examination, including imaging studies as necessary, should be performed to assure that the “obvious” cause is not a “red herring.” For example, there is no reason to assume that referred pain from pharyngitis will present differently from an occult carcinoma in the nasopharynx. All suspicious lesions should be biopsied and there must be careful follow-up to assure that as the assumed cause for the referred pain is resolved, the pain itself is also resolved. Although carcinomas are the most common cause of neoplastic disease referred to the ear, mesenchymal malignancies must also be considered. Pain may be referred to the ear from carcinomas arising in the soft tissues of the oral cavity, tonsillar pillars and base of tongue, nasopharynx, soft palate, oropharyngeal wall, hypopharynx, larynx (including epiglottis, vocal cords, and pyriform sinus), lung, and thyroid gland. Pain may be referred to the ear from carcinoma arising in the maxilla or centrally within the mandible and from carcinoma or adenocarcinoma involving the salivary glands. Mesenchymal malignancies including rhabdomyosarcoma, fibrosarcoma or neurofibrosarcoma (in soft tissue or bone), osteosarcoma or chondrosarcoma, and malignant proliferative disorders from both lymphatic and extralymphatic sites may also present as otalgia. Intracranial neoplasms producing traction on structures innervated by the cranial or cervical nerves as well as metastatic disease to the distribution of CN V, VII, IX, X, C2, and C3 must also be considered.

REFERENCES 1. Paparella MM, et al: Otolaryngology, vol 2, 3rd ed. Philadelphia, WB Saunders, 1991, pp 1237–1242. 2. Bonica JJ: The Management of Pain, vol 1, ed 2. Philadelphia, Lea & Febiger, 1990, pp 18–27.

Otalgia

3. Poletti CE: C2 and C3 radiculopathies: Anatomy, patterns of cephalic pain, and pathology. APS 1(4):272–275, 1992. 4. Fromm GH, Sessle BJ: Trigeminal Neuralgia: Current Concepts Regarding Pathogenesis and Treatment. Boston, ButterworthHeinemann, 1991, pp 71–104. 5. Sessle, BJ: Recent insights into brainstem mechanisms underlying craniofacial pain. J Dent Educ 66:108–112, 2002. 6. Bonica JJ: The Management of Pain, vol 1, ed 2. Philadelphia, Lea & Febiger, 1990, pp 28–94. 7. Stacey MJ: Free nerve endings in skeletal muscle of the cat. J Anat 105:231–254, 1969. 8. Jerger J: Handbook of Clinical Impedance Audiometry. Dobbs Ferry, NY, American Electromedics Corp, 1975, pp 85–126. 9. Laskin DM: Current concepts in the management of temporomandibular joint disorders: Continuing education course presented at annual meeting of the American Academy of Oral Pathology, 1982. 10. Campbell SM: Regional myofascial pain syndromes. Rheum Dis Clin N Am 15(1):31–44, 1989. 11. Travell JG, Simons DG: Myofascial Pain and Dysfunction: The Trigger Point Manual. Baltimore, Williams & Wilkins, 1983, p 3. 12. Simons DG, Travell JG, Simons LS: Myofascial Pain and Dysfunction: The Trigger Point Manual, vol 1. Upper Half of Body. Philadelphia, Lippincott, Williams & Wilkins, 1999, p 5. 13. Fricton JR: Myofascial pain syndrome. Neurol Clin 7(2):413–427, 1989. 14. Mense S, Simons DG (eds.): Myofascial pain caused by trigger points. In Muscle Pain: Understanding Its Nature, Diagnosis, and Treatment. Philadelphia, Lippincott Williams & Wilkins, 2001 pp 205–288. 15. McNeil C (ed.): Craniomandibular Disorders: Guidelines for Evaluation, Diagnosis and Management. Chicago, Quintessence, 1990, p 7. 16. Dalessio DJ, Soloman S: Facial pain: Differential diagnosis and treatment. Clin J Pain 2:11–18, 1986. 17. Woda, A: Mechanisms of Neuropathic Pain. In Lund JP, Lavigne GJ, Dubner R, Sessle BJ: Orofacial Pain: From Basic Science to Clinical Management. Chicago, Quintessence, 2001, pp 67–78. 18. Remick RA, et al: Psychiatric disorders associated with atypical facial pain. Can J Psychiatry 28:178–181, 1983. 19. Fromm GH: Trigeminal neuralgia and related disorders. Neurol Clin 7(2):385–391, 1989. 20. Oleson J (chair), Headache Classification Committee of the International Headache Society: Classification and diagnostic criteria

21. 22. 23.

24.

25.

26. 27. 28. 29. 30. 31. 32. 33. 34. 35.

36. 37. 38.

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for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8 (Suppl 7):1–96, 1988. Bullitt E, TewJM, Boyd J: Intracranial tumors in patients with facial pain. J Neurosurg 64:865, 1986. Devor M, Amir R, Rappaport H: Pathophysiology of trigeminal neuralgia: The ignition hypothesis. Clin J Pain 18:4–13, 2002 Fromm GH, Terrence CF, Chatthaas AS: Baclofen in the treatment of trigeminal neuralgia: Double-blind study and long-term follow-up. Ann Neurol 15:240–244, 1984. Zakrzewska JM, Chaudhry Z, Nurmikko TJ, et al: Lamotrigine (Lamictal) in refractory trigeminal neuralgia: Results from a doubleblind placebo controlled crossover trial. Pain 73:223–230, 1997. Chalmers AC, Olson JL: Glossopharyngeal neuralgia with syncope and cervical mass. Otolaryngol Head Neck Surg 100:252–255, 1989. Katz JA, et al: Herpes zoster management. Anesth Prog 36:35–40, 1989. Bonica JJ: The Management of Pain, vol 1, ed 2. Philadelphia, Lea & Febiger, 1990, pp 676–686. Chawla JC, Falconer MA: Glossopharyngeal and vagal neuralgia. Br Med J 3:259–531, 1967. Bonica JJ: The Management of Pain, vol 1. Philadelphia, Lea & Febiger, 1953, pp 790–797. Diamond S, Medina JL: Headaches. Clin Symp 41(1):1–32,1989. Raskin NH: Headache, ed 2. New York, Churchill Livingstone, 1988. Dalessio DJ: Wolff’s Headache and Other Head Pain, ed 5. New York, Oxford Univ Press, 1987. Sjaastaed O, Fredrikson TA, Pfaffenrath V: Cervicogenic headache: Diagnostic criteria. Headache 30:725–726, 1990. Kudrow L: Cluster headache: Diagnosis and management. Headache 19:142–150, 1979. Tew R, Headache Classification Committee of the International Headache Society: Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia Suppl 8(7):1–96, 1988. Campbell JK: Facial pain due to migraine and cluster headache. Sem Neurol 8(4):324–331, 1988. Hochman MS: Chronic paroxysmal hemicrania: A new type of treatable headache. Am J Med 71:169–170, 1981. Sjaastad O, Dale 1: Evidence for a new (?) treatable headache entity. Headache 14:105–108, 1974.

Chapter

11 Aristides Sismanis, MD, FACS

Pulsatile Tinnitus Advances in Diagnosis and Treatment Outline Pathophysiology and Classification Arterial Causes Atherosclerotic Carotid Artery Disease Intracranial Vascular Abnormalities Venous Causes Pseudotumor Cerebri Syndrome Idiopathic Tinnitus Nonvascular Causes

P

ulsatile tinnitus (PT) is an uncommon otologic symptom that often presents a diagnostic and management dilemma to the otolaryngologist. In contrast to continuous subjective tinnitus, the majority of patients with PT have a treatable underlying process. Furthermore, identifying the cause of this symptom is imperative in order to avoid disastrous consequences from associated life-threatening intracranial pathology.

PATHOPHYSIOLOGY AND CLASSIFICATION Pulsating tinnitus most commonly originates from vascular structures within the cranial cavity, head, and neck region, as well as the thoracic cavity, and is transmitted to the cochlea by vascular and bony structures. Pulsatile tinnitus can arise either from increased blood flow or stenosis of the vascular lumen. Vascular PT can be classified as arterial or venous according to the vessel of origin. Differentiation between these two types is made by applying light digital pressure over the ipsilateral internal jugular vein (IJV). This maneuver does not affect the intensity of arterial PT, but it makes the venous type subside. The venous type can originate not only from primary venous pathologies, but also indirectly from conditions causing increased intracranial pressure (ICP) by transmission of arterial pulsations to the dural venous sinuses.1 Pulsatile tinnitus originating from nonvascular structures is classified as nonvascular. Classification of PT as objective or subjective is based on whether it is audible by both patient and examiner or by the patient only. 204

Palatal, Stapedial, and Tensor Tympani Muscle Myoclonus Evaluation History Examination Audiologic and Electrophysiologic Testing Metabolic Work-up Ultrasound Studies Radiologic Evaluation Management

Arterial Causes Atherosclerotic Carotid Artery Disease In the author’s experience, atherosclerotic carotid artery disease (ACAD) has been the most common cause of PT in patients older than 50 years of age, especially when associated with certain risk factors such as atherosclerosis, hypertension, angina, hyperlipidemia, diabetes mellitus, or smoking. Objective PT can be the first manifestation of ACAD in these patients.2 Pulsatile tinnitus in ACAD is secondary to bruit(s) produced by turbulent blood flow at stenotic segment(s) of the carotid artery. In a series of 12 patients with PT secondary to ACAD, an ipsilateral carotid bruit was present in all of them.2 Diagnosis can be established by duplex ultrasound studies.2 In cases of suspected intracranial atherosclerotic vascular disease, head magnetic resonance angiography (MRA) can be very useful. Intracranial Vascular Abnormalities Intracranial vascular abnormalities are uncommon causes of tinnitus; however, misdiagnosis may have catastrophic consequences for the patient. In the author’s experience, the most common of these abnormalities presenting with PT have been dural arteriovenous fistulae (AVFs). Aneurysms, with the exception of dissecting aneurysms of the internal carotid and vertebral arteries, do not present with PT. Dural AVFs constitute approximately 15% of intracranial arteriovenous malformations (AVMs) and usually become symptomatic during the fifth or sixth decade of life.3,4 The transverse and sigmoid sinuses are the most common dural sinuses involved, followed by the cavernous sinus. In contrast to AVMs, AVFs are usually acquired and thought

Pulsatile Tinnitus: Advances in Diagnosis and Treatment

to result from dural venous sinus thrombosis. Thrombosis may be caused by trauma, obstructing neoplasm, surgery, or infection, or it may occur spontaneously. As the thrombosed segment recanalizes, ingrowth of dural arteries takes place and artery-to-sinus anastomoses are formed.4 Patients with dural AVFs usually present with PT of the arterial type. A loud bruit over the involved dural sinus as well as objective PT are audible. Mortality from hemorrhage of a dural AVF is 10% to 20%.4 In cases with retrograde drainage into the cortical veins, the chance of subarachnoid or parenchymal hemorrhage is much higher.4 The following are two representative cases. Dissecting aneurysms are rare and more often involve the internal carotid artery (ICA) and less often the vertebral artery. Manifestations include PT, pain, transient ischemic attacks, cranial neuropathies, Horner’s syndrome, and

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subarachnoid hemorrhage.4 Sudden head rotation, especially when accompanied by extension (i.e., the tennis “ace serve”), is the most likely precipitating event.5 Fibromuscular dysplasia, various arteriopathies such as Marfan syndrome, and osteogenesis imperfecta are predisposing factors. A patient with ICA dissection following a severe episode of vomiting was recently seen by the author. Pulsatile tinnitus and ipsilateral retroauricular bruit were present. Table 11-1 summarizes the arterial causes of PT.

Venous Causes Pseudotumor Cerebri Syndrome In the author’s experience, pseudotumor cerebri syndrome has been the most common cause of venous PT in obese

ILLUSTRATIVE CASE HISTORIES

Case 1 Fifty-five-year-old female presented with left PT of 8 months’ duration. A bruit over the left retroauricular area as well as objective tinnitus were audible. Figure 11-1 is a selective

angiogram, anterior-posterior view, of the left middle meningeal artery demonstrating an AVF with rapid shunting between the occipital meningeal branch and the transverse sinus.

Case 2 Forty-five-year-old male presented with right PT of 6 months’ duration. Six months prior to this he had sustained a severe facial injury. A loud bruit was audible over the right

Figure 11-1. Angiography, anterior-posterior view, in case 1. Microcatheter placed in the left middle meningeal artery (A) demonstrates a small AVF (B) with rapid shunting between an occipital meningeal branch (C) and the transverse sinus (D).

orbit. Figure 11-2 shows a carotid angiogram, lateral view, demonstrating an AVF between the right internal carotid artery and the cavernous sinus.

Figure 11-2. Right carotid angiogram, lateral view, in case 2 shows a carotid-cavernous fistula between the right internal carotid artery (A) and the cavernous sinus (B). Note the rapid shunting through the cavernous sinus into the “arterialized” ophthalmic vein (E) and both the superior (C) and inferior (D) petrosal sinuses.

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TABLE 11-1. Arterial Causes of Pulsatile Tinnitus Atherosclerotic carotid artery disease2 Intra- and extracranial arteriovenous malformations6–8 Dural arteriovenous fistulas and aneurysms7–10 Atherosclerotic subclavian artery disease11 Atherosclerotic occlusion of the contralateral common carotid artery12 Fibromuscular dysplasia of the internal carotid arteries13–15 Carotid artery dissection4,5,16 Intrapetrous carotid artery dissection17 Brachiocephalic artery stenosis18 External carotid artery stenosis19 Ectopic intratympanic carotid artery20–22 Persistent stapedial artery23 Aberrant artery in the stria vascularis24 Vascular compression of the eighth nerve25 Increased cardiac output anemia, thyrotoxicosis, pregnancy26,27 Aortic murmurs28 Paget’s disease9,29,30 Otosclerosis31 Hypertension—antihypertensive agents31 Vascular neoplasms of skull base and temporal bone32–35 Tortuous carotid and vertebral arteries36

female patients. This syndrome is characterized by increased intracranial pressure without any focal signs of neurologic dysfunction with the exception of occasional fifth, sixth, and seventh cranial nerve palsies.37 Synonyms of this entity include idiopathic intracranial hypertension and benign intracranial hypertension syndrome. Diagnosis of this syndrome is made by exclusion of lesions producing intracranial hypertension such as obstructive hydrocephalus, mass lesions, and venous sinus occlusion. Pseudotumor cerebri syndrome is of unknown cause; however, it has been associated with various medical conditions and intake of certain medications.38 Tables 11-2 and 11-3 summarize the various conditions and medications associated with pseudotumor cerebri syndrome. In the majority of patients, this syndrome has a benign and TABLE 11-2. Conditions Associated with Pseudotumor Cerebri Syndrome Obesity Anemia Iron deficiency Pernicious Polycythemia Steroids Deficiencies Addison’s disease Steroid withdrawal Excess Cushing’s disease Iatrogenic Hypoparathyroidism Hyperthyroidism Pituitary adenoma Uremia Cystic fibrosis Vitamins Deficiencies Vitamin D Excess Vitamin A From Fishman RA (ed.): Benign intracranial hypertension. In Cerebrospinal Fluid in Disease of the Nervous System. Philadelphia, WB Saunders, 1980, pp 128–139.

TABLE 11-3. Medications Associated with Pseudotumor Cerebri Syndrome Steroids Dilantin Chlorpromazine Lithium Tetracycline TMP/SMX Amiodarone Growth hormone Oral contraceptives Indomethacin Nalidixic acid TMP/SMX, trimethoprim/sulfamethoxazole. From Fishman RA (ed.): Benign intracranial hypertension. In Cerebrospinal Fluid in Disease of the Nervous System. Philadelphia, WB Saunders, 1980, pp 128–139.

self-limiting course; however, in 25% of patients it may become chronic.37 The exact pathophysiology of this syndrome remains unclear; however, increased resistance to cerebrospinal fluid (CSF) absorption resulting in interstitial brain edema is suspected.38 Increased intracranial venous pressure secondary to elevated intraabdominal, pleural, and cardiac filling pressures has been documented in patients with central obesity and associated pseudotumor cerebri.39–41 This is consistent with the theory according to which increased resistance to CSF absorption results in pseudotumor cerebri syndrome. Although the classic presentation of pseudotumor cerebri syndrome consists of headaches or visual disturbances (or both), PT alone or in association with hearing loss, dizziness, and aural fullness has been reported as the main manifestation(s) of this syndrome.1,42–46 Many of these patients are morbidly obese (body weight more than 100 lb above ideal weight) and have associated papilledema. Absence of papilledema, however, does not exclude this entity.47–49 Head CT or MRI is normal in the majority of these patients, although an empty sella or small ventricles and cortical sulci may be present.31 Diagnosis is established by lumbar puncture and confirmation of CSF pressure of more than 200 mm H2O with normal constituents. The modified Dandy diagnostic criteria for pseudotumor cerebri syndrome are summarized in Table 11-4.50 Pulsatile tinnitus in these patients is believed to have the following pathophysiology. Systolic CSF pulsations originating from the pulsations of the circle of Willis arteries are transmitted to the exposed and compressible medial aspects of the dural venous sinuses, resulting in TABLE 11-4. Modified Dandy Diagnostic Criteria for Pseudotumor Cerebri Syndrome Symptoms and signs of increased intracranial pressure Absence of localizing neurologic findings except for occasional sixth and seventh nerve palsies Awake and alert patient Absence of deformity, displacement and obstruction of the ventricular system, and otherwise normal neurodiagnostic studies except for increased CSF pressure No other cause of increased intracranial pressure From Wall M, George D: Idiopathic intracranial hypertension a prospective study of 50 patients. Brain 114:155–180, 1991.

alterations of the lumen diameter and conversion of the normal laminar blood flow to abnormal turbulent flow and PT.1,51 The low-frequency sensorineural hearing loss, present in many of these patients, is secondary to the masking effect of the PT since light digital compression over the ipsilateral IJV results in immediate cessation of this symptom and improvement or normalization of hearing.1 Figures 11-3 and 11-4 show representative audiograms of a pseudotumor cerebri patient with lowfrequency hearing loss secondary to the masking effect of PT. This type of hearing loss should be from the lowfrequency hearing loss seen in patients with Ménière’s disease by performing this very simple maneuver. Stretching or compression of the cochlear nerve and brainstem, caused by the intracranial hypertension or possible edema, could also play a role in the hearing loss and dizziness encountered in these patients. This is supported by the abnormal auditory evoked responses present in one third of these patients.52 Idiopathic Tinnitus

Hearing level (HL) in dB (RE: ANSI, 1964)

Idiopathic or essential PT and venous hum are synonyms used interchangeably in the literature to describe patients with PT of unclear cause.6,53,54 The most common age group of patients with idiopathic PT is between 20 and 40 years, and there is a marked female preponderance.55 A possible cause of idiopathic PT is believed to be turbulent blood flow produced in the IJV as it curves around the lateral process of the atlas.55 Other anatomic abnormalities of the IJV and dural venous sinuses can also produce PT. Diagnosis of this condition should be made only after appropriate evaluation and elimination of other disorders such as pseudotumor cerebri syndrome. Since many of the idiopathic PT patients reported in the literature have not had an adequate work-up to rule out

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Pulsatile Tinnitus: Advances in Diagnosis and Treatment

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Figure 11-4. Repeated audiogram while digital pressure is applied over the ipsilateral internal jugular vein reveals normalization of hearing.

increased ICP, it is suspected that in at least some of them this symptom was secondary to undiagnosed pseudotumor cerebri syndrome. Associated symptoms of headaches and blurred vision, especially in morbidly obese female patients, should alert the physician to pseudotumor cerebri syndrome. Table 11-5 summarizes the venous causes of PT.

Nonvascular Causes Palatal, Stapedial, and Tensor Tympani Muscle Myoclonus Myoclonic contractions of the tensor veli palatini, levator veli palatini, salpingopharyngeus, and superior constrictor muscles can result in objective PT. These contractions can range between 10 and 240 per minute and should not be confused with the arterial pulse. This disorder is seen in young patients, usually within the first 3 decades of life, although it may be encountered in older individuals as well.63,64 Neurologic disorders such as brainstem infarctions, multiple sclerosis, trauma, and syphilis have also been reported in association with this condition. Involvement of the olivary tracts, posterior longitudinal bundle, dentate nucleus, and reticular formation has been identified in these patients.63,65 Myoclonic contractions of the stapedial muscle have also been reported as a cause of pulsatile tinnitus.53,66

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TABLE 11-5. Venous Causes of Pulsatile Tinnitus

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Figure 11-3. Pure tone audiogram of a patient with PT and associated pseudotumor cerebri without neck pressure. A low-frequency “sensorineural” hearing loss is present.

Pseudotumor cerebri syndrome1 Jugular bulb abnormalities56–59 Hydrocephalus associated with stenosis of the sylvian aqueduct60 Increased intracranial pressure associated with Arnold-Chiari malformation60 Abnormal condylar and mastoid emissary veins61,62 Idiopathic or essential tinnitus6,53–55

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EVALUATION History The history is of utmost importance in evaluating patients with PT. Most patients will describe their symptom as hearing their “own heartbeat” or a “thumping noise,” making diagnosis of PT apparent. Occasionally, however, patients may not volunteer the pulsatile component of their tinnitus and this may lead to overlooking this very important information. Associated symptoms of hearing loss, aural fullness, dizziness, headaches, and visual disturbances, such as visual loss, transient visual obscurations, retrobulbar pain, and diplopia are highly suggestive of associated pseudotumor cerebri syndrome.1,46 Older patients with a history of cerebrovascular accident, transient ischemic attacks, hyperlipidemia, hypertension, diabetes mellitus, and smoking should be suspected of having ACAD.2 Females with associated headaches, dizzy spells, syncope, fatigue, and lateralizing neurologic deficits should be evaluated for fibromuscular dysplasia (FMD).13–15 The clinician should highly suspicious of extracranial or intrapetrous carotid artery dissection in patients with sudden onset of PT in association with cervical or facial pain, headache, and symptoms of cerebral ischemia.16,17

Examination Pseudotumor cerebri syndrome should be strongly suspected in young and morbidly obese females with PT.1,45 Otoscopy is essential for detecting middle ear pathology such as a high or exposed jugular bulb, aberrant carotid artery, glomus tumor, and Schwartze’s sign. Rhythmic movements of the tympanic membrane can be present in patients with tensor tympani myoclonus. Complete head and neck examination is also very important. A palpable thrill may be present with cervical AVM.8 Myoclonic contractions of the soft palate can be identified in patients with palatal myoclonus. Wide opening of the oral cavity during examination may result in elimination of the soft palate contractions.7 Auscultation of the ear canal, periauricular region, orbits, neck, and chest should be performed for detection of objective PT, bruits, and heart murmurs. Particularly special attention should be paid when auscultating the

postauricular/upper neck regions, since most dural AVFs occur in this area. Presence of a bruit in this area should be considered an intracranial vascular abnormality until proven otherwise. Auscultation should be performed in a very quiet room, preferably in an audiology booth using a modified electronic stethoscope. Auscultation with an electronic stethoscope has been found to be more sensitive than traditional auscultation techniques.67,68 The Litmann electronic stethoscope model 2000 can be used for this purpose. When objective PT is detected, its rate should be compared with the patient’s arterial pulse. The effect of light digital pressure over the ipsilateral IJV should be checked. Pulsatile tinnitus of venous origin such as in patients with pseudotumor cerebri syndrome decreases or completely subsides with this maneuver.1,46 In patients with an arterial type of PT this maneuver has no effect on the intensity of the tinnitus. The effect of head rotation on tinnitus intensity should also be evaluated since venous PT often will decrease or completely subside when the head is rotated toward the side of the PT. This is probably due to compression of the IJV between the contracting sternocleidomastoid muscle and the transverse process of the atlas.1,46 A complete neurologic examination, including cranial nerve examination, should also be performed. Consultation with neurology or neuro-ophthalmology should be obtained for patients suspected of pseudotumor cerebri syndrome. Papilledema is compatible with pseudotumor cerebri syndrome; its absence, however, does not exclude this entity.47–49 Diagnosis of this condition is established by lumbar puncture and documentation of CSF pressure greater than 200 mm H2O.50 The characteristics of PT in patients with pseudotumor cerebri syndrome, ACAD, glomus tumors, and AVFs are summarized in Table 11-6.

Audiologic and Electrophysiologic Testing Pure tone (air and bone conduction) and speech audiometry should be performed in all patients. When hearing loss of 20 dB or more is detected, a repeat audiogram should be obtained while the patient is applying light digital pressure over the ipsilateral IJV. Due to elimination of the masking effect of the tinnitus, this maneuver typically results in improvement or normalization of pure tones in patients

TABLE 11-6. Characteristics of Pulsatile Tinnitus

Age Sex Weight Retrotympanic mass Objective PT Arterial PT Venous PT Head bruit Neck bruit Papilledema

Pseudotumor Cerebri Syndrome

ACAD

Glomus Tumors

AVF

<40 years More common in females Obese − + − + − − Common

>50 years More common in females NR − + + − − + −

40 years, average More common in females NR + − + − − − −

40 years, average NR NR − + + − + − −

ACAD, Atherosclerotic carotid artery disease; AVF, arteriovenous fistula; NR, not relevant; PT, pulsatile tinnitus.

Pulsatile Tinnitus: Advances in Diagnosis and Treatment

with venous type PT such as in pseudotumor cerebri syndrome.1 Discrimination is typically excellent in these patients. Impedance audiometry should be obtained for suspected cases of tensor tympani myoclonus. Auditory brainstem evoked responses (ABR) should be considered in patients with suspected pseudotumor cerebri syndrome. Abnormalities of this test, consisting mainly of prolonged interpeak latencies, have been detected in one third of patients with this syndrome.52 Normalization or improvement of these abnormalities has been noticed in the majority of these patients following successful management.52

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abnormalities are diagnosed, no other imaging studies are needed. For patients with glomus jugulare tumors, CT examination of the neck should also be obtained to assess for additional chemodectomas along the carotid arteries. Carotid angiography is indicated only for prospective surgical cases to evaluate the collateral circulation of the brain (arterial and venous) in anticipation of possible vessel ligation or preoperative tumor embolization.28 Figure 11-5 depicts a diagnostic algorithm for patients with pulsatile tinnitus.

Metabolic Work-up

MANAGEMENT

Complete blood count and thyroid function tests should be obtained in cases of suspected anemia and hyperthyroidism, respectively. Serum calcium levels and studies for systemic lupus erythematosus should be considered when pseudotumor cerebri syndrome is suspected. Serum lipid profile and fasting blood sugar should be performed in suspected cases of ACAD.

Management should be directed toward treating any underlying cause. Management of the most common causes of PT are as follows: Pulsatile tinnitus secondary to idiopathic pseudotumor cerebri syndrome responds well to weight reduction and medical management with acetazolamide (Diamox) 250 mg tid or furosemide (Lasix) 20 mg bid.1,49 Both of these medications are thought to reduce CSF production. Short courses of steroids should be considered only for acute exacerbations of the syndrome. Lumbar–peritoneal shunt should be considered for patients with progressive deterioration of vision, persistent headaches, and disabling PT.1,31,46 In morbidly obese patients, however, this procedure is often complicated by shunt occlusion due to increased intraabdominal pressure.71 Weight reduction surgery has been found effective in relieving PT in morbidly obese patients with associated pseudotumor cerebri syndrome and should be considered when conservative management has failed. Thirteen out of 16 patients who underwent this procedure experienced complete resolution of their PT.72 Optic nerve sheath fenestration has been reported to be very helpful for patients with progressive visual loss and headaches.73 Repair of a symptomatic high-dehisced jugular bulb has been reported by using pieces of mastoid cortical bone and septal, conchal, or tragal cartilage and surgical wax.21,74–76 Pulsatile tinnitus secondary to otosclerosis may respond to stapedectomy.31 Tensor tympani and stapedial myoclonus may respond to sectioning of the respective muscles via tympanotomy.77 Botulinum toxin has also been reported for the management of palatal myoclonus.78,79 Patients with ACAD benefit from carotid endarterectomy when carotid obstruction is more than 60%.80 Angioplasty has relieved PT secondary to atherosclerotic obstruction of the subclavian and intracranial carotid arteries.81,82 Pulsatile tinnitus secondary to antihypertensive medication such as enalapril or verapamil subsides soon after discontinuation of these agents.31 Dural AVFs can be treated in the majority of patients with selective embolization.83,84 Figures 11-6 and 11-7 are the postprocedure films of the internal carotid artery/cavernous sinus fistula (case 2) following embolization with platinum coils. Radiosurgery or selective embolization followed by radiosurgery are other modalities of treatment.85,86 Vascular neoplasms such as glomus jugulare tumors can be treated surgically in the majority of patients.

Ultrasound Studies Duplex carotid ultrasound (including the subclavian arteries) or echocardiogram studies (or both) should be obtained in suspected cases of ACAD, atherosclerotic subclavian artery disease, or valvular disease.2,31 In particular, patients with carotid bruits should have a carotid ultrasound study prior to any radiologic evaluation because if diagnosis of ACAD is established, the need for any radiologic evaluation may be obviated.

Radiologic Evaluation Radiologic evaluation should to be individualized according to the history and physical examination findings such as retrotympanic mass, objective PT, bruit, and papilledema. The following represents the author’s current radiologic evaluation algorithm: 1. For patients with normal otoscopy, screening with high-quality MRA/magnetic resonance venography (MRV) in conjunction with brain magnetic resonance imaging (MRI), should be initially obtained. Small ventricles or empty sella are findings occasionally seen in patients with pseudotumor cerebri syndrome.31 MRI demonstration of dilated cortical veins is suggestive of an AVM; however, neither the arterial supply nor the nidus of an AVM may be detectable on MRI.69 In 12 patients with angiographic diagnosis of AVMs, 8 had dilated cortical veins on MRI.70 Dural venous sinus thrombosis also can be diagnosed with MRV. In patients with normal MRI/MRA/MRV associated with objective arterial PT or a head bruit, carotid angiography should be strongly considered to exclude dural AVFs and fibromuscular dysplasia.23,70 2. Patients with a retrotympanic mass should have a highresolution, temporal bone computed tomography (CT) as their initial evaluation.31 If glomus tympanicum, aberrant internal carotid artery, or jugular bulb

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SYMPTOMS OF NEUROTOLOGIC DISEASE

Retrotympanic Mass Present

CT of temporal bones

Glomus tympanicum Aberrant carotid artery Jugular bulb abnormalities

Glomus jugulare

Neck CT Carotid angiography?

A Normal Otoscopy

Suspicion of increased ICP

Suspicion of carotid artery abnormality

MRI-MRA, funduscopy

Duplex ultrasound

Hydrocephalus Thrombosis of dural sinuses

LP

Pseudotumor cerebri syndrome

ACAD Carotid tortuosity

MRI-MRA

Normal

Carotid angiogram if head bruit present LP: Lumbar puncture ICP: Intracranial pressure ACAD: Atherosclerotic carotid artery disease

B Figure 11-5. Pulsatile tinnitus diagnostic algorithm.

Figure 11-6. Carotid angiogram, lateral view, of case 2 following embolization of the fistula with platinum coils (single arrow). The normal ophthalmic artery can now be identified (double arrows).

Figure 11-7. Postembolization transorbital view of case 2 showing the platinum coils in the area of the right cavernous sinus (arrow).

Pulsatile Tinnitus: Advances in Diagnosis and Treatment

Stereotactic surgery may be considered for patients who are poor surgical candidates.87 Finally, in patients with idiopathic PT, tinnitus typically subsides with light pressure over the ipsilateral IJV making ligation of this structure a very tempting procedure. The results of this procedure, however, have been very inconsistent and poor overall. In a series of 13 patients with essential tinnitus, 3 underwent ligation of the ipsilateral IJV and only 1 benefited permanently. The other two patients experienced return of their PT within a few days.55 Furthermore, we have become aware of a significant number of cases from different parts of the country who underwent this procedure and developed intracranial hypertension. Diagnosis of pseudotumor cerebri was made in some of these cases, and in several, malpractice litigation followed. Therefore, there is rarely, if ever, an indication for this procedure solely for the purpose of alleviating pulsatile tinnitus.88

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18. Campbell JB, Simons RM: Brachiocephalic artery stenosis presenting with objective tinnitus. J Laryngol Otol 101:718–720, 1987. 19. Fernandez AO: Objective tinnitus: A case report. Am J Otolaryngol 4:312–314, 1983. 20. Bold EL, Wanamaker HH, Hughes GB, Kinney SE, et al: Magnetic resonance angiography of vascular anomalies of the middle ear. Laryngoscope 104:1404–1411, 1994. 21. Glasscock ME, Dickins JRE, Jackson CG, et al: Vascular anomalies of the middle ear. Laryngoscope 90:77–88, 1980. 22. Steffen TN: Vascular anomalies of the middle ear. Laryngoscope 78:171–197, 1968. 23. Levegue H, Bialostozky F, Blanchard CL, et al: Tympanometry in the evaluation of vascular lesions of the middle ear and tinnitus of vascular origin. Laryngoscope 89:1197–1218, 1979. 24. Gulya AJ, Schuknecht HF: Letter to the editor. Am J Otolaryngol 5:262, 1984. 25. Lesinski SG, Chambers AA, Komray R, et al: Why not the eighth nerve neurovascular compression: Probable cause for pulsatile tinnitus. Otolaryngol Head and Neck Surg 87:89–94, 1979. 26. Cochran JH, Cosmicki PW: Tinnitus as a presenting symptom of pernicious anemia. Ann Otol Rhinol Laryngol 88:297, 1979. 27. Cary FH: Symptomatic venous hum. N Engl J Med 264:869–870, 1961. 28. Remly KB, Coit WE, Harrisberger HR, et al: Pulsatile tinnitus and the vascular tympanic membrane: CT, MR, and angiographic findings. Radiology 174:383–389, 1990. 29. Gibson R: Tinnitus in Paget’s disease with external carotid ligation. J Laryngol Otol 87:299–301, 1973. 30. Davies DG: Paget’s disease of the temporal bone. Acta Otolaryngol 65(Suppl 242):1–47, 1968. 31. Sismanis A, Smoker WRK: Pulsatile tinnitus: Recent advances in diagnosis. Laryngoscope 104:681–688, 1994. 32. Spector GJ, Ciralsky RH, Ogura JH: Glomus tumors in the head and neck: Analysis of clinical manifestations. Ann Otol Rhinol Laryngol 84:73–79, 1975. 33. Pensak ML: Skull base surgery. In Glasscock ME, Shambaugh GE (eds.): Surgery of the Ear. Philadelphia, WB Saunders, p. 503, 1990. 34. Holgate RC, Wortzman G, Noyek AM: Pulsatile tinnitus: The role of angiography. J Otolaryngol 6:49–62, 1977. 35. Taber JR: Cavernous hemangioma of the middle ear and mastoid. Laryngoscope 75:673–677, 1965. 36. Pelaez JM, Levine RL, Hafeez F, Dulli DA: Tortuosity of carotid and vertebral arteries: A magnetic resonance angiographic study. J Neuroimaging 8(4):235–239, 1998. 37. Sorensen PS, Krogsaa B, Gjerris F: Clinical course and prognosis of pseudotumor cerebri: A prospective study of 24 patients. Acta Neurol Scand 77:64–172, 1988. 38. Fishman RA (ed.): Benign intracranial hypertension. In Cerebrospinal: Fluid in Disease of the Nervous System. Philadelphia, WB Saunders, 1980, pp 128–139. 39. Sugerman HJ, Demaria EJ, Felton WL, et al: Increased intraabdominal pressure and cardiac filling pressures in obesity-associated pseudotumor cerebri. Neurology 49:507–511, 1997. 40. Johnston I: Reduced CSF absorption syndrome. Reappraisal of benign intracranial hypertension and related conditions. Lancet 2:418–421, 1973. 41. Felton WL, Marmarou A, Bandon K: Cerebrospinal fluid pressure dynamics in pseudotumor cerebri (abstract). Neurology 41(Suppl 2): 348, 1991. 42. Guidetti B, Giuffre R, Gambacorta DL Follow-up study of 100 cases of pseudotumor cerebri. Acta Neurochir (Wien) 18:259–267, 1968. 43. Johnston I, Paterson A: Benign intracranial hypertension: Diagnosis and prognosis. Brain 97:289–300, 1974. 44. Weisberg LA: Benign intracranial hypertension. Medicine (Baltimore) 54:197–207, 1975. 45. Sismanis A, Hughes GB, Abedi E, et al: Otologic symptoms and findings of the pseudotumor cerebri syndrome: A preliminary report. Otolaryngol Head Neck Surg 93:398–402, 1985.

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46. Sismanis A, Butts FM, Hughes GB: Objective tinnitus in benign intracranial hypertension: An update. Laryngoscope 100:33–36, 1990. 47. Marcelis J, Siberstein SD: Idiopathic intracranial hypertension without papilledema. Arch Neurol 48:392–399, 1991. 48. Lipton HL, Michelson PE: Pseudotumor cerebri syndrome without papilledema. JAMA 220:1591–1592, 1972. 49. Spence JD, Amacher AL, Willis NR: Benign intracranial hypertension without papilledema: Role of 24-hour cerebrospinal fluid pressure monitoring in diagnosis and management. Neurosurgery 7:326–336, 1980. 50. Wall M, George D: Idiopathic intracranial hypertension a prospective study of 50 patients. Brain 114:155–180, 1991. 51. Langfitt TW: Clinical methods for monitoring intracranial pressure and measuring cerebral blood flow. Clin Neurosurg 22:302–320, 1975. 52. Sismanis A, Callari RH, Slomka WS, Butts FM: Auditory evoked responses in benign intracranial hypertension syndrome. Laryngoscope 100:1152–1155, 1990. 53. Chandler JR: Diagnosis and cure of venous hum tinnitus. Laryngoscope 93:892–895, 1983. 54. Engstrom H, Graf W: On objective tinnitus and its recording. Acta Otolaryngol Suppl (Stock) 95:127–137, 1951. 55. Hentzer E: Objective tinnitus of vascular type. Acta Otolaryngol 66:273–281, 1968. 56. Overton SB, Ritter FN: A high placed jugular bulb in the middle ear: A clinical and temporal bone study. Laryngoscope 83:1985–1991, 1983. 57. Buckwalter JA, Sasaki CT, Virapongse C, et al: Pulsatile tinnitus arising from jugular megabulb deformity: A treatment rationale. Laryngoscope 93:1534–1539, 1983. 58. Robin PE: A case study of upwardly situated jugular bulb in the left middle ear. J Laryngol Otol 86:1241–1245, 1972. 59. Smythe GO: A case of protruding jugular bulb. Laryngoscope 75:669–672, 1975. 60. Wiggs B, Sismanis A, Laine FJ: Pulsatile tinnitus associated with congenital central nervous system malformations. Am J Otol 17:241–244, 1996. 61. Lambert PR, Cantrell RW: Objective tinnitus in association with abnormal posterior condylar emissary vein. Am J Otolaryngol 7:204–207, 1986. 62. Forte V, Turner A, Liv P: Objective tinnitus associated with abnormal emissary vein. Otolaryngology 18(5):232–235, 1989. 63. Herrmann C, Crandall PH, Fang HC: Palatal myoclonus: A new approach to the understanding of its production. Neurology 7:37–51, 1957. 64. Bjork H: Objective tinnitus due to clonus of the soft palate. Acta Otolaryngol Suppl (Stock) 116:39–45, 1954. 65. Heller MF: Vibratory tinnitus and palatal myoclonus. Acta Otolaryngol (Stock) 55:292–298, 1962. 66. Pulec JL, Hodell SF, Anthony PF: Tinnitus: Diagnosis and management. Ann Otol Rhinol Laryngol 87:821–833, 1978. 67. Sismanis A, Williams GH, King MD: A new electronic device for evaluation of objective tinnitus. Otolaryngol Head Neck Surg 100:644–645, 1989. 68. Sismanis A, Butts FM: A practical device for detection and recording of objective tinnitus. Otolaryngol Head Neck Surg 110:459–462, 1994.

69. DeMarco JK, Dillon WP, Halbalbach VV, Tsuruda JS: Dural arteriovenous fistulas: Evaluation with MR imaging. Radiology 175: 193–199, 1990. 70. Dietz RR, Davis WD, Harnsberger HR, et al: MR imaging and MR angiography in the evaluation of pulsatile tinnitus. AJNR 15:879–889, 1994. 71. Sugerman HJ, Felton WL, Salvant JB Jr, et al: Effects of surgically induced weight loss on idiopathic intracranial hypertension in morbid obesity. Neurology 45:1655–1659, 1995. 72. Michaelides EM, Sismanis A, Sugerman HJ, Felton WL: Pulsatile tinnitus in patients with morbid obesity: The effectiveness of weight reduction surgery. Am J Otol 21(5):682–685, 2000. 73. Corbett JJ, Nerad JA, Tse DT, Anderson RL: Results of optic nerve sheath fenestration for pseudotumor cerebri: The lateral orbitotomy approach. Arch Ophthalmol 106:1391–1397, 1988. 74. Rouillard R, LeCrec J, Savary P: Pulsatile tinnitus: A dehiscent jugular vein. Laryngoscope 95:188–189, 1985. 75. Presutti L, Laudadio P: Jugular bulb diverticula. ORL 53:57–60, 1991. 76. Couloigner V, Grayeli AB, Julien N, Sterkers O: Surgical treatment of the high jugular bulb in patients with Meniere’s disease and pulsatile tinnitus. Eur Arch Otorhinolaryngol 256(5):224–229, 1999. 77. Badia L, Parikh A, Brookes GB: Management of middle ear myoclonus. J Laryngol Otol 108(5):380–382, 1994. 78. Jero J, Salmi T: Palatal myoclonus and clicking tinnitus in a 12-year-old girl: Case report. Acta Otolaryngol Suppl 543:61–62, 2000. 79. Bryce GE, Morrison MD: Botulinum toxin treatment of essential palatal myoclonus tinnitus. J Otolaryngol 27(4):213–216, 1998. 80. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study: Endarterectomy for asymptomatic carotid artery stenosis. JAMA 273(18):1421–1428, 1995. 81. Onald JJ, Raphael MJ: Pulsatile tinnitus relieved by angioplasty. Clin Radiol 43:132–134, 1991. 82. Emery DJ, Ferguson RDG, Williams JS: Pulsatile tinnitus cured by angioplasty and stenting of petrous carotid artery stenosis. Arch Otolaryngol Head Neck Surg 124:460–461, 1998. 83. Vinuela F: Update of intravascular functional evaluation and therapy of intracranial arteriovenous malformations. In: Vinuela F, Dion J, Duckwiler G (eds.): Neuroimaging Clinics of North America, volume 2, number 2. Philadelphia, WB Saunders, pp 279–289, 1992. 84. Urtasun F, Biondi A, Casaco A, et al: Cerebral dural arteriovenous fistulas: Percutaneous transvenous embolization. Radiology 199:209–217, 1996. 85. Flickinger JC, Kondziolka D, Lunsford LD: Radiosurgery of benign lesions. Semin Radiat Oncol 5(3):220–224, 1995. 86. Link MJ, Coffey RJ, Nichols DA, Gorman DA: The role of radiosurgery and particulate embolization in the treatment of dural arteriovenous fistulas. J Neurosurg 84(5):804–809, 1996. 87. Jordan JA, Roland PS, McManus C, et al: Stereotactic radiosurgery for glomus jugulare tumors. Laryngoscope 110:325–338, 2000. 88. Jackler RK, Brackmann DE, Sismanis A: A warning on venous ligation for pulsatile tinnitus. Otol Neurotol 22:427–428, 2001.

12

Outline General Physical Examination Cranial Nerve I Cranial Nerve II Cranial Nerves III, IV, VI Cranial Nerve V Cranial Nerve VII Cranial Nerve VIII

Chapter

The Neurotologic Examination

Cochlear Vestibular Oculomotor Examination Cranial Nerves IX, X Cranial Nerve XI Cranial Nerve XII

T

he bedside neurotologic examination allows the examiner to gather information efficiently and accurately. In many cases, more sophisticated tests simply verify a diagnosis initially made on clinical impression alone. This chapter reviews the general physical examination of neurotologic patients with special focus on the function of their cranial nerves.

GENERAL PHYSICAL EXAMINATION Physical clues to a patient’s pathology may be obvious before formal examination even begins. An abnormal gait, stance, or head tilt may indicate pathology of the vestibular system in patients complaining of vertigo or dizziness. Physical deformities associated with neurotologic disease may accompany rheumatoid arthritis, congenital syphilis, or Paget’s disease. Skin stigmata, such as those associated with scleroderma, neurofibromatosis, or lupus, may be associated with neurotologic symptoms. Other findings associated with syndromic disease, such as branchiootorenal, Waardenburg’s, or Pendred’s, may be obvious on meeting the patient. Sometimes, evidence of previous injury or surgery leads the clinician to consider trauma, metastatic disease, or iatrogenic causes of neurotologic symptoms. Formal examination of the neurotologic patient begins with the external ear. Congenital conditions such as preauricular pits or aural atresia suggest internal malformations, while an aural polyp is a sign of cholesteatoma with a sensitivity of 33% in previously unoperated ears and 71% in ears with an attic or marginal defect.1 Signs of trauma or scars from previous surgery, including evidence of cartilage grafts, can provide the examiner with valuable information about the patient’s otologic history. Chronic inflammatory conditions, such as chondrodermatitis nodularis chronica helicis or relapsing polychondritis, may cause a painful, reddened pinna.2 Otorrhea may represent

Timothy E. Hullar, MD Lloyd B. Minor, MD, FACS

simple otitis externa, or it may be a manifestation of a first branchial arch sinus or parotitis tracking through the fissures of Santorini into the external canal. Postauricular edema occurs in 76% of patients with mastoiditis.3 Tenderness and redness of the mastoid cortex and stand-off of the external ear, a softening of the postauricular skin and inability to palpate bony contours behind the ear, or effacement of the postauricular crease can indicate a subperiosteal abscess, a complication in 50% of patients with coalescent mastoiditis.4 Battle’s sign, or postauricular ecchymosis,5 has a 100% positive predictive value for recent skull base fracture.6 An earlobe crease, although not indicative of otologic disease, may be noted by the neurotologist and is an indicator (with a sensitivity of 73% and a specificity of 84%) for coronary artery disease.7 Although handheld otoscopic examination is handy and quick, patients referred to a neurotologist deserve the more thorough examination only a binocular microscope and thin-walled metal speculum allows. The microscope increases the examiner’s sensitivity to small movements of the tympanic membrane caused by muscular contraction, respirations through a patulous eustachian tube, or autoinsufflation.8 A Siegle speculum’s angled faceplate allows pneumatic otoscopy under the microscope without glare; using this technique, “perforations” diagnosed with a handheld otoscope are sometimes shown to be monomeric tympanic membranes. Microscopy frees both of the examiner’s hands to manipulate the patient’s head and speculum, allowing safe removal of foreign bodies or tightly impacted cerumen. A video camera mounted on the microscope can feed paired video monitors so the supine patient may follow the clinician’s exam of either ear. The otoscope allows visualization of many otologic disease processes or their stigmata. The external canal may show signs of infection, such as fungus associated with otitis externa or vesicles of the Ramsay Hunt syndrome.9 Mechanical obstructions including osteoma or exostoses 215

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of the ear canal can predispose patients to infection. Inflammatory processes such as Wegener’s granulomatosis can cause otitis media and otorrhea.10 Aural tuberculosis can cause multiple perforations of the drum with painless otorrhea.11 Otoscopy may reveal masses, such as a highriding jugular bulb, cholesteatoma, glomus tumor, or aural foreign body, and can sometimes allow visualization of a dislodged stapes prosthesis. Hypervascularity on the promontory due to otosclerosis causes Schwartze’s sign, a blush behind the drum.12,8 A general otolaryngologic examination may uncover findings pointing to a particular neurotologic source. This examination includes an ocular examination, detailed in a later section under the cranial nerves responsible for ocular movement. A nasal exam can show a bluish nasal mucosa, especially over the inferior turbinates, indicating allergies contributing to eustachian tube dysfunction. Irritative lesions of the nose, including mucosal contact points, may cause patients to present with headache or ear pain.13 Examination of the mouth may reveal a submucous cleft palate causing eustachian tube dysfunction, or poor dentition leading to temporomandibular joint dysfunction and referred otalgia. Cervical lymphadenopathy can represent metastases from a nasopharyngeal carcinoma obstructing the eustachian tube or pharyngeal malignancy, whereas a neck abscess under the sternocleidomastoid may be a Bezold’s abscess derived from a suppurative mastoiditis.14 Pain can be referred to the ear from pathology in the distributions of the 5th, 7th, 9th, and 10th cranial nerves as well as the cervical plexus. Some causes of referred otalgia are erupting teeth, pharyngeal malignancies, peritonsillar abscess, pathology of the temporomandibular joint, peritonsillar abscess, laryngitis, thyroiditis, and Eagle syndrome, consisting of pain secondary to styloid process irritation.15 Palpation of the scalp may find crepitus in patients with syphilis, infantile rickets, hydrocephalus, or other causes of bony loss,16 whereas the occiput may be tender in patients with tumors of the posterior fossa.17 Tenderness over the maxillary and frontal sinuses may reveal sinus disease with a sensitivity of 48% to 50% and a specificity of 62% to 65%.18 Percussion of the head can elicit a dull “crackedpot” sound in children with hydrocephalus, a finding known as Macewen’s sign.19 Auscultation helps in the diagnosis of some patients. The Toynbee tube can be used to listen for a crackle when the eustachian tube opens,20 although the relative patency of the eustachian tube can also be determined from the approximate length of time it takes for a patient with a perforated drum to note the taste of antibiotic drops placed in the ear. Pulsatile tinnitus may be due to a glomus tumor, but noise transmitted from turbulent flow in a diseased carotid artery or stenotic aortic valve can cause a similar perception. Auscultation of the neck and chest can discriminate between these causes. The most common site of vertebral artery stenosis is at its branch from the subclavian and is best heard in the supraclavicular fossa.21,22 Intracranial bruits are best heard over the globes17 although reported sensitivity for this test varies widely.23 Palatal24 or laryngeal25 myoclonus can cause objective tinnitus, as can myoclonus of the intrinsic muscles of the middle ear.26

CRANIAL NERVE I Olfaction in humans is derived from both cranial nerves I and V. Noxious chemicals such as ammonia, acids, and the penetrating odors of peppermint and menthol stimulate intranasal branches of cranial nerve V.27 What we perceive as taste is largely a function of cranial nerve I, although cranial nerve VII carries fibers to chemoreceptors on the oral tongue and soft palate and IX carries fibers to the oropharynx. Lesions attributable to cranial nerve I are analogous to those of VIII in that they are either conductive or neural in origin. Conductive losses prevent airborne molecules from reaching the olfactory epithelium in the superior nasal cavity. Air bypasses the nasal mucosa entirely in laryngectomees and patients with nonfenestrated tracheostomies. Patients with nasal masses or deforming nasal trauma suffer olfactory loss due to mechanical obstruction. Localized inflammation, perhaps incited by a prior upper respiratory infection, may also block olfactory receptors, although respiratory pathogens may be directly toxic to olfactory neurons as well.28 Neural losses include those of the olfactory epithelium itself, such as caused by chemicals or topical medications, or central injury due to head trauma shearing the fibers as they enter the cribriform plate or expanding tumors. Neurodegenerative diseases such as Alzheimer’s can also cause olfactory loss.29 A quick bedside test of olfaction is the alcohol sniff test.30 A 70% isopropyl alcohol wipe is gradually moved closer to the nose of a patient until he smells the odor of the alcohol; this process is repeated five times. An average distance less than 5 cm indicates anosmia, although this procedure may give false-negatives due to activation of cranial nerve V. A commercial version to test sensory thresholds of cranial nerve I is the Smell Threshold Test using rose scent (phenyl ethyl alcohol). This type of test provides a more quantitative measure of threshold than other odor identification tests, such as the 40-odorant scratch-and-sniff University of Pennsylvania Smell Identification Test, known commercially as the SIT; the 12-odor Brief Smell Identification Test (B-SIT), also known as the Cross-Cultural Smell Identification Test; and the 3-odor Pocket Smell Test (all from Sensonics, Inc, Haddon Heights, NJ).31

CRANIAL NERVE II Examination of the optic nerve includes measuring pupillary reflexes, acuity, color perception, visual fields, and funduscopy. Illuminating each eye in succession determines whether defects in the pupillary reflex are afferent or efferent in nature. Both eyes should contract consensually. Failure to constrict the illuminated eye only indicates a defect in the efferent parasympathetic pathway on that side. Failure to constrict either eye indicates an optic nerve problem. With vergence, normal pupils constrict slightly. The Argyll Robertson pupil of patients with syphilis is small, irregular, and does not react to light but does react to accommodation. Other conditions affecting pupillary function include diabetes, encephalitis, sarcoidosis, Horner’s syndrome, Lyme disease, and intracranial

The Neurotologic Examination

mass; these patients require prompt ophthalmologic referral. Acuity is measured using a standard Snellen chart at 20 ft. Dynamic visual acuity is a measure of the vestibulo-ocular reflex and is described under the vestibular examination. Loss of color perception is an early indicator of loss of function of the optic nerve. Ishihara or other standard tests can be used to measure color perception. Abnormal findings can be seen in patients with pituitary lesions32 or pathology of the optic nerve. Visual fields can be tested at the bedside using confrontation or in a formal visual field testing booth. To test the visual fields using confrontation, the patient and examiner sit closely looking at each other with the patient covering one eye and the examiner covering his opposite eye. The examiner then moves his outstretched hand in from the four quadrants of the patient’s visual field until the patient can see his gently wiggling fingers. The test is repeated after switching eyes. Common field cuts and their causes are shown in Figure 12-1. Funduscopy is the specialty of the ophthalmologist and requires dilation for anything more than a cursory examination. Elevated intracranial pressures, such as caused by meningitis, sigmoid sinus thrombosis, or bleed, cause a loss of venous pulsations and papilledema. Signs of papilledema include a blurring of the margin of the optic disc, engorged veins, and “cotton-wool” spots, each of which is caused by increased intracranial pressure. Papilledema and optic neuritis cause elevation of the optic disc, with the latter usually accompanied by an early loss of vision. Cavernous sinus thrombosis can cause venous stasis in the entire orbit including the fundus and sclera.

Homonymous hemianopsia

Bitemporal hemianopsia

Binasal hemianopsia

Figure 12-1. Binocular field defects. Visual field defects are represented in black, from the patient’s perspective. Homonymous hemianopsia is a consequence of a postchiasmal defect. The degree of the defect (from a “pie wedge” to half of the entire field) and the congruity of the defect between the two sides can help determine the exact position of the defect. A total homonymous hemianopsia, as shown here, can be caused by any postchiasmal defect. Bitemporal hemianopsia is caused by a chiasmal lesion if the defect respects the vertical meridian, as shown here. A binasal defect can be due to optic nerve disease or, rarely, compression of the lateral optic chiasm. (From Wilson-Pauwels L, Akesson E, Stewart P: Cranial Nerves. Toronto, BC Decker, 1988.)

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CRANIAL NERVES III, IV, VI The third nerve innervates all extraocular muscles except the abducens (from cranial nerve VI) and the superior oblique (from cranial nerve IV). A significant palsy of any of these nerves will cause diplopia, although central processes such as multiple sclerosis (MS) may cause similar symptoms. Restriction of extraocular muscle movement due to entrapment, mass effect, or endocrine orbitopathy may mimic a nerve palsy.33 These conditions can be distinguished from a true palsy using a forced duction test, during which the sclera of the anesthetized eye is grasped using a forceps and passively drawn toward the side of the apparent paresis. A true third nerve palsy leaves the eye laterally deviated from unopposed action of the lateral rectus muscle, mydriatic from loss of third nerve parasympathetic input, and with a ptosis of the upper lid from paralysis of the levator palpebrae muscle. A unilateral complete paralysis can be caused by elevated intracranial pressure, posterior communicating artery aneurysm, or subarachnoid hemorrhage; more benign conditions such as diabetes may reassuringly spare pupillary reflexes.34 Other causes of ptosis include congenital ptosis, myasthenia gravis, aging, or Horner’s syndrome paralyzing Müller’s muscle. Loss of function of Müller’s muscle leaves the superior orbital crease intact, while a ptosis due to third nerve palsy relaxes the levator aponeurosis insertion on the eyelid and may obliterate this fold. Other findings in a Horner’s syndrome include ipsilateral anhidrosis and anisocoria (inequality of pupil size, with the smaller, miotic pupil on the affected side). Any interruption of the cervical sympathetic pathway within the skull base, neck, or thorax can cause these symptoms. A suspected Horner’s syndrome can be confirmed by instilling 4% cocaine in the eyes bilaterally. A Horner’s-induced miotic pupil will not dilate, whereas a normal variant will.35 The Paredrine test determines the site of a lesion producing a Horner’s syndrome. In this test, 1% hydroxyamphetamine (Paredrine) instilled in the eyes bilaterally should cause symmetrical dilation if the postganglionic nerve is intact, as is common in brainstem lesions, such as Wallenberg’s syndrome,36 or other interruptions of the preganglionic pathways. The eyes of a patient with a postganglionic lesion will not dilate normally, although false-negatives have been reported.37 The fourth (trochlear) cranial nerve controls the superior oblique muscle, rotating the eye downward and causing inward torsion. Its downward effect is more prominent on medial gaze and its torsional effect more evident on lateral gaze. It is particularly susceptible to trauma , probably due to its intracranial course, the longest of any cranial nerve. Injuries to the trochlear nerve cause extorsion and hypertropia of the affected eye with consequent diplopia; a patient can partially compensate for this by tipping the head toward the unaffected side. This effect should not be confused for torticollis caused by birth trauma or other causes, including an attempt by the patient to extinguish a positional nystagmus. The Bielschowsky head-tilt test can help distinguish the side of a superior oblique lesion causing diplopia: By tilting the head toward the side of the lesion, the diplopia should worsen with the unbalanced action of the contralateral, intact superior rectus.38

218

NEUROTOLOGIC DIAGNOSIS

The abducens nerve innervates the lateral rectus muscle. This nerve is commonly affected in cases of skull base trauma or inflammatory conditions and in MS via interruption of the medial longitudinal fasciculus. Tumors of the cerebellopontine angle can affect the sixth nerve, occasionally bilaterally.35 Along with cranial nerves III, IV, V1, and V2, pathology in the vicinity of the cavernous sinus can affect function of the sixth nerve. A paralysis of lateral gaze in an immunocompromised patient with fungal sinusitis, for example, indicates cavernous sinus involvement and is a contraindication to surgical intervention.39 Möbius syndrome includes congenital paralysis of nerves VI and VII40 although this term has also been applied to episodic cranial nerve III palsy associated with migraine.41 Gradenigo’s syndrome, caused by petrosal disease, comprises the symptoms of a draining ear, pain in the distribution of V1, and abducens palsy. It can also cause excessive lacrimation.42,43

CRANIAL NERVE V The fifth cranial nerve has three major branches: the ophthalmic (V1), maxillary (V2), and mandibular (V3) divisions (Fig. 12-2). V1 provides sensation to the upper face, including the cornea, bridge of nose, upper nasal mucosa, and frontal sinus. V2 provides sensation to the midface, including the lower nose and nasal mucosa, cheek, maxillary sinus, and entire oral cavity except the lower lip. V3 provides sensation to the lower teeth, lower lip, and tongue (except for taste, supplied from cranial nerve VII via the chorda tympani). Sensation on the face should be tested in the conventional way, using a wisp of cotton for light touch, warm and

cold objects for temperature, and a pin or sharply broken wooden stick for pain. A cotton-tipped swab touched to the mucosa of the nose is a noxious but inoffensive stimulus to rouse an unresponsive patient. Corneal reflexes are a particularly important part of the neurotologic examination. If possible, the patient turns his eyes to the opposite side to expose as much sclera as possible, protecting the cornea and preventing the patient from observing the test. The examiner then “walks” a fine wisp of cotton across the sclera (which should not be reactive) toward the cornea (which should be). A bilateral blink indicates an intact V1 on the tested side and seventh nerve bilaterally; a contralateral blink indicates loss of seventh nerve function on the tested side, and no response indicates loss of the fifth nerve on the tested side or loss of seventh nerve function bilaterally. The muscles of mastication, including temporalis, masseter, and medial and lateral pterygoid as well as the mylohyoid, anterior belly of digastric, and tensor veli palatini and tensor tympani muscles, are controlled by the fifth nerve via V3. Pronounced wasting of the temporalis can be due to chronic disease or starvation or, in unilateral cases, nerve or CNS injury. A significant weakening of the temporalis or masseter will prevent the patient from closing his mouth tightly. A reflex jaw jerk will stimulate the muscles of mastication to close the partially opened mouth after a sharp tap on the chin, although this response may give little information about degree of strength. Oropharyngeal inflammation, mass, or tumor invasion can cause spasm of the pterygoids and trismus; a process involving the pterygoids can be palpated transorally. A temporomandibular joint disorder is much more likely than a muscular

Frontal nerve Lacrimal gland Deep temporal nerve Mesencephalic nucleus

Lacrimal nerve

Pontine trigeminal nucleus Trigeminal ganglion Motor (masticator) nucleus Nucleus of the spinal trigeminal tract

Ciliary ganglion Nasociliary nerve Zygomatic nerve

Infraorbital nerve Pterygopalatine ganglion Pterygopalatine nerve (cut) Lingual nerve Mental nerve Nerve to anterior belly of the digastric and mylohyoid

Buccal nerve

Foramen ovale Foramen rotundum Nerve to the medial pterygoid Auriculotemporal nerve Superior orbital tissue Inferior alveolar nerve Masseteric nerve

Figure 12-2. Trigeminal nerve. Major motor and sensory branches of the fifth cranial nerve are shown. (From Wilson-Pauwels L, Akesson E, Stewart P: Cranial Nerves. Toronto, BC Decker, 1988.)

The Neurotologic Examination

problem to cause deviation in jaw movement, although in unilateral muscular paralysis the jaw will deviate to the affected side.

CRANIAL NERVE VII The facial nerve is of utmost importance to neurotologists. Careful appreciation of its function in all branches before treatment allows accurate monitoring of pathologic processes and surgical results. Thorough examination of the facial nerve includes evaluation of its intracranial and extracranial branchings and of both its sensory and motor fibers. The initial branch of the facial nerve is at the geniculate ganglion, where the greater superficial petrosal nerve (GSPN) travels forward as the nerve turns toward the tympanic segment (Fig. 12-3). Preganglionic parasympathetic fibers in the GSPN synapse in the pterygopalatine ganglion before innervating the nasal mucosa and lacrimal glands. Lesions of the facial nerve can cause either a dry eye or excessive tearing: Division of the nerve proximal to the geniculate causes a dry eye, but distal division of the nerve can allow exposure and irritation of the eye and excessive tearing. The modified Schirmer test is a semiquantitative way to measure lacrimal function. It depends on a noxious stimulus, such as ammonia or mechanical irritation of the nasal mucosa with a cotton swab that stimulates cranial nerve V and stimulates tearing. Inhalation of the

219

substance causes reflex tearing if the GSPN is intact. The test itself is performed after protecting or topically anesthetizing the eye against direct irritation. The examiner places folded pieces of filter paper from the lateral portion of the lower eyelid, with the rounded tip of filter paper inserted in the conjunctival fornix without stimulating the cornea. Five minutes of tear absorption onto the filter paper are measured and compared; a distance in the tested eye of less than 50% of the control eye indicates dysfunction.44 Patients with unilateral Bell’s palsy may have bilaterally reduced lacrimation, so false-negatives may result unless a minimum total distance (summed from both eyes) of 25 mm is reached.45 The facial nerve contributes parasympathetic fibers to the submandibular ganglion via the chorda tympani. A loss of parasympathetic function from a lesion of the facial nerve may reduce salivary flow enough to cause symptoms of xerostomia. Fibers of taste innervating the anterior two thirds of the tongue originate in the nervus intermedius and branch from the facial nerve in the mastoid process, cross the inner ear as the chorda tympani, and join the lingual nerve. In addition to lesions of the facial nerve, MS, hypothyroidism, diabetes mellitus, liver or kidney failure, vitamin deficiency (zinc or B3), or a history of oral radiation treatment can alter taste. Some free endings of the fifth cranial nerve are also present on the tongue, and disorders of this nerve can cause altered taste sensation. Fibers of the seventh nerve innervate taste buds on the ipsilateral tongue with sensation for sweet, sour, salty, and

Lacrimal gland Pterygopalatine ganglion Motor nucleus of VII Superior salivatory (lacrimal) nucleus Nucleus solitarius (rostral gustatory portion)

Figure 12-3. Facial nerve. Major motor and sensory branches of the seventh cranial nerve are shown. (From WilsonPauwels L, Akesson E, Stewart P: Cranial Nerves. Toronto, BC Decker, 1988.)

Spinal nucleus of trigeminal nerve

Internal acoustic meatus Stylomastoid foramen Submandibular ganglion Submandibular gland Sublingual gland

Petrotympanic fissure (chorda tympani nerve)

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NEUROTOLOGIC DIAGNOSIS

bitter. Inspection of the taste buds may reveal a loss of their normal pink velvety texture on the side of a tongue affected by a chorda tympani injury, as denervation disrupts actin filaments in taste pore cells.46 Chemical testing involves placing a cotton-tip applicator soaked in salty or sugary water or weak vinegar on the tongue. The patient must indicate the taste by pointing rather than speaking, as pulling the tongue into the mouth to speak permits rapid diffusion and a false-negative result for unilateral loss. In cases of Bell’s palsy, taste may return quicker than muscle function.47 Electrogustometry may be a valuable addition to bedside testing for taste if further questions persist. A tiny branch of the facial nerve supplies the stapedius muscle in the middle ear. Tonic motion of this muscle may cause objective tinnitus,26 while patients with hypofunction of this muscle (following section of its tendon during stapes surgery, for example) may complain about hyperacusis. An audiologist can directly test its function by eliciting stapedial reflexes, a test also critical in distinguishing otosclerosis from superior canal dehiscence. The seventh nerve supplies sensation to the posterior tympanic membrane and external auditory canal, lateral concha and helix, lobule, and mastoid. Loss of sensation in the external auditory canal may be an early indicator of acoustic neuroma.48 Motor branches carry fibers to the posterior auricular muscles, to the stylohyoid and posterior belly of the digastric, and to the muscles of facial expression via the temporal, zygomatic, buccal, marginal mandibular, and cervical branches. Weakness of the marginal mandibular nerve can be mimicked by separation of the platysma muscle during neck dissection. Lyme disease, syphilis, Guillain-Barré syndrome, amyotrophic lateral sclerosis, tuberculosis, or MS may accompany weakness or paralysis of the facial nerve.49 Crossed central fibers sometimes allow the ipsilateral forehead to function normally after a central lesion. The House-Brackmann scale affords a quantifiable way to evaluate facial nerve weakness (Table 12-1).50 Paramount on this scale is noting if the patient has a rating of 4 or greater, indicating incomplete eye closure. Serious corneal damage and permanent loss of vision can occur rapidly in patients with exposed corneas, especially in those with lesions of cranial nerve V rendering the cornea anesthetic. Lubricant and a moisture chamber should be placed over the eye of any patient with questionable closure, as an intact Bell’s phenomenon cannot be relied on to protect

the cornea from desiccation during sleep. Eye patches are not appropriate for these patients as they may not prevent opening of the eye and may allow drying of the eye hidden behind the patch. Any question about ability of the patient to close the eye warrants examination of the cornea using fluorescein and a Wood’s lamp or a slit lamp to rule out conjunctival irritation or keratitis. Overactive movements of the facial nerve can give diagnostic information. Hemifacial spasm can be caused by arterial irritation of the facial nerve at the root entry zone51 and may be a symptom of acoustic neuroma.52

CRANIAL NERVE VIII Cochlear Examination of the eighth nerve is divided into cochlear and vestibular segments (Fig. 12-4). Audiologic assessment is an integral part of the examination of the cochlear nerve, but bedside tests can guide initial diagnostic thinking. The most common tuning fork tests are the Weber and Rinne tests, both commonly performed with a 512-Hz fork. The Weber is usually performed by placing the vibrating tuning fork on the patient’s forehead; the patient will lateralize the sound to the ear with a conductive loss or away from the ear with a sensorineural loss.53 Placing the handle of the fork on the upper teeth or gums increases the patient’s awareness of the tone by 10 dB.54 Sensitivity of this test is 58% for sensorineural loss greater than 30 dB and 54% for conductive loss greater than 20 dB, while specificity is 79% and 92%, respectively.55 The airconduction Rinne test is performed with the tines of the fork along the interauricular axis and the bone-conduction test on the mastoid cortex.56 To avoid overtones, the fork must not be struck on a hard surface or too forcefully.57 A Rinne test is termed positive if the air-conduction signal is louder than the bone-conduction signal.58 A negative Rinne test with a 512-Hz tuning fork indicates a 25- to 30-dB hearing loss. A similar result with a 256-Hz fork implies a gap of 15 dB, while at 1024 Hz the gap is at least 35 dB.59 There is no need to use masking during a Rinne test.60 The sensitivity of the Rinne test at 512 Hz is 60% to 90% and the specificity is 95% to 98%.61,62 Infrequently used tuning fork examinations include the Bing test and the Schwabach test. In the Bing test, the tuning

TABLE 12-1. The House-Brackmann Facial Nerve Grading System Grade

Description

Gross Function

Resting Appearance

Dynamic Appearance

1 2

Normal Mild dysfunction

Normal Slight weakness with possible slight synkinesis

Normal Normal

3

Moderate dysfuntion

Normal

4 5

Moderately severe dysfunction Severe dysfunction

Obvious asymmetry; noticeable but not severe synkinesis, contracture, or hemifacial spasm Obvious weakness or disfiguring asymmetry Barely perceptible motion

6

Total paralysis

None

Asymmetrical

Normal Slight oral asymmetry; complete eye closure with minimum effort; moderate to good forehead function Slight oral asymmetry; complete eye closure with effort; slight to moderate forehead movement Asymmetrical mouth, incomplete eye closure, no forehead movement Slight oral movement, incomplete eye closure, no forehead movement No movement

Normal Asymmetrical

The Neurotologic Examination

221

Figure 12-4. The labyrinth. Major structures of the right inner ear, seen from the lateral aspect. Structures shown include the utricle (utr.), sacculus, anterior or superior semicircular canal (sup.), posterior semicircular canal (post.) and horizontal or lateral semicircular canal (lat.). The superior vestibular nerve innervates the horizontal and anterior semicircular canals and the utricle. The inferior vestibular nerve innervates the posterior semicircular canal and the saccule. The cell bodies for the vestibular nerves are located in Scarpa’s ganglion (Gangl. Scarpae). (Drawing from the Brödel Archives, No. 933. With permission of the Department of Art as Applied to Medicine, Johns Hopkins University.)

fork is placed on the mastoid and the external auditory canal is alternately occluded and opened. A patient with conductive hearing loss will note no change in intensity, while normal patients or those with sensorineural hearing loss will find that the tone becomes louder with occlusion. This test is not as sensitive as the Rinne test but its specificity is equivalent.63 The Schwabach test consists of placing a vibrating tuning fork on the patient’s mastoid and removing it when he can no longer hear it. If the examiner can still hear the fork, the patient has a sensorineural loss, but if the patient hears the fork longer than the examiner, the loss is conductive.64 This test depends, of course, on an examiner with normal hearing. Although more formally tested by an audiologist, a neurotologist can also test a patient’s response to words at the bedside. The examiner must mask the contralateral ear and cover his mouth to prevent lip reading or stand behind the patient while whispering letter or number triplets as quietly as possible. If the patient fails to recognize more than 50% of the items, the test is positive. Patients with pathology of the auditory nerve (rather than the cochlea) may have more difficulty with words than suggested by their response to tuning forks or other pure tones. The sensitivity of this test is greater than 90% and its specificity greater than 80%.65

Vestibular The clinical history is critical to guiding appropriate examination of the vestibular system. History-taking is notoriously difficult in patients complaining of disturbed equilibrium, however, because normal sensation depends on subconsciously integrating inputs from somatosensory receptors, vision, and the vestibular system. Particular attention should be paid to whether the patient has actual

sensations of vertigo (illusory sense of rotatory, linear, or tilting motion) or just light-headedness; direction of perceived motion; sensitivity to head motion leading to oscillopsia (sensation of movement of objects known to be stationary); relationship to other otologic symptoms such as hearing loss, fullness, and tinnitus; duration and frequency of symptoms; exacerbating or provoking factors; and other medical problems, including psychological disorders and conditions requiring medications that may cause symptoms of dizziness. In some patients, this history combined with a thorough bedside examination is sufficient to make a diagnosis and treatment plan, but many others will require further testing such as calorics, rotatory chair testing, and imaging in order to make a diagnosis.

Oculomotor Examination The exquisite control of eye movements by the vestibular system allows them to serve as particularly valuable measures of vestibular function. Eye movements are classified into several categories. Fixation allows an image to be held steady on the retina, while saccades bring an image onto the fovea and smooth pursuit holds it there as it moves across the field of view. Vergence moves the eyes in opposite directions to keep an image on the foveae as it approaches or moves away from the observer. Nystagmus is oscillatory movement of the eyes and can be normal or pathologic. The examiner must understand the physiological mechanisms underlying nystagmus in order to use it as a diagnostic tool. Normally, three neurologic mechanisms collaborate to control the eye’s position in the orbit: gaze-holding, or the ability to hold the eye at an eccentric position despite its natural tendency to drift back to neutral position; visual fixation, which detects drift of images across the retina and suppresses unwanted saccades; and the vestibulo-ocular

222

NEUROTOLOGIC DIAGNOSIS

reflex (VOR), which uses vestibular input to keep the fovea directed stably at a target despite head motion in space.66 Nystagmus is a characteristic finding in disorders of any of these three mechanisms. It can consist of either sinusoidal movements, termed pendular nystagmus, or alternating slow and fast phases, called jerk nystagmus. Jerk nystagmus is described by the direction of its fast phases, although these are simply resetting motions separating the physiologically more relevant slow phases that guide the eye smoothly across the orbit. Failure of the gaze-holding system can cause several types of jerk nystagmus: gaze-evoked nystagmus, centripetal nystagmus, or rebound nystagmus. The “neural integrator” is responsible for holding the eye at an eccentric position and is typically weakened following unilateral vestibular loss. Gaze-evoked nystagmus is characterized by slow phases caused by the drift of the eye toward its neutral position in the orbit. Centripetal nystagmus is the reversal of this direction. Rebound nystagmus is the short-lived nystagmus, also opposite to the direction of gaze-evoked nystagmus, that occurs after the eye returns from an eccentric to a neutral position. The patient’s gaze-holding ability is tested by maintaining eccentric horizontal, then vertical positions of gaze (approximately 30 degrees from center orientation). Minimal drift should normally be encountered for periods up to 15 sec. Nystagmus due to errors in gaze-holding is most commonly found as a side effect of medications (including sedatives67 and anticonvulsants68 although it can also indicate a structural lesion in the nucleus prepositus hypoglossi, medial vestibular nucleus,69 or interstitial nucleus of Cajal.70 It is also seen in familial episodic ataxia, a channelopathy responsive to acetazolamide.71 Gaze-evoked nystagmus is a normal finding at extremes of gaze, where it is called “end-point” nystagmus. End-point nystagmus may be asymmetrical, sustained, occur with less than full deviation of the eye, and may even have a torsional component. It has a relatively slow velocity and is not accompanied by other pathologies. Disorders of the visual pathway can cause either jerk or pendular nystagmus. Vertical, horizontal, or torsional jerk nystagmus with a drifting “null” position can result in patients with total blindness.72 Pendular nystagmus can occur in patients with subtotal visual loss preventing rapid feedback during normal drifting of the eye; corrective motions are therefore delayed and ocular oscillations result.73 Pendular nystagmus may be congenital, although acquired pendular nystagmus may be seen in demyelinating disorders, brainstem injury, or hypoxic encephalopathy. Congenital nystagmus, likely due to miswiring of anterior visual pathways, characteristically shows an increase in velocity during each slow phase, and patients may favor an eccentric angle of gaze where the nystagmus is minimized.66 Dynamic eye motion is first tested by asking the patient to perform saccades. The patient fixates on the examiner’s nose, then shifts rapidly to a finger target held about 15 degrees away. Velocity, accuracy, and latency are noted. Smooth pursuit is tested by having the patient follow a target moving horizontally at less than 20 degrees/sec. Corrective saccades in one direction reflect asymmetries in horizontal tracking and are more significant than a symmetrical decrease in smooth tracking. VOR cancellation is tested by following a target (e.g., the examiner’s finger) by turning the head.

The vestibular system is the third source for the signals that produce nystagmus. Nystagmus may originate anywhere in the vestibulo-ocular pathway, including the vestibular periphery, the eighth nerve, and the vestibular nucleus and cerebellum. Unilateral vestibular hypofunction causes a static imbalance in the activity of the semicircular canal-related VOR and results in a spontaneous jerk nystagmus. This can be either centrally based, as in the case of periodic alternating nystagmus, or due to a peripheral lesion. Peripheral dysfunction tends to cause motion of the eyes in the planes of the semicircular canals, such as with the horizontal-torsional nystagmus typically observed acutely following unilateral labyrinthectomy. The horizontal component fast phases beat toward the “stronger” (intact) ear, and the torsional component involves beating of the superior poles of the eyes toward the intact ear. The speed of the slow phase is generally constant for peripheral vestibular disturbances. Because nystagmus caused by peripheral lesions is relatively suppressed with visual input, examination is best carried out using Frenzel lenses. These special high-diopter goggles prevent patients from fixating on their environment while allowing magnified examination of the eyes, making them an essential tool for the neurotologist. Vestibular imbalance may also cause a skew deviation, or vertical misalignment of the eyes caused by an imbalance of input along otolith-ocular pathways. Both a skew deviation and an ocular motor palsy can present with diplopia, although the misalignment due to a skew deviation is usually constant, while a fourth cranial nerve palsy’s effects worsen with gaze downward and medially. Patients with a skew deviation often complain of vertical or torsional diplopia (two images tilted relative to each other). A subtle skew can be detected as the eyes are alternately covered by the examiner, or by covering one eye with a red lens (Maddox rod) to dissociate the images and allow the patient to describe the diplopia. The lower (hypotropic) eye is usually on the side of the lesion, although lesions higher than the vestibular nucleus (where the pathways decussate) may cause the higher eye to be on the side of the lesion. The head is usually tilted toward the lower eye. A combination of defects in gaze-holding and vestibular input contribute to several types of nystagmus. Bruns’ nystagmus, found in patients with cerebellopontine angle tumors, is a combination of gaze-evoked nystagmus with low-frequency, large-amplitude fast phases on looking toward the side of the lesion and jerk nystagmus with highfrequency, small-amplitude fast phases on looking away from the lesion.74 The gaze-holding nystagmus may represent the body’s way of canceling the jerk nystagmus caused by vestibular imbalance.75 Nystagmus arising from a peripheral lesion and many central lesions is more intense (slow-phase velocity higher) when the eye is deviated in the direction of the quick phase (Fig. 12-5).76 Known as Alexander’s law, this effect is due to the addition of gazeevoked nystagmus caused by loss of the neural integrator following a peripheral lesion and the vestibular nystagmus caused by the static asymmetry of the lesion itself. The two factors tend to add when looking away from the lesion and cancel each other out when looking toward it.75 Head shaking nystagmus (HSN) evaluates the patient for an imbalance in dynamic vestibular function. The patient is instructed to shake the head vigorously about

The Neurotologic Examination

Vestibular Gaze-holding

Vestibular Gaze-holding

Vestibular Gaze-holding Figure 12-5. Alexander’s law. After unilateral vestibular loss, the eye tends to drift to center. The addition of this effect and the imbalance in vestibular activity between the two labyrinths causes nystagmus to be more pronounced when looking away from the lesion. In straight-ahead gaze (top), only the imbalance in vestibular activity caused by a right-sided vestibular lesion (denoted with an X) causes eye motion; the direction of slow phases are indicated with an arrow. When the eyes look to the direction of the slow phase (middle), the eyes drift back towards the center, subtracting from the vestibular slow phase. When the eyes look away from the direction of the slow phase (bottom), the same centripetal drift of the eyes adds to the vestibular slow phase, and the net slow phase velocity increases. (After Carey JP, Minor LB: Mixed peripheral and central vestibular disorders. In JA Goebel, [ed.]: Practical Management of the Dizzy Patient, Philadelphia, Lippincott, Williams, and Wilkins, 2000, p 237.)

30 times horizontally with the chin placed about 30 degrees downward while wearing Frenzel goggles. The examiner looks for any nystagmus immediately after the patient stops shaking the head. Normal subjects usually have none or occasionally just a beat or two of HSN. With a unilateral loss of labyrinthine function, however, there is usually a vigorous nystagmus with slow phase components initially directed toward the lesioned side.77 HSN arises because there is asymmetry of peripheral inputs during high-velocity head rotations, with more activity generated during rotation toward the intact side than toward the affected side. This asymmetry allows an accumulation of activity within central “velocity storage” mechanisms during head shaking, and nystagmus following head shaking reflects discharge of that activity. The amplitude and duration of the initial phase of HSN depends on the state of the velocity storage mechanism. Because velocity storage is typically ineffective during the immediate period after an acute unilateral vestibular loss, the primary phase of HSN may be absent or attenuated in these circumstances. The head thrust test examines more rapid, high-acceleration motion than does the test for HSN (Fig. 12-6). With the patient looking carefully at the examiner’s nose, the head is turned rapidly a small arc to the right or left. Eye movements of abnormally low amplitude will be evoked in response to head thrusts toward a lesioned or hypoactive labyrinth78 and will be followed by the corrective saccade required to bring the eyes back to the intended point of fixation.79 These saccades can be quite subtle, but the

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sensitivity of the test can be improved by beginning each head movement with the patient’s eyes in primary gaze position and moving the head at random intervals and order to the right and left. The test can also be used to detect dysfunction in the vertical canals by delivering the head thrusts in approximately the plane of each anterior canal, moving the head down and to the ipsilateral side, and each posterior canal, moving the chin up and to the contralateral side.80 Side-to-side “head heaves” are being investigated as an analogous measure of high-frequency otolith function.81 Patients with reduced vestibular function, particularly bilaterally, may show up to a five line decline in acuity with head movement while reading a Snellen chart.82 Normal subjects typically show no more than a one line decline in visual acuity. Dynamic visual acuity is tested during horizontal head oscillations at a frequency of about 2 Hz. Subjects with corrective lenses are instructed to wear their glasses or contact lenses during this testing. A general measure of these changes can be determined with bedside tests, although predictive mechanisms during repetitive oscillations of the head may augment performance during this test and decrease its sensitivity.83 Patients often complain of dizziness on moving their head into a certain position. Positional (sustained) and positioning (transient) nystagmus are tested in these patients. DixHallpike positioning for identification of posterior canal benign paroxysmal positioning vertigo (BPPV) is performed first (Fig. 12-7).84 The patient sits upright on an examination table. For testing to detect the presence of right posterior canal BPPV, the head is turned 45 degrees such that the chin is toward the right shoulder. The patient is then brought straight back rapidly into a right head-hanging position. This position is maintained for at least 30 sec.

Figure 12-6. Head-thrust test in a case of left horizontal canal paresis. The patient’s head is turned slightly off center (A) and then thrust rapidly to her right (B). Note that her eyes remain fixed on the examiner during this maneuver toward the intact side. After the identical maneuver toward the affected side, her eyes lag momentarily (C) before refixating on the examiner (D). This test is essentially a high-acceleration version of the familiar doll’s eyes maneuver (After Halmagyi GM, Curthoys IS: A clinical sign of canal paresis. Arch Neurol 45:737, 1988).

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Right horizontal canal excitation

Right superior canal excitation

Right posterior canal excitation

Figure 12-7. Eye movements evoked by vestibular stimulation. The effects of individual stimulation of each of the right semicircular canals is shown. The arrows depict the slow-phase components of the nystagmus. Excitation of the right horizontal canal causes a horizontal nystagmus with leftward slow phases. A vertical-torsional nystagmus is caused by excitation of the superior or posterior canals. Note that, while turning the eyes toward the side of the stimulus, the superior canal induces a predominantly linear motion and the posterior canal a rotatory motion. Turning the eyes away from the side of the stimulus causes the superior canal to induce a more rotatory motion and the posterior canal a more linear motion. This distinction can be helpful in diagnosing BPPV and superior canal dehiscence syndrome. (After Minor LB: Superior canal dehiscence syndrome. Am J Otol 21:9, 2000.)

The nystagmus characteristic of BPPV begins after a latency of 2 to 10 sec, increases in amplitude over about 10 sec, and declines in velocity over the next 30 sec. Posterior canal BPPV results in a vertical-torsional nystagmus with the slow phase components of the nystagmus directed inferiorly and toward the uppermost ear. Thus, the fast-phase components of the nystagmus are superior and toward the lower ear. Due to the orientation of pulling directions for the oblique and vertical recti muscles, the planar characteristics of the nystagmus change with direction of gaze (when described with respect to an eye-fixed coordinate system): On looking to the dependent ear it becomes more torsional; on looking to the higher ear it becomes more vertical. BPPV can also involve the horizontal canal. In affected patients, a strong horizontal nystagmus builds up and declines over the same time course as for posterior canal BPPV. The nystagmus either beats toward the dependent ear (geotropic) or away from the dependent ear (ageotropic) depending on where in the canal the pathology is located. The standard Dix-Hallpike maneuver may not elicit nystagmus in cases of horizontal canal BPPV, but nystagmus can be provoked by bringing the patient backwards into the supine, head-hanging position and then turning the head left ear down or right ear down. The nystagmus seen with horizontal canal BPPV may last longer than that seen in posterior canal BPPV. A sustained, usually horizontal, positional nystagmus of low velocity is a common finding in patients with central or peripheral vestibular lesions and may also be present in

asymptomatic human subjects.85 A central lesion is most likely when positional nystagmus is purely vertical or purely torsional, or if there is a sustained unidirectional horizontal positional nystagmus of high enough intensity to be observed without Frenzel lenses. Valsalva-induced nystagmus is produced either with the glottis open, by pinching the nose, or with the glottis closed. With the glottis open, middle-ear pressure is raised, while with the glottis closed, intracranial pressure increases. Craniocervical junction anomalies (e.g., Arnold-Chiari malformation), superior semicircular canal dehiscence syndrome, and perilymph fistula can produce nystagmus with this maneuver; superior canal dehiscence can reverse its direction depending on whether intracranial or intratympanic pressure increases. Tullio’s phenomenon is the occurrence of vestibular symptoms and eye movements with sound. Hennebert’s sign is the occurrence of these symptoms and signs with motion of the tympanic membrane and ossicular chain. Eye movements evoked by sound or changes in middle ear pressure are observed using Frenzel lenses while giving pure tones from 500 to 4000 dB at intensities of 100 to 110 dB. Hennebert’s sign is elicited with tragal compression or insufflation through a Siegle’s speculum (fistula test). Otic syphilis, Ménière’s disease, and perilymph fistula have also been reported to cause these signs, although the specific features of the evoked eye movements have not been well characterized. These signs, have recently been documented in patients with superior semicircular canal dehiscence syndrome,86,87 with the evoked eye movements aligning with the plane of the affected superior canal (Fig. 12-8).88 Hyperventilation may provoke symptoms in patients with anxiety or phobic disorders but does not usually produce nystagmus. Patients with demyelinating lesions of the vestibular nerve (e.g., an acoustic neuroma or through compression by a small blood vessel) or of central structures (e.g., caused by MS) may show hyperventilation-induced nystagmus.89 Hyperventilation reduces PCO2, which leads to an increase in serum and cerebrospinal fluid (CSF) pH. This relative alkalosis increases the binding of extracellular calcium to albumin and leads to an increase in the discharge rate and conduction in partially demyelinated axons. Because of this sudden jump in activity of the lesioned nerve, the direction of nystagmus with hyperventilation reflects a relative weakness on the contralesional side. The vestibulospinal system is critical for maintaining posture and balance and is evaluated as part of a work-up for dizziness and imbalance. A complete examination of (1) gait; (2) strength, reflexes, and sensation in the legs; and (3) cerebellar function is essential for the interpretation of postural instability and dysequilibrium. Both static and dynamic balance are tested. Static imbalance in vestibulospinal reflexes is identified from Romberg testing, tandem walking, stepping tests, and evaluation of past-pointing. The Romberg test was originally described in syphilitic patients with tabes dorsalis90 but was later applied to cerebellar disorders by Babinski and Duchenne.91 In the standard Romberg test, the patient stands with eyes closed and feet together; half of patients with sensory ataxia last only 10 sec in this position, while all normals and half of those with cerebellar

The Neurotologic Examination

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Anterior canal Figure 12-8. The Dix-Hallpike maneuver. A medial view of the right labyrinth, showing debris in the posterior canal, is pictured along with the patient’s corresponding position. 1. Initially, the patient’s head is turned slightly to the side and the otoconial debris is located in the inferior portion of the posterior canal near the ampulla. 2. The patient is then brought flat, with the head hanging and the neck extended. The motion causes the crystals to fall away from the ampulla, eliciting a sensation of rotatory motion. The patient’s head is supported at all times during the maneuver. (From Hullar TE, Minor LB: Vestibular physiology and disorders of the labyrinth In Glasscock E 3rd, Gulya AJ, [eds.]: Surgery of the Ear, 5th ed. Hamilton, Ontario, BC Decker, 2003.)

Lateral canal

Posterior canal

1.

ataxia may be able stand a minute or more.92 Increased swaying is common in normals and the degree of swaying cannot differentiate among peripheral vestibular and cerebellar disorders.93 Falls during tandem walking may be indicative of horizontal canal dysfunction. Fukuda stepping tests (marching in place for 30 sec with eyes closed) can show excessive turning toward the side of a unilateral vestibular lesion.94 An ataxic gait may also be noted during walking tests. Ataxia is characterized by a widened base (more than the normal 2 to 4 in. separating the feet laterally) and irregular or even staggering steps. Sensory ataxia is caused by proprioceptive loss; patients tend to look at their feet, which often slap on the ground. Patients with a reeling, staggering gait are more likely to have a cerebellar ataxia, which is often accompanied by other cerebellar signs. There is poor interobserver reliability of what constitutes an “abnormal gait”.95 Past-pointing of the arms to previously seen targets with eyes closed may also be a sign of vestibulospinal imbalance. Dynamic vestibulospinal function is assessed by observing postural stability during rapid turns or in response to external perturbations imposed by the examiner (i.e., a gentle shove forward, backward, or to the side). The “eyes-closed turning test” (staggering when turning to the side of the lesion after walking with eyes closed) has been described with a sensitivity of 88% in patients with a perilymph fistula.96

CRANIAL NERVES IX AND X The vagus nerve, via its auricular division (Arnold’s nerve), carries sensation from the concha, inferoposterior external auditory canal, a portion of the external surface of the tympanic membrane, and postauricular skin. The glossopharyngeal nerve, as Jacobson’s nerve, carries sensation from the entire middle ear including the eustachian tube and mastoid cells and carries taste sensation from the posterior one third of the tongue. Cranial nerve IX is responsible for

2.

sensation during testing of the gag reflex. Cranial nerve X is responsible for elevation of the palate via the levator palati muscle. Difficulties voicing normally or swallowing without coughing can indicate disorders of the tenth nerve. When appropriate, flexible laryngoscopy can help distinguish tenth nerve disorders from other problems. A new technique has been reported for measuring the sensory component from the superior laryngeal nerve using an air puff from a modified laryngoscope onto the supraglottic mucosa.97 Damage to the recurrent laryngeal nerve often results in a flaccid, lateralized cord with a breathy voice that gradually medializes to a paramedian position. Spasmodic dysphonia can cause medialization of the vocal cord and a choking voice or lateralization of the cord and a breathy voice, depending which set of laryngeal muscles is most affected.98

CRANIAL NERVE XI The spinal accessory nerve innervates the trapezius and sternocleidomastoid muscles. The sternocleidomastoid is tested for symmetry by feeling the muscle’s contraction while pushing against the patient’s chin on the opposite side. Weakness of the trapezius can be evaluated by examining the muscle for symmetry, observing the shirtless patient from behind. Shrugging of the shoulders is insufficient to test the eleventh nerve, as patients can mimic this motion with spinal muscles to compensate for shoulder weakness. Raising the arm laterally (not anteriorly) above the level of the shoulder indicates adequate trapezius function.

CRANIAL NERVE XII The hypoglossal nerve supplies the intrinsic muscles of the tongue. The tongue of a patient with an acutely denervated hypoglossal will deviate toward the affected

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NEUROTOLOGIC DIAGNOSIS

side when thrust out of the mouth, but patients with chronic unilateral palsy may not show this deficit. They are unlikely to be able to lateralize their tongue to the unaffected side, however. The hypoglossal nerve is particularly susceptible to inflammation or edema of the dura from distant processes due to its relatively narrow path through the dura.99

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78. Halmagyi GM, Curthoys IS, Cremer PD, et al: The human horizontal vestibulo-ocular reflex in response to high-acceleration stimulation before and after unilateral vestibular neurectomy. Exp Brain Res 81:479, 1990. 79. Tian J, Crane BT, Demer JL: Vestibular catch-up saccades in labyrinthine deficiency. Exp Brain Res 131:448, 2000. 80. Cremer PD, Halmagyi GM, Aw ST, et al: Semicircular canal plane head impulses detect absent function of individual semicircular canals. Brain 121:699, 1998. 81. Ramat S, Zee D, Minor L: Translational vestibulo-ocular reflex evoked by a “head heave” stimulus. Ann NY Acad Sci 942:95, 2001. 82. Kasai T, Zee DS: Eye-head coordination in labyrinthine-defective human beings. Brain Res 144:123, 1978. 83. Tian JR, Shubayev I, Demer JL: Dynamic visual acuity during transient and sinusoidal yaw rotation in normal and unilaterally vestibulopathic humans. Exp Brain Res 137:12, 2001. 84. Dix MR, Hallpike CS: The pathology, symptomatology and diagnosis of certain common disorders of the vestibular system. Proc R Soc Med 45:341, 1952. 85. McAuley JR, Dickman JD, Mustain W, et al: Positional nystagmus in asymptomatic human subjects. Otalaryngol Head Neck Surg 114:545, 1996. 86. Minor LB: Superior canal dehiscence syndrome. Am J Otol 21:9, 2000. 87. Minor LB, Solomon D, Zinreich JS, et al: Sound- and/or pressureinduced vertigo due to bone dehiscence of the superior semicircular canal. Arch Otolaryngol Head Neck Surg 124:249, 1998. 88. Cremer PD, Minor LB, Carey JP, et al: Eye movements in patients with superior canal dehiscence syndrome align with the abnormal canal. Neurology 55:1833, 2000. 89. Minor LB, Haslwanter T, Straumann D, et al: Hyperventilationinduced nystagmus in patients with vestibular schwannoma. Neurology 53:2158, 1999. 90. Romberg M: Lehrbuch der Nervenkrankheiten des Menschen. Berlin, Alexander Dunckner, 1840. 91. Schiller F: Staggering gait in medical history. Neurology 37:127, 1995. 92. Notermans NC, van Dijk GW, van der Graaf Y, et al: Measuring ataxia: Quantification based on the standard neurological examination. J Neurol Neurosurg Psychiatry 57:22, 1994. 93. Baloh RW, Jacobson KM, Beykirch K, et al: Static and dynamic posturography in patients with vestibular and cerebellar lesions. Arch Neurol 55:649, 1998. 94. Fukuda T: The stepping test: Two phases of the labyrinthine reflex. Acta Otolaryngol (Stockh) 50:95, 1958. 95. Eastlack M, Arvidson J, Snyder-Mackler L, et al: Interrater reliability of videotaped observational gait-analysis assessments. Phys Ther 71:465, 1991. 96. Singleton GT: Diagnosis and treatment of perilymph fistulas without hearing loss. Otalaryngol Head Neck Surg 94:426, 1986. 97. Aviv J, Kim T, Sacco R, et al: FEESST: A new bedside endoscopic test of the motor and sensory components of swallowing. Ann Otol Rhinol Laryngol Suppl 5 Pt 1:378, 1998. 98. Blitzer A, Brin M, Stewart C: Botulinum toxin management of spasmodic dysphonia (laryngeal dystonia): A 12-year experience in more than 900 patients. Laryngoscope 108:1435, 1998. 99. Wullstein H, Wullstein S: Surgery of tumors of the middle ear and the otobase. In Naumann H (eds.): Head and Neck Surgery. Philadelphia, WB Saunders, 1982. 100. Newman N: Neuro-Ophthalmology. Norwalk, CT, Appleton & Lange, 1992.

Chapter

13 Steven A. Newman, MD Paul R. Lambert, MD

T

Neuro-Ophthalmic Manifestations of Neurotologic Disease Outline Ocular Stabilizing Systems Vestibulo-Ocular Reflexes Symptoms Decreased Visual Acuity Diplopia Oscillopsia Pain Signs Nystagmus Vestibular Nystagmus Gaze Paretic Nystagmus Congenital Nystagmus Central Nystagmus Downbeat Nystagmus Upbeat Nystagmus

he contralateral vestibular nuclei provide direct dynamic input to the position of the globe in the orbit. It is therefore not surprising that any disturbance in the normal function of the vestibular apparatus or its connections has a direct and immediate effect on the orientation of the globes and on their ability to move. Vestibular pathology is often brought to the attention of the clinician by patient complaints of diplopia and blurred vision and can be diagnosed specifically by studying ocular motility. Although the vestibular ocular connection probably represents the phylogenetically oldest ocular motor system, its importance has only recently been recognized. Erasmus Darwin in 1796 first noted ocular movement induced by body rotation.1 In 1824, Flourens2 recognized the physiology of the semicircular canals. It has only been within the 20th century that detailed central vestibular connections and vestibular testing have been outlined. The role of the vestibular system in the generation of eye movements is better understood if the five major eye movement systems are examined teleologically. The eyes need to move for three basic reasons. The first is to maintain a stable image of the world around us. Image drag across the retina at more than 3 to 5 degrees/sec results in a marked degradation of the image and consequent loss of acuity.3–6 The vestibular system is responsible for maintaining the eye stable in space during head movements, while the optokinetic system matches the movement of the surrounding environment with an appropriate eye movement. The second reason eyes move is based on our development of a specialized area of maximal spatial resolution (acuity), the fovea. The saccadic system is responsible for 228

Seesaw Nystagmus Dissociative Nystagmus Periodic Alternating Nystagmus Physiological Nystagmus Misalignment of the Visual Axes Afferent System Pathology Horner’s Syndrome Evaluation History Examination Specific Disease Processes Conclusions

bringing the fovea into alignment with an object of interest, while the pursuit system uses continuous visual feedback to maintain foveal alignment when the target moves. The third reason for ocular motility is the consequence of forward ocular migration resulting in overlapping visual fields. Thus to maintain simultaneous foveal alignment of both visual axes while a target moves closer or further away, the eyes must move relative to each other. This is accomplished by the convergence system. A primary function of the vestibular system is to coordinate eye movements with rotational and translational movements of the head, thus maintaining clear and stable retinal images. Visual pursuit relies on relatively slow (approximately 75-msec) retinal processing, and therefore cannot maintain image stability during natural head rotations, which occur at frequencies of 0.5 to 5.0 cycles/sec.7,8 The semicircular canals, by contrast, can respond in less than 16 msec to drive the eyes at exactly the head velocity, but in the opposite direction.9,10 Compensatory eye movements for linear head movement are generated by the otolithic organs with a latency of less than 35 msec.11

OCULAR STABILIZING SYSTEMS Because final eye movements are a combination of the action of all the ocular motor systems, it is often possible for one or more of the intact systems to compensate for a compromised vestibular system. Thus, it is important to be able to evaluate all ocular motor systems, not just the vestibular. Ocular stability requires the integration of

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a number of visual systems with the vestibulo-ocular reflex (VOR), including the optokinetic, smooth pursuit, and saccadic systems. The pursuit system in particular can be used to compensate for abnormalities or asymmetries within the vestibular system, and it may therefore prevent development of immediate symptomatology or obvious pathologic findings with local vestibular damage. Attempts to track a moving object by moving the head require additional neural mechanisms that combine pursuit and vestibular signals.12,13 Some evidence suggests that the VOR is suppressed.14 These neural pathways are incompletely understood, but appear to involve activation of the ocular motor neurons by the VOR signal or its copy with an opposite sign.15,16 It should be apparent that these stabilization systems require visual input and are absent with severely compromised vision.17–19 The ability to maintain eccentric gaze requires a gazeholding neural integrator mechanism.20 Aside from the dynamic forces producing changes in ocular position, static “elastic restoring forces” within the orbit tend to bring the eyes back to the primary position. These may be modeled simply as a system of soft tissue “springs” that increase their tension as the eye is directed relatively more eccentrically. To supply an appropriate continuous signal that overcomes the elastic restoring forces, a “tonic” increase must be made in the input to the extraocular muscles. Obviously, this tonic force must be increased as the eccentricity becomes greater. A neural integrator located in the area of the nucleus propositus hypoglossi adjacent to the medial vestibular nucleus21 automatically adjusts the tonic signal to match the dynamic impulse needed to move the eyes eccentrically. The pathology that affects this neural integrator results in what is referred to as a pulse-step mismatch. Although the “pulse” produces an appropriate saccadic (rapid) conjugate movement of the eyes to a particular eccentric position, the inadequacy of the subsequent “step” results in a drift of the eyes back toward the primary position. As the elastic restoring forces increase with increasing eccentricity, the drift back toward fixation results in an exponentially decreasing slow velocity. This characteristic waveform may be helpful in distinguishing various abnormalities in ocular motility.

Vestibulo-Ocular Reflexes The anatomy of the vestibular system is covered elsewhere. Briefly, stimulation of the semicircular canal results in a three-neuron reflex arc involving the vestibular ganglion, vestibular nuclei, and ocular motor nuclei. This reflex arc and alternative interneuron projections result in eye movements parallel to the plane of the stimulated canal.22 Theoretically, therefore, identification of a diseased semicircular canal could be readily ascertained by noting the direction of nystagmus. It is instructive to review briefly extraocular muscle movement in response to stimulation of a specific semicircular canal.23,24 Electrical stimulation of neural fibers from the horizontal semicircular canal results in horizontal conjugate deviation of both eyes toward the contralateral side. This eye movement involves both excitatory pathways (contralateral abducens nucleus/lateral rectus muscle and ipsilateral oculomotor nucleus/medial rectus muscle) and inhibitory

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pathways (contralateral oculomotor nucleus/medial rectus muscle and ipsilateral abducens nucleus/lateral rectus muscle). This is coordinated through the horizontal gaze center located within the ipsilateral sixth nerve nucleus in the dorsal pontine tegmentum.25 Its primary input is the contralateral medial vestibular nucleus. The vertically oriented canals also produce a combination of excitatory and inhibitory signals. While excitatory signals cross to the contralateral midbrain, inhibitory information remains ipsilateral. Electrical stimulation of neural fibers from the anterior semicircular canal causes both upward and torsional eye movements, with the upper pole of each eye moving toward the contralateral side. The vertical eye movement is stronger ipsilaterally. The ipsilateral superior rectus and contralateral inferior oblique muscles are excited, and the ipsilateral inferior rectus and contralateral superior oblique muscles are inhibited. This is largely mediated by fibers crossing in the rostral medulla to ascend in the contralateral medial longitudinal fasciculus (MLF) to the contralateral third nerve nucleus where the superior rectus and inferior oblique subnuclei are stimulated. As the superior rectus subnucleus innervates the contralateral superior rectus, both eyes rise. Electrical stimulation of neural fibers from the posterior semicircular canal produces conjugate deviation of the eyes downward, with torsional eye movements directed again contralaterally. The downward eye movement is stronger in the contralateral eye, and eye rotation is more apparent in the ipsilateral eye. The ipsilateral superior oblique and contralateral inferior rectus muscles are stimulated, whereas their antagonists, the ipsilateral inferior oblique and contralateral superior rectus muscles, are relaxed. Stimulatory projections from the posterior semicircular canal also travel in the MLF to innervate the contralateral trochlear nucleus and the inferior rectus subnucleus within the oculomotor complex. In addition, evidence shows that accessory pathways from the vertical canals cross at the pontomedullary junction rising in the brachium conjuneticum.26,27 The anterior semicircular canal pathways are anatomically separated from those arising in the posterior semicircular canals, which makes them asymmetrically sensitive to pathology. Selective involvement of the pathways from the anterior or posterior canals leads to vertical drift of both eyes and upbeat or downbeat nystagmus.26,28 Balanced input from the left and right utricles also affects globe position. The utricular fibers project to the ipsilateral medial rectus and to the contralateral superior oblique, superior rectus, inferior oblique, inferior rectus, and lateral rectus muscles.29 Thus, stimulation of the utricular nerve leads to torsion of the eyes toward the contralateral side while the ipsilateral eye rises and the contralateral eye falls.30

SYMPTOMS Decreased Visual Acuity Although the vestibular system may be affected in myriad ways, the symptoms appreciated by the patient are limited. Patients may occasionally complain of decreased visual acuity. This can occur when the image slip across the retina

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cannot be controlled to within 3 to 5 degrees/sec. The patient may be aware that this visual “blurring” increases with eccentric gaze or in one particular position. This may represent local increase in abnormalities of visual stabilization. This symptom is usually binocular, but it can be monocular31 or substantially asymmetrical. In that case, the patient may complain of unilateral decreased visual acuity. Lack of attention to ocular motor problems may lead to a misdirected work-up conversely. Careful attention to asymmetrical spontaneous eye movements may provide an explanation for unilateral decreased visual acuity. Thus, it is imperative to check for an afferent pupillary defect (MarcusGunn pupil) or optic atrophy, which would indicate definite pathology within the optic nerve or visual pathways.

is distinctly uncommon in patients with congenital nystagmus.37 Primary overaction of one or more of the extraocular muscles, as in superior oblique myokymia, is another uncommon cause of oscillopsia. In this syndrome, repetitive firing of the fourth nerve results in tiny torsional and vertical oscillations of the eye, accompanied by a unilateral sensation of the world jumping. Oscillopsia has its highest frequency of occurrence in patients with bilateral peripheral vestibular pathology.28 Such patients frequently report the inability to read signs while walking.38 When the head is stabilized, however, the vision is normal. Central abnormalities in VOR gain may also lead to severe motion-induced oscillopsia. Oscillopsia may occur at rest in the setting of acquired pendular nystagmus.39

Diplopia

Pain

The major eye complaints related to vestibular pathology are diplopia and oscillopsia. Diplopia arises from misalignment of the two visual axes. This can be horizontal, but vertical deviations are more commonly associated with vestibular abnormalities. Partial involvement of the sixth cranial nerve or of the MLF will lead to horizontal misalignment. The sixth cranial nerve and its nucleus are located just rostral to the vestibular nuclei in the area of the pontomedullary junction. Tumors of the cerebellopontine angle often compromise abducens function occasionally bilaterally. When lesions affect the MLF, the patient will usually complain of horizontal diplopia on contralateral gaze. As additional vertical inputs are carried by the MLF, more extensive lesions, particularly with bilateral involvement, may also produce problems with vertical gaze and vertical diplopia.32 This is usually seen as vertical gaze paresis and a skew deviation, as discussed later. Vertical double vision occurs when relative vertical separation of the visual axes occurs. Involvement of the fourth cranial nerve exiting the brainstem dorsally in the midbrain is a frequent cause. If the classical findings of a fourth nerve palsy are not present, the most likely central cause of vertical diplopia is a skew deviation representing asymmetrical involvement of the vertical prenuclear input.33,34 Vertical double vision can also occur as an isolated phenomenon due to local orbital pathology such as occurs following orbital trauma (blowout fracture) or as related to extraocular muscle tightening seen in thyroid orbitopathy or orbital inflammatory disease. Less commonly, neoplastic processes may affect the muscles. Restrictive problems usually can be distinguished from paretic abnormalities by performing forced duction testing or checking intraocular pressure in eccentric gaze. Local pathology may also be suspected in the setting of proptosis, injection, numbness, or globe displacement (dystopia).

Pain associated with neurotologic disease may also be accompanied by ocular complaints. In Gradenigo’s syndrome, infection involving the petrous bone (usually following otitis media) results in pain due to stimulation of the recurrent dural branches of the fifth cranial nerve.40 Diplopia develops secondary to involvement of the sixth cranial nerve as it crosses the petrous apex in Dorello’s canal. More commonly, however, painful double vision represents pathology affecting the skull base in the area of the cavernous sinus.41 Here, involvement of the fifth cranial nerve in combination with the third, fourth, and sixth nerves produces ocular misalignment and discomfort. In the older population, a pseudo-Gradenigo’s syndrome is not uncommonly related to nasopharyngeal carcinoma, which invades that base of the skull through the foramen lacerum.

Oscillopsia Oscillopsia is one of the most suggestive complaints seen with vestibular dysfunction.35 This is the abnormal perception that a stationary object is in motion.36 It may be distinguished from vertigo, in which the subjective sensation is of the entire world spinning. Oscillopsia rarely occurs with abnormalities of eye movements, and in fact it

SIGNS In neuro-ophthalmology, signs are usually separated into those affecting the afferent visual system (those connections between the eye and visual cortex responsible for visual perception) and the efferent visual system (those pathways responsible for ocular motility, simultaneous binocular alignment, and ocular stabilization). Neurotologic pathology most frequently affects the efferent visual system and, in particular, the vestibular input and connections.

Nystagmus Nystagmus is a repetitive oscillation of the eyes.42 Although some individuals may produce a nystagmus-like picture voluntarily,43 most nystagmus is the result of asymmetrical tonic input into either the horizontal or vertical gaze center, resulting in a tendency of the eyes to drift. When not suppressible by the fixation system or by smooth pursuit, the resultant drift and secondary corrective eye movements occur in a rhythmic fashion. Nystagmus is most commonly binocular, although it may be asymmetrical. It is also usually conjugate. That is, the two eyes are moving in the same direction simultaneously. Disconjugate nystagmus in which the eyes are moving in different directions, includes retraction convergence nystagmus and seesaw nystagmus.

Neuro-Ophthalmic Manifestations of Neurotologic Disease

Nystagmus has been classified in a number of ways. Probably the simplest is based on direction. The repetitive eye movements may be purely vertical, purely horizontal, purely torsional, or some combination of the three. The second method of classification is based on the motility pattern. Nystagmus is termed pendular when the eyes move to and fro with equal velocity and jerk when there is a fast component in one direction and a slow drift in the other. Although nystagmus is usually “defined” (labeled) by the direction of the fast component, it is the slow drift that indicates pathology in tonic input. Nystagmus can be further characterized by the waveform of its slow component.42 Although this usually requires ocular motor recording techniques, this characterization can be valuable in separating out the presumptive pathophysiology. The slow phase may be of constant velocity, exponentially decreasing, or exponentially increasing. Nystagmus has also been defined by degrees: In firstdegree nystagmus, the abnormal ocular movements are present only while looking in the direction of the quick phases. In second-degree nystagmus, abnormal ocular movements occur in the primary position, and with third-degree nystagmus, movements are present in all fields. However, a relative area of least motility (a relative null point) may still be present. Vestibular Nystagmus Nystagmus usually arises from one of two basic abnormalities: vestibular pathology or pathology affecting the neural integrator. Asymmetrical input from the vestibular nuclei or secondarily from dysfunction of the vestibular end organ can result in ocular drift. Lesions of the peripheral vestibular system rarely affect just one semicircular canal, but rather involve the entire labyrinth or vestibular nerve on one side. The resulting imbalance in neural activity reaching the central vestibular system causes eye movements that reflect the summed influence of each semicircular canal. Nystagmus therefore often has both a horizontal and torsional component; the vertical eye movement from the anterior and posterior semicircular canals negate each other. Because the tonic input is contralateral in the case of the horizontal canals, pathology affecting the vestibular system on one side will produce a drift of the eyes toward the affected side. This is due to the loss of tonic input into the contralateral horizontal gaze center, whereas the ipsilateral gaze center supplied from the opposite vestibular system is unaffected. Thus, the eyes will drift toward the pathologic side, with quick corrective phases away from it. In almost all cases of vestibular pathology, loss of signal from part of the vestibular system leads to relative drift. One exception to that rule is benign paroxysmal positional vertigo (BPPV). In this syndrome periodic over-reaction from debris on the cupula is induced by change in position. BPPV is thought to involve only the posterior semicircular canal.44,45 The nystagmus noted when a patient is placed in a provocative position corroborates this hypothesis.46 The pathologic eye movement is both vertical (stronger in the eye contralateral to the diseased posterior semicircular canal) and torsional (stronger in the eye ipsilateral to the diseased posterior semicircular canal). An electronystagmograph

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does not record torsional eye movement; therefore, the main eye movement noted will be vertical. Gaze Paretic Nystagmus Impairment of the neural integrator causes gaze-evoked or gaze paretic nystagmus.21 In this circumstance, the tonic extraocular muscle activity needed to keep the eyes in a certain eccentric position is inadequate, thus allowing the eyes to drift back toward fixation in an exponentially decreasing form. Corrective saccades return the eyes to the desired eccentric position. Multiple pathophysiologic processes may affect the neural integrator. These include lesions of the brainstem and cerebellum, especially the flocculus and paraflocculus, and various drugs such as sedatives,47 alcohol,48 and anticonvulsants.49–52 Gaze-evoked nystagmus can be symmetrical or asymmetrical. Symmetrical gaze-evoked nystagmus has equal amplitude with right and left lateral gaze. The most common cause of this nystagmus is ingestion of drugs such as alcohol48 and anticonvulsants.53,54 It is also frequently noted in patients awakening from various general anesthetics, and therefore must be differentiated from pathological nystagmus secondary to otologic or neurotologic surgery. Specific central nervous system (CNS) lesions such as multiple sclerosis55 and cerebellar atrophy56 are additional causes of symmetrical gaze-evoked nystagmus. Asymmetrical gaze-evoked nystagmus is caused by asymmetrical involvement of the neural integrator often due to structural lesions of the cerebellum or brainstem. Large cerebellopontine angle tumors42,57,58 that produce brainstem and cerebellar compression can cause asymmetrical gaze-evoked nystagmus (Bruns’ nystagmus).59 Bruns’ nystagmus is characterized by a low-frequency, largeamplitude nystagmus with ipsilateral gaze due to the leaky neural integrator. This in turn is secondary to the compression of the area of the nucleus propositus hypoglossi by the extra-axial mass. When the patient gazes in the opposite direction, a higher frequency, small-amplitude nystagmus secondary to the vestibular imbalance is induced by the compression of the ipsilateral vestibular pathways to the contralateral horizontal gaze center. Congenital Nystagmus Both gaze paretic nystagmus, due to a leaky neural integrator, and vestibular nystagmus, representing the most common form of acquired nystagmus, must be distinguished from congenital nystagmus. Certain characteristics of hereditary nystagmus, if present, can help with this differential diagnosis. As a rule, congenital nystagmus has an exponentially increasing slow phase (although pendular nystagmus is possible).60,61 Although it is possible for congenital nystagmus to be vertical or torsional, horizontal movement is most common. Classically, congenital nystagmus remains horizontal with both up and down gaze. Additional characteristics of congenital nystagmus include accentuation by visual fixation62 and diminution by convergence63 or by gaze in a certain direction (null region). Congenital, vestibular, and gaze paretic nystagmus tend to follow Alexander’s law; that is, the amplitude and possibly even the frequency of the corrective saccadic movements

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increase with gaze in the direction of the quick phase.64 The cause of congenital nystagmus is unknown, but presumably represents asymmetrical tonic input into the horizontal gaze centers that is not compensated for by other eye movement systems. Because most of these other systems require visual input, it is not surprising that the incidence of congenital nystagmus is higher in patients with various afferent system pathologies that cause decreased visual acuity. This undoubtedly explains in part the association of albinism and a number of other ophthalmologic abnormalities with congenital nystagmus.65–67 Central Nystagmus The presence of vertical or torsional nystagmus implies a relatively selective involvement of either the anterior or posterior semicircular canal or of the utricle. This is possible because of the anatomic separation, seen particularly in the area of the pontomedullary junction, as discussed earlier. The posterior canal inputs cross dorsally in the medulla beneath the nucleus propositus hypoglossi prior to the ascending in the MLF. Except for the condition of BPPV, a peripheral vestibular lesion does not affect just one vertical canal. Thus vertical nystagmus almost always represents central vestibular pathology. Isolated torsional nystagmus also strongly suggests a central origin.68 When vertical and torsional nystagmus are combined, a peripheral cause is possible. Most frequently, nystagmus is not pure, but rather combines varying degrees of torsional, horizontal, and vertical movements. It is usually possible on clinical examination to distinguish nystagmus due to peripheral vestibular pathology from that caused by central abnormalities. Peripheral vestibular nystagmus is often suppressed by visual fixation and, in fact, may only become apparent when fixation is prevented (e.g., through the use of Frenzel lenses or recording eye movements in the dark). The patients’ ability to use intact smooth pursuit and visual fixation systems to negate a tendency toward drift accounts for this phenomenon. Conversely, visual fixation has little or no effect on central nystagmus, including both downbeat and upbeat varieties. One exception to this is the upbeat nystagmus presumably related to nicotine seen in smokers only when fixation is interrupted.69 Habituation may occur with time in the setting of peripheral involvement, but usually does not occur with nystagmus of central origin. Downbeat Nystagmus Two relatively pure isolated forms of central nystagmus are downbeat and upbeat nystagmus. In the case of downbeat nystagmus pathology usually interrupts the fibers crossing in the dorsal tegmentum of the medulla. This relatively selective involvement of information coming from the posterior canals leads to a slow phase drift of the eyes up and a secondary correctional movement with a fast phase down.70 Clinically, downbeat nystagmus is usually seen with cerebellar degeneration or pathology at the cervical medullary junction.28,71–73 Specific causes include ArnoldChiari malformation,74,75 basilar invagination, and tumors (most commonly meningiomas) at the craniocervical junction. It can also be seen in a number of other conditions

affecting the cerebellum or brainstem, including multiple sclerosis71,76 and anticonvulsant therapy.77,78 Several interesting clinical aspects surround downbeat nystagmus. Its intensity is consistently increased with lateral gaze and often increased with downward gaze.79 Thus, in cases of subtle downbeat nystagmus, more dramatic clinical findings may be elicited by having the patient gaze laterally and downward. Patients with downbeat nystagmus also have a very high incidence of associated pursuit deficit.76 Asymmetrical downbeat nystagmus may be seen with more of a torsional component in one eye. This is usually accompanied by evidence of an internuclear ophthalmoplegia.80 Upbeat Nystagmus Upbeat nystagmus,81–85 represents relative selective involvement of input from the anterior canals.86 Unlike downbeat nystagmus, upbeat nystagmus does not usually increase on lateral gaze,76 but it is enhanced by looking upward. Selective involvement of the anterior canal input may occur from the same anatomic separation at the level of the pontomedullary junction, but interestingly in the cat there is also additional anterior canal input through the ventral tegmentum of the medulla.86 Selective involvement of this area could lead to a slow drift of the eyes down and compensatory rapid up movements. An alternative explanation for upbeat nystagmus is based on the selectivity of neural transmitters. In rabbits, flocculus Purkinje cells project inhibitory stimuli to the anterior canal projections, but not to the posterior canal projections.87 Thus, pharmacoselective involvement may provide an explanation for this form of central vestibular dysfunction. Clinically, upbeat nystagmus is usually secondary to infarction, tumor infiltration, or multiple sclerosis involving the midbrain, medulla, or cerebellum.82,83,85,88–90 Seesaw Nystagmus Pathology of the otolith pathways produces a unique form of nystagmus.91–93 In seesaw nystagmus, the ipsilateral eye rises and intorts while the contralateral eye falls and extorts. As mentioned earlier, it is also likely that this asymmetrical otolith input is responsible for the ocular tilt reaction and the development of a skew deviation94 usually with an ipsilateral hypotropia.95 In this setting, an incomitant vertical separation is present between the visual axes. Thus, the deviation changes with change in gaze position. Seesaw nystagmus and the ocular tilt syndrome may both arise with pathology in the area of the interstitial nucleus of Cajal,96 which is located just rostral to the third cranial nerve nucleus within the midbrain. This area receives input from the vertically oriented semicircular canals as well as the otolithic organs.97 Large parasellar masses are the most frequent cause.91,92,98 Mesencephalic skew deviations usually have the pathology ipsilateral to the hypertropic eye.34 Dissociative Nystagmus Asymmetry in nystagmus may also occur when an abnormality is present in the ocular motor cranial nerves or their

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internuclear connections. An example of dissociative nystagmus is that seen with an internuclear ophthalmoplegia (INO).99 Involvement of the MLF causes weakness in adduction associated with abducting nystagmus in the contralateral eye. An INO is most frequently seen with small vessel disease (vertebrobasilar insufficiency) in the elderly population100 and occurs secondary to demyelinating disease101 in the young. Any pathology that affects the MLF within the brainstem, including vascular anomalies, neoplastic, and infectious processes, may produce a similar picture. Periodic Alternating Nystagmus Nystagmus may not remain fixed in pattern. Periodic alternating nystagmus (PAN) is an acquired or congenital horizontal nystagmus in which a slow drift occurs in the null point from one side to the other over a cycle of approximately 4 minutes.102 Thus the nystagmus will beat in one direction for approximately 1.5 to 2 minutes, stop beating, then reverse direction for the remaining 1.5 to 2 minutes. This abnormality in null point position is thought to be secondary to pathology within the vestibulocerebellum,103 including the nodulus.104–107 Discovery that the inhibitory pathways were controlled by γ-aminobutyric acid (GABA) lead to the theoretical use of baclofen (a GABA agonist) in patients with PAN.108 This has often been successful in abolishing the drifting null position, although not in patients with congenital PAN. Physiologic Nystagmus Nystagmus is not always pathologic. Simple rotation, which produces a normal vestibular slow phase in the opposite direction, does induce nystagmus as the rotation continues. Similarly, a moving background target produces not only the slow phase drift to compensate for the full-field movement, but also the compensatory reset saccades seen in optokinetic nystagmus. After sustained movement of the environment, slow phase drift will continue as optokineticafter-nystagmus (OKAN). This has been conceptualized as a slow discharge of the “capacitor,” which has been charged by the moving environment. Teleologically, the presence of OKAN is important to counteract the induced VOR in the opposite direction that is seen when persistent rotation is suddenly stopped.109,110 Endpoint nystagmus is a common finding in normal patients when eye deviation from midposition is extreme (greater than 40 degrees).111,112 The low intensity of the nystagmus (slow phase velocity of less than 3 degrees/sec) and the absence of other ocular abnormalities confirm its benign nature.

Misalignment of the Visual Axes Static misalignment of the visual axes is another form of efferent visual system abnormality that can be present with neurotologic disease. This may be due to pathology affecting the ocular motor cranial nerves, their internuclear connections, or the horizontal and vertical gaze centers. The pathophysiology may be due to intrinsic brainstem pathology or more commonly to extrinsic lesions that secondarily affect either the peripheral cranial nerves or their

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brainstem origins. Pathology that is likely to affect both the cranial nerves and the vestibular system includes vascular abnormalities, neoplastic processes, and inflammatory lesions.

Afferent System Pathology Although far less common than efferent system involvement, the afferent visual pathways may be pathologically involved in association with neurotologic disease. Pathology that obstructs normal cerebrospinal fluid (CSF) outflow may result in increased intracranial pressure with secondary evidence of disc edema. In this setting, transmission of the elevated intracranial pressure along the optic nerve sheath to the optic disc at the back of the eye results in constipation of axonal transport. This is manifest clinically as hyperemia, disc elevation, and obscuration of the nerve fiber layer as it crosses the disc margin. Variable hemorrhage and soft exudates may occur over the optic nerve head surface. Clinically, the patients often complain of headache and may have visual obscurations (transient, characteristically brief, visual loss), particularly in association with change in position (bending or rising rapidly). Although visual acuity is often normal until late in the course of this condition, variable optic nerve dysfunction may occur.113 This can manifest itself as visual field defects, including a combination of superior and inferior arcuate defects, often described as peripheral constriction. If not treated, the optic neuropathy may be progressive and can lead to permanent irreversible visual loss. The optic neuropathy associated with increased intracranial pressure is usually symmetrical. On occasion, however, it may affect one eye more than the other, resulting in an afferent pupillary defect. This is detected with a swinging flashlight test and may be quantified by the use of neutral density filters. Involvement of the optic nerve, however, will not produce inequality in the pupil size. Rarely, visual acuity may be affected by an autoimmune phenomenon that attacks both the auditory system and the cornea. In Cogan’s syndrome, an interstitial keratitis is associated with auditory nerve involvement, resulting in decreased visual acuity.114,115 Other forms of afferent visual system pathology include the occurrence of visual field defects. These are probably even less common than involvement of the optic nerves due to papilledema, but they can happen when distal vertebrobasilar system pathology results in compromised circulation to the occipital lobe. Embolism, dissection, or simple atherosclerosis can all affect posterior fossa circulation and lead to various forms of homonymous hemianopsia.

Horner’s Syndrome It is possible to see inequality in pupil size (anisocoria) associated with neurotologic disease. This most commonly occurs as a manifestation of Horner’s syndrome. Interruption of the sympathetic fibers, usually as they descend within the intermediolateral column in the brainstem, results in a smaller pupil on that side. The difference between the two pupils is exaggerated in a low-light environment. Other manifestations of sympathetic denervation to the orbit include a small amount of ptosis and anhydrosis over the

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ipsilateral forehead. Horner’s syndrome may be confirmed with the cocaine test. Placement of a drop of 4% to 10% cocaine in both eyes will result in normal dilation of the larger pupil. On the side of the smaller pupil, however, lack of normal sympathetically released norepinephrine leads to failure of dilation, thus exaggerating the difference in size. Most patients with Horner’s syndrome have pathology affecting the carotid artery and secondarily the third-order sympathetic neuron, which runs in the adventitia of that artery. When associated with neurotologic pathology, however, it is most likely that the first-order neuron extending from the hypothalamus to the cervical thoracic junction is affected. The Paredrine test can distinguish first-order from the more common form of third-order neuron involvement in Horner’s syndrome. Hydroxyamphetamine 1%, when placed in both cul-de-sacs, will cause dilation of both pupils even in the setting of Horner’s if the third-order neuron is intact. If, however, the pathology affects the carotid artery and therefore the third-order neuron, no dilation is seen. Horner’s syndrome in the setting of neurotologic disease is frequently seen as part of Wallenberg’s lateral medullary plate syndrome, as discussed later.

EVALUATION History As in all other areas of medicine, a detailed history can often provide clues to a specific diagnosis. In the case of diplopia, it is clearly important to distinguish local effects from intracranial pathology. A prior history of thyroid disease or trauma, and certainly the occurrence of increasing proptosis or globe displacement, suggests a local cause for the misalignment. A progressive neoplastic or inflammatory process affecting the cavernous sinus region should be considered, especially with a prior history of facial pain or numbness. Complaints of decreased hearing, associated with diplopia on ipsilateral gaze, raise the question of Gradenigo’s syndrome. In an older patient, this would require exclusion of nasopharyngeal carcinoma. The unusual complaint of tilt in the environment strongly suggests involvement of the otolith pathways and the vestibular system.116 When combined with Horner’s syndrome, a lateral medullary plate syndrome may be suspected. Vertical oscillopsia involving one eye raises the possibility of superior oblique myokymia.117 Oscillopsia in general suggests an acquired disorder of ocular motility most commonly associated with pathology of the vestibular pathways. When exacerbated by any head movement, severe bilateral vestibular dysfunction may be suspected. A prior history of aminoglycoside therapy is often elicited.38,118 Oscillopsia may also occur in association with other disorders of spontaneous ocular motility. Opsoclonus represents a condition in which spontaneous conjugate irregular movements occur in all directions without an intersaccadic latency characteristic of nystagmus.119 This is felt to represent pathology affecting the pause cells within the brainstem120 and may be seen with various toxic and inflammatory causes. In a young patient, the possibility of neuroblastoma should be investigated,121 and in the older age group,

paraneoplastic syndrome with autoantibodies to cerebellar tissue should be suspected.122 When confined to the horizontal, rapid eye movements without intersaccadic latency are referred to as ocular flutter. Patients with this symptom have a pathophysiology similar to opsoclonus. In the young adult group, demyelinating disease is a strong possibility. If nystagmus is observed, it is most important to establish whether it is acquired or congenital. Old ophthalmic records can be very useful. As mentioned, it would be highly unlikely for congenital nystagmus to be associated with vertigo or oscillopsia. On the other hand, these patients may have problems with blurred vision, particularly when looking in a certain direction. Patients can discover their own null point, and a prior history of head posturing suggests a problem of long duration. Details from the patient’s history that suggest specific disease processes include exacerbation of vertigo and blurred vision with change in posture or head position (BPPV) or with straining, sneezing, or laughing (perilymph fistula or Arnold-Chiari malformation).

Examination The second part of the evaluation involves accurate observation of the visual system. A neuro-ophthalmic examination is appropriate for any patient who complains of oscillopsia, blurred vision, or diplopia. Complete evaluation includes a detailed exam of both the afferent and efferent visual systems. Although the incidence of afferent visual pathology is far lower in neurotologic disease, it is important to document the patient’s best corrected visual acuity, the lack of an afferent pupillary defect, and the normality of visual fields. Patients should always be checked wearing their appropriate glasses or lens prescription. When it is impossible to do a complete refraction, a pinhole acuity test may indicate that reduction in vision is related to an uncorrected refractive cause. In patients with complaints of oscillopsia, visual acuity should be assessed with the head at rest and in motion. The patient is asked to read a Snellen chart, first with the head stationary, then with the head randomly rotated about the visual axis by the examiner. A drop of four lines or more in visual acuity with motion indicates a problem with the VOR. The fundus should be carefully checked for evidence of increased intracranial pressure, optic atrophy, hemorrhages, exudate, or nerve fiber bundle dropout. Vascular sheathing or cotton wool spots may be a clue of a microvasculopathy or a systemic vasculitis. Any degree of head posturing should be noted; old photographs may be of help in this regard. A head turn may indicate a long-standing problem either with restriction or with a paretic lateral rectus muscle. Similarly, a head tilt may indicate a congenital fourth nerve palsy, compensated for by tilting the head away from the side of the lesion. The efferent system remains of paramount concern. The initial portion of the examination of the efferent system is to ensure that the eyes are stable in primary position. Subtle low-amplitude nystagmus may be overlooked on direct examination, but is often brought out by the use of Frenzel glasses that both illuminate and magnify the globe. If these are not available, a simple means of picking up subtle ocular instability is to examine the disc with the direct ophthalmoscope after the patient’s eyes

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have been dilated.123 Although microsquarewave refixation movements are always present in normals, even extremely low amplitude nystagmus (less than 0.5 degree in excursion) may be readily appreciated with the direct ophthalmoscope. If nystagmus is present in the primary position, it is essential to observe the direction of both the slow and the fast phases to characterize the amplitude and velocity and to ensure no change takes place over time. As mentioned earlier, it is important to distinguish among horizontal, vertical, oblique, and torsional components. When both a vertical and a horizontal component are present, the nystagmoid movements may be either in phase, resulting in oblique nystagmus, or out of phase, resulting in circular or elliptical nystagmus (often occurring in the setting of demyelinating disease124). Several provocative stimuli should be employed to see if nystagmus can be induced. These include positional changes (Hallpike’s maneuvers) when BPPV is suspected, as outlined in other chapters. When an inner ear fistula is suspected, the Valsalva maneuver, a loud noise, or pneumatic otoscopy may result in change in the ocular drift. Subtle abnormalities in the normal VOR may be detected by rotating the patient’s head around an ocular axis in the dark while monitoring the optic disc with a direct ophthalmoscope.123 If the VOR is entirely normal, the disc will remain stationary. If the gain is greater than 1, the disc will drift in the direction of the head rotation; if the gain is less than 1, the drift will be in the opposite direction. Even after adaptation, abnormalities in the peripheral vestibular system may be detected by having patients rapidly shake their heads horizontally and then open their eyes.125,126 Examining the patient with a direct ophthalmoscope in the dark will indicate subtle drift of the eyes. This will occur if asymmetrical involvement of the vestibular system is present with the eyes drifting toward the side of the affected peripheral vestibular system, even if habituation has led to stability of the eyes when not stimulated. Having established the patient’s stability in primary position, the effect of change in gaze position should be sought. Evidence of centripetal drift with eccentric saccades suggests an abnormality in eccentric gaze position holding, most likely related to abnormalities in the neural integrator. This may be isolated only to the horizontal, but usually occurs in all directions. Attention should also be directed to the effect of eccentric gaze into all nine cardinal positions on nystagmus already noted to be present. Alexander’s law holds that in most forms of nystagmus, the amplitude and possibly the velocity will be exacerbated when the eye looks in the direction of the fast phase.127 If a patient’s nystagmus changes as gaze direction is altered, notation should be made of a possible null point where the nystagmus is least apparent. Often a change in the torsional component occurs as the patient looks either up or down, as well as eccentrically. This may represent relative involvement of the utricular connections. It certainly suggests some variety of vestibular involvement. As mentioned earlier, it is common to find downbeat but not upbeat nystagmus exacerbated by lateral gaze. Although it is sometimes possible to judge the waveform of the slow velocity by simple observation, particularly with Frenzel glasses, detailed evaluation requires ocular motor recording. This could be done most simply with video recording

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and slow-motion analysis. Much better data may be obtained through the use of electronystagmography, in which an electro-oculogram (EOG) signal is generated by placing electrodes on either side of the eye. This gives a largely linear signal that corresponds to ocular position. Absolute numbers require suitable calibration, but relatively detailed data are possible. Simultaneously, vertical eye movements may be studied in a similar fashion with electrodes placed above and below the eye. A somewhat more sophisticated approach to ocular motor recording is the use of infrared (IR) tracking. This requires specialized equipment, but gives an even more detailed and linear recording of ocular motility. Unfortunately, it is not good for recording vertical movements because of problems with lid occlusion. In addition, most systems available will not track with the lids closed and therefore will suffer multiple interruptions with normal blink frequency. Nonetheless, it is still a simple, noncontact means of obtaining extremely accurate recordings. Earlier systems were fixed, requiring the use of a reinforced head fixation device or bite bar. More recent IR systems use detectors mounted on spectacles. Currently, the gold standard in ocular motor recording is that of the magnetic search coil. Placement of a fine copper coil within a contact lens on the surface of the eye will yield a signal linearly related to the position of the globe when the patient’s head is placed within a uniform magnetic field. Extremely detailed recordings are thus possible not only of horizontal and vertical movements, but also of torsional movements, when a specially designed double coil is used. By combining an eye coil with a coil placed on the patient’s head, both eye and head movements as well as eye in space movements may be studied accurately. Because of the equipment involved, as well as the need for placing the contact lenses directly on the eye, this testing remains largely a research tool in certain academic centers. Fortunately, this degree of precision is usually not necessary to distinguish the various forms of nystagmus discussed. The problem of ocular misalignment may be examined by measuring the relative displacement of the two visual axes with loose or bar prisms. By simply alternating fixation occlusion and adding prism until any movement of redress is abolished, a good measurement of ocular misalignment may be obtained in the primary position and in all nine cardinal positions of gaze. When the deviation is equal in all nine positions it is said to be comitant. Although this usually represents long-standing or congenital strabismus, paretic (ocular motor disorders), restrictive (most frequently seen with thyroid disease or following trauma), or even the rare causes of primary extraocular muscle overaction may progress to increasingly comitant deviations with time. This so-called spread of comitance probably represents the ocular motor system’s plasticity in separately adjusting individual gain. With cross cover testing, any tendency for the eyes to deviate (phoria) is measured along with the manifest deviation (tropia). Any system that dissociates the two eyes will also permit phorias to become manifest. The difference between the tropia (actual deviation) and the phoria is referred to as the fusional vergence. Fusional amplitudes are much greater in the horizontal than the vertical and also greater for convergence than for divergence.

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Increased vertical fusional amplitudes suggest an extremely long-standing deviation such as that seen with a congenital fourth nerve palsy. Vergence amplitudes are affected by generalized health. Fatigue, stress, alcohol, and various drugs may substantially reduce the fusional vergence possible and result in the development of a tropia in the place of a previously compensated phoria. The simplest means of dissociating the visual axes is with a red glass placed over one eye. The patient then reports the separation between the red and white spots, seen when a flashlight is directed toward the patient’s eyes. This may produce both a horizontal and vertical component. A Maddox rod consisting of a set of parallel small half cylinders is more dissociative. When looking at light through a Maddox rod a line is seen running perpendicular to the orientation of the half cylinders. Therefore the rod is placed horizontally if a horizontal deviation is suspected or vertically if there is a problem with vertical separation. In the usual situation both are done with the flashlight briskly moved through all nine cardinal positions. Although this can be made more quantitative by placing prisms in front of one eye, usually the deviation is simply estimated by the patient. By identifying the field where maximal separation occurs, one can frequently identify the paretic (or restricted) muscles. Although using a Maddox rod requires more time than a red glass (needs to be done both for horizontal and vertical separation), breaking down the deviation into a horizontal and vertical component actually makes analysis easier and therefore is in many ways preferred. Dissociation of the visual axes may be obtained with higher technical approaches (amblyoscope, Maddox wing, etc.), although these offer little advantage over the combination of Maddox rod and cross-cover prism testing. An exception, the Lancaster red-green test or Hess screen, however, does offer one additional advantage. This test will not only identify the area of maximal deviation, but will give a hardcopy recording so that the patient’s deviation may be compared over time. Thus one can determine whether the problems with ocular alignment are progressing or improving. One additional useful technique is assessment of the area of binocular single vision. This is usually done on a Goldmann perimeter and makes use of a size III test object. The patient has both eyes opened and the machine is centered on the bridge of the nose. By indicating when two objects are visible instead of one, areas of diplopia can be identified. This is a very useful functional test because it gives the investigator an immediate idea of the direction of the patient’s visual gaze that will not result in double vision. This also can be followed over time.

SPECIFIC DISEASE PROCESSES Many neurotologic disease processes will have neuroophthalmic manifestations. Without attempting to duplicate what exists in other chapters, we can briefly outline those processes. It is most convenient to separate them into ones that involve the end organ (semicircular canals, utricle, saccule, and their nerves) and ones that involve the central vestibular pathways and connections. Inflammatory,

infectious, neoplastic, compressive, traumatic, toxic, degenerative, vascular, and idiopathic pathologies are all possible. The end organs are most commonly affected by ototoxins such as aminoglycosides; idiopathic or degenerative processes, such as Ménière’s disease and BPPV; inflammatory conditions; trauma; and vascular disease. The neural pathways are frequently affected by tumors of the cerebellopontine angle, including acoustic neurinomas, meningiomas, epidermoids, and metastatic disease.128–132 Inflammation (e.g., meningitis) may affect the eighth nerve directly. The labyrinth or the eighth cranial nerve may be injured in the petrous bone secondary to basilar skull fracture or shearing forces.133,134 Ectatic vessels or aneurysms in the posterior fossa may secondarily exert a mass effect directly on the eighth cranial nerve. Demyelinating disease usually affects the central vestibular connections, but may also result in peripheral cranial nerve involvement. Microvasculopathy and ischemic changes are possible, particularly in the elderly vasculopathic patient. They may or may not be associated with more systemic involvement, such as polyarteritis, allergic vasculitis, or giant-cell arteritis (a disease almost exclusively of the elderly). Vascular changes may also be induced by inadvertent embolization of the vascular supply during interventional neuroradiologic procedures. Prior damage of any kind to the vestibular nerve makes it more susceptible to dysfunction associated with change in pH and calcium concentration. This may be brought out clinically by hyperventilation. The central vestibular system and its cerebellar connections may similarly be affected by a myriad of pathophysiologic processes. The same tumors that affect the peripheral vestibular nerve in the cerebellopontine angle may also compress the brainstem, resulting in central vestibular pathology. In addition, primary intra-axial tumors, such as gliomas, ependymomas, and medulloblastomas135 in young patients may produce central vestibular dysfunction.136,137 Metastatic disease is uncommon. Unusual tumors, including hemangioblastomas,138 hemangiomas,139 and germ cell line tumors, may also present with neurotologic signs. Arteriovenous malformation may produce a mass effect, but also may cause local irritating phenomena or other effects when associated with a bleed. Compromise of the vascular supply to the lateral portion of the medulla (usually the posterior inferior cerebellar artery) produces the so-called lateral medullary plate syndrome of Wallenberg.140 In this syndrome, torsional nystagmus141 is often combined with a skew deviation94 and an associated ipsilateral Horner’s syndrome. An almost unique complaint in these patients is the perception of the world being tilted by 90 or 180 degrees.116 An additional finding is ipsilateral pulsion of saccades142 in contradistinction to the lateropulsion seen with infarction in the territory of the superior cerebellar artery.143–145 Certain inflammatory lesions may affect both the vestibular system and the efferent visual pathways. The inflammatory process may be idiopathic, as with systemic lupus erythematosus and nonspecific neuronitis,146 or it may be related to a specific infectious agent, such as the herpes viruses,147 HIV, various gram-positive and gramnegative bacteria, mycobacteria, or syphilis.148,149 Inflammatory lesions may be due to local contiguous spread or to

Neuro-Ophthalmic Manifestations of Neurotologic Disease

embolic phenomena associated with subacute bacterial endocarditis. An uncommon form of involvement, particularly in patients who are immunosuppressed, is that of the gram-positive rod, Listeria. A peculiar syndrome referred to as rhombencephalitis results from an abscess in the area of the connection between the cerebellum and the lower brainstem. These patients often present with motility disturbance, diplopia, and various auditory and vestibular complaints. In patients who are immunosuppressed secondary to HIV infection, parasitic infections may also occur in an abscess form. Toxoplasmosis represents a common form of intracranial posterior fossa pathology that may produce a myriad of visual as well as neurotologic symptoms. A gaze palsy is frequently the consequence of involvement of the horizontal or vertical gaze centers (pons or midbrain). These may go unnoticed unless they are also associated with involvement of the ocular motor nerves. If there is pure gaze palsy, there is no disconjugate eye movement, and therefore the patient may not have diplopia and may be unaware of other problems. The patient may note that he or she has to turn the head more often and may describe the problem as visual “blurring.” Toxins, including inadvertent poisoning and routine medications, can affect the central vestibular system. Lithium taken as an antidepressant medication, for example, can potentially cause downbeat nystagmus.150,151 Nicotine can produce upbeat nystagmus,69 but this is latent unless fixation is abolished. Alcohol may produce abnormalities in the neural integrator as well as a direct decrease in the vestibular gain.48 Hydrocarbon solvents have been increasingly recognized as toxic to the central vestibular system.152–155 Patients complain of unsteadiness and difficulty coordinating eye movements, not of vertigo. The most common objective abnormality is loss of VOR cancellation. It has been hypothesized that solvents act acutely by blocking the inhibitory neurotransmitter GABA; long-term solvent exposure may actually cause loss of neurons.156 Anatomic abnormalities, either developmental or degenerative, may result in pathology at the cervical medullary junction. One of the more common causes of central vestibular pathology is the Arnold-Chiari malformation.79,157 This may be combined with abnormalities in the skull base, leading to basilar invagination and secondary external compression. Associated pursuit deficit often occurs, indicating intra-axial pathology as well. This is particularly true of an Arnold-Chiari malformation that may be associated with central cord and brainstem diastasis, referred to as a syrinx.158 An additional potential source of mass effect would be an enlarged or ectatic vertebrobasilar artery system. This may act as a compressive lesion or lead to vascular compromise. Other vertebrobasilar disease may be on the basis of atherosclerosis, embolic phenomena, or dissection. Although most dissections in the posterior fossa originate where the vertebral artery penetrates the dura, dissection can specifically involve the intracranial vertebral arteries or the basilar artery itself. The posterior inferior cerebellar artery branching from the distil vertebral artery is commonly involved. One of the more common causes of acquired vestibular dysfunction in the young adult patient is demyelinating

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disease.159 White matter plaques can affect any of the vestibular pathways and connections, producing a plethora of findings. Degenerative disease that includes cerebellar and olivopontocerebellar degeneration160 may produce various degrees of abnormalities affecting both the vestibular system and the efferent visual pathways.56,161,162 Paraneoplastic syndrome is most frequently seen with small cell carcinoma, but has also been reported with carcinoma of the ovaries and breast, and occasionally with gastrointestinal tumors. This often produces opsoclonus or flutter, but may also underlie downbeat nystagmus or various problems with vestibular gain.163 Metabolic depletion syndromes may also affect central vestibular function. These include Wernicke’s encephalopathy,164,165 B12 deficiency, and magnesium depletion.166

CONCLUSIONS The vestibular system is the primary input for tonic activity to the extraocular muscles. Any abnormality within the peripheral or central vestibular systems is likely to produce both static and dynamic abnormalities in ocular position. This can be manifested symptomatically as diplopia and less commonly as oscillopsia. It may be discovered on clinical testing as nystagmus, skew deviation, or other forms of ocular misalignment. A detailed neuro-ophthalmic examination is likely to add substantial information about the location of pathology affecting the vestibular and neurotologic pathways. Although high-technology detailed eye movement recording may be necessary for precise definition of waveforms, careful direct examination will often supply information adequate to produce a precise localizing diagnosis and an appropriate differential. Information obtained on clinical examination may be most helpful in directing further testing, including the selection of imaging studies and possible therapeutic intervention.

REFERENCES 1. Cohen B: Erasmus Darwin’s observations on rotation and vertigo. Hum Neurobiol 3:121–128, 1984. 2. Flourens P: Recherches Experimentales sur les Propriétés et les Fonctions du Système Nerveux dans les Animaux Vertebras. Paris, Crevot, 1824. 3. Barnes GR, Smith R: The effects on visual discrimination of image movement across the stationary retina. Aviat Space Environ Med 52(8):466–472, 1981. 4. Murphy BJ: Pattern thresholds for moving and stationary gratings during smooth eye movement. Vision Res 18:521–530, 1978. 5. Westheimer G, McKee SP: Visual acuity in the presence of retinal image motion. J Opt Soc Am A 65:847–850, 1975. 6. Wheeler SD et al: Visual acuity in the presence of retinal image motion. J Opt Soc Am A 65:847–850, 1975. 7. Carl JR et al: Short latency ocular following responses in humans. Invest Ophthalmol Vis Sci 28(Suppl):332, 1987. 8. Grossman GE et al: Frequency and velocity of rotational head perturbations during locomotion. Exp Brain Res 70:470–476, 1988. 9. Lisberger SG: The latency of pathways containing the site of motor learning in the monkey vestibulo-ocular reflex. Science 225:74–76, 1984.

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10. Maas EF et al: Behavior of human horizontal vestibuloocular reflex in response to high-acceleration stimuli. Brain Res 499:153–156, 1989. 11. Bronstein AM, Gresty MA: Short latency compensatory eye movement responses to transient linear head acceleration: A specific function of the otolith-ocular reflex. Exp Brain Res 71:406–410, 1988. 12. Collewijn H, Conijn P, Tamminga EP: Eye-head coordination in man during the pursuit of moving targets. In Lennerstrand G, Zee DS, Keller EL (eds.): Functional Basis of Ocular Motility Disorders. Pergamon Press, Oxford, 1982, pp 369–378. 13. Leigh RJ et al: Comparison of smooth pursuit and combined eye head tracking in human subjects with deficient labyrinthine function. Exp Brain Res 66:458–464, 1987. 14. Barnes GR, Eason RD: Effects of visual and non-visual mechanisms on the vestibulo-ocular reflex during pseudo-random head movements in man. J Physiol 395:383–400, 1988. 15. Robinson DA: A model of cancellation of the vestibuloocular reflex. In Lennerstrand G, Zee DS, Keller EL (eds.): Functional Basis of Ocular Motility Disorders. Oxford, Pergamon Press, 1982. 16. Tomlinson RD, Robinson DA: Is the vestibulo-ocular reflex cancelled by smooth pursuit? In Fuchs AF, Becker W (eds.): Progress in Oculomotor Research. Amsterdam, Elsevier, 1981. 17. Hoyt CS, Gelbart SS: Vertical nystagmus in infants with congenital ocular abnormalities. Ophthalmic Pediatr Genet 4:155–162, 1984. 18. Leigh RJ et al: Effect of monocular visual loss upon stability of gaze. Invest Ophthalmol Vis Sci 30:288–292, 1989. 19. Leigh RJ, Zee DS: Eye movements of the blind. Invest Ophthalmol Vis Sci 19:328–331, 1980. 20. Robinson DA: Oculomotor control signals. In Lennerstrand F, Bachy-Rita P (eds.): Basic Mechanisms of Ocular Motility and Their Clinical Implications. Oxford, Pergamon Press, 1975. 21. Cannon SC, Robinson DA: Loss of the neural integrator of the oculomotor system from brain stem lesions in monkey. J Neurophysiol 5:1383–1409, 1987. 22. Lorente de No R: Vestibulo-ocular reflex arc. Arch Neurol Psychiat 30:245–291, 1933. 23. McCrea RA, Strassman A, Highstein SM: Anatomical and physiological characteristics of vestibular neurons mediating the vertical vestibulo-ocular reflexes of the squirrel monkey. J Comp Neurol 264:571–594, 1987. 24. McCrea RA et al: Anatomical and physiological characteristics of vestibular neurons mediating the horizontal vestibulo-ocular reflex of the squirrel monkey. J Comp Neurol 264:547–570, 1987. 25. Bronstein AM et al: Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. I. Abducens palsy. J Neurol Neurosurg Psychiat 53:194–199, 1990. 26. Nakada T, Remier MP: Primary position upbeat nystagmus. Another central vestibular nystagmus? J Clin Neuroophthalmol 1:185–189, 1981. 27. Yamamoto M, Shimoyama I, Highstein SM: Vestibular nucleus neurons relaying excitation from the anterior canal to the oculomotor nucleus. Brain Res 148:31–42, 1978. 28. Baloh RW, Jacobson K, Honrubia V: Idiopathic bilateral vestibulopathy. Neurology 39:272–275, 1989. 29. Fernandez C, Goldberg JM: Physiology of peripheral neurons innervation otolith organs of the squirrel monkey. III. Response dynamics. J Neurophysiol 39:996–1008, 1976. 30. Curthoys IS: Eye movements produced by utricular and saccular stimulation. Aviat Space Environ Med 58(Suppl):A192–A197, 1987. 31. Nathanson M, Bergman PS, Bender MB: Monocular nystagmus. Am J Ophthalmol 40:685–692, 1955. 32. Ranalli PJ, Sharpe JA: Vertical vestibulo-ocular reflex, smooth pursuit and eye-head tracking dysfunction in internuclear ophthalmoplegia. Brain 111:1299–1317, 1988. 33. Keane JR: Ocular skew deviation. Analysis of 100 cases. Arch Neurol 32:185–190, 1975. 34. Keane JR: Alternating skew deviation: 47 patients. Neurology 35:725–728, 1985.

35. Gresty MA, Hess K, Leech J: Disorders of the vestibulo-ocular reflex producing oscillopsia and mechanisms compensating for loss of labyrinthine function. Brain 100:693–716, 1977. 36. Bender MB: Oscillopsia, Arch Neurol 13:204–213, 1965. 37. Leigh RJ et al: Oscillopsia, retinal image stabilization and congenital nystagmus. Invest Ophthalmol Vis Sci 29:279–282, 1988. 38. JC: Living without a balancing mechanism. N Engl J Med 246:458–460, 1952. 39. Wist ER, Brandt T, Krafczyk S: Oscillopsia and retinal slip. Evidence supporting a clinical test. Brain 106:153–168, 1983. 40. Gradenigo G: A special syndrome of endocranial otitic complications (paralysis of the motor oculi externus of otitic origin). Ann Otol Rhinol Laryngol 13:637, 1904. 41. Yamashita J et al: Abducens nerve palsy as an initial symptom of trigeminal schwannoma. J Neurol Neurosurg Psychiat 40: 1190–1197, 1977. 42. Baloh RW: Pathologic nystagmus: A classification based on electro-oculographic recordings. Bull Los Angeles Neurol Sci 41:120–141, 1976. 43. Hotson JR: Convergence-initiated voluntary flutter: A normal intrinsic capability in man. Brain Res 294:299–304, 1984. 44. Schuknecht HF: Cupulolithiasis. Arch Otolaryngol 90:765–778, 1969. 45. Schuknecht HE, Ruby RRF: Cupulolithiasis. Adv Otorhinolaryngol 20:434–443, 1973. 46. Baloh RW, Honrubia V, Jacobson K: Benign positional vertigo: Clinical and oculographic features in 240 cases. Neurology 37:371–378, 1987. 47. Lessell S, Wolf PA, Chronley D: Prolonged vertical nystagmus after pentobarbital sodium administration. Am J Ophthalmol 80:151–152, 1975. 48. Kattah JC et al: Oculomotor manifestations of acute alcohol intoxication. In Smith JL, Katz RS (eds.): Neuro-ophthalmology Enters the Nineties. Hialeah, FL, Duton Press, 1988, pp 233–243. 49. Robinson DA: The effect of cerebellectomy on the cat’s vestibuloocular integrator. Brain Res 71:195–207, 1974. 50. Waespe W et al: Role of the flocculus and paraflocculus in optokinetic nystagmus and visual-vestibular interactions: Effects of lesions. Exp Brain Res 50:9–33, 1983. 51. Westheimer G, Blair SM: Oculomotor defects in cerebellectomized monkeys. Invest Ophthalmol 12:618–621, 1973. 52. Zee DS et al: Effects of ablation of flocculus and paraflocculus on eye movements in primate. J Neurophysiol 46:878–899, 1981. 53. Herishanu Y, Osimand A, Louzoun Z: Unidirectional gaze paretic nystagmus induced by phenytoin intoxication. Am J Ophthalmol 94:122–123, 1982. 54. Rashbass C: Barbiturate nystagmus and mechanics of visual fixation. Nature 183:897–898, 1959. 55. Reulen JPH, Sanders EACM, Hogenhuis LAH: Eye movement disorders in multiple sclerosis and optic neuritis. Brain 106:121–140, 1983. 56. Zee DS et al: Ocular motor abnormalities in hereditary cerebellar ataxia. Brain 99:207–234, 1976. 57. Baloh RW et al: Cerebellar-pontine angle tumors. Arch Neurol 33:507–512, 1976. 58. Baloh RW et al: Cerebellar-pontine angle tumors. Arch Neurol 33:507–512, 1976. 59. Nedzelski JM: Cerebellopontine angle tumors: Bilateral flocculus compression as a cause of associated oculomotor abnormalities. Laryngoscope 93:1251–1260, 1983. 60. Abadi RV, Dickinson CM: Waveform characteristics in congenital nystagmus. Doc Ophthalmol 64:153–167, 1986. 61. Dell’Osso LF, Daroff RB: Congenital nystagmus waveforms and foveation strategy. Doc Ophthalmol 39:155–182, 1975. 62. Furman JM, Stoyanoff S, Barber HO: Head and eye movements in congenital nystagmus. Otolaryngol Head Neck Surg 92:656–661, 1984. 63. Dickinson CM: The elucidation and use of the effect of near fixation in congenital nystagmus. Ophthalmic Physiol Opt 6:303–311, 1986.

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64. Robinson DA et al: Alexander’s law: Its behavior and origin in the human vestibulo-ocular reflex. Ann Neurol 16:714–722, 1984. 65. Abadi R, Pascal E: The recognition and management of albinism. Ophthalmic Physiol Opt 9:3–15, 1989. 66. Collewijn H, Apkarian P, Spekreijse H: The oculomotor behavior of human albinos. Brain 108:1–28, 1985. 67. Simon JW et al: Albinotic characteristics in congenital nystagmus. Am J Ophthalmol 97:320–327, 1984. 68. Noseworthy JH et al: Torsional nystagmus: quantitative features and possible pathogenesis. Neurology 38:992–994, 1988. 69. Sibony PA, Evinger C, Manning KA: Tobacco induced primary position upbeat nystagmus. Ann Neurol 21:53–58, 1987. 70. Dejong JMBV et al: Midsagittal pontomedullary brain stem section: Effects on ocular adduction and nystagmus. Exp Neurol 68:420–442, 1980. 71. Bronstein AM et al: Down beating nystagmus: Magnetic resonance imaging and neuro-otological findings. J Neurol Sci 81:173–184, 1987. 72. Chambers BR, Ell JJ, Gresty MA: Case of downbeat nystagmus influenced by otolith stimulation. Ann Neurol 13:204–207, 1983. 73. Halmagyi GM et al: Downbeating nystagmus. A review of 62 cases. Arch Neurol 40:777–784, 1983. 74. Spooner JW, Baloh RW: Arnold-Chiari malformation. Improvement in eye movements after surgical treatment. Brain 104:51–60, 1981. 75. Yee RD et al: Episodic vertical oscillopsia and downbeat nystagmus in a Chiari malformation. Arch Ophthalmol 102:723–725, 1984. 76. Baloh RW, Yee RD: Spontaneous vertical nystagmus. Rev Neurol 145:527–532, 1989. 77. Alpert JN: Downbeat nystagmus due to anticonvulsant toxicity. Ann Neurol 4:471–473, 1978. 78. Berger JR, Kovacs AG: Downbeat nystagmus with phenytoin. J Clin Neuro-ophthalmol 2:209–211, 1982. 79. Baloh RW, Spooner JW: Downbeat nystagmus: A type of central vestibular nystagmus. Neurology 31:304, 1981. 80. Nozaki S, Mukuno K, Ishikawa S: Internuclear ophthalmoplegia associated with ipsilateral down-beat nystagmus and contralateral incyclorotatory nystagmus. Ophthalmologica 187:210–216, 1983. 81. Daroff RB, Troost BT: Upbeat nystagmus. JAMA 225:312, 1973. 82. Fisher A et al: Primary position upbeat nystagmus: a variety of central positional nystagmus. Brain 106:949–964, 1983. 83. Fisher A et al: Primary position upbeating nystagmus. A variety of central positional nystagmus. Brain 106:949–964, 1983. 84. Gilman N, Baloh RW, Tomiyasu U: Primary position upbeat nystagmus. A clinicopathologic study. Neurology 27:294–298, 1977. 85. Keane JR, Itabashi HH: Upbeat nystagmus: clinico-pathologic study of two patients. Neurology 37:491–494, 1987. 86. Ranalli PJ, Sharpe JA: Upbeat nystagmus and the ventral tegmental pathway of the upward vestibulo-ocular reflex. Neurology 38:1329–1330, 1988. 87. Ito M, Nisimaru N, Yamamota M: Specific patterns of neuronal connections involved in the control of the rabbit’s vestibuloocular reflexes by the cerebellar flocculus. J Physiol 265:833–854, 1977. 88. Elliot AJ et al: Nystagmus after medulloblastoma. Dev Med Child Neurol 31:43–46, 1989. 89. Kato I et al: Primary position upbeat nystagmus. Localizing value. Arch Neurol 42:819–821, 1985. 90. Troost BT et al: Upbeat nystagmus and internuclear ophthalmoplegia with brainstem glioma. Arch Neurol 37:453–456, 1980. 91. Daroff RB: See-saw nystagmus. Neurology 15:874–877, 1965. 92. Drachman DA: See-saw nystagmus. J Neurol Neurosurg Psychiat 29:356–361, 1966. 93. Mastaglia FlL: See-saw nystagmus: An unusual sign of brain-stem infarction. J Neurol Sci 22:439–443, 1974. 94. Brandt T, Dieterich M: Pathological eye-head coordination in roll: Tonic ocular tilt reaction in mesencephalic and medullary lesions. Brain 110:649–666, 1987.

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95. Halmagyi GM, Gresty MA, Gibson WPR: Ocular tilt reaction with peripheral vestibular lesion. Ann Neurol 6:80–83, 1979. 96. Kanter DS et al: See-saw nystagmus and brainstem infarction. MRI findings. Neuroophthalmol 7:279–283, 1987. 97. Suzuki JI, Tokumasu K, Goto K: Eye movements from single utricular nerve stimulation. Acta Otolaryngol 68:350–362, 1969. 98. Druckman R et al: See-saw nystagmus. Arch Ophthalmol 76: 668–675, 1966. 99. Baloh RW, Yee RD, Honrubia V: Internuclear ophthalmoplegia: I. Saccades and dissociated nystagmus. Arch Neurol 35:484–489, 1978. 100. Cogan DG: Internuclear ophthalmoplegia, typical and atypical. Arch Ophthalmol 84:583–589, 1970. 101. Muri RM, Meienberg O: The clinical spectrum of internuclear ophthalmoplegia in multiple sclerosis. Arch Neurol 42:851–855, 1985. 102. Furman JM, Wall C III, Pang DL: Vestibular function in periodic alternating nystagmus. Brain 113:1425–1439, 1990. 103. Leigh RJ, Robinson DA, Zee DS: A hypothetical explanation for periodic alternating nystagmus: Instability in the optokineticvestibular system. Ann N Y Acad Sci 374:619–635, 1981. 104. Dibartolomeo JR, Yee RD: Periodic alternating nystagmus. Otolaryngol Head Neck Surg 99:552–557, 1988. 105. Keane JR: Periodic alternating nystagmus with downward beating nystagmus. A clinicoanatomical case study of multiple sclerosis. Arch Neurol 30:399–402, 1974. 106. Kennard C et al: The association of periodic alternating nystagmus with periodic alternating gaze. J Clin Neuro Ophthalmol 1: 191–193, 1981. 107. Waespe W, Cohen B, Raphan T: Dynamic modification of the vestibulo-ocular reflex by the nodulus and uvula. Science 228: 199–202, 1985. 108. Halmagyi GM et al: Treatment of periodic alternating nystagmus. Ann Neurol 8:609–611, 1980. 109. Barratt HJ, Hood JD: Transfer of optokinetic activity to vestibular nystagmus. Acta Otolaryngol 105:318–327, 1988. 110. Cohen B et al: Velocity storage, nystagmus, and visual-vestibular interactions in humans. Ann N Y Acad Sci 374:421–433, 1981. 111. Abel LA et al: Endpoint nystagmus. Invest Ophthalmol Vis Sci 17:539–544, 1978. 112. Shallo-Hoffmann J et al: A reexamination of end-point and rebound nystagmus in normals. Invest Ophthalmol Vis Sci 31: 388–392, 1990. 113. Corbett JJ et al: Visual loss in pseudotumor cerebri: Fifty-seven patients followed 5 to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol 39:461–474, 1982. 114. Cogan DG: Syndrome of non-syphilitic interstitial keratitis and vestibulo-auditory symptoms. Arch Ophthalmol 33:144–149, 1945. 115. Cogan DG: Nonsyphilitic keratitis with vestibuloauditory symptoms. Arch Ophthalmol 43:42–49, 1949. 116. Hörnsten G: Wallenberg’s syndrome. Part II. Oculomotor and oculostatic disturbances. Acta Neurol Scand 50:447–468, 1974. 117. Hoyt WF, Keane JR: Superior oblique myokymia: Report and discussion on five cases of benign intermittent uniocular microtremor. Arch Ophthalmol 84:461–467, 1970. 118. Hybels RL: Drug toxicity of the inner ear. Med Clin North Am 63:309–319, 1979. 119. Smith JL, Walsh FB: Opsoclonus-ataxic conjugate movements of the eyes. Arch Ophthalmol 64:244–250, 1960. 120. Zee DS, Robinson DA: A hypothetical explanation of saccadic oscillations. Ann Neurol 5:405–414, 1979. 121. Solomon GE, Chutorian AM: Opsoclonus and occult neuroblastoma. N Engl J Med 279:475–477, 1968. 122. Anderson NE et al: Opsoclonus, myoclonus, ataxia, and encephalopathy in adults with cancer: A distinct paraneoplastic syndrome. Medicine 67:100–109, 1988. 123. Zee DS: Ophthalmoscopy in examination of patients with vestibular disorders. Ann Neurol 3:373–374, 1978.

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124. Aschoff JC, Conrad B, Kornhuber HH: Acquired pendular nystagmus with oscillopsia in multiple sclerosis: A sign of cerebellar nuclei disease. J Neurol Neurosurg Psychiat 37:570–577, 1974. 125. Hain TC, Fetter M, Zee DS: Head-shaking nystagmus in patients with unilateral peripheral vestibular lesions. Am J Otol 8:36–47, 1987. 126. Takahashi S et al: The clinical significance of head-shaking nystagmus in the dizzy patient. Acta Otolaryngol 109:8–14, 1990. 127. Robinson DA et al: Alexander’s law: Its behavior and origin in the human vestibulo-ocular reflex. Ann Neurol 16:714–722, 1984. 128. Brackmann DE, Bartels LJ: Rare tumors of the cerebellopontine angle. Otolaryngol Head Neck Surg 88:555–559, 1980. 129. Gherini SG et al: Cholesterol granuloma of the petrous apex. Laryngoscope 95:659–664, 1985. 130. Granick MS et al: Cerebellopontine angle meningiomas: Clinical manifestations and diagnosis. Ann Otol Rhinol Laryngol 94:34–38, 1985. 131. Keville FJ, Wise BL: Intracranial epidermoid and dermoid tumors. J Neurosurg 16:564–569, 1959. 132. Schuknecht H et al: Pathology of secondary malignant tumors of the temporal bone. Ann Otol Rhinol Laryngol 77:5–22, 1968. 133. Cannon CR, Jahrsdoerfer RA: Temporal bone fractures: Review of 90 cases. Arch Otolaryngol 109:285–288, 1983. 134. Schuknecht H, Davison R: Deafness and vertigo from head injury. Arch Otolaryngol 63:513–528, 1956. 135. Watson P et al: Positional vertigo and nystagmus of central origin. Can J Neurol Sci 8:133–137, 1981. 136. Pobereskin L, Treip C: Adult medulloblastoma. J Neurol Neurosurg Psychiat 49:39–42, 1986. 137. White HH: Brain stem tumors occurring in adults. Neurology 13: 292–300, 1963. 138. Tognetti F et al: Haemangioblastoma of the brain stem. Neurochirurgia 29:230–234, 1986. 139. Sundaresan N, Eller T, Ciric I: Hemangiomas of the internal auditory canal. Surg Neurol 6:119–121, 1976. 140. Fisher CM et al: Lateral medullary infarction-the pattern of vascular occlusion. J Neuropath Exp Neurol 20:223–279, 1961. 141. Morrow MJ, Sharpe JA: Torsional nystagmus in the lateral medullary syndrome. Ann Neurol 24:390–398, 1988. 142. Meyer KT et al: Ocular lateropulsion. A sign of lateral medullary disease. Arch Ophthalmol 98:1614–1616, 1980. 143. Benjamin EE, Zimmerman CF, Troost BT: Lateropulsion and upbeat nystagmus are manifestations of central vestibular dysfunction. Arch Neurol 43:962–964, 1986. 144. Ranalli PJ, Sharpe JA: Contrapulsion of saccades and ipsilateral ataxia: A unilateral disorder of the rostral cerebellum. Ann Neurol 20:311–316, 1986. 145. Uno A et al: Lateropulsion in Wallenberg’s syndrome and contrapulsion in the proximal type of the superior cerebellar artery syndrome. J Neuroophthalmol 9:75–80, 1989.

146. Schuknecht HE: Neurolabyrinthitis. Viral infections of the peripheral auditory and vestibular systems. In Nomura Y (ed.): Hearing Loss and Dizziness. Tokyo, IgakuShoin, 1985. 147. Zajtchuk J et al: Temporal bone pathology in herpes oticulus. Ann Otol Rhinol Laryngol 81:331–338, 1972. 148. Karmody C, Schuknecht H: Deafness in congenital syphilis. Arch Otolaryngol 83:18–27, 1966. 149. Saltiel P et al: Sensorineural deafness in early acquired syphilis. Can J Neurol Sci 10:114–116, 1983. 150. Corbett JJ et al: Downbeating nystagmus and other ocular motor defects caused by lithium toxicity. Neurology 39:481–487, 1989. 151. Halmagyi GM et al: Lithium-induced downbeat nystagmus. Am J Ophthalmol 107:664–670, 1989. 152. Hodgson MJ et al: Encephalopathy and vestibulopathy following short-term hydrocarbon exposure. J Occup Med 31:51–54, 1989. 153. Larsby B et al: Effects of trichloroethylene on the human vestibulooculomotor system. Acta Otolaryngol 101:193–199, 1986. 154. Lazar RB et al: Multifocal central nervous system damage caused by toluene abuse. Neurology 33:1337–1340, 1983. 155. Rosenberg NL et al: Toluene abuse causes diffuse central nervous system white matter changes. Ann Neurol 23:611–614, 1988. 156. Moller C et al: Otoneurological findings in psychoorganic syndrome caused by industrial solvent exposure. Acta Otolaryngol 107:5–12, 1989. 157. Banerji NK, Millar JHD: Chiari malformation presenting in adult life. Brain 97:157–168, 1974. 158. Thrush DC, Foster JB: An analysis of nystagmus in 100 consecutive patients with communicating syringomyelia. J Neurol Sci 20:381–386, 1973. 159. Grenman R: Involvement of the audiovestibular system in multiple sclerosis: An otoneurologic and audiologic study. Acta Otolaryngol 420(Suppl):1–95, 1985. 160. Wadia NH: A variety of olivopontocerebellar atrophy distinguished by slow eye movements and peripheral neuropathy. In Duvoisin RC, Plaitakis A (eds.): The Olivopontocerebellar Atrophies. New York, Raven Press, 1984, pp 149–177. 161. Barber HO, Stoyanoff S: Vertical nystagmus in routine caloric testing. Otolaryngol Head Neck Surg 5:574–580, 1986. 162. Berciano J: Olivopontocerebellar atrophy––a review of 117 cases. J Neurol Sci 53:253–272, 1982. 163. Anderson NE, Rosenblum MK, Posner JB: Paraneoplastic cerebellar degeneration: Clinical-immunological correlations. Ann Neurol 24:559–567, 1988. 164. Furman JMR, Backer JT: Vestibular responses in Wernicke’s encephalopathy. Ann Neurol 26:669–674, 1989. 165. Victor M et al: The Wernicke-Korsakoff Syndrome. Philadelphia, FA Davis, 1971. 166. Saul R, Selhorst JB: Downbeat nystagmus with magnesium depletion. Arch Neurol 38:650–652, 1981.

14

Outline Introduction Otolith Organ Dysfunction Otolith-Ocular Reflexes Otolith Anatomy Otolith Symptoms Testing Otolith Function Superior Semicircular Canal Dehiscence Syndrome Pathology Symptoms Etiology of Symptoms Examination and Testing Treatment Labyrinthine Hemorrhage Otic Barotrauma

Chapter

Otolith Dysfunction and Semicircular Canal Dysfunction

Air Travel Underwater Diving Hearing Loss Etiology Treatment Options Decompression Sickness Labyrinthitis Viral Serous Suppurative Perilymph Fistula Pathogenesis Symptoms Diagnosis and Testing Management Congenital Perilymph Fistula

Post-Traumatic Vertigo Eighth Nerve Trauma Labyrinthine Concussion Post-Traumatic BPPV Post-Traumatic Endolymphatic Hydrops Luetic Vestibulopathies Ototoxicity Aminoglycosides Loop Diuretics Salicylates Cisplatin Diagnosis Management

INTRODUCTION This chapter is concerned with the less common etiologies of peripheral vertigo. Emphasis is on the understanding and definitions of these conditions, although it will be necessary to include some of the evaluation and treatment of these conditions to explain these entities. Although many technologic advances have occurred in the field of neurotology, the history remains the most important part of the evaluation of a patient complaining of dizziness. A complete history should include a patient’s description of the character of the dizziness, time course, precipitating factors, associated symptoms, and predisposing factors. Following a thorough history, a complete otoneurologic examination should be performed. The diagnostic evaluation and management differ markedly depending on the category of dizziness; therefore, it is critical that the examining physician determine the type of dizziness before proceeding with exhaustive diagnostic studies. It is crucial that the clinician be available to reexamine the patient when the symptoms are present to confirm the diagnosis. Only with this approach can appropriate therapeutic plans be instituted to treat the patient.

OTOLITH ORGAN DYSFUNCTION Otolith-Ocular Reflexes The otolith organs elicit eye movements provoked by static head tilt as well as during periods of acceleration. As the

Vincent B. Ostrowski, MD Dennis I. Bojrab, MD

human head tilts from side to side, the otoliths provide a compensatory ocular torsion or ocular counterrolling. Otoliths also provide compensatory ocular torsion as the head tilts forwards and backwards. Human ocular roll or tilt is inefficient with a maximum torsion of about 5 to 6 degrees or a gain of about 0.1.1 Linear stimulation is the strongest stimulation to the otolith organs. Acceleration along the interaural axis causes a compensatory horizontal eye movement, whereas acceleration in the occipital nasal axis does not induce horizontal eye movements.2 The purpose of the reflex is to enhance visual pursuit during linear displacement of the head. Most natural head movements are a combination of linear and angular displacements. In contrast to the semicircular canals, the otolith organs sense change in linear velocity, or acceleration, and sense static changes of the head with regard to the gravitational vector. In contrast, the semicircular canals sense angular acceleration. As the canals mediate compensatory reflexes for head rotation, the otoliths are responsible for otolith ocular reflex eye movements (OOR), which compensate for linear components of head motion. The function of the otolithic organs is to perceive gravity, linear acceleration, and centrifugal force. The utricle detects both translations and tilt in the lateral, fore, aft, and side-to-side directions. The saccule senses the pull of gravity, as well as up and down and fore and aft translations of the head. The canal and otolith ocular reflexes must work in unison to permit stable ocular fixation. Only one functioning otolith set is needed to maintain a normal OOR. In patients with bilateral vestibulopathy, 241

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the OOR may be absent or hypoactive patients with unilateral loss have a normal OOR.3 In combined linear and angular acceleration, the velocity of the eye adjustments is too fast to be visually directed. The ocular system uses a rapid, nonvisual estimate of current target location relative to the head by combining available visual, auditory, and proprioceptive information.4 The velocity storage feedback pathways in the central vestibulo-ocular reflex (VOR) provides a key mechanism for otolith canal interactions.5,6

Otolith Anatomy The utricle and saccule are two individual structures contained within the vestibule. The utricle belongs to the pars superior of the inner ear, and the saccule belongs to the pars inferior of the inner ear. The otoliths contain endolymph and are surrounded by perilymph. The endolymph of the utricle has five paths of egress: the utricular duct joining to the endolymphatic duct, the saccular duct joining the utricle to the saccule, and ducts joining to each semicircular canal. The vestibular aqueduct or the endolymphatic duct joins the utricle to the endolymphatic sac.7 The saccule communicates with the endolymphatic duct by the saccular duct and with the cochlear duct by the ductus reuniens. The utricle and saccular sensory neuroepithelium is the macula. The utricular macula is 2.2 by 2.2 mm and the saccular macula is 2.4 by 1.3 mm.7 Hair cells of the otoliths have cilia embedded in a gelatin layer. On the surface of

the gelatin layer are the calcium carbonate otoconial crystals or otoliths. Otoconia are produced by the macular supporting cells and after fracturing and becoming dislodged from the macula are absorbed by the dark cells.8 Linear displacement of the otoconial-gelatinous layer stimulates the afferent nerves of the otoliths, allowing linear movement detection. (See Fig. 14-1.) The maculae are at a 90-degree angle to one another. The utricle is a curved structure roughly parallel to the lateral canal and the macula of the saccule is a curved structure in a parasagittal plane.9 The horizontal portion of the macula is tilted back and down by 25 degrees and laterally upward by about 10 degrees. A small anterior portion of the utricular macula is curved upward. The saccular macula is oriented almost at right angles to the utricle. Within each macula, the sensory hair cells (HCs) are morphologically oriented in opposite directions on either side of, and at right angles to, a central line of demarcation named the striola. Kinocilia are directed away from the striola in the saccule and toward the striola in the utricle. In the striolae, the otolithic layer of the utricle is thinnest and that of the saccule is the thickest. Both maculae contain HC orientation vectors in all directions. Striolae have more type I HCs and are innervated by thicker axons, conducting at greater velocities. The otoconia inertia causes their relative displacement in a direction opposite to an imposed linear acceleration. With both maculae nonplanar and both striolae curved, the hair cell activation patterns are complex. Detailed examination of the pathways from the otolithic maculae to

Figure 14-1. Three-dimensional spatial orientation of the inner ear with its associated otolith organs. Inset shows detail of the utricle and saccule.

Otolith Dysfunction and Semicircular Canal Dysfunction

the eye muscles is much more difficult than it is for the canals because the macular nerves carry information about all conceivable directions of movement. Gross stimulation of the whole utricular nerve causes torsional movements of the eyes with intorsion of the ipsilateral eye and extorsion of the contralateral eye. The ipsilateral eye elevates and adducts and the contralateral eye depresses and abducts.

Otolith Symptoms Symptoms of otolithic dysfunction have not been widely described in the otolaryngologic literature. Practitioners may not be familiar with the symptoms of otolithic dysfunction and thus cannot easily or confidently attribute symptoms to a diagnosis. Patients may present with symptoms suggestive of a vestibular disorder but without the typical signs of vestibular disease such as spontaneous nystagmus and asymmetrical rotational and deranged caloric responses. Patients may complain of a sensation of linear motion such as rocking or that the ground is moving up and down. Feelings of falling or actual falls, lateropulsion sensations, or inability to align things horizontally or vertically are also possible complaints. Potential etiologies of otolith dysfunction are numerous. (See Fig. 14-2.) Benign paroxysmal positional vertigo has been linked to dislodged otoconia from an otolith macula causing stimulation of the cupula of the semicircular canal, most commonly the posterior canal. This may be related to a post-traumatic event to the head that caused otoconia to separate from the macula.10 Otoconia could theoretically be released from a vascular insult to the otolith, freeing the crystals. Also, dysfunction of the dark cells, thought to be responsible for otoconia resorption, could lead to an excess of freed otoconia. Symptoms can arise not only from the free otoconia causing stimulation of the semicircular canals but also from the resultant asymmetric loading between right and left maculae after otoconia are dislodged. Patients with endolymphatic hydrops or Ménière’s disease may receive pathologic stimulation of the otoliths.11 Deformation or pressure changes in the membranous labyrinth may result in pushing or pulling forces on the maculae, giving the patient sensations of linear, vertical, or

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rocking motions while symptomatic. Sudden changes in endolymphatic fluid pressure with inappropriate otolith stimulation have also been proposed as a source of vestibular drop attacks, or Tumarkin crisis. Sudden otolithic stimulation may elicit a reflex-like vestibulospinal loss of postural tone.12 Additionally, post-traumatic forms of imbalance have been linked to otolithic stimulation. A sudden shearing force applied to the head can be severe enough to shear to otoconia from the macula. This may lead to unequal tone between the right and left otoliths, resulting in asymmetric vestibular input to the brain.13 Barotrauma or surgical trauma has been associated with perilymphatic fistula formation and pathologic otolith stimulation.14 Rocking vertigo and imbalance with sneezing, coughing, or straining can be associated with leakage of perilymph fluid. This may be secondary to stapes subluxation onto the otolith or otolith movement with leakage of the surrounding perilymph. Observations have also been made where the membranous lining of the vestibule pulls away from the bony walls and lies directly on the otolith organ. This vestibular atelectasis may then become a mechanical link between the undersurface of the footplate and the membrane of the otolith organ.15 A similar mechanism has been proposed as the etiology behind the otolith: Tullio’s phenomenon, in which the patient may experience paroxysms of head tilt, ocular torsion, and tilting of the visual surround with certain tonal stimulation.14,16,17 Unilateral vestibular loss results in asymmetric otolith function. In the weeks following the loss, there is a progressive recovery of the asymmetrical response, suggesting that otolith symptoms recover after vestibular damage, just as some static canal symptoms recover. There is likely a process of otolithic compensation as well as one of canal compensation.18

Testing Otolith Function Direct testing of otolith function is difficult and currently requires a specialized testing environment. The contributions of the otoliths to the vestibulo-ocular reflex can be classified into several categories:19 (1) compensation for translational components of head motion, (2) compensation

Figure 14-2. Multiple pathologic states can arise from a variety of etiologies that affect the otoliths.

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for rotational components of head motion when the axis of rotation is directed away from the pull of gravity (offvertical axis rotation), and (3) compensation for static tilt of the head or ocular counterroll. Gresty and colleagues were the first to use off-vertical axis rotation or eccentric yaw rotation to assess otolith function.20 The subject is seated in a rotational chair and leaning forward such that the head is anterior to the vertical axis of rotation (off-axis or eccentric rotation). These tests stimulate both the otoliths and the horizontal canals. Translational testing is able to test only the otolith functions and can be performed on a linear sled, cart, or parallel swing. This testing requires specialized equipment and currently does not lend itself well to office testing. With a tonic lateral head tilt, the eyes counterroll, presumably as part of a normal attempt to align the horizontal meridian of the retina with the horizon. Spontaneous ocular tilt reactions presumably reflect otolith, particularly utricular, imbalance. The ocular tilt reaction (OTR) has also been associated with both midbrain and peripheral lesions.21–23 OTR is part of the expected compensatory postural reaction to an unexpected lateral tilt of the body. The otolith response of OTR consists of a vertical ocular skew deviation, ocular counterroll, and head tilt. The alternate cover test can aid the detection of skew deviation. A vertical corrective eye movement on switching a cover from one eye to the other eye can detect a vertical misalignment. With peripheral and vestibular nucleus lesions, the lower eye is on the side of the lesion. The otolith ocular pathway crosses at the level of the vestibular nuclei, so that with lesions above the decussation, the higher eye is on the side of the lesion.24 In a peripheral lesion, the eye on the side of the head tilted toward the ground has a downward vertical deviation and the eye opposite the side tilted toward the ground has an upward vertical deviation. Also, the superior pole of the eye on the side of the head tilted toward the ground extorts while the superior pole of the eye opposite the side tilted toward the ground intorts. The head usually tilts toward the side of the lesion with peripheral labyrinthine and lateral medullary lesions.19 Utricular function can be assessed in the office using the subjective vertical visual (SVV) test. The SVV is a measure of otolith and especially utricular function. Bilateral otolith inputs provide humans with their dominant perception of gravity. A patient sits with the head fixed in the upright position and looks forward at an illuminated line in darkness. The patient adjusts the line from various starting positions to his or her SVV. This is repeated 10 times for each eye. With acute peripheral vestibular lesions including the utricles, there is an ipsilateral deviation of the SVV of about 10 to 15 degrees.25,26 Patients with otolithic dysfunction, however, are not the only patients who have difficulty with the SVV test. Patients with acute unilateral brainstem infarctions may also exhibit pathologic tilts of static SVV from the true vertical.27 The SVV test is simple and cost effective; however, it lacks specificity at this time—it shows positive results with both vestibular and nonvestibular mechanisms. Clinically, patients must be queried about vertical diplopia, tilting of their visual surround, and sound or pressure triggers to their imbalance. In such patients, examination must

include looking for head tilt, skew deviation, and elicitation of these symptoms or signs on application of pressure or sound to the offending ear. Signs of otolith dysfunction can be observed as a tonic (constant) OTR and skew deviation in the settings of perilymphatic fistula, stapes hypermobility or subluxation, acute labyrinthine loss, or posterior fossa lesion.28 These patients may have pressure sensitivity or Tullio’s phenomenon.29 Certain tones may provoke a tonic OTR or skew deviation in patients with utricular imbalance known as Tullio’s phenomenon.30 Separately, these tests may not be specific to otolith dysfunction; however, combinations of tests should increase overall specificity, sensitivity, and reliability. It remains to be shown whether isolated unilateral deficits of otolith function, that is, otolithic defects in the presence of normal semicircular canal functions, and partial deficits of otolith function can be detected with these tests. It is difficult to develop a clinical test for patients suspected of suffering from otolith dysfunction when there is an absence of an adequate criterion reference group of patients with proved, isolated, complete or partial, unilateral deficits only of otolith function. Another obstacle to testing isolated otolith function is the convergence of otolith and semicircular canal inputs on secondary vestibular neurons in the vestibular nuclei.31

SUPERIOR SEMICIRCULAR CANAL DEHISCENCE SYNDROME Pathology Dehiscence of the superior semicircular canal is an entity first described by Minor and colleagues in 1998.32 In these patients the bony covering between the top of the superior semicircular canal and the middle cranial fossa is missing. (See Fig. 14-3.) This can be spontaneous or presumably congenital. The most likely explanation of patient symptoms of imbalance is that the superior canal dehiscence creates a mobile third window to the inner ear. With this third mobile window, the endolymphatic system has an increased compliance. Pressure or sound creates a pressure differential across the ampulla, which in turn allows the canal ampulla to be responsive to changes in inner ear pressure associated with sound stimulation. Superior canal dehiscence is rare, arising in 0.5% of temporal bones in a temporal bone survey or 0.7% of individuals. The condition is often bilateral. Also, an additional 1.4% of temporal bones have a very thin bony covering (smaller than 0.1 mm) such that they might appear dehiscent on high-resolution CT scan of the temporal bone.33

Symptoms Patients with superior semicircular canal dehiscence (SCD) may experience vertigo, tilting of their visual surround, and nystagmus without skew deviation when pressure changes occur in the external auditory canal, the middle ear, or the intracranial space.34 Also, these patients may experience imbalance and nystagmus with applications of certain tones or sounds to the ear, or Tullio’s phenomenon.35

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Figure 14-3. A coronal view, highresolution, CT scan of the temporal bone demonstrating a dehiscence of the right superior semicircular canal.

Etiology of Symptoms Patients may experience sensitivity to pressure or certain tones applied to the external ear canal. The origin of the nystagmus in patients with SCD has been determined. From Ewald’s first law, one would expect eye movement directed in the plane of the affected canal. Vector analysis of the elicited nystagmus during stimulation has mapped the source of the nystagmus to the superior semicircular canal in patients with SCD.35,36 The axis of evoked nystagmus in the superior canal dehiscence syndrome aligns with the plane of the affected superior canal, indicating that the response originates mainly from that canal. The chinchilla has been used as an animal model of SCD.37 Fenestration of the superior semicircular canal produced an increase in superior canal afferents after positive pressure in the external canal and a decrease in firing with negative pressure. Responses could be ablated by rigidly repairing the dehiscence. The ocular movements elicited on tests were initially thought to be results of possible utricular stimulation. Although appropriate stimulation of the utricle could produce ocular torsion with horizontal eye movement, and stimulation of the saccule could produce vertical eye movement, one would expect a tonic response with otolith stimulation rather than the phasic-torsional nystagmus responses that are observed.29,35,36 The evoked eye movements in patients with SCD syndrome arise from the superior canal, not the utricle. In some patients, vertigo is elicited by sound applied to the ear. Tullio’s phenomenon is the combination of vertigo and abnormal eye and/or head movements provoked by sound. This vestibular response to sound was first described by Tullio, who studied fistulized labyrinths of pigeons in 1926.38 Two possible sources of Tullio’s phenomenon have been put forth: otolithic and semicircular canal stimulation.39,40 Tullio’s phenomenon has been associated with Ménière’s syndrome,39 congenital inner ear anomalies,41

infectious etiologies such as syphilis and chronic ear pathology,40 trauma,42 perilymphatic fistula,43 and iatrogenic fistulae, that is, fenestration surgery.44

Examination and Testing A keen examiner must inquire about pressure sensitivity symptoms as well as sensitivity to certain sounds or tones. A patient with pressure sensitivity or Tullio’s phenomenon warrants consideration for SCD. During testing, the patient’s vision must be controlled to eliminate visual fixation during the exam. This can be accomplished with Frenzel lens testing, examination in the dark with infrared video oculography, or scleral search coil. If the patient is allowed visual fixation, nystagmus will likely be suppressed and abnormalities not appreciated. Patients will present with vertical-torsional eye movements consistent with activation of the superior semicircular canal. A high index of suspicion is needed to differentiate SCD from perilymphatic fistula (PLF). Detailed imaging and careful observation of eye movements during exam aids in the diagnosis. Highresolution CT scan of the temporal bone is needed to show a superior canal dehiscence.

Treatment For symptomatic patients, middle fossa craniotomy may be needed to allow plugging of the canal or resurfacing of the dehiscence. Imbalance symptoms are improved or eliminated after surgery.45 Animal models of SCD have shown that rigid repair of the dehiscence eliminates symptoms better than soft-tissue patch repair.46 If the trigger of vertigo is sound, avoidance of the offending tone may be all that is needed. If pressure sensitivity is the trigger, a trial with a simple ventilation tube may be beneficial to eliminate the pressure differential across the tympanic membrane.

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This, however, would not alleviate symptoms caused by intracranial pressure fluctuations.

LABYRINTHINE HEMORRHAGE A rare but notable condition described more recently in the literature is vertigo associated with spontaneous hemorrhage into the vestibule, labyrinth, and cochlea. This condition has been described in the radiology literature in patients with a history of sickle cell anemia. Patients can present with sudden onset of vertigo, sensorineural hearing loss, and pathologic findings on magnetic resonance imaging (MRI). High signal intensity can be seen on T1-weighted images without contrast in the vestibule and labyrinth. Patients present spontaneously similarly to a sickle cell crisis. Sickling of red blood cells causes capillary occlusion with resultant ischemia that may lead to spontaneous bleeding.47 This may be secondary to injury to the capillary vascular bed. Labyrinthine hemorrhage has been described in conjunction with leukemia and thrombocytopenia,48,49 aplastic anemia,50 leukemoid reactions of malignant neoplasms, and in the setting of DIC.51 As a group, these case reports have a uniformly poor prognosis of regaining vestibular or cochlear function after hemorrhage. An MR screening examination consisting of either a high-resolution T2-weighted sequence or a contrast-enhanced T1-weighted sequence will not by itself accurately diagnose hemorrhage. Noncontrast, thinsection, T1-weighted MR images are the study of choice for diagnosing intralabyrinthine hemorrhage.1,47

OTIC BAROTRAUMA Barotrauma can be defined as tissue damage resulting from a change in gas pressure present in a closed space. The air-filled spaces of the middle ear and mastoid constitute a closed volume if the eustachian tube is malfunctioning. Using the universal gas law, PV/T = PV/T, as ambient pressure varies, the pressure within a closed volume must also change. When the normal communications between the air-filled spaces and the environment are blocked, pressure cannot equilibrate. This pressure differential causes tissue injury. The usual mechanisms include underwater diving, flying or air travel, blunt head trauma, and hyperbaric oxygen therapy. A sudden change in ambient pressure is the common denominator.

Air Travel As a pressure reference, sea level is 1 atmosphere (ATM), 18,000 feet of altitude is 1/2 ATM. During ascent in an aircraft, air pressure decreases at an approximate rate of 15 mm Hg every 400 feet of altitude. During descent, relative air pressure increases. “Pressurization” in an aircraft is a relative term and not all aircraft are equal. A typical airliner may be pressurized to 8.5 psi, which translates into a “sea-level” cabin up to 16,000 feet but a 7,000-foot cabin altitude when the aircraft is at 40,000 feet. Overall, pressurization reduces but will not eliminate the risk of barotrauma. Air usually flows passively from the middle ear on ascent; however, on descent the eustachian tube must be actively

opened to equilibrate pressure. One usually experiences otalgia when a pressure differential across the tympanic membrane exceeds 60 mm Hg and the eustachian tube “locks” at 90 mm Hg. To rupture the tympanic membrane (TM), 100 mm Hg to 500 mm Hg is needed.52 Goodhill’s “implosive” and “explosive” mechanisms for ear trauma are applicable.53 Implosive ear trauma is caused by an acute increase in middle ear pressure or ossicular pressure forcing the stapes footplate into the vestibule. Explosive ear trauma is caused by either an increase in cerebrospinal fluid (CSF) pressure or forceful Valsalva’s maneuver, resulting in an increase in intracochlear pressure and possible rupture of a round or oval window.

Underwater Diving Otolaryngologic barotrauma is most common with diving. Pain and damage usually occur during descent (middle ear squeeze) due to the inability or failure to equalize pressure. Symptoms include facial, tooth, or ear pain; sudden hearing loss; vertigo; tinnitus; or fullness. Otologic findings include petechial hemorrhages, blebs in the EAC, serous effusion, TM retraction, conductive or sometimes a sensorineural hearing loss, and TM rupture. As a pressure reference, sea level is 1 ATM, 33 feet below sea level is 2 ATM, and 150 feet below sea level is 3 ATM. Farmer described a grading system for middle ear barotrauma: type I is middle ear fullness, pain, but normal otoscopy; type II is pain, hearing loss, TM erythema, effusion, and hemotympanum; and type III is TM perforation.54

Hearing Loss Etiology Hearing loss can be either conductive or sensorineural. Conductive etiologies include serous effusions, hemotympanum, ossicular disruption, and tympanic membrane perforation. Neural loss etiologies include gas embolus in the cochlea, labyrinthine membrane tear, intracochlear hemorrhage, and perilymphatic fistula.55,56 Hearing prognosis from intracochlear hemorrhage is poor due to the resultant fibrosis. Prognosis for return of hearing is excellent if the patient presents only with auditory symptoms.57

Treatment Options To prevent or avoid barotrauma, several conservative and preventive measures can be performed. These may include no flying within 24 hours of diving, staying awake on airplane descent, yawning, swallowing, and maintaining good control of allergies. Pressure relief measures are also available. Self-politzerization involves pinching the nose, closing the mouth, and gently exhaling to force air back into the middle ear or sinuses. The Toynbee maneuver involves pinching the nose, closing the mouth, and swallowing to increase nasopharynx pressure. Last, the Frenzel maneuver involves contracting the muscles of the floor of the mouth and nasopharynx with the mouth closed. Medications can also provide benefit to the patient. Oxymetazoline HCl and pseudoephedrine taken 1 to 2 days before a flight might provide some degree of decongestion and vasoconstriction. A myringotomy with or without a tube is indicated in refractory conditions as long as

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a nasopharyngeal mass is ruled out. A middle ear exploration may be needed if severe cochleovestibular symptoms are present.

of the organ of Corti, tectorial membrane, and stria vascularis. These findings are similar to the histopathologic studies of patients with mumps and measles.

Decompression Sickness

Serous

Decompression sickness (DCS) occurs when the surrounding atmospheric pressure decreases too rapidly. As the atmospheric pressure decreases, the nitrogen-carrying capacity of the blood decreases. If the atmospheric pressure decreases too rapidly, the excess nitrogen coming out of solution from the blood will not be able to be excreted by the lungs quickly enough. DCS arises when nitrogen bubbles form in the blood. The body tries to rid nitrogen faster than the lungs can exchange it with the environment. Type I DCS includes musculoskeletal pain and cramping, cutaneous modeling, skin discoloration, and joint pain. Type II DCS includes severe, emergent symptoms.58 Neurologic signs include deafness, vertigo, loss of vision, paraplegia, and in some cases cardiopulmonary shock. Factors potentiating DCS include unpressurized altitudes above 25,000 feet, long duration at altitude, a rapid ascent (either flying or diving), and flying within 24 hours of diving. To reduce the risk of DCS, one can ascend from a dive slowly with decompression stops and use pressurized aircraft when flying. “Prebreathing” pure oxygen for 30 minutes before a deep dive or high-altitude flight makes a nitrogen diffusion gradient so as to reduce the overall volume of nitrogen in tissues. Mixing helium with oxygen instead of nitrogen for deep dives reduces the risk of nitrogen bubbles forming in the bloodstream. Type I DCS treatment includes 100% oxygen and observation with the expectation that symptoms will resolve in a matter of hours. Type II DCS treatment necessitates a hyperbaric oxygen chamber with recompression to 3 ATM greater than when the symptoms started. Transport to the hyperbaric oxygen (HBO) facility should be at no greater than 800 to 1000 feet above ground level or in a pressurized transport.59

Serous labyrinthitis is a sterile inflammatory condition of the inner ear, induced by chemical or toxic irritation of the membranous labyrinth. This may occur from acute or chronic otitis, or from trauma or surgery. Patients typically develop mild to moderate vertigo with nystagmus directed toward the affected ear. Mild to moderate, temporary or permanent, sensorineural hearing loss is common especially in the high-frequency range nearest to the oval window and presumed proximity to toxins in the middle ear.

LABYRINTHITIS Viral Viral labyrinthitis is the most common form of membranous labyrinthitis seen in clinical practice. It may complicate the course of systemic viral infections such as measles, mumps, influenza, and chickenpox. Viral labyrinthitis may also occur in the absence of systemic viral disease. The initial symptoms are severe vertigo exacerbated by head movement. When associated with systemic viral infection, patients often develop a sensorineural hearing loss. The hearing loss may be transient but is more often permanent. Early examination usually reveals an irritative nystagmus toward the affected ear. The vestibular symptoms usually improve in 48 to 72 hours but may take weeks to resolve. Lingering episodes of dysequilibrium or unsteadiness may follow the acute episode for a variable time depending on the patient’s physical activity level and other factors that affect compensation. Histopathologic study of the temporal bones of such patients has shown the principal changes to consist of atrophy

Suppurative Suppurative labyrinthitis occurs when pyogenic bacteria enter the inner ear. This may occur in acute or chronic otitis media with or without cholesteatoma, meningitis, or rarely, in systemic bacterial infections. Iatrogenic fistula during middle ear surgery may also result in suppurative labyrinthitis. Patients are often violently ill with fever, severe vertigo, and profound hearing loss. The route of meningitic spread is via the cochlear aqueduct to the scala tympani and is usually bilateral. Ossification of the cochlea may ensue within weeks to months after recovery of meningitis, necessitating prompt consideration of and cochlear implantation if warranted. Nystagmus is directed away from the affected ear and the patient falls and past points to the affected side. In suspected cases of fistula, caloric investigation is contraindicated because it may spread the infection by intralabyrinthine fluid.60 The combined vestibular and auditory loss is usually permanent. Fortunately, suppurative labyrinthitis is rare in the antibiotic era. Treatment of the vestibular symptoms in all forms of labyrinthitis involves use of vestibular suppressant medications for the acute attack and vestibular rehabilitation to enhance compensation as soon as practical after the acute stage has passed. If no contraindications exist, high-dose steroids may be given for a viral labyrinthitis. Parenteral antibiotics will likely be needed for patients with a suppurative labyrinthitis.

PERILYMPH FISTULA A perilymphatic fistula (PLF) is an abnormal connection between the inner and middle ear due to a defect in the labyrinthine bone or in the round or oval windows. Such fistulas cause sudden or fluctuating sensory hearing loss and dizziness. There are various causes of perilymphatic fistula including both acquired and, more rarely, congenital causes. Acquired PLF may arise secondary to erosive cholesteatoma, syphilitic gummas, benign or malignant neoplasm, or traumatic and iatrogenic etiologies. Congenital PLF may be present with or without cranial anomalies. The existence of other causes that do not involve the labyrinthine bone but involve one of its windows is not well accepted by all surgeons. The reason for this is that there is no clear method of determining the diagnosis preoperatively, and

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even surgical exploration often depends on subjective interpretation of the findings.

Pathogenesis The arguments of Goodhill53 regarding the “implosive and explosive” etiology of perilymph fistula and those of Simmons61 regarding an alternate lesion causing the same symptoms have received the most attention, and both have supporting experimental findings. Goodhill theorized that sudden or severe changes in middle ear pressure, via the eustachian tube, could direct force internally toward the inner ear, causing rupture of the oval window or round window seals (implosive route). Autoinsufflation of the eustachian tubes may cause fistula by this mechanism. Blunt head trauma including whiplash and even low-velocity head trauma can result in PLF.62 Acoustic trauma or external atmospheric pressure, which causes relatively large displacement of the tympanic membrane, may also cause fistula by this mechanism, according to Goodhill. Similarly, force could be directed externally toward the inner ear by increased CSF pressure, via the cochlear aqueduct or internal auditory canal (explosive route). Physical exertion such as lifting weights, coughing, and sneezing could cause fistula this way. In humans, we know that a patent cochlear aqueduct can exist and that the largest volume displacement of perilymph occurs at relatively low-pressure changes.63 Furthermore, round window ruptures have been documented after barotraumatic events such as scuba diving.64,65 Just prior to Goodhill’s presentation on the theory of labyrinthine window rupture, Simmons had presented an alternative theory for sudden sensorineural hearing loss. His theory suggested the CSF pressure changes are transmitted to the labyrinth, which result in intracochlear membrane breaks, and the subsequent mixing of endolymph and perilymph causes the symptoms.61 This theory was based on earlier experimental evidence in cats showing intralabyrinthine membrane rupture and deafness.64

Symptoms The classic symptoms of perilymph fistulas are sudden severe sensorineural hearing loss, vertigo, and tinnitus. Several of the early reports emphasized sudden sensory hearing loss as the presenting symptom of perilymph fistula, particularly seen related with a history of physical exertion. Further experience has shown that many patients actually complain of fluctuating hearing loss.64,65 As such, the symptoms of perilymph fistula can often be identical to those of Ménière’s disease. The severity of the hearing loss bears no relationship to the extent of the perilymph leakage, nor does it help predict the likelihood of finding a perilymph fistula. In some, PLF symptoms may arise immediately or within days after head trauma; however, Ménière’s type symptoms may take months to years to develop. Patients with fistula can present with vertigo, positional dizziness, or dysequilibrium. Findings of nystagmus have shown no definite pattern and have not been predictive for fistula.

Diagnosis and Testing The fistula test is the most widely used clinical test for this condition. Patients with PLF often become vertiginous

after pressurization of the external ear canal on the side of the fistula. Observing this phenomenon, the fistula test was first described by Lucae in 1881.66 It consists of registration of ocular deviation or nystagmus following pressurization of the external ear canal. There are three types of ocular response to the fistula test thought to indicate abnormality and the potential presence of fistula. The fistula sign is a nystagmus that continues for 10 to 15 seconds following application of positive or negative pressure.67,68 Hennebert’s sign is a slow conjugate horizontal ocular deviation at the onset of pressurization and a movement in the opposite direction at the end of stimulation.66,67,69 The ocular tilt reaction, described more recently, is a combined vertical and torsional movement of the eye, of rapid onset and resolution, provoked by pressure.14,70 The fistula test is used to select patients for exploratory tympanotomy in an attempt to detect and repair a PLF. However, inconsistent criteria are often used to interpret the fistula test. The fistula test as conventionally performed is insensitive for the diagnosis of PLF.71 In normal subjects, the change in nystagmus between prepressure and postpressure tests ranged from −1.3 to 0.9 degrees per second. In patients, change in nystagmus greater than the 95th percentile limits of normal was not a reliable indication of PLF.71 The test may be falsely positive in patients with Ménière’s disease and caloric testing is nonspecific. Patients with fistula present with a wide variety of hearing loss patterns, and in fact no audiometric parameter has been found to be predictive of a perilymph fistula. Accurately diagnosing a fistula remains difficult and disputed. Each surgeon must establish reasonable guidelines before considering surgical exploration of patients with dizziness. A diagnosis may be considered when a clear history of a traumatic event or other predisposing cause is documented. Furthermore, the presence of vestibular symptoms alone, with no hearing loss or tinnitus, makes the diagnosis less tenable. There is no clear evidence for the existence of spontaneous (idiopathic) perilymph fistula. In the experience of most practitioners, perilymph fistula remains a relatively uncommon cause of dizziness and hearing loss.72

Management Initial care of a patient with perilymph fistula involves conservative measures. Bed rest, head elevation at all times, avoidance of physical straining and blowing of the nose, and controlled sedation is advised for 10 days. Persistent otologic symptoms after this period, particularly with a history of recent trauma, warrant an exploratory tympanotomy for definitive diagnosis and repair of a fistula. Under local anesthesia with sedation, the surgeon can carefully expose and observe the round and oval windows. Placement of the patient in the Trendelenburg position, application of external pressure on the jugular vein, and the Valsalva maneuver will help reveal a fistula. Because labyrinthine defects are not always associated with perilymph leakage, repair at the windows is undertaken whether or not a fistula is clearly seen. Small pieces of autogenous perichondrium can be packed over the round window membrane and around the annular ligament and stapes footplate after the respective niche is scarified with a fine pick or knife. Hearing improvement after fistula repair is infrequently seen (about

Otolith Dysfunction and Semicircular Canal Dysfunction

25% of patients) but improvement in vertigo occurs in a majority of patients (60% to 80%).

Congenital Perilymph Fistula Congenital perilymph fistulas are unlike acquired perilymph fistulas in the character of the leakage and in etiology. Suspect a congenital perilymphatic fistula when progressive sensorineural or mixed hearing loss, with or without vertigo, is associated with one or more of the following: otitis media, labyrinthitis, or meningitis.73 These patients may present with CSF otorrhea or rhinorrhea and frequently have had recurrent episodes of meningitis because communications between the intracranial space and the middle ear provide an easy pathway for the spread of infection. The most common finding has been leakage from the oval window area. Anatomic anomalies of the ossicles, windows, or labyrinth are often noted.

POST-TRAUMATIC VERTIGO Eighth Nerve Trauma Blunt head trauma can cause shearing force on intracranial structures due to sudden head acceleration forces. A collision of only 8 mph can generate a 5g force on the head.74 These shearing forces can cause damage to the eighth nerve root entry zone of the brainstem. Petechial hemorrhages may be observed in the region of the vestibular nuclei.75,76 These patients may have a persistent form of imbalance that compensates poorly. This compensation is poor due to only partial damage to the end organ as well as damage to the vestibular nuclei. For compensation to be effective, one needs a normally functioning vestibular nucleus on the side of the acute loss.77 Symptoms may persist because of an incomplete unilateral loss as well as a dysfunctioning vestibular nucleus. Testing may show an acute hemorrhage on MRI. Electronystagmography (ENG) may show a unilateral caloric hypofunction. Rotary chair testing may demonstrate an asymmetry of gain during low-frequency sinusoidal harmonic acceleration testing and an increased phase lag at low frequencies. With time, the asymmetry of gain may disappear, but the increased phase lag would remain indefinitely.78,79 Treatment may include intensive vestibular physical therapy to maximize compensation. If conservative measures fail, consideration can be given to chemical or surgical labyrinthectomy or vestibular nerve section to eliminate a partially functioning vestibular system.

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Treatment resides in determining a peripheral source of the vertigo. If the vertigo persists following rehabilitation, the patient may obtain relief from a chemical or surgical labyrinthectomy or a vestibular nerve section. Before any destructive means are taken, the diagnosis must be certain, central etiologies must be ruled out, and the patient should be capable of postoperative rehabilitation to speed compensation. Ideally, the patient’s vision and proprioceptive senses are intact.

Post-Traumatic BPPV The sudden blunt force from head trauma can result in direct shearing force to the utricle. The otoconia from the otolith organ can be sheared off their gelatinous matrix into the endolymph. The patient not only will have the BPPVlike symptoms and positive Dix-Hallpike test, but also may have resultant otolith dysfunction. This otolith dysfunction may persist several weeks until new otoconia are formed and the otolith organ ad can restore the structure and function to the utricle or saccule. The examiner should be aware of this possible dual diagnosis and be keen during the history and examination to detect multiple complaints and findings that do not necessarily “fit” the classic diagnosis of BPPV.

Post-Traumatic Endolymphatic Hydrops Post-traumatic endolymphatic hydrops is an entity that presents with aural fullness, tinnitus, fluctuating sensorineural hearing, and episodes of vertigo. This presentation is very similar to that of classic Ménière’s disease. Hydrops can arise even without evidence of temporal bone fracture. Intralabyrinthine hemorrhage can theoretically cause scarring of the vestibular aqueduct and delayed symptoms that may arise months to years following the traumatic event.84–86 Treatment options are similar to those for Ménière’s disease, as described elsewhere in this text. The practitioner should also be aware of the possible risk of CNS etiology due to the trauma as well as possible bilaterality. These factors may reduce the efficacy of treatment when compared with success rates with conventional treatment of Ménière’s disease. Also, since symptoms may be similar and traumatic in etiology, traumatic perilymphatic fistula may be possible and should be considered in a patient with temporal bone fracture, pressure sensitivity, or penetrating mechanism.

Labyrinthine Concussion Following blunt head trauma, the semicircular canals can be injured even if there is no obvious temporal bone fracture. The complete pathophysiologic mechanisms of trauma are not yet fully understood. Mechanisms for labyrinthine concussion have been proposed. Sudden acceleration forces can cause shearing trauma to the vestibular end organs and disruption of the sensory epithelium.80 Labyrinthine hemorrhage may result in fibrous tissue deposition, scarring, and new bone growth.81,82 The delicate vasculature to the vestibular end organs can be disrupted by shearing forces, and small clot formation results.83

LUETIC VESTIBULOPATHIES Otologic syphilis can arise from either a congenital or an acquired infection, and symptoms may occur either early or late in the infection. It is a multisystem, multistage disease caused by infection with the spirochete, Treponema pallidum. Infection can be present with long periods of latency and late progression. Otosyphilis should be considered in any patient with unexplained vestibular symptoms. Vestibular symptoms may be the sole presentation of the infection.87 Awareness of this disease is especially relevant because of the increased

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incidence of syphilitic infections in recent years. This rise has been directly correlated to the spread of the human immunodeficiency virus (HIV).88 Congenital syphilis has two stages. The early stage results from transplacental infection from the mother. Thirty-eight to 64% of patients may be asymptomatic. Those affected may have profound hearing loss and multisystem disease.89 Late-stage congenital syphilis is disease presenting after 2 years of age. Children usually present with hearing loss with vestibular symptoms, whereas adults may present with episodes of vertigo, tinnitus, and fluctuating hearing loss. Most late-stage, congenital syphilitic patients have other physical findings including interstitial keratitis, Hutchinson’s teeth, saber shins, frontal bossing, and Clutton’s joints (painless hydrarthrosis).90 Acquired syphilis can be divided into various stages. Primary stage is evident by a painless solitary chancre on the skin. Secondary stage presents several months after the initial infection as a fever, malaise, rash, and constitutional complaints. Vestibular symptoms are usually minimal. A latent period then follows for a variable length of time, often years. Forty percent to 70% of patients do not progress beyond this phase. The remaining patients progress to tertiary syphilis. These are partitioned approximately equally between gummatous syphilis (benign late syphilis), cardiovascular syphilis, and neurosyphilis.91 Vestibular symptoms vary depending on the stage of active syphilis. In the early stage (less than 2 years after exposure) of both the congenital and the acquired forms, vestibular symptoms are rare.90,92 With late stages of syphilis, the audiovestibular symptoms are variable. Symptoms may be indistinguishable from those of Ménière’s disease.93 The patient may also demonstrate vertigo or imbalance when exposed to certain sounds or tones (Tullio’s phenomenon). The patients may demonstrate vestibular symptoms with atmospheric pressure change suggestive of a perilymphatic fistula. There may be no other “classic” syphilis findings on exam. Unsteadiness or vertigo as the initial symptom has been found in 20% to 100% of all congenital and 30% to 50% of all acquired forms of otosyphilis.93,94 Apart from episodes of vertigo, the patient may have fluctuating sensorineural hearing loss, relatively poor speech discrimination, tinnitus, and bilateral, somewhat symmetric decreased caloric responses. The signs easily mimic Ménière’s disease, perilymphatic fistula, or autoimmune hearing loss. Other diseases that must be kept in the differential diagnosis are multiple sclerosis, migraine variant, Cogan’s syndrome, Vogt-Koyanogi Harada syndrome, cerebellopontine angle masses, and vasculitic diseases. Syphilitic infection of the otic capsule starts as a mononuclear leukocyte infiltration and progresses to an obliterative endarteritis and osteitis of all three layers of the otic capsule. This results in narrowing of the endolymphatic duct and sac with resultant hydrops. Additionally, a gummatous deposit can form a perilymph fistula. Physical exam may produce a positive Hennebert’s sign or Tullio’s phenomenon. Slit-lamp exam of the cornea may reveal an interstitial keratitis in 90% of late-stage syphilis.93 ENG findings often show either unilateral or bilateral reduced vestibular response.94 Along with the appropriate cochleovestibular symptoms, the diagnosis of otosyphilis rests on a positive serum fluorescent treponemal antibody

absorption test (FTA-ABS). This test may be false-positive in autoimmune diseases and hepatic cirrhosis. Surgical treatment in the form of endolymphatic sac surgery has been found by most to be unsuccessful in alleviating symptoms.95 Failure is presumed to result from obstruction in the vestibular aqueduct proximal to the site of surgery. Linthicum and Abd El-Rahman have shown microgammas obstructing the endolymphatic duct.96 Medical treatment includes benzathine penicillin 2.4 million units intramuscularly once weekly for 3 weeks. Prednisone may be considered in the face of rapidly declining otologic function. Doxycycline 200 mg twice daily for 30 days can be used for penicillin-allergic patients. If neurosyphilis is confirmed by lumbar puncture, penicillin desensitization may have to be considered because it remains the only proved therapy for neurosyphilis.97

OTOTOXICITY Ototoxicity is “the tendency of certain therapeutic agents and other chemical substances to cause functional impairment and cellular degeneration of the tissues of the inner ear, and especially of the end organs and neurons of the cochlear and vestibular divisions of the eighth cranial nerve.”98 This entity has been recognized since the late 1800s when quinine and acetylsalicylic acid produced dizziness, tinnitus, and hearing loss. Streptomycin in the 1940s had great therapeutic potential as an antibiotic to treat tuberculosis, but the delayed ototoxic effects devastated patients and the earlier form was discontinued. Since then, other drugs have been found to have ototoxic effects, such as newer antibiotics, antineoplastic agents, and diuretics. Many reports concerning ototoxic agents must be reviewed quite carefully since the compromised patient who develops ototoxicity may have previously received other potentially ototoxic agents or actually may be receiving synchronously ototoxic agents or potentiating medications. Also, one must carefully review the condition of the patient at the time the medication is used to see if that patient may be in an oliguric state or receiving chemotherapy or radiation therapy. Patients who receive ototoxic drugs are often bedridden and suffer from multiple symptoms of systemic illness, so additional symptoms of auditory and vestibular dysfunction may be easily overlooked. Vestibular symptoms are particularly difficult to identify in this setting. Only after the patient begins to recover will the devastating effects of vestibular loss become apparent. By this time, the damage is irreversible. The examining physician must be keenly aware of the potential auditory and vestibular toxicity of any drug that is used if ototoxicity is to be prevented. Currently, there is no standard of practice as to the appropriate auditory or vestibular monitoring test to obtain or guidelines as to the frequency of any monitoring technique.

Aminoglycosides All aminoglycoside antibiotics can produce both auditory and vestibular damage. Streptomycin and gentamicin are relatively specific for the vestibular system and kanamycin,

Otolith Dysfunction and Semicircular Canal Dysfunction

tobramycin, and amikacin produce more damage to the auditory system.99,100 Aminoglycosides have bactericidal activity that results from inhibition of protein synthesis at the level of the ribosome. This class of antibiotic is used to treat serious aerobic gram-negative infections. The aminoglycosides do not undergo any significant degradation in the body and are excreted unaltered into the urinary tract by glomerular filtration. The concentration of aminoglycoside in the perilymph rises slowly, reaching its peak 2 to 5 hours after injection, at a level 3% to 5% of peak serum level. The half-life of aminoglycoside in perilymph has been reported to be from 3 to 5 hours, which permits significant accumulation of aminoglycosides.101,102 Patients with renal impairment cannot excrete the drug, so the aminoglycoside accumulates in the blood and inner ear tissues. Aminoglycosides have been shown to cause ototoxicity by several means. Outer hair cells, spiral ganglion cells, dark cells, and stria vascularis structures can all be damaged by aminoglycosides.103 Toxicity is seen at the level of the cochlear hair cell calcium channels, transduction channels at the stereocilia tips, and N-type and P/Q-type channels in the neurons in addition to uptake mechanisms and cellular actions.104 The earliest effect of the vestibulotoxic compounds such as streptomycin and gentamicin is a selective destruction of type I hair cells in the crista. Later, type II hair cells are destroyed, but the supporting cells remain unaffected. With the cochleotoxic agents such as kanamycin and amikacin, selective destruction of the outer hair cells in the basal turn of the cochlea occurs first, followed by total hair cell loss throughout the cochlea as the dose and duration of treatment are increased. Even after treatment is terminated, some of the aminoglycosides (dihydrostreptomycin, gentamicin, and tobramycin, in particular) have been shown to produce continued damage to the sensory structures of the organ of Corti. Experimentally, certain growth factors such as neurotrophin-3 can at least partially protect against aminoglycoside-induced ototoxicity. However, systemic application has been limited due to the significant amount of cell cycle mediation of nonotic cell lines.105 Brain-derived neurotrophic factor (BDNF) has also shown protective properties for the hair cells against aminoglycosides in experimental models.106 Also, studies of the NMDA excitotoxic pathway have demonstrated that antagonizing the NMDA system allows cytoprotection of vestibular hair cells and only partial loss of apical sensory hair cells in experimental studies.107 Recently, Sha and Schacht108 found that salicylates protect against gentamycin-induced ototoxicity, putatively by serving as both antioxidants and iron-chelating agents. Salicylates decreased threshold shifts and basal outer hair cell loss in the guinea pig model. Genetics of aminoglycoside ototoxicity appear to have a random or multifactorial inheritance pattern related to the ribosomal RNA gene of mitochondrial DNA.109

Loop Diuretics The two main ototoxic loop diuretics, furosemide and ethacrynic acid, act by inhibiting active resorption of chloride in the loop of Henle of the proximal renal tubule, thereby preventing the renal resorption of sodium that passively follows chloride.110 The mechanism of their

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ototoxic effect is not completely known, although these drugs clearly influence ion pumps in the kidney and in the cochlear duct. The ototoxic effects of the loop diuretics appear to be confined mostly to the cochlea, although histopathologic changes in the vestibular end organ have been documented.111 About 6% of patients who receive furosemide develop a temporary hearing loss that is nearly always reversible. Several characteristic features of loop diuretic ototoxicity are readily apparent because most patients affected have concomitant renal disease and most receive furosemide intravenously. Other case reports involve the co-administration of an ototoxic drug such as an aminoglycoside, or in fact the drug was given to an oliguric patient. Histologically, the major changes that have been observed in animal temporal bones involved the stria vascularis: intercellular edema, capillary narrowing, and degeneration of the intermediate cell layer. Degeneration of the outer hair cells, primarily of the basal turn, have also been observed, but are less common. Changes in the vestibular labyrinth have also been observed, with degeneration of both type I and type II hair cells in the ampullae and maculae.112 Clinical experience with ethacrynic acid and furosemide indicates that they may produce transient or permanent hearing loss following either oral or intravenous administration. There are certainly risk factors in their administration that have been identified. One must consider the rate of intravenous infusion, the dosage, and other potentiating medication that the patient may be receiving. The renal status is particularly important for the oliguric patient who may receive a relatively high dose intravascularly since it is not cleared effectively.

Salicylates Patients receiving high-dose salicylate therapy frequently complain of hearing loss, tinnitus, loss of balance, and occasionally of vertigo. Sensorineural hearing loss involves all frequencies and is associated with recruitment, which suggests a cochlear rather than a nervous system etiology. The tinnitus is high pitched and frequently precedes the onset of the hearing loss. Both hearing loss and tinnitus invariably occur when the plasma salicylate level approaches 0.35 mg/ml. Caloric testing often reveals bilateral depressed responses consistent with bilateral vestibular end organ damage.113 All symptoms and signs are rapidly reversible after the cessation of salicylate ingestion (usually within 24 hours). As with the aminoglycosides, salicylates are highly concentrated in the perilymph.

Cisplatin Cisplatin is commonly associated with both auditory and vestibular toxicity. It is an extremely effective drug in the treatment of patients with nonseminomatous germ cell tumors, ovarian carcinoma, and squamous cell carcinomas of the head and neck, cervix, and genitourinary tract. Cisplatin is administered intravenously. It appears to undergo basically renal excretion without metabolism in the body. The drug is frequently administered with the patient well hydrated, with mannitol being administered to protect against nephrotoxicity.

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Cisplatin effects its activity in at least two mechanisms. The first involves the blockade of ion transduction channels within the membranes of outer hair cells, producing hair cell hyperpolarization and auditory threshold elevations.114 The other mechanism of cisplatin ototoxicity involves the formation of reactive oxygen species in the cochlea. Free radicals deplete intracellular glutathione levels and alter antioxidant enzyme activity. Lipid peroxidation increases, resulting in hair cell, supporting cell, stria vascularis, and auditory nerve cell apoptosis.115 Ototoxicity induced by cisplatin has been directly related to damage within the organ of Corti. The cochlear hair cells visualized by scanning electron microscopy showed actual degeneration. The outer hair cells are more involved than the inner hair cells, as well as the basilar turns being more involved than the apical turns. Although the vestibular effects were markedly less than cochlear effects following the chemotherapy, reports have demonstrated extensive degeneration changes of the vestibular receptor organs. Cristae showed dramatic hair cell loss (type I involvement is greater than type II). Advanced neuroepithelial degeneration was also seen in the otolith organs, where there was almost total loss of otoconia as well as hair cell loss. There has also been some direct neural effects and decreased myelinization. A cytoprotective effect has been found with D-methionine in the rat model. Reduction in outer hair cell loss and reduction in auditory brainstem response (ABR) threshold shifts is evident. D-methionine may function as both a metal binder and an antioxidant.116 Feghali and colleagues have demonstrated protective effects of L-N-acetylcysteine on auditory neurons and hair cells from the toxic effects of cisplatin in vitro.117 In vivo studies have not yet been performed, and applications to prevent vestibulotoxicity have yet to be assessed. Clinically, hearing tests are performed with conventional frequencies from 250 to 8000 Hz and demonstrate that the first sign of hearing loss usually appears within 3 to 4 days of cisplatin administration. Recent studies using ultrahigh-frequency measurements indicated that substantial shifts in hearing thresholds occur initially and in some cases are restricted to frequencies above the conventional range of 8000 Hz. Wide variations in individual ototoxic susceptibility to cisplatin have been reported. Ototoxicity appears to be directly related to several factors: the method of administration (bolus versus slow infusion), the dose per treatment, and total accumulated dose. Patients older than 40 years of age, patients with previous hearing or vestibular conditions, patients with previous renal conditions, or patients in whom other ototoxic agents are used appear to be at a higher risk for the development of cisplatin ototoxicity.

Diagnosis The clinician must be constantly alert for the early detection of symptoms or signs of ototoxicity. This is particularly important in critically ill patients, bed-confined patients, or any patient who has renal impairment, particularly renal failure. Clinical bedside evaluation of these individuals becomes very important because of their limited access to a soundproof audiologic testing center or vestibular testing center. Some high-frequency hearing testing equipment is

available that may be useful in certain bedside situations. A large-scale prospective study simultaneously comparing the efficacy of conventional audiometry, high-frequency audiometry, and otoacoustic emissions in detecting ototoxicity does not yet exist.118 Assessing vestibulotoxic effects of potentially ototoxic medications is important. Identifying vestibular hypofunction early in its course prior to development of end-stage oscillopsia is the goal in ototoxic vestibular testing. Bedside vestibular testing incorporates head thrust testing and assessment of dynamic visual acuity. When fixation is inhibited, spontaneous nystagmus and positional nystagmus can be identified with the use of Frenzel glasses. One must remember to test these at-risk patients if possible so as to have a baseline for comparison. In our experience, bedside caloric evaluation is useful only in the severely vestibular ablated patient. Ambulatory patients may be assessed with quantitative caloric and rotation testing as part of the ENG examination. High-frequency rotational chair testing is ideal for identifying early vestibular ototoxic effects and is the testing method of choice in patients suspected of having a bilateral vestibular loss or those patients who have minimal remaining vestibular function. Rotational chair testing stimulates the VOR at higher frequencies (usually 2 Hz or less, some can test up to 10 Hz) than does caloric testing (0.025 Hz). Cost and availability of this testing equipment may be an issue in vestibular labs. Head autorotation testing, which relies on voluntary head movements by the patient, tests the VOR at 2 to 6 Hz. Head velocity is recorded using a velocity sensor attached to a special helmet. Cost is usually low and the unit is portable. Autorotation testing has not yet gained wide clinical appeal secondary to issues of test-retest reliability and need for standardization of tests.119 Also, self-generated predictable head movement paradigms, such as head autorotation testing, are less accurate than passive (examiner-initiated) head thrust testing. The patient controlling his or her own head movements can preprogram expected eye movement strategies and thus artificially augment an otherwise deficient VOR and compensate for a planned or anticipated head movement. Tests using passive high-acceleration head thrusts delivered unpredictably in time and direction should be more sensitive for discerning VOR hypofunction than tests using active and predictable stimuli.120

Management The key to the management of ototoxicity is prevention. Kidney function should be measured before beginning a potentially ototoxic drug. Drug levels are not necessarily predictive of ototoxicity risk. Patients in high-risk groups should be monitored with periodic auditory and vestibular testing, although the standard of measurement has not been established. When the earliest detection of ototoxicity is detected, adjustments in the dosage schedule often can reduce the degree or likelihood of symptom progression. Sometimes drugs with fewer ototoxic effects may be substituted. Management of patients with permanent bilateral vestibular ablation should be directed at retraining the nervous system to use other sensory signals to replace the lost vestibular signals. Younger patients will have a greater propensity

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to recover substantial vestibular activity over a period of years, but elderly patients are rarely able to compensate fully. In a retrospective study, 51% of patients were found to improve after vestibular rehabilitation therapy, 34% showed little or no change, and 15% were lost to follow-up. Patients without improvement are those with chronic disorders and medical comorbidities. Lower gains (<0.2) and lowered time constants (<2 sec) on rotatory chair testing were also seen in the patients that did not improve.121 Vestibular rehabilitation progress can be measured through platform posturography and evaluating improvements in both gain and time constant during rotatory chair testing.

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48. Schuknecht H, Igarachi M, Chasin W: Inner ear hemorrhage in leukemia. Laryngoscope 75:662–668, 1965. 49. Xencher G, Altmann F: The temporal bone in leukemia: Histological studies. Ann Otol Rhinol Laryngol 78:375–387, 1969. 50. Ogawa K, Kanzaki J: Aplastic anemia and sudden sensorineural hearing loss. Acta Otolaryngol 75:662–668, 1994. 51. Ishii T, Toriyama M, Takiguchi T: Pathological findings in the cochlear duct due to endolymphatic hemorrhage. Adv Otorhinolaryngol 31:148–154, 1983. 52. Keller: Laryngoscope 68:2015–2019, 1958. 53. Goodhill V: Sudden deafness and round window rupture. Laryngoscope 81:1462–1474, 1971. 54. Farmer JC: Diving injuries to the inner ear. Ann Otol Rhinol Laryngol 86(1 Pt.3 Suppl 36):1–20, 1977. 55. Shupak A, Doweck I, Greenberg E: Diving-related inner ear injuries. Laryngoscope 101:173–179, 1991. 56. Parell GJ, Becker GD: Conservative management of inner ear barotrauma resulting from scuba diving. Otol Head Neck Surg 93(3):393–397, 1985. 57. Lamkin R, Axelsson A, McPherson D: Experimental aural barotraumas. Electrophysiological and morphological findings. Acta Otol 335(Suppl):1–24, 1975. 58. Francis TJR, Gorman DF: Pathogenesis of the decompression disorders. In Bennett P, Elliott D (eds.): The Physiology and Medicine of Diving, 4th ed. London, WB Saunders, 1993. 59. Rudge FW, Shafer MR: The effect of delay on treatment outcome in altitude-induced decompression sickness. Aviat Space Environ Med 62(7):687–690, 1991. 60. Paparella MM, Sugiura A: The pathology of suppurative labyrinthitis. Ann Otol Rhinol Laryngol 76:554–586, 1967. 61. Simmons FB: Theory of membrane breaks in sudden hearing loss. Arch Otolaryngol 88:41, 1968. 62. Fitzgerald DC: Head trauma: Hearing loss and dizziness. J Trauma 40(3):488–496, 1996. 63. Schuknecht HF, Gulya AJ: Endolymphatic hydrops: An overview and classification. Ann Otol Rhinol Laryngol 92(5 Suppl 106): 1–20, 1983. 64. Althaus, SR: Perilymph fistulas. Laryngoscope 91:538, 1981. 65. Bhansali SA: Perilymph fistula. Ear Nose Throat J 68:11–30, 1989. 66. Nylen CO: A clinical study of the labyrinthine fistula symptoms and pseudo-fistula symptoms in otitis. Acta Otol (Stockh) 3(Suppl 4):501–511, 1923. 67. Perlman HB, Leek JH: Late congenital syphilis of the ear. Laryngoscope 62:1175–1196, 1952. 68. Nadol JB: Positive Hennebert’s sign in Ménière’s disease. Arch Otolaryngol Head Neck Surg 103:524–530, 1977. 69. Hennebert C: A new syndrome in hereditary syphilis of the labyrinth. Presse Med Melge Brussels 63:467–470, 1911. 70. Brandt T, Dieterich M, Fries W: Otolithic Tullio phenomenon typically presents as paroxysmal ocular tilt reaction. Adv Otorhinolaryngol 42:153–156, 1988. 71. Hain TC, Ostrowski VB: Limits of normal for pressure sensitivity in the fistula test. Audiol Neurootol 2:384–390, 1997. 72. Huges GB, Sismanis A, House JW: Is there consensus in perilymph fistula management? Otolaryngol Head Neck Surg 102:11, 1990. 73. Bluestone CD: Otitis media and congenital perilymphatic fistula. Pediatr Infect Dis J (11 Suppl):S141–145, 1988. 74. Fitzgerald DC: Head trauma: Hearing loss and dizziness. J Trauma 40(3):488–496, 1996. 75. Strick SJ: Shearing of nerve fibers as a cause of brain damage due to head injury. Lancet 11:443, 1961. 76. Makishima K, Snow JB Jr: Electrophysiological responses from the cochlea and inferior colliculus in guinea pigs after head injury. Laryngoscope 85:1947, 1975. 77. McCabe BF, Ryu JH, Sekitani T: Further experiments on vestibular compensation. Laryngoscope 82:381, 1972. 78. Hamid MA: Determining side of vestibular dysfunction with rotatory chair testing. Otolaryngol Head Neck Surg 105:40, 1991.

79. Bahloh RW, Sakala SM, Yee RD: Quantitative vestibular testing. Otolaryngol Head Neck Surg 92:145, 1984. 80. Schuknecht HF: Mechanism of inner ear injury from blows to the head. Ann Otol Rhinol Laryngol 78:253, 1969. 81. Lindsay JR, Zajtchuk J: Concussion of the inner ear. Ann Otol Rhinol Laryngol 79:699, 1970. 82. Weissman JL, Curtin HD, Hirsch BE: High signal from the otic labyrinth on unenhanced magnetic resonance imaging. Am J Neuroradiol 13:1183, 1992. 83. Axelsson A, Hallen C: The healing of the external cochlea wall in the guinea pig after mechanical injury. Arch Otolaryngol 76:136, 1973. 84. Ylikoski J, Palva T, Sonna M: Dizziness after head trauma: Clinical and morphological findings. Am J Otol 3:343, 1982. 85. Nadol JB, Weiss AB, Parker SW: Vertigo of delayed onset after sudden deafness. Ann Otol Rhinol Laryngol 84:841, 1975. 86. Paparella MM, Mancini F: Trauma and Ménière’s syndrome. Laryngoscope 93:1004, 1983. 87. Becker GD: Late syphilitic hearing loss: A diagnosis and therapeutic dilemma. Laryngoscope 89:1273–1288, 1979. 88. Smith ME, Canalis RF: Otologic manifestations of AIDS: The otosyphilis connection. Laryngoscope 99:365–372, 1989. 89. Zenker PN, Rolfs RT: Treatment of syphilis, 1989. Rev Infect Dis 12(Suppl 6):S590–S609, 1990. 90. Karmody CS, Schuknecht HF: Deafness in congenital syphilis. Arch Otolaryngol 83:18–27, 1966. 91. Clark EG, Danbolt N: Oslo study of the natural history of untreated syphilis: An epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material. J Chron Dis 2:311–344, 1955. 92. McNulty JS, Fassett RL: Syphilis: An otolaryngologic perspective. Laryngoscope 91:889–905, 1981. 93. Steckelberg JM, McDonald TJ: Otologic involvement in late syphilis. Laryngoscope 94:753–757, 1984. 94. Wilson WR, Zoller M: Electronystagmography in congenital and acquired syphilitic otitis. Ann Otol Rhinol Laryngol 90:21–24, 1981. 95. Shih L, McElveen JT, Linthicum FH: Management of vertigo in patients with syphilis: Is endolymphatic shunt surgery appropriate? Otolaryngol Head Neck Surg 99(6):574–577, 1988. 96. Linthicum FH, Abd El-Rahman AG: Hydrops due to syphilitic endolymphatic duct obliteration. Laryngoscope 97:568–574, 1987. 97. Amenta CA, Dayal VS, Flaherty J: Leutic endolymphatic hydrops: Diagnosis and treatment. Am J Otolaryngol 13:6, 516–524. 1992. 98. Hawkins J: Drug ototoxicity. In Keidel WD, Neff WD (eds.): Handbook of Sensory Physiology, vol 3. New York, Springer, 1976, pp 704–748. 99. Ferraro J, Best LG, Arenberg IK: The use of electrocochleography in the diagnosis, assessment, and monitoring of endolymphatic hydrops. Otolaryngol Clin North Am 16(1):69–82, 1983. 100. Smith CR, et al: Double blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med 302:1106, 1980. 101. Fee WE: Aminoglycoside ototoxicity in the human. Laryngoscope 90(Suppl 24):1–19, 1980. 102. Lerner SA, Matz GJ: Aminoglycoside ototoxicity. Am J Otolaryngol 1(2):169–179, 1980. 103. Hinojosa R, Nelson E, Lerner S: Aminoglycoside ototoxicity: A human temporal bone study. Laryngoscope 111:1797–1805, 2001. 104. Forge A, Schacht J: Aminoglycoside antibiotics. Audiol Neurootol 5:3–22, 2000. 105. Yagi M, Magal E, Sheng Z: Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell linederived neurotrophic factor. Hum Gene Ther 10:813–823, 1999. 106. Lopez I, Honrubia V, Lee S: The protective effect of brain-derived neurotrophic factor after gentamycin ototoxicity. Am J Otolaryngol 20:317–324, 1999. 107. Basile AS, Brichta AM, Harris BD: Dizocilpine attenuates streptomycin-induced vestibulotoxicity in rats. Neurosci Lett 265:71–74, 1999.

Otolith Dysfunction and Semicircular Canal Dysfunction

108. Sha S, Schacht J: Salicylate attenuates gentamycin-induced ototoxicity. Lab Invest 79:807–813, 1999. 109. Torroni A, Cruciani F, Rengo C: The A1555G mutation in the 12S rRNA gene of human mtDNA: Recurrent origins and founder events in families affected by sensorineural deafness. Am J Hum Genet 65:1349–1358, 1999. 110. Rybak LP: Pathophysiology of furosemide ototoxicity. J Otolaryngol 11(2):127–133, 1982. 111. Matz GJ, Hinojosa R: Histopathology following use of ethacrynic acid. Surg Forum 488–489, 1973. 112. Bosher SK: Ethacrynic ototoxicity as a general model in cochlear pathology. Adv Otorhinolaryngol 22:81–89, 1977. 113. Bernstein JM, Weiss AD: Further observations on salicylate ototoxicity. J Laryngol Otol 81:915, 1967. 114. Peters RC, Mommersteeg PMC, Heijmen PS: The electroreceptor organ of the catfish, Ictalurus melas, as a model for cisplatininduced ototoxicity. Neuroscience 91:745–751, 1999. 115. Rybak LP, Whitworth C, Somani S: Application of antioxidants and other agents to prevent cisplatin Ototoxicity. Laryngoscope 109:1740–1744, 1999.

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116. Campbell KCM, Meech RP, Rybak LP: D-Methionine protects against cisplatin damage to the stria vascularis. Hear Res 138:13–28, 1999. 117. Feghali JG, Wei L, Van De Water T: L-N-acetyl-cysteine protection against cisplatin-induced auditory neuronal and hair cell toxicity. Laryngoscope 111:1147–1155, 2001. 118. Campbell KCM, Kalkanis J, Glatz FR: Ototoxicity: Mechanisms, protective agents, and monitoring. Curr Opin Otolaryngol Head Neck Surg 8:436–440, 2000. 119. Paydarfar JA, Goebel JA: Integrated clinical and laboratory vestibular evaluation. Curr Opin Otolaryngol Head Neck Surg 8:363–368, 2000. 120. Della Santina CC, Cremer PD, Carey JP, Minor LB: Comparison of head thrust test with head autorotation test reveals that the vestibulo-ocular reflex is enhanced during voluntary head movements. Arch Otolaryngol Head Neck Surg 128:1044–1054, 2002. 121. Gillespie MB, Minor LB: Prognosis in bilateral vestibular hypofunction. Laryngoscope 109(1):35–41, 1999.

Chapter

15 Courtney D. Hall, PhD Susan J. Herdman, PhD

Dynamic Posturography Outline Introduction Historical Perspective Methodology Sensory Organization Test Limits of Stability Test Motor Control/Adaptation Tests Reliability and Validity of Dynamic Posturography Application to Patient Management Risk for Falls in Older Adults Vestibular Deficits Central Balance Deficits Nonphysiological Component of Balance

INTRODUCTION Postural control involves the dynamic interplay between multiple body systems, including the sensory, central nervous, and musculoskeletal systems. In order to meet the demands of a constantly changing environment (1) body position and movement must be detected via information gathered from the visual, somatosensory, and vestibular systems; (2) the central nervous system must integrate this sensory information and select an appropriate response; and (3) the response must be executed by the musculoskeletal system with adequate force and within a task-appropriate time. Failure in any one of these systems can result in an impaired ability to control posture. By incorporating dynamic posturography into the balance assessment, clinicians and researchers can quantify each aspect of postural control and identify specific system impairments or functional limitations. Appropriate interventions to improve balance can then be initiated. Research demonstrates that interventions targeted to improve specific deficits are successful in improving postural control and in reducing risk for falls.1

Historical Perspective The measurement of postural sway during static stance has been used for over 100 years in the clinical assessment of patients with neurologic disorders. The Romberg test was originally used to distinguish between cerebellar and somatosensory deficits. Although the Romberg test is now a standard part of the assessment of patients with balance 256

Treatment Considerations and Limitations Sensory Organization Test Conditions 1 and 2 Age Diagnosis Motor Control/Adaptation Tests: Automatic Postural Responses Center of Gravity Alignment Subject Characteristics Initial Center of Gravity Alignment Summary

problems, its utility is limited. It is not sensitive to subtle problems of postural instability, can be normal in the presence of relatively severe postural deficits, and cannot be used to distinguish among deficits from different causes. The use of computerized force plates in clinical assessment has extended our ability to identify subtleties of postural sway in patients and better define patients’ problems. Dynamic posturography can quantify multiple aspects of postural control including quiet stance, the use of sensory cues, voluntary weight shifting, and automatic postural reactions. Recent advances include the assessment of daily activities including sit-to-stand, turns, and gait. At this time, there are little data on the use of dynamic posturography to assess these latter activities, so discussion of these assessments will not be included in this chapter. While dynamic posturography itself does not allow the clinician to identify the cause of dysfunction, some of the force platform measures yield information that aids in diagnosis. For the most part, however, dynamic posturography test results are used to improve patient treatment by identifying functional deficits and establishing and monitoring treatment.

METHODOLOGY A dynamic posturograph, or a computerized dynamic posturograph, as it is often called, is a device with a force platform and a computerized system that controls it.2 Critical elements of dynamic posturography include the ability of the force platform to move abruptly in a translational or rotational (pitch) direction, as well as the ability

Dynamic Posturography

to synchronize movements of the force platform and a visual surround with an individual’s movements. Finally, dynamic posturography must include the collection and analysis of the force data. The most common method of measuring the vertical and horizontal forces applied to the force platform uses transducers located under a separate force plate for each foot. The sums of the vertical and horizontal forces for each foot are calculated and combined to locate the center of (foot) pressure. The patient’s height and force data are used to estimate the vertical location of the center of gravity (COG) of the body. The force plate system does not directly measure COG because this requires information about the position of each body segment in space. Rather COG is estimated based on theoretical assumptions about the location of COG relative to height, ankle position, and center of pressure.3 COG angle of sway is also estimated. Data from dynamic posturography can be expressed as peak-to-peak anterior–posterior or medial–lateral sway, sway path length and time, sway frequency and velocity, direction of sway, and reaction time.

Sensory Organization Test The dynamic posturography test that assesses use of sensory information is known as the sensory organization test (SOT). Postural sway is measured under conditions in which visual and somatosensory feedback is altered (Table 15-1). In the most commonly available apparatus (NeuroCom International, Inc., Clackamas, OR), the change in sway angle is used to move either a visual surround or the support surface in synchrony with the individual’s sway.4 Movement of the visual surround in parallel with the individual alters visual cues normally used for postural stability. For example, in quiet stance we normally have a small amount of anterior and posterior (AP) sway. This sway results in changes in retinal disparity and image size, which are visual cues used to determine whether you or the world is moving.5 If the visual world around you (visual surround) is moved in parallel with your sway, these visual feedback cues are inaccurate and cannot be used effectively to maintain postural stability. Similarly, when the support surface is moved in parallel with sway there is little change in ankle angle. This alteration in somatosensory feedback renders it a less effective signal in the maintenance of upright posture. The ability of the visual and somatosensory surrounds to be moved in parallel with AP sway is imperfect, however. At frequencies of sway greater than 0.3 Hz, the mechanism cannot perfectly match sway, so

257

visual and somatosensory cues are altered rather than minimized or absent. Other systems (e.g., Balance System, Biodex Medical Systems, Shirley, NY; Balance Quest, Micromedical Technologies, Chatham, IL; the modified clinical test of sensory interaction in balance [M-CTSIB] test, NeuroCom International, Inc.) alter somatosensory feedback by having the individual stand on dense foam or an unstable surface, rather than by sway-referencing the support surface. In addition, vision is not sway-referenced; rather, it is removed by closing the eyes. These tests are modifications of the SOT and comprise four other conditions (eyes open/closed and firm/compliant surface) that can be assessed. The SOT is organized into a series of six conditions of increasing difficulty. The first three conditions are performed on a firm surface with eyes open, eyes closed, and finally with vision sway-referenced. The final three conditions are performed with the support surface swayreferenced with eyes open, eyes closed, and with vision sway-referenced (see Table 15-1). Results of the SOT are calculated based on maximum peak-to-peak AP sway expressed as an equilibrium score ranging from 0 to 100, with 0 indicating loss of balance and 100 indicating perfect stability (Figure 15-1). Data also include sway path and COG alignment at the start of each trial. Performance on the different conditions is used to determine relative use of different sensory cues and is depicted in bar graph form. Determination of motor strategy used (ankle or hip) is inferred from the relative amount of shear force during each trial. The ankle strategy, in which the body primarily rotates about the ankle joint, is defined by the predominance of vertical forces. The hip strategy, in which movement occurs about the hip, is defined by the predominance of horizontal (or shear) forces.

Limits of Stability Test The test of voluntary sway is known as the limits of stability (LOS) test. LOS measures the maximum COG sway angle an individual is willing or able to shift the COG. During the test, the individual views a screen that displays the COG location and a series of visual targets. The patient is required to shift his or her weight to move the COG cursor toward a visual target, without moving the feet. The support surface does not move during this test. The individual is instructed to move directly to the target as quickly as possible. The targets are positioned at eight places around a circle at either 75% or 100% of limits

TABLE 15-1. Sensory Organization Test Conditions

Sensory Cues

Cues Available for Stability

Condition 1 (C1) Condition 2 (C2) Condition 3 (C3) Condition 4 (C4) Condition 5 (C5) Condition 6 (C6)

Eyes open, visual surround and platform stable Eyes closed, visual surround and platform stable Eyes open, moving visual surround, platform stable Eyes open, visual surround stable, platform moving Eyes closed, visual surround stable, platform moving Eyes open, visual surround and platform moving

Normal visual, somatosensory, and vestibular cues No visual cues, normal somatosensory and vestibular cues Normal somatosensory and vestibular cues, altered visual feedback Normal visual and vestibular cues, altered somatosensory feedback Normal vestibular cues, no visual cues, altered somatosensory feedback Normal vestibular cues, altered visual and somatosensory feedback

258

NEUROTOLOGIC DIAGNOSIS

EQUILIBRIUM SCORE 100 75 50 25 Fall 1

2

3

A

4

5

6

Conditions

Composite 88

of stability based on patient’s height (Figure 15-2). Data include reaction time, movement velocity, end point excursion, maximum excursion, and directional control. Reaction time is the time between the “go” signal and the patient’s first movement. Movement velocity is the average speed of COG movement in degrees per second. End point excursion is the distance of the initial movement of the COG toward the target as a percentage of maximum LOS distance. Maximum excursion is the maximum distance the COG moved during the trial. Directional control is an indication of the amount of deviation from a direct path to the target and is expressed as a percentage, with 100% representing a direct path.

Motor Control/Adaptation Tests COG ALIGNMENT

B Trial 1

Trial 2

Trial 3

C1 Normal vision Fixed surface C2 Absent vision Fixed surface C3 SwayRef vision Fixed surface C4 Normal vision SwayRef surface C5 Absent vision SwayRef surface C6 SwayRef vision SwayRef surface 10 degrees

C Figure 15-1. Normal sensory organization test (SOT) results: A, Equilibrium scores for three trials of each condition with 100 indicating perfect stability; the shaded area indicates performance outside of age-referenced norms; B, each mark represents center of gravity (COG) alignment at the start of each trial relative to the center of the force plate; C, sway path of COG during each trial with reference to the center of the force plate; C1–C6 indicates conditions 1–6.

Successful mobility in the environment requires an individual to react to external disturbances of balance, such as occurs when a bus suddenly starts or stops or the individual steps in a hole because of uneven terrain. Therefore, tests of reactive balance involve sudden, brief displacement of the support surface in order to assess automatic postural responses used in the recovery of balance. These responses must be appropriately timed and scaled to prevent a loss of balance or fall. Muscle activity in the distal musculature occurs at approximately 110 msec following movement of the support surface, while center of pressure changes (i.e., as a result of active application of force or torque) begin at approximately 130 msec.6 Both timing and amplitude of surface reactive force are measured to assess the automatic postural responses. The motor control test (MCT) uses forward and backward translational movements of the surface, and the adaptation test uses rotational pitch (either toes up or toes down) of the surface. The MCT involves three trials in each of three progressively larger translations of the support surface (Figure 15-3). The weight symmetry, or relative weight distribution on each leg, latency of onset of force development used to regain postural stability, and the amplitude or strength of the response is recorded (Figure 15-3B, C). The larger the displacement of the support surface, the greater the response needed to regain balance. Normal subjects and patients with bilateral vestibular deficits exhibit a relative increase in the initial rate of change of torque developed as the amplitude of surface displacement increases. In contrast, patients with cerebellar disorders fail to modify their automatic postural responses as measured by surface reactive force.7 The adaptation test uses a sudden tilt of the support surface in a pitch (toes up or down) direction to evoke postural responses. This shifts the COG alignment and destabilizes the individual. Measurements of the magnitudes of response to five identical toes-up or toes-down perturbations are used to assess motor learning or adaptation. Repeated perturbations of the same amplitude should result in a decrease in the amplitude of the force developed to maintain postural stability (Figure 15-3D). Normal individuals quickly learn to maintain their balance during this paradigm, and loss of balance is unusual except during the initial trial in younger subjects.8 In older subjects (>70 years), the likelihood of loss of balance increases on all trials of toes-up perturbations, although adaptation still occurs.8

Dynamic Posturography

The addition of electromyography (EMG) during toes-up perturbations allows the clinician to measure muscle activity. Rotation of the support surface results in a very different pattern of muscle activity from translational perturbations (Figure 15-4). The toes-up movement of the platform elicits both a short-latency and a middle-latency response in the gastrocnemius–soleus muscle group (Figure 15-4B, D). The short-latency response is equivalent to the monosynaptic stretch reflex, and the middle-latency response is a multisegmental spinal reflex.9 This is followed by a longlatency response in the anterior tibialis muscle, which acts to shift the COG alignment forward (Figure 15-4C, E). The long-latency response is believed to encompass a transcortical pathway.9 Examination of the presence, absence, or delay in any of the reflex responses has been correlated with site of neurologic lesion (Table 15-2).

LIMITS OF STABILITY

A 100% LOS

B

Forward Back

Deg/sec 10.0 8.0 6.0 4.0 2.0 0.0

C

D

E

Left

Comp

Right

Left

Comp

ENDPOINT & MAX EXCURSIONS (EPE & MXE)

Forward Back

% 100 80 60 40 20 0

Right

MOVEMENT VELOCITY (MVL)

Forward Back

% 120 100 80 60 40 20 0

Reliability and Validity of Dynamic Posturography

REACTION TIME (RT)

Sec 2.0 1.6 1.2 0.8 0.4 0.0

Right

Left

259

Comp

Two important attributes of any assessment tool are reliability and validity.10 Good test–retest reliability must be established if dynamic posturography is to be used to identify changes in postural control associated with treatment. At present, there are few studies on the reliability of dynamic posturography testing. Studies of SOT in community-dwelling older adults show that the test-retest reliability is greater when the average of three trials is used rather than the first trial score only, although reliability across the six conditions ranges from poor to good (ICCs = 0.26 to 0.68).11 The use of a composite score (average of C1 + average of C2 + all other trials for C3 to C6/14) also improves reliability to good (ICC = 0.66). Test-retest reliability of the LOS has been found to be moderate to high for two days of testing in community-dwelling older adults who have not fallen (generalizability coefficients = 0.69 to 0.89),12 as well in individuals after a stroke (ICCs = 0.84 to 0.88).13 No studies examining reliability of the motor control tests were found. Validity refers to whether a test measures what it intends to measure. Dynamic posturography was developed as an objective measure of postural control. Because postural control is multifaceted, any tool claiming to evaluate the construct of posture must assess multiple dimensions. Dynamic posturography is capable of assessing voluntary (LOS) and reactive postural control (MCT/adaptation), as well as balance under differing sensory conditions (SOT). Thus, dynamic posturography appears to have content validity. Another test of validity is concurrent validity, in other words, the degree to which the results of dynamic posturography correlate with a measure known to be valid.

DIRECTIONAL CONTROL (DCL)

Forward Back

Right

Left

Comp

Figure 15-2. Normal limits of stability (LOS) test results: A, sway path of center of gravity to each target located at 100% limits of stability, B, reaction time in seconds, C, movement velocity in degrees/second, D, endpoint (EPE) and maximum excursion (MXE) in percentage of total possible excursion, and E, directional control in percentage value indicating directness of path to target. In graphs B-E, the shaded area represents performance outside of age-referenced norms. Forward, back, right, and left is calculated to indicate performance in those primary directions, and Comp is a calculated composite score from all the targets.

260

NEUROTOLOGIC DIAGNOSIS

WEIGHT SYMMETRY Forward translation

WEIGHT SYMMETRY Backward translation Left

Left

Right

Right S M L

S M L

A 0

100

200

0

100

LATENCY (ms) Forward translation

LATENCY (ms) Backward translation

Figure 15-3. Motor test scores include A, weight symmetry at the onset of the perturbation, B, latency until reactive force is developed, and C, relative amplitude of response during backward and forward translational perturbations of three different magnitudes for a normal subject. Note that the latency decreases and the “force” of the response increases with larger perturbations. D, Five repeated perturbations of the same magnitude (shown here for rotational or pitch perturbations) result in a reduction in the amplitude or strength of the response (the scale ranges from 0 to 200) in normal subjects. In graphs A–D, the shaded area represents performance outside of age-referenced norms.

200

200

180

180

120

120

80

4

4

4

4

M

L

M

L

B

Left

80

25

20

20 Left = +

15

C

+ X

+ X

L

M

L

S

M

S

150

100

100

50

50

0

0

There is no gold standard against which to judge dynamic posturography. However, postural sway does correlate with the Berg balance scale, which is an accepted test of functional balance.14 The final aspect of validity is construct validity, which implies predictive capabilities. Because balance impairment is a major risk factor for falls, if dynamic posturography is

5

M

L

ADAPTATION–TOES DOWN

150

4

+ X

+ X

L

200

3

Right

+ X

5 0

2

M

Right = X 10

+ X

200

1

4

15

ADAPTATION–TOES UP

D

4

AMPLITUDE SCALING

25

0

4

Left

AMPLITUDE SCALING

5

4

Right

10

200

1

2

3

4

5

to have construct validity, it should be able to predict falls. The results regarding the ability of posturography to identify older individuals as either fallers or nonfallers have been mixed.4,15,16 Although a single measure of postural stability—sway velocity—did not successfully differentiate older fallers from nonfallers,4 the use of composite scores (from SOT or LOS) or a combination of variables—reaction time

Dynamic Posturography

A

261

AVERAGE 20 OF 20 TRIALS Fast toes-up rotation

B

L. GASTROC

100

C

0

100

312 ␮v SL ML

300

L. TIBIA

E

LL

312 ␮v SL ML

SL1

ML1

Time (ms)

35

73

L. TIBIA

LL1

Time (ms)

102

R. TIBIA

Figure 15-4. Automatic response of a normal subject, averaged from a series of 20 pitch (toes-up) perturbations of the support surface (A). The ramped line indicates the perturbation of the support surface with the arrow indicating the initiation of the perturbation. Short-latency (SL) and middle latency (ML; B, D) responses elicited in the left (L) and right (R) gastrocnemius/ soleus muscles. The long-latency response (LL; C, E) occurs in the left (L) and right (R) anterior tibialis muscles and acts to correct for the sudden shift in the center of mass posteriorly.

R. GASTROC

SL1

ML1

Time (ms)

37

66

625 ␮v LL

400 msec

L. GASTROC

625 ␮v

R. GASTROC

D

200

R. TIBIA

LL1

Time (ms)

111

TABLE 15-2. Short-, Middle- and Long-Latency Responses and Site of Lesion Lesion

Short-Latency Response

Middle-Latency Response

Long-Latency Response

Normal (mean + 1 SD) Normal (mean + 2 SD) Peripheral neuropathy Anterior lobe cerebellar atrophy; diffuse cerebellar disease Friedreich’s ataxia

43.5 + 4.2 msec 51.9 msec Delayed Delayed due to concomitant peripheral neuropathy

89.5 + 10 msec; absent in 25% Latency = 109.5 msec Delayed Normal

125.3 + 17.8 msec; duration 76 + 19 msec Latency = 160.9 msec; duration = 114 Delayed Increased duration in 66%

Absent in 66%;

Cerebellar hemispheric Parkinson’s disease

Normal Absent if is peripheral neuropathy, normal latency; integral normal Normal Normal latency

Absent in 66%; when present, is delayed Normal Normal latency; greatly increased integral

Prolonged rate of rise (>50 msec); delayed (>225 msec); Delayed (146 msec) Normal latency; normal integral

Absent 50% of subjects Normal latency

Delayed (>164 + 36.5 msec) Delayed latency

Spinal cord lesion Intra-cranial lesions

From Diener HC, Dichgans J: Long loop reflexes and posture. In Bles W, Brandt T (eds.): Disorders of Posture and Gait. Amsterdam: Elsevier Science, pp. 41–51, 1986.

262

NEUROTOLOGIC DIAGNOSIS

and movement velocity from LOS and sway velocity during condition 1 (eyes open, firm surface) of the M-CTSIB—did differentiate between these groups.15,16

APPLICATION TO PATIENT MANAGEMENT Risk for Falls in Older Adults The increased incidence of falling in older adults is well documented. Nearly one third of adults older than age 65 experience a fall in a given year, and this incidence increases to 50% by the age of 80.17 Of those who do fall, 10% to 15% experience a fall-related injury. Given the consequences of falls, it is important to identify individuals at risk before they fall in order to provide appropriate intervention. Several studies have found the use of dynamic posturography valuable in identifying older individuals who are at risk for falling. In a study comparing performance-based tests and posturography-based tests, the LOS maximum excursion composite score was the most accurate at predicting fallers, whereas the performance-based tests such as Tinetti’s performance-oriented mobility assessment and the timed up and go were most accurate at identifying nonfallers.15 The combination of reaction time and movement velocity composite scores from LOS and sway velocity during condition 1 (eyes open, firm surface) of the MCTSIB was found to have an overall accuracy of 73% in differentiating fallers from nonfallers.15 In a comparison among the functional reach, SOT (composite score), and LOS (anterior score only),16 only the SOT (composite score) differentiated between older fallers and nonfallers. Thus, dynamic posturography appears to be useful in identifying older adults at risk for falls, but only if composite scores or multiple measures are used.

Vestibular Deficits Dynamic posturography, by itself, is not an appropriate tool for the identification of vestibular deficits. Posturography and rotary chair test results agree in only 25% of all patients.18,19 The difference in test results may be ascribed to several factors. First, dynamic posturography measures the output of the vestibulospinal and other

balance systems acting in concert. In contrast, caloric and rotary chair tests assess only one system, the vestibuloocular system.20 Thus, during posturography testing, vestibular deficits may be masked by other functioning balance systems. Second, the caloric, rotary chair, and posturography tests assess the function of different components of the vestibular apparatus (horizontal canals versus vertical canals plus otoliths, respectively). This might result in different test results in some vestibular disorders, such as vestibular neuronitis, where the deficit can be limited to only the distribution of the inferior vestibular nerve. Finally, balance, as measured by dynamic posturography, may recover fully,21 whereas caloric and rotary chair test results continue to be abnormal in the majority of patients. In terms of identifying individuals with vestibular deficits, dynamic posturography has sensitivity and specificity of approximately 50% compared with other tests of vestibular function including caloric and rotary chair testing.22 When used as an adjunct to caloric and rotary chair tests, posturography testing increases the likelihood of identifying a vestibular problem.19,23 Although the SOT dynamic posturography should not be used as a diagnostic tool, the results of studies on patients with different problems show performance patterns that are useful as guides to expectations for certain diagnoses (Table 15-3). The overlap in findings across diagnoses can be clearly seen; therefore, difficulty on tests 5 and 6 cannot be interpreted as indicating a vestibular deficit. Although it is well documented that patients with severe bilateral vestibular loss are unable to maintain their balance under conditions in which both visual and somatosensory cues are altered,24–27 the results of the SOT are not specific for vestibular loss. Patients with other balance problems, as diverse as Huntington’s disease and fear of falling, may lose their balance under these same conditions.4,28 It is probably most appropriate to interpret the results of the SOT in terms of the functional implications of the test performance. Several common patterns in test performance have been identified and ascribed to difficulties in using different sensory cues (Table 15-4) rather than diagnoses. It is important to remember that although this test provides us with reliable data, test performance can be strongly influenced by subjective factors, including patient effort, fear, and cognition.

TABLE 15-3. Diagnosis

Posturography Performance Pattern

Peripheral vestibular deficits24,25,30 Severe bilateral vestibular loss24,25,39

Abnormal sensory organization tests; Rare motor test abnormality (<2%) Loss of balance C5, C6 with increased sway C3, C4; Correlation of sensory organization tests with severity of deficit (VOR Tc) Increased number of falls C3, C5, C6 but not necessarily on all trials Increased sway or loss of balance especially on C5, C6; Can be normal within few days postonset Normal sensory organization tests but evidence on decrement in performance several months out Increased sway C3, C6 in BPPV plus head injury Increased sway C5, C6 in BPPV, no head injury Increased sway all tests pretreatment, improved with remission of symptoms following treatment >90% have abnormal motor tests (especially latencies) as well as abnormal sensory organization tests

Incomplete bilateral vestibular deficit Acute unilateral vestibular deficit31 Compensated unilateral vestibular deficit40,42 Benign paroxysmal positional vertigo46–48

Central deficits30

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TABLE 15-4. Test Performance Pattern

Possible Interpretations

Loss of balance or increased sway on C2, C3, C5, C6 Loss of balance or increased sway on C4, C5, C6 Loss of balance or increased sway on C5, C6 Generally increased sway, stopping test by putting hands out to touch wall; verbalized expression of concern or fear Increased sway or loss of balance occurring on later trials only with normal performance on initial trials of same condition Loss of balance or increased sway on initial trial of each sensory condition Regular periodicity of sway across all SOT trials and conditions Better performance on more difficult conditions than on easier conditions Inconsistency in performance from trial to trial on SOT Abnormal responses to support surface perturbations including inconsistent responses and exaggerated responses

Visual dependency Somatosensory dependency Vestibular deficit or reflects increased difficulty of these conditions Fear of falling Fatigue Inability to handle novel postural challenges Functional or nonphysiological

or with Friedreich’s ataxia have large-amplitude, omnidirectional sway with a tendency for more lateral sway.29 Patients with atrophy of the anterior lobe of the cerebellum display prominent AP sway with markedly increased amplitude of sway with eyes closed.29 Research paradigms use Fourier analysis of sway to identify the dominant sway frequency when a subject is standing quietly. Although this analysis is not used extensively in clinical studies, it is available and promises to contribute significantly to the ability of posturography to aid in diagnosis. Studies reveal a dominant frequency of sway (2.5 to 3.5 Hz) in subjects with atrophy of the anterior lobe of the cerebellum that is not found in normal

Central Balance Deficits Although dynamic posturography is less sensitive for identifying peripheral vestibular dysfunction than ENG, it can provide significant information for certain central disorders.22,23 Although the amplitude of peak-to-peak AP sway seen during conditions 1 and 2 of the SOT does not discriminate among different balance disorders, direction of sway and sway frequency sometimes can be useful diagnostically.29 Normal subjects present with omnidirectional sway of small amplitude (Figure 15-5). Eye closure (no vision) results in a small increase in sway amplitude. In contrast, patients with lesions of the vestibulocerebellum NORMAL 10 cm

VESTIBULO-CEREBELLAR LESION 10 cm

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Figure 15-5. Patients with cerebellar disorders differ from normal subjects both in their sway path and in the sway direction as indicated by a histogram. All patients had increased sway paths compared with the normal subject with both the eyes open and the eyes closed. The patient with the vestibulocerebellar lesion and the patient with Friedreich’s ataxia showed more lateral sway while the patient with atrophy of the anterior lobe of the cerebellum had marked increase in anterior/posterior sway. Note the different scales for the sway direction histogram for both the patient with Friedreich’s ataxia and the patient with atrophy of the anterior lobe of the cerebellum. (Modified from Dichgans J, Clinical Symptoms of Cerebellar Dysfunction and Their Topodiagnostical Significance in Human Neuro-biology 1984, vol 2, pages 269–279.)

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subjects.29 This characteristic frequency is present during the earlier stages of degeneration and may disappear in patients with chronic degeneration of the anterior lobe. Assessment of automatic postural responses is also useful in identifying patients with central lesions affecting stability.30 In patients with nonvestibular central balance problem, either the latency or symmetry of the reactive torque is abnormal in 80% of patients. In contrast, the automatic postural responses are rarely abnormal in patients with peripheral vestibular deficits.24,30,31 Delays in the onset of the short-, middle- and longlatency responses give site of lesion information (see Table 15-2).8,32,33 The short-latency response is affected by peripheral neuropathy. The middle-latency response is delayed in patients with spinal cord disease such as multiple sclerosis or syringomyelia. The long-latency response can be delayed with lesions in the peripheral nerve or anywhere in the long tracts of the central nervous system. The short- and middle-latency responses appear to be independent of cerebellar influences, but the cerebellum may modulate the long-latency response.9

Nonphysiological Component of Balance Poor performance on the SOT does not necessarily indicate a specific physiological problem. One of the difficulties in medicine is identifying those patients with psychological or functional components to their postural instability. These functional components can include fear of falling as well as anxiety, somatoform disorders, and true malingering. For example, older individuals who report fear of falling exhibit increased sway velocity during the M-CTSIB compared with those who were not fearful.4 Nonphysiologic balance problems (e.g., occurs in conversion disorder or malingering) can be characterized by several components of the patient’s performance on the SOT and the motor tests (Table 15-5).34–37 Cevette and colleagues35 found that patients with symptoms unrelated to organic findings had erratic performance within each condition (i.e., greater intertrial variability) and relatively

better performance on the more difficult conditions than on the easier conditions of the SOT (Fig. 15-6). Additionally, they described a discrepancy between the patients’ abnormal performances on dynamic posturography and their ability to walk. Goebel and colleagues34 identified two additional criteria from the MCTs—exaggerated responses to small perturbations and inconsistent responses to small and large perturbations—that had a high specificity for identifying persons who were deliberately feigning instability. By combining criteria from the SOT and MCT, the falsepositive rate (i.e., identifying a problem where there is no organic cause) was reduced to zero.34 The criteria used to identify nonphysiological sway was validated in a recent study, which found that only 8% of patients without secondary gain exhibited exaggerated patterns, but 76% of those with secondary gain had exaggerated patterns.36 One concern about the use of computerized posturography in identifying malingerers is that individuals may learn to successfully manipulate their results. That is, people deliberately malingering may learn how to produce results that mimic real disorders rather than producing results that are clearly identifiable as nonphysiological patterns. Fortunately, Morgan and colleagues38 showed that an individual’s ability manipulate the results does not improve when they have additional information regarding dynamic posturography.

Treatment Dynamic posturography is useful in establishing treatment and in monitoring patient recovery, especially as part of the rehabilitation process. For example, patients may use different sensory cues to maintain postural stability. Figure 15-7 illustrates the results of the sensory organization test in three patients with bilateral vestibular loss secondary to aminoglycoside ototoxicity. None of the patients can maintain balance when both visual and somatosensory cues are altered (conditions 5 and 6), which is consistent with the findings of numerous studies on patients with bilateral vestibular loss.24,25,39 The first patient (Fig. 15-7A),

TABLE 15-5. Citation

Criteria for Nonphysiological

Goebel et al 1997; Otolaryngol Head Neck Surgery 117:293–30234

Substandard performance on C1 Score = number of points below norm for the best trial of C1 Exaggerated motor responses to small translations Score = average number of degrees of sway across trials for small forward and backward translations (should be <2 degrees) Inconsistent motor responses to small and large translations Score = number of tests with at least 2 of 3 concordant trials per tests (max = 4) Lower scores on C1 and 2, higher on C5 and 6 Score = [(C1−norm1) + (C2-norm2)] – [(C5-norm5) + (C6-norm6)] Highest score on the following 3 equations: Nonphysiologic = −158.2 + (1.94 × C1) + (1.09 × C2) + (1.37 × C4) – (0.15 × C6) Normal = −238.14 + (2.24 × C1) + (1.45 × C2) + (1.70 × C4) – (0.13 × C6) Vestibular = −251.21 + (2.31 × C1) + (1.54 × C2) + (1.89 × C4) – (0.58 × C6) Substandard performance on C1 and C2 Large amplitude AP sway without falls Score = average number of AP sways >5 degrees on C4, 5, 6 without falls Large amplitude lateral sway Score = average number of lateral sways >1.25 degrees on C4, 5, 6 without falls Excessive intertrial variability (no score calculated) Circular sway (no score calculated)

Cevette et al 1995; Otolaryngol Head Neck Surg 112:676–68835

Gianoli et al 2000; Otolaryngol Head Neck Surg 122:11–1836

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Figure 15-6. A, Performance on the sensory organization test by patients with nonphysiological balance problems is characterized by inconsistent performance on different trials of the same condition and by better performance on more difficult conditions than on easier conditions (compare condition 3 to 1 and condition 5 to 2). B, Inspection of the anterior/posterior sway trace often reveals a regular periodicity to sway.

AP sway 2

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however, is able to maintain balance within normal limits as long as either visual cues (conditions 1 and 4) or somatosensory feedback (conditions 2 and 3) is present. In contrast, other patients rely on somatosensory cues for stability and therefore lose their balance when somatosensory feedback is altered (Fig. 15-7B). Similarly, patients may rely on visual cues (Fig. 15-7C). Identifying reliance on a particular sensory cue can then be used to establish specific exercises for the patient. Studies have reported the rapid spontaneous recovery of postural stability in patients with acute and chronic unilateral vestibular deficits.31,40,41 Cass and colleagues42 followed patients for up to 20 months following vestibular nerve

section. They found that all patients had normal sensory organization tests by one month after surgery. Surprisingly, 21% of the patients showed a decrease in stability 3 to 20 months after surgery, suggesting that reevaluation and possible reinstitution of vestibular exercises would be appropriate in these patients. Computerized dynamic posturography results also have been used in numerous studies to monitor the effectiveness of vestibular rehabilitation of patients with vestibular disorders.31,43–45 Improved postural stability has been documented in patients with acute and chronic vestibular deficits compared with control groups21,31,44 and in patients with benign paroxysmal positional vertigo.46–48 Dynamic

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100 75 50 25

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posturography can be used to predict the outcome of vestibular rehabilitation. Patients with a poor prerehabilitation condition (including severe disability or spontaneous or continuous symptoms in conjunction with motion sensitivity) and abnormalities on four or more of the sensory organization tests have poorer outcomes following a course of rehabilitation.41,42,50 Computerized dynamic posturography has many potential benefits as an adjunct to treatment: The patient can be safely exposed to challenging balance situations including perturbations; the visual component of the computerized system gives useful biofeedback that can be withdrawn; the immediate feedback on performance is motivating. Controlled studies using computerized balance training have demonstrated improvements in postural stability (as measured by SOT and LOS), as well as functional improvements on the Berg balance scale and fall reduction in community-dwelling older adults.51,52

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CONSIDERATIONS AND LIMITATIONS Sensory Organization Test Conditions 1 and 2

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Figure 15-7. Performance of three patients with bilateral vestibular loss secondary to aminoglycoside ototoxicity on the sensory organization test demonstrates the variability in test performance that can occur even within the same diagnostic groups. A, One subject loses his balance only when both visual and somatosensory cues are altered (conditions 5 and 6). The other two subjects have additional difficulty when B, somatosensory feedback is altered (condition 4) or C, when visual feedback is altered (conditions 2 and 3). Equilibrium scores (higher number indicates more stable) for three trials of each condition are shown. Loss of balance is indicated by “stop.”

posturography has been used to document that a supervised program of customized vestibular exercises results in a greater improvement in stability than unsupervised generic exercises.45 In fact, subjects with peripheral vestibular dysfunction who underwent individualized vestibular rehabilitation improved performance on the SOT to within normal limits, while subjects in the control group did not change their SOT scores.21 In individuals with bilateral vestibular loss (BVL), improvements have been noted in functional limitations, as well as measures of disability and balance confidence although no significant changes were reported for the SOT.49 These findings indicate that although patients with BVL improve following therapy, they continue to demonstrate significant physical impairments.49 There is also some evidence that dynamic

The first two conditions (C1 and C2) of the SOT are static conditions (eyes open and closed) and as such have limited utility in documenting changes in postural stability with time or treatment. Most patients with unilateral vestibular lesions, for example, have normal static postural control, for their age, within 3 to 6 days after onset.31 The results from C1 and 2 may be more useful in documenting change in patients with bilateral vestibular loss. These patients have increased peak-to-peak AP sway during the early period after onset and continue to have a small but significant increase in AP sway even in the chronic stage.25 Age Equilibrium scores results obtained during testing must be interpreted based on the age of the subject (Figure 15-8). Across all ages, AP sway increases (lower equilibrium scores) for conditions in which somatosensory feedback is altered (conditions 4, 5 and 6).8,53,54 Additionally, performance on tests in which both visual and somatosensory cues are altered (tests 5 and 6) shows the greatest instability in all normal subjects, suggesting that these are the more difficult test conditions. The effect of altering both visual and somatosensory cues is greatest in subjects older than 70 years.8,53 Presumably, when both visual and somatosensory cues are altered, the subject must rely on vestibular cues in order to maintain balance (see Table 15-1). Increased difficulty maintaining balance on tests 5 and 6 in older subjects, therefore, may reflect age-related changes in the vestibular system or the increased difficulty of those tests.55,56 Wolfson and colleagues8 suggest that the poorer performance of older persons on tests in which visual and somatosensory feedback is altered is due to either biomechanical factors or to changes in central processing of sensory information. Regardless, test results of patients who are older must be made taking the normal age-related test scores into consideration.

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EQUILIBRIUM SCORES BY AGE

Equilibrium score

100 80 60 40 20 0 C1

C2

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C4

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C6

Figure 15-8. Anterior/posterior sway, as reflected by the equilibrium score, is shown for each of the different conditions of the sensory organization test for subjects of different ages. The higher the equilibrium score, the more stable the subjects. All age groups show an increase in AP sway (indicated by lower equilibrium scores) as the conditions become more difficult. Note that there is little variation in stability in people age 20 to 69 years across the different sensory organization test conditions (identified as C1–C6). In people 70 years and older, a decrement in postural stability is obvious primarily in conditions 5 and 6 (C5 and C6) in which both visual and somatosensory feedback are altered concurrently.

Sensory test conditions 20–29

30–59

60–69

70–85

Diagnosis

Center of Gravity Alignment

Presently, the results of the sensory organization tests are not considered to be useful in the diagnosis of specific disorders. This is because the results are variable even within specific diagnostic groups. Furthermore, considerable overlap occurs in results among different diagnostic groups and even between normal and abnormal subjects in the older population.8 The sensitivity of the sensory organization test in identifying vestibular disorders has been reported as between 45% and 95%, depending on the clinical criteria used to identify vestibular dysfunction.22,30,57 Goebel and Paige19 concluded that posturography testing did not distinguish between patients who did or did not experience vertigo. Attempts have been made to improve the sensitivity of dynamic posturography as a diagnostic tool by assessing postural stability with the subject’s head in different positions. The rationale is that head position will affect vestibular input if a unilateral vestibular deficit is present. Neither head extension nor lateral tilt has improved the sensitivity of dynamic posturography.58,59 Other work has examined the effect of horizontal head movement during the SOT. The results suggest that the addition of the head movements increases the difficulty of condition 5 of the SOT and therefore the sensitivity of posturography testing in identifying compensated peripheral vestibular lesions (Shepard, personal communication). It is also possible that the sensitivity of dynamic posturography may be increased if a measure other than peak-to-peak AP sway were used; for example, measures such as sway velocity may be more sensitive.60

The ability or inability to maintain balance may also be affected by COG alignment prior to the toes-up or toesdown perturbation. Shifts in static alignment posteriorly would be likely to result in loss of balance with toes-up perturbations, whereas shifts anteriorly would result in loss of balance with toes-down perturbations. Although loss of balance when the support surface is rotated toes-up may indicate retropulsion, it should be remembered that patients afraid of falling backward may shift their center of mass forward and therefore may lose their balance during toes-down perturbations.

Motor Control/Adaptation Tests: Automatic Postural Responses Abnormalities in force development and the latency to onset of force development of the automatic responses can be due to pain, leg length differences, limitation in ankle range of motion, and weakness as well as neurologic problems. Subject age has only a minimal effect on responses to translational perturbations.6

Subject Characteristics Age, gender, and height all affect the long-latency responses measured using surface electrode EMG. Increasing age of the subject results in increased latency to onset and duration of the short-latency response and in increased integrated amplitude and duration of the longlatency responses.61 Although Lawson and colleagues61 found subject height was correlated significantly with time to onset, it accounted for a relatively small amount of the variance of the latencies (3% to 21%). Initial Center of Gravity Alignment It is clinically important to recognize that these latencies can be altered if the subject leans either forward or backward. Leaning forward, for example, increases the length of the gastrocnemius/soleus muscle group prior to the stretch produced by the support surface movement. The added stretch imposed by rotating the support surface toes-up elicits a short-latency response with a shorter time to onset. Similarly, the latencies do not seem to be affected by head position or vision.9 Other than by leaning forward or backward, it is not possible to voluntarily modify the time to onset of the automatic postural responses.62 Measurement of reactive torque can be used as a screening test. When it yields abnormal results, a combination of measurement of reactive force and EMG activity can be used to determine

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whether abnormalities in the automatic postural responses are due to biomechanical or neurologic factors.

SUMMARY The use of force platforms has provided more detailed objective data in the assessment of postural control than that available through clinical examination alone. Current technology enables us to measure a patient’s ability to use different sensory cues for balance, to voluntarily weight shift, and to react to external perturbations. Some of these tests can assist in diagnosis, such as measures of sway frequency during quiet stance and EMG recordings of lower extremity muscle activity during automatic postural responses. Of particular interest is the ability of dynamic posturography to identify individuals who are at risk for falling; an ability that can lead to the initiation of appropriate intervention to prevent falls. In addition, posturography is effective in identifying performance abnormalities that suggest nonphysiologic balance problems. Dynamic posturography is a useful tool for establishing and monitoring treatment. Newly developed testing protocols should enable us to quantify postural stability during functional activities such as moving from sitting to stand or during ambulation.

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40. Fetter M, Zee DS, Proctor LR: Effect of lack of vision and of occipital lobectomy upon recovery from unilateral labyrinthectomy in Rhesus monkey. J Neurophys 59:394–407, 1988. 41. Shepard N, Telian SA: Programmatic vestibular rehabilitation. Otolaryngol Head Neck Surg 112:173–182, 1995. 42. Cass SP, Kartush JM, Graham MD: Clinical assessment of postural stability following vestibular nerve section. Laryngoscope 101:1056–1059, 1991. 43. Shepard N, Telian SA, Smith-Wheelock M: Habituation and balance retraining therapy: A retrospective review. Neurol Clin 8:459–475, 1990. 44. Horak FB, Jones-Rycewicz C, Black FO, Shumway-Cook A: Effects of vestibular rehabilitation on dizziness and imbalance. Otolaryngol Head Neck Surg 106:175–180, 1992. 45. Szturm T, Ireland DJ, Lessing-Turner M: Comparison of different exercise programs in the rehabilitation of patients with chronic peripheral vestibular dysfunction. J Vestib Res 4:461–479, 1994. 46. Black FO, Nashner LM: Postural disturbances in patients with benign paroxysmal positional nystagmus. Ann Otol Rhinol Laryngol 93:595–599, 1984. 47. Di Girolamo S, et al: Postural control in benign paroxysmal positional vertigo before and after recovery. Acta Otolaryngol 118:289–293, 1998. 48. Blatt PJ, et al: The effect of the canalith repositioning maneuver on resolving postural instability in patients with benign paroxysmal positional vertigo. Am J Otol 21:356–363, 2000. 49. Brown KE, Whitney SL, Wrisley DM, Furman JM: Physical therapy outcomes for persons with bilateral vestibular loss. Laryngoscope 111:1812–1817, 2001. 50. Telian SA, Shepard N, Smith-Wheelock M: Habituation therapy for chronic vestibular dysfunction: Preliminary results. Otolaryngol Head Neck Surg 103:89–95, 1990.

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51. Rose DJ, Clark S: Can the control of bodily orientation be significantly improved in a group of older adults with a history of falls? J Am Geriatr Soc 48:275–282, 2000. 52. Wolf SL, Barnhart HX, Ellison GL, Coogler CE: The effect of Tai Chi Quan and computerized balance training on postural stability in older subjects. Atlanta FICSIT Group. Frailty and Injuries: Cooperative Studies on Intervention Techniques. Phys Ther 77:371–381, 1997. 53. Camicioli R, Panzer VP, Kaye J: Balance in the healthy elderly: Posturography and clinical assessment. Arch Neurol 54:976–981, 1997. 54. Cohen H, et al: Changes in sensory organization test scores with age. Age Ageing 25:39–44, 1996. 55. Baloh RW, Jacobson KM, Socotch TM: The effect of aging on visuo-vestibulo-ocular responses. Exp Brain Res 95:509–516, 1993. 56. Paige GD: Senescence of human visual-vestibular interactions. 1. Vestibulo-ocular reflex and adaptive plasticity with aging. J Vestib Res 2:133–151, 1992. 57. Hamid MA, Hughes GB, Kinney SE: Specificity and sensitivity of dynamic posturography, Acta Otolaryngol 481 (Stockh) (Suppl):586–600, 1991. 58. Barin K, Seitz CM, Welling DB: Effect of head orientation on the diagnostic sensitivity of posturography in patients with compensated unilateral lesions. Otolaryngol Head Neck Surg 106:355–362, 1992. 59. Chandra NS, Shepard NT: Clinical utility of lateral head tilt posturography. Am J Otol 17:271–277, 1996. 60. Baloh RW et al: Posturography and balance problems in older people. J Am Geriatr Soc 43:638–644, 1995. 61. Lawson GD, et al: Electromyographic responses of lower leg muscles to upward toe tilts as a function of age. J Vest Res 4:203–214, 1994. 62. Diener HC, et al: Early stabilization of human posture after a sudden disturbance: Influence of rate and amplitude of displacement. Exp Brain Res 56:126–134, 1984.

Chapter

16 Steven D. Rauch, MD

Vestibular Evoked Myogenic Potentials Outline Introduction Discovery of Vestibular Evoked Myogenic Potentials Basic Physiology of Vestibular Evoked Myogenic Potentials

INTRODUCTION Brief (0.1 msec) loud (>90 dB sound pressure level, SPL) monaural clicks or tone bursts produce a large (60 to 300 μV ) short-latency (8 msec) inhibitory potential in the tonically contracted ipsilateral sternocleidomastoid muscle, known as vestibular evoked myogenic potentials (VEMP). Considerable robust evidence supports the contention that VEMP is a vestibulocolic reflex whose afferent limb arises from acoustically responsive neurons in the saccule, with signals conducted centrally via the inferior vestibular nerve. Thus the VEMP can be used as a test of otolith organ and peripheral vestibular function. Since it depends on both sound transmission through the middle ear and structural integrity of the saccule, it also has merit in diagnosis of superior semicircular canal dehiscence syndrome and in Ménière’s syndrome (cochleosaccular hydrops).

DISCOVERY OF VESTIBULAR EVOKED MYOGENIC POTENTIALS Thirty-five years ago, when the science of averaged evoked response measurement was in its infancy, Bickford, Cody, and others first characterized the range of evoked responses in human subjects.1–5 The postauricular response was determined to be an acoustically evoked contraction, or “sonomotor” response, of the postauricular muscle. The integrity of the cochlea and cranial nerve VII were required for this response to be present. In contrast, the inion response, named for the posterior scalp location where it was maximally recorded, was present in deaf patients but absent in patients after vestibular neuronitis or vestibular neurectomy. Though initially thought to arise from cortex, the averaged inion response was eventually demonstrated to originate from extracranial musculature.2 Furthermore, the inion response was preserved in patients with semicircular canal ablation due to streptomycin toxicity and in 270

Measuring Vestibular Evoked Myogenic Potentials Clinical Applications of Vestibular Evoked Myogenic Potentials Future Directions

patients with benign paroxysmal positional vertigo, but absent in patients with advanced Ménière’s disease and Ménière’s patients having undergone a Cody tack procedure.6 Based on these observations, Townsend and Cody proposed that the averaged inion response to acoustic stimulation was mediated by the saccule.6

BASIC PHYSIOLOGY OF VESTIBULAR EVOKED MYOGENIC POTENTIALS Speculation about the origin of VEMP has been supported by animal research. McCue and Guinan identified acoustically responsive fibers in the cat vestibular nerve.7,8 Singleunit recordings from the inferior vestibular nerve in these animals revealed fibers with irregular background activity that phase-lock to low-frequency (800 Hz) tone bursts of 80 dB SPL and show increased firing rates with increasing stimulus intensity. In these same fibers acoustic clicks evoked action potentials with minimum latencies of 1.0 msec. Fibers fell into two classes: with the shortest latency either to compression (“push” fibers) or rarefaction (“pull” fibers) clicks. The observation of preferred response phases approximately 180 degrees apart was interpreted to mean that fibers innervate hair cells having opposite morphologic polarity, an arrangement found in the saccule. Biocytin fiber labeling and tracing confirmed bipolar cell bodies in the inferior vestibular ganglion with peripheral processes innervating saccular epithelium and central processes going to vestibular nuclei and a region ventromedial to the cochlear nucleus.

MEASURING VESTIBULAR EVOKED MYOGENIC POTENTIALS Short broadband clicks or tone bursts of 0.1-msec duration delivered via headphones can be used as stimuli for VEMP testing. The response is recorded electromyographically

Vestibular Evoked Myogenic Potentials

(EMG) using surface electrodes over the ipsilateral sternocleidomastoid muscle. The positive electrode is positioned over the upper third of the muscle, and the negative electrode is positioned over the muscle tendon just above the clavicle. Patients are seated upright and instructed to turn their head forcefully away from the test ear (i.e., try to push their chin over the contralateral shoulder). This tenses the ipsilateral sternocleidomastoid muscle, a necessity for measuring the inhibitory VEMP response. Ongoing EMG activity is visually monitored on an oscilloscope to ensure uniform muscle tension during testing, and patients are instructed to relax their neck muscles between runs. The EMG recording is bandpass filtered and averaged as in evoked response audiometry. The resultant response consists of a biphasic wave with an initial positive peak (P1) at 12–13 msec latency and a subsequent negative peak (N1) at 22–23 msec latency (Fig. 16-1). A number of investigators have sought to characterize the normal VEMP response.9–16 These studies have shown that the VEMP is more consistently detectable and has a lower threshold for click than tone burst stimuli. The click-evoked VEMP has a normal threshold of 85 to 90 dB SPL. With tone bursts, there is a “tuning curve” showing greatest sensitivity (i.e., lowest threshold) for frequencies of 500 to 1000 Hz. Systematic variation of stimulus rate shows decreasing VEMP P1 latency with increasing rate. Above the 5-Hz stimulus rate, VEMP peak-to-peak amplitude decreases with increasing rate. Above the threshold, VEMP amplitude increases with stimulus level. Amplitude of the VEMP response is proportional to the mean level of tonic muscle activation of the sternocleidomastoid during recording.

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CLINICAL APPLICATIONS OF VESTIBULAR EVOKED MYOGENIC POTENTIALS Clinical utility of VEMP testing has been demonstrated in three areas: assessment of vestibular nerve function, diagnosis of superior semicircular canal dehiscence syndrome, and evaluation of Ménière’s syndrome. Colebatch and Halmagyi first noted that the VEMP response was extinguished following ipsilateral vestibular neurectomy and speculated that the response may provide useful information in assessment of patients with hearing and balance disorders.17 Murofushi and colleagues studied VEMP and its relation to vestibular neuritis and benign paroxysmal positional vertigo (BPPV).18 They found the VEMP absent in 16 of 47 vestibular neuritis patients, none of whom went on to develop BPPV. In 10 of 47 patients with vestibular neuritis, BPPV did develop and all 10 had intact VEMP. These findings indicate that absent VEMP in acute vestibular neuritis is indicative of inferior vestibular nerve involvement. Such patients lose innervation of the saccule and posterior semicircular canal and therefore lose the VEMP reflex and cannot develop BPPV. Acute vestibular neuritis patients with intact VEMP have involvement of their superior vestibular nerve. A significant proportion of them go on to degeneration of the utricle, with subsequent shedding of otoconia and symptomatic BPPV. In another study, Murofushi and colleagues showed that the VEMP is abnormal in 80% of acoustic neuroma patients, even in the presence of normal calorics.19 As might be predicted, the test is particularly sensitive for inferior vestibular nerve involvement.19–21 The value of VEMP in diagnosis of superior canal dehiscence syndrome is due to the fact that the dehiscence creates a “path of least resistance” that shunts acoustic energy through the vestibular labyrinth rather than through the cochlea. This yields three clinical effects: a pseudoconductive hearing loss, a Tullio phenomenon of acoustically evoked vertigo, and a lowered VEMP threshold. The VEMP threshold is typically about 20 dB lower in superior canal dehiscence cases than in normal subjects (70 dB vs. 95 dB).22–24 All patients with classic Ménière’s syndrome have cochleosaccular hydrops.25 Because saccular afferents give rise to the VEMP response, it is logical to expect that altered motion mechanics of the distended saccule might create an altered VEMP in Ménière’s patients. This has been confirmed in several studies.26–32 De Waele and coworkers studied click-evoked potentials in 59 Ménière’s patients and found the neck response absent in 54%.26 Likewise, Murofushi and colleagues found the VEMP response delayed or absent in 51% of Ménière’s subjects.30 A few studies have also combined the VEMP with glycerol or furosemide “dehydration testing” and shown alteration of the VEMP response after administration of the osmotic agent.31–33 Whether this refinement of the VEMP test significantly enhances its sensitivity or specificity remains to be seen.

Latency (ms) Figure 16-1. Normal VEMP response. A typical VEMP response, evoked by a 250-Hz tone burst stimulus at 123 dB peak pressure (90 dB HL). The response shows a positive peak, P1, at approximately 12 msec and a negative peak, N1, at approximately 22 msec. Values measured include peak-to-peak amplitude, P1 latency, and N1 latency.

FUTURE DIRECTIONS Notwithstanding existing demonstrations that the clickevoked and tone burst-evoked VEMP are altered in

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peripheral vestibulopathies, such as vestibular neuritis, superior canal dehiscence syndrome, and Ménière’s syndrome, much work remains to be done to understand, characterize, and use the VEMP clinically. Specifically, the effects of stimulus rate and intensity on click-evoked response, the frequency-specific thresholds (“tuning curve”) of the tone burst-evoked response, and the modulating effect of gravitational input to the saccule during testing have not been adequately defined for different disorders. The specific nature of these alterations will have implications for biophysical models of the saccule. Correlation of VEMP results with other vestibular function tests, and especially with other otolith organ tests, such as subjective visual vertical (SVV) or off-vertical axis rotation (OVAR), has not been systematically studied. Results of such investigations are likely to improve our understanding of the physiology of the otolithic vestibular organs as well as provide the refinements of the VEMP test protocol that improve its diagnostic sensitivity and specificity.

REFERENCES 1. Bickford RG, Jacobson JL, Cody DTR: Opportunities and pitfalls in the processing of neuroelectric data: Observations on averaged potentials recorded from the scalp in man. In Fifth IBM Medical Symposium, 1963. 2. Bickford RG, Jacobson JL, Cody DTR: Nature of average evoked potentials to sound and other stimuli in man. Ann NY Acad Sci 112:204, 1964. 3. Cody DTR, Jacobson JL, Walker JC, Bickford RG: Average evoked myogenic and cortical potentials to sound in man. Ann Otol Rhinol Laryngol 73:763, 1964. 4. Jacobson JL, Cody DTR, Lambert EH, Bickford RG: Physiologic properties of the post-auricular response (sonomotor) in man [abstr]. Physiology 7:167, 1964. 5. Kiang NYS: An auditory physiologist’s view of Ménière’s syndrome. In Second International Symposium on Ménière’s Disease. Cambridge, MA, Kugler & Ghedini Publications, 1988. 6. Townsend GL, Cody DTR: The averaged inion response evoked by acoustic stimulation: Its relation to the saccule. Ann Otol Rhinol Laryngol 80:121, 1971. 7. McCue MP, Guinan JJ Jr: Influence of efferent stimulation on acoustically responsive vestibular afferents in the cat. J Neurosci 14:6071, 1994. 8. McCue MP, Guinan JJ Jr: Acoustically responsive fibers in the vestibular nerve of the cat. J Neurosci 14:6058, 1994. 9. Colebatch JG, Halmagyi GM, Skuse NF: Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190, 1994. 10. Bath AP, Harris N, Yardley MP: The vestibulo-collic reflex. Clin Otolaryngol 23:462, 1998. 11. Wu CH, Young YH, Murofushi T: Tone burst-evoked myogenic potentials in human neck flexor and extensor. Acta Otolaryngol 119:741, 1999. 12. Wu CH, Murofushi T: The effect of click repetition rate on vestibular evoked myogenic potential. Acta Otolaryngol 119:29, 1999.

13. Welgampola MS, Colebatch JG: Characteristics of tone burstevoked myogenic potentials in the sternocleidomastoid muscles. Otol Neurotol 22:796, 2001. 14. Ochi K, Ohashi T, Nishino H: Variance of vestibular-evoked myogenic potentials. Laryngoscope 111:522, 2001. 15. Cheng PW, Murofushi T: The effects of plateau time on vestibularevoked myogenic potentials triggered by tone bursts. Acta Otolaryngol 121:935, 2001. 16. Cheng PW, Murofushi T: The effect of rise/fall time on vestibularevoked myogenic potential triggered by short tone bursts. Acta Otolaryngol 121:696, 2001. 17. Colebatch JG, Halmagyi GM: Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. Neurology 42:1635, 1992. 18. Murofushi T, Halmagyi GM, Yavor RA, Colebatch JG: Absent vestibular evoked myogenic potentials in vestibular neurolabyrinthitis. An indicator of inferior vestibular nerve involvement? Arch Otolaryngol Head Neck Surg 122:845, 1996. 19. Murofushi T, Matsuzaki M, Mizuno M: Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg 124:509, 1998. 20. Tsutsumi T, Tsunoda A, Noguchi Y, Komatsuzaki A: Prediction of the nerves of origin of vestibular schwannomas with vestibular evoked myogenic potentials. Am J Otol 21:712, 2000. 21. Chen CW, Young YH, Wu CH: Vestibular neuritis: Threedimensional videonystagmography and vestibular evoked myogenic potential results. Acta Otolaryngol 120:845, 2000. 22. Streubel SO, Cremer PD, Carey JP, et al: Vestibular-evoked myogenic potentials in the diagnosis of superior canal dehiscence syndrome. Acta Otolaryngol Suppl 545:41, 2001. 23. Brantberg K, Bergenius J, Tribukait A: Vestibular-evoked myogenic potentials in patients with dehiscence of the superior semicircular canal. Acta Otolaryngol 119:633, 1999. 24. Ostrowski VB, Byskosh A, Hain TC: Tullio phenomenon with dehiscence of the superior semicircular canal. Otol Neurotol 22:61, 2001. 25. Rauch SD, Merchant SN, Thedinger BA: Ménière’s syndrome and endolymphatic hydrops. Double-blind temporal bone study. Ann Otol Rhinol Laryngol 98:873, 1989. 26. de Waele C, Huy PT, Diard JP, et al: Saccular dysfunction in Ménière’s disease. Am J Otol 20:223, 1999. 27. Heide G, Freitag S, Wollenberg I, et al: Click evoked myogenic potentials in the differential diagnosis of acute vertigo. J Neurol Neurosurg Psychiatry 66:787, 1999. 28. Akin FW, Murnane OD: Vestibular evoked myogenic potentials: Preliminary report. J Am Acad Audiol 12:445, 2001. 29. Colebatch JG: Vestibular evoked potentials. Curr Opin Neurol 14:21, 2001. 30. Murofushi T, Shimizu K, Takegoshi H, Cheng PW: Diagnostic value of prolonged latencies in the vestibular evoked myogenic Potential. Arch Otolaryngol Head Neck Surg 127:1069, 2001. 31. Murofushi T, Matsuzaki M, Takegoshi H: Glycerol affects vestibular evoked myogenic potentials in Ménière’s disease. Auris Nasus Larynx 28:205, 2001. 32. Shojaku H, Takemori S, Kobayashi K, Watanabe Y: Clinical usefulness of glycerol vestibular-evoked myogenic potentials: Preliminary report. Acta Otolaryngol Suppl 545:65, 2001. 33. Seo T, Yoshida K, Shibano A, Sakagami M: A possible case of saccular endolymphatic hydrops. ORL J Otorhinolaryngol Relat Spec 61:215, 1999.

Assessment and Remediation

17

Outline Introduction Definition of Auditory Processing Prevalence of Auditory Processing Disorders Historical Perspective Behavioral Tests of Auditory Processing Manner of Presentation Monaural Measures Binaural Measures Dichotic Measures Anatomical Level Tested Electrophysiologic Tests Auditory Brainstem Response Auditory Middle-Latency Response The P300 Mismatch Negativity Other Late Auditory Evoked Responses Factors Affecting Auditory Processing Test Results Subject’s Age Peripheral Hearing Loss

Chapter

Central Auditory Processing Disorders

Intelligence, Cognition, and Language Medications Auditory Processing Testing Children Adults Screening for Auditory Processing Disorders A Multidisciplinary Approach Goals Test Battery Components Test Interpretation Remediation of Auditory Processing Disorders Auditory Processing Abilities in the Elderly Auditory Processing Testing in Hearing Aid Applications Future Directions Functional Magnetic Resonance Imaging Brain Mapping and Scalp Topography Summary

INTRODUCTION For many years clinicians have recognized, according to pure tone thresholds and other standard audiometric tests, a population of patients whose ability to hear in everyday situations is poorer than expected. These patients may have hearing that is within normal limits to pure tones but still have difficulty hearing in noisy situations, when several persons are speaking at a time, or when in a reverberant room. Patients who have a chronic disease that affects the central nervous system may have problems with comprehension of auditory information. In many cases, a disorder of auditory processing has been identified. This chapter was written for the neurotologist with two purposes in mind: to provide an understanding of the basics of auditory processing testing and remediation and to discuss the latest developments and issues in this ever-growing field. A note about terminology is in order. Until recently, auditory processing disorders were referred to as central

Wileen Chang, MS Robert W. Keith, PhD

auditory processing disorders, auditory perceptual disorders, and auditory language-learning disorders.1 The most recent change of terminology from central auditory processing disorders (CAPD) to auditory processing disorders (APD) was made to avoid the implication of the exact site of lesion and to emphasize the interaction of peripheral and central disorders and processes.2

DEFINITION OF AUDITORY PROCESSING According to the American Speech-Language-Hearing Association (ASHA) Task Force on Central Auditory Processing, central auditory processes [auditory processing] are “auditory system mechanisms and processes responsible for the following behavioral phenomena: Sound localization and lateralization Auditory discrimination Auditory pattern recognition 273

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Temporal aspects of audition, including temporal resolution, temporal masking, temporal integration, and temporal ordering Auditory performance decrements with competing acoustic signals Auditory performance decrements with degraded acoustic signals These mechanisms and processes are to apply to nonverbal as well as verbal signals and to affect many areas of function, including speech and language.”3 A central auditory processing disorder [auditory processing disorder] “is an observed deficiency in one or more of the above-listed behaviors.”3 To further define these terms, sound localization refers to a person’s ability to find the direction of a sound source. Sound lateralization refers to a person’s ability to determine where inside the head a sound appears to be (e.g., on the right side of the head, left side, or in the center). Auditory discrimination refers to one’s ability to determine if two sounds are the same or different. Temporal resolution describes the process in which timing cues are distinguished (e.g., a measure of how much time must be inserted between two tones for them to be perceived as two distinct tones [gap detection]). Temporal masking refers to forward and backward masking. In this phenomenon, noise that is presented slightly before or after a stimulus can partially mask or cover part of the stimulus. Temporal integration is the increase in sound intensity required to hear a sound of shorter duration. So, for example, a tone of 200 milliseconds will have a 10-dB lower threshold than a tone that lasts only 20 milliseconds. Finally, temporal ordering involves the ability to recognize the sequence of acoustic stimuli as they occur in time.

PREVALENCE OF AUDITORY PROCESSING DISORDERS Prevalence of APD varies; there is no “gold standard” for measuring the prevalence of APD. Many children who have learning disabilities (prevalence of 4% to 5%) also have APD.4,5 Chermak and Musiek6 estimate that APD occurs in 2% to 3% of all children, with a 2:1 male-to-female ratio. The literature presents the prevalence of auditory processing disorders in adults across a broad range, depending on the investigator and criterion used. The prevalence in adults ranges from 0% to 75% (1% to 23% in Cooper & Gates,7 19% in Gang,8 58% in Kricos et al,9 60% in Rodriguiez et al,10 74% in Arnst,11 74% in Shirinian and Arnst,12 and 75% in Stach et al13).

HISTORICAL PERSPECTIVE Early research of central auditory testing was conducted in the 1950s in Milan, Italy, by a group of otolaryngologists that included Bocca, Calearo, Antonelli, and Teatini.14 Those early investigators recognized that routine audiometric tests do not identify lesions affecting the central hearing pathways. Special techniques, called sensitized speech tests, were needed to identify those lesions. Sensitized speech measures use speech stimuli (syllables, words, or sentences)

that are distorted in some way to reduce the intelligibility of the message. The basic principle of sensitized speech testing is that the distorted message can be understood by persons with normal hearing and a normal central auditory system. When an auditory processing disorder is present, however, speech intelligibility will be poor. The construct of sensitized speech testing is extremely powerful and is the basis of all behavioral speech tests of central auditory function. The purpose of central auditory testing—initially to identify lesions of the brainstem and cortex—has changed as a result of developments in radiology with techniques such as magnetic resonance imaging. Currently, auditory processing testing in children focuses on identifying problem areas that affect academic performance. In adults the focus is on determining how APD affects communication and vocational achievement. In both populations, then, the focus is on what Bergman and colleagues15 refer to as the “functional disorders of communication” or “functional auditory performance deficits.”3

BEHAVIORAL TESTS OF AUDITORY PROCESSING The premise of behavioral testing of auditory processing lies in the concept of using sensitized speech measures to reduce extrinsic redundancy. Speech contains multiple acoustic and linguistic cues, not all of which are necessary to understand the incoming message. For example, in the sentence “the cats are drinking milk,” it is not necessary to hear the s at the end of “cats” to know that more than one cat is being discussed; the verb are signals the plural form. Speech carries a multitude of other redundant linguistic cues, such as tense and intonation. In addition, the speech signal typically contains a greater amplitude and a wider range of frequencies than is necessary for understanding. For instance, most people can easily understand quiet speech even though the frequency and amplitude spectrum is very different from normal conversational speech. In addition, most persons can understand speech on the telephone, which has a limited frequency range compared to normal face-to-face communication. The frequency range on a telephone is 300 to 3000 Hz, whereas face-to-face communication has a range of 250 to 6000 Hz. The structure of the central auditory nervous system (CANS) itself creates intrinsic redundancy. The CANS is well documented as a complicated neural network of ipsilateral and contralateral connections that originate and terminate at multiple points. Auditory information is conveyed via many neural pathways to the auditory cortex, and the system is wired to be intrinsically redundant. Therefore, if one neural pathway is damaged, the system can often perform normally in ideal, quiet listening situations. The system with a lesion in the CANS can compensate, given the extrinsic redundancy that exists in this situation. However, if a damaged system with decreased intrinsic redundancy is placed in an environment that has decreased extrinsic redundancy (e.g., hearing in background noise), the system is unable to compensate. The information needed to understand the speech signal cannot reach the auditory cortex and the person cannot understand the incoming speech. Most behavioral tests of central auditory

Central Auditory Processing Disorders: Assessment and Remediation

processing decrease the extrinsic redundancy of the incoming signal to “tax” the central auditory nervous system. Despite the vast number of them, behavioral auditory processing tests can be classified by two methods: the manner of stimulus presentation16 or the anatomic level being tested. In the first method of categorization, called the manner of presentation, the tests are distinguished by how the stimuli are presented: monaural, binaural, and dichotic. In monaural tests, a single stimulus or multiple stimuli are presented to one ear. In binaural tests, stimuli are presented to both ears. The third category, dichotic testing, is a special kind of binaural test. During dichotic testing, two different signals with equal onset and offset times are presented to the two ears simultaneously. This form of testing is separated out from other binaural tests because of its importance in APD assessment.

Manner of Presentation Behavioral AP tests are broadly classified as monaural, binaural, or dichotic according to the manner in which they are presented and the way in which the signal is configured. Monaural Measures

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ratio or “10dB S/N ratio.” Signal-to-noise ratios can be positive or negative, depending on whether the speech or noise is higher in intensity. Examples of this form of test include the Auditory Figure Ground subtests of the SCAN–C17 and SCAN–A,18 the Speech Perception in Noise (SPIN) test,21 and the QuickSIN test.22 A notable instrument that has withstood the test of time is the Synthetic Sentence Identification–Ipsilateral Competing Message (SSI-ICM) test, developed by Jerger, Speaks, and Trammel.23 Frequency and Duration Pattern Recognition The frequency patterns test (FPT) includes two frequencies presented in six patterns of high and low. The patient is asked to identify the tone pattern (e.g., high-high-low, low-high-low). The duration patterns test (DPT) presents one frequency in six patterns of two durations (e.g., 350 msec and 500 msec). The patient identifies the pattern of the signal (e.g., short-long-short, long-long-short). The FPT and the DPT are nonlinguistic (nonlanguage) tasks; however, the response can be either linguistic (the patient labels the stimulus pattern) or nonlinguistic (the patient manipulates blocks to represent the stimulus pattern). Recent research states that abnormalities in DPTs may indicate the presence of a cortical lesion.24

Filtered Speech or Frequency-Altered Speech

Temporal Processing Disorders/Gap Detection Tests

In this form of sensitized speech measure, the patient is asked to repeat single-syllable words. These words, however, are low-pass filtered to reduce the amount of highfrequency information. Low-pass filtering is commonly done using cut-off frequencies of 500, 750, or 1000 Hz at either 18 dB or 32 dB per octave. Two current, normreferenced tests for filtered speech are the Filtered Words subtest of the SCAN–C Test for Auditory Processing Disorders in Children–Revised17 and the same subtest in the SCAN–A Test for Auditory Processing Disorders in Adolescents and Adults.18

Temporal processing disorders can be identified using gap detection tests. In this method, two tones are presented with a variable time interval between the tones. The patient reports whether one or two tones were heard. The gap detection threshold is the shortest time gap in which the patient perceived two tones. Patients with a normal auditory system can identify time intervals as brief as 2 milliseconds between tones, with a normal average gap detection threshold of approximately 10 milliseconds. When gap detection thresholds exceed 20 milliseconds, the individual is likely to have difficulty discriminating speech sounds, and a temporal processing disorder is said to exist. A current test of gap detection is the Random Gap Detection Test (RGDT).25

Time-Compressed Speech In this test speech is compressed in a shorter time frame by removing some segments of the speech signal and putting the remaining segments back together. Beasley, Schwimmer, and Rintleman19 found that persons with normal auditory perception understand speech with time compression rates up to 50% but have difficulty with time compression of 60% or greater. An example of this test is the Time Compressed Sentence Test (TCST),20 which presents sentence material at 40% and 60% time compression. This test is norm-referenced for children from 6 to 12 years old. Background Noise Three terms—speech recognition in noise, auditory figure ground, and speech in competition—describe the same basic task. The subject is asked to repeat words or sentences spoken when background noise is present. The competing signal can be linguistic, ranging from a single speaker to a multiple-speaker speech babble, or it can be nonspeech, such as white noise or speech noise. The level of the speech in relation to the competing signal is often described in terms of a signal-to-noise ratio. Thus, a speech signal that is 10 dB higher in intensity than the competing noise is described as a 10-dB signal-to-noise

Binaural Measures Masking Level Differences Masking level differences (MLDs) are tested to determine the presence of brainstem abnormalities based on a phenomenon called binaural release from masking. This process is tied to the auditory system’s ability to detect timing differences between ears. Detecting timing cues is actually the detection of phase differences between ears and is used in the localization of sounds, especially lowfrequency ones. The concept of binaural release from masking is as follows. Tones can be presented between ears which are in phase and out of phase with one another. In-phase tones are presented first. A masking noise is introduced to just cover the tone. If the tones are changed to be out of phase, the tone becomes audible again and is “released from masking.” Binaural release from masking is a result of brainstem processing at the level of the superior olivary complex.26 In addition, speech can be used instead of tones as the target stimulus.

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In the MLD test, the MLD is the difference in intensity needed for the tone to be just audible over the masking noise between the in-phase and out-of-phase conditions. For a 500-Hz tone, the MLD should be greater than 7 dB with an average of approximately 12 dB.26 Wilson and colleagues27 found MLDs of approximately 13 dB for a 500Hz tone in normal young adult listeners. MLDs lower than normal are consistent with lower brainstem dysfunction. A number of studies indicate that abnormal MLDs are consistent with disorders of the brainstem.28–32 The largest MLD effects are seen in the lower frequencies (300 to 600 Hz).33 The introduction of a prerecorded MLD test on compact disc by Wilson and colleagues27 simplifies the procedure and makes it feasible for more clinics to perform this test.

Abnormal dichotic test results are associated especially with lesions of the corpus callosum or auditory cortex.26 Dichotic measures include the following:

Localization

Auditory processing tests can also be categorized according to the presumed anatomic level being assessed (see Table 17-1). The bottleneck principle, discussed in the “Test Interpretation” section, should be considered as well.

Localization is the ability to identify the source of sounds in the surrounding environment. Poor localization ability is associated with auditory brainstem disorders26,34,35 and cortical disorders.26,35,36 Although tests that use localization are common when investigating hearing in infants behaviorally (visual reinforcement audiometry), testing of localization for purposes of central auditory disorders is not practiced in most centers. A promising strategy has been recently described by Koehnke and Besin’s 3-D (three-dimensional) auditory test of localization, in which virtual reality techniques and digital signal processing are used to assess localization under headphones.37 Dichotic Measures Dichotic testing is an extremely sensitive measure of auditory maturation and auditory nervous system function and dysfunction. During dichotic testing, different speech signals with equal onset and offset times are presented simultaneously to both ears. A number of speech stimuli are used, including nonsense syllables, numbers (referred to as “digits”), monosyllabic words, compound words or spondees, sentences, and nonsense sentences. Test instructions include both free recall (the subject replies with whatever was heard in no given order) or directed ear (both stimuli are repeated under instructions of “right ear first” or “left ear first”). Dichotic tests of young subjects find a strong right ear advantage (REA), that is, better scores in the right ear than the left. The REA results from the direct relationship between the right ear and the dominant left language hemisphere. As children approach 12 to 14 years, the REA disappears, which is a sign of auditory maturation. In normal adults, a slight REA is often observed. However, individuals with lesions of the auditory regions of the central nervous system (CNS) or those with APD show various response patterns including: Deficits in left ear performance Poor overall performance Enhanced right ear advantage Switch from right ear advantage on a “directed right” condition to a left ear advantage on “directed left” listening condition

Dichotic Consonant-Vowel (CV) test Dichotic Digits38 Staggered Spondaic Word (SSW) test39 Competing Sentence Test40 Dichotic Sentence Identification (DSI) test41 Competing Words and Competing Sentences subtests of the SCAN–C Test for Auditory Processing Disorders in Children–Revised17 and SCAN–A Test for Auditory Processing Disorders in Adolescents and Adults18

Anatomic Level Tested

ELECTROPHYSIOLOGIC TESTS The role of electrophysiologic testing has great promise in the auditory processing test battery. A large body of literature has emerged in the past decade in this arena. Electrophysiologic tests discussed for use in APD assessment include the auditory brainstem response (ABR), the middle-latency response (MLR), the P300, the mismatch negativity (MMN), and other late auditory evoked responses. One reason to conduct electrophysiologic tests is to rule out auditory neuropathy. This phenomenon is characterized by normal otoacoustic emissions, absent or abnormal ABR, and absent acoustic reflexes. The implication of these findings is that persons with auditory neuropathy have normal cochlear outer hair cell function with abnormal neural synchrony of cranial nerve VIII or abnormal cochlear inner hair cell function.42 The remediation efforts for auditory neuropathy are significantly different from those for APD, and they include possible cochlear implantation. Nevertheless, the requirement that all children

TABLE 17-1. Auditory Processing Tests Anatomic Level

Type of Test

Brainstem

Masking level differences, lower brainstem lesions Binaural fusion of low- and high-pass filtered speech Rapidly alternating speech Localization Lateralization Dichotic tests Low-pass filtered word tests Auditory figure ground, speech recognition in noise Time-compressed speech Difficult monaural tasks Impaired localization Reduced temporal processing Frequency and duration pattern recognition

Cerebral cortex

Nondominant hemisphere

Central Auditory Processing Disorders: Assessment and Remediation

undergo electrophysiologic tests as part of an APD assessment remains controversial.2,43,44 Electrophysiologic testing does have significant limitations and considerations. First, although these are physiologic responses, they are not truly objective because they need to be interpreted by an examiner. In addition, subjects must often cooperate during testing. This may mean that subjects need to rest quietly during the test or need to pay close attention to a task. Middle-latency and cortical evoked potentials especially are affected by sleep states and attention.

Auditory Brainstem Response The best known of the auditory evoked potentials, the ABR is a series of neurologic responses that are assumed to reflect the sequence of activity of the auditory nerve and nerve tracts and nuclei of the ascending auditory pathway.45 These compound action potentials result from an acoustic stimulus of a fast rise time (a click) and occur within the first 10 milliseconds following the stimulus. Because the ABR reflects pontine-mesencephalic transmission of neural activity, it is a measure of central auditory processing at the brainstem level. Early investigators reported abnormalities in the ABR in children with auditory processing and language-learning disorders.46–49 Stein and Kraus report various studies showing ABR abnormalities in patients with confirmed hydrocephalus, autism, and Down syndrome.50 Lynn and colleagues report ABR abnormalities in patients with olivopontocerebellar degeneration.51 Keith and Jacobson report ABR abnormalities commonly observed in patients with multiple sclerosis.52 A newer application of the ABR in auditory processing is maximum-length sequences. (See Jirsa53 for further information.) Since these early studies, a vast literature has grown to document the validity and efficacy of ABR testing in a wide range of populations.

Auditory Middle-Latency Response The middle-latency components of the auditory evoked response occur after the ABR and within the first 100 milliseconds following the presentation of an effective auditory stimulus.6 There are two major positive and negative peaks in the response, typically labeled Na, Pa, Nb, and Pb.54 The MLR is believed to have multiple generators, including the temporal lobe or thalamocortical projects, the reticular formation, thalamus, and inferior colliculus, as well as contributions outside of the central auditory nervous system.55 It is affected by the depth of sleep, which may explain the variability found in the MLR of children. It is best obtained when awake.55 In regards to age effects, MLRs in infant and young children have different morphologies and latencies from those in adults. Kraus and colleagues reported that detectability of the MLR increased significantly as a function of age. Detection of MLR Na components increased from 75% to 90% as subjects’ age increased from 0 to 20 years. The detection of the Pa component increased from 40% to 90% during the same time frame.56 Jerger and colleagues published a case report of an 11-year-old boy with a classic history of auditory processing

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disorder.57 The MLR obtained on that child was abnormal with no repeatable patterns in the responses from either ear. Fifer and Sierra found a correspondence with abnormal performance on the SSW test and the MLR in a 7-year-old with auditory processing disorder.58 Jerger and colleagues, Fifer and Sierra, and Ozdamar and Kraus all postulated that the MLR has potential for identifying and understanding central auditory processing disorders.57–59 This evoked response’s degree of success in the assessment of auditory processing disorders is yet to be established.

The P300 The P300 is a cognitive evoked potential that evaluates attention and information processing. One of the late auditory evoked responses, it is also known as P36. It consists of one large peak that occurs approximately 300 milliseconds after an effective stimulus,54 hence the name P300. To elicit the P300, an “oddball paradigm” is employed. A series of stimuli are presented to the patient, with an occasional different stimulus, or “oddball,” presented about 20% of the time. The patient’s task is often to attend to the oddball stimuli, often by counting them. The attention to the oddball stimuli causes the P300 to appear. The P300 is greatly influenced by the subject’s attention, alerting, arousal, and psychological state with small or delayed amplitude responses occurring when there is some abnormality of cognitive processing.60 As such it has been used to study attention deficit and auditory processing disorders in children. For example, Jirsa and Clontz found reduced amplitude of the P300 in a group of children with auditory processing disorders.61 Jirsa also found that the P300 decreased in latency and increased in amplitude after structured treatment in an APD group of children.62

Mismatch Negativity The mismatch negativity is a late, endogenous evoked potential that occurs after 100 milliseconds and after the P2 late cortical response. Kraus and colleagues studied the MMN in detail.63 They report that the MMN is associated with neurophysiologic processing during discrimination of acoustic stimuli. They note that it is especially appealing because it is not influenced by attention and does not require a behavioral response from the subject, even though it is elicited with an oddball paradigm, as with the P300. It also is free of the confounding effects of language development, cognitive ability, and behavioral development. They also indicate that the MMN is stable throughout the school years (ages 6-15 years) and provide MMN normative data for speech syllable stimuli. It is interesting to note that they found changes in the MMN that occurred with some speech stimuli but that were not distinguished in conscious behavioral discrimination tasks. They suggest that the MMN may be related to preconscious discrimination ability. Some data indicate that the MMN in normal, healthy subjects may not be quite as robust as described. For example, Kurtzberg and colleagues, Dalebout and Stach, and Cunningham all found MMN to be absent in 25% to 35% of normal children and adults.64–66 Other work with the MMN and auditory processing has been done by Liasis and colleagues, Naatanen, Kraus and colleagues,

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Jansson-Verkasalo, Purdy and colleagues, Hugdahl and colleagues, Bertoli and colleagues, and Schulte-Korne and colleagues.67–74 Therefore, while MMN continues to be a promising research tool for groups of subjects, its use in the assessment of individual subjects should be approached with caution.

Other Late Auditory Evoked Responses Research is being conducted to investigate other late auditory evoked responses in the assessment of APDs. These responses occur after 80 to 100 milliseconds. Besides the MMN and P300, other responses are the N1, P2, and N2. Research related to APD populations include the work of Jirsa and Clontz, who found that the N1 and P2 had increased latencies in a group of children with APD.61 Tonnquist-Uhlen found significant differences in N2 and P2 latencies in language-impaired children.75 Purdy and colleagues found different P1 and P3 responses in learningdisabled children.71 Ponton and colleagues suggest that late potentials can provide information about the maturation of the CANS.76 Hayes and colleagues also measured differences in P1 and N2 in children with learning problems, after a computer remediation program was used.77 This also corresponded with a change in behavioral performance measures.

FACTORS AFFECTING AUDITORY PROCESSING TEST RESULTS Subject’s Age The age of the subject vastly affects the performance on auditory processing tests. The effects of age are based on changes resulting from neural maturation, changes in the auditory nervous system in aging, and language level. When referring a patient for APD assessment, the corrected age based on language ability, and not just the chronological age, should be considered. Electrophysiologic tests also are affected by age.

Peripheral Hearing Loss Peripheral hearing loss, both conductive and sensorineural, is a significant factor in testing and interpretation of auditory processing. Patients with peripheral hearing loss cannot be tested reliably with most of the central auditory measures that incorporate speech signals because of cochlear distortion and asymmetrical hearing loss. For example, the dichotic consonant-vowel (CV) test, masking level difference test, low-pass filtered speech tasks, and time-compressed speech tasks are affected by hearing loss. Fortunately, some tests have been researched or adapted for testing subjects with peripheral hearing loss. According to Stach,26 these tests include: Dichotic Sentence Identification (DSI) test, which can be used with PTA of 50 dB or lower41 Synthetic Sentence Identification (SSI) test, which has normative data based on degree of hearing loss78 Dichotic digits test, interpretation of which can be adjusted based on hearing loss present38

Staggered Spondaic Word (SSW ) test, which has corrections for hearing sensitivity loss39,79 Competing sentences, MLR, and P300 are less likely to be affected by peripheral hearing loss.3 In addition, a wide range of nonlinguistic tests that use tones can be considered when attempting to identify an auditory processing disorder in this population; they include Random Gap Detection, Median Plane Localization, differential thresholds for frequency and intensity, and tone decay tests.

Intelligence, Cognition, and Language The effect of intelligence and cognitive ability is well documented. Subjects’ performance will generally be commensurate with their mental age and should be interpreted appropriately. Language ability is an important factor as well because many auditory processing measures are language based. For instance, vocabulary knowledge is essential for the recognition of words with reduced extrinsic redundancy. In addition, native language and language dialect can have an impact on test results. It has been demonstrated that normal adult subjects who are not native speakers of English typically have difficulty performing sensitized speech tasks, even years after being immersed in the English language.80,81 Native English speakers from other English-speaking countries also have difficulty taking American-accented speech tests of auditory processing. Marriage found that normally performing children in Great Britain fell at the 16th percentile of performance on SCAN–C because they were unable to interpret some of the American-accented test items.82

Medications The effect of medications on auditory processing tests is beginning to emerge in the field. Keith and Engineer found that children with attention deficit disorder (ADD) who were taking methylphenidate (Ritalin) had significantly improved auditory processing performance.83 Tillery and colleagues found auditory attention improved with Ritalin in children with both APD and attention deficit hyperactivity disorder (ADHD), but auditory processing abilities were unchanged.84 The effect of selective serotonin reuptake inhibitors (SSRIs) such as fluvoxamine and fluoxetine on auditory processing abilities needs investigation, as shown by the case study presented by Gopal and colleagues.85 Chermak reviews this subject briefly.86

AUDITORY PROCESSING TESTING Children Children younger than 5 years old are difficult to test with these special measures, and there are few normative tests available. After the age of 6 years, children can be tested with relative ease using standardized tests. Nonverbal persons or persons with limited intelligence are not candidates for testing. For further information, consult the

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guidelines for referring children for APD assessment published by a group of Houston audiologists.87 The focus of testing children’s auditory processing is to investigate a possible factor for poorer school performance, language delays, reading problems, learning difficulties, and behavior difficulties. The majority of children referred for testing do not have specific identifiable brain lesions and many have completely normal neurologic examinations. The purpose of APD testing of children is to identify those who have an auditory processing disorder that may underlie or contribute to a child’s poor social skills, use of language, or academic performance. Children with auditory processing disorders often misunderstand what is said, give inconsistent responses to auditory stimuli, and frequently request that information be repeated. These children have poor auditory attention, have difficulty listening in the presence of background noise, and are easily distracted. They have difficulty with phonics and speech sound discrimination and have poor auditory memory. Their speech and language skills, both receptive and expressive, may be poor. These problems occur without hearing loss, but there might also be hearing loss. The relationship of language acquisition and auditory processing is complex. A vast body of literature addresses different theories about this relationship. In the normal child, auditory processing abilities develop in a parallel or a reciprocal relationship with language abilities. Children with auditory processing disorders are a subset of children with receptive and/or expressive language disorders. In addition, issues of attention need to be considered. APD can coexist with attention deficit hyperactivity disorder or attention deficit disorder. The relationships among all these disorders is not yet completely understood.88 Nevertheless, APD can be distinct clinically from ADHD.89

formal screening tests.2 Examples of questionnaires include the Children’s Auditory Performance Scale (CHAPS) and the Screening Instrument for Targeting Educational Risk (SIFTER).96,97 An example of a formal screening test is the Selective Auditory Attention Test (SAAT).98 A word of caution: Auditory processing tests designed for screening should not be used to diagnose auditory processing disorders, as has been done in the past.2 This results in an overdiagnosis of auditory processing disorders.

Adults

The components of the APD test battery vary, based on the model of auditory processing. The tests chosen are especially important for assessment of children’s hearing because they are still learning the basic components of language. Audiologists tend to approach APD testing with a bottom-up approach, believing that language problems stem from deficit(s) in basic auditory processes. Speechlanguage pathologists tend to approach auditory processing with a top-down approach, believing that the auditory processing difficulty is due to problems with higher-level influences, such as language, cognition, information processing, and attention. Not surprisingly, then, the essential auditory processing test battery is highly variable among audiologists. The American-Speech-Language-Hearing Association Task Force on Central Auditory Processing consensus statement provides a workable guideline. For both adult and pediatric populations, the test battery can include the following3:

Auditory processing disorders in adults often manifest themselves in everyday communication, either socially or vocationally. Like children with APD, adults with APD have more than normal difficulty in challenging listening situations. They often report difficulty hearing in noisy environments, when speaking with an individual with a foreign accent, or with someone who speaks very fast. APD in this population may be related to acquired etiologies; it has been documented with Parkinson’s disease, chronic alcoholism, Alzheimer’s disease, stroke and head trauma, tumors, multiple sclerosis, and chemical exposure. APD also may be identified in previously undiagnosed learning-disabled adults.90–94 As mentioned earlier, APD testing of adults can be useful in identifying lesions of the central auditory nervous system, although this is not the typical purpose today. APD testing can be used to track the recovery of auditory processing skills95 and provide information on the impact of APD on everyday function.

Screening for Auditory Processing Disorders Mostly, children are screened for APD. According to the 2000 Bruton Conference on APD, this can be done by observation of the child using questionnaires and/or

A Multidisciplinary Approach The test battery used in auditory processing assessment needs to be part of a multidisciplinary approach. Essential members of this team are the audiologist and speechlanguage pathologist. For assessment of children, teachers and parents are also essential members of the team. This team approach is recommended in two consensus statements by specialists in central auditory processing.2,3 Other specialists, such as psychologists, also may be involved.

Goals The ASHA Task Force reveals that “the purpose of the central auditory assessment is to determine the presence of a central auditory processing disorder and to describe its parameters.”3 Concerning children specifically, there is controversy as to whether the assessment should focus on delineating a deficit specific to the auditory realm, differentiating APD from other disorders such as language and learning problems, or determining management strategies.2,43

Test Battery Components

I. Case history II. Nonstandard but systematic observation of auditory behavior III. Audiologic test procedures A. Behavioral techniques 1. Measures of peripheral function a. Pure tone thresholds b. Speech recognition

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NEUROLOGIC DIAGNOSIS

c. Acoustic immittance measures d. Otoacoustic emissions, when possible 2. Auditory processing tests a. Temporal processes—ordering discrimination, resolution (e.g., gap detection), and integration b. Localization and lateralization c. Low-redundancy monaural speech (time-compressed, filtered, interrupted, competing, etc.) d. Dichotic stimuli, including competing nonsense syllables, digits, words, and sentences e. Binaural interaction procedures B. Electrophysiologic procedures can also be used IV. Speech-language pathology measures In the ASHA statement, the test battery is not standard; instead, an individual approach to assessment and selection of tests is taken. This means that the tests that comprise the battery vary, depending on the individual and the observed problem areas. In addition, the tests chosen should be appropriate for the age of the population. Keith suggests specific tests that relate to the ASHA recommendations.1 These have been updated and are reprinted in Table 17-2. Another approach to CAP testing is the recommendation of a minimal test battery. An example of this was suggested by the 2000 Bruton Conference Consensus statement on APD in school-age children, as reproduced in Table 17-3.2 This minimal test battery is not agreed on by all audiologists.43 Indeed, Emanuel found that none of the practicing audiologists surveyed used all of the tests in the minimal test battery recommended by the Bruton conference.99 For further examples of usable test batteries, TABLE 17-2. Auditory Processing Tests Related to ASHA Test Battery Areas ASHA Test Battery Area

Auditory Processing Tests

Temporal processing, resolution and gap detection Frequency and temporal ordering Sound localization and lateralization

Auditory Fusion Test (Revised) Random Gap Detection Test

Low-redundancy monaural speech

Dichotic stimuli

Binaural interaction Electrophysiologic procedures

Pitch Pattern Test Duration Patterns Test Clinical localization of sounds through earphones or speakers Median plane localization task Time Compressed Sentence Test Filtered Words test from SCAN–C or SCAN–A Auditory Figure Ground test from SCAN–C or SCAN–A QuickSIN test, for older children Dichotic Digits Test Dichotic Words Test from SCAN–C or SCAN–A Staggered Spondee Word Test Competing Sentence Test from SCAN–C or SCAN–A Masking Level Differences Auditory Brainstem Response Middle Latency Response

ASHA, American Speech-Language-Hearing Association. From Keith RW, Auditory processing disorders. In Roser R, Downs, M (eds.): Auditory Disorders in School Children: Law, Identification, Remediation, 4th ed. New York, Thieme Medical Publishers, 2004.

TABLE 17-3. Recommended Minimal Test Battery for Diagnosis of APDs in School-Age Children Behavioral measures

Electroacoustic and electrophysiologic measures

Pure tone audiometry Performance-intensity functions for word recognition A dichotic task Duration pattern sequence test Temporal gap detection Immittances Otoacoustic emissions Auditory brainstem response Middle latency response

Data from Jerger J, Musiek F: Report of the consensus on the diagnosis of auditory processing disorders in school-aged children. Journal of the American Academy of Audiologists 11:467, 2000.

see Bellis,55 Masters, Stecker, and Katz,100 Hall and Mueller,101 Musiek and Chermak,102 and Margolis.103 In test selection, Musiek and Chermak recommend the following considerations: availability of normative data, test sensitivity and specificity, test reliability, ease of administration, comprehensive assessment, use of test data (guided by the use of the results), patient factors, and test medium (e.g., compact disc, cassette).102 In addition, the qualifications of the professional who will administer the test(s), in auditory processing specifically, must be considered because they vary greatly.104

Test Interpretation There are a number of important basic principles in auditory processing test interpretation. The first, the bottleneck principle, states that lower auditory anatomic-level function typically affects higher-level responses. Cranial nerve VIII is often thought of as the bottleneck. A deficiency in a cortically sensitive measurement may have been affected by a lesion lower in the central auditory processing pathway, such as in the cochlea, auditory nerve, or brainstem. Similarly, the subtlety principle states that “the more central the lesion, the more subtle its impact will be.”105 For example, a brainstem lesion can result in profound, rising to mild hearing loss to pure tones.106 On the other hand, temporal lobe lesions are not likely to affect hearing sensitivity to pure tones or word recognition in quiet surroundings.26 There are exceptions to the subtlety principle, such as in the case of bilateral temporal lobe lesions. These can cause “cortical deafness,” such as a seeming auditory agnosia or profound hearing sensitivity loss.107–109 A few other key principles also apply. Sensitized speech tests show no dominance effect in normal adults; scores are equivalent for both ears. When a lesion of the auditory cortex is present, sensitized speech tests yield mild to moderately reduced intelligibility scores in the ear contralateral to the lesion, although both ipsilateral and contralateral deficits are sometimes found.3 On the other hand, temporal lobe lesions that extend deep toward the midline reveal a paradoxical ipsilateral ear lesion.110 Brainstem lesions affect the sensitized speech scores to a greater extent than cortical lesions do. The reduced intelligibility occurs on either the same or the opposite side of the brainstem lesion, depending on the neural pathways

Central Auditory Processing Disorders: Assessment and Remediation

involved. Scores are often reduced bilaterally when the lesion crosses the midline or through secondary effects of pressure, even from remote lesions.111 In difficult monaural tasks, with lower brainstem lesions, the performance is poorer usually ipsilateral to the lesion. With higher brainstem lesions, performance can be poorer ipsilateral and contralateral to the lesion.26 One recent trend in APD assessment is the development of the concept of a central auditory processing disorder divided into subtypes of deficits. For example, Bellis and Ferre delineate auditory processing disorders into three primary subprofiles and two secondary subtypes. The three primary subtypes are Auditory Decoding Deficit, Prosodic Deficit, and Integration Deficit. The two secondary subtypes are Associative Deficit and Output Organization.55 As a second example, the subtypes of auditory processing deficits have been described by Masters, Stecker, and Katz in the Buffalo Model.100 This model uses four clusters of test results and behavioral characteristics, speech-language test results, and academic factors. The four clusters are Decoding, Tolerance-Fading Memory, Integration, and Organization. Although these models of auditory processing have been popularized, there is no evidence to substantiate claims that the remediation proposed to be associated with each model has an effective outcome.

REMEDIATION OF AUDITORY PROCESSING DISORDERS Different management strategies of auditory processing disorders exist. Regardless of the management approach, it is important that the management approach be multidisciplinary. It also should be individualized based on the areas of weakness or deficit identified in the auditory processing assessment. Additionally, it is important to be specific in the management approach; some professionals still believe that intervention strategies are not specific enough to warrant auditory processing testing.112 An example of the possible downfalls of a nonindividualized approach is the use of FM assistive listening devices for school-age children. FM systems are not necessarily the best recommendation in all cases. It is possible that this reduction of background noise may not allow the auditory skills to develop in those environments with some individuals.55 Strategies for remediation of APD fall into three major categories: 1. Management of the environment, which includes strategies such as preferential seating, FM systems, sound field systems, teaching suggestions (comprehension checks, use of visual aids, etc.), classroom acoustics, and communication strategies. 2. Remediation techniques designed to improve the person’s auditory processing skills. This includes training in auditory closure, speech in noise, dichotic listening, localization, prosody, and temporal patterning. It also includes computer-assisted therapy with such software programs as Fast ForWord (Scientific Learning Corp.) and Earobics (Cognitive Concepts).

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3. Compensatory strategies designed to teach the individual how to overcome residual dysfunction and maximize use of auditory information. These focus on improving learning and listening skills. They include teaching the person to be an active listener, increasing motivation, attribution training, whole body listening techniques, and metacognitive strategies.55 Remediation of APD in children needs to take full advantage of the neural plasticity of the central auditory nervous system.113,114 Neural maturation must also be taken into account. The treatment plan for adults may focus more on management of the environment and compensatory strategies and less on direct remediation training techniques. This makes sense because of the decreased neural plasticity in adulthood. For more thorough and comprehensive sources of management approaches and issues, consult Bellis,55 Masters, Stecker, and Katz,100 and Chermak.115 In addition, Musiek describes three useful and practical management approaches that can be used as part of a comprehensive APD management program.116 Of course, the existence of a strategy does not mean it is an effective strategy. In the area of auditory processing, a great amount of research is needed to determine treatment effectiveness and outcome measures. Hayes and colleagues did such a study in which children with learning problems, including an auditory perceptual deficit, underwent a computerized training program, Earobics.77 Not only did their performance improve in measures of auditory processing, but changes in cortical potentials were also measured. Other studies that report improved auditory abilities and language function after formal training were conducted by Merzenich and colleagues, Tallal and colleagues, and Habib and colleagues.117–119

AUDITORY PROCESSING ABILITIES IN THE ELDERLY In the 1990s special interest was focused on auditory processing abilities and the elderly population. The familiar concept of phonemic regression and central presbycusis was revisited. Recall that phonemic regression describes the phenomenon in which an elderly adult’s ability to understand words, often measured by word recognition scores, is disproportionately poorer than would be expected based on pure tone thresholds. This, indeed, was simply referring to an auditory processing disorder becoming evident with aging. It is often forgotten that Gaeth found the prevalence rate of phonemic regression in 1000 elderly individuals to be only 2.7%.120 Research suggests that auditory processing disorders in the normal elderly may not be the rule, but the exception, which is consistent with Gaeth’s early findings. A number of studies challenge the common assumption that auditory processing decreases with age in most or all individuals. Hearing loss is often a confounding variable. Humes and Christopherson found that the threshold elevation in sensorineural hearing loss was the primary factor affecting the speech identification performance of elderly subjects, and not just age alone.121 To read other studies

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that challenge the common assumption that auditory processing declines with aging, consult Surr,122 Grady123 Holmes, Kricos, and Kessler,124 Jerger and colleagues,125 Humes and colleagues,126 and Harris and Reitz.127 Thompson discusses several alternative hypotheses to explain phonemic regression.128 They include experimental artifacts that include failure to account for the fact that elderly persons are less willing to guess, prolonged reaction time in this population, insufficient stimulus presentation level, and the effects of decreased hearing sensitivity. In addition, she suggests that cognitive factors such as changes in attention, declining memory, need for more practice, and social expectations (defined as the expectation that the elderly person’s hearing is poorer than a normal adult’s) are factors in tests of auditory processing. These studies serve as a reminder to neurotologists and audiologists who work with seniors that central auditory processing disorders in the elderly may not be a global phenomenon, characteristic of all elderly. On the other hand, there still exists a strong argument that auditory processing does decrease during the aging process. Histologic and morphologic evidence still seem to support this concept; age-related changes in the cochlea, the auditory nerve, and the central auditory pathways at both the brainstem and temporal lobe levels have been described.129,130 Declined performance on behavioral auditory processing measures also are presented in the literature. Jerger and colleagues used a number of auditory processing disorder tests on 130 elderly subjects. They concluded that the speech discrimination problems of the elderly cannot be explained on the basis of degree of peripheral hearing loss or degree of cognitive decline.130 Neils and colleagues,131 Von Wedel,132 Baran,133 and Willott134 also provide evidence that suggests that auditory processing changes do occur with aging.

AUDITORY PROCESSING TESTING IN HEARING AID APPLICATIONS Interestingly, auditory processing tests to help determine hearing aid success has been discussed more recently. Givens, Arnold, and Hume found statistically significant correlations between certain auditory processing tests and hearing aid satisfaction. They suggest that a full battery with auditory processing tests may be helpful.135 Studies by Chmiel and Jerger and by Stach and colleagues further investigate this application.136,137 Auditory processing tests may also be helpful in determining when to recommend binaural versus monaural hearing aids. This is related to a phenomenon called bilateral interference. Some people with APD find that their ability to perform binaurally is actually poorer than the best monaural performance. This has been seen in some elderly individuals and in a multiple sclerosis patient.138,139 An interesting case study of an elderly patient who performed better with monaural hearing aid use was published by Chmiel and colleagues.140 Another interesting concept applicable to hearing aid use is acquired suprathreshold asymmetry. Evidence is suggesting that when an individual develops an asymmetry caused by a peripheral hearing loss, the auditory processing in the

poorer ear is disproportionately affected compared with the other ear. Using concepts of auditory neural plasticity, then, it would be recommended to aid the poorer ear as soon as possible to preserve auditory processing in that ear. It should be noted that the concept of acquired suprathreshold asymmetry is still controversial and is not supported in all studies conducted.26 Last, late-onset auditory deprivation should also be considered in hearing aid use. This can occur in monaural hearing aid fittings with bilateral, symmetric hearing loss. In some individuals, the unaided ear decreases in word recognition ability, whereas the aided ear does not. However, the plasticity of the auditory system becomes apparent as this negative effect is reversible if the other ear is aided soon enough.26

FUTURE DIRECTIONS Further research is needed to collect and refine norms for many behavioral APD tests. More information needs to be gathered on electrophysiologic tests, such as MMN, MLR, and P300. Outcome measures and efficacy measures are needed to assess different remediation and treatment methods. There is a need for a “gold standard” definition of auditory processing, providing the basis for studies of sensitivity and specificity for different auditory processing tests. This will pave the way for improved models of assessment and management. In addition, the use of functional MRI and brain mapping and scalp topography show promise.

FUNCTIONAL MAGNETIC RESONANCE IMAGING An exciting advance in assessment of APD developed in the early 1990s is functional imaging based on magnetic resonance methods (fMRI). This technique allows visualization of brain activity resulting from increases in regional cerebral blood flow associated with processing of sensory information. Through fMRI, auditory neuroscience will be able to investigate aspects of auditory nervous system organization, attention, memory, and other factors in ways that were unimaginable several years ago. Cacace, Tasciyan, and Cousins summarize that this new research frontier provides insights into fundamental properties of human sensory, motor, and cognitive functions in both normal and pathologic states. They state that the appeal of this technique is “based on its noninvasive nature, temporal and spatial resolution, suitability for studying humans, and its potential for wide-range future availability.”141 See the article by Cacace and colleagues for an excellent tutorial on this subject.141 Other researchers looking at fMRI and auditory processing are Suzuki and colleagues,142 Poldrack and colleagues,143 Seifritz and colleagues,144 Sevostianov and colleagues,145 Novitski and colleagues,146 Engelien and colleagues,147 and Hall and colleagues.148

Brain Mapping and Scalp Topography Scalp topography of auditory evoked potentials with color imaging techniques provide a scheme for easy visualization of the voltage distribution of evoked potentials at key

Central Auditory Processing Disorders: Assessment and Remediation

latencies. These has also been called event-related potentials and event-related potential (ERP) topography. Color imaging of the scalp topography of the middle-latency response was first described by Kraus and McGee.149 These authors examined MLR scalp topography in 40 normal-hearing subjects. Jerger and colleagues used this technique in an interesting case study with two twins, only one of which exhibited symptoms of APD.150 Although results of behavioral auditory processing tests were comparable for the two twins, the ERP topographies were quite different. The ERP results were consistent with a deficit in the efficiency of interhemispheric transfer of auditory information in the twin who exhibited APD symptoms. In this way, ERP topography was used to differentiate among possible diagnoses. Pros and cons of brain mapping are discussed by Cranford and Hymel.151 This technique provides interesting avenues of studying auditory processing disorders in subjects of all ages and is the subject of other researchers, among them Estes and colleagues152 and Tonnquist-Uhlen.153

SUMMARY Auditory processing disorders, formerly referred to as central auditory processing disorders, are complex phenomena that can be assessed systematically with a number of different behavioral tests. Although the minimal test battery is controversial, there are many guidelines provided by a multitude of authors. Electrophysiologic techniques are deemed essential in the APD assessment by some and nonessential by others. These tests include ABR, MLR, P300, MMN, and other late auditory evoked potentials. Either way, it is clear that electrophysiologic techniques are an area of promise that requires more research. The essentials of auditory processing assessment and remediation encompass many factors, including age, hearing loss, language, and intelligence. The role of auditory processing testing in children is focused on improving language and academic abilities. In adults, the emphasis is on “functional disorders of communication” in social and vocational situations. The occurrence of auditory processing that occurs with aging is a debatable topic. The use of auditory processing testing in hearing aid assessment is also an area of promise. Future techniques for use in this intriguing field of auditory processing may include functional MRI and brain mapping.

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58. Fifer R, Sierra B: Clinical applications of the auditory middle latency response. Am J Otol 9:47, 1988. 59. Ozdamar O, Kraus N: Auditory middle latency responses in humans. Audiology 22:32, 1983. 60. McPherson DL (ed.): Late Potentials of the Auditory System. San Diego, Singular, 1996. 61. Jirsa RE, Clontz KB: Long latency auditory event-related potentials from children with auditory processing disorders. Ear Hear 11:222, 1990. 62. Jirsa RE: The clinical utility of the P3 AERP in children with auditory processing disorders. J Speech Hear Res 35:903, 1992. 63. Kraus N, Koch DB, McGee TJ, et al: Speech-sound discrimination in school-age children: Psychophysical and neurophysiologic measures. J Speech Lang Hear Res 42:1042, 1999. 64. Kurtzberg D, Vaughan H, Kreuzer J, et al: Developmental studies and clinical applications of mismatch negativity: Problems and prospects. Ear Hear 16:118, 1995. 65. Dalebout SD, Stach JW: Mismatch negativity to acoustic differences not differentiated behaviorally. J Am Acad Audiol 110:388, 1999. 66. Cunningham RF: Mismatch Negativity in Normally Developing Children [unpublished dissertation]. Cincinnati, University of Cincinnati, 2000. 67. Liasis A, Bamiou DE, Campbell P, et al: Auditory event-related potentials in the assessment of auditory processing disorders: A pilot study. Neuroped 34:23, 2003. 68. Naatanen R: The mismatch negativity: a powerful tool for cognitive neuroscience. Ear Hear 16:6, 1995. 69. Kraus N, McGee T, Carrell TD, et al: Neurophysiologic bases of speech discrimination. Ear Hear 16:19, 1995. 70. Jansson-Verkasalo E, Ceoniene R, Kielinen M, et al: Deficient auditory processing in children with Asperger’s syndrome, as indexed by event related potentials. Neurosci Lett 338:197, 2003. 71. Purdy SC, Kelly AS, Davies MG: Auditory brainstem response, middle latency response, and late cortical evoked potentials in children with learning disabilities. J Am Acad Audiol 13:367, 2002. 72. Hugdahl K, Heiervang E, Nordby H, et al: Central auditory processing, MRI morphometry and brain laterality: Applications to dyslexia. Scand Audiol Suppl 49:26, 1998. 73. Bertoli S, Heimberg S, Smurzynski J, et al: Mismatch negativity and psychoacoustic measures of gap detection in normally hearing subjects. Psychophys 38:334, 2001. 74. Schulte-Korne G, Deimel W, Bartling J, et al: Auditory processing and dyslexia: Evidence for a specific speech processing deficit. Neuroreport 9:337, 1998. 75. Tonnquist-Uhlen I: Topography of auditory evoked long-latency potentials in children with severe language impairment: The P2 and N2 components. Ear Hear 17:314, 1996. 76. Ponton CW, Eggermont JJ, Kwong B, et al: Maturation of human central auditory system activity: Evidence from multichannel evoked potentials. Clin Neurophysiol 111:220, 2000. 77. Hayes EA, Warrier CM, Nicol TG, et al: Neural plasticity following auditory training in children with learning problems. Clin Neurophysiol 114:673, 2003. 78. Yellin MW, Jerger J, Fifer RC: Norms for disproportionate loss of speech intelligibility. Ear Hear 10:231, 1989. 79. Arnst DJ, Doyle PC: Verification of the corrected staggered spondaic word (SSW) score in adults with cochlear hearing loss. Ear Hear 4(5):243, 1983. 80. Gat I, Keith RW: An effect of linguistic experience: Auditory word discrimination by native and non-native speakers of English. Audiology 17:339, 1978. 81. Keith RW, Katbamna B, Tawfik S: The effect of linguistic background on staggered spondaic word and dichotic consonant vowel scores. Brit J Audiol 21:21, 1987. 82. Marriage J, King J, Lutman M: The reliability of the SCAN test: Results from a primary school in the UK. Brit J Audiol 35:199, 2001.

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83. Keith RW, Engineer P: Effects of methylphenidate on auditory processing abilities of children with attention deficit-hyperactivity disorder. J Learn Disabil 24:630, 1991. 84. Tillery KL, Katz J, Keller WD: Effects of methylphenidate (Ritalin) on auditory performance in children with attention and auditory processing disorders. J Speech Lang Hear Res 43:893, 2000. 85. Gopal KV, Daly DM, Daniloff RG, et al: Effects of selective serotonin reuptake inhibitors on auditory processing: Case study. J Am Acad Audiol 11:454, 2000. 86. Chermak GD: Deciphering auditory processing disorders in children. Otolaryngol Clin North Am 35:733, 2002. 87. Kent M: Houston educational audiologists establish guidelines for referring for an auditory processing evaluation. Educa Audiol Rev, Summer, 19:3–4, 2002. 88. Musiek FE, Chermak GD: Three commonly asked questions about central auditory processing disorders: Management. Am J Audiol 4:15, 1995. 89. Chermak GD, Hall JW, Musiek FE: Differential diagnosis and management of central auditory processing disorder and attention deficit hyperactivity disorder. J Am Acad Audiol 10:289, 1999. 90. Jerger J: Observations on auditory behavior in lesions of the central auditory pathways. Arch Otolaryngol 71:797, 1960. 91. Spitzer J, Ventry I: Central auditory dysfunction among chronic alcoholics. Arch Otolaryngol 106:224, 1980. 92. Grimes AM, Grady CL, Pikus A: Auditory evoked potentials in patients with dementia of the Alzheimer type. Ear Hear 8:157, 1987. 93. Bergman M, Hirsch S, Solzi P: Interhemispheric suppression: A test of central auditory function. Ear Hear 8:87, 1987. 94. Hasbrouk J: Diagnosis of auditory perceptual disorders in previously undiagnosed adults. J Learn Disab 16:206, 1983. 95. Mueller H, Sedge R, Salazar A: Auditory assessment of neural trauma. In Miner M, Wagner K (eds.): Neurotrauma: Treatment, Rehabilitation and Related Issues. Boston, Butterworths, 1986. 96. Smoski WJ, Brunt MA, Tannahill JD: Listening characteristics of children with central auditory processing disorders. Lang Speech Hear Serv Sch 23:145, 1992. 97. Anderson KI: Screening instrument for targeting educational risk (S.I.F.T.E.R.). Tampa, Educational Audiology Association, 1989. 98. Cherry R: Selective auditory attention test (SAAT). St. Louis, Auditec of St. Louis, 1980. 99. Emanuel DC: The auditory processing battery: Survey of common practices. J Am Acad Audiol 13:93, 2002. 100. Masters MG, Stecker NA, Katz J (eds.): Central Auditory Processing Disorders—Mostly Management. Needham Heights, Mass, Allyn & Bacon, 1998. 101. Hall JW, Mueller HG: Audiologists’ Desk Reference, vol I. San Diego, Singular, 1997. 102. Musiek FE, Chermak GD: Three commonly asked questions about central auditory processing disorders: Assessment. Am J Audiol 3:23, 1994. 103. Margolis RH: Audiology Clinical Protocols. Needham Heights, Mass, Allyn & Bacon, 1997. 104. Chermak GD, Traynham WA, Seikel JA, et al: Professional education and assessment practices in central auditory processing. J Am Acad Audiol 9:452, 1998. 105. Jerger J: Audiological manifestations of lesions in the auditory nervous system. Laryngoscope 70:417, 1960. 106. Jerger S, Jerger J: Low-frequency hearing loss in central auditory disorders. Am J Otol 2:1, 1980. 107. Hood LJ, Berlin CI, Allen P: Cortical deafness: A longitudinal study. J Am Acad Audiol 5:330, 1994. 108. Jerger J, Weikers M, Sharbrough F, et al: Bilateral lesions of the temporal lobe: A case study. Acta Otolaryngol Suppl 258:1–51, 1969. 109. Jerger J, Lovering L, Wertz M: Auditory disorder following bilateral temporal lobe insult: Report of a case. J Speech Hear Dis 37:525, 1972.

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145. Sevostianov A, Fromm S, Nechaev V, et al: Effect of attention on central auditory processing: An fMRI study. Int J Neurosci 112: 587, 2002. 146. Novitski N, Alho K, Korzyukov O, et al: Effects of acoustic gradient noise from functional magnetic resonance imaging on auditory processing as reflected by event-related brain potentials. Neuroimage 14:244, 2001. 147. Engelien A, Stern E, Silbersweig D: Functional neuroimaging of human central auditory processing in normal subjects and patients with neurological and neuropsychiatric disorders. J Clin Exp Neuropsychol 23:94, 2001. 148. Hall DA, Haggard MP, Akeroyd MA, et al: Modulation and task effects in auditory processing measured using fMRI. Hum Brain Mapp 10:107, 2000. 149. Kraus N, McGee T: Color imaging of the human middle latency response. Ear Hear 9:159, 1988. 150. Jerger J, Thibodeau L, Martin J, et al: Behavioral and electrophysiologic evidence of auditory processing disorder: A twin study. J Am Acad Audiol 13:438, 2002. 151. Cranford JL, Hymel MR: Pros and cons of brain mapping as a tool for investigating central auditory pathology. Semin Hear 19:345, 1998. 152. Estes RI, Jerger J, Jacobson G: Reversal of hemispheric asymmetry on auditory tasks in children who are poor listeners. J Am Acad Audiol 13:59, 2002. 153. Tonnquist-Uhlen I: Topography of auditory evoked cortical potentials in children with severe language impairment. Scand Audiol Suppl 44:1, 1996.

18

Outline Introduction Otoacoustic Emissions Electrocochleography Auditory Brainstem Response Detection of Hearing Loss Using the Auditory Brainstem Response Estimating Amplification Benefit: Electrophysiologic Procedures

Chapter

Objective Measures of Auditory Function

Acoustic Neuroma Diagnosis with the Auditory Brainstem Response Measurement Criteria for Diagnostic Auditory Brainstem Response Case Studies Middle Latency Responses Auditory Potentials in Cochlear Implant Surgery

INTRODUCTION Beginning with the 1939 discovery of human auditory evoked potentials by Pauline Davis1 there has been remarkable progress in the clinical application and effectiveness of electrophysiologic and other objective measures of auditory function. These developments have been prompted in part by distinct technological changes since the advent of the first electronic response averager, devised by G. D. Dawson in 1952. It consisted of a revolving commutator charging condensers, resulting in a total of 124 time points. The advent of digital averagers brought a veritable explosion of productivity in the area of clinical auditory neurophysiology marked by significant events such as the first human scalp–recorded auditory brainstem response (ABR) by Jewett, Romano, and Williston.2 Over the years, clinical auditory neurophysiology has contributed to both diagnostic and surgical monitoring applications. Electrophysiologic measures are now used for both diagnosis and enhancement and support of sophisticated microsurgical interventions in the temporal bone, subtemporal skull base, and posterior fossa. In the diagnostic arena, it is possible to evaluate the function and the integrity of the auditory pathway from end-organ receptor to cerebral cortex. Evoked otoacoustic emissions provide information regarding the status of cochlear outer hair cells. Electrophysiologic measures provide us with information about functional characteristics of outer hair cells via the cochlear microphonic as well as the status of the cochlea in presumed Ménière’s disease using electrocochleography. Also, the cochlear nerve and brainstem auditory pathway for neurodiagnostic or hearing threshold applications is assessed via the auditory brainstem

Paul R. Kileny, PhD Bruce M. Edwards, AuD

response; other electrophysiologic applications involve the subcortical and cortical auditory regions. Methods for the electrophysiologic assessment of auditory system activation by electrical stimulation including cochlear implants have been developed and refined, allowing one to record preoperative and postimplant electrically evoked auditory brainstem or middle latency potentials. All of these may be accomplished by noninvasive or minimally invasive stimulation and recording techniques. This chapter reviews principles and practices of auditory neurodiagnostic tests in current clinical use.

OTOACOUSTIC EMISSIONS Otoacoustic emissions (OAEs) are sounds produced actively by the human ear as part of the normal hearing process and were first described by Kemp.3 The active nonlinear mechanism of outer hair cell (OHC) motility amplifies the motion of the cochlear partition 100- to 1000-fold and, as a byproduct, produces various forms of OAEs.4 Because OAEs are acoustic byproducts of the inner ear, they are often referred to as “cochlear echoes.” There are two primary types of OAE: spontaneous OAEs (SOAEs) are present even in the absence of an exogenous stimulation of the ear; evoked OAEs (EOAEs) occur in response to the presentation of an acoustic stimulus to the ear.5 Evoked OAEs may be further divided into the categories of transiently evoked OAEs (TEOAEs), which are elicited by an acoustic transient such as a click or tone burst, stimulus frequency OAEs (SFOAEs), which are elicited by a single continuous pure tone, and distortion product OAEs (DPOAEs), which are generated by two 287

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NEUROTOLOGIC DIAGNOSIS

continuous pure tones separated by a specific frequency difference.5 Evoked OAEs can be detected in most ears with normal hearing and are reduced or absent in ears affected by cochlear disorders.5 The test procedure for obtaining OAEs requires little subject preparation and relatively brief examination periods, and it is performed in a relatively straightforward manner. During testing, a probe that contains both a miniature loudspeaker and a microphone is sealed into the ear canal. The loudspeaker delivers the stimulus to the ear canal while the microphone samples the output (emission) for approximately 20 ms following stimulus presentation. The signal from the microphone is then amplified and averaged in order to enhance the signal-to-noise ratio. Signals used to generate TEOAEs consist of clicks or tone bursts. Transient OAEs in response to click stimuli consist of a delayed, nonlinear, frequency-filtered echo of the stimulus.3 Healthy ears typically demonstrate several regions of strong response for TEOAEs between 0.4 and 6 kHz and between 0.5 and 8 kHz for DPOAEs.5–7 The latency of TEOAEs is typically 5 to 20 ms in humans and tends to decrease as frequency increases, supporting a cochlear origin of TEOAEs.5 Signals used to generate DPOAEs consist of two stimulus tones, separated in frequency, presented at 55 to 85 dB SPL. Nonlinear cochlear processes are responsible for the emission of responses at frequencies that are not present in the two-tone input. The output requires averaging to measure DPOAEs at specific frequencies. The most prominent DPOAE occurs at the cubic difference frequency described by the expression “2F1-F2,” in which F1 represents the lower frequency stimulus and F2 the higher frequency primary tone.5,8,9 Distortion product OAEs are low in amplitude, usually about 60 dB lower than the levels of the eliciting primary tones. Otoacoustic emissions have shown promise as occupational audiologic test tools not only because they can be obtained and measured in a relatively straightforward manner, but also because they have considerable potential for assessing the role of OHC dysfunction in hearing impairment.5,7 OAEs specifically test the micromechanical activity of OHCs, that is, the auditory receptors most sensitive to the damaging influence of noise.5 Additionally, OAE measures demonstrate excellent intrasubject test/ retest reliability,5,10,11 as well as stability over several years for any one ear.3,12 An additional advantage is that OAEs test discrete frequency-specific regions of the cochlea, thereby enabling one to clearly denote differences between areas of normal and abnormal function and also to accurately track dynamic changes in outer hair cell–based disease such as noise-induced hearing loss. Factors known to cause sensorineural hearing loss may reduce or abolish OAEs. Studies have shown that acoustic overstimulation that results in a temporary threshold shift reduces OAEs.5,13 Several variables affect the presence and magnitude of OAEs including middle and outer ear disorders, environmental and biologic noise levels, the number of averaged sweeps, and primary tone characteristics (in DPOAE). Because both the forward and reverse transmission of acoustic energy are necessary for the documentation of an OAE, external and middle ear conditions such as increased

mass resulting from middle ear effusion or increased stiffness caused by eustachian tube dysfunction may adversely affect an OAE. Thus, even in cases in which cochlear function is normal, attenuation resulting from mass or stiffness effects could render OAEs unmeasurable. Significant for neonatal hearing loss detection, Doyle and colleagues have shown14 that the obstruction of the external ear canal by debris/ vernix was significantly related to more hearing screening referrals using OAEs. The majority of the infants in the study, however, did pass an ABR hearing screening. The discrepancy between results of hearing screening by DPOAE and ABR was further demonstrated by Barker and colleagues15 who screened a population of 569 newborns using ABR and DPOAEs. All infants passed the ABR hearing screening. Since no universally accepted standards exist for a DPOAE hearing screening pass, several pass criteria based on response replication and/or presence of a DPOAE at 2000 Hz were applied post hoc. With the most stringent pass criteria for DPOAE, only 64.4% of ears passed, whereas with the least stringent criteria, 88.9% passed. This represents a discrepancy in the pass rate between ABR and DPOAE of 11% to 35% when the ABR is considered the gold standard. None of the infants enrolled in this study carried risk factors for hearing loss, and long-term follow-up did not identify any delayedonset hearing loss. Koivunen and colleagues16 investigated the effects of the physical properties such as the weight and fluid viscosity of middle ear effusion on emissions and tympanogram configuration. These authors demonstrated that 7% of ears with normal tympanogram findings and 46% of ears with abnormal tympanograms yielded reduced or absent emissions. A significant correlation was found among the mean weight of the effusion, the reproducibility of emissions, and the tympanogram configuration. Fiftyseven percent of ears with mucoid effusion and 26% with nonmucoid effusion had no emissions recorded. Koivunen and colleagues asserted that the effects of middle ear function on the ability to record an otoacoustic emission are not related specifically to tympanogram configuration. Figure 18-1 shows side-by-side recordings of distortionproduct (“A”) transient-evoked (“B”) otoacoustic emissions from the same ear of a normal hearing young female. These two modes of eliciting an OAE provide analogous information but require stimulus paradigms that result in different displays. For the TEOAE, the emission is presented in the frequency domain with added information regarding magnitudes at discrete frequencies and reproducibility. For the DPOAE, the emission is presented in an audiogram form (hence, “DP-gram”) that plots emission intensity as a function of the F2 frequency. In general, the distortion product method results in a better frequency resolution for higher frequencies. Clinical applications for otoacoustic emissions may be divided into two areas: estimation of auditory thresholds and site of lesion differential diagnosis. In terms of auditory threshold estimation, otoacoustic emissions cannot be used to determine specific thresholds, only to infer threshold ranges. Generally, when otoacoustic emissions are present, one can infer the presence of auditory thresholds no poorer than approximately 30 to 35 dB HL (hearing level); analyzing individual band reproducibility and signal-tonoise ratios of those bands will aid in understanding the

Objective Measures of Auditory Function

significance of “fragmented responses.”17 In terms of differential diagnosis, the otoacoustic emissions may be used in cases of confirmed vestibular schwannoma to make inferences regarding cochlear reserve, possibly using this information to decide on the feasibility of a hearing preservation procedure. For instance, in a case of a diagnosed cerebellopontine (CP) angle mass, mild to moderate hearing loss with otoacoustic emissions may indicate a purely neural hearing loss with cochlear blood supply (and hence cochlear function) spared. Intuitively, this type of a clinical picture may be compatible with a good prognosis for hearing preservation. Conversely, absence of otoacoustic emissions along with an abnormal ABR in the presence of only a mild hearing loss may indicate cochlear involvement. In extreme situations of severe to profound hearing loss, a very abnormal ABR but intact emissions accurately predicted hearing recovery to normal in a case of a very large CP angle meningioma that extended into the internal auditory canal (IAC).18 In addition to comparing two modes of obtaining and displaying evoked otoacoustic emissions, Figure 18-1 also indicates the sensitivity of this measurement tool for inner ear pathology. Each version of this subject’s OAEs is characterized by a reduction of the OAE output (signal-to-noise ratio) at approximately 3 kHz in spite of normal audiometric thresholds from 0.5 to 4 kHz (including the interoctave frequencies) in this young subject. Significantly, her history includes several years of playing in a university marching band and orchestra without consistent use of appropriate noise attenuators. The “dips,” or notches, in each OAE record could be an early indication of noise-induced damage. Another application of otoacoustic emissions is in the diagnosis of so-called auditory neuropathy/auditory dyssynchrony. These patients have hearing losses that range from moderate to profound and have reduced or absent speech recognition and absent ABRs with normal or near normal otoacoustic emissions. These patients retain their cochlear microphonic, which indicates functioning outer hair cells. For those patients who benefit from cochlear implantation and exhibit auditory thresholds and speech recognition scores similar to other cochlear implant recipients, the diagnosis of “neuropathy” is problematic. These patients also exhibit electrically evoked auditory potentials in the absence of acoustically evoked responses. While this manifestation is compatible with some form of neural dyssynchrony, the overall clinical picture may be more compatible with inner hair cell dysfunction or a deficit of afferent transduction. Hence one observes physiologic responses associated with outer hair cell function and effective electrical stimulation associated with hearing. The following case documents such a clinical scenario. A female patient was diagnosed with severe to profound sensory neural hearing loss at 10 months of age. Earlier, she had failed her initial newborn ABR hearing screening and follow-up testing. Further diagnostic evaluation resulted in the following: Auditory brainstem responses were absent with the exception of polarity-inverting responses to rarefaction and condensation clicks and tone bursts within a latency range compatible with the cochlear microphonic, as illustrated in Figure 18-2. This prompted an attempt to obtain otoacoustic emissions. The patient’s distortion product otoacoustic emissions were interpreted

F2:F1=1.218

F1=65.0dB spl DP-gram

289

F2=55.0db spl

20

dBspl 10

0

800 1K

2K 3K 4K 5K6K 8K10K Hz (F2)

A Stimulus @0dB .3Pa

20 RESPONSE FFT

RESPONSE 23.0dB

+

WAVE REPRO 99% OCT RPR% SNRdB 1.0 1.5 2.0 3.9 4.0 kH 99 99 99 99 99 % 24 24 29 25 23 dB

NOISE INPUT 32.6dB REJECTION AT 46.7dB

STIMULUS 78 dB pk

A+B MEAN 22.9dB

0 −.3Pa 4ms

− 20 dB

0

kHz

6

MEAN STIMULUS STABILITY 96%

Response Waveform

60 Stim = 78.2dB 30

+0.5 mPa (28 dB)

0 ms

A−B DIFF −0.6dB

10 ms

20 ms

B Figure 18-1. A, Distortion product and B, transient evoked otoacoustic emissions from a young female with normal hearing thresholds measured at octave and interoctaves (0.25 to 8 kHz). History is significant for repeated noise exposure during orchestral practice and marching band performances. Note the 3-kHz emission notch in each display.

to be within normal limits (Fig. 18-3), which indicated, along with the presence of cochlear microphonics, the presence of appropriately functional outer hair cells. Her preimplant audiogram is shown in Figure 18-4. Prior to implantation, electrically evoked auditory brainstem responses (EABRs) were obtained. They consisted of a large wave III and a smaller amplitude wave V (Fig. 18-5). No such components were present with acoustic stimulation.

290

NEUROTOLOGIC DIAGNOSIS

Preoperative Pure Tone Thresholds Hearing level in dB (ANSI-96)

Click ABR: Right Ear 95 alt. CM 95 rev. CM 75 rev. 55 rev. Figure 18-2. Auditory brainstem responses from the right ear of a 10-month-old patient with a severe to profound hearing loss as documented following behavioral audiometric testing. Observe the cochlear microphonic responses in the middle two traces (95 rev. and 75 rev.) obtained by recording ABRs using positive polarity clicks; the polarity is reversed, and negative polarity clicks are used in the subsequent recording at 95 and then at 75 dB nHL. The cochlear microphonic is absent after further attenuation of the stimulus level (55 rev.).

Consequently, the EABR results indicated that electrical stimulation was more effective than acoustic stimulation in synchronously activating the auditory pathway for this patient. She received a cochlear implant at age 2. Using the cochlear implant, detection threshold levels in the 35 to 40 dB HL range were established (Fig. 18-6), which compared favorably with her preimplant audiometric studies.

ELECTROCOCHLEOGRAPHY The term electrocochleography refers to the recording of acoustically evoked neuroelectric events generated by the cochlea and the auditory nerve. Early cochlear-produced potentials and auditory nerve action potentials constitute the electrocochleographic response. Electrocochleographic measurements may be obtained using several recording techniques. The original method of electrocochleographic recording involves placing a transtympanic needle electrode on the promontory. dB 60 40

L1 L2 DP NF

0 10 20 30 40 50 60 70 80 90 100 110 250

1K

2K

Although this type of recording results in a very large amplitude response, it is an invasive method not well accepted by a substantial proportion of patients. Noninvasive methods are available (i.e., a gold foil “Tiptrode,” or Coats’ “Leaf” electrode) but may be less efficient in providing an interpretable response or may be uncomfortable for the patient. Another noninvasive recording device uses a soft hydrogel-tipped electrode placed against the lateral tympanic membrane surface under direct visual control (“TM-ECHochGtrode,” manufactured by BioLogic Systems Corp.). This electrode can provide consistent, satisfactory resolution of the cochlear microphonic, summating potential, and action potential. Although response amplitudes obtained with the hydrogel device are reduced when compared to those obtained with a transtympanic needle electrode, the noninvasive, comfortable nature of this recording paradigm obviates the need for a physician’s involvement in electrode placement without sacrificing test sensitivity. Following placement, the impedance of the electrode is measured to ascertain appropriate positioning. The electrode is held in place with a standard, foam insert transducer tip, and in our experience it is tolerated well by patients as young as 10 and 12 years of age.

.25 uV

−20 0.25

III

III v

0.5 1.0 2.0 4.0 8.0 Distortion-product otoacoustic emissions

kHz

Figure 18-3. Distortion product otoacoustic emissions (see Fig. 18-2), and severe to profound hearing loss from the right ear of the patient with cochlear microphonic responses in the right ear. Response strength (signalto-noise ratio) ranges from 8 to 24 dB. DP, distortion product emission; NF, noise floor.

8K

Figure 18-4. Preimplantation audiogram of a patient with a severe to profound sensorineural hearing loss, cochlear microphonics, absent auditory brainstem responses, and distortion product otoacoustic emissions. Right ear implantation was successful.

v @4.5 msec. 0

4K

Frequency in Hz

+

20

500

800 uA 600 uA

.25 uV − EABR: Right Ear Figure 18-5. Preimplantation electrically evoked auditory brainstem responses from a young patient with auditory nerve dys-synchrony (see Figs. 18-2 through 18-4).

Objective Measures of Auditory Function

Hearing level in dB (ANSI-96)

CI Detection Skills 0 10 20 30 40 50 60 70 80 90 100 110

ECoG

AP amp Base

SP amp

ABR

C

C

C

C

C

291

v

CM

ECoG/ABR recording Sensitivity and Sweep Time/Division ECoG: 1.24 uV 1.0 msec ABR : 1.24 uV 1.0 msec CM : 0.31 uV 1.0 msec

250

500

1K

2K

4K

8K

Frequency in Hz Figure 18-6. Postactivation implanted sound-field pure tone thresholds from a 2-year-old patient with auditory nerve dys-synchrony (see Figs. 18-2 through 18-5).

Electrocochleography components:

consists

of

the

following

1. The cochlear microphonic (CM), an alternating current (AC) potential that closely resembles the waveform of the acoustic stimulus and reflects changes in the resistance of the outer hair cells during stimulation. To obtain a cochlear microphonic, click or tonal stimuli must be delivered in a constant polarity fashion. 2. The summating potential (SP), a direct current (DC) potential that follows the stimulus envelope, appearing as a baseline shift of the recorded cochlear microphonic. It arises from DC intracellular potentials generated by hair cells. To resolve the SP better, stimuli must be delivered in an alternating polarity fashion; otherwise, individually obtained condensation and rarefaction responses are summed to cancel out the cochlear microphonic. 3. The eighth nerve action potential (AP) is the equivalent to wave I of the ABR, reflecting the summed activity of synchronously firing cochlear nerve fibers. We recommend the following recording technique: prior to placement of the tympanic membrane surface electrode, self-adhering surface electrodes are placed in the midline of the forehead just below the hairline, and on each mastoid. This allows one to simultaneously record an electrocochleogram (ECoG) from the ear with the tympanic membrane (TM) electrode as well as an ABR wave V from the contralateral side. Clicks of alternating or constant polarity and tone burst stimuli are presented at an intensity of 85 dB nHL or greater if the patient has a substantial hearing loss. One or two kilohertz (kHz) tone bursts have a 5-millisecond rise time and a 10-millisecond plateau. Figure 18-7 shows a click-evoked ECoG with well-defined SP and AP components (top trace), a contralaterally recorded ABR with the wave V marked, and a tone burst ECoG consisting of a cochlear microphonic with no discernible SP. Electrocochleography is used most as a neurotologic diagnostic aid in identifying cochlear hydropic conditions associated with Ménière’s disease and other cochleopathies. It is thought that the presence of hydrops alters the

Figure 18-7. Two-channel recording consisting of electrocochleographic and auditory brainstem responses (top two traces); the lowermost tracing is the cochlear microphonic response to a tone burst stimulus with no discernible summating potential.

mechanical characteristics of the basilar membrane and contributes to the increased amplitude of the SP considered to be diagnostic of endolymphatic hydrops.19 In order to reduce interpatient variability, the ratio between the amplitude of the SP and the AP (SP/AP ratio) is employed instead of measuring the absolute amplitude of the SP.20 Owing to the increase of the SP amplitude associated with endolymphatic hydrops, patients are expected to exhibit larger SP/AP ratios. In a study of subjects with normal hearing for age,21 SP/AP amplitude ratios recorded extratympanically ranged from 0.04 to 0.59. Other studies have found similar values of the ratio in normalhearing patients. Using transtympanic recordings, Gibson and colleagues22 calculated SP/AP ratios that ranged from 10% to 63%. However, the sensitivity of this measurement appears limited because an overlap exists between SP/AP ratios of patients with (nonhydropic) cochlear hearing loss and patients with classic symptoms of endolymphatic hydrops. Coats and colleagues23 found that 44% of Ménière’s ears tested fell under the 95% upper limits of normal ears. This translates into a sensitivity of only 56%, reflecting the fluctuant nature of hydropic conditions. Increased amplitude of the SP/AP ratio is not limited to hydropic conditions. Marangos and colleagues24 reported increased SP/AP amplitude ratios in patients with CP angle tumors. Therefore, caution should be exercised to avoid the missed diagnosis of CP angle tumors that may be associated with increased SP amplitude. A normal SP/AP amplitude ratio does not rule out endolymphatic hydrops and an increased ratio should be considered a supportive, but a nonpathognomonic finding of hydrops. The following clinical criteria for electrocochleography are used in our clinic: SP/AP ratio exceeding a value of 0.40 with click stimuli; summating potential amplitude for tone burst stimulation of 2 microvolts or more. The N1 (or AP) component condensation-versus-rarefaction click latency difference has not been used systematically in our clinic.25 If it is used, a difference greater than 0.38 milliseconds (condensation latency is greater than rarefaction latency) is considered abnormal. The electrocochleography criteria are based on the following clinical assumptions: In the presence of hydrops, a distended scala

292

NEUROTOLOGIC DIAGNOSIS

media results in an increase of the negative SP amplitude and in a possible increase in cochlear microphonic and cochlear nerve AP thresholds. Additionally, in more advanced disease the amplitude of the AP may be reduced. The increase in the amplitude of the negative SP alone or in combination with a decrease in AP amplitude is the underlying cause for the increased SP/AP amplitude ratio for clicks. With tone burst stimuli, an increase in SP amplitude appears as a shift of the cochlear microphonic baseline, which indicates an increase in SP amplitude. A 42-year-old woman came to our clinic with a 5-year history of episodic vertigo, progressive right ear hearing loss that fluctuated, and right-sided tinnitus and aural pressure. Figure 18-8 illustrates her audiogram characterized by normal hearing in the left ear and a moderate, lowfrequency sensorineural hearing loss in the right ear with minimally reduced word recognition scores. She underwent an electrocochleographic evaluation. Both clicks and 1000-Hz tone bursts were used as stimuli. As illustrated in Figure 18-9, she presented with a normal SP/AP ratio of 0.3 in her left, nonsymptomatic ear and an elevated SP/AP ratio of 0.6 in the symptomatic right ear. Also, as illustrated in Figure 18-10, her tone burst electrocochleography was characterized by a prominent SP with amplitude of approximately 2 microvolts in her right ear (top trace) as opposed to a barely measurable SP with the same stimulus in the left ear (lower trace). The increased SP ratio on the right side as well as the large amplitude SP obtained with tone burst stimulation helped confirm a diagnosis of Ménière’s disease in her right, symptomatic ear. Notably, the caloric test results obtained during the patient’s vestibular evaluation showed a reduced caloric response in the right ear compared to the left but in absolute terms still within normal limits. Consequently, the interpretation was “paretic lesion in the right ear or an irritative lesion in the left ear.” The presence of abnormal electrocochleography in conjunction with right ear symptoms helped determine the laterality of the disease. 0

dB (ANSI S 3.6, 1996)

10

AP amp

SP amp

LE: 0.3 Base

AP amp

SP amp

Base

RE: 0.6

ECoG: SP/AP
Electrocochleography may also be used as an objective indicator of treatment efficacy. This is illustrated by the following case involving a 55-year-old patient with a severalyear history of left-sided Ménière’s disease. Over the years, he had been treated conservatively with low-sodium diet and diuretics; however, he continued to have spontaneous vertiginous episodes and fluctuating low-frequency hearing loss. He was seen in our clinic, where he received a pressure equalization tube placed in the left tympanic membrane in preparation for treatment with the Meniett device (Medtronic Xomed). This device is recommended to alleviate symptoms of Ménière’s disease and it delivers brief pressure pulses through a tympanometry-like ear tip placed into the ear canal. For some patients this type of treatment, which is recommended 3 times a day for 5 minutes, results in both subjective and objective changes.26 Figure 18-11 illustrates pre- and post-treatment click-evoked electrocochleography obtained within a 4-month interval. The figure illustrates a normalization of the SP/AP ratio from a value of 0.7 to a value of 0.34. It is of note that the

20 30 40 50

RE

60

SP

70 80 90 RE LE

SRT 30 05

% 92 100

250

500 1,000 2,000 4,000 Frequency in hertz (Hz)

LE 1.2 uV

8,000

Figure 18-8. Audiogram of a 42-year-old woman with right ear hearing loss, tinnitus, and aural pressure. Normal pure tone thresholds are present in the left ear and a moderate lower frequency hearing loss in the right ear; speech audiometrics are compatible with the pure tone information.

2 msec

ECoG: CM on large SP, RE Figure 18-10. Tone burst-evoked electrocochleography reveals a prominent summating potential from right ear responses (top trace); combined with an SP/AP ration of 0.6, it helped to confirm Ménière’s disease.

Objective Measures of Auditory Function

SP amp

AP amp

Base

Pre: 0.7 AP amp SP amp Base

Post: 0.34 ECoG: pre- v. post-treatment Figure 18-11. Electrocochleography results from a patient treated with a Meniett device (Medtronic Xomed) for Ménière’s disease. Note the increased amplitude of the action potential (AP) in the post-treatment condition. A delay in the absolute latencies of responses in the lower trace is due to a pressure equalization tube in the left tympanic membrane.

amplitude of the AP is increased in the post-treatment waveform. The post-treatment latency is slightly delayed with respect to the treatment latency owing to the presence of the PE tube.

AUDITORY BRAINSTEM RESPONSE The ABR is the averaged surface-recorded activity from multiple-source neural generators in the peripheral and lower central auditory nervous system and represents the synchronous discharge activity of onset-sensitive single units from first- through sixth-order neurons (Fig. 18-12). The high-intensity ABR is characterized by five or more waves, the positive peaks of which are conventionally labeled with Roman numerals.2,27 Studies by Moller and

Primary auditory cortex

Probable ABR Generators:

Inferior colliculus V

Dorsal cochlear nucleus Ventral cochlear nucleus

Janetta28 localize the neural generators of ABR wave peaks I through V to the auditory pathway between the cochlear nerve and the nucleus of the lateral lemniscus in the midbrain. Waves I and II are generated by activity at the distal and proximal cochlear nerves, respectively. The presence of two action potentials originating from activity within the same cranial nerve is attributed to a transition in nerve fiber covering from the central neuroglial cells to the peripheral Schwann cell endoneurium at the segment of the auditory nerve nearest the porus acusticus. Near-field recordings enhance both waveform peaks, as seen in electrocochleography. Activity in the cochlear nucleus and in the superior olivary complex is represented by ABR waveform peaks III and IV, respectively. Moller and Janetta28 reported that waveform peak V reflects activity in the lateral lemniscus. Neural activity in the area of the inferior colliculus corresponds temporally with the post-wave V negativity recorded on the scalp. Waveform peaks IV through VI are highly complex and probably reflect multiple neural generator activity. Acoustic stimuli used to evoke the ABR include wideband clicks and tone bursts and are delivered via insert or supraaural earphones or a bone-conduction transducer. Clicks are brief rectangular pulses of constant or alternated polarity, while tonal stimuli may be characterized as sinusoidal signals with brief rise, fall, and plateau durations. To be effective in evoking a response, the intensity level of the acoustic stimuli must lie within a patient’s dynamic range. Therefore, patients with severe to profound hearing losses are less likely to have an ABR. In order to ensure that the highest-quality ABRs are recorded, stimulating and recording parameters are carefully adjusted for the patient’s hearing levels (Table 18-1). Therefore, audiologic

Medial geniculate body

VI

Nucleus of lateral lemniscus

Wave I Wave II Wave III Wave IV Wave V Wave VI I

Distal auditory nerve Proximal auditory nerve Cochlear nucleus Superior olivary complex Lateral lemniscus Inferior colliculus III IV V

II III

293

VI

IV II

I Trapezoid body

Superior olivary nucleus

Figure 18-12. Probable auditory brainstem response generators and associated waveform peaks. [Adapted with permission from Olsen WO: Special auditory tests. In Jacobson JT, Northern JL (eds.): Diagnostic Audiology. Austin, TX: Pro-ed, 1991, p 38.]

294

NEUROTOLOGIC DIAGNOSIS

TABLE 18-1. Selected ABR Parameters for Neurodiagnostic and Hearing Estimation Investigations Neurodiagnostic

Hearing Estimation

Stimulus type*

Click, 1-kHz tone burst

Stimulus rate† Stimulus rise, fall time‡ Number of sweeps Intensity (or range) Stimulus delivery§

21.1/sec Click: NA; tone: 2-0-2 2000–3000 75–95 dB nHL Insert earphone

Bandpass settings (Hz) Amplification Analysis duration

100–3000 × 100 k 15 msec

Click; 0.5 to 2-kHz tone burst 31.1/sec Click: NA; tone: 2-0-2 1200–4000 05–95 dB nHL Insert, supra-aural, bone-conduction transducers 20/30–3000 Hz × 100 k 20–25 msec

*Alternating polarity used for neurodiagnostic testing to reduce spread of stimulus artifact into recording; single polarity clicks useful to visualize cochlear microphonic in auditory neuropathy/auditory dys-synchrony. † Rate, number of averages increased in studies of the effects of demyelinating disease. ‡ Rate lowered for bone conduction measurements to reduce vibrotactile spread of stimulus. Ramping for 2 kHz tonal stimuli changes to 2-1-2. § Appropriate transducer is selected for routine testing or for patients with atretic ears and the like.

assessments should be conducted before neurodiagnostic ABR testing. The ABR is a far-field representation of responses along the auditory pathway. The term far-field indicates that recording electrodes do not directly contact anatomic generators. There are at least two deleterious effects of recording electrical potentials from the scalp. First, far-field recordings are less robust, partly due to the distance between generator site(s) and recording site. Second, other sources of electrical noise may obscure the ABR. Such “competing” electrical signals may have electroencephalographic, electrocardiac, or electromyographic sources, or they may originate from electrical devices in or proximal to the test location or from an essential medical monitoring device such as a pulse oximeter. Unless properly controlled and canceled, the competing electrical potentials can easily diminishing ABR waveform quality. Optimizing the electrode sites via thorough cleansing and gentle abrasion techniques is crucial. So, too, properly selected recording parameters enhance the ABR recording. For example, the ABR consists of energy in a specific band. Bandwidth filters set to record responses in the approximate frequency range 20 to 3000 Hz provide a high-quality recording that includes all waveform peaks (Fig. 18-13). In the figure, note that relatively smaller changes are evident after opening bandpass settings beyond 20 to 1000 Hz, attesting to the dependence of the ABR on energy at or below 1000 Hz. Several technological tools exist that allow an examiner to extract electrophysiologic target responses from competing noise. These include the following: 1. Differential amplification, which functions by rejecting voltages with equal or common amplitude and phase at positive and negative inputs, referenced to ground; then, the remaining difference in voltage at those two inputs is amplified. This process is known as common mode rejection. 2. The ratio of common mode noise rejected, specified in decibels; larger decibel ratings indicate better

20–250 Hz

20–1000 Hz

III

v

I

20–3000 Hz 0.31 uV 1.5 msec

Figure 18-13. ABR waveforms reflect alterations in bandpass filter settings. Note the slow-wave component of the ABR in the uppermost ABR tracings, upon which wave peaks ride; second, observe improved clarity of waveform peaks once the high-frequency cutoff reaches or exceeds 1000 Hz, confirming ABR dependence on relatively low-frequency energy.

amplifier gain.29 The capacity for common mode signal rejection depends largely on preparation, that is, the physical layout of the test area in relation to devices that generate electrical fields, the shielding of the measurement channel(s), and the quality of components such as leads used to record responses. 3. Signal averaging, which is important for measurement of low-amplitude, repetitive responses time-locked with a precise trigger source (synchronized response summing); the amplitude of unsynchronized noise diminishes with successive averaging, decreasing by the square root of the number of sweeps resulting in a signal-to-noise ratio above unity. Larger response amplitudes are obtained with greater stimulus intensity and generally require fewer averages. Approximately 1500 to 2500 samples typically produce adequate signal-to-noise ratios. Figure 18-14 demonstrates the improvement in ABR waveform morphology that can be expected when additional sweeps are included in the averaging process. Investigators have used four-channel recordings to more accurately identify individual components of the ABR in patients who have intracranial injuries30 or acoustic nerve tumors.31 In the latter report, the investigators used Tiptrode ear canal reference electrodes and reported that of the four recording choices, the ipsilateral record afforded the best neurodiagnostic information. Presumably, this reflected the somewhat “nearer-field” recording of ABR responses, adding to the amplitude of individual components and leading to improved signal-to-noise ratios. A four-channel ABR was obtained at 80 dB nHL from a normal-hearing subject in order to demonstrate the capacity for

Objective Measures of Auditory Function

v

125 clicks

v

III

500 clicks

v III I

2,000 clicks

0.31 uV 1.5 msec

Figure 18-14. ABR signal-to-noise ratio increases and morphology improves as sweeps are added to the averaged response. Note that wave V may be seen with as few as 125 clicks presented. In neurodiagnostic ABR evaluation, additional averaging is required to facilitate wave peak identification (2000 clicks).

enhancing individual components of the neurodiagnostic ABR, leading to more precise measurements and reporting (Fig. 18-15). The recording employed ipsilateral, contralateral, “horizontal,” and “vertical” references simultaneously; note the absence of waveform peak I in the

v

III I II

IV

Cz-A2 (ipsilateral)

Cz-A1 (contralateral)

A1-A2 (horizontal)

Cz-C2 (vertical)

0.31 uV 1.5 msec

Figure 18-15. Four-channel ABR recorded at 80 dB nHL from a normal-hearing female using reference electrode at ipsilateral and contralateral earlobes and at the second cervical vertebra; note differences in amplitude and absolute latency of waveform peaks throughout this four-channel recording.

295

contralateral channel, and the enhancements of peaks III and V in the horizontal and vertical channels, respectively. The amplitude of waveform peak V in the vertical channel is more than four times that recorded in the horizontal channel owing to the presumed orientation of the respective dipole vector for wave peak V. The authors have found that appropriate control of the recording montage is very useful in neurodiagnostic ABR measurements, particularly in the case of patients with moderate to severe high-frequency sensorineural hearing losses. In summary, the ABR reflects activity from multiple generators along the auditory pathway in response to various acoustic stimuli. Stimulus and recording parameters should be optimized to provide a record of the neurophysiologic function of the auditory nerve based on the results of a concomitant audiologic assessment. Importantly, ABR waveform morphology is affected by mass lesions on or near the auditory nerve. Neurologic lesions that are manifestations of demyelinating disease also affect ABR recordings by desynchronizing spike propagation along the myelinated auditory pathway. Thus, the ABR can be a good neurophysiologic indicator of auditory nerve and auditory brainstem functional integrity.

DETECTION OF HEARING LOSS USING THE AUDITORY BRAINSTEM RESPONSE Newborns and infants are incapable of participating in behavioral hearing evaluations to the extent that detailed ear-specific information cannot be obtained until children are 2 to 4 years old.32 Given a mandate that calls for early identification of congenital or early-onset hearing loss by several months of age,33 the ABR becomes an ever more important part of the collection of clinical instruments that audiologists use to estimate the magnitude and type of hearing loss in children. ABR has similar value in the estimation of peripheral hearing sensitivity in noncompliant, older patients. Attenuated stimulus levels produce ABRs with decreased amplitude and prolonged absolute latencies. Figure 18-16 demonstrates that ABR wave V typically has the largest amplitude and is more easily identified as stimulus levels diminish, making wave V the most useful waveform component for estimating ABR thresholds. By convention, in the clinical setting ABR recordings are replicated to ensure proper identification of waveform components. Manufacturers of electrophysiology equipment offer software that computes correlation coefficients as statistical representations of replicability, and single-point F ratios (Fsp) can be measured to assist in describing the variances of two ABR samples. Making use of such statistical measures helps to enhance clinical descriptors (“good,” “fair,” or “poor” waveform morphology) typically used in reporting ABR results. The ABR as a carefully used hearing screening instrument in the well-baby unit or in the neonatal intensive care unit can be valuable using either automated, default protocols or operator-controlled parameters. Delivering low-intensity stimuli monaurally, it aids in the eventual detection of unilateral and bilateral mild or greater hearing losses.34 Relative to other measures such as otoacoustic emissions,

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Alternating click I

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Auditory brainstem responses Figure 18-16. Grand averages of multiple recordings of a right ear ABR using click (left panel ) or 500-Hz tone burst (right panel ) auditory stimuli. The latencies of the responses to tonal stimuli are prolonged relative to the click ABR responses, and tonal amplitudes are reduced as well.

the technique has higher sensitivity and associated costs, requires a more sophisticated and experienced operator, and limits screening statements to higher-frequency hearing. “Refer” results mandate rescreening with ABR or otoacoustic emissions. Based on the outcome, diagnostic evoked potential testing may be needed. Click-evoked ABR threshold testing continues to be a common procedure, despite the significant limitations associated with use of transient stimuli.35 Investigators continue to search for protocols that produce threshold results that simulate the “speech-frequency band,” that is, 0.5 to 2 kHz of the audiogram. Retrospectively, click threshold results have been found to correlate best with high-frequency thresholds near 2000 Hz.36–38 These findings are partially attributable to changes in the frequency and amplitude characteristics of broadband, rapid-onset stimuli that are delivered to the diminutive, pliable infant ear canal via an insert transducer through 26 centimeters of flexible, polyethylene tubing. Gorga and colleagues39 compared click-evoked ABR threshold and latency characteristics to pure tone audiometric findings in normal-hearing (N = 22) and sensorineural hearing impaired subjects (N = 194). The latter group was composed of 125 people with high-frequency configurations of hearing loss, while the remaining 69 people had flat hearing loss. These investigators reported that when comparing ABR thresholds to audiometric data, agreements between those two indices were highest when audiometric test frequencies were 2 kHz and 4 kHz (r = 0.75 and 0.73, respectively). Correlations to pure tone thresholds at 1 kHz and 8 kHz were poorer (0.65 and 0.6, respectively). Behavioral thresholds at frequencies below 1 kHz were not analyzed in this report. A normal threshold ABR result, based on the use of click stimuli, should be carefully reported suggesting that (a) normal hearing exists in the approximate frequency range of 1 to 4 kHz in the test ear or that (b) an island of normal hearing resides in that same frequency range.40 While broadband click stimuli are used to perform ABR during hearing screening and in subsequent hearing threshold estimation, tonal stimuli are used with ever greater regularity. This is due to the recognition of certain inherent limitations associated with the use of click stimuli

as well as the desire to more closely approximate the behavioral audiogram for precise amplification fitting. Lowerfrequency hearing estimates via the click ABR are less predictable.41 So-called ramped tonal stimuli have longer temporal characteristics (on and off times as well as plateau duration) and reflect the activity of fewer neural fibers.42 The morphology of the tonal ABR waveform is dissimilar to click-evoked responses, reflecting fewer contributing neural elements and a more apical orientation in its generation along the basilar membrane. Absolute latencies of tonal ABRs are prolonged and amplitudes may be reduced (see Fig. 18-16). Extended averaging will result in improved morphologic characteristics such as improved signal-tonoise ratios and more distinct waveform peaks while providing averaged results that are better suited to threshold determination. As alluded to earlier, the impetus to establish universal hearing screening and provide appropriate, comprehensive habilitation propels the desire to record frequency-specific ABRs. Appropriately programmed amplification will be fit to newly identified hearing impaired infants. There are numerous methodologies for tonal ABR evaluation and Hyde43 summarized many of them. For example, a spectrally constrained transient stimulus with a nominal center frequency is delivered to the test ear; masking may be used in the contralateral ear. It is useful to know how much side band energy is present above and below the center frequency. Nonlinear gating functions (e.g., Blackman, cosine square) help to attenuate side band energy characterized by approximately 30 dB of attenuation within one octave from the nominal center frequency (Fig. 18-17). However, differences in results obtained using various gating strategies may be less than expected. Purdy and Abbas44 reported 2-kHz and 4-kHz tone burst ABR thresholds exceeded behaviorally elicited thresholds by 10 to 13 dB using either linear or Blackman gating. This investigation emphasized the importance of setting appropriate filter bandwidths when using tone burst stimuli; that is, appropriate lowfrequency weighting must be a recording parameter choice when using tone burst stimuli with a center frequency below 1000 Hz.

2.031 kHz

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Figure 18-17. Spectral waveform of a Blackman-gated tone burst with a center frequency equal to 2031 Hz used in ABR frequency-specific estimates of hearing sensitivity. Sideband energy peaks were −28 dB relative to peak energy at 2031 Hz.

Objective Measures of Auditory Function

The efficiency with which tonal ABR thresholds predict behavioral audiometric thresholds continues to be scrutinized. Stapells45 performed a meta-analysis of the literature concerning air conducted tone-evoked ABR testing in children and adults. Thirty-two investigations were reviewed, representing the results from 1203 subjects including 388 subjects with sensorineural hearing loss. He reported that tonal ABR thresholds in normal listeners ranged from 10 to 20 dB nHL. In the group of hearingimpaired subjects, tonal thresholds were 5 to 15 dB higher than behavioral thresholds in adults and were ± 10 dB than behavioral thresholds in infants. The use of the toneevoked ABR was strongly encouraged. In a retrospective study that compared behavioral pure tone and electrophysiologic thresholds, Edwards and colleagues46 reported that a combination of click, 0.5 kHz, and 1.0 kHz frequency tone burst thresholds, when averaged and given one of four data set assignments reflecting average thresholds from normal to severe, compared favorably to similarly ranked behavioral assignments. They reported that despite a 100% incidence of recurring otitis media, a combination of air- and bone-conducted ABR testing produced results with good predictive value for identifying both type and magnitude of hearing loss. Notably, the data were skewed toward moderate and greater degrees of hearing loss, reflecting the common hearing status of multiply involved children with CHARGE syndrome. Several salient points must be considered when comparing electrophysiologic and behavioral test results. They include the following: 1. Significant differences in calibration methodologies for electrophysiologic and audiometric tonal stimuli 2. Discrepancies between ABR stimulus intensity as “set” on test equipment versus the actual output measured in the ear canal (particularly in younger patients with small volume ear canals), which can lead to underestimation of actual ABR stimulus intensity 3. The possibility of fluctuating or progressive hearing loss, as in patients with large vestibular aqueduct syndrome or those with a genetic predisposition for progressive hearing loss 4. Spectral differences between electrophysiologic stimuli, particularly brief, broadband clicks, and audiometric thresholds38

ESTIMATING AMPLIFICATION BENEFIT: ELECTROPHYSIOLOGIC PROCEDURES The early provision of appropriately fitted amplification is a worthy goal toward which hearing professionals strive. Unfortunately, until newborns and infant children achieve developmental levels that allow one to obtain reliable and valid behavioral test results, “appropriately fitted amplification” is an objective reached via a combination of care provider observation and subjective scaling measures. Prescriptive fitting measures based on electrophysiologic data are helpful for managing multiple amplification characteristics but do not functionally describe the effect of the intervention on hearing sensitivity. Thus, efforts continue

297

that aim to develop an objective clinical technique to gauge aided benefit better in very young patients. Many investigations have analyzed the use of the ABR as an objective measure of amplification benefit for infants vis-à-vis the absolute latency of ABR wave V referenced to normal listeners.47 Although transient clicks have been shown to have a role, tonal stimulus artifacts contaminate evoked responses,48 and an inability to describe changes in evoking stimuli by amplification has presented challenges. Further, the failure of click-evoked ABR to adequately define lower-frequency gain49 and demonstrate the utility of compression circuits in hearing aids50,51 has curbed investigational interest. Despite these hurdles, objective techniques continue to be examined to determine their role in assessing aided benefit. For example, Purdy and Kelly52 reported that the cortical auditory evoked potential (CAEP)53 might be effective during hearing aid assessments by using speech stimuli. Until approximately 7 years of age, a large, late P1 response dominates the CAEP and may help to demonstrate the benefits of amplification in youngsters reported by Rapin and Graziani54 and Gravel and colleagues.55 With inherently higher face validity than tonal stimuli, longer duration speech stimuli (cumulative durations of 30 to 75 ms, onset duration longer than 10 ms) might also better assess the utility of compression circuitry, broadening the scope of hearing aid assessment56 and may help to moderate several of the technical difficulties mentioned earlier such as stimulus ringing and an inability to demonstrate input-output characteristics of an amplification device. Auditory steady-state responses (ASSRs) are elicited by amplitude-modulated tones that are common in infants and unaffected by sleep.57 Multiple tones can be presented simultaneously to each ear for threshold testing, while amplitude-modulated tones transduced through free-field speakers resist distortion, making them ideal stimuli for assessing aided hearing. Picton and colleagues58 sought out aided threshold responses using ASSRs in a group of 35 older children with hearing impairment. One goal of the study was to compare ASSRs and behavioral thresholds in developmentally advanced children in order to be able to estimate the predictive ability of ASSR results for very young children and others who would not be able to offer behavioral responses. The investigators discovered that amplitude-modulated ASSR stimuli provided more frequency specificity than ABR click or tonal stimuli, and reported physiological-to-behavioral differences of 13 to 17 decibels (+/− 8 db) at 0.5, 1.0, and 2.0 kHz for the group of aided, cooperative children. Picton’s group suggested that responses to such amplitude and frequencymodulated stimuli might better evaluate aided speech perception processes while determining both audibility and discrimination ability.57

ACOUSTIC NEUROMA DIAGNOSIS WITH THE AUDITORY BRAINSTEM RESPONSE Mass lesions of the retrocochlear pathway are thought to produce ABR abnormalities through pressure on, displacement of, or attenuation of the auditory nerve or auditory brainstem. Depending on its volume and location, a mass

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in proximity to retrocochlear auditory structures may attenuate, delay, or abolish certain ABR waveform components. This model for ABR interpretation may be applicable in cases where tumor involvement with the auditory pathway is discrete and when preexisting hearing thresholds are normal. However, these principles frequently may not apply because of preexisting pathology leading to extensive interplay between brainstem components in processing auditory stimuli.59,60 Therefore, use of the ABR for diagnostic purposes mandates consideration of other supporting audiologic information. A good example is provided by the absence of an ABR in an ear with a severe hearing loss. If an inadequate stimulus level is used to generate electrophysiologic responses, test results may be misinterpreted inappropriately and elevate one’s index of suspicion for an eighth nerve or brainstem lesion. Clearly, the ABR should be evaluated with suitable attention paid to the patient’s hearing levels at the time of the test. Accordingly, cochlear dysfunction can often be compensated to enhance the accuracy in the ABR-directed assessment of the auditory pathway. Differential diagnosis based on the ABR involves a strategy that considers several characteristics of evoked waveforms. This “hierarchy of analysis” assesses the overall configuration of the response and its composing waves in the context of the hearing status. The first step in the analysis is to determine the presence or absence of an ABR evoked by an appropriate stimulus. For instance, in the presence of severe to profound hearing impairment at frequencies exceeding 500 Hz, morphologically defined responses to 75 dB nHL clicks are not anticipated. The second level of ABR analysis verifies the presence of all major composite peaks and their replicability. If the recorded waveforms are of sufficient technical quality, the following characteristics apply: 1. Wave V should stand out as the most robust of the ABR components in normal-hearing subjects and the most resilient component in patients with cochlear pathology, with threshold preserved at or near behavioral threshold levels. 2. Wave I is less robust and its morphology fails to resolve at stimulus levels below 40 dB SL. An absent or poorly resolved wave I (with waves III and V present) with moderate to severe sensorineural hearing loss carries little implication for retrocochlear function; however, the absence of waves III or V, or both, with a robust and well-defined wave I is highly suggestive of auditory brainstem impairment. Absence of components beyond wave I can occur in cases of acoustic neuroma with or without significant hearing loss. The third level of ABR interpretation measures the latencies of waveform peaks and intervals between peaks, provided the morphology of the response permits. I–III and III–V interpeak latencies are measured and compared with normative data. Normative data are plotted as a frequency distribution that incorporates standard deviation intervals. I–III and III–V latencies are classified as normal if the values fall within the 95% confidence interval for mean latencies.

When wave I is not attainable, the absolute latencies of wave V should be determined bilaterally, and interaural differences (ILD-V) calculated. Hearing impairment, whether conductive, cochlear, or retrocochlear, prolongs wave V latency. In the presence of a hearing loss, ILD-V is interpreted with consideration given to the magnitude of the hearing loss at 4 kHz. Appropriate adjustment of wave V latency diminished the false-positive rate from 24% in the uncorrected condition, to 8% of a group of 266 patients with unilateral sensorineural hearing loss. In a group of 94 confirmed cases of acoustic neuroma, the same correction for hearing loss at 4 kHz produced a false-negative rate of 2.3% (3 patients).61 Rosenhamer and colleagues62 recommend an adjustment of 0.1 ms/10 dB increment in hearing threshold above 30 dB at 4 kHz. The audiometric configuration has been shown to influence the I–V interpeak latency. Keith and Greville59 found increased I–V interpeak latencies in patients with notched high-frequency hearing loss in the absence of CP angle lesions. This probably reflects the greater role assumed by high-frequency generators in producing wave I relative to those responsible for wave V. The I–III interpeak latency is influenced to a lesser extent by cochlear hearing loss. Moreover, the most reliable ABR manifestation of an acoustic tumor appears to be an increase in the I–III interpeak latency on the affected side.63,64 This interval is therefore recommended for neurotologic diagnostic applications whenever these peaks are available. When the lack of definition of the ABR obtained with clicks prevents measurement of interpeak latencies, narrowband tonal stimuli may take advantage of lower thresholds at specific frequencies. To use lower thresholds at 1000 Hz in evoking the ABR, 1000-Hz tone pips can supplement the click-evoked ABR. Suggested parameters for 1000-Hz tone pips include gating with a nonlinear function (Blackman) using a 1-ms rise-fall time and a very brief plateau (100 ms). In selected cases, Telian and Kileny65 found the use of 1000-Hz tone pips helpful in circumventing the effects of elevated thresholds in the 2000 to 4000 Hz range on the click-evoked ABR. Of 17 patients with surgically confirmed acoustic neuromas, 15 of which presented with sloping high-frequency SHL, reliable evidence of retrocochlear involvement could be made from the click-evoked ABR in only 5 cases based on abnormal interpeak latencies and ILD-V. In two patients, wave V was the only replicable and identifiable component for both clicks and 1000-Hz tone pips, and the diagnosis of retrocochlear involvement. Some of these were cases where click responses were absent and the diagnosis was based on the significant prolongation of wave V latency for tone pips. In other cases, despite the fact that the ILD-V for clicks normalized after correcting for hearing loss at 4000 Hz as recommended by Selters and Brackmann,61 the ILD-V for tone pips was significantly prolonged in spite of symmetric hearing sensitivity at 1000 Hz. Recently, the auditory brainstem response has come under scrutiny for the detection of small acoustic neuromas; that is, sensitivity has been reported to range from 63% to 93%. A recent study66 reported on 25 patients with surgically proven small acoustic neuromas measuring 1 cm or less.

Objective Measures of Auditory Function

The ABR was abnormal in 92% of patients in this series. Our data shows that when using optimal technique including the combination of click- and tone-evoked ABR, the ABR sensitivity for small acoustic neuromas can be increased to a clinically acceptable 90+%. Like other diagnostic tests, the ABR is only as good as the operator and the interpreter. This is also true for imaging studies with a theoretical sensitivity approximating 100%; however, poor imaging quality or interpretation error can alter this high sensitivity. A novel approach to diagnosing small acoustic neuromas with the ABR was developed by Don and colleagues.67 These investigators coined the concept of the “stacked derived-band ABR.” The diagnostic criterion here is the amplitude of a reconstructed auditory brainstem response from the sum of click-evoked ABRs obtained with different ipsilateral high-pass filtered noise. By embedding clicks in high-pass filter noise with different cut-off frequencies, ABRs are generated that represent different, specific frequency regions along the basilar membrane. Responses within this set have different latencies dictated by place of stimulation along basal and more apical basilar membrane. Those obtained from the more apical regions have a longer latency than those obtained from the basal region. Averaged responses are realigned and summed to obtain a reconstructed grand average. Don and colleagues found that the amplitude of the reconstructed ABR was sensitive to the presence of small acoustic neuromas; that is, it was reduced when compared to normal ears with no acoustic neuroma or to the contralateral ear of a patient with a unilateral acoustic neuroma. These investigators surmise that summing the ABRs obtained from different regions along the basilar membrane provides the total neural-synchronous response to stimulation. Amplitude reduction most likely reflects the reduction in the number of stimulable neural elements in an ear with an acoustic neuroma. This technique is not in widespread use, although the software is available on at least one commercial-evoked potential instrument.

Measurement Criteria for Diagnostic Auditory Brainstem Response The diagnostic sensitivity and specificity of absolute and interpeak latency measures depends on how normal limits are specified. For example, “normal” defined by wave latency +/− one standard deviation of the mean (derived from a population of normal subjects) will produce few missed cases (high sensitivity) and a larger number of “false-positive” findings (low selectivity). Thomsen and colleagues68 analyzed the effects of the criteria choice on diagnostic outcome. ILD-V values in 27 patients with surgically confirmed acoustic neuromas were compared with ILD-V values in 70 patients with Ménière’s disease. A criterion of ILD-V more than 1.0 ms for ABR positivity produced no false-positives and a 15% false-negative rate (i.e., confirmed tumor cases classified as nontumor). When ILD-V criteria were restricted to 0.5 ms, there was an increase in the false-positive rate to 11% and a reduction of the false-negative rate to 4% (only one tumor case classified as nontumor). Further restriction of the ILD-V criterion to 0.3 ms left the false-negative rate at 4% but raised the false-positive rate to 23%, clearly an effect that can make the ABR test results misleading.

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Mangham69 investigated the performance of ABR with and without sinusoidal harmonic acceleration testing. The study included 74 patients with acoustic tumors and 78 controls. ABR testing outperformed harmonic acceleration alone or in combination with the ABR and proved to be more cost-effective than a protocol that included both ABR and sinusoidal harmonic acceleration. When the Selters and Brackmann61 criterion for ABR positivity (ILD = V > 0.2 msec) were applied, the sensitivity of the ABR testing alone was 94% and its specificity was 79%. In a hypothetical case with a posterior probability for an acoustic tumor of 0.01, an ILD-V of 0.2 msec increases the probability of an acoustic neuroma to 0.047. The probability of a tumor increases monotonically until the ILD-V reaches a value of 0.7 ms, the point at which there is little increase in the posterior probability for a tumor. Based on data collected in normal subjects and confirmed cases of acoustic neuroma in the Audiology Clinic at the University of Michigan Medical Center, criteria for a positive test result are as follows: I–III > 2.3 msec; III–V > 2.1 msec; I–V > 4.4 msec; ILD-V > 0.4 msec; ILD-V (1-kHz tone burst) > 0.60 msec. For several years, the authors have evaluated the neurodiagnostic applications of tonal or frequency-specific ABR. Previously, we investigated the feasibility of using 1-kHz tonal ABR in normal-hearing subjects and in patients with high-frequency hearing loss beyond 1 kHz. A comparison of wave V latencies between these two groups indicated an absence of statistically significant differences for 1-kHz stimuli, indicating the utility of this stimulus for neurodiagnostic applications. The mean latency for the normal group was 6.35 ms compared with 6.45 for those with high-frequency hearing loss. That is, the latency of 1 kHz was not affected by the presence of high-frequency hearing loss. The mean latency for clicks was 5.6 ms for normals and 5.9 ms for high-frequency losses, which was statistically significant. We then compared wave V latencies to 1-kHz tonal stimuli between two audiometrically matched groups, one with cochlear hearing loss and the other with confirmed acoustic neuromas. As expected, patients with acoustic neuromas had significantly prolonged wave V latencies when compared with their audiometrically matched cochlear hearing loss counterparts. Patients with cochlear losses had a mean latency of 6.7 ms, while the acoustic neuroma patients had a mean latency of 7.6 ms, representing a statistically significant difference.65 Gorga and colleagues70 also reported reliability in ABRs to tone bursts covering a wide range of frequencies and levels in normal subjects. They found the flexibility offered by tonal stimuli to be helpful in evaluating subjects with various configurations of hearing loss. Fowler and Mikami71 in a retrospective analysis of patients with asymmetrical cochlear losses reported a high correlation between ears for wave V latency evoked with 1-kHz tone bursts. She further suggested that 1-kHz tone bursts can supplement interpretation of clickevoked ABR in patients with significant high-frequency hearing loss.

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Case Studies

10 dB (ANSI S 3.6, 1996)

1: A 54-year-old male presented to our clinic with primary complaints of tinnitus and unilateral progressive hearing loss. The audiogram showed normal hearing in the left ear and a mild sloping to severe to profound sensorineural loss in the right ear (Fig. 18-18A). Traditional click-evoked ABR yielded a robust normal waveform for the left ear with readily identifiable waves. An expectedly poor response was obtained for the right ear (Fig. 18-18B). A 1-kHz tonal ABR was able to elicit a response with a better morphology. Had only click studies been performed, we could not have ruled out the effects of hearing loss. The data from the 1-kHz ABR furthered the diagnosis of a retrocochlear lesion since the effect of hearing loss at this frequency was negligible (Fig. 18-18C). Subsequent to our evaluation, a magnetic resonance imaging (MRI) was performed, which confirmed the presence of a 1.5-cm acoustic neuroma. The patient underwent tumor resection with pathology, which further confirmed a vestibular schwannoma. 2: A middle-aged woman self-referred to Otolaryngology and Audiology with complaints of chronic, increasing right ear tinnitus, and bilateral hearing loss greatest in the right ear. She had no complaints of otalgia, dizziness, or facial muscle weakness. Previously, her primary care physician had obtained a temporal bone MRI; the radiologist’s report was negative for neoplasm in either internal auditory canal or cerebellopontine angle. On the day of her otology clinic visit, she was worked in for audiologic assessment and ABR. These results, portrayed in Figure 18-19A–C, indicate a slightly asymmetric mild to moderate sensorineural hearing loss greatest in the right ear. Word recognition scores are 88% and 68% for the left and right ears, respectively (see Fig. 18-19A). The ABR results were dramatic: Normal interpeak and absolute latencies were calculated for the left ear, and for the right ear, the wave I–III, III–V, and I–V interpeak latencies are far outside our clinic’s normative values; the right ear waveform morphology following click stimuli was very poorly formed, while responses to 1-kHz stimuli are marginally better (see Fig. 18-19B–C). This patient eventually underwent planned hearing preservation surgery for a 2-cm vestibular schwannoma.

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The most useful component of the auditory evoked response in the diagnosis of auditory cortical involvement is the middle latency auditory evoked response (MLR). The most prominent and robust component of this response is a scalp-positive peak with a midpoint latency of 25 to 35 ms in neurologically normal adults. This component is widely distributed over the scalp but is most prominent over frontocentral regions. There is some evidence that this component is at least in part generated by the auditory cortex because it is attenuated or diminished in cases of temporal bone lesions.38,72 In patients with unilateral lesions of the auditory cortex, the Pa component of the MLR is greatly reduced in amplitude or absent over the affected hemisphere. In those rare cases with bilateral hemorrhagic temporal lobe infarcts manifesting as true

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Figure 18-18. A, Preoperative audiogram of a 54-year-old man with a right-sided 1.5-centimeter vestibular schwannoma. B, Preoperative click ABR from a 54-year-old man with a right-sided vestibular schwannoma. Interpeak latencies are normal for the unaffected left ear (top trace), while the waveform morphology for the right ear is poorly formed after wave I (bottom trace). C, Preoperative 1-kHz tone burst ABR from the same 54-year-old man with a 1.5-centimeter vestibular schwannoma. Averaged responses for the left ear are repeatable and within normal clinical values, while for the right ear the response is poorly formed.

central deafness (with indication of an intact auditory periphery), the MLR may be absent or substantially reduced in amplitude bilaterally as well as at midline electrodes.73 Improvements in the configuration of the MLR generally coincide with improvement in hearing abilities in such cases evolving from a return of appropriate hearing sensitivity to slow, gradual improvements in speech recognition

Objective Measures of Auditory Function

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Figure 18-19. A, Preoperative audiogram of a female with chief complaints of right ear tinnitus, hearing loss, and no benefit from right ear amplification. B-C, Neurodiagnostic ABRs; in the left panel, right ear grand averages of more than 10k clicks and 1-kHz tone bursts; interpeak and absolute latencies are far beyond two standard deviations of clinical normative values; left ear responses (right panel) are normal for clicks and tones.

presumably in association with the absorption of blood and reductions in the intracranial pressure. An intact auditory periphery coupled to an interrupted central nervous system (CNS) pathway or a severely damaged auditory cortex will result in a complete absence of functional hearing.

AUDITORY POTENTIALS IN COCHLEAR IMPLANT SURGERY The advent and expanded application of the cochlear implant has introduced the need for an objective assessment of auditory pathway response to electrical stimulation particularly in young patients. It is advantageous to have the ability to determine the electrical excitability of auditory neural elements before committing an ear to implantation. Along with other preoperative data, this information serves as a basis for counseling and helps avoid implantation in a nonexcitable ear. Some cochlear implant clinicians perform preoperative electrical promontory testing in adults as a guide for selecting the ear to be implanted provided other preoperative measures indicate candidacy.74

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Preoperative electrical testing typically consists of electrical stimulation applied to the promontory or round window niche with an electrode placed transtympanically or under direct vision through a tympanotomy incision or tympanomeatal flap. Response to stimulation can be assessed with behavioral techniques such as an adaptive procedure. Adult patients who have had experience with acoustic stimulation are easily assessed with behavioral techniques. The inclusion of congenitally deaf adults and infants in the prospective implantable patient population has created the need for nonbehavioral techniques of determining the presence of responses of the auditory system to electrical stimulation. Both electric ABRs and electric middle latency responses have been used as indicators of the electrical responsiveness.75 Miyamoto and Brown76 have successfully obtained electric ABRs in the operative setting following implantation with the 3M/House single-channel device. Rectangular biphasic pulses were applied to the implanted electrode through a modified external coil placed over the receiver coil following the closure of the incision. This approach to confirming the electrical excitability of the auditory system is limited by the necessity to conduct the test after the surgical procedure is completed. Electrically evoked ABRs may be obtained both with preperioperative transtympanic stimulation77 as well as postimplant by stimulating selected electrodes of the cochlear implant. The transtympanically evoked EABR is typically obtained in the operating room while the patient is under general anesthesia and with neuromuscular blockade. Muscle paralysis reduces the likelihood of an artifactual myogenic responses that may either contaminate the EABR or masquerade as an EABR. Stimuli are delivered by a needle electrode placed transtympanically on the cochlear promontory. A custom-designed battery-operated stimulator activated by a trigger pulse from an evoked potential system was used to generate the necessary stimuli. This stimulator is capable of delivering biphasic pulses with an output limit of 999μ amps. These biphasic stimulus pulses have a typical duration of 200μ seconds per phase and we record the EABR with a contralateral earlobe or mastoid reference. We recommend that EABRs be obtained on pediatric patients who fulfill the following criteria: 1. Confirmed temporal bone malformation 2. Uncertain preoperative audiometric threshold due to the patient’s young age or developmental status 3. Preoperative audiometric thresholds exceeding the limits of the audiometer Figure 18-20 illustrates EABRs obtained perioperatively from three patients aged 18 months, 14 months, and 13 months. The responses resemble an acoustically evoked ABR with several differences. First, latency of wave V ranges from 4 to 4.5 milliseconds, which is at least 1 to 1.5 milliseconds earlier than wave V latency obtained at high stimulus intensities. Second, it is difficult to resolve the early components of the response (waves I and II) because of the presence of a large stimulus artifact derived from electrical stimulation. In order to minimize contamination by the stimulus artifact, the initial 2 milliseconds of the recorded trace were digitally blanked; therefore, neither artifactual nor physiologic electrical activity is discernible within this initial time.

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18 months +

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.25 uV − Latency 1.0 ms/division Figure 18-20. Preoperative electrically evoked auditory brainstem responses from three patients. Absolute latencies of waves III and V are earlier than responses obtained using acoustic stimuli delivered through earphones.

Figure 18-21 is an illustration of the application of the transtympanic electric ABR technique to select an ear for implantation. These responses were obtained from a 21/2-year-old with symmetrical, bilateral severe to profound sensorineural hearing loss. With right ear stimulation (top set of traces), responses could be obtained only at 900 mircroamps. While these responses indicated the presence of excitable auditory neural elements, our prior experience indicates that effective implant performance coincides with transtympanic electric ABR thresholds of 600 microamps or less. With left ear stimulation, responses

could be tracked down to a threshold of 600 microamps as illustrated in this figure. No attempt was made to obtain responses at lower levels. In this case the electric ABR responses helped us select the left ear for implantation based on lower perioperative electric thresholds. Another important application of perioperative transtympanic stimulation is in cases of congenital temporal bone malformations such as common cavity deformities, and an apparent absence of IAC or a very narrow IAC. The following case illustrates this application. Figure 18-22 illustrates a computed tomography (CT) from a 31/2-year-old patient who was a cochlear implant candidate based on audiologic criteria. Imaging studies helped identify the presence of bilateral common cavity deformities with a wide IAC on the left side and an apparent absence of IAC on the right side. Transtympanic electrical stimulation helped determine that indeed the right ear was most likely devoid of a cochlear nerve based on an absent response with electrical stimulation (Fig. 18-23, bottom trace). The top trace illustrates well-defined electric ABR obtained with stimulation of the left ear, which was subsequently selected for implantation with effective cochlear implant use. The electrically evoked auditory brainstem response may also be used following implantation to facilitate programming, particularly in young children. Instead of delivering a stimulus transtympanically to the promontory and attempting to record a response, following implantation the cochlear implant and its programming equipment may be interfaced with evoked potential instrumentation and responses may be recorded with selective activation of electrodes or electrode pairs. Several studies have shown the efficacy and usefulness of this technique.78–80 In general, EABR thresholds are closer to actual, behavioral comfort levels than to thresholds but their presence can be helpful to set stimulation parameters. The practical disadvantage of the EABR applied in such a manner is that particularly with young children it would be necessary to obtain it under sedation because the EABR is very vulnerable for

EABR: 2.5-Year-Old Boy with Congenital Deafness +

v

RE 900 uA

III

v

LE III

v

700 uA 650 v 600

− Latency 1 msec/div Figure 18-21. Electric auditory brainstem responses from the right ear (RE) and the left ear (LE) of a patient who underwent a successful left ear cochlear implantation.

Figure 18-22. Computed tomography image of a 3-year-old cochlear implant candidate showing bilateral common cavity defects; the internal auditory canal is widened on the left side, while the IAC is absent on the right side.

Objective Measures of Auditory Function

+

III

303

Neural Response Telemetry

v

II

4 180 4 183 4 186 4 189 4 192

LE RE

4 195 4 195 127 uV

.50 uV 2 msec

0.0

0.5

− EABR @ 600 uA Figure 18-23. Transtympanic electrocochleography from a 3-year-old boy undergoing cochlear implant workup. Note the absence of a response from the right ear (IAC absent on CT).

contamination by movement and myogenic artifacts. The alternatives are the measurement of electric auditory potentials (EAPs) recorded via telemetry procedures, hence the term neural response telemetry, or NRT. These measurements use the two-way telemetry (currently commercially available for only Cochlear Corporation/Nucleus implants and Advanced Bionics implants). This can be accomplished by using one pair of electrodes to deliver the stimulus and a nearby pair to record the response that is returned via back-telemetry. The response recorded by electrodes designated as recording electrodes of the implants array are transmitted back transcutaneously to the speech processor interface. With certain additional manipulations, these responses are averaged much like an evoked potential, displayed on the computer screen, stored, or printed for the record. This technique does not require surface recording of electrodes as is the case for standard evoked potential recording. Because this technique does not employ surface recording electrodes, these responses are immune to movement and myogenic artifacts so it allows a patient to engage in some activity during the measurement, which makes this technique very useful with young patients during initial programming. Figure 18-24 illustrates a series of EAPs obtained via neural response telemetry with the Nucleus 24R in a 7-year-old patient with some cognitive delay. He was difficult to program, although based on these responses, the map could be established. This illustration shows responses obtained on electrode 4 with a threshold of approximately 186 clinical units. A threshold of 155 units was estimated for this electrode with a C level of 204, based on the assumption that these values fall somewhere between the actual comfort (C) level and the threshold (T) level. As shown by Brown and colleagues,79 EAP threshold at times coincides with actual comfort levels and at other times falls between threshold and comfort levels. The responses never exceed actual psychophysical C levels; therefore, it is safe to use EAP threshold in estimating mapping characteristics. Hay-McCutcheon and colleagues81 investigated differences between EAPs and EABRs in adult recipients of the Nucleus CI 24R cochlear implant.

1.0 1.5 Time (msec)

2.0

Figure 18-24. Neural response telemetry responses from a 7-year-old boy. Responses were used to estimate programming levels for this difficult-to-test youngster. A threshold of 186 clinical units was established for electrode 4.

They found no significant differences between EAP and EABR threshold levels; therefore, these two techniques may be used interchangeably in adult populations. It is still preferable, however, to use the EAP in children who may necessitate sedation to obtain an EABR.

ACKNOWLEDGMENTS We would like to acknowledge the contributions of John K. Niparko, MD, and Karin E. Young, MA, who helped write the first version of this chapter in 1994. Also, we would like to recognize and thank Mrs. Janice LaPointe, secretary to the senior author, who helped prepare the manuscript.

REFERENCES 1. Davis PA: Effects of acoustic stimuli on the waking human brain. J Neurophysiol 2:494–499, 1939. 2. Jewett DL, Romano MN, Williston JS: Human auditory evoked potentials: Possible brain stem components detected on the scalp. Science 167:1517–1518, 1970. 3. Kemp DT: Stimulated acoustic emission from within the human auditory system. J Acous Soc Am 64:1386–1391, 1978. 4. Brownell WE, Bader CR, Bertrand D, et al: Evoked mechanical responses of isolated cochlear outer hair cells. Science 227:194–196, 1985. 5. Lonsbury-Martin BL, Whitehead ML, Martin GK: Clinical applications of otoacoustic emissions. J Speech Hear Res 34:964–981, 1991. 6. Sutton GJ: Suppression effects in the spectrum of evoked otoacoustic emissions. Acustica 58:57–63, 1985. 7. Wilson JP: Subthreshold mechanical activity within the cochlea. J Physiol 298:32P–33P, 1980. 8. Brown AM, Kemp DT: Suppressibility of the 2f1-f2 stimulated acoustic emissions in gerbil and man. Hear Res 13:29–37, 1984. 9. Martin GK, et al: Acoustic distortion products. II. Sites of origin revealed by suppression and pure-tone exposures. Hear Res 28:191–208, 1987. 10. Martin GK, et al: Distortion-product emissions in humans. II. influence of sensorineural hearing loss. Ann Otol Rhino Laryngol 147(Suppl):30–42, 1990.

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11. Vedantam R, Musiek FE: Click evoked otoacoustic emissions in adult subjects: Standard indices and test-retest reliability. Am J Otol 12(6):435–442, 1991. 12. Kemp DT: Cochlear echoes: Implications for noise-induced hearing loss. In Hamernik D, Henderson D, Salvi R (eds.): New Perspectives on Noise-Induced Hearing Loss. New York, Raven, 1982, pp 189–207. 13. Kim DO: Cochlear mechanics: Implications of electrophysiological and acoustical observations. Hear Res 2:297–317, 1980. 14. Doyle KJ, Rodgers P, Fujikawa S, et al: External and middle ear effects on infant hearing screening test results. Otolaryngolol Head Neck Surg 122(4):477–481, 2000. 15. Barker SE, Lesperance MM, Kileny PR: Outcome of newborn hearing screening by ABR compared with four different DPOAE pass criteria. Am J Audiol 9(2):142–148, 2000. 16. Koivunen P, Uhari M, Laitakari K, et al: Otoacoustic emissions and tympanometry in children with otitis media. Ear Hear 21(3): 212–217, 2000. 17. Harris FP, Probst R: Otoacoustic emissions and audiometric outcomes. In Robinette MS, Glattke TJ (eds.): Otoacousti Emissions: Clinical Applications. New York, Thieme, 1997, pp 151–180. 18. Kileny PR, Edwards BM, Disher MJ, et al: Hearing improvement after resection of cerebellopontine angle meningioma: Case study of the preoperative role of transient evoked otoacoustic emissions. J Am Acad Audiol 9:251–256, 1998. 19. Dauman R, Aran J, Savage R, et al: Clinical significance of the summating potential in Ménière’s disease. Am J Otol 9:31–38, 1988. 20. Eggermont JJ: Analysis of compound action potential responses to tone bursts in the human and guinea pig cochlea. J Acoust Soc Am 60(5):1132–1139, 1976. 21. Chatrian G, et al: Cochlear summating potentials to clicks detected from the external auditory meatus. Ear Hear 6:130–138, 1985. 22. Gibson WPR, Prasher DK, Kilkenny GPG: Diagnostic significance of transtympanic electrocochleography in Ménière’s disease. Ann Otol Rhino Laryngol 92:155–159, 1983. 23. Coats A, Jenkins H, Monroe B: Auditory evoked potentials; the cochlear summating potential in detection of endolymphatic hydrops. Am J Otol 5:443–446, 1984. 24. Marangos N, Mausolf A, Ziesmann B: Electrocochleography possibilities in the differential diagnosis of hydrops and neural hearing loss. HNO 38(2):56–58, 1990. 25. Sass K, Densert B, Magnusson M, et al: Electrocochleographic signal analysis: Condensation and rarefaction click stimulation contributes to diagnosis in Ménière’s disorder. Audiology 37(4): 198–206, 1998. 26. Gares GA, Green DJ, Tucci DL, Telian SA: The effects of transtympanic micropressure treatment in people with unilateral Ménière’s disease. Arch Otolaryngol Head Neck Surg 130:718–725, 2004. 27. Jewett DL, Williston JS: Auditory evoked far-fields averaged from the scalp of humans. Brain 95:681–696, 1971. 28. Moller AR, Janetta PJ: Neural generators of the auditory brainstem response. In Jacobson JT (ed.): The Auditory Brainstem Response. Boston, College Hill, 1985, pp 13–31. 29. Schwartz DM, Morris MD, Jacobson JT: The normal auditory brainstem response and its variants. In JT Jacobson (ed.): Principles and Applications in Auditory Evoked Potentials. Needham Heights, MA, Allyn Bacon, 1994. 30. Hall JW, et al: Neuro-otologic applications of simultaneous multichannel auditory evoked response recordings. Laryngoscope 94: 883–889, 1984. 31. Pratt TL, Olsen WO, Bauch CD: Four-channel ABR recordings: Consistency in interpretation. Am J Audiol 4(2):47–54, 1995. 32. Northern JL, Downs MP: Behavioral hearing testing. In Hearing in Children, 5th ed. Philadelphia, Lippincott Williams & Wilkins, 2002. 33. Joint Committee on Infant Hearing: Year 2000 position statement: Principles & guidelines for early hearing detection & intervention programs. Am J Audiol 9:9–29, 2000.

34. Bess FH, Humes LE: Screening auditory function. In Audiology: The Fundamentals, 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 2003. 35. Arehart KH, Yoshinaga-Itano C, Thompson V, et al: State of the states: The state of universal hearing identification and intervention systems in 16 states. Am J Audiol 7:101–114, 1998. 36. Bauch CD, Olsen WO: The effect of 2000–2000 Hz hearing sensitivity on ABR results. Ear Hear 7:314–317, 1986. 37. Hyde ML, Riko K, Malizia K: Audiometric accuracy of the click ABR in infants at risk for hearing loss. J Am Acad Audiol 1:59–66, 1990. 38. Kileny PR, Magathan MG: Predictive value of ABR in infants and children with moderate to profound hearing impairment. Ear Hear 4:217–221, 1987. 39. Gorga MP, Worthington DW, Reiland JK, et al: Some comparisons between auditory brain stem response thresholds, latencies, and the pure tone audiogram. Ear Hear 6:105–112, 1985. 40. Kileny PR: The frequency specificity of tone-pip evoked auditory brainstem responses. Ear Hear 2:270–275, 1982. 41. Gorga MP, Abbas PJ,Worthington DW: Stimulus calibration in ABR measurement. In Jacobson JT (ed.): The Auditory Brainstem Response. San Diego, College Hill, 1985, pp 49–64. 42. Weber BA: Auditory brainstem response: Threshold estimation and auditory screening. In Katz J (ed.): Handbook of Clinical Audiology, 4th ed. Baltimore, Williams & Wilkins, 1994. 43. Hyde ML: Frequency-specific BERA in infants. J Otolaryngol 14(Suppl 14):19–27, 1985. 44. Purdy SC, Abbas PJ: ABR thresholds to tone bursts gated with Blackman and linear windows in adults with high-frequency sensorineural hearing loss. Ear Hear 23(4):358–368, 2002. 45. Stapells DR: Threshold estimation by the tone-evoked ABR: A literature meta-analysis. J Speech Lang Path Audiol 24(2):74–83, 2000. 46. Edwards BM, Kileny PR, Van Riper LA: CHARGE syndrome: A window of opportunity for audiologic intervention. Pediatrics 110:119–126, 2002. 47. Hecox KE: Role of auditory brainstem responses in the selection of hearing aids. Ear Hear 4:51–55, 1983. 48. Kileny P: Auditory brainstem responses as indicators of hearing aid performance. Ann Otology 91:61–64, 1982. 49. Beauchaine KA, Gorga MP, Reiland JK, et al: Application of ABRs to the hearing-aid selection process: Preliminary data. J Speech Hear Res 29:120–128, 1986. 50. Brown E, Klein AJ, Snydee KA: Hearing aid processed tone pips. Electroacoustic and ABR characteristics. J Am Acad Audiol 10:190–197, 1999. 51. Gorga MP, Beauchaine KA, Reiland JK: Comparison of onset and steady-state responses of hearing aids: Implications for use of the auditory brainstem response in the selection of hearing aids. J Speech Hear Res 30:130–136, 1987. 52. Purdy SC, Kelly AS: Cortical auditory evoked potential testing in infants and young children. New Zealand Audiol Soc Bull 11:16–24, 2001. 53. Ponton CW, Don M, Eggermont JJ, et al: Maturation of human cortical auditory function: Differences between normal-hearing children and children with cochlear implants. Ear Hear 17:430–437, 1996. 54. Rapin I, Graziani LJ: Auditory evoked responses in normal, braindamaged, and deaf infants. Neurology 17:881–894, 1967. 55. Gravel J, Kurtberg D, Stapells DR, et al: Case studies. Sem Hear 4:51–55, 1989. 56. Hyde M: The N1 response and its applications. Audiol Neurootol 2:281–307, 1997. 57. Picton TW, Dimitrijevic A, van Roon P, et al: Possible roles for the auditory steady-state responses in fitting hearing aids. In Seewald RC, Gravel JS (eds.): A Sound Foundation Through Early Amplification 2001: Proceedings of the Second International Conference, Great Britain, St. Edmundsbury Press, 2002, pp 63–74. Available at: www.immediateproceedings.com.

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58. Picton TW, Durieux-Smith A, Champagne SC, et al: Objective evaluation of aided threshold using auditory steady state responses. J Am Acad Audiol 9:315–331, 1998. 59. Keith WJ, Greville K: Effects of audiometric configuration on the auditory brainstem response. Ear Hear 8:49–55, 1987. 60. Moller AR, Janetta PJ, Bennett M, et al: Intracranially recorded responses from the human auditory nerve: New insights into the origin of brainstem evoked potentials. Electroencephalog Clin Neurophysiol 52:18–27, 1981. 61. Selters WA, Brackmann DE: Brainstem electric response audiometry in acoustic tumor detection. In House W, Luetje C (eds.): Acoustic Tumors, vol I: Diagnosis. Baltimore, University Park Press, 1979. 62. Rosenhammer JH, Lindstrom V, Lundborg P: On the use of click-evoked electric brainstem responses in audiological diagnosis. III. Latencies in cochlear hearing loss. Scand Audiol 10:3–11, 1981. 63. Beck HJ, Beatty CW, Harner SG, et al: Acoustic neuromas with normal pure tone hearing levels. Otolaryngol Head Neck Surg 94:96–103, 1986. 64. Musiek FE, et al: ABR results in patients with posterior fossa tumors and normal pure tone hearing. Otolaryngol Head Neck Surg 94:568–573, 1986. 65. Telian SA, Kileny PR: Usefulness of 1000 Hz tone-burst evoked responses in the diagnosis of acoustic neuroma. Otolaryngol Head Neck Surg 101:466–471, 1989. 66. El-Kashlan HK, Eisenmann D, Kileny PR: Auditory brain stem response in small acoustic neuromas. Ear Hear 21(3):257–262, 2000. 67. Don M, Masuda A, Nelson R, et al: Successful detection of small acoustic tumors using the stacked derived-band auditory brain stem response amplitude. Am J Otol 18(5):608–621, 1997. 68. Thomsen J, Terkildsen K, Osterhammel P: Auditory brainstem responses in patients with acoustic neuromas. Scand Audiol 7:179, 1978. 69. Mangham CA: Decision analysis of auditory brainstem responses and rotational vestibular tests in acoustic tumor diagnosis. Otolaryngol Head Neck Surg 96:22–29, 1987. 70. Gorga MP, Kaminski JR, Beauchaine KA, et al: Auditory brainstem responses to tone bursts in normally hearing subjects. J Speech Hear Res 31:87–97, 1988.

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71. Fowler CG, Mikami CM: Effects of cochlear hearing loss on the ABR latencies to clicks and 1000 Hz tone pips. J Am Acad Audiol 3(5):324–330, 1992. 72. Kraus N, et al: Auditory middle latency responses (MLRs) in patients with cortical lesions. Electroencephalog Clin Neurophysiol 45:275–287, 1982. 73. Ho KJ, Kileny PR, Paccioretti D, et al: Neurologic, audiologic and electrophysiologic sequela of bilateral temporal lobe lesions. Arch Neurol 44:982–987, 1987. 74. Kileny PR, Kemink JL: Electrically evoked middle-latency auditory potentials in cochlear implant candidates. Arch Otolaryngol Head Neck Surg 13:1072–1077, 1987. 75. Firszt JB, Kileny PR: Electrically Evoked Middle Latency and Cortical Auditory-Evoked Potentials. In Cullington HE (ed.): Cochlear Implants: Objective Measures. London, Whurr Publishers, 2003. 76. Miyamoto RT, Brown DO: Electrically evoked brainstem responses in cochlear implant recipients. Otolaryngol Head Neck Surg 96:34–38, 1987. 77. Kileny PR, Zwolan TA, Zimmerman-Phillips S, et al: Electrically evoked auditory brain-stem response in pediatric patients with cochlear implants. Arch Otolaryngol Head Neck Surg 120(10):1083–1090, 1994. 78. Abbas PJ, Brown CJ, Shallop JK, et al: Summary of results using the nucleus CI24M implant to record the electrically evoked compound action potential. Ear Hear 20(1):45–59, 1999. 79. Brown CJ, Abbas PJ, Gantz BJ: Preliminary experience with neural response telemetry in the nucleus CI24M cochlear implant. Am J Otol 19(3):320–327, 1998. 80. Firszt JB, Rotz LA, Chambers RD, et al: Electrically evoked potentials recorded in adult and pediatric CLARION implant users. Ann Otol Rhino Laryngol (Suppl) 177:58–63, 1999. 81. Hay-McCutcheon MJ, Brown CJ, Clay KS, et al: Comparison of electrically evoked whole-nerve action potential and electrically evoked auditory brainstem response thresholds in nucleus CI24R cochlear implant recipients. J Am Acad Audiol 13(8):416–27, 2002.

Chapter

19 Manuel Don, PhD Curtis W. Ponton, PhD

Functional Imaging of Auditory Cortical Activity Outline Introduction Functional Imaging of Neuroelectrical and Neuromagnetic Scalp Activity Background and Principles Electric Fields Magnetic Fields The Need for Multichannel Recordings Electrical Multichannel Recordings Magnetic Multichannel Recordings Brain Maps Technical Aspects Kinds of Information that Maps Provide Advantages and Disadvantages of Topographic Maps Clinical Applications of Maps Dipole Source Modeling Early Dipole Source Localization Methods: Single- and Moving Dipole Models

INTRODUCTION In the version of this chapter included in the previous edition of this book, we identified emerging clinical issues and fundamental questions in the study and evaluation of the auditory system concerned with (1) identifying the anatomic sites where various aspects of auditory processing occur in the brain, (2) the temporal nature of the processing, (3) whether such processing can be measured objectively, and (4) how such measurements change with various kinds of pathology. Answers to these issues and questions are critical prerequisites in understanding the origin and extent of hearing disorders, which in turn may be helpful in assessing and guiding rehabilitation processes. 306

Spatiotemporal Source Modeling: Technical Aspects Advantages and Disadvantages of Spatiotemporal Source Modeling Clinical Applications of Dipole Source Analyses Positron Emission Tomography Background and General Principles Advantages and Disadvantages of Positron Emission Tomography Clinical Applications Cochlear Implant Stimulation Tinnitus Studies with Positron Emission Tomography

Functional Imaging with Magnetic Resonance Imaging Background and General Principles Blood Oxygenation Level– Dependent Contrast Imaging Blood Perfusion Imaging Using Vascular Contrast Agents Blood Perfusion Imaging Using Inversion Recovery Methods Auditory Studies Using Functional Magnetic Resonance Imaging Advantages and Disadvantages of Functional Magnetic Resonance Imaging Clinical Applications and Combining Imaging Techniques Summary

Previously, we focused on functional imaging with evoked electrical and magnetic potentials recorded at the surface of the head by means of topographic mapping (“brain-mapping”) and spatiotemporal source modeling (STSM) techniques. Although our major emphases in the previous edition were electromagnetic approaches, we also touched on functional imaging with positron emission tomography (PET) and the then newly emerging attempts to image functionally with magnetic resonance imaging (fMRI). Since the publication of this chapter over 10 years ago, significant advances have taken place in all of these technologies. Much more research has focused on the potential clinical applications of these techniques. In particular, the research and application of fMRI has experienced tremendous growth. Numerous published studies

Functional Imaging of Auditory Cortical Activity

have attempted to identify and characterize neural activity in cortical areas of the brain while processing simple and complex (e.g., speech) auditory stimuli. In this chapter, we now expand our review of the fMRI work in addition to updating the information on other brain imaging techniques. Again, for each of the various methods we present a brief description of the technical aspects, the kinds of information obtained, their advantages and disadvantages, and the current and future clinical applications in evaluating the auditory system. The technical complexities and vast literature on the development and application of these methods preclude a comprehensive review of either the technical aspects or application results. Our intention in this revised chapter, despite its brevity, is that this review will provide an effective overview of the basic principles of these techniques, their current and potential value, and the limitations of the clinical evaluation of auditory function. We emphasize at the outset that the techniques described in this chapter are physiologically based and are concerned with characterizing the distribution, location, and temporal variations in amplitude of electric, magnetic, and metabolic activity from auditory-evoked sources of neural activity in the cortex. Ten years ago, clinical application of these techniques for assessing auditory function was limited, but we suggested that with continued development and evolution, these techniques would prove to be very valuable in the assessment of cortically mediated auditory function. During these last 10 years or so, ample evidence has emerged to support this suggestion.

FUNCTIONAL IMAGING OF NEUROELECTRICAL AND NEUROMAGNETIC SCALP ACTIVITY Before embarking on a discussion of functional imaging of electrical and magnetic activity, we review briefly some of the principles and technical aspects of these kinds of activity. Such a simple review should help the reader understand these imaging techniques. Also, our focus will be on the middle and late auditory evoked potential activity because they originate in subcortical areas including the thalamus and neocortical areas including primary and secondary (including association) auditory cortices.

and magnetic fields associated with neural activation following auditory-sensory stimulation. However, it is important to acknowledge that some neural activity produces local current paths that are contained close to the generator and may not generate the far-field electric and magnetic fields that extend to and are recordable from the scalp. It is generally accepted that the far-field scalp-recorded brain activity primarily represents excitatory postsynaptic potentials (EPSPs) produced by pyramidal cells that are uniformly organized perpendicular to the cortical surface. It is likely that this far-field activity represents the synchronous EPSPs of tens of thousands to millions of cortical pyramidal cells. This far-field activity produces intrinsically related electric and magnetic fields at the scalp. A simplistic view of this relationship is to consider activation of a small segment of neural tissue, as schematically shown in Figure 19-1. This activation can be represented in a short length of current flow. The direction of this small current flow is shown by the arrow and, in this example, is oriented tangential to the surface of the head. This is often described as an equivalent current dipole. Current flows out of the head of the arrow (+ pole) and flows into the tail of the arrow (−pole), producing both an electric and magnetic field. The electric field (Fig. 19-1A) is perpendicular to the magnetic field (Fig. 19-1B). Temporal variations in the current flow result in temporal variations in both the electric and magnetic fields. The advantage of brain-generated electrical potentials and magnetic fields is the sensitivity to spontaneous and induced changes in the functional brain state coupled with extremely high (submillisecond) temporal resolution.4 Although there are differences in recording these fields, both electrical and magnetic responses should, in general, provide similar information because they are intrinsically related phenomena resulting from current flow due to ionic movement in the underlying tissue. Electric Fields In the past, most auditory evoked response studies measured the voltage (electrical potential) between two electrodes on the scalp. One electrode was usually placed

Background and Principles We recall from basic neurophysiology that neural stimulation results in changes in permeability of neural membrane tissues to various ions. These changes in permeability create net imbalances in the local concentrations of negative and positive charges as ions move in response to concentration and electrical gradients. For thorough reviews of the complexities of the relationship between intracellular and extracellular currents generated by ionic movement and the corresponding electric and magnetic fields, the reader is referred to Nunez,1 Scherg,2 and Williamson and Kaufman3 for rigorous but readable explanations of these important principles. The point of departure for us is that from the scalp surface, we can record electrical potentials

307

A

B

Figure 19-1. Current dipoles and resulting electric (A) and magnetic (B) fields.

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at the vertex and the other (reference) at some other location such as the mastoid or earlobe. Because the magnitude of stimulus evoked, time-locked neural activity is very small (orders of magnitude smaller) relative to the background electrical activity, response averaging techniques are required to average the nonstimulus-locked component of the electroencephalograph (EEG). The resultant averaged responses, or voltage waveforms, are assumed to represent electrical activity from neural structures at the brainstem, thalamic, or cortical levels depending on the recording parameters of sampling rate, filtering, and amplification. The data of interest have been the latency and amplitude of component peaks in these averaged waveforms. The most important limitation associated with averaged evoked scalp-recorded electrical potentials is that the waveform from any given location on the scalp represents compounded electrical activity evoked by the stimulus. Given the possibility that more than one area of the brain contributes to the activity, it is not possible to separate the contributions from differential recordings between a single pair of electrodes. That is, the evoked response waveform from a differentially recorded pair of electrodes is basically the linear summation of all volumeconducted electrical activity originating from different structures and areas of the brain. Furthermore, the waveform recorded depends not only on the pattern of activity of the sources, but also on the location, distance, and orientation of these sources relative to the recording electrodes. It is possible that peak activity observed at the surface for a given electrode pair occurs at a time when none of the contributing sources shows peak activity. The frequently used method of simply measuring the latencies and amplitudes of peaks and valleys as direct evidence of the time and magnitude of specific neural events is often inappropriate. Such simple recordings cannot provide unambiguous information about the local origin of brain activity, nor the true temporal nature of the underlying activity pattern(s). Nevertheless, we can still record and use these measures for diagnostic purposes as long as we do not assume they represent the true activity patterns of the underlying sources. Magnetic Fields The recording of the magnetic fields associated with cortical currents requires special technical considerations as well as a magnetically shielded environment to avoid artifact contamination from extraneous sources. Several studies5–11 have described recording methodologies for these minute magnetic fields using magnetic sensors and SQUID (superconducting quantum interference device) magnetometers. Just as variations in voltage can be plotted over time, so can the corresponding variations in magnetic flux. Thus, magnetic recordings show “peaks” and “troughs” of magnetic flux amplitude over time. Some of the issues noted earlier for electrical evoked potentials also apply for evoked magnetic fields except for the issue of a reference; magnetic recordings are reference-free. Unlike electric fields, magnetic fields recorded at the surface are nearly undistorted by the skull and other tissue. Compared with the EEG, which is volumeconducted through fluids, tissue, and bone to the scalp,

smearing and spreading of the magnetoencephalograph (MEG) is extremely limited. Furthermore, the sensitivity of MEG drops off approximately twice as fast as a function of the angle (θ) of the sensor to the source as the sensitivity of EEG. Consequently, sources of pure tangential orientation are much more accurately localized by MEG than EEG.12 However, sources of current in the brain that are radially (perpendicularly) oriented to the surface are not detectable magnetically. Moreover, because of the more rapid drop in sensitivity, magnetic fields from deep brain structures are typically too weak to be detected at the scalp surface. Thus, studies that make use of magnetic recordings are predominately focused only on surface cortical activity. However, MEG resolution continues to improve with the advent of technology that decreases the distance between the detector and the head and by improvements in signal-to-noise ratios.12 Other than extremely deep or radially oriented sources, a magnetic counterpart to any EEG activity can always be measured. Both MEG and EEG have advantages and disadvantages. Some debate still persists about which is best for a given application. Since MEG more accurately locates sources oriented tangentially and EEG is more accurate for radial sources, the techniques can be complimentary.12 Williamson and colleagues13 and Hari11 provide clear succinct reviews of the different advantages of electrical and magnetic recordings and stress that a combination of both kinds of recordings will provide the best and most complete information about underlying neural activity. Aside from the theoretical issues, practical considerations may be just as important in determining which technique is more suitable for a specific clinical application. For example, MEG recordings require that a patient’s head remains essentially stationary (in the same position beneath a set of sensors imbedded in a helmet) for the duration of a recording. Because EEG electrodes are fixed to scalp with a water-soluble conductive gel or paste, some movement is possible. Consequently, for young children, or for individuals with uncontrollable tremor (e.g., those with Parkinson’s disease), EEG-based recording may be more practical. Conversely, the setup and acquisition time to obtain good-quality (high signal-to-noise ratio) recordings can be much shorter for MEG data. Additionally, the equipment and maintenance costs for multichannel magnetic field recordings (i.e., SQUID devices) are far greater (orders of magnitude) than that for electrical recordings (i.e., EEG systems). Thus, controversy remains about whether MEG provides sufficient additional information and advantages to justify the cost.

The Need for Multichannel Recordings Single-channel recordings provide limited information about how the compounded or net electrical or magnetic activity at a single location on the scalp varies over time. This is usually appropriate and sufficient when the need for information regarding the location(s), activity, or the distribution of the sources is unnecessary for the analyses and if the requisite information can be observed in that single-channel recording. However, as Lehmann4 points out, the electrical potential at any point on the scalp is an

Functional Imaging of Auditory Cortical Activity

ambiguous value since it is only defined in relation to the electrical potential at another point. In the following sections we discuss the principles and techniques of multichannel recordings and advantages for functional imaging. Electrical Multichannel Recordings In order to assess the loci of sources that contribute to the surface evoked electrical activity, recordings from multiple locations on the scalp are required. Figure 19-2 (top) shows typical location of 32 electrodes according to the standard 10–20 system14 and the associated potential waveforms recorded from those locations. Today, sophisticated systems permitting the recording, display, and analyses of 256 channels (electrodes) of electrical potential data

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are not uncommon. In general, the more channels and, therefore, the closer the spacing between electrodes, the better the resolution in characterizing the distribution and in computing the estimated loci of underlying sources at the brain surface. The upper limit of the number of electrodes to use remains a practical and theoretical issue. Typically, evoked responses from sources deep in the brain (e.g., the brainstem) are recorded with very few channels because that activity tends to be widely distributed at the surface of the head. Although it has been shown that auditory brainstem responses (ABRs) can also be analyzed with spatial information,15,16 multichannel recordings to describe the spatial distribution of the electrical activity are applied mainly to potentials generated by the cortical areas of the brain. When recording

Figure 19-2. (Top) The scalp distribution for cortical activity evoked by monaural stimulation to the left ear. The major peaks of the auditory evoked potentials are marked in the inset. (Bottom) On the left, a voltage distribution for N100 of the auditory evoked potentials is shown for the activity shown at top of this figure. In center, the scalp voltage distribution is shown for the P150 potential. The voltage distribution for a left median nerve somatosensory N54 is shown on the right. (See Color Plate 1)

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from many locations on the scalp, as in typical EEG and for describing the scalp surface potential distribution, the recording at each location must be made, by definition of a voltage potential, with reference to some other locus on the scalp or body. The issue of the reference electrode is an important one that can affect interpretation.17 A typical reference is the mastoid of one ear. Many studies have been conducted with the two electrodes on the mastoids or earlobes linked together for a reference in an effort to minimize certain electrical artifacts of nonneural origin. However, linking electrodes creates an inherent problem in that it modifies the electrical potential distribution over the whole scalp by imposing the same potential on both ears. In essence, linking electrodes, although not affecting the generators, may distort the recorded electric fields by providing an electric “short” between these two locations.17 Furthermore, the undistorted field cannot be recovered. Whether such distortions are significant for typical recording conditions is controversial, but it is best to avoid this problem by not recording the activity using linked mastoid or earlobe electrodes. A recommended approach now adopted by many laboratories is to compute reference-free data by using an average reference, which is simply the average of potentials recorded at each electrode at all times subtracted from each individual electrode.17,18 Typically, we are interested in examining changes in the evoked responses across the scalp, which are easier to detect when activity common to all scalp locations (in essence, a constant, which may be very large relative to the remaining activity) is removed from the data. Magnetic Multichannel Recordings Similar to electrical recordings, the assessment of the loci of sources that contribute to the surface-recorded evoked magnetic activity also requires recordings from multiple locations on the scalp. Although in the early 1980s only single-channel magnetometers were available, SQUIDs containing more than 120 channels are now the standard. The main reason for the increase in channels is the same as for electrical studies: to improve the resolution for isolating the loci of the source of activity.

Brain Maps In brain mapping, the emphasis is no longer on analysis of waveforms recorded at selected scalp sites but rather on analysis of the spatial potential distribution over the scalp at selected times. Thus, spatial analysis by means of multichannel recordings is necessary because it transforms the potential differences between electrodes into reference-independent values, which can provide descriptions of activity across the scalp. In early work, Vaughan and Ritter19 and a number of laboratories analyzed data from multichannel electrical recordings. They demonstrated the use of methods and mathematical algorithms for converting activity from multiple electrode sites into a topographic map, the so-called brain map, that approximates an almost continuous plot of evoked potential amplitudes or current source densities (CSDs) across the scalp.20–22 These topographic maps,

enhanced by color or gray-scale representation of the distribution of surface activity, became a popular tool for studying electrical brain activity during the 1980s. (For general reviews, see Lehmann et al.,18 Picton et al.,23 and other studies.24–26) Now these color or gray-scale representations of the distribution of surface activity are giving way to the use of equipotential maps1 to avoid bias by the selection of the color scale and also to emphasize the shape of the voltage or CSD distribution rather than the peak areas. Technical Aspects The principles for constructing a map are similar for electrical or magnetic activity. The example we discuss is for electrical activity, that is, voltage maps. At any given instant, that is, latency, the voltage at each of the recording sites can be presented visually by colors or pseudo gray scales.20,27 For example, we can specify that the voltage range of ±100 μV can be presented by the two major colors, red and blue. The darkest shade of red represents the maximum positive value of +100 μV. The less positive the voltage value, the lighter the shade of red. Zero and nearly zero values will be white. When the voltage becomes negative, the value is represented by shades of blue. The more negative the value, the darker the blue. Similarly, when color use is inappropriate, a computed pseudo gray-scale map of the activity can be used, with the dithered gray pattern representing negative and black representing positive potentials. Since the recorded activity is only at the specified electrode locations, a map of the whole surface of the head requires much interpolation. There are various schemes of interpolation. Thus, if the value at one location was 40 μV and 60 μV at an adjacent electrode, then the area between these electrodes would show, depending on the kind of interpolation, a gradient of increasing darkness of the red or gray colors, that represents the increasing positivity from +40 to +60 μV. Obviously, the more electrodes and closer spacing, the more accurate the interpolation. In the earlier edition of this chapter, we provided a detailed example of the use of the gray-scale method that will not be repeated here. Instead, we now briefly review equipotential voltage or CSD maps because they provide better information about the distribution of electrical or magnetic activity. Figure 19-2 (bottom, left) shows the grand mean waveforms evoked by a brief click-train recorded from various locations on the scalp and an equipotential map of the activity. In this figure, the equipotential maps are shown for latencies of 100 msec at the maximum of the N1 component. For the 100-msec N1 component map, there is a clearly asymmetrical representation of the activity with a strong negative/positive reversal over the right scalp, contralateral to the stimulus left ear. These results are consistent with those reported by Borg and colleagues,28 who found that on isovoltage maps, the focus of the N1 auditory potential is slightly contralateral to the stimulated ear for most subjects. In Figure 19-2 (bottom, center), the distribution at a later time (158 msec) is shown corresponding to the maximum

Functional Imaging of Auditory Cortical Activity

of the P2 wave. The distribution map for the P2 component at 158 msec is much more symmetrical with a large peak at the midline. In a similar fashion, for each sampled instant of time, an equipotential brain map can be generated. Thus, if the waveforms were composed of 500 data points sampled at 1-msec intervals, 500 equipotential brain maps could be generated. Each 1-msec map can be displayed consecutively to illustrate how the distributions on the scalp change over time. Also, less time-specific maps can be created by calculating a representative potential over an epoch of time (i.e., several sampled points) instead of the value at one instant. Grandori and coworkers9 and Kraus and McGee29 have performed extensive map analyses on auditory middle-latency potentials in normal-hearing individuals. As mentioned earlier, another form of the electric field, CSD, can be also be mapped.30 (CSD is the second derivative of the spatial voltage field.) Maps can also be generated to show the distribution of the magnetic flux over the surface of the head. More recently, infrared radiation has been used to identify cortically activated areas.31 Mapping in essence is simply a graphical representation of the distribution of some form of activity, usually at a given instant, at the surface of the head. Sophisticated maps can be generated with realistic head models obtained from MRI data and dense arrays of electrodes as demonstrated by Gevins and colleagues.32 Kinds of Information that Maps Provide Significant changes in the maps or in the nature and location of estimated sources may provide significant information regarding auditory processing. The kinds of information sought in the analyses of these brain maps are: (1) Do specific maps or changes in the maps relate to auditory processing? (2) How do maps differ between the normal-hearing population and a hearing-impaired population? (3) What are the location(s) of the neural tissues within the brain responsible for generating a particular scalp map2? One can produce average maps for both a single subject and across subjects. Changes in the maps are evaluated visually and statistically. A real, statistically measurable change33,34 in the map or distribution from one stimulus condition to the next is evidence that the sources underlying the activity have changed. Thus, differences in the maps signal different underlying sources and may be used in well-controlled studies to delineate pathology. There are several types of measures of topographic maps. For example, Duffy35 has applied significance probability mapping (SPM) and grid sector analysis (GSA) to assess whether the maps are similar to maps of a reference group. Global field power is a measure of the hilliness of the scalp potential distribution or the spatial variance.18 Weaknesses of statistical maps are the assumptions of normality and independence of the data. For example, Grandori and colleagues9 found that map differences that could be visually detected between right and left ear stimulation could not be verified using z statistics. Likewise, Kraus and McGee29 had difficulties in using the z score to determine abnormalities.

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Advantages and Disadvantages of Topographic Maps The basic advantages of maps are (1) they are easy to generate; (2) they provide a quick view of the surface distribution of voltages, magnetic flux, or CSD; and (3) they can show how these surface distributions change over a short period after stimulus onset. Maps also have several disadvantages. First, and most notable is that the maps are only two-dimensional; they simply characterize the amplitude distributions of the summed source activities projected to the surface of the scalp at a given instant. Although the analyses of such topographic maps can provide useful information, they cannot be used for assessing the cortical location or fine temporal activity of the neuroelectrical generators in the brain that produce the topography. Simply visualizing the color or gray-scale, the equipotential or CSD maps of the voltage distribution do not allow us to evaluate the various possible sources. Furthermore, these surface maps provide little information regarding the cortical depth of the sources. For example, with a montage of 20 electrodes evenly distributed over the scalp, it can be shown that for a given instant, auditory and somatosensory stimulation generate the same spatial maxima (similar location) in surface maps over the hemisphere contralateral to the side of stimulation. Thus, it would be difficult to differentiate the cortical origins of such activity patterns because of the similarity between the two-dimensional maps. Furthermore, it has been shown that a surface generator localized in one hemispheric fissure can produce a surface field with an apparent locus in the other hemisphere.36 Thus, the use of surface distributions as a tool for assessing laterality of function may be misleading and could result in serious misinterpretation and diagnosis. Thus, one should be cautious with the use of two-dimensional brain maps to identify sources of electrical activity. A second disadvantage of maps is the need for extensive interpolation. The appearance of the maps is highly affected by the method of interpolation.26 Nonlinear interpolation or spatial filtering can result in map topographies with peaks and troughs at locations where electrodes were not located.4 Finally, different baselines or references produce maps with different appearances. Some of the problems of map interpretation are presented by Scherg and von Cramon.37 A useful method of interpolation for equipotential and CSD maps is the spherical spline method described by Pascual-Marqui.38 Clinical Applications of Maps Despite the disadvantages noted, maps initially seemed to have some promise as a clinical tool in certain medical disciplines. Consequently, they have been applied to studies of epilepsy, cortical infarcts, tumors, emotional disturbance and dementia, headache, learning disabilities, and other neurologic diseases.24,35 Kraus and McGee29 suggested that there could be some clinical utility in brain maps of cortical auditory potentials, particularly in patients with cortical lesions in the temporal lobes. However, clinical application of topographic maps for auditory evaluation has yet to be clearly demonstrated. Although some

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approaches can statistically distinguish one map from another, Wong26 suggests pessimistically that it is unlikely that useful statistical techniques that can quantify a map as normal or abnormal will be widely available in the near future. Furthermore, given the limitations of twodimensional information, such maps have given way to three-dimensional imaging techniques. The following sections review the various techniques for providing activity information in three dimensions.

Dipole Source Modeling A major drawback of electric or magnetic field maps is their inability to provide definitive information about the sources in the brain that produce the maps or distributions. This is the classic “inverse problem” in electric field theory, which is to calculate the electrical sources within a volume conductor (i.e., the brain) given the empirical potential field on the surface. This inverse problem has no unique solution because a given potential field (map) can be produced by any number of source configurations.1,17,39 Although one cannot solve the inverse problem, a number of studies have attempted to get around it by taking the “forward problem” approach. The forward problem in electric field theory as applied to human evoked potentials involves the calculation of the potential field distribution on the surface of the head when the sources and their locations in three dimensions, the geometry of the head, and the conductivities of the various compartments of the head are given, assumed, or known.39,40 One can then compare the modeled distribution with the recorded distribution and estimate the goodness of fit for the source configuration and activity. Some models simplify the calculations by assuming certain properties and conductivities for the various compartments (e.g., skin, skull, cerebral spinal fluid [CSF], and brain tissue) of the head. Such simplifications often yield results that are sufficiently accurate for certain conditions and assumptions. In the preceding discussion of the inverse and forward problems, we have referred to “sources” that generate the potential field. Source analysis is an examination of the reciprocal inverse problem in which the goal is to determine the location and configuration of generators within the head that produced the observed potentials on the scalp.17,41 In laminarly structured cortex where most neurons have a common orientation that is perpendicular to the cortical surface, synchronous neuronal activity can be modeled by current dipoles.42 Figure 19-3 is a schematic diagram adapted from Scherg2 showing activation of various small segments of a cortical fold. Because of the columnar organization, current sources (+) and sinks (−) are displaced perpendicular to the cortical surface. Thus, if the segment of activated cortex lies on the surface of the brain (Fig. 19-3, top) or is parallel to the lateral convexity, the associated dipole is radial. If the activated segment lies in the depths of the fissure (Fig. 19-3, middle), the associated dipole is tangential. An oblique dipole results from activation of the banks of the fissure (Fig. 19-3, bottom). For most applications we use the extended definition of equivalent dipole to represent the dipole whose electric field best approximates summated fields of a number of closely spaced sources and sinks.2 These dipoles are called equivalent

A

B

C Figure 19-3. Schematic of an equivalent dipole with radial (A), tangential (B), and oblique (C) orientation relative to the surface of the head. Each equivalent dipole represents the sum of a number of activated elements shown in the shaded area. (Modified from Scherg M: Fundamentals of dipole source analysis. In Grandori F, Hoke M, Romani GL [eds.]: Auditory evoked magnetic fields and electrical potentials. Adv Audiol, vol 6, Basel, Karger, 1990.)

because their field provides an equivalent description of the compound activity of all neuronal elements in their vicinity that are oriented parallel to the dipole axis. Note in Figure 19-3 that a single radial and a single tangential equivalent dipole provide a good approximation of the

Functional Imaging of Auditory Cortical Activity

compound activity of all cortical segments on one side and in the vicinity of the right side of the cortical fold. Even the oblique activity can be represented by the radial and tangential dipoles. Early Dipole Source Localization Methods: Single- and Moving Dipole Models Early dipole localization methods tried to account for the instantaneous spatial distribution of the scalp potential, magnetic field, or CSD at a fixed time (see Wood39 for a good review). These methods involve the use of a physical model of signal propagation in the head to compute the expected surface topography usually associated with a current dipole source having arbitrary parameters. For electrical potentials, six parameters are usually required to specify a source (three for position, two for orientation, and one for strength). For magnetic recordings, five parameters are required to specify the source (three for location, one for strength, and only one for orientation since MEG is sensitive to only tangentially oriented sources). The position, orientation, and intensity of the source are iteratively adjusted to reproduce maximally the target topography.43 Usually, interpretation is restricted to latencies at which a single equivalent dipole source accounts well for the data. These early methods restricted analysis to a single equivalent dipole because the number of independent parameters underlying a single instantaneous scalp map is only less or equal to the number of recording channels. The use of a single source keeps the number of parameters small relative to the number of data values, which is an essential prerequisite for reliable estimates in the presence of recording noise.43 Hence, for a given instant, not much more than a single equivalent dipole, which already has six coordinates, can be extracted with confidence.44 Instantaneous single equivalent dipole solutions have some problems. When a part of the brain becomes activated while a previous part is still active, instantaneous single-dipole solutions often describe virtual sources remote from both actual sources. In other words, the location of this equivalent dipole does not necessarily coincide with the loci of the activated brain structures if multiple sources instead of a single source underlie the actual scalp map39,43; rather the solution may represent the “center of gravity” for the distributed activity at that instant. For cortically mediated neural activity, it is quite likely that more than one distinct source contributes to the scalp activity at any given instant. Certainly for the auditory system, it is well documented that bilateral cortical activity exists even to monaural stimulation. Consequently, a single-dipole or moving dipole model of such activity will frequently generate a source located along the midline of the head, which clearly represents a physiologically implausible solution. In such cases, single-dipole or moving dipole models are poor representations based on their physiologic plausibility.43 This does not rule out the value of single- or moving dipole solutions under all conditions. For example, if a single-dipole model is used to describe a generator with an established single underlying source over the period of its activation, the clustering of the single-dipole sources can provide information about (1) the validity of the single generator model or (2) the quality of

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the data based on the density of the clustering of the individual dipole fits (or both). Thus, a cluster with a large spatial extent that changes systematically as function of time point to a generator configuration consisting of more than one time-varying source. Alternatively, a cluster with locations that change nonsystemically (randomly) over a specified time interval may provide an indication of the reliability of the source location based on the spatial extent (or volume) of the cluster of single dipoles. Spatiotemporal Source Modeling: Technical Aspects The dipole solution cannot provide an unambiguous statement about sources because there is no unique solution to the inverse problem, and each potential distribution may be generated by many simultaneously activated processes.18 However, Scherg15 and Scherg and von Cramon16 created a different viewpoint and asked whether a combined spatiotemporal approach would not greatly enhance the validity of dipole source analyses. They demonstrated that with the use of a precise definition of the equivalent of a model dipole in conjunction with reasonable spatial constraints (hemispheric symmetry etc.), the source problem can be reduced so that a unique solution likely exists for a certain hypothesis.2 The principles of this approach are (1) use available information from anatomy and physiology to construct an electrical model of the head, (2) put forward different hypotheses of the origin of an evoked potential by placing equivalent model sources within all structures known or assumed to respond to a certain stimulus, and (3) attempt to explain the complete evoked potential data set over space and time by such a model. The solution can then be tested and compared with competitive hypotheses.2 Thus, spatiotemporal dipole modeling is fundamentally a hypothesis-driven technique for examining the origins of cortical activity. Spatiotemporal source modeling as developed by Scherg15 and Scherg and von Cramon16,45 is an approach to brain source localization that accounts for the whole sequence of scalp topographies by a few equivalent dipole sources having fixed positions and orientations but a varying strength over time. STSM solutions provide the locations, the orientations, and the strengths of activity over time of equivalent dipoles that could explain the measured spatiotemporal data. Although equivalent dipoles can now be computed in several ways, Figure 19-4 summarizes the STSM approach developed by Scherg.15 Although the figures are schematically shown in two dimensions, the process must be visualized in three dimensions. Recall that the activity recorded from any given electrode site on the surface of the head is the sum of all the active sources. This is illustrated in Figure 19-4A for four sources (two pairs of bilateral sources). The amount of contribution from any source to that electrode site depends on the conductivity of the medium, the distance, the orientation, and the strength of the activity. The activity recorded at each of the four electrode sites relative to the reference at the top of the head (Cz) is the sum of these four equivalent dipole sources. The bipolar voltage waveform recordings shown in Figure 19-4B are simply the difference in activity between the reference and the

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A

B

C

Figure 19-4. Schematic summary of the STSM approach. A, Voltage at any point on the surface of the head is the sum of active sources in the head. The amount of contribution from any source to that electrodes depends on the conductivity of the medium, the distance, the orientation, and the strength of the activity. B, Bipolar derivations with Cz as reference. C, Surface waveforms and source waveforms. (Modified from Scherg M: Fundamentals of dipole source analysis. In Grandori F, Hoke M, Romani GL [eds.]: Auditory evoked magnetic fields and electrical potentials. Adv Audiol, vol 6. Basel, Karger, 1990.)

recording electrode sites. As shown in Figure 19-4C the four equivalent dipole sources that are active in the brain have a simple time-varying source waveform. Thus, the sum at each electrode is different as shown by the surface waveforms because the relative contribution from each

source is different owing to these parameters of the dipole activity. Note that even though the source activity is relatively simple, the summed activity as shown by the bipolar derivation can be more complex because of threedimensional summation of the source activity.

Functional Imaging of Auditory Cortical Activity

Each electrode site has an associated equation for the summed voltage activity. For a given distance and orientation, and a head model for which size and conductivities of the various compartments (brain, CSF, skull, and skin) are known or assumed, the source activities are computed by an iterative procedure, by means of matrix algebra. These computations produce a modeled set of waveforms corresponding to the actual location of electrodes on the scalp. These modeled waveforms are then compared with the recorded data in a statistical least-squares procedure. The iterative procedure is completed when the best fit, which is the smallest residual variance for a given solution, is achieved. In essence, the procedure attempts to construct a set of dipoles whose location, orientation, and strength over time will add at the surface of the modeled head and come close to matching the data recorded from the subject. The following is an example of this process: Figure 19-5 shows the scalp waveforms (top, left), dipole source location (top, right), and source waveforms (bottom, left) for the auditory evoked potential data previously shown in Figure 19-2. This solution was obtained with an approximated three-shell head model. Computationally, the few sources are fitted simultaneously to all data across space and over time. This fitting over both space and time has the effect of increasing the reliability of the modeling.43 A best fit solution is shown for a bilateral set of regional dipoles, which are a set of three dipoles having a common location but orthogonal orientations. Therefore, the total number of dipoles for a pair of bilateral regional dipoles is six. The computed source waveforms for each of the six dipoles is shown for the best fit solution (Fig. 19-5, bottom, left. It can be seen that all three pairs of dipoles in each set of regional dipoles show significant activity. The tangential dipoles contain the typically observed N1–P2 complex, indicating a predominate site of origin on the superior surface of the temporal lobe. The second pair of dipole sources shows activity consistent with the T complex. The T complex represents a set of peaks and troughs that are generated along with the larger N1–P2 complex. The dipoles associated with this activity have a radial orientation, indicating a site of generation predominately on the lateral surface of the temporal lobe, likely reflecting activation of secondary, parabelt areas of auditory cortex. The third set of dipole waveforms contains two major peaks that correspond in latency to the middle latency response peaks Pa and Pb. It is interesting that the orientation of these sources is along the sagittal plane, orthogonal to the tangential orientation of the N1–P2 peaks. The origin of the regional dipoles localized to the area of superior temporal cortex of the head model, which is consistent with the expectation of auditory processing. The statistical best fit approach indicates that more than 95% of the variance in the original scalp recordings is accounted for by the modeled waveforms over the response time epoch. Many complex issues are involved in the modeling process, including the assumptions of the nature of the head model. Initially, most analyses relied on simple spherical, multishell head models because more realistic models were too computationally intensive. However, with the widespread availability of high-speed computing in personal computers, use of more realistic boundary element and

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finite element models are becoming more widespread. Application of these models may be particularly appropriate for assessing the auditory system. Although a spherical shell model conforms reasonably well to the geometry of occipital cortex, it is much less appropriate for temporal cortex. Both boundary and finite element models conform to the natural shape of volume conductor compartments (skull, CSF, and brain). Consequently, these volume conductors serve to minimize the localization errors inherent in applying a volume conductor model that does not conform to the shape of the brain. Details of dipole modeling based on these volume conductors are beyond the discussion of this chapter. However, note that, as is true with scalp voltage mapping, the dipole analysis can be improved by generating more realistic head models obtained from individual anatomic MRI data (e.g., Teale et al. and Fuchs et al.),46–48 as seen in Figure 19-5 (middle and bottom right. With current available commercial software, the localization accuracy of the STSM approach for electrical potentials approaches about 1 cm, but is highly dependent on the signal-to-noise ratio in the data. More accurate localization with the use of dipole modeling is possible with magnetic fields,49 but with the limitation that radially oriented activity cannot be characterized. However, considerable continuing work seeks to improve accuracy and speed of dipole localization estimations through the use of sophisticated algorithms.46,50–55 For example, by generating precalculated matrices, Fuchs and coworkers47,48 have provided the capacity to use more realistic boundary and finite element models in near real-time operations. These improvements are necessary if evoked electrical potentials and magnetic fields are used to estimate sources of neural activity. Modeling electric or magnetic fields produces comparable results.56 The focus is now more on the determination of the temporal properties of the neural activity and only their general potential locations rather than accurate specific loci. Instead, accurate localization and temporal characterization of the neural activity can be obtained by combining dipole modeling or current density reconstruction with other metabolic (PET or single-photon emission-computed tomography, SPECT) or hemodynamic (fMRI) techniques discussed later in this chapter.

Advantages and Disadvantages of Spatiotemporal Source Modeling In summary, Achim and colleagues43 noted the following advantages of the STSM approach: 1. Compared with two-dimensional surface color or gray-scale maps, localizing the origin of distributed brain activity is more adequately resolved by fitting a number of sources simultaneously from a number of consecutive scalp topographies. Much of the power of STSM arises from its capitalization on both spatial and temporal information. The temporal aspect is the important distinction from earlier dipole localization models. 2. For phasic neuroelectric activity, STSM is typically more plausible physiologically than the alternative

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interpretation of a moving dipole, which models timevarying topographies as the displacement of a unique focus of activity whose position, orientation, and intensity vary across time and often successfully accounts only for a fraction of the observed topographies. 3. STSM is more parsimonious than the moving singlesource model, requiring fewer parameters to account for a complete spatiotemporal data matrix. 4. It has been shown that large localization errors can occur with source analysis techniques for a given time, depending on the type of head model.57 These errors are reduced by performing the fitting over many time points instead of one, as is the case with STSM. Nonetheless, the complexities of source analyses require careful interpretation. The major disadvantages of this technique are its complexities and the need to use models and assumptions that are imperfect. Furthermore, for electrical activity, with current commercially available software, localization accuracy is limited to about 1 cm depending on the head model and various other assumptions. Current research demonstrates several ways to improve the technique when used alone. Nonetheless, even with the currently commercially available software, one can, through cautious and careful application, use these techniques to provide information about auditory processing not available otherwise.

Clinical Applications of Dipole Source Analyses Although the STSM or dipole source localization techniques have proved useful in clinical studies aimed at localizing epileptic spike activity58–63 and cerebral tumors,64 clinical application of STSM alone has yet to become routine in the assessment of auditory problems. Clinical application of dipole source-modeling techniques to problems related to hearing require studies of processing in normal auditory systems. During the previous decade, numerous studies have focused on such processing laying the groundwork for comparisons related to clinical issues. In their early work, Scherg and von Cramon37 showed that the STSM analysis may have clinical value in patients with cortical lesions affecting the auditory system. They demonstrated varying types of abnormalities in the dipole source waveforms associated with lesions of primary auditory cortex, acoustic radiations, and auditory association cortex. We attempted to use the source localization technique with cochlear implant patients, particularly younger children, to determine (1) the extent that responses (behavioral and physiologic) are auditory only and (2) if the different channels of stimulation activate different neural subpopulations in the periphery.65 Because electric current stimulation can potentially activate any nearby neural pathway, often other neural structures (vestibular and sensorimotor) may be stimulated. Such nonauditory evoked potentials have been observed.66 Our preliminary findings suggest that this technique may be very useful in identifying auditory and somatosensory contributions to evoked electrical activity from implant stimulation.

Even more valuable is the possibility that we may be able to determine if different channels of cochlear implant stimulation are reflected tonotopically in auditory cortex as revealed by the loci of the best fitting regional diploes. Evoked magnetic fields produced by acoustic stimulation have demonstrated tonotopic organization of auditory cortex.67–69 An example of using STSM in evaluating cochlear implant patients from our work65 is shown in Figure 19-6. At the time of these recordings, the subject was an 8-year-old child implanted with the 22-channel Nucleus Cochlear Corp. cochlear implant. The stimuli consisted of short bursts of biphasic current pulses spaced 2 msec apart and presented at a burst rate of one per second. Electrode pairs were activated at three locations in the cochlea: near the basal end of the array (electrodes 2 and 6), adjacent to this basal location (electrodes 6 and 10), and at the apical end of the array (electrodes 18 and 22). The locus of the regional dipole source solution for electrical stimulation of each of the three cochlear regions is shown in Figure 19-6. For all three stimulus conditions, the locus of the regional dipole best fit solutions was consistent with activation of auditory cortex. Furthermore, as seen in the sagittal view of the model, the loci for the three different areas of cochlear stimulation were organized such that the most basal stimulation was posterior and the most apical stimulation was most anterior along the supratemporal plane of auditory cortex. This organization is consistent with a tonotopic arrangement of going from high frequency to low frequency found in the magnetic studies with acoustic stimulation. The shift in the loci is significant and consistent with magnetic studies.67–69 For this individual, we are confident that the shifts are not accounted for by simple variability of the solutions. However, it is important to point out that, although differences in source location as a function of site of stimulation within the cochlea have been obtained in many implanted adults, the patterns do not consistently match previously observed tonotopic maps. This inconsistency might reflect variability unrelated to the site of stimulation. Alternatively, these variable patterns of spatial representation may reflect reorganizational differences between individuals with varying causes of deafness. Much work remains to determine whether this approach is viable means for assessing multichannel cochlear implant stimulation to ascertain the degree of separation and overlap in activating different neural channels. Most of the studies to date have been demonstrations of the feasibility of the technique and its application to various types of evoked potential activity related to auditory processing such as the mismatch negativity (MMN) potential70 and P300.71 Other studies focused on the localization of evoked potentials related to processing various sounds including speech.72–74 Because the accuracy of source localization using dipole modeling alone is limited, much of the current research is now focused on using a combination of dipole and other imaging techniques. As discussed later, combining dipole source analyses with metabolic or fMRI techniques may provide a powerful approach for studying the function of brain structures related to hearing. The dipole source analyses estimates the neural activity with good temporal resolution, and the other imaging techniques provide good source localizations.

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Figure 19-5. (Upper left): Grand mean scalp-recorded cortical activity evoked by left ear stimulation from a group of young adults. (Lower left): Dipole waveforms for each component of regional sources location in homologous left and right hemisphere locations. The sagittal sources contain the middle latency peaks Pa and Pb, contralateral (upper) and ipsilateral (lower) to the stimulation ear. The radial source waveforms contain the T complex components Ta and Tb. The tangential source waveforms contain the classic P1, N1, and P2 components. (Upper right): Location of the regional dipole sources superimposed on a schematic diagram of the head and brain. (Middle right): Source solutions superimposed on an average MRI (from the Montreal Neurological Institute). The sources are localized to the surface of the superior temporal gyrus. (Lower right): Source solutions superimposed on a structural MRI from and individual subject showing the location of activity relative to distinct anatomical landmarks. (See Color Plate 2.)

POSITRON EMISSION TOMOGRAPHY Background and General Principles Positron emission tomography (PET) is an imaging technique that delineates the magnitude of metabolic activity in the brain. PET is used to measure blood flow, oxygen and glucose metabolism, amino acid metabolism, tissue acid–base balance, membrane transport, and receptor– ligand interactions in the human body.75 The measurement of metabolism is indirect since PET devices detect concentrations of positron-emitting isotopes that have been injected into the bloodstream. These isotopes or radionuclides become concentrated in areas of the body where metabolic demand is high. The nucleus of the radionuclide contains an excess positive charge, which diminishes in one of two ways. Negatively charged electrons orbiting the nucleus may be captured or the nucleus may emit a positron. A positron emitted from the nucleus quickly combines with an electron in a process known as annihilation. During annihilation, the masses of the electron and positron convert to electromagnetic radiation in the form of two gamma rays of equal intensity that are emitted 180 degrees to each other.76 Positron emission is registered by the PET imaging system only when annihilation photons traveling in opposite directions activate coincidence detectors simultaneously.77 By adjusting the location of the coincidence detectors, concentration patterns for photon emission can be generated for the whole body or for a specific organ of interest such as the brain.

Advantages and Disadvantages of Positron Emission Tomography PET images can provide extensive information on functional neurochemical activity in the brain. Radionuclides such as proton-rich isotopes of carbon, nitrogen, or oxygen are used as tracers in PET studies of blood flow or oxygen

metabolism. Tracers such as 18F-dopa, 11C-raclopride, and 11 C-SCH23390 may be used to assess function in dopaminergic systems. Other tracers may be used to target specifically function of monoamine oxidase, benzodiazepine, or opiate receptors.75,77 PET studies generate three-dimensional representations with an effective resolution of better than 2 cm, so comparisons of metabolic activity between adjacent cortical regions are possible.75,78 However, analysis of functional organization within a region is limited because most subcortical and cortical structures such as auditory cortex have dimensions equal to or less than 2 cm. Attempts to resolve detail of less than 2 cm produce a partial volume effect in which gray and white matter of the brain are blended in the PET image. Errors in PET data introduced by the partial volume effect can be minimized through correcting PET79 or by performing baseline PET studies for comparison.75 Baseline studies are also important for establishing local background metabolic rates, which vary from one part of the brain to another in both nonhuman species and in humans.75,80 Although the spatial resolution of PET limits the study of functional organization within auditory cortex, the temporal resolution of PET studies also places limits on stimulation paradigms. For example, transitional changes on the order of 20 to 200 msec in a speech segments are sufficient to allow discrimination between phonemes. However, changes in cortical regional blood flow and metabolism follow a much longer time course. According to Mazziotta and Phelps,75 30 to 40 minutes may be required for metabolic activity to achieve a stimulusdependent steady-state necessary for PET imaging with deoxyglucose. Thus, it is likely that cortical activation patterns represented in PET data not only reflect local activation of sensory cortices but also activations associated with manipulations of task demands and expectations that may vary from one experimental condition to another. PET activations can be obtained with 15O-labeled compounds, which require less than 60 seconds to obtain

Figure 19-6. The loci for three stimulus conditions that differed in which implant electrodes were activated. Stimulation of the basalmost electrodes produces the most posterior source location; stimulation of the apicalmost implant electrodes produces the most anterior source location.

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sufficient flow information during stimulation. However, even 60-second epochs are too long to examine local neural responses to the microstructure of speech. One additional limitation for PET imaging results from the use of radioactive tracers. Although these tracers clear the body quite rapidly, the number of times an individual may be safely exposed to these elements is limited. Consequently, repeated PET imaging of a single individual over a short interval (weeks) is not possible. Moreover, the use of radioactive isotopes necessary for PET studies essentially precludes the use of this to assess central auditory function in children.

Clinical Applications PET studies may not be useful for examining rapid changes in neural activity in response to transient acoustic stimulation, but global studies of auditory function and brain organization are possible with PET. Early PET or SPECT studies have been conducted with a variety of acoustic stimuli, including noise, tones, words, stories, and music.81–91 An early study of auditory function using PET performed by Reivich and coworkers81 reported that monaurally presented stories produced a 20% to 25% increase in local cerebral metabolism throughout the right temporal lobe regardless of the ear of stimulation. Other studies have found lateralized patterns of activation dependent on the manner of presentation or the content of the presented material. Results of Greenberg and colleagues85 showed that the local cerebral metabolism rate for glucose was 7% higher in the temporal lobe on the side contralateral to the stimulated ear. Mazziotta and coworkers88 used PET to study cerebral activation patterns to verbal and nonverbal acoustic stimulation. Although verbal discourse increased metabolism in left hemisphere structures including the thalamus and frontal cortex, the pattern of metabolic asymmetry for nonverbal stimuli was dependent on the processing strategy used by the subject. Metabolic activity was greater in the left than in the right hemisphere for musically trained individuals or individuals who used visual imagery to process the nonverbal stimuli. In contrast, metabolic activity was greater in the right than the left temporal lobe in subjects who did not use visual imagery or who lacked an extensive musical background. During the past decade numerous additional studies have been aimed at localizing brain areas devoted to these various aspects of auditory function and to the processing of speech stimuli.92–97 Cochlear Implant Stimulation PET has also been used to assess cortical neural activation produced by electrically stimulating nerve fibers with a cochlear implant array. In an early PET study, Ito and colleagues78 studied preimplantation and postimplantation cortical activity in a 38-year-old man who had suffered from profound hearing loss at age 11/2 years following treatment with streptomycin. PET images obtained as a baseline before implantation showed broadly distributed areas of low metabolic activity in the left middle-frontal, posterotemporal, and parietal cortices. The parietal and temporal lobe, as well as Heschl’s gyrus in the right hemisphere, showed little metabolic activity, although activity levels were somewhat higher in the right than in the left

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hemisphere. Three months after implant surgery, the areas of low metabolic activity and the asymmetry between left and right hemisphere metabolic activity were no longer apparent. PET images obtained while the patient listened to recorded speech showed increased levels of metabolic activity in the left parietal cortex. According to Ito and colleagues,78 the increased metabolism found in auditory cortex extended to auditory association cortex, perhaps indicating that the neural activity evoked by the implant had been perceived as speech. Although this conclusion may be somewhat premature, PET imaging provided evidence of changes in local patterns of cortical metabolism following implantation and demonstrated that regions of the brain normally associated with auditory function were activated by implant stimulation. Many additional PET or SPECT studies during the previous decade have examined the distribution of activated brain areas to stimulation with a cochlear implant. For the most part, the basic findings are similar and demonstrate that electrical stimulation of the auditory pathway results in activation of areas seen with normal acoustic stimulation or consistent with behavioral responses to the stimuli98–105 as well as for evaluating the effectiveness of the implant106–113 or for assessing neuroplasticity resulting from deafness or use of the cochlear implant.114–120 The exploration of central auditory function in normalhearing children will likely remain limited due to the necessity of using radioactive isotopes. However for deaf children and adults, the use of PET or SPECT imaging is more justifiable if such data can add significantly to preoperative decisions regarding the appropriateness of cochlear implantation as a therapeutic treatment. Recent data reported by Roland and coworkers112 examined SPECT activations to auditory stimulation before and after cochlear implantation in three adults with pure-tone average audiograms of 90 dB or greater bilaterally. Results of the study showed that despite having relatively similar hearing losses across subjects, significant differences in patterns of cortical activation were observed between ears. Such results might provide important insights about which side should be implanted. For adults and postlingually deafened individuals, behavioral testing can often provide sufficient information for such decisions. However, for young children or prelinguistically deafened individuals, PET studies of cortical activation patterns provide a preoperative method of assessing objectively which ear would provide the best postoperative activation of cortex. PET imaging might also be used to determine the extent of damage and preserved auditory function following traumatic or ischemic brain injury.75 PET data may be useful for delineating deficits associated with damage to primary auditory receiving areas from those associated with damage to higher-order speech reception areas in temporoparietal cortex. PET studies might also provide insight on the origins of so-called central auditory processing disorders.121 Atypical cortical metabolism patterns might exist in those individuals affected by central auditory processing disorders. Tinnitus Studies with Positron Emission Tomography Several studies have explored PET imaging as a technique for objective detection and identification of origin (i.e.,

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peripheral or central) for tinnitus. PET studies may provide general information regarding activity and its locus. Whether the source of the tinnitus lies in the auditory periphery or in central structures of the auditory pathway, auditory cortex might show evidence of chronic activation by a change in metabolic activity. For example, it has been suggested that tinnitus associated with unilateral activation of cortex is an indication of a central origin since a peripheral origin should have bilateral representation.122 Studies comparing cortical metabolic patterns from patients with tinnitus and those without have been performed. The results of Arnold and colleagues123 and Wang and coworkers124 using 18F-deoxyglucose (FDG)-PET studies on patients with disabling chronic tinnitus showed increased metabolic activity mostly in the left primary auditory cortex compared with nontinnitus subjects. PET studies have evaluated those patients whose tinnitus can be altered in loudness by orofacial movements125 or by eye movements.126 Studies during habitual tinnitus and when the tinnitus has been suppressed in the same patient have also been studied.128–130 In addition, individuals whose tinnitus is triggered by consuming certain foods or drinks such as caffeine might be appropriate for repeated studies comparing PET images obtained before and after ingesting the tinnitus-inducing foods or beverages. Many of these studies also suggest that other brain areas may be involved in the response to emotional responses to the adverse percept of tinnitus (e.g., Mirz et al.).131 Johnsrude and colleagues132 recently published a review of the use of PET for functionally imaging the auditory system. However, its poor temporal resolution, its need for radioisotopes, its invasiveness, and its high cost have limited its clinical utility. For many applications, it may be replaced in the future by fMRI. Although, PET may still have the major role in imaging cortical activity to electrical stimulation when prostheses with metal, such as the cochlear implant, are used.

FUNCTIONAL IMAGING WITH MAGNETIC RESONANCE IMAGING Background and General Principles A technical description of MRI is not presented here. The reader is referred to the brief review by Andrew.133 In essence, MRI involves imaging in a slice of the head, the distribution of protons that have been selectively excited (i.e., in resonance) by applying a magnetic field gradient. In its most basic application, MRI does not use ionizing radiation and is noninvasive. However, contrast improvement can be achieved by intravenous injection of a paramagnetic solution such as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Most MRIs are maps of the proton nuclear magnetic resonance (NMR) signals from water and fat in the tissues but images of blood flow and diffusion can also be obtained.133 Currently, the spatial resolution of MRI, below 1 mm, is far superior to that of other neuroimaging techniques. The early application of MRI provided mainly anatomic imaging technique devoid of dynamic functional information. However, during the past 15 years, a variant of MRI was developed to provide functional maps of the human

brain with better temporal and spatial resolution than PET techniques. The new functional imaging MRI (fMRI) method relies on changes in the blood supply to the brain that accompany sensory stimulation or changes in cognitive state. An excellent review of the early work with this technique is provided by Tank and colleagues.134 Following this early work, numerous fMRI studies have been conducted of many aspects of auditory function, which we will briefly review later. Other recent reviews of studies that use fMRI to investigate the auditory system can be found in Huckins and coworkers,135 Cacace and colleagues,136 Seifritz and coworkers, and Bernal and Altman.137,138 Currently, three basic methods are used to image functionally with MRI. Two of the three methods are noninvasive approaches, and the third uses exogenous vascular contrast agents. Blood Oxygenation Level–Dependent Contrast Imaging Blood oxygenation level–dependent (BOLD) contrast imaging is based on the magnetic properties of hemoglobin. For example, because deoxyhemoglobin (hemoglobin without a bound oxygen molecule) is paramagnetic, a blood vessel containing deoxyhemoglobin placed in a magnetic field will alter the field in its vicinity. The greater the amount of deoxyhemoglobin, the greater the local distortion of the magnetic field surrounding the blood vessel. This distortion surrounding the blood vessel can, in turn, affect the magnetic resonance images of nearby water protons. Thus, the changes in the hemoglobin that are present in low concentrations are difficult to monitor directly by MRI. However, these changes affect the signal characteristics of water molecules that are easier to measure since water molecules are 100,000-fold higher in concentration. Ogawa and colleagues139 showed that at high magnetic fields, blood vessels could be imaged, and the images of the blood vessels were affected by induced changes in cerebral blood flow and oxygen utilization. Blood Perfusion Imaging Using Vascular Contrast Agents For the commonly used magnetic field strength in clinical MRI systems, the signal changes observed by the BOLD contrast technique are only a few percent. One can obtain significantly larger changes in signal intensity, ranging from 50% to 100%, by intravenous injection of an exogenous paramagnetic contrast agent. These perfusion-based maps have excellent spatial resolution. Furthermore, maps can be calibrated to provide quantitative changes in cerebral blood flow and cerebral blood volume. Belliveau and coworkers,140,141 using Gd-DTPA, first reported perfusion-based maps with a focus on cerebral blood volume changes accompanying stimulation of the visual system. Blood Perfusion Imaging Using Inversion Recovery Methods Kwong and coworkers142 demonstrated that the perfusion of blood in brain areas can be measured noninvasively with a method called inversion recovery (IR). This method

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depletes the concentration of MRI-visible water protons in a brain region and measures water protons that enter the region through blood flow, providing a direct measurement of flow without the use of exogenous contrast agents. Improvement in resolution can also be achieved by increasing the strength of the magnet. In the past, typical clinical systems had a magnet strength of 1.5 T (teslas); now it is much more common to find systems with magnet strengths of 3 to 4 T, with the occasional research lab having more high-powered magnets of 7 T. The use of fMRI to study auditory neural function is based on the fact that changes in neural activity are accompanied by changes in energy metabolism. Tank and colleagues134 discuss several lines of evidence that support the notion that increased metabolic rate is correlated in many mammalian species, including humans, with an increase in blood flow that can be controlled locally.143–146 In addition to the variety of methods that have evolved for acquiring fMRI, two major stimulus presentation/ experimental design paradigms have been adopted for use in most fMRI experiments: the so-called box or block designs and event-related, or sparse stimulation, designs. A number of excellent reviews have been written describing the benefits and drawbacks of these techniques. Briefly, boxcar designs are experimental sequences in which stimulation is simultaneous with (occurs at the same time as) the imaging sequence. Event-related, or sparse, designs are those in which a series of stimuli are presented during a period prior to the onset of the MR scanning sequence. The justification for this approach is that for BOLD studies, a buildup time of approximately 4 seconds is needed for the response to reach its peak. For auditory studies, this is an advantageous over the boxcar design because experimental acoustic stimulation can be separated from the artifactual acoustic stimulation produced by the scanning sequence. It is now well established for many auditory processes that psychophysical data obtained in the presence of high levels of background masking noise do not always match those for stimuli presented in quiet. For example, Shtyrov and coworkers147 demonstrated that for speech-evoked MEG responses, the degree of lateralized cortical activity evoked by the presentation of a deviant stimulus (MMN) changes dramatically between no-noise and background noise conditions. Thus, with no background noise, speech-evoked MMN dipole activity was strongly lateralized to the left hemisphere. However, in the presence of background white noise, the magnitude of the left hemisphere response decreased, while activity in the right hemisphere increased. These results, combined with psychophysical studies of the effects of background noise on auditory perceptual processes, would suggest that the event-related or sparse experimental paradigm would be preferable for fMRI studies of central auditory processes. A brief review of the advantages and disadvantages of these two techniques as described by Horwitz and colleagues148 is outlined in the following sections. Advantages and Disadvantages of Boxcar Designs As one advantage, boxcar design experiments are typically able to measure higher levels of cortical activation, resulting in greater statistical power. This in turn leads to faster fMRI acquisition times. Because the interstimulus interval

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is shorter than the hemodynamic response function for each stimulus item, data collected with boxcar designs are interpreted as a brain state- (task-induced) dependent measure. The disadvantage of boxcar designs is that the acoustic noise of the imaging sequence is concurrent with the fMRI stimulation, which may significantly affect the arousal and attention. In addition, the acoustic noise of the imaging sequence will act as a mask for experiments using auditory stimulation. Advantages and Disadvantages of Event-Related Designs In an event-related paradigm, stimulus presentation is asynchronous with fMRI acquisition sequences. One disadvantage of event-related design experiments is their somewhat lower level of cortical activation (compared with boxcar designs), thus resulting in lower statistical power. Lower levels of cortical activation lead to longer fMRI acquisition times. One advantage of event-related or sparse designs is that responses to single stimulus type can be characterized by averaging activation across multiple stimulus presentations.The data are more easily interpretable relative to specific types of stimulus events. As such, the fMRI data recorded during event-related sequences are much more comparable to evoked (or eventrelated) potentials. Another major advantage of event-related paradigms is that since stimulus presentation precedes each scanning sequence, the arousal and attentional effects produced by the high noise levels of the imaging sequence are not superimposed on cortical activations produced by the stimulus events. Auditory Studies Using Functional Magnetic Resonance Imaging Cortical Areas Involved in Basic Processing of Auditory Stimuli Functional imaging techniques have been trying to answer the fundamental question of where in the cortex certain types of auditory processing take place. The assumption is that with simple acoustic stimuli such as tones, one activated area must be primary auditory cortex. Examples are studies trying to identify areas involved in basic processing for simple tones to verify tonotopic organization at cortical levels or effects of parametric changes in the stimuli.149–162 Although a number of these studies suggest that tonotopic organization can be seen, the fMRI studies of Talavage and colleagues154 and Schonwiesner and coworkers163 suggest that multiple frequency-dependent activation sites exist and that it is difficult to demonstrate a single primary tonotopic organization. Another basic processing issue is where and how the brain is activated in response to simple monaural and binaural stimuli.164–168 Cortical Development, Maturation, and Plasticity In the study of activation and processing of simple auditory input, understanding the time course of the development and maturation of such processing is very valuable. Such knowledge is vital to understanding not only pathology but also the plasticity of a compromised auditory system. It has been demonstrated that fMRI studies can be carried out in

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children169 as well as in infants and neonates170 and could provide insight to cortical development and maturation when compared with studies in adults. Understanding development and maturation of cortical processes helps us to understand changes due to deafness and the related issues of reorganization and brain plasticity. For example, Tschopp and colleagues171 and Bilecen and coworkers172 used fMRI to study activation of auditory cortical areas in unilaterally deaf patients, and Suzuki and colleagues173 showed that cortical patterns change very quickly in patients who suffered sudden hearing losses. Studies in totally deaf patients who subsequently received cochlear implants may provide clues about brain plasticity and how it may be affected by deprivation and the reintroduction of auditory stimulation. Cross-modal Activation in Primary Auditory Cortex One of the more controversial issues related to deafness and plasticity is whether reorganization subsequent to deafness is such that stimulation in the visual modality produces activation in primary auditory cortex (PAC). Although ample fMRI evidence demonstrates that visual stimulation associated with communication (e.g., lip reading) can activate auditory cortical areas,174–178 as well as evidence that activity increases in auditory areas of the temporal lobe of deaf subjects performing visual tasks or stimulated visually,176,179–181 it is unclear that such visual stimuli activate the PAC. Some claim activation of PAC with visual stimuli alone.176,180,181 Others claim from their fMRI analyses that activation occurs in nonprimary auditory areas but not in primary auditory cortex.119,178 Animal work in congenitally deaf cats by Kral and colleagues182 also demonstrated that there was no evidence for crossmodal reorganization of primary auditory cortex. In other words, primary auditory cortex remains specific to auditory stimuli. A problem that leads to this controversy is the identification of primary auditory cortex from the MR scans. Such identification can be difficult. More cytoarchitectonic studies are needed to develop an accurate anatomic reference system.183,184 Cochlear Implant Assessment Assessing cortical plasticity may lead to an understanding of performance differences with a cochlear implant. Although a number of PET studies of cochlear implant patients have been done, little has been done with fMRI because of the metal content in implants (discussed later). Truy107 and Giraud and colleagues119 reviewed the use of various neurofunctional imaging techniques including fMRI to study cochlear implant patients and cortical plasticity and noted their advantages and disadvantages. Speech and Language Studies During the previous 10 years numerous fMRI studies have tried to determine the cortical areas involved in speech perception and discrimination as well as areas important for language processing. A review of these studies is not possible here. We simply provide a few examples of the kinds of studies that are being conducted. Studies of speech processing under dichotic and diotic conditions185 suggested differences in areas activated that may be due to attention factors. A number of studies investigated the

effect of attention186,187 and involuntary attention switching188,189 in the processing of sounds. Other issues related to the processing of speech and language are differences in activation between words and nonwords or speech and nonspeech,190–193 listening comprehension,194–196 semantic processing,196 sex differences in laterality of language comprehension,196,198 identifying where speech parameters are processed in the brain,199,200 and specific sensitivity to vocal sounds.201 Because of the complexities involved in speech and language processes, interpretations of the activations observed in fMRI studies are often difficult and do not always parallel findings with direct cortical stimulation.202 The popularity of language studies and fMRI was recently emphasized by a special journal issue devoted to “Functional Brain Imaging of Language” (Human Brain Mapping, vol. 18, 2003). Tinnitus We already discussed attempts to detect the presence of tinnitus with the PET imaging methods. Functional MRI has been similarly used to identify objectively the presence of certain kinds of tinnitus and the locations in the auditory system that might be involved. Thus far, only certain forms of tinnitus have been amenable to study with fMRI.203–206 Studying with fMRI the neural activity associated with the presence or onset of tinnitus is particularly difficult because of the high noise levels produced by the scanner. Attempts to overcome this inherent disadvantage of fMRI are discussed in the following section.

Advantages and Disadvantages of Functional Magnetic Resonance Imaging The obvious advantage of those fMRI techniques that image without exogenous contrast agents is their noninvasiveness. Unlike PET and SPECT, MRI has no known toxicity issues and many repetitions of experiments on individual subjects are possible. However, perfusion-based fMRI imaging techniques that use intravenous injections of paramagnetic solutions to improve the contrast suffer the same drawbacks of invasiveness and toxicity that limit the number of scans on a single patient. Also, only a single map is produced by imaging during the transit of a contrast agent, and the time course of the hemodynamic changes cannot be measured. A major disadvantage for auditory studies is that fairly high levels of noise are generated by MRI units, which makes it difficult to conduct auditory studies.188,207 A detailed specification of the spectral characteristics of the noise from the scanner can be found in Ravicz and colleagues.207 Several studies have addressed the noise issue. McJury and Shellock208 discuss in their review (1) the various types of acoustic noise produced during the operation of MRI systems, (2) the characteristics of the acoustic noise, and (3) information regarding noise control techniques. As described previously, it may be preferable for fMRI-based studies of central auditory processing to use those experimental designs that rely on the physiologic

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delays between the onset or the end of stimulation, and the corresponding hemodynamic response can be used to minimize the MRI noise in acoustic stimulation studies.137,209–214 Alternatively, developing effective methods to attenuate or cancel the noise generated by the MRI systems215 or use of a loudness-matching formula to reduce the effects of scanner noise on the activation measures should be considered.211 Another major disadvantage for auditory investigations is that the use of MRI with cochlear implants is contraindicated because of the possible torquing that can result when applying a magnetic field to metal containing ferrous material.216 However, Lazeyras and colleagues217 claim that fMRI scans can be safely obtained in patients with a cochlear implant with methodologic changes and careful techniques. Alwatban and coworkers218 and Schmidt and colleagues219 demonstrated methods for electrically stimulating the auditory system in deaf subjects and also studying them with fMRI in order to assess the patient’s suitability for a cochlear implant.

Clinical Applications and Combining Imaging Techniques Because each of the imaging techniques has advantages and disadvantages, which technique is appropriate depends on the type of patient and the information desired. It is obvious that if it were possible to gather information from more than one technique, better information could be obtained than from any single technique alone. The problem is that these imaging techniques are expensive and require facilities that are not always widely available. Nonetheless, the value of information that a combination of techniques can provide for clinical application is great, and we believe such combination studies will be more common as issues of cost and availability are resolved. The main advantage of fMRI and PET studies is their ability to localize sources of presumed activity with fairly good accuracy. However, their main disadvantage is that they provide poor temporal information, especially PET images. Localization of neural activity with dipole source analyses of electrical and magnetic surface recordings is less precise, but these methods provide good temporal information. Combining these methods yields both localization and temporal information. Some combinations rely on surface electrical potentials or magnetic fields to provide temporal aspects of the neural activity and on PET scans220–222 or fMRI166,223,224 scans to provide information of the neuroanatomic loci. For example, some studies combine PET scans with source localization of electrical potentials225 or with source localization of magnetic fields.226 Other studies have combined fMRI with MEG source localization.227 These studies also allow comparisons between the electric or magnetic dipole source localization techniques and the more precise localization techniques that use metabolic (PET) or hemodynamic (fMRI) changes. Studies that must rely only on dipole source localization of electrical or magnetic activity find it helpful to superimpose the calculated dipoles on static MRI images of the patient’s head.228 Although basic issues of the methodologies are still being investigated, methods for improving the measures230–232

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and clinical application of functional imaging techniques related to auditory evaluation are now emerging. Although a review of clinical application is not possible, we can examine some of the assumptions about the potential value of these imaging techniques. Many of the possible clinical uses for auditory evaluation can be seen from the various topics we have just reviewed. In addition, it has been shown that functional imaging with MRI can be useful in mapping epileptic foci and studying patients with psychiatric and neurologic disorders.121,233 We briefly mentioned that many of these metabolic and blood flow neuroimaging studies have directed their attention to determining the anatomic location of important language areas and mapping areas involved in higher cognitive processing.

SUMMARY Functional imaging of electrical, magnetic, and metabolic activity of the brain in response to sensory stimulation is a rapidly evolving area of investigation. Each of the techniques can provide different views of brain activity, and each has its own advantages and disadvantages. In general the neuroimaging methodologies can be categorized into those that have high temporal resolution (EEG and MEG) and those that have high spatial resolution (PET, SPECT, and fMRI). For investigations of central auditory processing, particularly those involved with speech, some advantage might be gained by acquiring the high temporal resolution of EEG and high spatial resolution of fMRI simultaneously. This technologically challenging approach will likely become a focus of much development and investigation over the next few years. Although the clinical value and applications of these techniques have not been clearly defined, the demonstration of their enormous potential for helping us understand the nature and location of sensory deficits is emerging. Realization of this potential will take some time, but the information provided by functional imaging techniques should be valuable in diagnosis and treatment of auditory-impaired patients.

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191. Vouloumanos A, Kiehl KA, Werker JF, Liddle PF: Detection of sounds in the auditory stream: Event-related fMRI evidence for differential activation to speech and nonspeech. J Cogn Neurosci 13:994–1005, 2001. 192. Samson Y, Belin P, Thivard L, et al: Auditory perception and language: Functional imaging of speech sensitive auditory cortex. Rev Neurol (Paris) 157:837–846, 2001. 193. Benson RR, Whalen DH, Richardson M, et al: Parametrically dissociating speech and nonspeech perception in the brain using fMRI. Brain Lang 78:364–396, 2001. 194. Michael EB, Keller TA, Carpenter PA, Just MA: fMRI investigation of sentence comprehension by eye and by ear: Modality fingerprints on cognitive processes. Hum Brain Mapp 13:239–252, 2001. 195. Friederici AD, Meyer M, von Cramon DY: Auditory language comprehension: An event-related fMRI study on the processing of syntactic and lexical information. Brain Lang 75:289–300, 2000. 196. Kansaku K, Kitazawa S: Imaging studies on sex differences in the lateralization of language. Neurosci Res 41:333–337, 2001. 197. Binder JR, Rao SM, Hammeke TA, et al: Functional magnetic resonance imaging of auditory semantic processing. Neurology (Suppl. 2) 43:189, 1993. 198. Zahn R, Huber W, Drews E, et al: Hemispheric lateralization at different levels of human auditory word processing: A functional magnetic resonance imaging study. Neurosci Lett 287:195–198, 2000. 199. Mohr CM, King WM, Freeman AJ, et al: Influence of speech stimuli intensity on the activation of auditory cortex investigated with functional magnetic resonance imaging. Acoust Soc Am 105:2738–27345, 1999. 200. Mathiak K, Hertrich I, Grodd W, Ackermann H: Cerebellum and speech perception: A functional magnetic resonance imaging study. J Cogn Neurosci 14:902–912, 2002a. 201. Belin P, Zatorre RJ, Lafaille P, et al: Voice-selective areas in human auditory cortex. Nature 403:309–12, 2000. 202. Lurito JT, Lowe MJ, Sartorius C, Mathews VP: Comparison of fMRI and intraoperative direct cortical stimulation in localization of receptive language areas. J Comput Assist Tomogr 24:99–105, 2000. 203. Cacace AT, Cousins JP, Moonen CTW, et al: Advances in the development of an objective tinnitus measurement tool: Use of functional magnetic resonance imaging (fMRI). J Assoc Res Otolaryngol (Abstr). 830, 1996. 204. Cacace AT, Cousins JP, Parnes SM, et al: Cutaneous-evoked tinnitus. I. Phenomenology, psychophysics and functional imaging. Audiol Neurootol 4:247–257, 1999. 205. Cacace AT, Cousins JP, Parnes SM, et al: Cutaneous-evoked tinnitus. II. Review of neuroanatomical, physiological and functional imaging studies. Audiol Neurootol 4:258–268, 1999. 206. Melcher JR, Sigalovsky IS, Guinan JJ Jr, Levine RA: Lateralized tinnitus studied with functional magnetic resonance imaging: abnormal inferior colliculus activation. J Neurophysiol 83:1058–1072, 2000. 207. Ravicz ME, Melcher JR, Kiang NY: Acoustic noise during functional magnetic resonance imaging. J Acoust Soc Am 108:1683–1696, 2000. 208. McJury M, Shellock FG: Auditory noise associated with MR procedures: a review. J Magn Reson Imaging 12:37–45, 2000. 209. Eden GF, Joseph JE, Brown HE, et al: Utilizing hemodynamic delay and dispersion to detect fMRI signal change without auditory interference: The behavior interleaved gradients technique. Magn Reson Med 41:13–20, 1999. 210. Yang Y, Engelien A, Engelien W, et al: A silent event-related functional MRI technique for brain activation studies without interference of scanner acoustic noise. Magn Reson Med 43:185–190, 2000. 211. Di Salle F, Formisano E, Seifritz E, et al: Functional fields in human auditory cortex revealed by time-resolved fMRI without interference of EPI noise. Neuroimage 13:328–338, 2001. 212. Hall DA, Haggard MP, Summerfield AQ, et al: Functional magnetic resonance imaging measurements of sound-level encoding in

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PLATE 1

Figure 19-2.Top, The scalp distribution for cortical activity evoked by monaural stimulation to the leftear. The major peaks of the auditory evoked potentials are marked in the inset. Bottom, On the left, a voltage distribution for N,oo of the auditory evoked potentials is shown for the activity shown at top of thisfigure. In center, the scalp voltage distribution is shown for the P150 potential. The voltage distribution for a left median nerve somatosensory N54 is shown onthe right.

PLATE 2

Figure 19·5. Upper left, Grand mean scalp-recorded cortical activity evoked by leftear stimulation from a group of young adults. Lower left, Dipole waveforms for each component of regional sources location in homologous leftand righthemisphere locations. The sagittal sources contain the middle latency peaks Pa and Pb, contralateral (uppe!') and ipsilateral (lowe!') to the stimulation ear. The radial source waveforms contain the T complex components Ta and Tb. The tangential source waveforms contain the classic P" N,. and P2 components. Upper righI, Location of the regional dipole sources superimposed on a schematic diagram of the head and brain. Middle right, Source solutions superimposed on an average MRI (from the Montreal Neurological Institute). The sources are localized to the surface of the superior temporal gyrus. Lower righI, Source solutions superimposed on a structural MRI from and individual subject showing the location of activity relative to distinct anatomical landmarks.

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Magnetic Resonance Imaging Techniques for the Labyrinth Labyrinthine Lesions Congenital Malformations of the Inner Ear Labyrinthine Hemorrhage Labyrinthitis Contrast Enhancement of the Labyrinth

Perilymphatic Fistula Labyrinthine Neoplasms Labyrinthine Schwannomas Other Tumors Involving the Labyrinth Postoperative Changes Endolymphatic Hydrops Conclusion

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ntil recently, the only appropriate imaging modality for diseases affecting the temporal bone was highresolution computed tomography (HRCT). Although this technique is obviously still important and in fact relied on by most centers for imaging many temporal bone diseases, the advent of magnetic resonance (MR) contrast agents has clearly expanded the role of MR imaging (MRI) in this region.1 Recent technical innovations in fast imaging and high-resolution techniques have finally made MRI appropriate for many of these conditions, and in some cases uniquely so. This chapter discusses the role of MRI in the evaluation of the labyrinthine pathology.2

MAGNETIC RESONANCE IMAGING TECHNIQUES FOR THE LABYRINTH The labyrinth is always imaged together with the internal auditory canal (IAC) and cerebellopontine angle. MRI of the labyrinth should include high-resolution pre- and postcontrast T1-weighted images in the axial plane and postcontrast T1-weighted images in the coronal projection. Conventional spin-echo 3-mm-thick T1-weighted images (14–16 field of view, 192 × 256 matrix, and four excitations on a 1.5-T imager) provide good images of the labyrinth. Nevertheless, today more and more thinner 2-mm spinecho or even 1-mm 3-D Fourier transform (3DFT) gradient-echo T1-weighted images are used.3 These images demonstrate the different turns of the cochlea, the vestibule, semicircular canals, and, in many cases, the endolymphatic sac in even more detail. Even the nerves and vessels inside the IAC and cerebellopontine angle become visible on the 1-mm-thick images. Precontrast T1-weighted images are necessary to differentiate enhancement from

Alexander S. Mark, MD

spontaneous hyperintensities inside the labyrinth, which can be caused by fat (lipoma), blood (trauma, cholesterol granuloma, vascular malformation), tumor (schwannomas), or a high protein concentration of the intralabyrinthine fluid (in case of acoustic schwannomas). In the coronal plane, fat-suppressed, T1-weighted spin-echo images should be used to eliminate the high signal intensity of the bone marrow, often present in the walls and especially in the roof of the IAC. These images can also be used to exclude a lipoma or to differentiate lesions from the fat used to close the surgical access route. Today, heavily T2-weighted gradient-echo or fast spinecho 3DFT images4 are mandatory if the labyrinth has to be evaluated in detail. These images must be very thin, 0.5 to 0.7 mm, and must provide high contrast between the cerebrospinal fluid, intralabyrinthine fluid, nerves, and bone. This sequence is mainly used to check the three branches of the vestibulocochlear nerve and the facial nerve in the IAC and to verify possible loss of intralabyrinthine fluid due to the presence of fibrosis or a tumor.5 Threedimensional reconstructions, multiplanar reconstructions, and virtual images6 of the fluid-containing membranous labyrinth can be obtained with these images,7 which are used more and more frequently prior to cochlear implantation.8 However, one must bear in mind these sequences are prone to magnetic susceptibility artifacts.9

LABYRINTHINE LESIONS In the past, the labyrinth was almost exclusively imaged with HRCT. CT still has its value for the evaluation of congenital SNHL although modern MR sequences can depict most of the pathology seen on CT and is even able to detect 331

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congenital malformations that remain invisible on CT. Recently, because of a number of technical advances coupled with the availability of intravenous contrast agents, a number of inflammatory and neoplastic lesions of the labyrinth diagnosed previously only at autopsy or at surgery can be imaged. This section describes some of the labyrinthine diseases that can be diagnosed by imaging modalities and emphasizes the respective strengths of HRCT and MRI.

CONGENITAL MALFORMATIONS OF THE INNER EAR Congenital malformations of the cochlea and vestibular system are frequently found in patients with sensorineural hearing loss (SNHL) and vertigo.10 These malformations can be detected on CT but patients presenting with SNHL or vertigo are today best first examined on MRI.11 Therefore the MRI technique must include thin T2-weighted gradient-echo images (3DFT-constructive interference in steady state, CISS) or fast spin-echo images because this pathology can be overlooked on the other MRI sequences. The most frequent congenital malformation is a large vestibular aqueduct (CT) or large vestibular duct and sac12,13 (MRI). The patients present with SNHL, often triggered by minor trauma, and vertigo and loss of equilibrium. The vestibular aqueduct or sac is considered too large when its diameter is larger than 1.5 mm or when it is larger than the diameter of the posterior semicircular canal or duct. Associated enlargement of the scala vestibuli/scala media in comparison with the scala tympani is often present in these patients and can only be detected on MRI.14 Semicircular canals or ducts with an abnormal shape, increased or decreased diameter, or that are partially absent can be detected on CT and on T2-weighted gradient-echo images. The most frequent malformation is, however, a saccular semicircular canal confluent with an enlarged vestibule. The term LCVD (lateral semicircular canal-vestibule dysplasia) is used when this occurs as a sole radiographically detectable anomaly. Cochlear malformations are often associated with severe congenital SNHL.15 Aplasia of the complete temporal bone, aplasia of the cochlea, common cavity formation (cochlea and vestibule form one cavity), dysplasia (severe malformation of the cochlea) and hypoplasia of the cochlea (cochlea is small, number of turns can be reduced), and less severe malformations (Mondini’s malformation) can all be detected on CT and MRI.16 However, some subtle signs can be seen only on MRI. For instance, the inter- and intrascalar defects inside the cochlea, described by Mondini, and the absence of a normal separation between scala tympani and vestibuli can be recognized only on MR. Abnormal connections can exist between the subarachnoid spaces and the perilymphatic space in patients with congenital inner ear malformations. In these patients the pressure of the cerebrospinal fluid is transmitted to the cochlea and causes a perilymphatic hydrops. These patients can present with recurrent meningitis, progressive fluctuating hearing loss, tinnitus, and/or vertigo. When these patients are operated on (e.g., stapedectomy), the intralabyrinthine fluid gushes out of the cochlea (gusher ear)

Figure 20-1. Labyrinthine hemorrhage. Eleven-year-old girl with leukemia and sudden total right-sided SNHL. Fine horizontal nystagmus to the left on left lateral gaze. Temporal bone specimen demonstrates hemorrhage in the cochlea and vestibule. (From Schuknecht HF: Hemolabyrinth. In Schuknecht HF [ed.]: Pathology of the Ear, 2nd ed. Philadelphia, Lea and Febiger, 1993, pp 303–306, with permission.)

and results in deafness.17 The most important imaging signs are (1) absence of a bony barrier between the cochlea and fundus of the IAC; (2) enlargement of the labyrinthine segment of the facial nerve canal; (3) convex angle anteriorly between labyrinthine and tympanic segment of the facial nerve canal; (4) large vestibular aqueduct/duct and sac; and (5) cochlear dysplasia.

LABYRINTHINE HEMORRHAGE In the absence of trauma, labyrinthine hemorrhage18 is a rare cause of SNHL and vertigo.19 It can occur in patients with coagulopathies, leukemia20 (Figs. 20-1 and 20-2), after

Figure 20-2. Elderly man with chronic myelocytic leukemia and bilateral SNHL. Coronal precontrast T1-weighted images demonstrate high signal in the cochleas (arrows).

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Figure 20-3. Cochlear hemorrhage secondary to an surgically proven intracanalicular arteriovenous malformation. A, Coronal nonenhanced T1-weighted MRI shows high signal (arrow) presumed to represent methemoglobin in the cochlea. B, Coronal T1-weighted MRI through the IAC shows high signal within it (arrowheads).

fistulization of an adjacent lesion (e.g., hemangioma, arteriovenous malformation, Fig. 20-3), cholesterol granuloma, or carcinoma of the endolymphatic sac21 (Fig. 20-4), or secondary to trauma with or without an associated fracture. Viral labyrinthitis may also be hemorrhagic22 (Fig. 20-5). Labyrinthine hemorrhage cannot be demonstrated by CT. However, it can be suspected when a fracture of the temporal bone23 is identified passing through the labyrinth.24 MRI is uniquely suited to the demonstration of labyrinthine hemorrhage. Precontrast studies demonstrate

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high signal intensity in the labyrinth consistent with subacute hemorrhage.25 Theoretically, acute hemorrhage should be diagnosed on T2-weighted images as a very low intensity signal, but we have not encountered such cases in our experience. Realistically, most patients will be studied at the subacute stage. If the bleeding was severe enough, the mixture of intralabyrinthine fluid and blood will eventually become a clot or show soft tissue/fibrotic characteristics. This can be recognized on the 3DFT, gradient-echo, T2-weighted images as

B

Figure 20-4. Hemorrhagic low-grade adenocarcinoma of the endolymphatic sac within the medial temporal bone fistulizes to the membranous labyrinth with subacute blood in vestibule. A, Axial CT image of the left temporal bone at the level of the vestibule (arrow) shows the adenomatous tumor (curved arrow) as an area of scalloping along the medial surface of the temporal bone. B, T1-weighted axial MRI at the same level as A reveals the high-signal tumor (curved arrow) with high signal within the vestibular membranous labyrinth (arrowhead), presumed to represent methemoglobin. (From Mark, et al: MRI of sensory neural hearing loss: More than the eye? AJNR 14:37–45, 1993, with permission.)

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LABYRINTHITIS The term labyrinthitis describes any inflammatory process of the membranous labyrinth. It is most often due to viruses26–28 such as rubella29 (Fig. 20-6), mumps30 (Fig. 20-7), herpes zoster,31 measles,32 or Lassa fever,33 but it may be secondary to pyogenic bacterial infections (Figs. 20-8 and 20-9) or syphilis34 (Fig. 20-10). The hallmark of labyrinthitis on MRI is demonstration of enhancement of the cochlea or vestibule on the postcontrast study.35 Labyrinthitis is the most frequent cause of labyrinthine enhancement. The intralabyrinthine fluid, mixed with gadolinium which leaked through the ruptured blood-labyrinth barrier, is only mildly hyperintense when the labyrinthitis is viral in origin. Bacterial labyrinthitis36 and especially labyrinthitis following pneumococcal labyrinthitis is often hemorrhagic and results very quickly in fibrous obliteration of the intralabyrinthine fluid spaces. In these patients high signal intensity can be seen in the labyrinth on the unenhanced T1-weighted images (when hemorrhagic), intralabyrinthine enhancement can be seen on the postcontrast study, and the high-signal-intensity intralabyrinthine fluid is replaced by fibrous tissue. Calcification can occur very quickly, even during the first 2 weeks following the infection, and can eventually lead to complete labyrinthitis ossificans. Calcified obliteration cannot be distinguished on MRI; only CT can identify the calcified areas. However, fibrous obliteration will remain unnoticed on CT. Therefore, MRI and CT are complementary in the study of patients with labyrinthitis. The detection of calcifications or fibrous obliteration inside the membranous labyrinth is, of course, essential in the preoperative assessment of cochlear implant candidates. As mentioned earlier, only a combined CT-MRI evaluation provides the surgeon with all the necessary information. Moreover, unlike CT, MRI is often capable of showing whether a single scala is still open and can be used for cochlear implantation.

Figure 20-5. Acute hemorrhagic viral labyrinthitis. Thirty-year-old woman with acute SNHL on the right and vertigo during the course of a viral illness. Axial unenhanced T1-weighted image reveals high signal intensity in the right cochlea and vestibule consistent with subacute hemorrhage. (Courtesy of Dr. D Schellinger, Washington, DC)

a region where the high signal intensity of the intralabyrinthine fluid is replaced by low-signal-intensity material. When a fracture is present, the loss of the high-signalintensity intralabyrinthine fluid can also be caused by leaking of the fluid into the middle ear cavity. The empty space inside the labyrinth is then very quickly obliterated by clot and fibrous tissue formation. A less well-known cause of labyrinthine hemorrhage and subsequent obliteration of the intralabyrinthine fluid spaces is surgery. Stapes surgery can result in intralabyrinthine bleeding. The drilling performed during middle or posterior fossa approach to treat acoustic schwannoma can also result in subtle intralabyrinthine bleeding (concussion) and can eventually cause complete obliteration of the intralabyrinthine fluid spaces.

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Figure 20-6. Rubella labyrinthitis. Axial (A) and coronal (B) contrast-enhanced images demonstrate enhancement of the membranous labyrinth and cochlea. The diagnosis was confirmed by serology.

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Figure 20-7. Mumps labyrinthitis. Young child with bilateral SNHL and vertigo 3 weeks following mumps orchitis. A, Axial T1-weighted postcontrast image demonstrates intense enhancement of the cochlea and membranous labyrinth. B, Late sequelae of measles labyrinthitis from another patient who had severe SNHL since age 4 years following measles infection. The study shows severe atrophy of the organ of Corti and endolymphatic hydrops. (From Schuknecht HF: Viral infection. In Schuknecht HF [ed.]: Pathology of the Ear, 2nd ed. Philadelphia, Lea and Febiger, 1993 pp 235–244, with permission.)

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Figure 20-8. Bacterial labyrinthitis. Middle-aged man with left middle ear infection, acute hearing loss, and facial nerve paralysis. Pre (A) and post (B) gadolinium-enhanced, axial T1-weighted images demonstrate enhancement of the left cochlea and vestibule endolymphatic sac and IAC. Note the cerebellar abscess. CT (C) demonstrates bony erosions in the temporal bone. (Courtesy of Dr. Jean Prere, Toulouse, France)

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Figure 20-9. Bacterial labyrinthitis. Middle-aged man with right middle ear infection, acute hearing loss, and facial nerve paralysis. Coronal gadolinium-enhanced, axial T1-weighted image demonstrates enhancement of the right cochlea and vestibule (arrow) consistent with extension of the infection to the labyrinth.

Bacterial labyrinthitis can result either from extension to the labyrinth of a middle ear infection (otogenic suppurative labyrinthitis), in which case the infection usually penetrates the labyrinth through the oval window, or after meningitis, in which case it is usually bilateral (meningococcal bacterial labyrinthitis). Otogenic suppurative labyrinthitis is characterized pathologically in the acute phase by a polymorphonuclear infiltrate in the perilymphatic space followed by a fine fibrillar precipitate and

endolymphatic hydrops. Necrosis of the membranous labyrinth and, if the patient survives, healing with new bone formation (labyrinthitis ossificans) develop in the later stages. In the preantibiotic era, syphilis37 was a major cause of SNHL. The disease could be acquired perinatally, resulting in congenital hearing loss, or in adult life. The pathology includes a meningoneurolabyrinthitis in the early stages of congenital syphilis and in the acute meningitides of the secondary and tertiary stage, and temporal bone osteitis in the late congenital forms and in tertiary syphilis. The chronic lesions are identical regardless of the acquisition mode and are characterized by endolymphatic hydrops and degeneration of the sensory and neural structures.38 Immune-mediated inner ear disease may be isolated or seen in the context of a systemic autoimmune disease. Primary autoimmune labyrinthitis is a relatively new cause of SNHL.39 The diagnosis is based on a positive lymphocyte transformation test to inner ear preparation and a positive response to steroid treatment. Systemic autoimmune disorders that may affect the inner ear include Cogan’s syndrome, polyarteritis nodosa,40 Wegner’s granulomatosis, and relapsing polychondritis. Cogan’s syndrome is an autoimmune disease characterized by interstitial keratitis and hearing loss in Venereal Disease Research Laboratory (VDRL)-negative patients. The disease responds to steroids. Enhancement of the cochlea and vestibule as well as obliteration of the membranous labyrinth has recently been reported in autoimmune labyrinthitis and in patients with Cogan’s syndrome41 (Fig. 20-11). Relapsing polychondritis is an autoimmune disease characterized by multiple episodes of cartilage inflammation, in particular,

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Figure 20-10. Syphilitic labyrinthitis. A 30-year-old man with decreased hearing and facial palsy on the right. A, Coronal T1-weighted, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced images. Enhancement of the right cochlea and of the right facial nerve (arrow). The left cochlea and facial nerve are normal. B, Congenital syphilis. Progressive bilateral hearing loss since age 18 years, progressing over 10 years. Extensive microgummata are noted in the pericochlear bone (arrowhead). A large gumma is noted in the internal auditory canal (IAC) in the place vacated by degenerated vestibular and cochlear nerves (arrow). There is marked endolymphatic hydrops (asterisks) and advanced atrophy of all structures in the IAC. (From Schuknecht HF: Infections of the inner ear. In Schuknecht HF [ed.]: Pathology of the Ear, 2nd ed. Philadelphia, Lea and Febiger, 1993, pp 247-253, with permission.)

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Figure 20-11. Cogan’s syndrome. A, Precontrast and, B, postcontrast axial T1-weighted images demonstrate enhancement of the right cochlea (arrow) and vestibule (arrowhead). C, A 0.7 mm high-resolution T2-weighted image demonstrates obliteration of the normal fluid in the cochlea and vestibule. D, HRCT demonstrates ossification in the basal turn of the cochlea. (From Casselman JW, Mojoor MHJM, Albers FW: MR of the inner ear in patients with Cogan syndrome. AJNR 15:131–136, 1994, with permission.)

of the earlobe. The condition may be associated with hearing loss and vertigo. We have recently demonstrated labyrinthine enhancement in this entity (Fig. 20-12). Finally, intralabyrinthine enhancement can also be seen in cases of tuberculosis and sarcoidosis, and can even occur after gamma-knife treatment in the vicinity of the labyrinth.

CONTRAST ENHANCEMENT OF THE LABYRINTH Study of the functional correlation between labyrinthine enhancement and objective and subjective cochlear and vestibular symptoms reveals that the enhancement is a highly specific finding of labyrinthine pathology.42 Indeed, all patients with enhancement of the cochlea or vestibule have cochlear or vestibular findings, both subjectively and objectively. Furthermore, these symptoms and signs are severe when the standard dose of contrast medium (0.1 mmol/kg) was used. We have recently used a triple-dose

contrast medium in the setting of only moderate SNHL. This study demonstrated marked enhancement of the cochlea and vestibule. Our anecdotal observation suggests that the use of higher doses may increase the sensitivity for such abnormalities. Thus, similar to enhancement in the meninges, there is a threshold effect (Fig. 20-13), with only the most severe inflammatory processes producing labyrinthine enhancement.43 The resolution of the enhancement may parallel resolution of the patient’s symptoms42 (Fig. 20-14), or, if the inflammatory process has resulted in permanent damage to the labyrinthine membrane, the enhancement may resolve but the patient’s symptoms persist indefinitely. Enhancement may also recur if the inflammatory process is reactivated, even in patients who have been deaf for years. In a subset of patients with SNHL, we have demonstrated segmental enhancement of different turns of the cochlea.44 In certain patients the level of enhancement correlates with the frequency range of the hearing loss; that is, enhancement of the basal turn of the cochlea results in

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Figure 20-12. Relapsing polychondritis. Thirty-year-old man with sudden SNHL and a history of recurrent pain and inflammation in the ear lobe. Axial (A) and coronal (B) postcontrast T1-weighted images demonstrate marked enhancement of the cochlea and vestibule and faint enhancement of the IAC.

high-frequency hearing loss (Fig. 20-15), and enhancement of the apical turn results in low-frequency hearing loss (Fig. 20-16). This correlation is not always present because certain patients with isolated enhancement of the basal turn will have complete hearing loss over all frequencies. The remarkable degree of correlation between highresolution-enhanced MRI and clinical examination in many cases should prompt further investigations using MRI in this highly specialized anatomic region.

PERILYMPHATIC FISTULA Perilymphatic fistula45 is a controversial condition defined as an abnormal communication between perilymph of the

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inner ear and the middle ear typically involving injury to the membranes of the oval window, round window, or both.46 This condition is one of the many causes of sudden hearing loss and vertigo. It is a difficult condition to diagnose even at surgery because the leakage of perilymph may be intermittent and such small amounts of fluid are involved that its direct observation may be difficult. The condition is associated with either direct trauma to the ear or barotrauma. Experimental studies in guinea pigs have shown that barotrauma can induce ruptures of the round window and oval window membranes and intralabyrinthine hemorrhage, which predominates in the basal turn of the cochlea,47 where the round window opens. We have seen three patients with perilymphatic fistulae suspected clinically or surgically proven in whom labyrinthine

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Figure 20-13. Selective enhancement of the cochlea. Viral labyrinthitis, 70-year-old woman with severe right-sided hearing loss and vertigo but only minimally abnormal electronystagmograph. A, T1-weighted, Gd-DTPA-enhanced image. Enhancement of the cochlea (solid arrow) but not the vestibule (open arrow) on the right side. No enhancement of the asymptomatic side. B, The enhancement and her symptoms resolved 6 months later. (From Seltzer S and Mark AS: Contrast enhancement of the labyrinth on MR scans in patients with sudden hearing loss and vertigo: Evidence of labyrinthine disease. AJNR 12:13–16, 1991, with permission.)

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Figure 20-14. Viral labyrinthitis. A, Abnormal cochlear and vestibular function right ear; initial study. T1-weighted, Gd-DTPA-enhanced image. Enhancement of the right cochlea (solid arrow) and vestibule (open arrow). No enhancement is seen on the contralateral side. B, One month after initial study, at which time the patient had some improvement in hearing and slight improvement on ENG testing. T1-weighted, Gd-DTPA-enhanced image. There is persistent labyrinthine enhancement. C, Five months after initial study, at which time the patient had marked improvement in hearing and resolution of vestibular symptoms. Axial T1-weighted, Gd-DTPA-enhanced image. The previously noted enhancement of the right cochlea and vestibule is no longer present. (From Seltzer S and Mark AS: Contrast enhancement of the labyrinth on MR scans in patients with sudden hearing loss and vertigo: Evidence of labyrinthine disease. AJNR 12:13–16, 1991, with permission.)

C enhancement was present (Fig. 20-17). As suggested in the experimental studies, the enhancement predominated in the basal turn of the cochlea but was also seen in the vestibule in some patients. Some of these patients improved following surgical patching of the oval window.

LABYRINTHINE NEOPLASMS Labyrinthine Schwannomas Labyrinthine schwannomas48 are the most common benign neoplasms of the labyrinth.49 They are histologically identical to their counterparts in the IAC. Isolated intralabyrinthine schwannomas are reported to be more common in the cochlea (Fig. 20-18) (based on the European experience), but in our experience they are more common in the vestibule.50 In patients with neurofibromatosis they are more frequent in the vestibular system. Schwannomas in the vestibule originate in the fibers of the vestibular nerves. Branches of these nerves reach the ampullae of the semicircular canals (superior vestibular nerve reaches the superior and lateral semicircular canal, the inferior vestibular nerve reaches the posterior semicircular canal), and therefore larger schwannomas will eventually grow into these ampullae. Labyrinthine schwannomas can present with SNHL or vertigo (or both)

and be clinically indistinguishable from Ménière’s disease.51 In fact, in the past these lesions were mostly diagnosed during destructive labyrinthectomy for intractable “Ménière’s disease.” In the past, the diagnosis on CT could be made only in the later stages when bony expansion of the cochlea or vestibule had occurred. Now these lesions can be easily diagnosed using contrast-enhanced MRI,52 which demonstrates a markedly enhancing mass in the cochlea (Fig. 2019) or vestibule (Fig. 20-20). The major differential diagnosis of labyrinthine schwannoma is labyrinthitis. Schwannomas usually enhance much more intensely, the enhancement persists over many months, and the lesions may expand, contrary to labyrinthitis, where the enhancement resolves over several months with or without resolution of the patient’s symptoms. In patients with labyrinthine schwannomas, the highsignal-intensity intralabyrinthine fluid is replaced by the hypointense tumor on the submillimetric T2-weighted spin-echo or gradient-echo images. On these very detailed images it is sometimes even possible to depict in which scala the schwannoma is located. On the contrary, the fluid retains its high signal intensity in the early stages of labyrinthitis. T2-weighted images are important, especially since two nonenhancing intralabyrinthine schwannomas have been recently reported.53 Schwannomas also have slightly higher signal intensity than the surrounding

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Figure 20-15. Selective enhancement of the basal turn of the cochlea. A 35-year-old woman with left-sided high-frequency hearing loss. Precontrast (A), and postcontrast, gadolinium-enhanced (B) axial T1-weighted images demonstrate enhancement of the basal turn (b) of the cochlea and vestibule (c). Notice also the enhancement of the endolymphatic sac bilaterally (a). Postcontrast, gadolinium-enhanced, consecutive coronal T1-weighted images (C, D). Notice enhancement of the basal turn but not of the apical turn of the left cochlea, correlating with the patient’s high-frequency hearing loss. (From Mark AS and Fitzgerald D: Segmental enhancement of different turns of the cochlea on Gd-enhanced MRI: Correlation with frequency of hearing loss and possible sign of perilymphatic fistula. AJNR 14:991–996, 1993, with permission.)

intralabyrinthine fluid on the unenhanced T1-weighted images. This is another sign that can be used to differentiate intralabyrinthine schwannomas from labyrinthitis. Moreover, in patients with intralabyrinthine schwannomas most frequently only one compartment (cochlea or vestibule/ semicircular canals) is involved, whereas in labyrinthitis both compartments are more frequently involved. Patients with labyrinthine schwannomas have stable or progressively worsening symptoms. Vestibular schwannomas may be associated with intracanalicular and cerebellopontine angle schwannomas in patients with neurofibromatosis (Fig. 20-21).

Other Tumors Involving the Labyrinth Malignant neoplasms of the cochlea are exceptional. Squamous cell carcinoma or adenoid cystic carcinoma in

the adult or rhabdomyosarcoma of the temporal bone in the child may extend into the labyrinth. Metastasis may extend perineurally along the cochlear nerve and penetrate the cochlea (Figs. 20-22 and 20-23). Endolymphatic sac tumors (ELSTs) are rare, low-grade malignant neoplasms of the temporal bone, which may be hemorrhagic54 and invade the vestibule and cochlea. Isolated reports suggest a possible association between ELSTs, which are extremely rare in the general population, and von Hippel-Lindau disease (VHL). In a recent large series, MRI revealed evidence of 15 ELSTs in 13 (11%) of 121 patients with VHL, but in none of the 253 patients without evidence of VHL.55 Middle ear cholesteatomas in the later stages may also invade the inner ear (Fig. 20-24), but the patient’s history and the CT findings are usually obvious. Other lesions growing or invading the membranous labyrinth include lipomas, histiocytosis X,56 cholesterol granulomas, granulation tissue, and pachymeningitis, among

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Figure 20-16. Forty-year-old man with low-frequency SNHL on the right. A, Axial, precontrast, T1-weighted image is normal. B, Postcontrast, axial, T1-weighted image demonstrates a small focus of enhancement in the apical turn of the cochlea (arrow). C, Coronal, postcontrast, T1-weighted image through the anterior aspect of the cochlea demonstrates enhancement of the right apical turn of the cochlea (arrowhead) and normal apical turn of the left cochlea (open arrow). D, Coronal, postcontrast, T1-weighted image through the basal aspect of the cochlea is normal. (From Mark AS, Fitzgerald D: Segmental enhancement of different turns of the cochlea on Gd-enhanced MRI: Correlation with the frequency of hearing loss and a possible sign of perilymphatic fistula. AJNR 14:991–996, 1993, with permission.)

others. Once these lesions invade the labyrinth, most of them will cause intralabyrinthine enhancement, visible on the postcontrast T1-weighted images. Only lipomas and cholesterol granulomas will not enhance and have spontaneous hyperintensities on the unenhanced T1-weighted images. All the previously mentioned lesions cause loss of highsignal-intensity intralabyrinthine fluid on the T2-weighted gradient-echo or fast spin-echo images.

POSTOPERATIVE CHANGES

Figure 20-17. Perilymphatic fistula. Thirty-year-old man with sudden SNHL after lifting heavy weights at the gym. Coronal, postcontrast, T1-weighted image demonstrates enhancement of the cochlea (arrow). The patient’s symptoms improved following surgical patching of the oval window.

Enhancement of the vestibule may be seen in patients who have undergone destructive vestibulectomies for incurable Ménière’s disease. In this case, an enhancing “mass” may be seen in the vestibule communicating with the mastoid. Clinical correlation is necessary not to confuse this finding with extension of middle ear infection into the vestibule. Postoperative enhancement of the labyrinth may also be seen in patients who have undergone surgery

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Figure 20-18. Presumed left cochlear schwannoma. Fifty-year-old man with slowly progressive high-frequency SNHL. A, Axial T1-weighted image demonstrates a 1-mm enhancing mass in the basal turn of the cochlea (arrowhead). The lesion remained unchanged over 3 years while the patient’s symptoms slowly progressed. B, Coronal, three-dimensional, T2-weighted images demonstrate a filling defect matching the enhancing lesion. C, Pathologic specimen from another patient demonstrates a 1-mm intracochlear schwannoma. (Courtesy of Dr. H Schuknecht, Boston, MA.)

Figure 20-19. Left cochlear schwannoma. Axial T1-weighted (A) precontrast and (B) postcontrast images demonstrate an enhancing lesion filling the left cochlea. C, Pathologic specimen from another patient demonstrates an intracochlear schwannoma. (Courtesy of Dr. H Schuknecht, Boston, MA.)

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Figure 20-21. Twenty-three-year-old man with neurofibromatosis type II. A, Temporal bone specimen. Simultaneous schwannoma in the right IAC and a 2 × 2.5-mm vestibular schwannoma is present between the footplate of the stapes and the lateral wall of the saccule. (Courtesy of HF Schuknecht, Boston, MA.) B, Presumed left vestibular schwannoma (short arrow) and intracanalicular schwannoma (long arrow) in another patient with left-sided SNHL and vertigo and no history of neurofibromatosis type II. (Courtesy of D Brown, Washington, DC.)

C Figure 20-20. Right vestibular schwannoma in a patient with a 1-year history of vertigo and hearing loss. A, Axial and, B, coronal T1-weighted images show globular enhancement of the right vestibule (arrow). The long-standing history and the focal enhancement suggest schwannoma rather than labyrinthitis. C, Pathologic specimen from another patient demonstrates an intravestibular schwannoma. (Courtesy of Dr. H Schuknecht, Boston, MA.)

in the IAC or cerebellopontine angle cistern for acoustic schwannomas or meningiomas. The enhancement is not usually clinically relevant because these patients have lost their hearing from their original tumor or the surgery. However, this finding may be significant in a patient with a small intracanalicular tumor in whom a hearing-sparing procedure was attempted, that is, “chemical labyrinthitis” from perioperative extension of hemorrhage from the IAC into the cochlea or vestibule. This finding, rather than direct injury to the cochlear nerve at the time of surgery, may explain some of the surgical failures in these cases. Membranous labyrinth fibrosis may also occur when surgery is performed in the vicinity of the membranous labyrinth. Postoperative intralabyrinthine hemorrhage in case of stapes surgery or surgery in the region of the

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Figure 20-22. Metastasis to the IAC and cochlea. Middle-aged woman with transient facial palsy 6 months prior to the scan interpreted clinically as Bell’s palsy. Now has new facial palsy and hearing loss. A, CT shows an enlarged acoustic canal. B,T1-weighted image with contrast confirms an intracanalicular mass extending into the cochlea.

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Figure 20-23. Metastatic lung carcinoma to the left IAC and left cochlea. A, Axial, T1-weighted precontrast and B, postcontrast images demonstrate an enhancing mass filling the left IAC and extending into the left cochlea (arrow), consistent with leptomeningeal tumor spread extending into the patient’s cochlea. C, Coronal image shows the associated parenchymal metastasis. (Courtesy of Dr. C Truwit, Minneapolis, Minn.) D, Metastatic adenocarcinoma of the breast in a 75-year-old patient who presented with acute hearing loss and facial palsy. (Courtesy of Dr. H Schuknecht, Boston, MA.)

Imaging of the Labyrinth

Figure 20-24. Cholesteatoma fistulizing into the labyrinth. Coronal, postcontrast, T1-weighted image demonstrates a nonenhancing mass in the middle ear with a peripheral rim of enhancement. Notice enhancement of the labyrinth.

geniculate ganglion of the facial nerve can also result in subsequent complete obliteration of the intralabyrinthine fluid spaces. This can also explain occasional poor postsurgical results in some patients.

ENDOLYMPHATIC HYDROPS Endolymphatic hydrops57 is defined pathologically as dilatation of the endolymphatic spaces. Extensive experimental evidence suggests that endolymphatic hydrops is the result of a functional failure of the endolymphatic sac to resorb the endolymph,58 resulting in dilatation of the endolymphatic spaces with or without rupture of Reissner’s membrane and communication of the endolymph and the perilymph. Schuknecht and Gulya59 classified endolymphatic hydrops in congenital, acquired, and idiopathic forms. Any congenital malformation can result ultimately in endolymphatic hydrops. Among the best known is the large vestibular aqueduct syndrome, in which a markedly dilated endolymphatic sac and vestibular aqueduct are associated with other inner ear malformations and congenital SNHL and vertigo. Any of the inflammatory or traumatic lesions mentioned earlier may have labyrinthine hydrops as the end result. Among the idiopathic forms of labyrinthine hydrops, Ménière’s disease is the best known. This condition is clinically characterized by fluctuating SNHL with or without vertigo and tinnitus. It is most often unilateral and, when bilateral, it is usually asynchronous. Ample laboratory evidence suggest that Ménière’s disease is caused by a functional failure of the endolymphatic sac to resorb the endolymph. Electromicroscopy study of biopsies of the endolymphatic sac60,61 in patients with Ménière’s have revealed a wide spectrum of findings from a near normal sac to an inflammatory reaction to fibrosis and complete atrophy and obliteration of the endolymphatic sac. This spectrum of histologic findings explains the great heterogeneity of the clinical findings in these patients from mild forms with occasional episodes of vertigo to severe

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vertigo and hearing loss and intractable vertiginous symptoms requiring hospitalization. The clinicopathologic correlation is complicated further by the discovery of labyrinthine hydrops at autopsy in patients with no reported symptoms of vertigo during their lifetime. The concept of Ménière’s disease being the consequence of a viral infection with a predilection for the endolymphatic sac is appealing in the sense that it may explain both the histologic findings and the patient’s clinical symptoms. Until recently, imaging of patients with Ménière’s disease has been disappointing.62 CT and MRI were primarily used to exclude other conditions such as acoustic neuroma, which may mimic Ménière’s disease. The endolymphatic sac can be seen on HRCT63,64 and MRI, and there is a statistically lower rate of visualization of the vestibular aqueduct and endolymphatic sac in patients with Ménière’s disease than in asymptomatic controls.65–67 We recently encountered a series of patients with symptoms compatible with Ménière’s disease in whom MRI demonstrated enhancement of the endolymphatic sac68 (Fig. 20-25). Similar to enhancement of the cochlea and vestibule, enhancement of the endolymphatic sac is consistent with an inflammatory process in this location,69 such as a viral infection,70 and may correlate with the acute stage of the disease. It is possible that in later stages the enhancement resolves and the fibrotic sac may not be seen at all on MRI in the later stages of the disease. Direct visualization of Reissner’s membrane on ultrahigh-field MRI (above 2T) is a hopeful new development that should allow direct diagnosis of endolymphatic hydrops in the future.71 Otosclerosis is a condition of unknown origin in which the normal endochondral bone is replaced by foci of spongy, vascular, irregular new bone that is less dense.72 These spongy decalcified foci in the later stages become less vascular and more solid. The condition is bilateral in most patients and often symmetrical. There is a 2-to-1 female predominance, and the disease usually appears in the second or third decade of life. Otosclerosis is classified into two major clinical categories. The fenestral type of otosclerosis involves the lateral wall of the labyrinth, including the promontory, facial nerve canal, and both the oval and round window niche. The involvement of the oval window results in fixation of the footplate of the stapes and conductive hearing loss. Retrofenestral otosclerosis occurs when the process of demineralization involves the otic capsule itself. These changes in the bone may affect the spiral ligament at the surface of the membranous labyrinth and result in SNHL; thus, a patient with otosclerosis may have a combined conductive and sensorineural hearing loss depending on the relative distribution and severity of the disease. CT is the imaging modality of choice for diagnosing otosclerosis.73 Depending on the location of the foci of demineralization along the cochlea, specific frequency ranges may be affected more than others.74 The lesions visualized on CT can sometimes be seen as enhancing lesions on MRI35 (Fig. 20-26). This finding probably reflects the leakage of gadolinium in the highly vascular spongiotic bone during the early stages of the disease. In the later stages of the disease, when the spongiotic bone is replaced by dense bone, the enhancement disappears.

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Figure 20-25. Probable Ménière’s disease. Fifty-year-old woman with sudden onset SNHL and vertigo. Hearing improved after 4 days. The patient had a similar episode 5 years earlier. A, Axial, T1-weighted, precontrast MRI is normal. B, Axial, enhanced fat-saturated, T1-weighted MRI reveals enhancement of the left endolymphatic sac.

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Figure 20-26. Cochlear otosclerosis: Enhanced axial (A) and coronal (B) T1-weighted images of the left temporal bone in a patient with the clinical and CT diagnosis of cochlear otosclerosis shows foci of enhancement within the bony labyrinth surrounding the cochlea. CT (C) shows the typical findings of otosclerosis. Pathologic specimen (D) shows a focus of otosclerosis anterior to the oval window. (From Schuknecht HF: Hemolabyrinth. In Schukenecht HF [ed.]: Pathology of the Ear, 2nd ed. Philadelphia, Lea and Febiger, 1993, pp 303–306, (with permission.)

Imaging of the Labyrinth

Paget’s disease and osteopetrosis are best evaluated with CT, and MRI has little to add. However, in patients with fibrous dysplasia, MRI may be helpful.75 Enlarged dense bone with a “ground glass” appearance is seen in fibrous dysplasia, and the bony changes can narrow the IAC or can encase the aqueducts or membranous labyrinth. The bone abnormalities in fibrous dysplasia vary considerably,76 but high signal intensity on T2-weighted spin-echo images and precontrast T1-weighted images and strong enhancement on the postcontrast images (isointense or hyperintense compared with fat) indicate active or progressive fibrous dysplasia.

CONCLUSION The availability of intravenous contrast agents sensitive to the disruption of the blood-brain and blood-labyrinth barriers coupled with high-resolution imaging have significantly expanded the potential role of MRI in the evaluation of the membranous labyrinth. Although many of the findings described in this chapter are still of uncertain significance in terms of patient management, the potential for insight into the natural history and pathophysiology of many of these poorly understood disease processes is clear.

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14. Davidson HC, Harnsberger HR, Lemmerling MM, et al: MR evaluation of vestibulocochlear anomalies associated with large endolymphatic duct and sac. Am J Neuroradiol 20:1435–1441, 1999. 15. Jackler RK, Luxford WM, House WF: Congenital malformations of the inner ear: A classification based on embryogenesis. Laryngoscope 97:2–14, 1987. 16. Casselman JW, Kuhweide R, Ampe W, et al: Inner ear malformations in patients with sensorineural hearing loss: detection with gradient-echo (3DFT-CISS) MR imaging. Neuroradiology 38:278–286, 1996. 17. Phelps PD, Reardon W, Pembrey M: X-linked deafness, stapes gushers and a distinctive defect of the inner ear. Neuroradiology 33:326–330, 1991. 18. Schuknecht HF: Hemolabyrinth. In Schuknecht HF (ed.): Pathology of the Ear, 2nd ed. Philadelphia, Lea and Febiger, 1993 pp 303–306. 19. Kumar A, Maudelonde C, Mafee M: Unilateral sensorineural hearing loss: Analysis of 200 consecutive cases. Laryngoscope 96:14–18, 1986. 20. Sando I, Egami T: Inner ear hemorrhage and endolymphatic hydrops in a leukemic patient with sudden hearing loss. Ann Otol Rhinol Laryngol 86:518–524, 1977. 21. Ouallet JC, Marsot-Dupuch K, Van Effenterre R, et al: Papillary adenoma of endolymphatic sac origin: A temporal bone tumor in von Hippel-Lindau disease. Case report. J Neurosurg 87(3):445–449, 1997. 22. Mark AS: Vestibulocochlear system. Neuroimag Clin North Am 3:153–170, 1993. 23. Swartz JD, Swartz NG, Korsvik H, et al: Computerized tomographic evaluation of the middle ear and mastoid for post traumatic hearing loss. Ann Otol Rhinol Laryngol 94:263–266, 1985. 24. Zimmerman RA, Bilaniuk LT, Hackney DB, et al: Magnetic resonance imaging in temporal bone fracture. Neuroradiology 29:246–251, 1987. 25. Weissman JL, Curtin HD, Hirsch BE, Hirsch WL Jr: High signal from the otic labyrinth on unenhanced magnetic resonance imaging. AJNR 13:1183–1187, 1992. 26. Schuknecht HF: Viral infections. In: Schuknecht HF, ed. Pathology of the Ear, 2nd ed. Philadelphia, Lea and Febiger, 1993, pp 235–244. 27. Massab HF: The role of viruses in sudden deafness. Adv Otorhinolaryngol 20:229–235, 1970. 28. Nomura Y, Hiraide F: Sudden deafness: A histopathological study. J Laryngol Otol 90:1121–1142, 1976. 29. Hemenway WG, Sando I, Mochesnay D: Temporal bone pathology following maternal rubella. Arch Klin Exp Ohren-NosenKehlkopfheiekol 193:287–300, 1969. 30. Westmore GA, Pickard BH, Stern H: Isolation of mumps virus from the inner ear after sudden deafness. BMJ 1:14–15, 1977. 31. Blackley B, Friedmann I, Wright I. Herpes zoster auris associated with facial nerve paralysis and auditory nerve symptoms. Acta Otolaryngol (Stockh) 63:533–550, 1967. 32. Lindsay JR, Hemenway W: Inner ear pathology due to measles. Ann Otol Rhinol Laryngol 63:754–771, 1954. 33. Liao BS, Byl FM, Adour KK: Audiometric comparison of Lassa fever hearing loss and idiopathic sudden hearing loss: evidence for viral cause. Otolaryngol Head Neck Surg 106:226–229, 1992. 34. Hendershot E: Luetic deafness. Otolaryngol Clin N Am 11:43–47, 1978. 35. Mark AS, Seltzer S, Harnsberger HR: MRI of sensory neural hearing loss: more than meets the eye? AJNR 14:37–45, 1993. 36. Schachern PA, Paparella MM, Hybertson R, et al: Bacterial labyrinthitis, meningitis, and sensorineural damage. Arch Otolaryngol Head Neck Surg 118:53–57, 1992. 37. Cole RR, Jahrsdoerfer RA. Sudden hearing loss: an update. Am J Otol 9(3):211–215, 1988. 38. Schuknecht HF: Infections of the inner ear. In: Schuknecht HF (ed.): Pathology of the Ear, 2nd ed. Philadelphia, Lea and Febiger, 1993, pp 247–253.

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39. McCabe BF: Autoimmune sensorineural hearing loss. Ann Otol 88:585–589, 1979. 40. Schuknecht HF: Disorders of the immune system. In Schuknecht HF (ed.): Pathology of the Ear, 2nd ed. Philadelphia, Lea and Febiger, 1993, pp 345–363. 41. Casselman JW, Mojoor MHJM, Albers FW: MR of the inner ear in patients with Cogan syndrome. AJNR 15:131–136, 1994. 42. Mark AS, Seltzer S, Nelson-Drake J, et al: Labyrinthine enhancement on GD-MRI inpatients with sudden hearing loss and vertigo: Correlation with audiologic and electronystagmographic studies. Ann Otol Rhinol Laryngol 101:459–464, 1992. 43. Seltzer S, Mark AS: Contrast enhancement of the labyrinth on MR scans in patients with sudden hearing loss and vertigo: Evidence of labyrinthine disease. AJNR 12:13–16, 1991. 44. Mark AS, Fitzgerald D: Segmental Enhancement of different turns of the cochlea on Gd-enhanced MRI: Correlation with the frequency of hearing loss and a possible sign of perilymphatic fistula. AJNR 14:991–996, 1993. 45. Althaus SR: Perilymph fistulas. Laryngoscope 91:538–556, 1981. 46. Gussen R: Sudden deafness associated with bilateral Reissner’s membrane ruptures. Am J Otolaryngol 9:27–32, 1983. 47. Nakoshima T, ltoh M, Sato M, et al: Auditory and vestibular disorders due to barotrauma. Ann Otol Rhinol Laryngol 97:146–152, 1988. 48. Babin RW, Harker LA: Intralabyrinthine acoustic neurinomas. Otolaryngol Head Neck Surg 88:455–461, 1980. 49. DeLozier HL, Gacek RR, Dana ST: Intralabyrinthine schwannoma. Ann Otol 88:187–191, 1979. 50. Fitzgerald DC, Grundfast KM, Hecht DA, Mark AS: Intralabyrinthine schwannomas. Am J Otol 20(3):381–385, 1999. 51. Green JD Jr, McKenzie JD: Diagnosis and management of intralabyrinthine schwannomas. Laryngoscope 109(10):1626–1631, 1999. 52. Mafee MF, Lachenauer CS, Kumar A, et al: CT and MR imaging of Intralabyrinthine schwannoma: report of two cases and review of the literature. Radiology 1990;174:395–400, 1999. 53. Zbar RI, Megerian CA, Khan A, Rubinstein JT: Invisible culprit: Intralabyrinthine schwannomas that do not appear on enhanced magnetic resonance imaging. Ann Otol Rhinol Laryngol 106(9):739–742, 1997. 54. Mukherji SK, Albernaz VS, Lo WW, et al: Papillary endolymphatic sac tumors: CT, MR imaging, and angiographic findings in 20 patients. Radiology 202(3):801–808, 1997. 55. Manski TJ, Heffner DK, Glenn GM, et al: Endolymphatic sac tumors. A source of morbid hearing loss in von Hippel-Lindau disease. JAMA 277(18):1461–1466, 1997. 56. Claros P, Claros A Jr, Claros A, Gilea I: Labyrinth involvement in Langerhan’s cell histiocytosis. Acta Otorhinolaryngol Esp 50(7): 549–552, 1999. 57. Schuknecht HF: Pathophysiology of endolymphatic hydrops. Arch Oto-Rhino-Laryngol 212:253–262, 1976.

58. Lundquist PG: Aspects on endolymphatic sac morphology and function. Arch Oto-Rhino-Laryngol 212:231–240, 1976. 59. Schuknecht HF, Gulya AJ: Endolymphatic hydrops-an overview and classification. Ann Otol Rhinol Laryngol 106 (Suppl):1–20, 1983. 60. Shea TT: Surgery of the endolymphatic sac. Otolaryngol Clin North Am 1:613–621, 1968. 61. Arenberg IK, Marovitz WF, Shambaugh GE Jr: The role of the endolymphatic sac in the pathogenesis of endolymphatic hydrops in man. Acta Oto-Laryngol 275(Suppl):1–49, 1970. 62. Clemis JD, Valvassori GE: Recent radiographic and clinical observations on the vestibular aqueduct. Otolaryngol Clin North Am 1:339–346, 1968. 63. Hall SF, O’Connor AF, Thakkar CH, et al: Significance of tomography in Ménière’s disease: visualization and morphology of the vestibular aqueduct. Laryngoscope 93:1546–1550, 1983. 64. Valvassori GE, Dobben GD: Multidirectional and computerized tomography of the vestibular aqueduct in Ménière’s disease. Ann Otol Rhinol Laryngol 93:547–550, 1984. 65. Xenellis J, Vlahos L, Papadopoulos A, et al: Role of the new imaging modalities in the investigation of Ménière’s disease. Otolaryngol Head Neck Surg 123(1):114–119, 2000. 66. Schmalbrock P, Dailiana T, Chakeres DW, et al: Submillimeterresolution MR of the endolymphatic sac in healthy subjects and patients with Ménière’s disease. AJNR 17(9):1707–1716, 1996. 67. Tanioka H, Kaga H, Zusho H, et al: MR of the endolymphatic duct and sac: Findings in Meniere disease. AJNR 18(1):45–51, 1997. 68. Fitzgerald DC, Mark AS: Endolymphatic duct/sac enhancement on gadolinium magnetic resonance imaging of the inner ear: Preliminary observations and case reports. Am J Otol 17(4):603–606, 1996. 69. Tomiyama S, Harris JP: The endolymphatic sac: Its importance in inner ear immune responses. Laryngoscope 96:685–691, 1986. 70. Arenberg IK, Lemke C, Shambaugh GE Jr: Viral theory for Ménière’s disease and endolymphatic hydrops: Overview and new therapeutic options for viral labyrinthitis. Ann N Y Acad Sci 830:306–313, 1997. 71. Koizuka I, Seo R, Kubo T, et al: High-resolution MRI of the human cochlea. Acta Otolaryngol Suppl 520 Pt 2:256–257, 1995. 72. Wiet RJ, Rasian W, Shambugh GE: Otosclerosis 1981 to 1985, our four year review and current perspective. Am J Otol 7:221–228, 1986. 73. Blakley BW, Hilger PA, Taylor S, Hilger J: Computed tomography in the diagnosis of cochlear otosclerosis. Otolaryngol Head Neck Surg 94:434–438, 1986. 74. Swartz JD, Mandell DW, Berman SE, et al: Cochlear otosclerosis (otospongiosis): CT analysis with audiometric correlation. Radiology 155:147–150, 1985. 75. Moreau S, Bourdon N, Goullet de Rugy M, et al: Temporal fibrous dysplasia with labyrinthine involvement. Apropos of a case and review of the literature. Ann Otolaryngol Chir Cervicofac 114(4):140–143, 1997. 76. Casselman JW, De Jonge I, Neyt L, et al: MRI in craniofacial fibrous dysplasia. Neuroradiology 35:234–237, 1993.

21

Outline Technical Considerations Classifications and Incidence of Cerebellopontine Angle Tumors Vestibular Schwannoma Meningioma and Simulants Epidermoid and Other Cysts

Chapter

Imaging of the Cerebellopontine Angle

Nonvestibular Posterior Fossa Schwannomas Vascular Lesions Extradural Lesions Intra-axial Tumors Intracanalicular Lesions Conclusion

TECHNICAL CONSIDERATIONS Modern imaging techniques for the cerebellopontine angle (CPA) and internal auditory canal (IAC) consist principally of magnetic resonance imaging (MRI) and computed tomography (CT). Angiography is occasionally employed when evaluating vascular lesions.1 Because of its superior soft tissue contrast, multiplanar capability, and lack of ionizing radiation, MRI holds a substantial advantage over CT in imaging the CPA.2 Furthermore, with paramagnetic contrast enhancement, MRI has become the unquestioned method of choice for visualization of small acoustic tumors.3 The frequent untoward reactions to intravenous (IV) iodinated contrast material for CT are obviated. Furthermore, recently developed heavily T2-weighted, submillimeter thinsection, spin-echo or gradient-echo images exquisitely outline cisternal nerves and vessels better than gas CTcisternography, and the otic labyrinth as well as or better than high-resolution CT.4–7 This chapter therefore focuses primarily on MRI. CT remains useful in special situations, for example, when MRI is not available, when patients are too claustrophobic or too large to be accommodated in the scanner, when visualization of calcium or bone changes is important,8 or when acute hemorrhage is in question.9,10 Although a detailed discussion of the technical aspects of MRI is beyond the scope of this chapter, a general understanding of the capabilities and limitation of the technique will greatly assist the clinician in effectively using MRI for investigation of the CPA or the IAC. Although not all CPA symptoms are caused by tumors, the principal concern raised is usually the presence or absence of a tumor. Because most of the tumors in the CPA are intradural extra-axial (outside the brain) and partly outlined by cerebrospinal fluid (CSF) and because T2-weighted images (T2WI) superbly outline nerves and

William W. M. Lo, MD Michael M. Hovsepian, MD

brain tissue against CSF, noncontrast, heavily T2-weighted, submillimeter thin-section images have been recommended for low-cost screening for acoustic tumors.11 Such images may be obtained by fast spin-echo (FSE) or by gradient-echo technique (constructive interference steady state, or CISS). Normal structures as demonstrated by CISS images are illustrated in Figure 21-1.4–7 However, gadolinium chelates as paramagnetic contrast agents administered intravenously, markedly enhance the signal intensity of most tumors, as well as inflammatory lesions on T1WI, and aid in characterization and differential diagnosis of lesions. Thus, contrast-enhanced T1WI is nearly always used for detection or evaluation of CPA and IAC tumors, in a comprehensive study.3,12–15 Normal T1WI are illustrated in Figure 21-2.16,17 Although T2WI add little to the detection of extra-axial tumors, they are useful in assisting characterization of tumors (e.g., in meningioma, lipoma, peritumoral cysts, peritumoral edema, hemorrhage, etc.). They are also more sensitive than T1WI for detection of intra-axial lesions (inside the brain) that can produce acoustic symptoms, such as occur in multiple sclerosis, infarct, and edema, as well as in hemosiderin deposition in superficial siderosis.18 Thus, a comprehensive study of the CPA would typically include T1WI in thin sections through the posterior fossa and IAC before and after the administration of gadolinium chelates, and T2WI in thicker sections to survey the brain. Under some circumstances, modified or additional techniques may be employed. For example, in neurofibromatosis 2 (NF2),19,20 in which multiple intracranial schwannomas and meningiomas, and spinal schwannomas, meningiomas, and ependymomas are often present, postcontrast T1-weighted surveys that include the entire head and spine may be desirable.19,21–22 When vascular lesions such as aneurysm, arteriovenous malformation (AVM), or vertebrobasilar dolichoectasia (VBD) are encountered or 349

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C

4

V

P

1 5

C sc

a

v

L

P IV

3 sc

F 2

B IV

A

B P

C sc

mp C v

IV

a IAC ce

P

C

ce

D

Figure 21-1. Normal structures in IAC on CISS images (A-C). A, CISS axial 0.8 mm through the superior aspect of the IAC demonstrating the parallel course of the facial nerve (1) anterior to the superior vestibular nerve (3). B, inferior aspect of the IAC where the divergent relationship or Y-shaped configuration of the cochlear nerve (4) anterior to the inferior vestibular nerve (5) is depicted. C, a prominent AICA loop is seen within the proximal IAC. D, T2W axial FSE 5.5 mm of posterior fossa. 1, facial nerve; 2, vestibulocochlear nerve; 3, superior vestibular nerve; 4, cochlear nerve; 5, inferior vestibular nerve; IV, fourth ventricle; a, AICA; B, basilar artery; C, cochlea; ce, cerebellar hemisphere; F, flocculus; L, lateral recess of the fourth ventricle; mp, middle cerebellar peduncle; P, pons; sc, semicircular canals; v, vestibule.

suspected, MR angiography may be added (Fig. 21-3).23 When confirmation of lipoma or fat, including operatively placed fat, is desired, a fat suppression technique may be invoked.24 Obviously, the desire for completeness and quality must be balanced against the constraints of time, cost, throughput, and patient tolerance. For practical purposes, a comprehensive study probably should not exceed half an hour per patient. A noncontrast, heavily T2-weighted, thin-section survey specifically used for screening for acoustic tumors may be accomplished in less than 15 minutes at considerably lower cost. Such a study, however, carries the disadvantage of not being able to differentiate lipomas or melanotic melanoma,25 which are hyperintense on preconstrast T1WI, from schwannomas, which are

isointense or mildly hypointense on precontrast images. Furthermore, multiple sclerosis (Fig. 21-4) or superficial siderosis (Fig. 21-5) may be completely missed, should either be present. A fat-suppressed postcontrast sequence is generally necessary for evaluation of postoperative recurrence.3 A precontrast T1-weighted sequence is necessary for evaluation of paragangliomas, which may become nearly isointense with bone marrow on postcontrast images (Fig. 21-6). Thus, each institution or facility must devise protocols best suited to its own needs or practice and adapt to new technical developments that emerge. Our current protocol is offered as an example in Table 21-1. Although one study showed that 5-mm sections compared favorably with 3-mm sections in detection of

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A

C

351

B

D

Figure 21-2. Normal structures in CPA. (A–H), Postcontrast T1WI (Gd-T1WI) overlapping 3-mm sections centered every 1.8 mm. A, Midpons. Dominant structure is pons itself (P) surrounded by prepontine cistern anteriorly, CPA cisterns bilaterally, and fourth ventricle (IV ) posteriorly, and connected to cerebellar hemispheres (CH) posterolaterally by middle cerebellar peduncles (mp). Trigeminal nerves traverse CPA cistern to enter Meckel cave (mc in B–E) inferior to attachment of tentorium cerebelli (TC). Basilar artery (B) ascends anterior to pons. B, Mid-lower pons. Contrast-enhanced choroid plexus (ch) is seen on roof of fourth ventricle (IV). Lateral recess (I) of the fourth ventricle leads toward foramen Luschka (black arrow in D). Meckel cave (mc) filled with CSF lies adjacent to contrast-enhanced cavernous sinus (CS). C, Lower pons. Facial (7) and acoustic (8) nerves traverse cistern toward IAC in close relationship to loop of anterior inferior cerebellar artery (a). Cochlear nuclei are located immediately anterior to lateral recess (I). Rostral ends of cerebellar tonsils (t) are seen flanking caudal end of inferior vermis (vr). Inferior petrosal sinus (IP) communicates with cavernous sinus (CS). Petrous apex (pa) is filled with hyperintense fatty marrow. D and E, Pontomedullary junction. Belly of pons (P) extends far anteriorly beyond medulla (M). Posterior to medulla is foramen of Majendie (white arrow) opening to vallecula (long white arrow) between the tonsils (t). Lateral recess is flanked by inferior cerebellar peduncle (ip) anteriorly and contrast-enhanced choroid plexus (ch) posteriorly. The latter protrudes into CPA cistern through foramen of Luschka (short black arrow) posterior to acoustic nerve (8) and inferior to flocculus (f in C). Continued

acoustic tumors,26 most facilities use the thinnest sections practicable for imaging of the IAC whenever permitted by the capability of their equipment, most commonly 2- to 3-mm sections,3,27 because intracanalicular tumors are often only a few millimeters in diameter and may be suboptimally visualized or even obscured by partial volume effect in thicker sections. The interslice gap also differs, from varying degrees of overlap up to perhaps 20% gaps. A minimum qualitative standard, which perhaps should be insisted on, is that the facioacoustic nerves through their cisternal and canalicular portions be recognizable bilaterally, either on T1WI or T2WI (see Figs. 21-1 and 21-2). An unfocused study of the brain with 5-mm or thicker sections is inadequate for imaging the IAC.

Images in a second orthogonal plane should be obtained when a tumor is encountered20 to demonstrate the relationship of tumor to the tentorium and the jugular fossa, and when volumetric measurements are desired. Gadolinium contrast agent should be routinely used in comprehensive studies because it markedly improves visualization of small tumors, permits identification of residual or recurrent tumor, and adds precision to the delineation of tumor in the IAC (Fig. 21-7).3 There are only a few contraindications to its use, and side effects rarely occur. Furthermore, gadolinium chelate enhancement confirms labyrinthitis28 and reveals nondestructive intralabyrinthine schwannomas.29,30 Numerous studies have been performed to identify the potential biologic effects of MRI, but none of them have

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E

F

G

H

Figure 21-2, cont’d. Facial nerve (7 ) and superior vestibular division of acoustic nerve (8) extend into labyrinthine facial nerve canal (7l ) and vestibule (v), respectively, in D; and cochlear and inferior vestibular divisions of acoustic nerve (8), respectively, into cochlea (c) and vestibule (v) in E. Geniculate ganglion (7g) and tympanic segment (7t) of facial nerve show normal contrast enhancement. Abducens nerve (6) crosses cistern to enter cavernous sinus (CS). Mastoid segment (7m) of facial nerve is at times paralleled by a fatty collection posteriorly (also in F, G, and H) F and G, Upper medulla. Glossopharyngeal and vagus nerves (9–10) extending from lateral medulla toward jugular foramen are difficult to separate from each other. Greater superficial petrosal nerve (gsp) extends from geniculate ganglion (7g in E) anteromedially on floor of middle fossa. Cranial opening of cochlear aqueduct (ca) closely overlies pars nervosa of jugular foramen (not well shown). H, Lower medulla. Spinal accessary nerve (11) ascending toward jugular foramen is also difficult to distinguish from glossopharyngeal and vagus (9–10 in F and G). Rootlets of hypoglossal nerve extend from preolivary sulcus anteriorly toward hypoglossal canal inferior to jugular tubercle (jt), which is separated from petrous apex (pa) by petro-occipital fissure (pof). Posterior inferior cerebellar artery (p) arises from vertebral artery (V). Artifact from flow is seen streaking between sigmoid sinuses (S ). Carotid artery (C), jugular vein (J ), tympanic cavity (T ), and external auditory canal (E ) are all signal-free.

A

B

Figure 21-3. Vertebrobasilar dolichoectasia. A, Axial Gd-T1WI. Tortuous left vertebrobasilar artery (long arrow) crosses left to right anterior to pons. Small arterial branch (open arrow) coursing toward left CPA probably represents left AICA. Note normal enhancement of geniculate ganglion and proximal tympanic facial nerve and posterior fossa veins (small arrows). Serration across cerebellum between sigmoid sinuses is caused by pulsating flow of blood in sigmoid sinuses. B, Coronal MR angiography. 3-D time-of-flight technique, maximum intensity projection. Same vertebrobasilar artery (long arrow) and probable left AICA (open arrow) as in A. Superior cerebellar and posterior cerebral arteries and right posterior inferior cerebellar artery (small arrows) are also seen. No contrast injection is necessary for MRA.

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B

Figure 21-4. Multiple sclerosis. A, T1WI. Subtle pontine lesion (arrowhead) shows easily overlooked minimal hypointensity. B, T2WI. Hyperintensity of lesion is obvious.

A

B

Figure 21-5. Superficial siderosis. Patient has bilateral progressive sensorineural hearing loss several years after surgical resection of left inferior frontal arteriovenous malformation. A, T1WI. No abnormality is apparent. B, T2WI. Thin layer of hypointensity from pial and subpial deposition of hemosiderin is visible on pons, cerebellum, and acoustic nerves (arrows). (Compare with Fig. 21-1). Thin layer of hypointensity is also present on inferior surfaces of cerebral hemisphere (not illustrated). Hypointensity of dentate nuclei may be physiologic.

A

B

Figure 21-6. Jugular paraganglioma (glomus jugulare tumor) with PF extension. A, T1WI. B, Gd-T1WI. Note loss of natural contrast between tumor and clivus marrow after Gd-DTPA and importance of precontrast images to serve as baseline. Tumor circumferentially narrows intrapetrous carotid (open arrow) and extends to protympanum (short arrow) to surround cochlea (arrow). Note dural tails (long thin arrows) and arterial branch (arrowhead) supplying tumor. (Compare with Fig. 21-28).

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TABLE 21-1. Sample Magnetic Resonance Protocol for Comprehensive Study of Cerebellopontine Angle/Internal Auditory Canal Axial survey of brain: T2WI, 5.5-mm thickness Axial posterior fossa detail: T1WI precontrast, 2.0-mm thickness Axial submillimeter posterior fossa detail: CISS, 0.8-mm thickness Axial survey of brain: DWI, 5.0-mm thickness Axial posterior fossa detail: T1WI post-Gd FS 2.0-mm thickness Coronal posterior fossa detail: T1WI post-Gd FS, 2.0-mm thickness If postoperative patient: Pre-Gd T1WI, FS, 2.0-mm thickness For NF2: include post-Gd T1WI axial and coronal whole brain, 5.5-mm thickness CISS, constructive interference steady state; DWI, diffusion-weighted images; FS, fatsuppressed; Gd, gadolinium chelate; NF2, neurofibromatosis 2; T1WI, T1-weighted images; T2WI, T2-weighted images.

determined any significant hazards.31,32 More directly related to otologic interest is acoustic noise produced by the activation and deactivation of the gradient magnetic filed.33,34 Reversible hearing loss may be induced by such noises.35 Disposable ear plugs or other noise reduction devices should be routinely used.31 Certain prosthetic implants and metallic materials are associated with potential hazards. Examples are cardiac pacemakers, ferromagnetic cerebrovascular aneurysm clips, and intraocular ferromagnetic foreign bodies.31 High-field MRI is strictly contraindicated for patients with cochlear implants,31,36 although low-field scanners may be safe. Stapes prostheses are safe for MRI with the exception of the Richards-McGee platinum-stainless steel piston manufactured in a relatively small quantity and only for a brief period after mid-1987, using C17NI4 stainless steel instead of the more common 316L stainless steel.37 Eyelid springs used for patients with facial nerve palsy have shown deflection in vitro but no significant ill effects in vivo.

A

CLASSIFICATIONS AND INCIDENCE OF CEREBELLOPONTINE ANGLE TUMORS Approximately 10% of intracranial tumors originate in the CPA.38 Most of them arise from the cranial nerve sheath, the meninges, the blood vessels, and the congenital rests located in the extra-axial compartment. Some arise from the petrous bone or the jugular foramen and are extradural in origin but intrude into the CPA. A few are exophytic growths of intra-axial lesions arising from the brain. Lesions in the CPA are extremely diverse. Provided in Table 21-2 for reference are the lesion types and numbers from three major series.39–41 The Brackmann series represents material from a neurotologic practice, excluding paragangliomas. Although the percentages differ, all three series show acoustic or vestibular schwannoma (VS), as by far the most common, comprising some 60% to 90% of all CPA lesions. The three series also agree that the distant second, third, and fourth most common tumors by narrow margins are meningioma, congenital intradural epidermoid tumor or cyst, and nonacoustic posterior fossa schwannomas, respectively. These four common tumor types account for about 75% to 98% of all CPA mass lesions. Beyond the four most common tumors, the types of mass lesions in the CPA are extremely diverse and numerous (see Table 21-2). The Revilla series of 205 CPA lesions includes 1 primary melanoma, 1 paraganglioma, and 13 cerebellar and petrous bone tumors infiltrating the CPA.40 The Brackmann series of 1354 CPA tumors includes 7 arachnoid cysts, 4 hemangiomas, 1 hemangioblastoma, 2 astrocytomas, 2 medulloblastomas, 3 metastatic tumors, 2 dermoids, 2 lipomas, 1 malignant teratoma, and 1 chondrosarcoma.39 The series of 455 CPA lesions of Valavanis41 includes among primary tumors, 1 melanoma and 3 hemangiomas; among secondary tumors, 47 paragangliomas, 1 ceruminoma, 2 chondrosarcoma, 8 chordoma, and 6 extensions of cerebellar and petrous bone

B

Figure 21-7. Intracanalicular vestibular schwannoma. A, T1WI. Typical small tumor isointense with brain without enlargement of IAC (arrow). Such a tumor may be isointense with CSF and not apparent on T2WI. B, Gd-T1WI. Extent of tumor (filling fundus of IAC) is more fully and precisely demonstrated postcontrast. (Compare with Figs. 21-30, 21-42, 21-43, 21-44, 21-46, and 21-47.)

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TABLE 21-2. Classification and Frequency of CPA Lesions Revilla (1947) No. Primary Tumors of the CPA Acoustic schwannoma Meningioma Epidermoid Arachnoid cyst Schwannoma of the fifth, seventh, ninth, tenth, and eleventh nerves Primary melanoma Hemangioma Lipoma, dermoid, teratoma Secondary Tumors of the CPA Paraganglioma Ceruminoma Chondroma-chondrosarcoma Chordoma Extension of cerebellar and petrous bone tumors Metastases Vascular Lesions Aneurysm Arteriovenous malformation Vertebrobasilar dolichoectasia

%

Brackmann (1980) No.

%

Valavanis (1987) No.

%

154 13 13 — 10 1 — —

75.1 6.3 6.3 — 4.9 0.5 — —

1236 42 32 7 19 — 4 5

91.3 3.1 2.4 0.5 1.4 — 0.3 0.4

275 31 17 9 18 1 3 —

60.5 6.8 3.7 2.0 4.0 0.2 0.7 —

1 — — — 13 —

0.5 — — — 6.4 —

— — 1 — 5 3

— — 0.1 — 0.4 0.2

47 1 2 8 6 12

0.3 0.2 0.4 1.8 1.3 2.6

— — —

— — —

— — —

— — —

4 4 17

0.9 0.9 3.7

From Lo WWM: Tumors of the temporal bone and the cerebellopontine angle. In Som PM, Bergeron RT (eds.): Head and Neck Imaging, 2nd ed, St. Louis, Mosby-Year Book, 1991.

tumors; among vascular lesions, 4 aneurysms, 4 AVMs, and 17 VBDs; and 12 metastases. Other rare lesions not listed may also appear as mass lesions in the CPA, for example, lymphoma,42 hypertrophic pachymeningitis,43 syphilis, sarcoidosis,44,45 rhabdoid tumor,46 and so forth. (See also Chapter 49, Rare Tumors of the Cerebellopontine Angle.) Such a long list of possibilities makes differential diagnosis difficult. To simplify discussion in this chapter, the CPA lesions are grouped into eight categories (Table 21-3). Five extra-axial groups: (1) vestibular schwannoma, (2) meningioma and simulants, (3) epidermoid and other cysts (arachnoid, cysticercal, dermoid, etc.), (4) nonvestibular posterior fossa (PF) schwannomas (V, VII, IX, X, XI, XII), and (5) vascular lesions (VBD, aneurysm, AVM, superficial siderosis, etc.); two extradural groups: (6) bone lesions (benign or malignant, primary or metastatic) and (7) paraganglioma; and finally an intra-axial group including astrocytoma, ependymoma, papilloma, hemangioblastoma, metastasis, lymphoma, and so on. Such a categorization does not follow traditional classifications based on cell origin but is more conducive to differential diagnosis based on location and appearance of the lesions as revealed by imaging. (See also Chapter 49, Rare Tumors of the Cerebellopontine Angle.) Intracanalicular lesions with a slightly different differential diagnosis are also discussed.

VESTIBULAR SCHWANNOMA Commonly but incorrectly termed acoustic neuromas,19,20,38 VSs are by far the most common tumor in the CPA and the IAC.39–41 Most characteristically they arise in the IAC and enlarge into the CPA, with a rounded mass in the CPA and a cone-shaped stem in the IAC enlarging the porus acusticus (Fig. 21-8). Some tumors arise in the CPA and

appear as a rounded mass centered at the porus (Fig. 21-9). As VSs enlarge they often assume an ovoid configuration with their long axis parallel to the posterior petrous wall (Fig. 21-10). Intracanalicular VSs initially appear as small TABLE 21-3. Imaging Differential Diagnosis of CPA Lesions I. Extra-axial Lesions A. Vestibular schwannoma B. Meningioma and simulants Leptomeningeal metastases Primary meningeal lymphoma Primary meningeal melanoma Meningeal sarcoidosis Hypertrophic pachymeningitis C. Epidermoid and other cysts Arachnoid cyst Cysticercal cyst Epithelial cyst Neuroenteric cyst Craniopharyngioma Lipoma D. Nonvestibular PF schwannomas V, VII, IX, X, XI, XII E. Vascular lesions VBD Berry aneurysm Giant aneurysm Arteriovenous malformation Superficial siderosis

II. Extradural Lesions A. Bone lesions 1. Cysts, e.g., cholesterol cyst epidermoid cyst mucocele 2. Tumors, e.g., chordoma chondroma chondrosarcoma giant cell tumor myeloma metastases xanthoma B. Paraganglioma (glomus jugulare tumor) III. Intra-axial Lesions A. Brainstem tumor Astrocytoma Lymphoma Hemangioma B. Cerebellar tumor Astrocytoma Hemangioblastoma Metastases Lymphoma Hemangioma Medulloblastoma C. Fourth ventricular tumor Ependymoma Choroid plexus papilloma D. Nontumorous Infarct Multiple sclerosis

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B

Figure 21-8. Typical large IAC-CPA VS. Smoothly marginated tumor mushrooms out of IAC into CPA, causing funnel-shaped widening of the IAC and forming an extra-axial mass deforming the pons. A, T1WI. Tumor is nearly homogeneous, mildly hypointense to brain, and hyperintense to CSF. A vessel is seen trapped between the tumor and pons (arrow). B, Gd-T1WI. Marked contrast enhancement is typical of VSs. Intratumoral cystic components (arrow) are much more obvious than precontrast.

A

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Figure 21-9. Medium-sized cisternal VS. Tumor is extra-axial, smoothly marginated, rounded, and centered to porus acusticus. A, T1WI. Tumor is mildly hypointense to brain, hyperintense to CSF, and slightly granular in texture. B, Gd-T1WI. Tumor shows marked nearly homogeneous enhancement postcontrast. (Compare with Fig. 21-27.)

A

B

Figure 21-10. Giant cisternal VS. Tumor is extra-axial, smoothly marginated, ovoid, centered over porus acusticus, and deforming pons, cerebellum, and fourth ventricle. A, T1WI. Tumor is mildly hypointense to brain and hyperintense of CSF and nearly homogeneous except for cystic component (arrowhead). Vessels are seen between tumor and brain (arrows). B, Gd-T1WI. Tumor shows marked contrast enhancement except for cystic component. Giant tumors are often entirely extracanalicular as in this case.

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357

B

Figure 21-11. Vestibular schwannoma with dural tail. A, T1WI. B, Gd-T1WI. Otherwise typical appearing IAC-CPA vestibular schwannoma shows enhancing dural tail (arrow) extending to posterior petrous surface. This finding was present in only 1 of 100 VSs in an unpublished series.

rounded masses and then become sausage-shaped as they grow to fill the canal (see Fig. 21-7). At times, intracanalicular VSs may be lobulated or globular and focally erode the canal. Schwannomas are typically isointense or mildly hypointense to brain on T1WI, enhance markedly on gadolinium, and are between brain and CSF in intensity

A

on T2WI (see Figs. 21-7 through 21-12). As a group, they enhance far more than any other benign extra-axial tumor, but sufficient overlap occurs among tumors of different types so that the degree of enhancement alone cannot always be relied on to differentiate the type of tumor.47 The enhancement may or may not be homogeneous because microcyctic and macrocystic components within

B

Figure 21-12. NF2. A, T1WI. B, Gd-T1WI. C, Sagittal Gd-T1WI. Patient has bilateral VSs (vertical arrows), bilateral trigeminal schwannomas (horizontal arrows), left facial schwannoma (open arrow), and left posterior fossa, falx, and parasagittal meningiomas (oblique arrows). Note also occlusion of left lateral sinus (blank arrow) and dural “tails” (long thin arrows).

C

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the tumor are common in schwannomas, reflecting the presence of Antoni type B tissue (see Figs. 21-8 and 21-10).1,38,48,49 Initially, nonenhancing microcystic components on a short sequence may attain enhancement in time as equilibration of contrast material in extracellular space takes place.1 Schwannomas may also be accompanied by one or more overlying arachnoid cysts (Fig. 21-13), and at times be dominated by one.50 Calcification is rarely present in schwannomas.41,49,51–54 Rarely, intratumoral hemorrhage may cause focal hyperintensity or hypointensity depending on the age of the hemorrhage.55–58 Even more rarely, subarachnoid hemorrhage may be the presenting symptom of a large VS.59,60 However, acute subarachnoid hemorrhage may not be apparent on MRI even when obvious on CT.10 CT is therefore indicated when the signs and symptoms suggest subarachnoid hemorrhage.14 A dural “tail” often observed in meningiomas (Figs. 21-12, 21-14, and 21-15), on rare occasions may be seen associated with a VS (see Fig. 21-11).61

A

C

Funnel-shaped enlargement of the IAC is common in VSs and rarely seen in other lesions (see Figs. 21-8 and 21-11).41,54 The incidence of hydrocephalus roughly correlates with tumor size. One report noted hydrocephalus in 17 of 44 patients in whom a tumor of 3 cm or larger was present.62 Rarely, a large VS compressing the brain may cause peritumoral edema.41 CT and MRI have been extremely useful in studying the natural history of VS. Many such studies have been published.63–73 Their methodologies may vary, but the results appear to concur that most tumors are stable or slowly growing (of the order of 2 mm or less a year) but some grow as much as 1 cm or more a year. These results appear to correlate with those revealed by monoclonal antibody studies.74 To establish the growth rate of a tumor, an initial follow-up study in perhaps 6 months may be done. If the tumor is found to be stable or very slow growing, subsequent follow-up studies then may be repeated at 1- to 2-year intervals. In postoperative studies for residual or recurrent tumor, precontrast and postcontrast studies at matching levels are

B

D

Figure 21-13. VS with arachnoid cysts. Tumor is extra-axial, slightly lobulated, centered over porus acusticus, and lies predominantly in CPA cistern with an overlying arachnoid cyst as large as the tumor itself laterally and a smaller arachnoid cyst medially. A, T1WI. Tumor is mildly hypointense to brain; arachnoid cysts (arrows) are isointense to CSF. B, Gd-T1WI. Tumor shows marked contrast enhancement, and arachnoid cysts (arrows) show no enhancement. C, T2WI. Tumor is slightly hypointense to CSF and slightly granular in texture. Arachnoid cysts (arrows) are isointense to CSF and homogeneous. D, Coronal Gd-T1WI. Tumor extends superiorly to undersurface of tentorium (down arrow) and inferiorly over contrast-enhanced sigmoid sinus (up arrow) medial to enhanced high jugular bulb (open arrow).

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A

B

C

D

359

Figure 21-14. CPA meningioma with classic features. A, T1WI. B, Gd-T1WI. C, T2WI. D, Coronal Gd-T1WI. Tumor is an extra-axial, hemispherical mass with its broad base against the posterior petrous wall, obtuse bone tumor angle, underlying focal hyperostosis (open arrow), central vascular pedicle (long thin arrow), and transincisural (arrowheads) and transtentorial (paired white arrows) middle fossa extensions. Tentorium is indicated by black arrows. Central hypointensity is consistent with fibrosis and calcification. Note dural tails (tandem arrowheads) in B.

A

B

Figure 21-15. En-plaque meningioma with transpetrous tumor in posterior and middle fossas. A, T1WI. B, Gd-T1WI. Tumor (arrows) is isointense and inconspicuous precontrast, but markedly hyperintense postcontrast. Note dural tail over clivus (arrowhead), tumor filling right Meckel’s cave in contrast to unfilled left Meckel’s cave (open arrow), and underlying focal hyperostosis (small arrows). Note also tentorial attachment (curved arrows). (Courtesy of James J. Hodge, MD)

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important for differentiation of surgically placed fat from tumor.75 Fat suppression technique should be used.24 After hearing-conservation techniques have been performed to remove small VSs, enhancement of varying degrees at the operative site is usually present.76 Serial follow-up studies are necessary to establish the presence or absence of tumors.77 After stereotactic radiosurgery, one series shows VSs often shrank (22%) but more commonly remained stable in size (73%) and rarely continued to grow (4%).78 The corresponding numbers for untreated tumors were 3%, 59%, and 38%, respectively.78 The majority (79%) of tumors after radiosurgery showed loss of central enhancement, which sometimes returned (Fig. 21-16). Some 5 to 15 months after treatment, 9% developed hyperintensity on T2WI in the adjacent pons and the cerebellar peduncle with associated contrast enhancement on T1WI suggestive of breakdown in the blood-brain barrier. Some of these changes resolved after months and were not necessarily associated with neurologic symptoms. Similarly, contrast enhancement was observed in the trigeminal nerve in some of the patients. Up to 10% of the patients developed hydrocephalus months after radiosurgery and required ventriculoperiotoneal shunts.78–80 Some tumors continued to grow and required reradiation or eventually surgical resection.79 The distinction of neurofibromatosis 1 (NF1) (von Recklinghausen’s disease) from NF2 (bilateral acoustic

A

neurofibromatosis), established by the National Institute of Health (NIH) Consensus Development Conference as separate disorders, represents a significant advance in the understanding and management of these disorders.19 Although both disorders are autosomal-dominant and may be inherited or acquired by mutation, they are associated with defects in different chromosomes.81,82 Because both disorders may have central nervous system (CNS) involvement, the terms peripheral and central neurofibromatosis should be discarded.83 It is important to be aware of their differences so that the MRI examination may be appropriately tailored to the disorders.83,84 The diagnostic criteria for NF1 may be found in Chapter 46. The criteria for NF2 include (1) bilateral eighth nerve masses seen with appropriate imaging techniques, such as CT or MRI (see Fig. 21-12) or (2) a first-degree relative with NF2 and either a unilateral eighth nerve mass or two of the following: neurofibroma, meningioma, glioma, schwannoma, or juvenile posterior subcapsular lenticular opacity.19 Besides bilateral VSs, NF2 patients are at risk for schwannomas of other cranial and spinal nerves, and intracranial and spinal meningiomas, often multiple (see Fig. 21-12).21,83 Members of some kindreds also develop ependymomas.22 Choroid plexus calcification is common.85 NF2 patients, however, are not at risk for optic gliomas, focal cerebral hamartomas, and many other stigmata common in NF1.83

B

Figure 21-16. VS after stereotactic radiosurgery. A, T1WI. Hypointensity in adjacent pons consistent with edema (arrow). B, Gd-T1WI. Central nonenhancement (curved arrow) consistent with cystic component or loss of enhancement seen in majority of VSs after stereotactic radiosurgery. Pontine enhancement (arrow) consistent with breakdown of blood-brain barrier seen in a small percentage of patients. C, T2WI. Hyperintensity in middle cerebellar peduncle and adjacent pons and cerebellum consistent with edema (arrows). (Courtesy of Barry D. Pressman, MD)

C

Imaging of the Cerebellopontine Angle

MENINGIOMA AND SIMULANTS In the CPA, meningioma is a distant second to VS in incidence.39,40,86 It is most often the lesion difficult to differentiate from VS.41,52,86,87 (See Chapter 47.) Meningiomas in the CPA most commonly arise from the posterior petrous surface (Fig. 21-17). Like VSs they are extra-axial, but unlike VSs they are usually eccentric to the porus (see Fig. 21-14). Also unlike VSs, meningiomas frequently herniate into the middle cranial fossa, (see Figs. 21-14 and 21-17).41 They may grow into the middle fossa through the tentorium or the temporal bone (see Figs. 21-15 and 21-17).41,87 Most characteristically, meningiomas are sessile and hemispherical in configuration, with their broad base against the petrous bone (see Fig. 21-14). They show obtuse bone tumor angles (see Fig. 21-14) in contrast to VSs, which are typically spherical or ovoid and show acute bone tumor angles (see Figs. 21-8 through 21-13 and 21-16).41 Less commonly, meningiomas are flat or plaquelike (en plaque) (see Fig. 21-15), and rarely pedunculated and nearly rounded.38 The en plaque meningiomas are notably prone to cause deep infiltration of the petrous bone (see Fig. 21-15).38 The surface of meningiomas is usually smooth or slightly lobulated. On MRI, like VSs, meningiomas are isointense or slightly hypointense on T1WI but, unlike VSs, they vary from hyperintense to hypointense on T2WI (see Fig. 21-14).8 (Hypointensity on T2WI may be due to calcification, fibrous tissue, melanotic elements, hemosiderin, fat, etc.)58 Gentry and colleagues8 found that when the intensity of the CPA mass was equal to or less than that of gray matter on T2WI, meninigioma was the most likely diagnosis. The variability in signal intensity of meningiomas on T2WI appears to reflect the histopathologic diversity of meningiomas. Tumors significantly hypointense to brain cortex tend to be composed primarily of fibroblastic or transitional elements, whereas those significantly hyperintense tend to be composed primarily of syncytial (meningothelial) or highly vascular elements.38,88,89 Generally, however, accurate prediction of histology by imaging is not possible,90,91 and tumor aggressiveness and recurrence rate does not necessarily correlate with histology.92 Metabolic rate as revealed by positron emission tomography (PET) may be a better prognosticator of tumor aggressiveness and likelihood of recurrence.93

Figure 21-17. Diagrammatic representation of locations of 19 meningiomas producing CPA symptoms (left and right sides combined). (From House JW and O’Connor AF [eds.]: Handbook of Neurotological Diagnosis, New York, 1987, Marcel Dekker, Inc, p 290, by courtesy of Marcel Dekker, Inc.)

361

Meningiomas often calcify on CT (25%).41,94 On MRI, calcification appears hypointense on both T1 and T2WI (see Fig. 21-14), although hyperintense calcification has also been reported.95 MRI is less sensitive to calcification than CT and may not detect faint calcifications. Underlying hyperostosis is infrequently seen but strongly diagnostic when present (see Figs. 21-14 and 21-15).41 The IAC is rarely if ever enlarged. Cystic foci may be present in the tumor but appear much less commonly in meningiomas that in VSs.52 Peritumoral edema is more commonly associated with meningiomas than with VSs. Meningeal blood supply in the form of an arborizing signal void is highly characteristic if present. Marginal vessels and surrounding CSF cleft may be seen but are nonspecific.96 Dural thickening surrounding meningiomas, best seen with gadolinium enhancement (see Figs. 21-12, 21-14, and 21-15)97 has been variously termed meningeal sign, dural tail, and flare sign.98–100 Initially found to correspond to tumoral extension within or around the dura,97,99 the dural thickening in many subsequent cases has been found to contain only connective tissue, hypervascularity, and no tumor.101 Hence, to establish the histopathology in a peritumoral meningeal thickening, biopsy is necessary. In most cases, the thickening represents reactive rather than neoplastic changes.102 Dural thickening has been found in 52% to 72% of the meningiomas on postcontrast MRI.98–100 It has also been found, although much less frequently, in nonmeningiomas, including oligodendroglioma, schwannoma (see Fig. 21-11),61,100 glioblastoma, metastases, and other tumors (see Figs. 21-6, 21-18, 21-19, and, later in this chapter, Fig. 21-35).102 Thus, peritumoral dural thickening is strongly suggestive but not diagnostic of meningioma. Aoki and coworkers98 found dural thickening and enhancement extending into the IAC in two of four CPA meningiomas that simulated the stem of a VS. Several rare neoplastic and inflammatory diseases involving the meninges may simulate meningiomas on CT or MRI. Among the neoplasms are loculated leptomeningeal metastasis (meningeal carcinomatosis)

Figure 21-18. Loculated and diffuse meningeal metastases from carcinoma of the prostate. Gd-T1WI, Loculated metastases are present in both IACs (arrows) and diffuse metastasis (long thin arrows) similar to dural “tail.” Differential diagnosis: meningeal lymphoma, melanoma, sarcoidosis, tuberculosis, syphilis, idiopathic pachymeningitis.

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A

B

C

D

Figure 21-19. Idiopathic hypertrophic pachymeningitis. A, Sagittal T1WI. B, T2WI. C, Gd-T1WI. D, Coronal Gd-T1WI. Mass (black arrows) is extra-axial, dural-based on clivus and posterior petrous surface, slightly inhomogeneous and hypointense on T1WI, A, and inhomogeneous in intensity of T2WI, B, with mild inhomogeneous enhancement postcontrast, C and D, except for dural tails (white arrow) where enhancement is more intense. The patient is a 50-year-old woman who had rubbery hypovascular prepontine mass at transtemporal exploration and well-formed granulomas and chronic inflammation of histopathologic examination. No organisms were found on stains and cultures. (Courtesy of Robert K. Jackler, MD.)

(Figs. 21-18 and 21-20),103–105 primary meningeal lymphoma,42,106 and primary malignant melanoma.41,107,108 Among the inflammatory diseases are meningeal sarcoidosis,44,109 tuberculosis, syphilis, and idiopathic hypertrophic cranial pachymeningitis (see Fig. 21-19).43 All of the preceding conditions may appear as diffuse dural thickening simulating en plaque meningiomas or localized dural-based masses simulating sessile meningiomas. However, they are not expected to have underlying hyperostosis, intratumoral calcification, or discernible arborizing meningeal arterial feeders.

EPIDERMOID AND OTHER CYSTS Congenital intradural epidermoid tumors or cysts are the third most common mass lesion in the CPA (Figs. 21-21 and 21-22).39,41 They may be anterolateral or posterolatral to the brainstem. They tend to expand where the physical resistance is low, often extending into the prepontine and suprasellar cisterns and “dumbbell” into the contralateral cistern or

the middle cranial fossa. Their shapes are thus quite variable. They tend to burrow into the surface crevices of the brain and possess a fine surface irregularity reminiscent of that of cauliflower.110 The petrous apex may be eroded.41,111 On CT they are well known to be isodense with CSF.8 But, rarely they may be hyperdense (see Fig. 21-22).112–114 On MRI they are slightly hyperintense to CSF on T1WI and isointense on T2WI in the vast majority of cases.8,110,115,116 But, rarely, they show reversed signal intensities and are hyperintense on T1WI and hypointense on T2WI (“white epidermoids”) (see Fig. 21-22).117,118 They often show fine internal strands and at times a thin capsule of brain intensity.116 They may surround rather than displace the cisternal arteries.116 Small punctate calcifications are infrequently seen in the periphery.119 Epidermoid cysts are nonenhancing (see Fig. 21-12).119 Association of an enhancing component should arouse the suspicion of a squamous carcinoma arising from an epidermoid cyst.120,121 A number of other cysts may simulate epidermoid cysts in the CPA. They are all nonenhancing extra-axial masses of nearly CSF attenuation (on CT) and intensity (on

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A

363

B

Figure 21-20. Loculated leptomeningeal metastasis simulating meningioma. Patient had right hearing loss for only 2 weeks, an unusually short duration of symptoms for a meningioma, and had previously had a malignant melanoma removed from her trunk. Metastatic melanoma was surgically confirmed. A, GdT1WI. Hemispherical homogeneously enhancing extra-axial mass eccentric to porus acusticus with extension into IAC, entirely consistent with a meningioma. B, Coronal Gd-T1WI. Subtle symmetric additional metastases within foramen magnum are seen (arrows). (Courtesy of Peter W. Joyce, MD.)

A

B

C

D

Figure 21-21. Intradural congenital epidermoid cyst (tumor). A, T1WI. B, Gd-T1WI. C, T2WI. D, Coronal Gd-T1WI. Irregular extra-axial mass displaces pons and insinuates toward fourth ventricle through widened lateral recess (arrowheads). Tumor is slightly hyperintense to CSF on T1WI, A, nonenhancing postcontrast, B, and nearly isointense to CSF on T2WI, C, and shows fine internal inhomogeneity and fine surface irregularity (A, B, and C). Note herniation (arrows in D) through tentorial incisura displacing midbrain.

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A

B

Figure 21-22. Intradural “white” congenital epidermoid. A, Noncontrast CT. B, T1WI. C, T2WI. This very rare “white” epidermoid in the right CPA deforming the medulla is hyperdense of CT, A, hyperintense of T1WI, B, and hypointense on T2WI, C, in complete reversal to the relatively common and more typical “black” epidermoid in the preceding figure. The MR intensities of a “white” epidermoid are similar to those of lipoma (see Figs. 21-25 and 21-44); the CT hyperdensity, however, is in contrast to the hypodensity characteristic of lipoma or fat. (Courtesy of Robert K. Jackler, MD.)

C

MRI)—hypointense on T1WI and hyperintense on T2WI. Lipoma is also considered at this time because it is nonenhancing, although its x-ray attenuation and MR signal intensities of fat are distinctive from those of most cysts.122,123 Arachnoid cysts in the CPA are usually large masses and, like epidermoid cysts, hypointense on T1WI and hyperintense on T2WI (Fig. 21-23).124,125 (See Chapter 55, Neurotologic Aspects of Posterior Fossa Arachnoid Cysts.) But unlike epidermoid cysts, their surfaces are smooth and their contents homogeneous. They displace rather than surround the arteries in the cistern. An attempt to differentiate the two lesions on the basis of imaging is worthwhile, since the symptoms of arachnoid cysts may be controlled by diuretics alone.126 Diffusion-weighted and fluid-attenuated MR sequences may help in differentiating the two lesions when routine spine-echo studies are inconclusive.127 Cysticercosis should be considered in endemic areas. Cisternal cysticercal cysts are also of CSF attenuation and intensity, but are usually smaller than arachnoid cysts and often detected only by the presence of focal cisternal widening (Fig. 21-24).128 Unlike parenchymal and ventricular cysticercal cysts, which are separate from one another, cisternal cysts are racemose, a few centimeters in diameters, and lack a scolex.128 The majority are detectable only

on T1WI, but T2WI demonstrate the surrounding parenchymal reaction to greater advantage.129 Coexistent parenchymal, ventricular, or additional cisternal cysts, when present, strongly support the diagnosis. Very rare congenital cysts that may be encountered in the CPA include epithelial cysts,130–133 neurenteric cysts,134 and craniopharyngioma.17,135 Although their CT and MR images have been illustrated, generalization of their findings is difficult on the basis of the very few cases reported. Some of them show CT attenuation and MR intensities atypical of uncomplicated cysts.132,134,135 In contrast to most CPA tumors and cysts, lipomas are hyperintense on T1WI and hypointense on T2WI and parallel the signal intensity of orbital and subcutaneous fat (Fig. 21-25).122,136–140 They show no contrast enhancement, and their hyperintensities on T1WI are diminished by fat suppression sequences.24 Without pregadolinium images for comparison, their inherent hyperintensity on T1WI will not be recognized when only postgadolinium T1WI are obtained; nor will their characteristic short T2 values be appreciated without adequate T2WI. Because conservative management for lipomas may be advisable,122,136,137,139,141–143 diagnosis on the basis of imaging findings is of considerable importance. Besides the characteristic MRI intensities, the negative Hounsfield values of lipomas on CT are also diagnostic.42,123,141

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Figure 21-24. CPA cysticercal cysts. T1WI. Bilateral cisternal cysts (arrows) isointense with CSF indent pons and slightly bow left facioacoustic nerves (curved arrow).

B

A

C Figure 21-23. CPA arachnoid cyst. A, T1WI. B, T2WI. C, Postcontrast CT. Cyst is isointense with CSF on MRI, A and B, and isodense with CSF on CT, C, and nonenhancing, similar to a typical epidermoid but is distinguishable from the latter by being smooth surfaced and homogeneous. Note notching on surface by basilar artery in A and B.

B Figure 21-25. CPA lipoma. A, T1WI. B, T2WI. Note characteristic hyperintensity on T1WI (arrow in A) and hypointensity on T2WI (arrow in B) in reverse of CSF. See also Fig. 21-44.

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NONVESTIBULAR POSTERIOR FOSSA SCHWANNOMAS Schwannomas arising from PF cranial nerves other than the vestibular are rare.38,44 They resemble VSs in appearance but differ from them in location.41,144 Not infrequently, facial and intracranial jugular foramen schwannomas are associated with symptoms relating primarily to the eighth nerve. Careful assessment of their relationship to the cranial foramina is important so that the correct diagnosis can be made and inappropriate use of the translabyrinthine approach avoided.145 Among the PF schwannomas, trigeminal schwannoma is a distant second to VS in frequency of occurrence.144 Trigeminal schwannomas may arise intradurally from the nerve root in the CPA and the Meckel cave or extradurally from the gasserian ganglion in the middle cranial fossa (Fig. 21-26).146–149 They often dumbbell into the posterior and middle fossae through the porus trigeminus.86,147–149 The foramen ovale or foramen rotundum (or both) may be enlarged. They tend to be larger than the average VS,149 and more often contain cystic components.41,150

Facial schwannomas are, in most cases, indistinguishable from VSs on CT or MRI when they arise in the CPA or the IAC (Fig. 21-27).1,138,151 When they arise in the CPA or the IAC, they tend to show vestibulocochlear symptoms and may be indistinguishable from VSs clinically as well,151–153 unless a cisternal facial schwannoma lies clearly anterior to the course of the acoustic nerve. Schwannomas of the glossopharyngeal, vagus, and spinal accessory nerves (jugular foramen schwannomas) may be predominantly intracranial (type A), predominantly in the skull base (type B), or predominantly extracranial (type C).154 Type A tumors tend to present with eighth nerve and cerebellar signs and symptoms, and type B and C tumors tend to present with palsies of the ninth, tenth, or eleventh cranial nerves.154–157 Thus type A tumors mainly need to be differentiated from VS and type B tumors from paraganglioma (glomus jugulare tumor), meningioma, and other tumors that may involve the jugular foramen (Fig. 21-28). (See also Chapter 61.) On CT the jugular foramen enlarged by a schwannoma shows a smooth rounded margin.1 On MRI, the prominent serpentine arborizing signal voids common in large paragangliomas are seldom present,158 and on angiography the

A

B

C

D

Figure 21-26. Cystic trigeminal schwannoma. A, T1WI. B, Gd-T1WI. C, PDWI. D, T2WI. Bulk of tumor lies in posterior fossa with a small middle fossa component enlarging left Meckel’s cave (arrow). Note similarity of tumor to arachnoid cyst (Fig. 21-19) on noncontrast images (A, C, and D). Tumor is nearly of CSF intensity of T1WI, A, because of predominance of intratumoral cystic components, and more obvious in B postcontrast, but also subtly suggested in A and C.

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B

Figure 21-27. CPA facial schwannoma. A, T1WI. B, Gd-T1WI. Isointense rounded extraaxial tumor centered at porus acusticus, A, intensely enhancing postcontrast, B, indistinguishable from VS (see Fig. 21-9).

tumors are less vascular than paragangliomas but more so than meningiomas.154,155,159 (See also Chapters 22 and 61.) When the pars nervosa of the jugular canal is selectively expanded, a glossopharyngeal schwannoma can be recognized. When the entire jugular foramen is diffusely and enlarged, however, differentiation among the jugular foramen schwannomas is not possible by imaging.1 Rarely a hypoglossal schwannoma may also appear as a mass in the CPA. Its identity can be traced if the hypoglossal canal is smoothly and selectively enlarged.160–162 When the bone erosion incorporates the adjacent jugular foramen, identification of precise origin of the tumor is then no longer possible.160

VASCULAR LESIONS Vascular lesions in the CPA are rare, but a number of them may clinically mimic neoplasms and should be considered in the differential diagnosis on imaging.163

A

VBD, or elongation and dilatation of the vertebrobasilar arteries, is probably the vascular lesion most commonly associated with compressive symptoms of the PF cranial nerves (Figs. 21-3 and 21-29).164 The basilar artery may be considered ectatic if its diameter is more than 4.5 mm (see Fig. 21-29) and elongated if it deviates beyond the lateral margin of the clivus (see Fig. 21-3) or the dorsum sellae or if it bifurcates above the plane of the suprasellar cistern.165 Patients with VBD may or may not be symptomatic.166 The incidence of cranial nerve compressive symptoms, however, appears to correlate with the degree of tortuosity.167 A symptomatic patient with a tortuous basilar artery of normal caliber is more likely to have involvement of a single cranial nerve (see Fig. 21-3); conversely, one with a dilated and tortuous artery is likely to have multiple compressive or ischemic neurologic deficits or hydrocephalus (see Fig. 21-29).164 In most cases the actual compression of a cranial nerve is exerted by the superior cerebellar artery on the trigeminal,

B

Figure 21-28. Jugular foramen schwannoma. A, T1WI. B, Gd-T1WI. Patient has NF2. Tumor is slightly lobulated and located partly in posterior fossa, deforming medulla and cerebellum, and partly in jugular foramen. It is mildly hypointense to brain, A, and intensely enhancing postcontrast, B. Vascularity is more prominent in this tumor than in a typical schwannoma, raising the question of a paraganglioma (see Fig. 21-6). Note signal from slowly flowing blood in left sigmoid sinus enhancing postcontrast.

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A

B

Figure 21-29. Vertebrobasilar dolichoectasia. A, Sagittal T1WI. Dilated and tortuous basilar artery (curved arrow) shows peripheral laminar hyperintensity due to very slow flow or thrombi (or both) and central moderate intensities due to moderately slow flow within the patent lumen. Normal flow void is seen in the undilated proximal and distal arteries (straight arrows). B, Gradient echo image. Flowing blood appears hyperintense on such images. Basilar artery (curved arrows) shows marked fusiform dilatation and marked tortuosity. Signal intensities in such dilated arteries are often complex due to presence of thrombi of varying are and flow of varying velocity. Similar complex intensity patterns may be also found in giant aneurysms, although the latter lesions are rounded or ovoid rather than fusiform. (Courtesy of William P. Dillon, MD.)

the anterior inferior cerebellar artery (AICA) on the facial or vestibulocochlear, or the posterior inferior cerebellar artery (PICA) on the glossopharyngeal. Hence, vascular cross-compression by a branch of the vertebrobasilar artery may occur without the vertebrobasilar itself necessarily being substantially dilated or tortuous. In fact, the offending vessel may at times be a vein instead of an artery.168 Furthermore, vessel-nerve contact or even vascular grooving of the nerve does not necessarily mean disease.169 Positive identification of the offending vessel by imaging is difficult. Angiographic localization, which visualizes the vessel but not the nerve, is indirect and invasive.170,171 CT with IV contrast shows the vertebrobasilar arteries and the brainstem but not adequately the branches of the vertebrobasilar or the cranial nerves in question.172 MRI offers improved resolution of the structures, but experience with MRI in this application is as yet limited.173–175

With future improvements MR angiography may become a useful adjunct (see Fig. 21-3).23 For preoperative diagnosis of neurovascular crosscompression, some centers use CT or MRI only to exclude other causes of symptoms,168,176 whereas others use, in addition, gas-CT cisternography for positive identification of the offending vessel before surgical microvascular decompression (Fig. 21-30).9,177 The point of contact may be in the cistern, the porus, or the canal and not necessarily limited to the canal as described in some reports.169,177 Concerns about postprocedural morbidity,178 even with 25-gauge rather than the “standard” 22-gauge spinal needles,179 have discouraged continued use of the gas-CT cisternogram in favor of the MR cisternogram with fast spin echo or CISS (see Fig. 21-1).4,5,11 Aneurysms of the vertebrobasilar system comprise about 10% of intracranial aneuryms.180 The common locations

Figure 21-30. AICA loop in IAC (also see Fig 21-1). High-resolution gas-CT cisternogram. Loop on AICA is marked with curved arrow; facial nerve, short arrow; acoustic nerve, long arrow.

Figure 21-31. AICA berry aneurysm. Selective vertebral angiogram. Patient had subarachnoid hemorrhage and hearing loss. Aneurysm (arrow) shows nipple-like configuration suggestive of recent bleeding. (Reprinted from Lo WWM: Tumors of the cerebellopontine angle. In Som PM, Bergeron RT [eds.]: Head and Neck Imaging, 2nd ed. St. Louis, Mosby-Year Book, 1991.)

Imaging of the Cerebellopontine Angle

A

369

B

Figure 21-32. Giant PICA aneurysm. A, Precontrast. B, Postcontrast CT. Aneurysm at PICA origin is partially thrombosed and slightly hyperdense to brain precontrast, A, and shows nonenhancing thrombus (open arrow) and enhancing lumen (long arrow) and outer rim (short arrow) postcontrast, B. (Courtesy of Duane E. Blickenstaff, MD.)

are the basilar bifurcation, the basilar trunk, the vertebral artery, and the PICA. Berry aneurysms usually present with subarachnoid hemorrhage (SAH) (Fig. 21-31), whereas giant aneurysms (those exceeding 2.5 cm) usually present instead as mass lesions (Fig. 21-32).181 AICA aneurysms, representing only 1% of intracranial aneurysms, are quite rare.182 In the past, AICA aneurysms have often been operated on with the erroneous diagnosis of acoustic tumor.182,183 A review of 22 reported cases revealed that 16 had acoustic and 14 had facial nerve symptoms and signs. Most had headaches, nausea, and vomiting, and 13 had documented SAH.182 Most were in the 5- to 7-mm range, although two exceeded 15 mm. Although VSs may on rare occasions present with SAH, they tend to be large, not small tumors.59,60 Berry aneurysms appear as signal voids on MRI and enhancing lesions on CT. Angiography is diagnostic (see Fig. 21-31). Giant aneurysms are usually partially thrombosed.41,181 A partially thrombosed aneurysm appears on MRI with a signal void in the patent lumen surrounded by layers of thrombi of varying signal intensities and sometimes a low-intensity outer rim (see Fig. 21-29).184–187 Signal loss from pulsating CSF around the basilar artery may mimic the signal void of an aneurysm.188 MR angiogram or contrast-enhanced CT would show the true size of the basilar artery. On CT a partially thrombosed aneurysm shows an enhancing outer rim with an isoattenuating nonenhancing mural thrombus surrounding an enhancing lumen (see Fig. 21-32), superficially resembling a partially enhancing cystic schwannoma.1,41,181,189 A thrombosed aneurysm is filled with a nonenhancing thrombus, and an unthrombosed one contains only the enhancing lumen.41 AVMs in the CPA are exceedingly rare (Fig. 21-33). Although they are generally intracerebral and cause primarily intracerebral hemorrhage, totally extracerebral AVMs, which are predisposed to primary subarachnoid bleeding, may be seen in the CPA.189 One or more cerebral aneurysms coexist with AVMs in about 20% of cases.190

Dilated enhancing vessels may be seen in the CPA on CT and serpentine hypointense loops on MRI.41,189 Superficial siderosis (SS), or pial siderosis of the acoustic nerves, is not a vascular lesion in itself but the result of chronic subarachnoid hemorrhage, often of venous or capillary origin such as from an occult ependymoma.191 It is rare, but has been recognized with increasing frequency with greater awareness and the increasing availability of high-field MRI. It should be considered in the differential diagnosis of CPA lesions since the affected patients commonly complain of bilateral progressive sensorineural hearing loss and ataxia (see Fig. 21-5).18,191,192 SS is characterized by intracellular and extracellular deposition of hemosiderin in the leptomeninges and subpial tissue of the brain, spinal cord, and cranial nerves. The acoustic nerve with its long glial-lined segment appears especially vulnerable. The characteristic hypointensity of pial and subpial tissue and the cranial nerves is seen only on T2WI on high-field MRI and gradient-echo imaging.18,192

Figure 21-33. CPA arteriovenous malformation. Selective vertebral angiogram. Principal feeder appears to be right AICA. (Courtesy of Livia G. Solti-Bohman, MD.)

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EXTRADURAL LESIONS

INTRA-AXIAL TUMORS

Bone lesions and paragangliomas are extradural lesions and are detailed in Chapter 22, Imaging of the Lateral Skull Base. Here they are briefly discussed only as a reminder that they may intrude into the CPA.1 Bone lesions in the petrous apex include cystic lesions such as cholesterol granuloma (cholesterol cyst) (Fig. 21-34), congenital intrapetrous epidermoid cyst, and petrous apex mucocele193; solid tumors such as chordoma, chondroma, chondrosarcoma (Fig. 21-35), giant cell tumor, myeloma, metastases, xanthoma,194 and so on; and intrapetrous carotid aneurysm. Papillary endolymphatic sac tumors, which may also protrude into the CPA, are discussed in Chapter 23, Imaging of the Facial Nerve. The more aggressive of the extradural tumors may at times transgress the dura and form an intradural mass (see Fig. 21-35). The same may be said for paragangliomas from the jugular foramen (see Fig. 21-6). The associated bone changes of an apparently intradural mass may reveal its true origin.

Intra-axial tumors arise from the brain and a detailed discussion is beyond the scope of this chapter. Some of them produce exophytic masses in the CPA and must be considered in the differential diagnosis. Intra-axial PF tumors arise from the brainstem, the cerebellum, or the fourth ventricle. Tumors of the brainstem are mainly astrocytomas that occur in children or young adults (Fig. 21-36).195–197 Exophytic growths are common. Tumors in the cerebellum may arise from the vermis or the hemispheres. The vermian tumors are principally medulloblastomas in childhood, now classified as primitive neuroectodermal tumors (PNETs).196,198,199 The hemispheric tumors include astrocytomas,196 usually of the pilocystic variety in young adults, hemangioblastomas in middle-aged individuals,200 and metastases.196 Any of the three may be cystic or solid.96 Lymphoma of the brain is seen with increasing frequency in recent years, particularly among immunosuppressed patients (Fig. 21-37).196,201

A

B

C

D

Figure 21-34. Triloculated cholesterol granuloma (cholesterol cyst) of petrous apex. Huge extra-axial mass partly in posterior and partly in middle fossa. A, T1WI shows markedly hyperintense contents in two of the loculations but a mixture of hyperintensities and hypointensities in the third. B, T2WI shows markedly hyperintense contents in two of the loculations but markedly hypointense contents in the third. Note increased thickness of hypointensity in capsule as compared to A. C, Postcontrast CT shows isodense contents and thin opaque capsules, in part formed by remodelled bone. D, Coronal HRCT shows extradural intrapetrous origin of mass, which has expanded into posterior and middle fossas (arrowheads). Note partitions between loculations (short arrow) and erosion of cochlea and semicircular canal (open arrows).

Imaging of the Cerebellopontine Angle

A

371

B

Figure 21-35. Petrous apex chondrosarcoma. A and B, Gd-T1WI. Highly conspicuous markedly enhancing intradural component (arrowhead) of tumor in CPA indenting pons represents merely “tip-of-iceberg” of the much larger but less conspicuous inhomogeneously enhancing extradural intrapetrous tumor extending into posterior fossa (twin arrows), middle ear (arrow), and Meckel’s cave (crossed arrow). Tumor also extends below skull base (black arrow). Note dural tail (long thin arrow).

Although any intra-axial tumor may grow into the CPA, tumors from the fourth ventricle are particularly prone to do so.202 They are ependymomas (Fig. 21-38)203,204 and choroids plexus papillomas (Fig. 21-39).205–208 Both of these tumors often contain granular calcifications. Although extra-axial tumors are more common in the CPA in adults and older teens,209 exophytic intra-axial tumors are more common in childhood.199 Nonneoplastic brain lesions such as multiple sclerosis (see Fig. 21-4)210–211 and infarct (Fig. 21-40)210,212 also enter into the differential diagnosis, as do AVMs,213 cavernous angiomas,214,215 developmental venous anomaly (venous angiomas), and capillary telangiectasia.214

In the IAC as in the CPA, tumors other than VSs are uncommon, but because therapeutic implications for some of the lesions are significantly different from those of VSs, each of the lesions should be carefully considered and if possible preoperatively identified. In general, few intracanalicular schwannomas, either vestibulocochlear or facial, are associated with signs of facial nerve involvement. Presence of such signs in a patient with an intracanalicular tumor should be a clinicoradiologic clue that arouses suspicion of a nonschwannomatous tumor.216 1. Vestibular schwannomas again constitute about 90% of the tumors.48,179,216 2. Facial schwannomas are rare and usually indistinguishable from VSs preoperatively.1,152,153 3. Meningiomas have been said to cause facial palsy more often than VSs but rarely have they been fully documented.217,218 They may be accompanied by hyperostosis or dural tail.

INTRACANICULAR LESIONS Intracanalicular lesions of the IAC carry a slightly different differential diagnosis from lesions of the CPA (Table 21-4).

A

B

Figure 21-36. Pontine astrocytoma. A, PDWI. B, T2WI. Intra-axial mass is mildly to moderately hyperintense and poorly marginated from pons and cerebellum (short arrows) and deforms fourth ventricle. Exophytic growth of tumor fills CPA cistern (open arrows). (Courtesy of Anton N. Hasso, MD.)

372

A

NEURORADIOLOGY

B

Figure 21-37. Primary cerebellar lymphoma. A, Gd-T1WI. B, PDMI. C, T2WI. Moderately enhancing intraaxial tumor in region of flocculus (arrow) mildly hyperintense on PDWI, B, and T2WI, C, with peritumoral edema (small arrows) not apparent on Gd-T1WI, A. Differential diagnosis: solid astrocytoma, hemangioblastoma, and metastasis.

C

A

B

Figure 21-38. CPA ependymoma. A, T1WI. B, T2WI. Exophytic tumor from foramen of Luschka, widening lateral recess and displacing medulla (short arrow) and fourth ventricle (arrow) from left cerebellum (open arrow). As in other exophytic intra-axial tumors (Fig. 21-36), brain tumor margins are less distinct than in extra-axial tumors. (Compare with Fig. 21-39.)

Imaging of the Cerebellopontine Angle

A

373

B

Figure 21-39. CPA choroid plexus papilloma. A, T1WI. B, T2WI. Tumor from foramen Luschka widening lateral recess, and displacing medulla (short arrow) and fourth ventricle (arrow) from right cerebellum (open arrow). Tumor is mildly hypointense on T1WI, A, and mildly hyperintense on T2WI, B. Because the choroid plexus is extra-axial, brain tumor margins of papilloma are better defined than in ependymoma (see Fig. 21-38) (Courtesy of Val M. Runge, MD.)

4. Intracanalicular vascular tumors (hemangioma/vascular malformation) are probably a distant second to VSs in incidences in the IAC.219–222 They tend to cause a greater degree of nerve deficits and are more commonly accompanied by facial nerve symptoms than VSs of comparable size.216,221,223–225 Some of them contain intratumoral bone spicules discernible on high-resolution CT with bone algorithm (Fig. 21-41)226,227; some may be associated with honeycomb changes of the adjacent bone (see Fig. 21-41).221 On MRI, some are isointense or hyperintense to CSF on T2WI and a few are moderately hyperintense on T1WI, but often they are indistinguishable from schwannomas, especially when precontrast T1WI and adequate T2WI are lacking (Fig. 21-42).220,222 5. Intracanalicular metastases may be suspected from a short duration of symptoms, facial weakness, a known history of malignancy, and a rapid growth rate on serial studies.1,228,229 Not infrequently they are bilateral (Figs. 21-18 and 21-43).

6. Lipochoristomas (lipomas) contain adipose and other ectopic mature mesenchymal tissues, such as smooth muscle, in varying proportions, with fat usually predominating. Fat shows distinctive MR signal intensities, being markedly hyperintense on T1WI and moderately hypointense on T2WI (Fig. 21-44)142,230 and can be confirmed by precontrast fat-suppressed T1WI.24,139 7. Melanotic melanomas are also hyperintense on T1WI and hypointense on T2WI, but amelanotic melanomas do not follow such a pattern (see Figs. 21-20 and 21-43).58,108,231 8. Lymphoma in the IAC may involve the leptomeninges.232 9. Glioma of the acoustic nerve is an extreme rarity.233 10. Osteomas of the IAC are also rare and are better demonstrated on CT than on MRI (Fig. 21-45). Osteomas containing purely cortical bone are hypointense on all sequences; those containing fatty marrow simulate lipomas in intensities.

TABLE 21-4. Intracanalicular Lesions Neoplastic Vestibular schwannoma Facial schwannoma Meningioma Hemangioma Metastasis Melanoma Lymphoma Glioma Osteoma

Nonneoplastic

Figure 21-40. AICA infarct. T2WI. Nonexpansile hyperintense right pontocerebellar lesion (open arrow) in territory of anterior inferior cerebellar artery hardly discernible on T1WI (not illustrated). (Compare with Fig. 21-4.) Note also hyperintensity from slowly flowing blood in tortuous basilar artery (arrow).

Lipochoristomas (lipomas) AICA loop AICA aneurysm Meningitis Neuritis Hamartoma AICA, anterior inferior cerebellar artery.

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A

B

C

D

Figure 21-41. IAC hemangioma A, T1WI. B, Gd-T1WI. C, T2WI. D, and E, HRCT. Tumor (white arrow) extending slightly anterointeriorly beyond IAC is nearly isointense on T1WI, A, strongly enhancing postcontrast, B, and hyperintense on T2WI C, similar to schwannomas. HRCT reveals characteristic intratumoral bone spicule (black arrow) in D and “honeycomb” bone erosion (black arrow) of the floor of IAC in E. Some hemangiomas however do not show the characteristic bone changes (see Fig. 21-37). (Courtesy of Malcolm D. Graham, MD.)

E

Hamartoma of the acoustic nerve has also been reported.216,234 Other nonneoplastic IAC lesions include (1) AICA loop in the IAC (see Figs. 21-30 and 21-1),169,177,235 which may at times simulate a tumor,236 (2) AICA aneurysm as previously discussed (see Fig. 21-31),182,183 (3) meningeal inflammation and adhesion (Fig. 21-46),237,238 and (4) neuritis of the facial or acoustic nerves (Fig. 21-47).239–243 One report described four cases of vestibulocochlear neuritis with hearing loss, positive auditory brainstem response, and MRI finding of focal nerve enhancement indistinguishable from small intracanalicular VSs.244 A period of observation was

thus advised for very small lesions to verify persistence of symptoms or tumor growth.244,245

CONCLUSION The variety of tumors and other lesions that may arise in the CPA and the IAC are indeed enormous. However, the common extra-axial types, which are well over 90% of the lesions, are quite consistent in their appearance on imaging. These include VS, meningioma, epidermoid and

Imaging of the Cerebellopontine Angle

Figure 21-42. IAC hemangioma/vascular malformation. Gd-T1WI. Tumor is markedly hyperintense postcontrast and indistinguishable from IAC schwannomas. Compare with Figs. 21-7 and 21-41.

A

B

Figure 21-43. Bilateral IAC metastases from melanoma. A, T1WI. B, Gd-T1WI. C, T2WI. Tumors are isointense on T1WI, mildly enhancing of Gd-T1WI. One is isointense with gray matter and one with white matter on T2WI. Patient had bilateral rapidly progressive hearing loss and facial palsies.

C

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A

B

Figure 21-44. IAC lipoma. A, Gd-T1WI. B, T2WI. On Gd-T1WI alone, hyperintense tumor is indistinguishable from a schwannoma or hemangioma (see Figs. 21-7 and 21-42). Hypointensity of tumor (arrow) on T2WI, however, suggests fat. See also Fig. 21-25. (Courtesy of Kenneth L. Kidd, MD.)

A

B

Figure 21-45. IAC osteoma. A, Coronal CT. Osteoma (arrow) consisting entirely of cortical bone arising from anterosuperior wall of porus acusticus caused sensorineural hearing loss relieved by resection. B, Gd-T1WI. Tumor (arrow) is hypointense in all sequences and nonenhancing postcontrast. A marrowcontaining osteoma would have shown central hyperintensity on T1WI similar to marrow in petrous apices. (Courtesy of Derald E. Brackmann, MD.)

A

B

Figure 21-46. Chronic inflammation. A, T1WI. B, Gd-T1WI. Small isointense soft tissue in fundus of IAC (arrowhead) enhancing postcontrast (arrow), indistinguishable from small VS except for perhaps presence of a small dural tail (small arrow). Compare with Figs. 21-7 and 21-47. Patient had progressive left sensorineural hearing loss of 3-year duration. Mass in fundus of left IAC adherent to dura and involving acoustic nerve was completely removed. Pathologic diagnosis: nongranulomatous active chronic nonspecific inflammation. (Courtesy of Robert D. Sostrin, MD.)

Imaging of the Cerebellopontine Angle

A

377

B

Figure 21-47. Focal cochlear neuritis. A, T1WI. B, Gd-T1WI. Globular thickening of acoustic nerve (arrow) with marked postcontrast enhancement (arrow) indistinguished from intracanalicular VS (see Fig. 21-7). Patient had progressive right sensorineural hearing loss of 1-year duration and abnormal acoustic brainstem reflex. C, Gd-T1WI, obtained 10 weeks after A and B. Considerable decrease in thickening and enhancement since initial study, B, with now only residual enhancement in cochlear nerve. Lack of clinical improvement lead to exploration by middle fossa approach, which found no tumor. (Courtesy of Michael J. O’Leary, MD.)

C other cysts, nonvestibular PF schwannomas, and vascular lesions. Most of the extradural and the intra-axial lesions are also recognizable under systematic analysis. With attention to technical detail, careful analysis of findings, a systematic approach to differential diagnosis, and close clinicoradiologic correlation, a correct radiologic diagnosis is possible, even for many of the rare lesions.

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190. Lasjaunias P, Piske R, Terbrugge K, Willinsky R: Cerebral arteriovenous malformations (C. AVM) and associated arterial aneurysms (AA). Analysis of 101 C. AVM cases, with 37 AA in 23 patients. Acta Neurochir (Wien) 91:29–36, 1988. 191. Zimmerman RS, Spetzler RF, Lee KS, et al: Bilateral pial siderosis and hearing loss. Paper presented at the Eleventh International Congress of Head and Neck Radiology, Uppsala, Sweden, June 9–10, 1988. 192. Gomori JM, Grossman RI, Bilaniuk LT, et al: High-field MR imaging of superficial siderosis of the central nervous system. J Comput Assist Tomogr 9:972–975, 1985. 193. Larson TL, Wong ML: Primary mucocele of the petrous apex: MR appearance. Am J Neuroradiol 13:203–204, 1992. 194. Jackler RK, Brackmann DE: Xanthoma of the temporal bone and skull base. Am J Otol 8:111–115, 1987. 195. Arnautovic KI, Husain MM, Linskey ME: Cranial nerve root entry zone primary cerebellopontine angle gliomas: A rare and poorly recognized subset of extraparenchymal tumors. J Neurooncol 49:205–212, 2000. 196. Hasso AN, Fahmy JL: Posterior fossa neoplasms. In Stark DD, Bradley WG Jr (eds.): Magnetic Resonance Imaging, 2nd ed. St. Louis, Mosby-Year Book, 1992. 197. Yuh WT, Nguyen HD, Mayr NA, Follett KA: Pontine glioma extending to the ipsilateral cavernous sinus and Meckel’s cave: MR appearance. Am J Neuroradiol 13:346–348, 1992. 198. Papaefthymiou G, Tritthart H, Kleinert R, Pendl G: Primitive neuroectodermal tumor (PNET) extending into the cerebellopontine angle: Case report. Wien Klin Wochenschr 105:614–617, 1993. 199. Segall HD, et al: Computed tomography in neoplasms of the posterior fossa in children. Radiol Clin North Am 20:237–253, 1982. 200. Lee SR, Sanches J, Mark AS, et al: Posterior fossa hemangioblastomas: MR imaging. Radiology 171:463–468, 1989. 201. Schwaighofer BW, Hesselink JR, Press GA, et al: Primary intracranial CNS lymphoma: MR manifestations. Am J Neuroradiol 10:725–729, 1989. 202. Naidich TP, Lin JP, Leeds NE, et al: Primary tumors and other masses of the cerebellum and fourth ventricle: Differential diagnosis by computed tomography. Neuroradiology 14:153–174, 1977. 203. Ahn MS, Jackler RK: Exophytic brain tumors mimicking primary lesions of the cerebellopontine angle. Laryngoscope 107:466–471, 1997. 204. Spoto GP, Press GA, Hesselink JR, Solomon M: Intracranial ependymoma and subependymoma: MR manifestations. Am J Neuroradiol 11:83–91, 1990. 205. Ford WJ, Brooks BS, el Gammal T, et al: Adult cerebellopontine angle choroid plexus papilloma: MR evaluation. Am J Neuroradiol 9:611, 1988. 206. Ken JG, Sobel DF, Copeland B, et al: Choroid plexus papillomas of the foramen of Luschka: MR appearance. Am J Neuroradiol 12: 1201–1203, 1991. 207. Martin N, Pierot L, Sterkers O, et al: Primary choroid plexus papilloma of the cerebellopontine angle: MR imaging. Neuroradiology 31:541–543, 1990. 208. McGirr SJ, Ebersold MJ, Scheithauer BW, et al: Choroid plexus papillomas: Long-term follow-up results in a surgically treated series. J Neurosurg 69:843–849, 1988. 209. Fukui MB, Hogg JP, Martinez AJ: Extraaxial ependymoma of the posterior fossa. Am J Neuroradiol 18:1179–1181, 1997. 210. Bradley WG Jr: Brainstem: anatomy and pathology. In Stark DD, Bradley WG Jr (eds.): Magnetic Resonance Imaging, 2nd ed. St. Louis, Mosby-Year Book, 1992. 211. Wessbecher FW, Maravilla KR: Multiple sclerosis. In Stark DD, Bradley WG Jr (eds.): Magnetic Resonance Imaging, 2nd ed. St. Louis, Mosby-Year Book, 1992. 212. Hinojosa R, Kohut RI: Clinical diagnosis of anterior inferior cerebellar artery thrombosis. Autopsy and temporal bone histopathologic study. Ann Otol Rhinol Laryngol 99:261–272, 1990.

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213. Garcia Monaco R, Alvarez H, Goulao A, et al: Posterior fossa arteriovenous malformations. Angioarchitecture in relation to their hemorrhagic episodes. Neuroradiology 31:471–475, 1990. 214. Goulao A, Alvarez H, Garcia Monaco R, et al: Venous anomalies and abnormalities of the posterior fossa. Neuroradiology 31:476–482, 1990. 215. Zimmerman RS, Spetzler RF, Lee KS, et al: Cavernous malformations of the brain stem. J Neurosurg 75:32–39, 1991. 216. Neely JG, Neblett CR: Differential facial nerve function in tumors of the internal auditory meatus. Ann Otol Rhinol Laryngol 92:39–41, 1983. 217. Langman AW, Jackler RK, Althaus SR: Meningioma of the internal auditory canal. Am J Otol 11:201–204, 1990. 218. Singh KP, Smyth GD, Allen IV: Intracanalicular meningioma. J Laryngol Otol 89:549–552, 1975. 219. Bird CR, Drayer BP, Yeates AE: Gas CT cisternography of an intracanalicular vascular malformation. Am J Neuroradiol 6:969–970, 1985. 220. Linskey ME, Jannetta PJ, Martinez AJ: A vascular malformation mimicking an intracanalicular acoustic neurilemoma. Case report. J Neurosurg 74:516–519, 1991. 221. Lo WW, Horn KL, Carberry JN, et al: Intratemporal vascular tumors: evaluation with CT. Radiology 159:181–185, 1986. 222. Lo WW, Shelton C, Waluch V, et al: Intratemporal vascular tumors: detection with CT and MR imaging. Radiology 171:445–448, 1989. 223. Dufour JJ, Michaud LA, Mohr G, et al: Intratemporal vascular malformations (angiomas): Particular clinical features. J Otolaryngol 23:250–253, 1994. 224. Shelton C, Brackmann DE, Lo WW, Carberry JN: Intratemporal facial nerve hemangiomas. Otolaryngol Head Neck Surg 104:116–121, 1991. 225. Sundaresan N, Eller T, Ciric I: Hemangiomas of the internal auditory canal. Surg Neurol 6:119–121, 1976. 226. Atlas MD, Fagan PA, Turner J: Calcification of internal auditory canal tumors. Ann Otol Rhinol Laryngol 101:620–622, 1992. 227. Gavilan J, Nistal M, Gavilan C, Calvo M: Ossifying hemangioma of the temporal bone. Arch Otolaryngol Head Neck Surg 116:965–967, 1990. 228. Jung TT, Jun BH, Shea D, Paparella MM: Primary and secondary tumors of the facial nerve. A temporal bone study. Arch Otolaryngol Head Neck Surg 112:1269–1273, 1986. 229. Nelson DR, Dolan KD: Cerebellopontine angle metastatic lung carcinoma resembling an acoustic neuroma. Ann Otol Rhinol Laryngol 100:685–686, 1991.

230. Smith MM, Thompson JE, Thomas D, et al: Choristomas of the seventh and eighth cranial nerves. Am J Neuroradiol 18:327–329, 1997. 231. Marx HF, Colletti PM, Raval JK, et al: Magnetic resonance imaging features in melanoma. Magn Reson Imaging 8:223–229, 1990. 232. Ierokomos A, Goin DW: Primary CNS lymphoma in the cerebellopontine angle. Report of a case. Arch Otolaryngol 111:50–52, 1985. 233. Kasantikul V, Palmer JO, Netsky MG, et al: Glioma of the acoustic nerve. Arch Otolaryngol 106:456–459, 1980. 234. Babin RW, Fratkin JD, Cancilla PA: Hamartomas of the cerebellopontine angle and internal auditory canal: Report of two cases. Arch Otolaryngol 106:500–502, 1980. 235. Bird CR, Hasso AN, Drayer BP, et al: The cerebellopontine angle and internal auditory canal: Neurovascular anatomy on gas CT cisternograms. Radiology 154:667–670, 1985. 236. Khangure MS, Mojtahedi S: Air CT cisternography of anterior inferior cerebellar artery loop simulating an intracanalicular acoustic neuroma. Am J Neuroradiol 4:994–995, 1983. 237. Downey EF Jr, Buck DR, Ray JW: Arachnoiditis simulating acoustic neuroma on air-CT cisternography. Am J Neuroradiol 2:470–471, 1981. 238. von Glass W, Haid CT, Cidlinsky K, et al: False-positive MR imaging in the diagnosis of acoustic neurinomas. Otolaryngol Head Neck Surg 104:863–867, 1991. 239. Anderson RE, Laskoff JM: Ramsay Hunt syndrome mimicking intracanalicular acoustic neuroma on contrast-enhanced MR. Am J Neuroradiol 11:409, 1990. 240. Daniels DL, Czervionke LF, Millen SJ: MR findings in the Ramsay Hunt syndrome. Am J Neuroradiol 9:609, 1988. 241. Korzec K, Sobol SM, Kubal W, et al: Gadolinium-enhanced magnetic resonance imaging of the facial nerve in herpes zoster oticus and Bell’s palsy: Clinical implications. Am J Otol 12:163–168, 1991. 242. Osumi A, Tien RD: MR findings in a patient with Ramsay-Hunt syndrome. J Comput Assist Tomogr 14:991–993, 1990. 243. Tien RD: Inflammatory disease of the cranial nerves. Neuroimaging Clin North Am 1:89, 1991. 244. Han MH, Jabour BA, Andrews JC, et al: Nonneoplastic enhancing lesions mimicking intracanalicular acoustic neuroma on gadolinium-enhanced MR images. Radiology 179:795–796, 1991. 245. Arriaga MA, Carrier D, Houston GD: False-positive magnetic resonance imaging of small internal auditory canal tumors: A clinical, radiologic, and pathologic correlation study. Otolaryngol Head Neck Surg 113:61–70, 1995.

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Outline Technical Considerations Computed Tomography Magnetic Resonance Imaging Pathology Petrous Apex Cholesterol Cysts or Granulomas Epidermoids Mucoceles Pseudolesions of the Petrous Apex Petrous Apicitis Aneurysms Chordomas and Chondrosarcomas Other Lesions Fibrous Dysplasia

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Benign Vascular Tumors Meningiomas Endolymphatic Sac Tumors Fifth Nerve Sheath Tumor and Cavernous Sinus Hemangiomas Direct Extension from Nasopharyngeal and Infratemporal Lesions Metastasis and Other Solid Lesions Superior Semicircular Canal Dehiscence Jugular and Carotid Region Paragangliomas Nerve Sheath Tumors Aberrant Carotid Arteries

Other Lesions Involving the Jugular and Carotid Area Middle Ear and Mastoid Inflammatory Middle Ear Disease Tumors of the Middle Ear External Auditory Canal Keratosis Obturans External Auditory Canal Cholesteatoma Exostosis and Osteoma Malignant Lesions of the External Canal Infection Malignant External Otitis Summary

he lateral skull base is not a precisely defined region. This terminology has recently evolved in the discipline of skull base surgery to describe the region coinciding roughly with the medial temporal bone. In this context, the other regions are the anterior skull base and the central skull base. The anterior skull base is predominantly the floor of the anterior cranial fossa and subjacent nasal cavity, upper ethmoid sinuses, and orbits. Central skull base refers to the region close to the sphenoid bone and includes the cavernous sinus, sella, and parts of the basiocciput as well as the sphenoid bone itself along with the various foramina transmitting the vascular and neural structures. This chapter emphasizes the petrous apex and medial temporal bone but also includes some description of the pathology in contiguous regions more appropriately assigned to the central skull base. Lesions of the middle ear and external auditory canal are briefly discussed. The proximity of the cavernous sinus and clivus to the temporal bone makes them appropriate for inclusion in a discussion of the lateral skull base. The differential diagnoses of lesions in these areas are closely related and pathology can certainly cross from one part of the skull base to the next. A large number of diagnostic possibilities must be considered when a lesion is detected in the temporal bone or lateral skull base. The diagnosis can be limited considerably depending on the precise location or apparent site of the lesion’s origin. A tumor arising in one location may have a diagnosis completely different from that of a lesion arising in another location only millimeters away.

Grace Fan, MD Hugh D. Curtin, MD

This chapter separates the temporal bone into four major regions: the petrous apex, the jugular and carotid region, the middle ear, and the external auditory canal (EAC). The internal auditory canal would represent a fifth major area but this is discussed in a separate chapter along with the cerebellopontine angle cistern. The seventh nerve has a tortuous course through the entire temporal bone and must be considered in the differential diagnosis in many regions.

TECHNICAL CONSIDERATIONS Computed tomography (CT) and magnetic resonance imaging (MRI) are used in evaluation of the skull base. Individual radiologists have certain preferences in some regions, but one modality may be clearly superior in certain situations. High-resolution CT scanning is usually preferred as the initial imaging study for the evaluation of most temporal bone disease other than that in the internal auditory canal. CT offers the greatest structural definition of current imaging modalities with the advantage of demonstrating thin bony septations and fine bony anatomy to localize and characterize disease. Air, thin plates of cortical bone, septations in the mastoids, and the otic capsule all have a similar appearance on MRI. All appear black or as a signal void and little structure is appreciated. MRI, however, has the ability to distinguish 383

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subtle differences in soft tissues. In some cases, the signal characteristics can strongly suggest a certain diagnosis. A gadolinium-enhanced MRI is also considered the most sensitive study for the evaluation of possible internal auditory canal pathology, particularly for acoustic neuromas (vestibular schwannomas).

Computed Tomography High-resolution axial thin section CT is usually performed to visualize the extent of bone involvement in lateral skull base lesions. Care should be taken to ensure that any extension above or below the skull base is included in the scanned area. To ensure maximal bone detail, bone algorithms should be performed on the data. Reformatted coronal images can be generated from the axial images. These images can give excellent information on the relationship of structures. Until recently, direct scanning has had a higher resolution and was required if bone erosions in a plane other than the axial were to be detected. The recent introduction of multidetector CT scanners has further improved image quality by improving spacial resolution. The images are obtained with very thin sections (as thin as 0.5 mm) allowing for less partial volume artifact. The cross-sectional data can be postprocessed or reformatted into multiple planes, most commonly axial and coronal. Occasionally, additional planes such at various obliquities are helpful in assessing certain pathologies and complex anatomies. Multislice multidetector CT has not only allowed finer slice imaging but also accelerates data acquisition times, thus decreasing motion-related artifacts and radiation risk. Currently, at our institution, we do not do direct coronal scanning. The middle ear, mastoid, and external auditory canal are often evaluated without intravenous contrast. In evaluation of the petrous apex and the carotid/jugular area, contrast is often helpful and is routinely used. Bolus injection is important for evaluating lesions involving the jugular fossa, particularly differentiating an occluded jugular vein from tumor. With multidetector machines, CT angiograms (CTA) and CT venograms (CTV ) can be useful in detecting arterial and venous pathologies such as aneurysms and venous sinus thrombosis.

Magnetic Resonance Imaging On MRI scans through the skull base, spin echo images are still the usual images used. For small lesions, the thinnest cuts possible should be performed. Unenhanced T1weighted images are best for demonstrating the fat planes beneath the skull base. Postcontrast images are essential for evaluating intracranial extension and certain pathologies. Routine T2-weighted images do not provide anatomic detail but are often helpful in narrowing the differential diagnosis. Very high resolution T2-weighted images are used as pseudocisternograms and give excellent detail regarding the anatomy of the IAC. Fat suppression on the enhanced images may be helpful in evaluating lesions that extend beyond the petrous bone into the extracranial tissues. Caution is necessary, however, when evaluating near air-containing structures, such as nasopharynx and sphenoid sinus. The suppression of fat

signal may fail, mimicking an enhancing lesion.1 Other artifacts may obscure important anatomy. Other current MRI techniques such as magnetic resonance angiography (MRA) and magnetic resonance spectroscopy (MRS) may also aid in the diagnosis. MRA should be performed if vascular lesions such as aneurysm or anatomical vascular variations are questioned. MRS may help further characterize a malignant lesion. Diffusion-weighted images (DWI) do not give good anatomic detail but may give information regarding molecular motion or Brownian movement within a lesion. Lesions with similar imaging characteristics on routine MRI sequences can sometimes be distinguished. For instance, epidermoids are bright on diffusion-weighted images while a cerebrospinal fluid (CSF)-containing structure tends to be dark.

PATHOLOGY To aid differential diagnosis, the lateral skull base is divided in four regions: petrous apex, jugular/carotid area, middle ear, and external canal. Although there is some overlap, the lesions that arise in each of these regions are fairly distinct so the regions are discussed separately in the following sections. Although regional divisions are important, some lesions such as metastasis, multiple myeloma, and soft tissue sarcomas may involve any portion of the petrous bone.

PETROUS APEX The petrous bone is a simple block of bone covered by dura and frequently penetrated by air cells from the middle ear or mastoid. The bone is separated from the greater wing of the sphenoid by the petrosphenoidal fissure and from the clivus by the petroclival or petro-occipital synchondrosis. Lesions in the petrous apex typically are related to the bone, the dura, or the air cell system with its associated modified respiratory epithelium. Many lesions involve the apex secondarily.

Cholesterol Cysts or Granulomas The petrous apex cholesterol cyst, or granuloma, consists of variable amount of granulation tissue and fluid in what is considered an expanded air cell of a pneumatized petrous apex. The cholesterol cyst is most likely the end point of a continuum of pathology beginning with a simple obstructive effusion and ending with an expanded air cell that contains fibrosis, granulation tissue, fluid, and blood breakdown products. The narrow drainage path of an apex air cell may be compromised by a minor infection or simple mucosal edema related to pressure changes in the middle ear. Fluid may accumulate, giving an effusion. At some time in the evolution of the lesion small hemorrhages may occur from the wall (Fig. 22-1). The blood breakdown products are poorly absorbed from the closed cavity and contribute to the characteristic findings on CT and particularly MRI. On CT scans, the cholesterol cyst is an expansile lesion at the petrous apex. The bone is smoothly remodeled similar to a mucocele (Fig. 22-1A). Indeed, the findings of an apex cholesterol cyst have similarities to a hemorrhagic mucocele in

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the paranasal sinuses. Typically, the cyst has similar density to the brain (Fig. 22-2A), denser than usually seen in an epidermoid. Sometimes the wall of the cholesterol cyst enhances but no enhancement occurs in the lumen of the cyst. MRI demonstrates a characteristic bright signal on a T1-weighted sequence (Fig. 22-2B). The signal on a T2-weighted signal is predominantly bright but may have a mixture of high and low signals (Fig. 22-2D). Areas of very dark signal are also characteristic and most likely represent hemosiderin, a breakdown product of blood.2,3 A cholesterol cyst of the petrous apex shares some characteristics with the cholesterol granuloma of the middle ear. The cholesterol granuloma of the middle ear contains cholesterol clefts and granulation tissue but does not tend to cause cystic expansion.4 Imaging not only suggests the diagnosis but can also determine the relationship of the lesion to the carotid artery and to the labyrinth and internal auditory canal. Computed tomography can usually define the air cell tract that originally led to the air cell that is now expanded.

Epidermoids

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Epidermoids are less common than previously thought, yet they represent a major differential consideration for expansile masses at the petrous apex. There is a wall of stratified squamous epithelium and a central mass of keratin. Desquamation of the cells from the wall of these lesions is responsible for their slowly progressive expansion and resultant bony remodeling. Although the wall may enhance, the central keratin mass does not. In the petrous apex, an epidermoid can show expansion of bone that is very similar to a cholesterol granuloma. In our experience, the epidermoid may appear to follow lines of least resistance and expand above or below the otic labyrinth and at times may reach the middle ear. The CT density tends to be slightly lower than that of a cholesterol granuloma but differentiation of the two entities is easier with MRI. Epidermoids usually have a low T1 signal and a high T2 signal (Fig. 22-3), distinguishing them from cholesterol cysts, which have a high T1 signal.3,5 The T1-weighted sequence is the key consideration. Almost all epidermoids are high signal on T1-weighted images; epidermoids are typically low signal on the T1-weighted sequence. Epidermoids may occur intracranially6; the most common location is in the cerebellopontine angle cistern. Of note, though rare intracranial epidermoids have been reported to have a bright T1 signal, this phenomenon is distinctly unusual particularly in the skull base. The imaging differentiation of cholesterol cyst and epidermoids is clinically relevant. To prevent recurrence, the walls of epidermoid tumors must be completely resected or exteriorized. This may entail extensive surgery.7,8 This surgery may not be necessary for cholesterol granulomas.

Figure 22-1. Hemorrhage in a cholesterol cyst. A, Axial CT in bone algorithm demonstrates an expansile mass in the left petrous apex (black arrows) partly surrounding the petrous carotid artery (black arrowhead). B, Axial T2-weighted image shows a fluid-fluid level in the mass (white arrow). Note the fluid in the mastoids (white arrowhead). The lesion is bright on axial T1-weighted view. This high signal represents blood breakdown products, not enhancement from gadolinium (C).

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Figure 22-2. Cholesterol cyst, or granuloma. A, Axial nonenhanced CT shows an expansile mass at the right petrous apex with soft tissue density (black arrowhead). B, Axial T1-weighted MRI without contrast. The mass demonstrates bright signal (white arrow). C, The lesion does not enhance on the postgadolinium fat-saturated T1-weighted image (double arrows). D, T2-weighted image demonstrates mixed signal. The low signal (white arrowhead) is probably a result of the hemorrhagic contents.

Many surgeons treat cholesterol granulomas by a drainage procedure and do not attempt to resect the walls of the mass.9

Mucoceles True simple mucoceles of apical petrous cells are rare but have been described. Such lesions have low T1 and bright

T2 signal with peripheral enhancement of the lining mucosa.10 Because mucoceles also arise in obstructed air cells, they may be part of the same spectrum of disease as cholesterol cysts or granulomas. Mucoceles in other sinuses have variable signals depending on their protein content, so theoretically they might be very bright on T1-weighted images and difficult to distinguish from

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B B Figure 22-3. Epidermoid. A, Axial T1-weighted MRI demonstrates an expansile low signal right petrous apex lesion (arrow). B, The lesion (arrowhead) has high signal on T2-weighted image.

cholesterol granulomas. Mucoceles, like epidermoids and cholesterol cysts, do not enhance centrally and therefore are distinguished from more solid tumors, which do have central enhancement. Chordomas, chondrosarcomas, metastasis, plasmacytomas, and pituitary adenomas enhance to some degree throughout their mass.

Pseudolesions of the Petrous Apex Several pseudolesions can be confused with cholesterol granuloma or epidermoid. For example, if there is nonpneumatized medullary bone at one petrous apex

Figure 22-4. Normal fat of the petrous apex. A, Noncontrast T1-weighted image shows asymmetry of the signal at the petrous apex. On the right, the petrous apex is pneumatized. On the left, medullary fat at the petrous apex has high signal (white arrow). B, CT scan at approximately the same level. Compare the pneumatized right petrous apex with the medullary bone in the left petrous apex (black arrow).

and pneumatization of the contralateral side, T1-weighted MRI images show a high signal in the nonpneumatized bone. The high signal represents medullary fat (Fig. 22-4A). The air in the pneumatized bone gives a signal void typical of air. T2-weighted images reveal the normal drop-off in signal from the medullary fat and exclude cholesterol granuloma. On fast spin echo images, this fading of the fat signal is less dramatic. In such cases, fat suppression sequences with T1 images can be used to eliminate the signal from fat and clarify the situation. CT can also differentiate these two entities. Fluid or mucus in apical air cells is more challenging. Mucus, depending on its protein concentration, has highly

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Figure 22-5. Fluid in apical air cells. CT scan demonstrates opacification of the right petrous apex (arrow). Note the preservation of the septae, excluding cholesterol granuloma and mucocele from the differential.

variable signal characteristics that could mimic cholesterol granuloma. In such cases, CT is revealing. If there is preservation of septae between the opacified air cells and no expansion, a cholesterol cyst or mucocele is excluded (Fig. 22-5). If obstruction persists, however, breakdown or expansion of air cells may occur and a mucocele or cholesterol cyst may develop. Hemorrhage into the obstructed air cell may set up the foreign body giant cell reaction characteristic of cholesterol cyst or granuloma. Obstructed air cells, mucocele, and cholesterol granuloma may represent a continuous spectrum of pathology. An alternative to immediate surgery is to follow these patients with CT or MRI. Rarely, a pocket of arachnoid extends into the petrous apex, usually from the region of Meckel’s cave (Fig. 22-6). These CSF-filled pockets can be difficult to differentiate from an epidermoid. Coronal and sagittal T2-weighted imaging are often useful planes for demonstrating the connection to the CSF space. In ambiguous cases, a CT with intrathecal contrast confirms these findings.

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Figure 22-6. Bilateral meningoceles of the petrous apex. A, Sequential high-resolution axial T2-weighted images demonstrate high signal in each petrous apex (arrows) extending from Meckel’s cave (arrowheads) with corresponding high-resolution coronal T2- and T1-weighted images (B and C ).

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Figure 22-7. Petrous apicitis presenting with cranial nerve six palsy. A, Axial T1-weighted image with contrast and fat saturation demonstrates abnormal focal enhancement at the right petrous apex with dural enhancement extending along the clivus in the region of Dorello’s canal (arrowhead), right cerebellopontine angle, and right internal auditory canal (white arrows). B, Axial CT bone algorithm shows fluid in the inferior right petrous apex but no definite bone destruction (black arrow).

Petrous Apicitis Petrous apicitis is a destructive infection involving the petrous apex. Facial pain, sixth nerve palsy, and ipsilateral ear drainage is a clinical triad described by Gradenigo in patients with petrous apicitis (Fig. 22-7). CT will show air cell opacification (Fig. 22-7B) and sometimes bone breakdown. The dura may enhance (Fig. 22-7A) and epidural abscess can develop as the infection progresses. MRI will show the enhancement of the apex extending to the dura and toward the gasserian ganglion in Meckel’s cave.

Aneurysms Aneurysms of the petrous segment of the carotid artery are rare.11 Because of their location they may grow quite large before compressing vital structures and producing symptoms. When these aneurysms erode into the middle ear cavity, they are particularly dangerous. The turbulent flow within the aneurysms produces a variable MRI signal that can be very confusing (Fig. 22-8A), particularly if flowsensitive MRI is not performed. In other cases, much of the aneurysm can be filled with thrombus. CTA and MRA are currently the most sensitive imaging modalities for assessing aneurysms. Clinically, aneurysms can mimic a middle ear mass such as a glomus tumor. In these cases, CT is helpful because it can show the remodeling or erosion of the wall of the petrous carotid canal (Fig. 22-8B). This thin wall of bone is invisible on most MR images because dense cortical

bone has the same signal as the adjacent air in the tympanic cavity. (See also the section on Aberrant Carotid Arteries.)

Chordomas and Chondrosarcomas Chordomas and chondrosarcomas share many imaging features and are therefore considered together. These lesions arise medial to the apex but can extend into the temporal bone as they enlarge. Chordomas are more often midline and arise from notochordal remnants in the basiocciput and basisphenoid (Fig. 22-9). Conversely, chondrosarcomas usually arise from cartilage in cranial base synchondroses. Most chondrosarcomas in the lateral skull base region arise off midline at the petroclival synchondrosis (Figs. 22-10 and 22-11). They may also arise from the smaller synchondroses in the spheno-occipital separation, nasal septum, paranasal sinuses, and the more anterior skull base.12–14 Both tumors are bright on T2-weighted images. This is important because several mimics lack this intense T2 signal. For example, metastasis, multiple myeloma, and invasive prolactinoma may all mimic the CT and T1-weighted MRI appearance of a chordoma. However, on T2-weighted images, these lesions generally do not have a bright T2 signal (Fig. 22-12D).15 The distinction is important because chordoma and chondrosarcoma may be managed by a major skull base resection and radiation, whereas the other lesions can be managed by biopsy and radiation or medical therapy.13,14,16

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C Figure 22-8. Petrous carotid aneurysm. A, Axial noncontrast T1-weighted MRI. A mass at the left petrous apex extending into the middle ear has mixed areas of high and low signal (outlined arrows). The patient was taken to surgery with the thought that this middle ear mass represented a cholesteatoma or cholesterol granuloma. At surgery it was observed that the mass was pulsatile and additional studies were obtained. B, Axial CT scan bone algorithm. The left carotid canal is enlarged (arrows). Note the normal lateral bony wall of the right carotid (curved arrow). C, AP view from a left common carotid angiogram. A multilobulated aneurysm (arrows) is present that involves the proximal aspect of the petrous segment of the internal carotid artery. The variable signal within the aneurysm is due to flow rate variations within the lumen.

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C Figure 22-9. Chordoma. A, Axial postcontrast CT shows a large enhancing mass in the central skull base. The mass invades both cavernous sinuses (straight arrows) and also extends to involve the petrous apex bilaterally (curved arrows). B, The bone algorithm at the same level as A. There is erosion of the petrous apex bilaterally (curved arrows) and also bilateral mastoid effusions (open arrows). C, Slightly higher cut shows small spicules of bone in the center of the mass (arrowheads). These most likely are remnants of preexisting bone rather than matrix mineralization.

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Figure 22-10. Skull base chondrosarcoma. A, Axial T2-weighted image shows a very high signal expansile mass in the right petroclival synchondrosis extending into the right petrous apex (black arrow). B-C, Coronal T1-weighted images without and with contrast demonstrates enhancement of the lesion (white arrows). D, Bone algorithm axial CT demonstrates central chondroid matrix within the mass that is eroding the bone at the synchondrosis (arrowhead).

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B A Figure 22-11. Chondrosarcoma. A, Coronal CT bone algorithm shows the dense chondroid mineralization in this chondrosarcoma (straight arrows). This lesion arose at the petroclival synchondrosis. Note the normal synchondrosis on the left (curved arrow). B, T2-weighted MRI. The mineralized portion of the tumor has low T2 signal (arrows). The nonmineralized portions of the chondrosarcoma are bright (outlined arrows) on T2.

Both chordomas and chondrosarcomas may calcify. In one study, 7 of 26 (27%) chordomas and 7 of 16 (44%) chondrosarcomas contained calcifications. Many times the mineralization or bone and calcium in a chordoma represent remnants of bone largely destroyed by the tumor (Fig. 22-9C). Large fragments may exist. Chondrosarcoma calcifications are variable and may be large and clumped (see Figs. 22-10D and 22-11A) and are often easily visualized on MRI as a region of very low signal on all imaging sequences (Fig. 22-11B). Some chondrosarcomas, however, show no obvious mineralization. Both chordomas and chondrosarcomas enhance moderately to intensely after contrast (Fig. 22-10B and C). The enhancement is often easier to appreciate on MRI. The position of the lesion is a major determinant in differentiating chordoma from chondrosarcoma. Chordoma is almost exclusively a midline lesion; chondrosarcomas, although they occur occasionally in the midline, are more commonly located off midline in the area of the synchondrosis separating the central skull base from the petrous apex.

Other Lesions Fibrous Dysplasia Fibrous dysplasia can present a serious diagnostic challenge with MRI. Elements in the dysplastic bone are metabolically active and enhance after contrast. On enhanced MRI scans, fibrous dysplasia may look like an enhancing skull base neoplasm (Fig. 22-13A–C). Most often it is hypointense on T2-weighted images because of the bone matrix within it;

however, occasionally parts of the fibrous dysplasia have a high T2 signal (Fig. 22-13D).17 Computerized tomography can be definitive if it reveals the dense “ground glass” characteristic of this lesion (Fig. 2213E–F ). However, fibrous dysplasia and other benign fibroosseous lesions are extremely variable in appearance radiologically (Fig. 22-14) and may be difficult to exclude from a list of differential diagnoses. This is particularly true in lesions where the fibrous elements dominate. Benign Vascular Tumors Benign vascular tumors, or ossifying hemangiomas, can arise in the petrous apex near the geniculate ganglion. The lesions often have indistinct margins and may have intratumoral bone spicules, which can be seen on high-resolution CT (Fig. 22-15). The intratumoral bone has led to the term ossifying hemangioma. Although the bulk of the tumor lies outside the facial nerve canal, expansion of the canal is common. Occasionally, the lesions are well circumscribed and lack internal bone spicules. These well-demarcated hemangiomas are hard to differentiate from a facial nerve sheath tumor. In most cases, however, the internal spicules and ill-defined bony margins suggest the correct diagnosis.18 Meningiomas can have a similar appearance.

Meningiomas Intracranial or dural processes may involve the petrous apex by remodeling or invading through the dural covering. Petroclival and cavernous sinus meningiomas commonly

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Figure 22-12. Multiple myeloma. A, Axial CT shows a large destructive lesion of the basiocciput (arrows). B, Coronal T1-weighted MR shows the mass to be isointense with brain (arrows). C, Postcontrast MRI at the same level as B shows intense uniform enhancement of the mass (arrows). D, T2-weighted axial MRI. The mass in the basiocciput is intermediate in signal (arrows). It extends into the prevertebral space and displaces the longus coli muscle anteriorly (open arrow). The lack of bright T2 signal helps differentiate this lesion from chordoma and chondrosarcoma.

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Figure 22-13. Fibrous dysplasia. A, Axial T1-weighted MRI shows a low signal mass involving the left temporal bone, left pterygoid bones, and left temporal mandibular joint (bracket). B-C, Axial and coronal T1-weighted with contrast. The lesion demonstrates irregular enhancement (bracket). D, Axial T2-weighted Continued image shows mixed areas of high and low signal (bracket).

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E Figure 22-13. Cont’d, E-F, Axial and coronal CT in bone algorithm show the characteristic “ground glass” appearance of fibrous dysplasia (arrows). Note the sparing of the otic capsule (arrowheads).

involve the petrous apex. Lesions may involve the posterior or superior surface of the bone. The margins usually taper to the surface of the bone at an obtuse angle. The tumor can cause remodeling of the bone, hyperostosis, or enhancement of the marrow cavity (Fig. 22-16). This may be best appreciated with fat-suppressed postcontrast images. The most common scenario is to have a meningioma growing along the petrous apex without apparent bone change. Occasionally, cavernous sinus tumors spread into the petrous bone along the carotid canal. Endolymphatic Sac Tumors Tumors thought to arise from the endolymphatic sac give the appearance of a locally destructive lesion in the bone just posterior to the labyrinth along the medial aspect of the posterior semicircular canal.19,20 This location is very characteristic and corresponds to the position of the endolymphatic sac and vestibular aqueduct. The papillary cystadenomatous lesion frequently contains hemorrhagic foci as well as cystic areas. The cysts appear as bright areas on T2-weighted images and the hemorrhagic areas can have a bright signal on T1-weighted images and dark areas on T1- and T2-weighted images, reflecting the appearance of various blood breakdown products in the tumors. The lesions are usually more cystic and more focally invasive than meningiomas that can also occur in this area. These lesions can occur in patients with von Hippel-Lindau disease in whom they can be bilateral. Fifth Nerve Sheath Tumor and Cavernous Sinus Hemangiomas Trigeminal nerve sheath tumors (trigeminal neuromas) may smoothly remodel the petrous apex. They are differentiated

from meningiomas because they almost never calcify, rarely have enhancing dural tails, and are usually higher in signal and less homogeneous on T2-weighted images (Fig. 22-17). Meningiomas may have moderate signal intensity on T2-weighted images, but they are seldom as bright as neuromas.21,22 Hemangiomas involving the cavernous sinus are rare, but when they are large they can erode the petrous apex. These lesions are indistinguishable from meningiomas by CT and on angiography they can show “puddling” of contrast, which can be confused with meningioma. MRI makes the distinction because hemangiomas are extremely bright on T2-weighted images.23 Differentiation of a cavernous sinus hemangioma from a nerve sheath tumor may be more difficult. Direct Extension from Nasopharyngeal and Infratemporal Lesions Malignancy arising in the nasopharynx or infratemporal fossa can grow into the lateral skull base. Although any location can be involved, the petroclival synchondrosis and contiguous foramen lacerum are particularly prone to invasion especially from nasopharynx carcinomas (Figs. 22-18 and 22-19). The petroclival and petrosphenoidal fissures are close to the fossa of Rosenmüller, where these neoplasms tend to arise. Extension beyond the fissures brings the tumor to the cavernous sinus. In most cases either CT or MRI suffices. CT better demonstrates the cortical bone destruction (see Fig. 22-18) and can visualize fairly gross involvement of the cavernous sinus. MRI visualizes the actual tumor within the bone and is considered by most to be more precise in showing cavernous sinus invasion (see Fig. 22-19) and more sensitive in demonstrating involvement of the petroclival synchondrosis.

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Figure 22-14. Benign fibroosseous lesion. Thirty-year-old woman with a 2-year history of facial paralysis. A, Axial CT bone algorithm shows an expansile lesion of the left petrous apex (arrows). B, Cut slightly lower than (A) shows erosion in the region of the geniculate ganglion (arrow). C, Coronal bone algorithm shows the lesion (arrows) that erodes the labyrinthine and tympanic segment of the facial nerve canal (arrowheads). D, Cut slightly posterior to (C ), shows erosion of the tegmen tympani (arrowheads) by this lesion. The tegmen is intact on the right (open arrow). At surgery, this proved to be a benign fibroosseous lesion.

Metastasis and Other Solid Lesions The petrous apex is a bone with a medullary space and so metastasis to the apex can occur. Metastasis results in a destructive mass. The center part enhances to some extent and gives a solid appearance rather than the “cystic” nonenhancing appearance of the epidermoid or the cholesterol cyst. In an adult, an enhancing destructive mass of the apex suggests a metastasis or meningioma. Plasmacytomas can arise in any bone, including the petrous apex. The lesions tend to be fairly homogenous on CT. They are relatively dark on T2-weighted images on

MRI. They enhance on either CT or MRI. The appearance overlaps with that of metastasis. Because they enhance, they are not confused with cholesterol cyst or epidermoid. Langerhans’ cell histiocytosis can involve the mastoid region and middle ear but can also involve the petrous apex. The lesion is frequently described as “punched out” with a sharp margin and without sclerosis but occasionally the margin can be more sclerotic. On MRI, the lesion is seen as a solid mass often with loss of the cortex. The signal is usually described as high on T2-weighted sequences but this is variable. The lesion enhances on either CT or MRI.

Figure 22-15. Ossifying hemangioma. Twenty-eight-year-old woman with a longstanding right facial weakness. Two bone algorithms from an axial CT scan. Abnormal bone appears along the anterior surface of the petrous ridge. There are small interruptions in the cortical bone (arrowheads). There is expansion of the labyrinthine segment of the facial nerve canal (wavy arrow). The bony spicules in the lesion produce a honeycomb appearance.

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Figure 22-16. Meningioma invading the petrous apex. A, Coronal postcontrast CT shows an enhancing lesion along the left petrous apex (outlined arrows) with extension of the enhancing tissue into the left internal auditory canal (curved arrow). Compare to the normal right internal auditory canal (open arrow), which contains low-density CSF. B, Bone algorithm at the same level as (A) shows slight irregularity of the superior cortex of the petrous apex (arrows). Compare this to the normal dense bone on the right side (open arrow). C, Postcontrast MRI confirms abnormal enhancement in the left internal auditory canal. Enhancement deep to the cortex of the petrous ridge confirms involvement of the marrow cavity (small straight arrows). Continued

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Figure 22-16. Cont’d, D, Axial postcontrast MRI shows tumor on both the anterior and posterior surfaces of the petrous bone (large straight arrows). There is enhancement within the petrous apex itself (small straight arrows). Abnormal enhancement extends across the midline of the clivus (curved arrow). A “tail” of tumor extends along the wall of the left transverse sinus (arrowheads) but does not occlude the sinus. E, Sagittal postcontrast MRI shows the enhancing tissue in the internal auditory canal (straight white arrow). In this plane the abnormal enhancement deep to the cortex of the petrous ridge is again apparent (wavy white arrow). “Dural tails” are seen extending from the tumor into the middle cranial fossa (open arrow), the posterior cranial fossa (straight black arrow), and along the tentorium (curved black arrow).

Superior Semicircular Canal Dehiscence Superior semicircular canal dehiscence is covered in the chapter on the labyrinth but is mentioned briefly here because it does involve the bone over the labyrinth. Several recent reports relate symptoms of sound (Tullio’s phenomenon) or pressure-induced (Hennebert’s sign) vertigo or nystagmus to a third “mobile” window in the bony labyrinth. Normally, the labyrinth is a closed hydraulic system. The oval and round windows are the only two movable openings in the system. As the acoustic energy is transmitted via the ossicles to the oval window, the footplate of the stapes vibrates slightly. Fluid is not compressible and so a compensatory motion must occur somewhere in the system if there is to be movement of the fluid or propagation of the vibration. There is subtle motion of the perilymph of the cochlea as the round window membrane moves outward in response to the inward movement of the footplate. Normally, there is no significant movement of the fluids in the semicircular canal. Each is a closed system with no external opening. If there is a dehiscence of the bony canal, however, subtle movement can occur and this compresses the endolymph. Motion within the endolymph is interpreted as dizziness. Most such “third windows” are related to fistulas into the labyrinth resulting from cholesteatoma and surgical interventions. An important cause that is potentially treatable is dehiscence of the superior semicircular canal roof (Fig. 22-20). The etiology of the dehiscence is not exactly known. These patients can undergo surgical packing of the dehiscent area, which often provides symptomatic relief.24,25

Coronal CT images demonstrate a defect in the superior curve of the superior semicircular canal.24 The reformatting capabilities of multidetector give excellent images in any plane. A 45-degree oblique (Stenver’s plane) image passing perpendicular to the arc of the superior semicircular canal often show the dehiscence best.

JUGULAR AND CAROTID REGION The jugular foramen and vertical portion of the carotid artery canal are grouped together because differential diagnoses of lesions affecting these areas overlap. The carotid canal is anterior to the jugular fossa. Both the artery and the vein are separated from the middle ear by very thin but very important cortical plates of bone. Anatomically, the jugular fossa is divided into the smaller medial pars nervosa and the larger lateral pars vascularis (Fig. 22-21B). Cranial nerves IX, X, and XI pass along the medial part of the jugular fossa. The more lateral pars vascularis contains the jugular vein. The size of the pars vascularis may vary greatly according to the variable size of the jugular vein. The bony wall separating the jugular bulb from the middle ear is very thin or may even be absent in the case of dehiscent jugular fossa (Fig. 22-21A). The vascular part of the jugular fossa is smoothly marginated (see Fig. 22-21B). Evaluation of these bony walls is best achieved with CT. The MRI appearance of the jugular fossa varies considerably. Signal of the flowing venous blood depends on

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the speed and turbulence of flow in the jugular bulb. The appearance depends on the size of the vein, the configuration of the jugular bulb, and the phase in the cardiac cycle. As a result, the signal from the jugular fossa can range from a flow void to a very bright signal on both T1- and T2-weighted images. The results of MRI contrast enhancement are also unpredictable because of this variable flow. A typical scenario for confusion occurs in assessing the patient with intermediate signal in the jugular fossa on unenhanced study who has enhancement on a postcontrast exam (Fig. 22-22). The question is whether this represents a normal vein with slow flow, clot within the vein, or an enhancing glomus jugulare tumor. It may be possible to make the distinction on flow-sensitive MRI or MRA. If the flow in a patent vein is demonstrated, there is no tumor or thrombosis. If flow is not definitely identified, however, the problem may remain. Slow flow is difficult to exclude. CT and particularly CT venography may be helpful in this regard. If a bolus of contrast is given, then the vein should opacify even if flow is very slow. Jugular thrombosis might confuse the issue because organized thrombus has been shown to enhance in some cases (see Fig. 22-22).

Paragangliomas

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Paragangliomas arise from the glomus formations found in many places in the temporal bone, particularly in the adventitia of the dome of the jugular bulb and in the mucosa covering the cochlear promontory and along branches of Arnold’s nerve between the descending facial nerve and the jugular foramen.26 A glomus tumor (paraganglioma) arising on the cochlear promontory and limited to the middle ear cavity is called a glomus tympanicum and usually gives a conductive hearing loss due to impingement on the oval window or ossicles (Fig. 22-23). A red mass is seen through the tympanic membrane. The plate of bone representing the lateral wall of the jugular foramen is intact in a glomus tympanicum. This important landmark is best demonstrated and evaluated on CT. Tumors along the wall of the jugular foramen erode the normally smooth walls of the jugular foramen (Fig. 22-24A). They may extend into the middle ear and produce a mass in the hypotympanum. Indeed, such a tumor, called glomus jugulare or glomus jugulotympanicum, commonly presents because of problems related to the middle ear component of the tumor. Once again the difference between a glomus tympanicum and glomus jugulare (jugulotympanicum) is determined by CT. Erosion of the plate of bone at the lateral aspect of the jugular fossa indicates that indeed the tumor is a glomus jugulare. If this plate is intact, then the lesion is limited to the middle ear and is a glomus tympanicum.

Figure 22-17. Trigeminal nerve sheath tumor (arrowheads). A, Axial T2-weighted MRI shows a high signal mass within the left Meckel’s cave, causing remodeling of the left petrous apex. B-C, Axial and high-resolution coronal T1-weighted image with contrast. The enhancing mass also involves the left cavernous sinus and prepontine cistern along the course of cranial nerve V.

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C Figure 22-18. Nasopharyngeal cancer invading the skull base. A, Axial CT shows effacement of the left fossa of Rosenmüller (thick straight arrow). Compare this with the normal right side (thin straight arrows). The prevertebral space is enlarged on the left (open arrow) and the left parapharyngeal space appears to be infiltrated rather than displaced (curved arrow). B, More superior cut shows abnormal enhancement along the petrous apex and posterior aspect of the left cavernous sinus (arrows). Meckel’s cave on the left has been replaced by enhancing tissue but the right side (curved arrow) appears normal. C, Bone algorithm at the same level as (B) shows destruction of the cortex as well as the marrow space of the left petrous apex (arrows).

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C Figure 22-19. MRI of nasopharyngeal cancer invading the skull. A-C, Sequential axial T1-weighted MRI with contrast. There is a large mass (arrowheads) in the nasopharynx extending into the left nasal cavity and into the left cavernous sinus. Note the narrowing of the left carotid flow void (arrow). D, Coronal postcontrast T1 shows tumor (arrowheads) extending through skull base.

Paragangliomas also arise from the ganglia of the vagus nerve immediately inferior to the skull base (Fig. 22-25). This tumor is called a glomus vagale. The glomus vagale can enlarge to involve the skull base or extend into the posterior fossa. Such tumor extension tends to follow the pars nervosa (medial jugular foramen). The lateral wall of the jugular fossa is usually intact. Paragangliomas can be multiple, so once one lesion is found the imaging study is usually extended to the level of the bifurcation of the carotid to search for carotid body tumors as well as glomus vagale tumors.27

Paragangliomas are easily detected on MRI. They enhance intensely, reflecting high vascularity. In larger lesions, there are flow voids that indicate large tumor vessels detected on standard spin echo or flow-sensitive MRI (see Figs. 22-24D and 22-25D) giving a “salt-and-pepper” appearance to the lesion. Flow voids in a lesion in this area suggest a paraganglioma. Occasionally, large vessels in a meningioma or vascular metastasis (from thyroid or renal cancers) create confusion with paraganglioma. On CT, tumor vessels usually cannot be resolved from adjacent enhancing tumor stroma. If the lesion is very small,

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C Figure 22-20. Superior semicircular canal dehiscence in a patient with sound-induced vertigo. A, Coronal CT bone algorithm shows a defect in the roof of the superior semicircular canal (arrowhead). B, Stenvers’ plane near the same level as (A), perpendicular to the arc of the semicircular canal confirms this (arrowhead). C, Pöschl plane, parallel to the superior semicircular canal, shows a good portion of the roof is dehiscent (arrowheads).

Figure 22-21. Dehiscent jugular bulb. A, Axial CT bone algorithm shows absence of the bony wall between the jugular fossa and the middle ear (arrow). B, Normal comparison. Note the smaller pars nervosa (arrowhead) and more lateral pars vascularis (double arrows).

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Figure 22-22. Venous sinus thrombosis. A, Axial T1-weighted image. There is intermediate signal in the right jugular fossa and right sigmoid sinus (straight arrows). Compare this with the flow void in the left jugular fossa (curved arrow). Also of interest is the small amount of fat located lateral to the jugular bulb on each side (white arrows). A small amount of medullary bone is frequently found lateral to the jugular fossa. B, Postcontrast MRI. There is enhancement in the right jugular bulb and right sigmoid sinus (straight arrows). It is uncertain from these images whether the jugular is patent. Enhancement can be seen due to slower turbulent flow or due to an organized thrombus with enhancement. A glomus jugulare tumor may also enhance. C, Contrasted CT shows less opacification of the right jugular and sigmoid (straight arrows) than the normal left jugular (curved arrow). Bone algorithms confirmed that there was no erosion of the right jugular fossa and therefore glomus tumor is unlikely. This represents organized thrombus in the right jugular and sigmoid. It is apparent from (B) that organized thrombus can enhance somewhat. CT with bolus injection of contrast will clarify ambiguous cases such as this one; there is greater enhancement of the patent lumen (curved arrow) than the thrombus (straight arrows). Dynamic scanning is often required to make this distinction.

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C Figure 22-23. Glomus tympanicum tumor causing secondary obstruction. A-B, Axial and coronal CT bone algorithm demonstrates an abnormal soft tissue mass in the left middle ear at the cochlear promontory (arrowheads). Note the fluid in the left mastoid air cells (asterisk). C-D, On axial and coronal gadoliniumenhanced T1-weighted MRI, the mass intensely enhances (arrow).

intratumoral vessels may not be visualized by imaging. This is particularly true of the paragangliomas arising at the cochlear promontory (glomus tympanicum). Although almost all paragangliomas are detectable on MRI, CT is usually used for the initial evaluation because of the importance of lateral plate of the jugular foramen in separating a glomus tympanicum from a glomus jugulare. That landmark is poorly seen with MRI and so its integrity is difficult to assess. Once the diagnosis of glomus jugulare is made, however, MRI can provide valuable information regarding potential intracranial extension and the patency of the jugular vein and sigmoid sinus. MRI visualizes tumor growing into the vein and sinus as well.

Nerve Sheath Tumors Nerve sheath tumors also occur in the jugular fossa. As schwannomas of cranial nerve IX, X, or XI enlarge, they erode or expand the medial part of the jugular foramen. The lateral plate of the pars vascularis is usually spared (Fig. 22-26A and B). The margin of the expanded foramen is usually smooth, unlike the more irregular margin of a paraganglioma. MRI features that suggest a nerve sheath tumor include high T2 signal, involvement of the medial jugular foramen, smoothly marginated bone remodeling, and cystic change (Fig. 22-26C and D).28,29 In some cases the cystic change in the tumor is so extensive that it mimics an arachnoid cyst

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Figure 22-24. Glomus jugulare. A, Axial CT bone algorithm shows expansion and permeative destruction of the walls of the right jugular fossa (black arrows). Compare this to the normal left jugular fossa (double arrows). B-C, Axial CT without and with contrast shows intense enhancement of the mass (black arrows). D, MRI at approximately the same level. Axial T2-weighted image shows multiple small flow voids within the mass (arrowhead). Continued

or epidermoid tumor.30 Nerve sheath tumors lack flow voids and have fairly abrupt margins with surrounding meninges.

Aberrant Carotid Arteries Normally, the vertical portion of the petrous carotid artery is covered by a thin plate or wall of bone separating it from the tympanic cavity.31 Absence of this plate of bone indicates an anomalous vessel. As with the plate of the jugular foramen, CT is the method of choice for visualizing the thin

plate of bone separating the artery from the tympanic cavity (Fig. 22-27A and B). The anomalous artery itself is a soft tissue density mass. It enters the tympanic cavity through an enlarged tympanic canaliculus and courses through the middle ear cavity next to the cochlea (Fig. 22-27C and D). If there is a persistent stapedial artery associated with the aberrant carotid, the tympanic segment of the facial nerve canal may be enlarged. The stapedial artery courses through this part of the facial nerve canal to enter the cranial cavity and form the middle meningeal artery. The foramen spinosum is absent in this instance.

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Figure 22-24. Cont’d, E-F, Axial T1-weighted image without and with contrast shows intense enhancement.

An aberrant carotid artery should be excluded in every imaging study of the temporal bone but particularly when a red mass is seen behind the tympanic membrane. CT can differentiate an aberrant carotid artery from a glomus tympanicum or jugulare. The differential depends on demonstration of the presence or absence of the lateral plates of the jugular and carotid canals.

Other Lesions Involving the Jugular and Carotid Area Meningiomas are rare in the jugular fossa. They probably arise from arachnoid cap cells that are in the sheaths that surround the cranial nerves as they exit the skull.32,33 Although they may be difficult to differentiate from more common paragangliomas, calcification, hyperostosis, and enhancing dural rims (dural tail) may suggest the correct diagnosis. The destruction or demineralization may be less obvious than in paraganglioma. Chondrosarcomas and chordomas are seldom confused with lesions of the jugular fossa because they are centered more medially. However, it is very important to evaluate the involvement of the jugular fossa in these lesions. This is particularly true in large lesions, which can involve the jugular fossa bilaterally. The lower cranial nerves are at risk during the surgical approach to these lesions. The hypoglossal canal is located just inferior and medial to the jugular fossa and is frequently involved with processes that occur there. It is well demonstrated in both the axial and coronal plane and by CT or MRI. Enhancement within the hypoglossal canal is frequently seen as a normal finding and should not be confused with pathology. Abnormality can be established only if there is an obvious mass, erosion,

or enlargement of the canal (Fig. 22-28) or enhancement of the medullary cavity surrounding the canal. Involvement of the hypoglossal nerve is clinically indicated by unilateral atrophy of the intrinsic and extrinsic muscles of the tongue. The imaging correlate of atrophy is fatty infiltration of one-half of the tongue, which is visible on CT or MR (Fig. 22-29C). During acute muscle atrophy, there may be enhancement of the muscle before fatty replacement is apparent. Similar findings are observed with atrophy of the muscles of mastication when the trigeminal nerve is involved with tumor.

MIDDLE EAR AND MASTOID Inflammatory Middle Ear Disease The majority of middle ear disorders are inflammatory and related to eustachian tube dysfunction. CT is preferred to MRI in most cases because of its superior demonstration of the ossicles, bony labyrinth, tegmen tympani, facial nerve canal, and the septations within the mastoid air cells; structures often affected by middle ear pathology. Acute and chronic otitis media may result in opacification of the middle ear. Fluid, mucosal thickening, and granulation tissue are usually indistinguishable on CT. These inflammatory responses are also difficult to differentiate on MRI; all tend to be intermediate in signal on T1-weighted images and bright on T2-weighted images. Gadolinium may enhance mucosal thickening or granulation tissue but obstructed fluid will not be enhanced. Cholesteatomas tend to occur in the upper tympanic membrane and grow into Prussak’s space and the upper middle ear (Fig. 22-30). These secondary cholesteatomas

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Figure 22-25. Glomus vagale. A, Postcontrast CT shows an enhancing mass (m) splaying the high cervical internal carotid artery (straight arrow) and the jugular vein (curved arrow). The mass enhances intensely, almost as much as the vessels. B, Higher cut at the level of the jugular foramen. The tumor has not reached this high. The pars nervosa (arrow) is relatively lucent, indicating that there is no tumor spread to this area. The pars vascularis (open arrow) enhances, but this is due to the jugular vein, not enhancing tumor. C, Bone algorithm CT at the same level as (B). The cortical margins of the jugular fossa (arrows) are sharp and smooth. There is no demineralization or erosion to suggest a glomus jugulare tumor involvement of the pars vascularis. D, T1-weighted MRI at approximately the same level as (A). The mass (m) splays the cervical internal carotid artery (straight arrow) and jugular vein (curved arrow). Note the flow void in this mass (outlined arrow), which indicates that the mass is highly vascular.

are associated with chronic ear disease dating to childhood and usually the mastoid air cell system is poorly developed. If a cholesteatoma is suspected, CT is the study of choice. Erosion of the scutum and tegmen tympani are best demonstrated by coronal CT (Fig. 22-30B). Erosion of the horizontal semicircular canal is best assessed in the axial CT because the entire lateral margin can be seen in a

single image slice (Fig. 22-31). Reading subtle erosions of the horizontal semicircular canal in the vertical plane can be difficult because an oblique slice through the anterior curve of the canal can suggest a false defect. The facial nerve canal can also be eroded. Primary epidermoid tumors (congenital or primary cholesteatoma) occur in the petrous apex, but they occa-

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Figure 22-26. Tenth nerve sheath tumor. A, Axial enhanced CT shows a ring enhancing lesion (large arrows) extending from the right jugular foramen into the cerebellopontine angle cistern. Incidentally, note the enhancing choroid plexus in the left foramen of Luschka (small arrow). B, Bone algorithm image demonstrates expansion of the pars nervosa of the right jugular foramen (arrows). C, T1-weighted MRI. The mass (straight arrow) has regions of intermediate and low T1 signal. There is an arachnoid cyst lateral to the mass (curved arrow). D, T2-weighted MRI. The mass shows regions of low and high T2 signal. The bright areas in the tumor (straight arrow) represent areas of cystic degeneration or necrosis. The arachnoid cyst (curved arrow) adjacent to the cisternal portion of the tumor is also bright on T2.

sionally arise in the middle ear as well. These are thought to result from the growth of a congenital rest of squamous epithelium. They are not related to chronic ear infections and the mastoid air cells may be well pneumatized. Intracranial complications of mastoiditis and cholesteatomas require careful imaging. Epidural, subdural, and brain abscesses are best evaluated with MRI. Small

extra-axial collections and meningeal enhancement may be obscured by artifact from the adjacent bone on CT scans. Septic thrombophlebitis may occlude the sigmoid sinus. Venous sinus thrombosis may be demonstrated by either MRI or CT. The CT demonstration of clot requires bolus injection of contrast (Figs. 22-22 and 22-32). The intraluminal thrombus will appear as a filling defect in the lumen

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Figure 22-27. Aberrant carotid artery. Thirty-seven-year-old woman with a pulsatile mass behind her right ear drum. A, Axial CT bone algorithm shows absence of the lateral bony wall of the carotid canal (outlined arrow), which is intact on the left (curved arrow). B, Slightly more inferior cut shows more bulbous protrusion of the right internal carotid artery into the middle ear (single outlined arrow). Again, note the intact bony wall of the left carotid canal (double outlined arrows). C, Coronal bone algorithm demonstrates the normal carotid canal on the left (curved arrow). On the right, the petrous carotid artery courses into the middle ear (outlined arrow). D, Slightly more anterior coronal image demonstrates the relationship of the aberrant carotid artery (outlined arrow) to the cochlea and ossicles. Again, note the normal lateral wall of the left carotid canal (curved arrow).

of the vein. The MRI demonstration of clot is more complicated; flow artifacts on standard spin echo sequences often give a false-positive impression of clot within the sinus and jugular bulb. Herniation of brain or meninges through a defect in the tegmen can present as a conductive hearing loss and a mass in the middle ear or mastoid. Such a defect may represent a congenital dehiscence. A cholesteatoma may erode or thin the tegmen and once the cholesteatoma

has been removed a herniation can occur through the weakened area. CT can suggest a defect in the tegmen and is better than MRI at demonstrating the thin cortical plate of bone (see Figs. 22-30 and 22-33B and C ). However, since the bone is very thin, a partial volume effect may average the bone with contiguous soft tissue and suggest a defect where there is none. Small defects can also be missed. Therefore, both the radiologist and the surgeon must be

Figure 22-28. Schwannoma, jugular foramen. A, Axial T1-weighted image shows an enhancing mass (arrowheads) originally thought to arise in the right hypoglossal canal. Note enhancement of the normal left hypoglossal canal (double arrows). B, Coronal CT bone algorithm demonstrates that the lesion extends through the jugular foramen (arrow) rather than the hypoglossal canal. The hypoglossal canal (double arrows) is normal. The jugular tubercle is eroded (arrowhead).

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Figure 22-29. Metastatic paraganglioma with hypoglossal nerve atrophy. A, Sagittal T1-weighted MRI shows a large mass in the left jugular fossa. The mass extends inferiorly within or adjacent to the jugular vein (outlined arrows). B, Axial T1-weighted MRI. There is a mass in the poststyloid parapharyngeal space (outlined arrows) just posterolateral to the left internal carotid artery (curved arrow). C, Section slightly inferior to (B) shows fatty infiltration of the left half of the tongue (arrows). Also note the abnormally enlarged left spinal accessory nodes (curved arrow). This paraganglioma had metastasized to cervical nodes. Metastatic paragangliomas do occur but are uncommon.

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Figure 22-30. Cholesteatoma. A-B, Axial and coronal CT bone algorithm shows and expansile mass involving the upper middle ear cavity (asterisk). Coronal view better demonstrates involvement of Prussak’s space and epitympanum, causing bony erosion of the scutum (arrowhead) and tegmen tympani (double arrows).

B

A Figure 22-31. Cholesteatoma eroding horizontal semicircular canal. A, Axial CT bone window shows abnormal soft tissue in the left middle ear and mastoid antrum (outlined arrow). This cholesteatoma erodes the horizontal semicircular canal (arrowheads). B, Two images from an axial CT bone algorithm of a different patient than shown in (A). There is a soft tissue mass in the left middle ear eroding the left horizontal semicircular canal (open arrow). Compare this to the normal bony margin of the right horizontal semicircular canal (outlined arrow).

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Figure 22-32. Jugular vein thrombosis. A, Postcontrast CT shows normal enhancement of the left jugular vein (open arrow) and of both carotid arteries (arrowheads). The right jugular vein (curved arrow) does not exhibit enhancement. B, Higher cuts in the same patient show a lack of enhancement in the lumen of the right sigmoid sinus (straight arrow). The smaller left sigmoid sinus (open arrow) enhances normally.

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Figure 22-33. Cholesteatoma with erosion of the tegmen tympani. A, Axial bone algorithm CT shows a mass eroding into the carotid canal (large straight arrow). B, Coronal view shows erosion of the tegmen tympani (arrowheads). Continued

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Figure 22-33. Cont’d, C, Soft tissue window at the same level as (B). It was not possible to determine by CT if the brain herniated into the defect (arrowheads). D, T2-weighted axial MRI shows the mass (white arrows) to be of high signal. E, Postcontrast axial T1-weighted image shows peripheral enhancement of the mass (white arrows). F, Coronal postcontrast MRI shows peripheral enhancement (arrowheads). The center of the mass (outlined arrow) does not enhance. Unlike CT, MRI is able demonstrate that no brain tissue has herniated into the tegmen defect.

aware that assessment of the tegmen by even high-resolution CT has its limitations. MRI can be very helpful in these situations. Even though the thin cortical bone of the tegmen is not seen, the status of the inferior surface of the brain is well defined. The coronal image can indicate if the brain is clearly separated from the area in question or, alternatively, protrudes down into the defect (Fig. 22-33F).

Tumors of the Middle Ear Tumors that involve the middle ear are uncommon. Paragangliomas (glomus tympanicum) arise at the cochlear promontory and have already been discussed. These tumors must be differentiated from aberrant carotid artery and glomus jugulare tumors, any of which can present as a mass in the middle ear.

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Malignant tumors in the middle ear are extremely rare and include squamous carcinomas, adenocarcinomas, and adenoid cystic carcinomas. These lesions are usually accompanied by considerable bone destruction. Otherwise, imaging findings are not specific. They are difficult to differentiate from metastasis or locally invasive tumors such as rhabdomyosarcoma or lymphoma. Histiocytosis X also may occur as a destructive lesion in the petrous bone and must be differentiated from malignancies or inflammatory pathology by biopsy.34 The margin of the lesion is frequently sharp. Signal on MRI can vary. Fibroosseous lesions may involve the middle ear but are usually better defined and less infiltrative than malignancies.

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EXTERNAL AUDITORY CANAL Keratosis Obturans Keratosis obturans gives a gradual smooth bony widening of the external auditory canal filled with soft tissue density on CT (Fig. 22-34). They are more commonly bilateral and occur in younger patients. They often present with acute severe pain and uncommonly with otorrhea.

External Auditory Canal Cholesteatoma Cholesteatoma involvement of external auditory canal is rare, as opposed to the more common cholesteatoma of the middle ear. Cholesteatomas of the EAC can be congenital,35 spontaneous, or secondary to infection, trauma, or surgery.36 They are often confused with keratosis obturans. EAC cholesteatomas tend to occur in older patients and has a milder presentation of chronic pain and otorrhea. The occurrence is more commonly unilateral. CT demonstrates soft tissue density often along the canal floor, sparing the tympanic membrane. Unlike the smooth bony widening of keratosis obturans, EAC cholesteatomas demonstrate focal erosions along the canal (Fig. 22-35).37

B Figure 22-34. Keratosis obturans. A-B, Axial and coronal CT bone algorithm shows soft tissue density in the external auditory canal causing smooth gradual widening (arrowheads).

Exostosis and Osteoma Two benign lesions associated with bony overgrowth are exostosis and osteoma. Exostoses (Fig. 22-36) are much more common and are often bilateral. They are considered to be induced by cold water swimming. They arise in the most medial aspect of the osseus canal adjacent to the tympanic membrane. They are broad based and very dense. Osteomas (Fig. 22-37) tend to be unilateral, arise more laterally, and are rounder or more focal.

Malignant Lesions of the External Canal Malignant lesions of the external canal are diagnosed by biopsy, but imaging is used to determine if the lesion is resectable. Squamous cell carcinoma is most common but basal cell carcinomas, minor salivary gland tumors (for example, adenoid cystic carcinoma), and spread from malignant parotid tumors also occur. Erosion of the bony external canal is best demonstrated by CT (Fig. 22-38).

Tumors of the external canal may spread along paths of least resistance—medially into the middle ear or laterally into the cartilaginous portion of the external canal. From here they can spread inferiorly beneath the skull base or anteriorly into the parotid gland. Such soft tissue extension can be demonstrated with CT or MRI (Fig. 22-39). Of particular importance is the stylomastoid foramen. Replacement of the fat beneath the stylomastoid foramen can be demonstrated with CT or MRI if thin sections are used. In general, CT can be used as the first examination because of its demonstration of bone erosion. If extension beneath the skull base is inadequately demonstrated, MRI should be performed. When the tumor extends across the middle ear, the bony labyrinth and the lateral plates of the carotid canal and jugular fossa again become important landmarks if a surgical resection is planned. Occasionally, severe radiation osteonecrosis produces bone destruction, which mimics a malignancy of the temporal

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B Figure 22-35. EAC cholesteatoma. A-B, Axial and coronal CT bone algorithm demonstrates a soft tissue density (arrowheads) in the right external auditory canal causing focal bony erosions (arrows).

B Figure 22-37. EAC osteoma. A-B, Axial and coronal CT bone algorithm shows a focal ossification protruding into the left external auditory canal from the inferior wall (arrowhead). It is partially obstructing the canal.

bone (Fig. 22-40). The history of radiation and biopsies negative for malignancy suggests the correct diagnosis.

INFECTION Malignant External Otitis

Figure 22-36. EAC exostosis. Axial CT bone algorithm demonstrates bony overgrowth into both external auditory canals causing narrowing (arrowheads).

Malignant external otitis (MEO) (necrotizing external otitis) can mimic carcinoma. At imaging, the appearance may be very similar with erosion of the bony canal and extension into the soft tissues beneath the skull base. Although MEO can erode into the middle ear and mastoid, this disease preferentially extends inferiorly at the junction of the bony and cartilaginous canals to involve the soft tissues beneath

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B Figure 22-38. Basal cell carcinoma of the external auditory canal (EAC). A, Enhanced CT shows soft tissue filling the left external auditory canal (arrows). B, Bone algorithm at the same level shows erosion of the posterior (straight arrow) as well as the anterior (curved arrow) walls of the EAC. The lesion also extends through the tympanic membrane into the middle ear. Note the handle of the malleus and the incus (arrowhead).

the external auditory canal. From here the disease can spread medially beneath the skull base to involve the cranial nerves. The seventh nerve is involved as it exits the stylomastoid foramen. Further extension involves the nerves of the jugular foramen and cranial nerve XII. Extreme cases of MEO spread across the midline and eventually involve the bone of the petrous apex and clivus. Newer antibiotics have significantly diminished the morbidity and mortality of this disease.

Figure 22-39. Squamous cell carcinoma of the external auditory canal. A, T1-weighted MRI shows an abnormal mass involving the left temporal bone (arrow). B, Postcontrast MRI at the same level as (A). There is marked enhancement of the mucosa of the middle ear cavity (white arrow). There is also more modest enhancement of the tumor (black arrow).

Differentiation of MEO from a malignant neoplasm of the external canal is usually not possible based on imaging. The distinction is made on clinical grounds. MEO is almost exclusively a disease of diabetic patients. Biopsy will be negative for neoplasm and pseudomonas can be cultured.

SUMMARY Imaging is used to detect and to stage lesions of the lateral skull base. Although opinions vary greatly, in most cases high-resolution CT (particularly multislice CT) is preferred because of the ability to visualize the fine bony anatomy,

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Figure 22-40. Focal radiation necrosis of the skull base. Axial CT bone algorithm shows destruction of the posterior wall of the right external auditory canal (straight arrow). There is marked sclerosis of the squamosal portion of the occipital bone adjacent to the mastoid (curved arrow). The cystic changes in the mandibular condyles (arrowheads) are of uncertain etiology.

which is very important in evaluating the region of the temporal bone.

REFERENCES 1. Anzai Y, Lufkin RB, Jabour BA, Hanafee WN: Fat suppression failure artifacts simulating pathology on frequency-selective fat-suppression MR images of the head and neck. Am J Neuroradiol 13:879–884, 1992. 2. Gherini S: Resident’s page. Arch Otolaryngol Head Neck Surg 112:674–677, 1986. 3. Rosenberg RA, et al: Cholesteatoma vs. cholesterol granuloma of the petrous apex. Otolaryngol Head Neck Surg 94:322–327, 1986. 4. Martin N, et al: Cholesterol granulomas of the middle ear cavities: MR imaging. Radiology 172:521–525, 1989. 5 Clifton AG, Phelps PD, Brookes GB: Cholesterol granuloma of the petrous apex: Case reports. Br J Radiology 63:724–726, 1990. 6. Horowitz BL, Chari MV, James R, Bryan RN: MR of intracranial epidermoid tumors: Correlation of in vivo imaging with in vitro 13C spectroscopy. Am J Neuroradiol 11:299–302, 1990. 7. Pyle GM, Wiet RJ: Petrous apex cholesteatoma: Exteriorization vs. subtotal petrosectomy with obliteration. Skull Base Surg 1(2): 97–105, 1991. 8. Yanagihara N, Nakamura K, Hatakeyama T: Surgical management of petrous apex cholesteatoma: A therapeutic scheme. Skull Base Surg 2(1):22–27, 1992. 9. Feghali JG, Kantrowitz AB: Periaqueductal approach to cholesterol granulomas of the petrous apex. Skull Base Surg 2(4):204–206, 1992. 10. Larson TL, Wong ML: Primary mucocele of the petrous apex: MR appearance. Am J Neuroradiol 13:203–204, 1992. 11. Linskey ME, et al: Aneurysms of the intracavernous carotid artery: Clinical presentation, radiographic features, and pathogenesis. Neurosurg 26:71–79, 1990. 12. Lee Y-Y, van Tassel P: Craniofacial chondrosarcomas: Imaging findings in 15 untreated cases. Am J Neuroradiol 10:165–170, 1989.

13. Meyers SP, et al: Chondrosarcomas of the skull base: MR imaging features. Radiology 184:103–108, 1992. 14. Meyers SP, et al: Chordomas of the skull base: MR features. Am J Neuroradiol 13:1627–1636, 1992. 15. Libshitz HI, et al: Multiple myeloma: Appearance at MR imaging. Radiology 182:833–837, 1992. 16. Oot RF, et al: The role of MR and CT in evaluating clival chordomas and chondrosarcomas. Am J Neuroradiol 9:715–723, 1988. 17. Utz JA, et al: MR appearance of fibrous dysplasia. J Comput Assist Tomogr 13(5):845–851, 1989. 18. Curtin HD, Jensen JE, Barnes L Jr, May M: “Ossifying” hemangiomas of the temporal bone: Evaluation with CT. Radiology 164:831–835, 1987. 19. Lo W: Endolymphatic sac tumor: More than a curiosity. Am J Neuroradiol 14:1322–1323, 1993. 20. Mukherji SK, et al: Papillary endolymphatic sac tumors: CT, MR imaging, and angiographic findings in 20 patients. Radiology 202(3):801–808, 1997. 21. Hirsch WL, Hryshko FG: Comparison of MR imaging, CT, and angiography in the evaluation of the enlarged cavernous sinus. Am J Neuroradiol 9:907–915, 1988. 22. Yuh WTC, et al: MR imaging of primary tumors of trigeminal nerve and Meckel’s cave. Am J Neuroradiol 9:665–670, 1988. 23. Linskey ME, Sekhar LN: Cavernous sinus hemangiomas: A series, a review, and a hypothesis. Neurosurg 30:101–108, 1992. 24. Minor LB, et al: Sound- and/or pressure-induced vertigo due to bone dehiscence of the superior semicircular canal. Arch Otolaryngol Head Neck Surg 124:249–258, 1998. 25. Mong A, et al: Sound- and pressure-induced vertigo associated with dehiscence of the roof of the superior semicircular canal. Am J Neuroradiol 20:1973–1975, 1999. 26. Lo WWM, Solti-Bohman LG, lambert PR: High-resolution CT in the evaluation of glomus tumors of the temporal bone. Radiology 150:737–742, 1984. 27. Arriaga MA, Lo WW, Brachman DE: Magnetic resonance angiography of synchronous bilateral carotid body paraganglia and bilateral vagal paragangliomas. Ann Otol Rhinol Laryngol 101:955–957, 1992. 28. Graham MD, LaRouere MJ, Kartush JM: Jugular foramen schwannomas: Diagnosis and suggestions for surgical management. Skull Base Surg 1(1):34–38, 1991. 29. Saski T, Takakura K: Twelve cases of jugular foramen neurinoma. Skull Base Surg 1(3):152–160, 1991. 30. Kawamura Y, SZE G: Totally cystic schwannoma of the tenth cranial nerve mimicking an epidermoid. Am J Neuroradiol 13:1333–1334, 1992. 31. McElveen JT Jr, Lo WW, Gabri TH, Nigri P: Aberrant internal carotid artery: Classic findings on computed tomography. Otolaryngol Head Neck Surg 94:616–621, 1986. 32. Geoffray A, Lee Y-Y, Jing B-S, Wallace S: Extracranial meningiomas of the head and neck. Am J Neuroradiol 5:599–604, 1984. 33. Malony TB, Brackman DE, LO WW: Meningiomas of the jugular foramen. Otolaryngol Head Neck Surg 106:128–136, 1992. 34. Cunningham MJ, Curtin HD, Butkiewicz BL: Histiocytosis X of the temporal bone: CT findings. J Comput Assist Tomogr 12(1): 70–74, 1988. 35. Quantin L, et al: Congenital cholesteatoma of external auditory canal. Int J Pediatr Otorhinolaryngol 62(2):175–179, 2002. 36. Vrabee JT, et al: External canal cholesteatoma. Am J Otol 21(5): 608–614, 2000. 37. Malcolm PN, et al: CT appearance of external ear cholesteatoma. Br J Radiol 70(837):959–960, 1997.

BIBLIOGRAPHY Som PM, Curtin HD: Head and Neck Imaging, 4th ed, vols 1 & 2. St. Louis, Mosby, 2003.

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Outline Technique Congenital Anomalies Normal Variants Congenital Ear Deformities Tumors Schwannomas Vascular Tumors Epidermoid Cysts Cholesterol Cysts

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Chapter

Imaging of the Facial Nerve

Carcinomas Rare Tumors Trauma Inflammatory Disease Intrinsic Inflammation Extrinsic Inflammation Hemifacial Spasm Summary

maging of the facial nerve has evolved into a precise procedure that employs both high-resolution computerized tomography (HRCT) and magnetic resonance imaging (MRI). It has gone from the era of plain films, followed by conventional polytomography,1,2 popularized in the 1960s, through cisternographic tomography,3 performed primarily through the mid-1970s, to the present standards of HRCT and MRI.4–9 The advantages of CT over the techniques in use previously are (1) high-contrast resolution; (2) simultaneous display of densities of air, soft tissue, and bone; (3) ease of examination; and (4) half of the radiation dose of polytomography. The advantages of MRI include (1) easy multiplanar projection without patient repositioning, (2) superior soft tissue resolution, and (3) lack of exposure to ionizing radiation. Facial nerve imaging is today accomplished by using MRI with gadolinium diethylenetriamine pentaacetic acid (DTPA) enhancement and HRCT, either jointly or alone. The facial nerve has a complex, multiplanar course, both intracranially and extracranially (Figs. 23-1, 23-2, and 23-3).10–12 The intracranial portion extends from the brainstem to the internal auditory canal (IAC), for a length of 23 to 24 mm, and includes the premeatal segment, which lies in the cerebellopontine angle (CPA). The intratemporal portion is subdivided into three segments. A length of 5 to 12 mm (average = 10 mm) passes through the IAC and then passes anteriorly and slightly inferiorly in its labyrinthine segment for 3 to 5 mm to reach the geniculate fossa. The nerve has its first surgical genu at the geniculate ganglion, where it turns at an acute angle of approximately 75 degrees to run posteriorly and slightly laterally and from which emerges anteromedially the greater superficial petrosal nerve. The tympanic portion of the facial canal is straight, 10 to 12 mm in length, and, in 65% of cases, covered by a thin bony lamella over its external wall. The mastoid, or second surgical, genu occurring

Sujana S. Chandrasekhar, MD Antonio De la Cruz, MD William W. M. Lo, MD Fred F. Telischi, MD

at the posterosuperior region of the tympanum, subtends an angle of 95 to 125 degrees and results in a nearly vertical descent of the nerve. The vertical (or mastoid) portion of the facial nerve canal descends 13 mm to the stylomastoid foramen. The extratemporal facial nerve, as it emerges from the stylomastoid foramen, runs anteriorly in the substance of the parotid gland and divides into two primary branches: the temporofacial, or superior, division and the cervicofacial, or inferior, division. These two divisions in turn elaborate main branches and break up into a plexus to supply the facial muscles. Accurate clinical history and physical examination are necessary when choosing the imaging modality that will best evaluate facial nerve lesions. Different sites of neural injury must be imaged differently. MRI and HRCT often yield complementary information and at times both are required for optimal demonstration of facial nerve pathology. MRI is the method of choice when (1) the site of involvement is clinically unlocalized because it is the only imaging modality that demonstrates the facial nerve comprehensively from the pons to the parotid gland; (2) the site of lesion is clinically localized to either the intracranial or the extratemporal portion of the nerve because it provides excellent soft tissue contrast; or (3) the onset of symptoms is acute because, with gadolinium enhancement, MRI is capable of showing changes of inflammation not seen on CT.13–15 Thin-section HRCT that makes use of a bone or edgeenhanced algorithm renders exquisite bony detail. It is the preferred initial imaging modality when a lesion is clinically localized in the middle ear or mastoid and is the method of choice in cases of temporal bone trauma.16–18 CT with a standard soft tissue algorithm with and without an intravenous iodinated contrast medium may be used to evaluate the CPA and the parotid gland, but results are 419

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Figure 23-1. Normal HRCT anatomy of the facial nerve-axial views, left ear. A, Arrowheads demonstrate IAC segment, labyrinthine segment, and geniculate ganglion. Note Bill’s bar (vertical crest) separating the facial and superior vestibular nerves. B, Arrowheads demonstrate the tympanic segment. C, The mastoid segment (arrowhead) lies at about 3 o’clock to the jugular fossa. D, Facial nerve (arrowhead) sitting in fat as it exits the stylomastoid foramen.

inferior to MRI in soft tissue contrast, and without intrathecal gas injection this modality does not exclude small IAC tumors.3 This is used only as a secondary option when MRI is not available or when the patient cannot be imaged on the MR scanner, for example, if the patient is too claustrophobic or too large.

TECHNIQUE The technical considerations for MRI of the facial nerve are nearly identical to those for MRI of the CPA and the IAC. These considerations are fully discussed in detail in Chapter 21, Imaging the Cerebellopontine Angle, and are not repeated here. When necessary, similar techniques are extended to cover the course of the extratemporal facial nerve through the parotid gland see (Fig. 23-3F). For detection and demonstration of facial nerve lesions, a well-focused MRI is indispensable because many of these are only a few millimeters in size. The technique employs imaging in transverse and coronal planes, with contiguous or overlapping thin sections of 3 mm each in thickness,

covering the pons to the parotid gland, before and after intravenous injection of a paramagnetic contrast agent. Sagittal or oblique sagittal images can be helpful in displaying lesions in the facial nerve canal (FNC) (see Fig. 23-3E) and do not require patient repositioning.9,14,19,20 Segments of the nerve in the facial canal enhance in the majority of normal subjects after the administration of intravenous gadolinium.21 This enhancement is due to the presence of a perineural vascular plexus in the FNC and may be asymmetrical in normal individuals. Compared with the findings in Bell’s palsy or Ramsay Hunt syndrome, the enhancement in normal subjects is less intense and does not extend into the premeatal segment of the nerve in the IAC (see Figs. 23-3A, B). HRCT for facial nerve evaluation is done in contiguous thin sections, no thicker than 2 mm, with a bone or edgeenhanced algorithm for maximal spatial resolution.4,22 Transverse sections of the temporal bone are obtained at either a 0- or 30-degree plane with respect to the infraorbital-meatal line. Scanning in either plane avoids direct radiation to the ocular lenses. The 30-degree plane is additionally advantageous in that it lies nearly parallel to

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Figure 23-2. Normal HRCT anatomy of the facial nerve-coronal views, left ear. A, Geniculate fossa (arrow). Note semicanal of tensor tympani (arrowhead). B, The labyrinthine and proximal tympanic segments (arrowheads) lie superior to the cochlear capsule, across from the malleus. C, The tympanic segment (arrowhead) is seen as it lies under the lateral semicircular canal, medial to the short process of the incus, and superolateral to the oval window niche. D, Mastoid segment (arrow), medial to the mastoid process, exiting the temporal bone at the stylomastoid foramen.

the tympanic or horizontal segment of the FNC and thereby avoids sectioning of this segment in a crosssectional or “salami” fashion.23 Additional images may be obtained in a modified coronal plane (by tilting the gantry) with the patient either supine or prone. With multirowdetector CT, which is now commonly available, coronal and sagittal images can now be reformatted from axially acquired data with ease and with little loss of resolution.

CONGENITAL ANOMALIES Normal Variants The labyrinthine FNC may originate from the midportion rather than the fundus of the IAC.24 The geniculate fossae may vary in size, although there is generally symmetry between the right and left sides.17 The most common variations in the course of the FNC involve the distal portion of the nerve.25–28 A “drooping,” or protruding, tympanic segment that overlies the oval window and

compromises surgical access may be seen on HRCT and should be recognized (Fig. 23-4A).29 The bony wall of the FNC may be developmentally dehiscent in 35% to 55% of the population, most commonly in the midtympanic segment over the oval window niche.26–28,30,31 The most common tympanic segment aberrations that may be encountered in surgery are: a course over the oval window; bifurcation proximal to the oval window; a course posteriorly either between the oval and round windows or inferior to the round window; a course through the stapedial arch; a course along the superior aspect of the lateral semicircular canal; or a course from the geniculate ganglion straight downward over the promontory.27 Imaging in the coronal plane is most helpful in excluding an aberrant tympanic segment.6 The anterior portion of the tympanic FNC may be enlarged by a persistent stapedial artery in its course from the tympanic cavity to the middle cranial fossa to terminate as the middle meningeal artery.32,33 Most individuals with this finding have few or no symptoms, and such a nonpathologic enlargement must not be mistaken for a

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Figure 23-3. Normal MRI of the left facial nerve-T1-weighted images. A, Axial, precontrast: arrows show normal geniculate ganglion and tympanic segment. B, Axial, postcontrast: same structures. C, Axial, precontrast: mastoid segment (arrowhead). D, Axial, postcontrast: same structure. E, Sagittal, precontrast: mastoid segment (arrow). F, Axial, precontrast: facial nerve (arrow) entering the substance of the parotid gland, posterolateral to the retromandibular vein (arrowhead).

tumor. A persistent stapedial artery can be suspected, even when the artery itself is too small to be visible on CT, in the absence of the ipsilateral foramen spinosum (Fig. 23-5).32 HRCT is diagnostic. MR angiography may be used for confirmation; conventional angiography is not indicated in

these cases. The marrow of the styloid process may mimic the mastoid segment of the facial nerve (see Fig. 23-4B) on HRCT; a distinction between the two structures can be made by following the course of the facial nerve on serial images.

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Congenital Ear Deformities A high incidence of aberrance of the tympanic segment of the facial nerve is seen in patients with other congenital middle ear abnormalities and should be sought.34 The vertical segment may be displaced anteriorly. The motor facial nerve may be congenitally absent, as in Möbius’ syndrome or aplasia of the facial motor nucleus, in which the FNC is very small because it needs to accommodate only sensory and parasympathetic fibers (see Fig. 23-5C).35 Abnormal enlargement of the geniculate fossa should be considered in the evaluation of spontaneous CSF otorrhea, as this condition has been described.36

TUMORS A

Although most neoplasms are extrinsic and involve the facial nerve only secondarily, facial nerve schwannomas and hemangiomas arise from facial nerve structures. The more common extrinsic tumors affecting the facial nerve are epidermoids, cholesterol granulomas, jugulotympanic paragangliomas, and squamous cell carcinomas. Rarer extrinsic tumors are primary fallopian canal paragangliomas, papillary adenomatous endolymphatic sac tumors, metastases, histiocytosis X, embryonal rhabdomyosarcoma, and choristoma.

Schwannomas

B

C Figure 23-4. Congenital variant: protruding tympanic segment–coronal HRCT, left ear. A, Tympanic segment of facial nerve (arrowhead) covers the oval window. B, Mastoid segment of facial nerve (arrow) should not be confused with the marrow of the styloid process (arrowhead). Both anomalies are associated with external auditory canal atresias. C, Lateral subcutaneous exit of the mastoid segment of the facial nerve, a rare but highly treacherous anomaly of the facial nerve canal.

Facial nerve schwannomas (FNSs) may involve any segment of the nerve or may involve more than one segment, not always in continuity. They are often sausage-shaped, expanding long segments of the FNC. Latack and colleagues37 have represented eight examples of FNS in diagrammatic form (Fig. 23-6). The clinical presentation and imaging findings depend on the segment(s) of the nerve involved. Because they involve the nerve by compression rather than invasion, facial palsy is generally a late finding. Intratemporal-segment schwannomas demonstrate facial nerve symptomatology earlier than do those at the CPA or the IAC. On MRI, FNSs are heterogeneous lesions hypointense to brain on T1-weighted images (T1WI), isointense on proton-density, and hyperintense on T2weighted images (T2WI) (Fig. 23-7). These tumors enhance briskly with gadolinium (Figs. 23-7B and 23-8). They are isodense to brain with enhancement after iodinated contrast on CT; however, tumors within the IAC or bony FNC can be missed; therefore, MRI is preferable for identifying small lesions.38,39 Lesions involving the distal tympanic and mastoid segments image more characteristically than do those in the perigeniculate, IAC, and parotid portions. An imaging distinction between facial and vestibular schwannomas in the CPA or the IAC is nearly impossible to make (see Fig. 23-7), although histologically they appear quite different.40 Certain imaging “clues” may aid in differentiating these lesions. Anterosuperior erosion of the IAC or erosion of the labyrinthine FNC on HRCT has been suggested as a diagnostic clue, but it is not reliable.41 Eccentric placement of the tumor in the IAC may help in making a preoperative diagnosis of facial schwannoma.42

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Figure 23-5. A and B, Congenital variant: persistent stapedial artery. A, Coronal HRCT, left ear: Arrowhead points to enlarged proximal tympanic segment of FNC caused by persistent stapedial artery. B, Axial CT of skull base: Arrowhead at normal foramen spinosum on right, immediately posterolateral to the foramen ovale. This structure is absent on the side of the persistent stapedial artery. (Courtesy of David F. Sobel, MD) C, Congenital variant: hypoplastic FNC in a child with congenital facial palsy. (left, abnormal; right, normal)

Figure 23-6. Eight types of FNS. The shaded areas represent segments of the nerve involved by tumor. Most FNSs involve long segments of the nerve. (Reproduced with permission from Latack JT, et al: Facial nerve neuromas. Radiologic evaluation. Radiology 149:731–739, 1983.)

There may be more than one component: one in the IAC/posterior cranial fossa and one in the middle cranial fossa connected via a narrow waist through the labyrinthine FNC (see Fig. 23-8). The dumbbell-shaped FNS from the posterior to the middle cranial fossa in the midpetrous region is highly characteristic. Large geniculate ganglion schwannomas may be mistaken for meningiomas, gliomas, or temporal lobe metastases. Coronal images are helpful in demonstrating the extradural origin of schwannomas; also smooth enlargement of the FNC favors the diagnosis of FNS (Fig. 23-9). Tumors arising from the tympanic segment may cause conductive hearing loss as the only symptom (Fig. 23-10). A pathognomonic finding is an enhancing enlargement of varying thickness along a significant length of the nerve (Figs. 23-11 and 23-12).37,38 During radiography of proximal tympanic segment schwannomas, one should not be misled by a persistent stapedial artery or developmental dehiscence of the FNC, as discussed previously. Differential diagnosis for geniculate ganglion lesions includes vascular tumors such as hemangiomas, epidermoid

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Figure 23-8. FNS in posterior and middle cranial fossae. A, Precontrast T1WI axial MRI. B, Postcontrast T1WI axial MRI.

C Figure 23-7. Axial MRI of an FNS. A, The tumor (arrow) is heterogeneous and mildly hypointense to brain on T1WI, precontrast. B, The mass enhances briskly with gadolinium–DPTA on postcontrast T1WI. C, On T2WI, the mass is mildly hyperintense to brain.

cysts, and meningiomas. Distinguishing among these lesions can be done with MRI and HRCT, based on the sharpness of their borders and on enhancement characteristics. On HRCT, the borders of hemangiomas are not sharp (Figs. 23-13 and 23-14), the borders of schwannomas are moderately sharp (see Fig. 23-12B), and the

borders of epidermoid cysts are extremely sharp (see Figs. 23-18A, and 23-20A). Hemangiomas are heterogeneously hyperintense on MRI and enhance strongly with gadolinium-DTPA (Figs. 23-15 and 23-16). Epidermoid cysts are isodense or hypodense on CT and are nonenhancing after contrast administration (see Figs. 23-19B and 23-20B). On MRI, epidermoid cysts are hypointense on T1WI and hyperintense on T2WI (see Figs. 23-18B, C and 23-19C, D), and they do not enhance with gadolinium (see Fig. 23-20D). The CT and MRI features of a meningioma at the geniculate ganglion resemble those in the CPA.

Vascular Tumors Intratemporal vascular tumors include hemangiomas, composed of thin-walled vascular spaces, and vascular malformations, composed of thick-walled vascular spaces lined with a layer of epithelium surrounded by fibroblasts and collagen. The two lesions may coexist in a single mass. The most common site of occurrence is the geniculate ganglion, followed by the IAC and then the mastoid genu. They are usually less than 1 cm in diameter. The nerve is involved by invasion and these tumors cause hemifacial spasm and facial palsy early. If located in the IAC, they

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Figure 23-9. Geniculate ganglion schwannoma, left. Presenting complaint: conductive hearing loss. A, Axial HRCT. Arrowhead points to small soft tissue mass between cochlear promontory and ossicles. B, Coronal T1WI MRI. Arrowhead to small component of tumor corresponds to soft tissue in the middle ear seen on CT. The large component protruding into the temporal lobe was clinically silent.

Figure 23-10. Tympanic FNS, left. A, Axial HRCT. Arrowhead points to soft tissue mass in middle ear, medial to the ossicles, lying along the tympanic FNC. B, Axial T1WI, postcontrast MR. Arrowhead shows enhancing mass along tympanic FN.

also cause a greater degree of sensorineural hearing loss than would be expected based solely on size.43 Early detection may allow complete removal with preservation of facial nerve function, avoiding facial nerve resection and grafting.44 Intratumoral bone spicules may be seen (see Fig. 23-13). This bone formation is a reaction to the hemangioma itself.45 Labyrinthine and geniculate ganglion lesions show subtle CT findings that include irregular and indistinct bone margins and reticular or “honeycomb” bone (see Fig. 23-14). Geniculate ganglion vascular tumors seen with MRI demonstrate nonhomogeneous intensities, which are the MRI correlate of the “honeycomb” seen on CT (see Fig. 23-15). They are difficult to distinguish from schwannomas when they occur at the mastoid genu. Their enhancement with contrast is not helpful on CT because density changes in such small lesions interspersed among bone are difficult to discern. HRCT with gas cisternography is usually required for lesions of the IAC, but MRI with gadolinium-DTPA enhancement demonstrates these lesions well and is preferred over CT (see Fig. 23-16).

Many of these tumors are similar to schwannomas in signal intensity on T1WI and T2WI, but some are most hyperintense than typical schwannomas on T2WI (Fig. 23-17).46,47

Epidermoid Cysts Petrous apex epidermoid cysts attain considerable size before involving the facial and acoustic nerves in the CPA or IAC. More common facial nerve involvement is seen with congenital epidermoid cysts of the supralabyrinthine region of the temporal bone.48 From this point of origin they readily erode the proximal FNC and can either reach around the superior semicircular canal and extend medially superior to the IAC or laterally into the epitympanum, or they can erode the cochlea or superior semicircular canal, which causes fistulization. CT demonstrates an expansile lesion-eroding bone, with sharp bone margins. Calcifications may be seen. T1WI MRI demonstrates low to intermediate signal, and T2WI shows high signal intensity (Figs. 23-18 and 23-19).

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Carcinomas

A

Survival in patients with squamous cell carcinoma of the temporal bone is related directly to the depth and extent of tumor involvement.49 Physical examination is unreliable, because the medial external auditory canal and tympanic membrane are visible in only 50% of patients.50 Plain film radiographs and tomograms are likewise inadequate. HRCT, however, is very accurate in assessing the depth and extent of tumor invasion.51 The technique uses a standardized protocol of bone and soft tissue algorithms with thin slices in both axial and coronal planes. Facial nerve involvement in these tumors occurs as a result of tumor extension through the fissures of Santorini into the extratemporal facial nerve, or in the middle ear/mastoid. Adenoid cystic carcinoma causes facial nerve palsy directly as it spreads along the perineurium. Both MR and HRCT are used in imaging this tumor.

Rare Tumors

B Figure 23-11. FNS–sagittal T1WI MRI. Note multifocal lesions from the geniculate ganglion to the stylomastoid foramen (arrowheads). Compare this to the normal sagittal view seen in Figure 23-3E. A, Precontrast. B, Postcontrast.

Acquired epidermoid cysts of the temporal bone may also cause facial nerve symptomatology. Radiologically, they are similar to congenital epidermoid cysts except that they originate from the middle ear and mastoid and may extend around the bony labyrinth to the petrous apex. A common location of FN involvement is in the geniculate ganglion region. Changes of chronic inflammation are seen in the middle ear and mastoid (Fig. 23-20).

Cholesterol Cysts Cholesterol granulomas form from obstruction of drainage of petrous apical air cells, followed by repetitive cycles of hemorrhage. They may cause irritation and initiate a foreign body reaction from their cholesterol crystals. They grow silently in the petrous apex until they exert pressure on cranial nerve V, VI, VII, VIII, IX, X, XI, or XII. These lesions are best imaged by combining HRCT and MRI. CT shows a sharply marginated, expansile lesion, without calcifications. MRI demonstrates high signal intensity on both T1WI and T2WI.

Fewer than 20 cases of paraganglioma of the facial canal (glomus faciale) without involvement of the jugular bulb have been reported in the literature.52–58 Two more cases have been diagnosed at our institution. Arnold’s nerve, the auricular branch of the vagus nerve, passes via one or two mastoid canaliculi from the jugular bulb to the facial canal and ascends in the vertical portion of the FNC.59 Paraganglia (glomus bodies) can be found along Arnold’s nerve within the vertical FNC. HRCT demonstrates expansion of the vertical FNC (Fig. 23-21A) and, with larger tumors, may show destruction in the mastoid (Fig. 23-21B). To demonstrate that the jugular foramen is not involved, catheter or MR venography is helpful. Jugulotympanic paragangliomas may grow to affect the facial nerve secondarily, which is demonstrated on imaging of the tumor. Other tumors of the temporal bone secondarily affecting the facial nerve are endolymphatic sac tumors (ELST), metastatic lesions, Langerhans’ cell histiocytosis, embryonal rhabdomyosarcomas, and non-neoplastic choristomas. Papillary adenomatous tumors of endolymphatic sac origin (ELST) are rare, locally invasive, and often extend into the medial mastoid to cause facial palsy (Fig. 23-22).60 Bilateral ELSTs have been found in patients with von HippelLindau disease.61 Of metastatic lesions to the temporal bone, 34% present with facial nerve palsy.62 The primary tumors are usually in the prostate, breast, or kidney. CT demonstrates bony destruction with tumor encroachment on the FNC; MR with gadolinium-DTPA is useful in equivocal cases.63 Langerhans’ cell histiocytosis causing facial palsy has been reported in 15 cases.39 The pathophysiology is histiocytic infiltration of the temporal bone leading to compression of the nerve within the eroded fallopian canal. CT shows an expansile soft tissue mass with bony labyrinthine and ossicular erosion. Embryonal rhabdomyosarcoma, an early childhood malignancy, involves the temporal bone in 7% of cases. Of 12 cases reported by Wiatrak and Pensak,64 6 had seventh cranial nerve paralysis as a presenting manifestation, and all of these 6 patients had middle ear tumors. The usual path of spread of

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Figure 23-12. FNS, left, extending from the IAC through the descending (mastoid) segment. A, Axial HRCT. Arrowheads at FNS in geniculate and tympanic segments. B, Coronal HRCT. Tumor in mastoid segment (arrowhead). C, Axial T1WI, postcontrast MRI. Tumor in IAC, geniculate and tympanic segments (arrowheads). D, Sagittal T1WI, postcontrast MRI. Tumor in tympanic and mastoid segments (arrowheads).

Figure 23-13. Hemangioma–axial HRCT, left side. Demonstrates intratumoral bone (arrowhead) within IAC hemangioma.

Figure 23-14. Hemangioma–axial HRCT, right side. Note irregular bony margins (arrow), honeycombing, and larger bone spicules (arrowhead).

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A Figure 23-15. Hemangioma of geniculate ganglion–axial T1WI, postcontrast MRI, right. Heterogeneous hyperintensity of the hemangioma (arrowheads) corresponds to the honeycomb appearance seen on HRCT (see Fig. 23-14).

B

Figure 23-16. Hemangioma of IAC–axial T1WI, postcontrast MRI, left. Note intense enhancement with gadolinium (arrows). This lesion cannot be differentiated radiologically from schwannoma. The enhancement seen at the geniculate ganglion (arrowhead) was not tumor at surgery.

C Figure 23-18. Suprageniculate congenital epidermoid cyst, left ear, axial projections. A, HRCT. Arrow demonstrates sharp margin of bony erosion. Note involvement of the ampullated end of the superior semicircular canal (arrowhead). B, This lesion has intermediate signal intensity on T1WI MRI. C, The same lesion has high signal intensity on T2WI MRI.

Figure 23-17. Hemangioma–axial T2WI MRI, right. Note hyperintensity of tumor on T2WI in IAC and CPA, distinguishing it from the typical schwannoma.

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Figure 23-19. Petrous apex congenital epidermoid cyst, left ear, axial projections. A, HRCT with bone algorithm. The large lesion is expanding the petrous apex (arrows). B, CT with soft tissue algorithm, postcontrast. The mass is isodense or mildly hypodense to brain and nonenhancing (arrows). C, T1WI MRI. The mass is mildly hypointense to brain with an isointense capsule (arrows). D, T2WI MRI. The mass is markedly hyperintense.

rhabdomyosarcoma of the middle ear cleft is by invasion and destruction of the FNC with infiltration of the facial nerve, extension to the IAC, and from there on to the leptomeninges. The imaging modality of choice in these cases is HRCT because it assesses bony destruction and can evaluate response to therapy. Middle ear salivary gland choristomas, which are tumors composed of normal cells not normally found at the site of occurrence, usually affect the tympanic segment of the facial nerve and the ossicles.65

TRAUMA Specific thin-section HRCT is necessary in the radiologic evaluation of temporal bone trauma, because approximately 60% of temporal bone fractures are not apparent on routine head CT examinations.66 It is preferable to obtain both axial and coronal sections; however, if the status of the patient’s cervical spine precludes positioning for direct coronal images, coronal reconstructions from direct axial images can suffice.6 Accurate preoperative

localization with HRCT is vital because the surgical approach to decompression varies with the exact site of facial nerve injury.67 Gadolinium-enhanced MRI has been advocated for identifying focal enhancement as a method for localizing traumatic injury to the facial nerve.68 Classically, temporal bone fractures have been divided into two types: longitudinal (70% to 90%) and transverse (10% to 30%), defined by the orientation of the fracture relative to the long axis of the petrous bone. Ten percent to 20% of longitudinal fractures result in facial nerve palsy, which is usually delayed in onset and incomplete. The fracture line is oriented along the long axis of the temporal bone and, in palsy cases transgresses the nerve in the perigeniculate region (Figs. 23-23A, B). Facial paralysis occurs in 50% of transverse fractures, and is more frequently of immediate onset and complete. The facial nerve is usually involved in the labyrinthine or tympanic segment (Fig. 23-24). More recent literature indicates that a large percentage of temporal bone fractures are “mixed,” in that the fracture line is both along and across the long axis of the petrous bone. Audiometric data associated with

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Figure 23-20. Acquired epidermoid cyst of the temporal bone, right ear. A, Axial HRCT shows a sharply and smoothly marginated lobular mass extending from the middle ear cavity, anterior to the cochlea to expand the petrous apex, eroding portions of the cochlear capsule. B, Axial CT with soft tissue algorithm shows the mass to be mildly hypodense to brain. The patient’s facial weakness was due to erosion in the geniculate ganglion region (arrow). C, Axial T1WI MRI shows that the mass is mildly hypointense, with a thin isointense capsule (arrowheads), similar to that seen in Figure 23-19, C. D, Coronal T1WI MRI, postcontrast. The cholesteatomatous material shows no enhancement; there is enhancement of tissue in the middle ear and surrounding the capsule (arrowheads) as a result of reactive inflammation.

differently oriented fracture lines are available.69 Other large series have looked at fractures as either otic capsule “sparing” or “involving,” with capsule-involving fractures having a higher incidence of facial palsy.70

INFLAMMATORY DISEASE Intrinsic Inflammation Bell’s palsy, or idiopathic isolated peripheral facial palsy, represents 50% to 85% of all cases of facial nerve palsy.71 The majority of cases have a typical clinical presentation and do not require imaging; however, in 15% there is an atypical presentation or a prolonged course.72,73 In these cases, gadolinium-enhanced MRI is useful and can help the clinician avoid missing a CPA/IAC tumor. The presumed accumulation of gadolinium in areas of inflammation and disruption of vessel integrity has provided the basis for evaluation by means of this modality.14 A number of studies have demonstrated significant enhancement of the facial

nerve in these individuals.74–77 The pathologic enhancement seen on gadolinium-enhanced MRI is much more intense than seen in normal subjects, usually involves the perigeniculate and labyrinthine segments, and can extend into the premeatal segment (Fig. 23-25). These findings are consistent with the theory of meatal nerve entrapment popularized by Fisch and Esslen.78 Nerve enhancement may persist 4 months or longer following the onset of paralysis. No difference is seen radiographically between acute and chronic cases, and there is no prognostic significance attributable to the presence or the degree of facial nerve enhancement in patients with viral inflammatory facial paralysis.79 Enhancement with enlargement of the nerve suggests tumor rather than inflammation. Herpes zoster oticus, or Ramsay Hunt syndrome, manifests as auricular vesicles, ear pain, and facial paralysis. Abnormal gadolinium enhancement of the facial nerve is seen, similar to that seen in Bell’s palsy. If the inflammation spreads to involve the eighth nerve and membranous labyrinth, variable enhancement of these structures is also noted on MRI.75,80,81

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A

B Figure 23-21. Facial canal paraganglioma (glomus faciale), left ear, axial HRCT. A, Expansion of vertical FNC (arrowhead). B, Arrows show extension of tumor beyond FNC to adjacent mastoid and external auditory canal, encroaching on the jugular fossa (arrowhead).

Lyme disease is a treponemal multisystemic infection that is transmitted by a deer tick (Ixodes dammini). Ten percent of all patients with Lyme disease and 50% of those patients with central nervous system infection will have unilateral or bilateral facial nerve palsies.82 Enhancement of the facial nerve on MRI is seen and is identical to that seen with herpes zoster oticus and Bell’s palsy.

Extrinsic Inflammation Acute otitis media, chronic otomastoiditis, and cholesteatoma have been associated with facial paralysis. Cholesteatoma is present in more than half of the cases of chronic otitis media and facial palsy.83 Imaging is indicated in patients with facial palsy and chronic otomastoiditis or cholesteatoma and is directed toward preoperative surgical planning. HRCT is the imaging modality of choice because it can clearly identify areas of the fallopian canal violated by surrounding inflammatory soft tissue.84 Other temporal bone infections secondarily causing facial nerve palsy include mucormycosis, tuberculosis, and syphilis.85–87 Malignant (necrotizing) otitis externa, a skull base osteomyelitis, can be complicated by facial palsy through spread of infection via the fissures of Santorini in the external auditory canal, which involves the nerve at the

B Figure 23-22. Papillary adenomatous tumor of the endolymphatic sac, left ear, axial projections. A, HRCT. The tumor is destroying bone in the retrolabyrinthine region with extension to the medial mastoid (arrowheads) at the area of the mastoid facial nerve genu. B, T1WI MRI. This tumor (arrowheads) is heterogeneous, containing hypointense, isointense and in particular, hyperintense foci, precontrast.

stylomastoid foramen.88 Nuclear medicine evaluation with technetium scanning to detect the extent of skull base osteomyelitis and gallium scanning for early detection of recurrence are invaluable in this disease. Facial nerve imaging per se is not indicated in these cases; however, CT and MRI are helpful in assessing the extent of disease because they can demonstrate evidence of inflammatory and soft tissue changes around the stylomastoid foramen and mastoid segments of the facial nerve.89

HEMIFACIAL SPASM Hemifacial spasm (Fig. 23-26) is a hyperactive facial nerve dysfunction characterized by painless paroxysmal spasms of the ipsilateral mimetic musculature. It is frequently the

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Figure 23-23. A, Longitudinal temporal bone fracture, left ear, axial HRCT. Comminuted longitudinal fracture (arrows), with large fragment (arrowhead) involving the geniculate fossa, and extension of the fracture laterally through the EAC (twin arrows). B, Longitudinal temporal bone fracture, left ear, axial HRCT. This is a similar but more subtle comminuted fracture compared with the fracture in A. The fracture lines involve the geniculate fossa and extend laterally through the mastoid cortex (arrowheads). Note blood in the mastoid cavity.

Figure 23-24. Transverse temporal bone fracture, left ear, axial HRCT. This patient presented with a complete ipsilateral sensorineural hearing loss and abrupt-onset facial paralysis. The fracture line courses through the ampullary limb of the lateral semicircular canal (arrowhead), transecting the underlying tympanic segment of the facial nerve.

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Figure 23-25. Bell’s palsy, left, postcontrast T1WI MRI. A, Axial. Arrowheads show marked enhancement in the premeatal segment in the fundus of the IAC, the geniculate ganglion, and the tympanic segment. Compare this to the mild to moderate enhancement seen on the asymptomatic right side. B, Coronal. Arrowheads demonstrate marked enhancement of the premeatal segment and the geniculate ganglion. The opposite (normal) side demonstrates mild enhancement in the geniculate ganglion only (line).

Figure 23-26. Hemifacial spasm. This heavily T2-weighted CISS image illustrates the neurovascular cross-compression that can be seen in hemifacial spasm.

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result of compression of the facial nerve at its root exit zone from the brainstem by vascular loops or aneurysms of the posterior or anterior inferior cerebellar artery, the vertebral artery, or the internal auditory artery. Both dynamic HRCT with contrast and MRI have been used to demonstrate the vascular aberrance. Angiography for diagnosis was reserved for equivocal cases in which CT failed to demonstrate the pathology; however, the use of conventional angiography has declined with the advent of MRI and MR angiography.90–93

SUMMARY Effective use of imaging for evaluation of facial nerve disorders requires knowledge of the multiplanar anatomic course of the nerve and an understanding of the clinical disease. Properly oriented, thin-section multiplanar imaging is necessary to evaluate the different facial nerve segments and their disorders. The predicted site and type of onset of facial nerve pathology determine the type of initial imaging modality used. Lesions suspected of involving the intracranial portion of the facial nerve are best seen with MRI with gadolinium-DTPA enhancement. These include brainstem, CPA, and IAC tumors, as well as intracranial vascular aberrancies. When involvement of the intratemporal portion of the facial nerve is suspected, as with cholesteatoma, chronic otitis media, congenital temporal bone abnormality, carcinoma, or trauma, HRCT is the imaging modality of choice. In Bell’s palsy, Ramsay Hunt syndrome, and Lyme disease, facial nerve inflammation is identified most readily on MRI, if indicated. For lesions of the extratemporal facial nerve, soft tissue resolution is best obtained with MRI. Acute palsies are best imaged with MRI. Most importantly, detailed communication between the clinician and the radiologist will result in the optimal combination of imaging techniques for maximal patient benefit.

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11. Proctor B: The anatomy of the facial nerve. Otol Clin N Am 24(3):479–504, 1991. 12. Proctor B, Nager GT: The facial canal: Normal anatomy, variations and anomalies. Ann Otol Rhinol Laryngol 91(5):33–61, 1982. 13. Baker HL: The application of magnetic resonance imaging in otolaryngology. Laryngoscope 96:19–26, 1986. 14. Millen SJ, et al: Gadolinium-enhanced magnetic resonance imaging in facial nerve lesions. Otolaryngol Head Neck Surg 102:26–33, 1990. 15. Valvassori GE: Applications of magnetic resonance imaging in otology. Am J Otol 7(4):262–266, 1986. 16. Aguilar EA, et al: High resolution CT scan of temporal bone fractures: Association of facial nerve paralysis with temporal bone fractures. Head Neck Surg 9:162–166, 1987. 17. Swartz JD: High-resolution computed tomography of the middle ear and mastoid. I. Normal radioanatomy including normal variation. Radiology 148:449–454, 1983. 18. Zonneveld FW, et al: Direct multiplanar computed tomography of the petrous bone. Radiographics 3:400–449, 1983. 19. Teresi LM, et al: MR imaging of the intratemporal facial nerve using surface coils. AJNR 8:49–54, 1987. 20. Teresi LM, et al: MR imaging of the intraparotid facial nerve. AJNR 8:253–258, 1987. 21. Gebarski SS, Telian SA, Niparko JK: Enhancement along the normal facial nerve in the facial canal: MR imaging and anatomic correlation. Radiology 183:391–394, 1992. 22. Virapongse C, et al: Computed tomographic anatomy of the temporal bone. AJNR 3:379, 1982. 23. Chakeres DW, Spiegel PK: A systematic technique for comprehensive evaluation of the temporal bone by computed tomography. Radiology 146:97–106, 1983. 24. Curtin HD, Vignaud J, Bar D: Anomaly of the facial canal in a Mondini malformation with recurrent meningitis. Radiology 144:335–341, 1982. 25. Gasser R, May M: Embryonic development of the facial nerve. In May M (ed): The Facial Nerve. New York, Thieme, 1986. 26. Nager GT, Proctor B: Anatomical variations and anomalies involving the facial nerve canal. Ann Otol Rhinol Laryngol 97(Suppl 1):45–61, 1982. 27. Nager GT, Proctor B: Anatomic variations and anomalies involving the facial canal. Otol Clin N Am 24(3):531–554, 1991. 28. Proctor B, Nager GT: The facial canal: Normal anatomy, variations and anomalies. Ann Otol Rhinol Laryngol 88(Suppl 1):33–44, 1982. 29. Swartz JD: The facial nerve canal: CT analysis of the protruding tympanic segment. Radiology 153:443–447, 1984. 30. Baxter A: Dehiscence of the fallopian canal: An anatomical study. J Laryngol Otol 85:587–594, 1971. 31. Hough JVD: Malformations and anatomical variations seen in the middle ear during the operation for mobilization of the stapes. Laryngoscope 68(8):1337–1379, 1958. 32. Guinto FC Jr, Garrabrant EC, Radcliff WB: Radiology of the persistent stapedial artery. Radiology 105:365–369, 1972. 33. Moret J, Delvert JC, Lasjaunias P: Vascularization of the ear: Normal, variations, glomus tumors. J Neuroradiol 9:209–260, 1982. 34. Jahrsdoerfer RA: The facial nerve in congenital middle ear malformations. Laryngoscope 91(8):1217–1225, 1981. 35. Kuhn MJ: Radiologic findings in Mobius syndrome. Sinai J Med 55(2):167–170, 1988. 36. Petrus LV, Lo WWM: Spontaneous CSF otorrhea caused by abnormal development of the facial nerve canal. AJNR 20:275–277, 1999. 37. Latack JT, et al: Facial nerve neuromas. Radiologic evaluation. Radiology 149:731–739, 1983. 38. Parnes LS, et al: Magnetic resonance imaging of facial nerve neuromas. Laryngoscope 101:31–35, 1991. 39. Pillsbury HC: Pathophysiology of facial nerve disorders. Am J Otol 10(5):305–312, 1989. 40. Linthicum FH: Personal communication, 1993.

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41. Inoue Y, et al: Facial nerve neuromas: CT findings. J Comput Assist Tomogr 11(6):942–947, 1987. 42. Fagan PA, Misra SN, Doust B: Facial neuroma of the CPA and the IAC. Laryngoscope 103:442–446, 1993. 43. Sundaresan N, Eller T, Ciric I: Hemangiomas of the internal auditory canal. Surg Neurol 6:119–121, 1976. 44. Shelton C, Brackmann DE, Lo WWM, Carberry JN: Intratemporal facial nerve hemangiomas. Otolaryngol Head Neck Surg 104:116–121, 1991. 45. Gavilan J, Nistal M, Gavilan C, Calvo M: Ossifying hemangioma of the temporal bone. Arch Otolaryngol Head Neck Surg 116:965–967, 1990. 46. Lo WWM, et al: Intratemporal vascular tumors: Evaluation with CT. Radiology 159(1):181–185, 1986. 47. Lo WWM, et al: Intratemporal vascular tumors: Detection with CT and MR imaging. Radiology 171:443–448, 1989. 48. Fisch U, Ruttner J: Pathology of intratemporal tumors involving the facial nerve. In Fisch U (ed.): Facial Nerve Surgery. Birmingham, AL, Kugler/Aesurlapius, pp 448–456, 1976. 49. Moody SA, Hirsch BE, Myers EN: Squamous cell carcinoma of the external auditory canal: An evaluation of a staging system. Am J Otol 21(4):582–588, 2000. 50. Kinney S: Squamous cell carcinoma external auditory canal. Am J Otol 10:111–116, 1989. 51. Arriaga M, Curtin HD, Takahashi H, Kamerer DB: The role of preoperative CT scans in staging external auditory meatus. Radiologic-pathologic correlation study. Otolaryngol Head Neck Surg 105:6–11, 1991. 52. Bartels LJ, et al: Primary fallopian canal glomus tumors. Otolaryngol Head Neck Surg 102(2):101–105, 1990. 53. Dutcher PO, Brackmann DE: Glomus tumor of the facial canal: A case report. Arch Otol Head Neck Surg 112:986–987, 1986. 54. Waldron MNH, Flood LM, Clifford K: A primary glomus tumor of the facial nerve canal. J Laryngol Otol 116:156–158, 2002. 55. Mafee MF, Raofi B, Kumar A, Muscato C: Glomus faciale, glomus jugulare, glomus tympanicum, glomus vagale, carotid body tumors, and simulating lesions. Role of MR imaging. Radiol Clin N Am 38(5):1059–1076, 2000. 56. Kania RE, et al: Primary facial canal paraganglioma. Am J Otolaryngol 20(5):318–322, 1999. 57. Petrus LV, Lo WMM: Primary paraganglioma of the facial nerve canal. AJNR 17:171–174, 1996. 58. Magliulo G, et al: Multiple familial facial flomus: case report and review of the literature. Ann Otol Rhinol Laryngol 112(3):287–292, 2003. 59. Guild SK: The glomus jugulare, a nonchromaffin paraganglion in man. Am Otol Rhinol Laryngol 62:1045–1071, 1953. 60. Lo WWM, et al: Endolymphatic sac tumors: Radiology diagnosis. Radiology 189:199–204, 1993. 61. Poe DS, Tarlov EC, Thomas CB, Kveton JF: Aggressive papillary tumors of temporal bone. Otolaryngol Head Neck Surg 108:80–86, 1993. 62. Maddox HE: Metastatic tumors of the temporal bone. Ann Otol 76:149–165, 1967. 63. Angeli SI, Luxford WM, Lo WW: Magnetic resonance imaging in the evaluation of Langherhan’s cell histiocytosis of the temporal bone: Case report. Otolaryngol Head Neck Surg 114(1):120–124, Jan 1996. 64. Wiatrak BJ, Pensak ML: Rhabdomyosarcoma of the ear and temporal bone. Laryngoscope 99:1188–1192, 1989. 65. Bottrill ID, Chawla OP, Ramsay AD: Salivary gland choristoma of the middle ear. J Laryngol Otol 106(7):630–632, 1992. 66. Holland BA, Brant-Zawadzki M: High resolution CT-temporal bone trauma. AJNR 5:291–295, 1984. 67. Gentry LR: Temporal bone trauma-current perspectives for diagnostic evaluation. Neuroimag Clin N Am 1(2):319–340, 1991.

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68. Haberkamp TJ, Harvey SA, Daniels DL: The use of gadoliniumenhanced magnetic resonance imaging to determine lesion site in traumatic facial paralysis. Laryngoscope 100:1294–1300, 1990. 69. Lee H-J, et al: Temporal bone fractures and complications: Correlation between high-resolution computed tomography and audiography. Emerg Radiol 5(1):8–12, 1998. 70. Brodie HA, Thompson TC. Management of complications from 820 temporal bone fractures. Am J Otol 18(2):188–197, Mar 1997. 71. May M, Klein SR: Differential diagnosis of facial nerve palsy. Otolaryngol Clin N Am 24(3):613–644, 1991. 72. May M, Hardin WD Jr, Sullivan J, Wette R: Natural history of Bell’s palsy: The salivary flow test and other prognostic indicators. Laryngoscope 86:704–712, 1976. 73. Pietersen E: The natural history of Bell’s palsy. Am J Otol 4:107–111, 1982. 74. Engstrom M, et al: Facial nerve enhancement in Bell’s palsy demonstrated by different gadolinium enhanced magnetic resonance imaging techniques. Arch Otol Head Neck Surg 119:221–225, 1993. 75. Korzec K, et al: Gadolinium-enhanced magnetic resonance imaging of the facial nerve in herpes zoster oticus and Bell’s palsy: Clinical implications. Am J Otol 12(3):163–168, 1991. 76. Murphy TP: MRI of the facial nerve during paralysis. Otol Head Neck Surg 104:47–51, 1991. 77. Schwaber MK, et al: Gadolinium-enhanced magnetic resonance imaging in Bell’s palsy. Laryngoscope 100:1264–1269, 1990. 78. Fisch U, Esslen E: Total intratemporal exposure of the facial nerve: pathologic findings in Bell’s palsy. Arch Otolaryngol 95(4):335–341, 1972. 79. Sartoretti-Schefer S, Brandle P, Wichmann W, Valavanis A: Intensity of MR contrast enhancement does not correspond to clinical and electroneurographic findings in acute inflammatory facial nerve palsy. AJNR 17:1229–1236, 1996. 80. Daniels DL, Czervionke LF, Millen SJ: MR findings in the RamsayHunt syndrome. AJNR 9:609, 1988. 81. Osumi A, Tien RD: MR findings in a patient with Ramsay-Hunt syndrome. J Comput Assist Tomogr 14(6):991–993, 1990. 82. Clark JR, et al: Facial paralysis in Lyme disease. Laryngoscope 95:1341–1345, 1985. 83. Takahashi H, et al: Analysis of 50 cases of facial palsy due to otitis media. Arch Otol 241:163–168, 1985. 84. Valavanis A, Kubik S, Schubiger O: High resolution CT of the normal and abnormal fallopian canal. AJNR 4(3):748–751, 1983. 85. Gussen R, Canalis RF: Mucormycosis of the temporal bone. Ann Otol 91:27–32, 1982. 86. Verduijn PG, Bleeker JD: Secondary syphilis of the facial nerve. Arch Otol 108:382–384, 1982. 87. Windle-Taylor PC, Bailey CM: Tuberculous otitis media: A series of 22 patients. Laryngoscope 90:1039–1044, 1980. 88. Chandler JR, Grobman L, Quencer R, Serafini A: Osteomyelitis of the base of the skull. Laryngoscope 96(3):245–251, 1986. 89. Rubin J, Curtin HD, Yu VL, Kamerer DB: Malignant external otitis: Utility of CT in diagnosis and follow-up. Radiology 174:391–394, 1990. 90. Nagaseki YN, et al: Oblique sagittal magnetic resonance imaging visualizing vascular compression of the trigeminal of facial nerve. J Neurosurg 77:379–386, 1992. 91. Pamir MN, et al: The aid of computerized tomography in hemifacial spasm. J Neuroradiol 19:293–300, 1992. 92. Tash RR, et al: Hemifacial spasms caused by a tortuous vertebral artery: MR demonstration. J Comput Assist Tomogr 12(3):492–494, 1988. 93. Girard N, et al: Three-dimensional MRI of hemifacial spasm with surgical correlation. Neuroradiology 39:46-51, 1997.

Chapter

24 Christopher F. Dowd, MD Van V. Halbach, MD Randall T. Higashida, MD

Diagnostic and Therapeutic Angiography Outline Introduction Techniques Arteriography Embolization Major Artery Occlusion Intraoperative Angiography Venography Disease Processes Vascular Aneurysms Arteriovenous Malformations Dural Arteriovenous

INTRODUCTION Radiologic evaluation of patients who present with symptoms or signs suggesting neurotologic disease usually commences with performance of plain-film radiography, computed tomography (CT), or magnetic resonance imaging (MRI). In selected circumstances, this evaluation can be enhanced by performing angiography to visualize the circulation of the head, neck, and brain optimally. Moreover, endovascular therapy (therapeutic angiography, embolization) has emerged as an accepted and valuable therapeutic option in treating many vascular conditions of the skull base and brain. The role of angiography and endovascular therapy in the evaluation and treatment of pathologic conditions producing pulsatile tinnitus, otalgia, otorrhagia, hearing loss, vertigo, and lower cranial nerve palsies, including angiographic techniques and indications for diagnostic and therapeutic angiography, will be presented in this chapter.

TECHNIQUES Arteriography It is important to review the pertinent history, both from the referring physician and from the patient, to document the necessity of the angiogram and to elicit any history of allergies. Review of all prior radiographic studies including CT or MRI scans is important to delineate the diagnostic goals of the angiogram. Assessment of peripheral pulses and a neurologic examination are necessary to properly 436

Fistulas Extracranial Arteriovenous Fistulas Atherosclerosis Fibromuscular Dysplasia Normal Variants Tumors Jugulotympanic Glomus Tumors Meningiomas Schwannomas Miscellaneous Tumors Conclusion

tailor the study. A full and informed consent is obtained from the patient including an explanation of the indications for the angiogram, the procedure itself, and risks. The majority of cerebral angiograms are performed via a transfemoral artery approach.1 The patient is placed in the supine position on the fluoroscopy table, a peripheral intravenous (IV) line is established, and mild IV sedation may be administered. The skin over the femoral artery is prepped and draped in a sterile fashion, and 1% lidocaine is administered as a local anesthetic. A hollow puncture needle is placed into the common femoral artery, through which a soft-tipped guidewire is directed retrograde into the aorta. The puncture needle is removed, and the angiographic catheter is advanced over the guidewire into the aorta. The catheter and guidewire combination may be advanced cephalad under fluoroscopic guidance to select one of the great vessels arising from the aortic arch, thus gaining access to the circulation of the neck and head. Once in position, iodinated contrast is injected through the catheter while radiographic films are exposed, either directly (“cut film” technique) or by computerized digital subtraction. Injection of multiple arteries in multiple projections is often necessary. Finally, the catheter is removed, and direct pressure is placed over the femoral puncture site for 15 minutes. The patient is instructed to remain supine with the leg used for the puncture straight for 6 hours, under observation. Alternatively, access to the arterial circulation may be achieved via axillary or brachial artery approach, using similar techniques. Rarely, direct puncture of the common carotid artery is performed.2

Diagnostic and Therapeutic Angiography

Embolization Devascularization of a tumor, arteriovenous malformation (AVM), or arteriovenous fistula (AVF) requires placement of embolic material into the affected artery (embolization) while maintaining patency of the normal surrounding vessels. Diagnostic angiography is performed and assessed initially, and an embolization plan is determined. A longer, softer, more slender embolization catheter (usually 2–3 French) is placed coaxially through the diagnostic guiding catheter and navigated to the site for embolization. Systemic anticoagulation is used if the catheter enters the intracranial circulation to prevent thrombus formation along the catheters and to avoid the risk of distal embolization to normal arteries. Once in position, superselective arteriography is performed to search for normal arteries that must be preserved. A provocative injection of Amytal Sodium (amobarbital sodium), a short-acting barbiturate, may also be used to detect supply to the central nervous system and retina. A positive test consists of production a reversible neurologic deficit. Two percent cardiac lidocaine is used to detect supply to cranial nerves. A negative test does not guarantee safety of embolization. If embolization is deemed safe, selection of the embolic agent is made based on the nature of the pathology, size of the vessels to be treated, and potential risks. Embolic agents include particulate material (polyvinyl alcohol [PVA], Gelfoam particles, and acrylic microspheres), detachable silicone or latex balloons, liquid adhesives (N-butyl cyanoacrylate), platinum or coils, custom-cut silk suture, and ethanol. Embolization of cerebral aneurysms requires placement of platinum coils directly into the aneurysm with the goal of preserving flow in the parent artery. The patient is monitored carefully for neurologic changes during the embolization. Control angiography is performed after embolization to document the adequacy of the procedure.

Major Artery Occlusion Large or fusiform aneurysms, arterial dissections causing thrombus formation, and malignant skull base or neck tumors3 may require permanent occlusion of the internal carotid or vertebral artery as definitive therapy or as a presurgical adjunct. Prior to permanent occlusion, a test occlusion of the artery in question is necessary to determine whether the collateral supply to the brain is adequate to avoid ischemia or infarction. A common site for test occlusion is the origin of the affected internal carotid artery (ICA). After systemically anticoagulating the patient, a double-lumen test occlusion catheter with a nondetachable balloon can be positioned in the proximal internal carotid.4 Under constant neurologic surveillance, the balloon is inflated to occlude the artery, and arterial back-pressures can be measured through the catheter lumen distal to the inflated balloon. The test occlusion is performed for 30 minutes. Neurologic tolerance of the test occlusion without new deficit and adequate pressure measurements are essential for predicting tolerance of a permanent occlusion. Some authors advocate the addition of cerebral blood flow evaluation using stable xenon CT5,6 or technetium hexamethylpropyleneamine oxime

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(99mTc-HMPAO) perfusion imaging,7–9 or provocative test occlusion by artificially lowering systemic blood pressure during test occlusion,10 but the role of these tests is not fully defined. In Higashida’s series of cavernous internal carotid aneurysms treated by detachable balloon occlusion,4 10% of patients developed new neurologic deficits despite tolerance of the test occlusion, although the majority of these deficits were transient and were treated successfully by volume expansion or antiplatelet therapy. Test occlusion of the smaller-caliber distal carotid circulation or vertebral artery may also be achieved using a nondetachable balloon catheter system; however, this precludes use of the double-lumen catheter measurement of distal pressures. Permanent occlusion is performed by simultaneously placing detachable balloons into the internal carotid in tandem, in order to ensure against deflation of one balloon. Platinum coils can also be used, but are often used in combination with a balloon, because coil use alone may allow thrombus formation while some antegrade flow persists, risking distal embolization and stroke. Vigorous IV fluid administration for volume expansion and strict limitation of activity, usually for a period of 3 days, to allow adequate cerebral perfusion is important to limit the possibility of delayed ischemia or infarction. These balloons are filled with radiopaque contrast material, so they can be visualized on serial plain skull radiographs, thus ensuring continued adequate positioning and guarding against deflation or distal migration.

Intraoperative Angiography The neuroradiologist is asked to perform diagnostic cerebral angiography in the operating theater to assist in surgical procedures with increasing frequency.11 Neurosurgeons in particular rely on excellent quality angiographic images obtained with a portable digital subtraction C-arm unit to evaluate the location of a vascular lesion such as an AVMs or to confirm proper aneurysm clip placement. This portable technique has application to skull base surgery as well, in evaluating aneurysms, AVMs, dural AVFs, and patency of major arteries. The technique is similar to conventional angiography, using a transfemoral arterial approach. It is helpful to place a femoral arterial introducer sheath at the beginning of the operation, which can be slowly perfused with saline during surgery. This sheath can be accessed for angiography at any desired time.

Venography Evaluation of skull base tumors or conditions that cause pulsatile tinnitus may require performance of a cerebral or jugular venogram. This is also the access route of choice for endovascular treatment of some dural AVFs. This can be performed safely via puncture of a femoral vein, with navigation of the catheter through the vena cava to the internal jugular vein. Vigilance must be maintained to avoid cardiac arrhythmia production by stimulation of the right atrial or ventricular wall during catheterization, an uncommon complication. The catheter can be placed at any location in the venous system and a venogram

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obtained. Smaller catheters are required for intracranial use to limit the risk of venous sinus perforation. Pressure measurements can also be performed to evaluate the hemodynamics at the site of a lesion, such as a meningioma invading the transverse sinus.12,13 With patient cooperation, provocative measures using Valsalva’s maneuver, lateral head turning, or flexion and extension may assist in recreating or temporarily obliterating subjective pulsatile tinnitus, and venography can be performed in those positions.

DISEASE PROCESSES Vascular Aneurysms An aneurysm is an abnormal focal arterial dilitation.13 Aneurysms can be classified in a number of ways. Morphologically, aneurysms can be termed saccular, fusiform, dissecting, or giant. Pathologic differentiation is made between true aneurysms, which are composed of normal arterial tissue layers with a defect in the media,14 and false aneurysms, or pseudoaneurysms, which are bounded only by adjacent bone, soft tissue, or even clot formed as a result of previous aneurysm rupture or vascular injury. Etiologically, aneurysms are classified as congenital, traumatic, atherosclerotic, mycotic, or dissecting.13 These categorizations overlap: for example, congenital aneurysms are true aneurysms, whereas traumatic or mycotic aneurysms are pseudoaneurysms. The majority of aneurysms are located intracranially. Common sites for congenital (or “berry”) aneurysms are in the regions of the anterior communicating artery, middle cerebral artery trifurcation, supraclinoid ICA, basilar artery, and at the origin of the posterior inferior cerebellar artery (PICA). A small percentage may arise in locations that can produce otologic symptoms, including lower cranial nerve palsies, otorrhagia, localized pain, and dizziness. This is especially true of traumatic pseudoaneurysms, which commonly occur at the skull base. The prevalence of congenital aneurysms is estimated from autopsy studies at 2%;13 this estimate varies considerably among these studies. Many of these individuals are never symptomatic. Unfortunately, there is no effective, noninvasive screening measure for detecting aneurysms. As a result, the most common presentation is subarachnoid hemorrhage (SAH), which can produce catastrophic symptoms ranging from severe headache and nuchal rigidity to coma and death. Secondary complications include aneurysm rerupture, most likely to occur within the 30 days following the initial hemorrhage,15,16 and vasospasm, which arises in 20% to 30% of aneurysmal SAH cases. Unruptured aneurysms can present with local mass effect, headache or pain, and ischemic neurologic events resulting from thromboemboli arising within a partially thrombosed aneurysm. A distinction must be made between aneurysms arising in a subarachnoid location and those arising extracranially (e.g., petrous or cavernous portion of ICA), as the latter are at considerably reduced risk of SAH. Associated conditions include polycystic kidney disease, coarctation of the aorta, fibromuscular hyperplasia, and AVMs.13 Congenital aneurysms are multiple in 20% of cases.

Traumatic pseudoaneurysms occur as a result of penetrating injuries (knife or missile wounds) or fractures of the skull base. The cervical portions of the carotid arteries are free, but become fixed as they enter the petrous bone, creating candidate sites for deceleration, hyperextension, or rotational injury. These pseudoaneurysms are associated with epistaxis,17,18 active hemorrhage per os, cranial nerve palsies from mechanical compression, otorrhagia (petrous segment of ICA),19 and traumatic extracranial AVFs (vide infra), in particular carotid-cavernous or vertebral artery fistulas. A pseudoaneurysm may form as a result of thrombosis of an AVF or may rupture in a delayed fashion to form a fistula. CT scanning has a 90% sensitivity for detecting aneurysmal SAH within 24 hours, but is much less sensitive in identifying the aneurysm. Larger aneurysms can be seen as focal, contrast-enhancing areas adjacent to the parent vessel. They may exhibit mural calcification, circumferential layers of internal thrombus that may not enhance, or adjacent mass effect. Giant aneurysms may erode the petrous or sphenoid bones, creating a smooth contour. MRI may demonstrate the aneurysm as a focal area of flowrelated signal void in the expected zones around the circle of Willis. Inhomogeneity of signal within the aneurysm may represent turbulent flow or partial thrombosis. MRI detects calcification in the aneurysm wall poorly. Angiography is the most effective method for identifying cerebral aneurysms. A thorough angiographic study is essential and includes examination of both internal carotid and vertebral arteries. Identification of aneurysms arising from the PICA origins may be accomplished by contrast injection of one vertebral artery, as long as reflux down the contralateral vertebral artery demonstrates its PICA origin. Common carotid compression during injection of the contralateral ICA may be necessary to opacify the anterior communicating artery, the most common site for congenital aneurysms and for aneurysms overlooked on initial angiography. Formerly, the treatment of choice for congenital intracranial aneurysms was craniotomy and surgical clipping. This may be precluded in giant or heavily calcified aneurysms, those with a wide or absent neck, in those occurring in locations difficult to access surgically, or in patients with severe underlying medical conditions.20–22 This is especially true of aneurysms located in the petrous or cavernous segments of the ICA, sites more likely to produce otologic symptoms.4,23,24 Endovascular therapy for aneurysms was introduced by Serbinenko in 1974,25 and the first large series were reported in the early 1980s26,27 using latex balloons. Higashida and colleagues subsequently reported the endovascular treatment of 215 aneurysms using a detachable silicone balloon as the embolic agent,22 as well as treatment of cavernous carotid4 and vertebrobasilar28 aneurysms. Fibered pushable coils were used in the late 1980s and early 1990s,29 but were supplanted by the detachable platinum microcoil. These were developed and introduced in 199230,31 and remain the current endovascular embolic agent of choice for aneurysm therapy with parent artery preservation. These detachable coils use a monopolar current to permit atraumatic coil detachment within the aneurysm. The goal of endovascular therapy is to exclude the aneurysm from

Diagnostic and Therapeutic Angiography

the circulation while preserving flow in its parent artery32 by placing the embolic device within the aneurysm. This is precluded in fusiform or wide-necked aneurysms, which permit migration of the embolic device into the parent arterial lumen. In such cases, permanent occlusion of the parent artery, if tolerated by the patient as predicted by test occlusion, can provide effective aneurysm thrombosis.4,33,34 The most widely used embolization device for treatment of fusiform aneurysms of the extracranial carotid artery has been the detachable balloon.35 Carotid test occlusion is followed by permanent occlusion using two balloons in tandem. The balloon is loaded onto a microcatheter and is directed from the femoral artery into the affected vessel. It is then inflated and detached within the artery. Halbach and coworkers have used these techniques to treat six aneurysms of the petrous portion of the ICA23 (Fig. 24-1), a location in which direct operative exposure is difficult. Presenting symptoms included hearing loss, vertigo, pulsatile tinnitus, trigeminal neuralgia, and headache. All aneurysms were cured, documented angiographically. Only one minor complication (amaurosis fugax) arose in this series. Despite the uncommon occurrence of petrous aneurysms,36–39 they may present emergently with otorrhagia spontaneously19 or after biopsy.40 Few petrous aneurysms have been reported in the literature, 27% of which present with hemorrhagic rupture, equally divided between otorrhagia and epistaxis.23 Larger aneurysms arising from the vertebrobasilar system can also produce cranial nerve deficits secondary to mass effect and can be treated in similar fashion.28 Trauma is the most frequent cause of aneurysms involving the cervical and petrous segments of the ICA, external carotid artery, and extracranial vertebral artery41 (Fig. 24-2). These are technically pseudoaneuryms and are treated by a different protocol. In the acute setting, the walls of these pseudoaneurysms are formed of fresh thrombus of insufficient strength to contain a balloon or other embolic devices. Direct embolization of the pseudoaneurysm is contraindicated, and parent vessel occlusion is required to prevent life-threatening epistaxis or massive pseudoaneurysm formation. Exception to this rule can be made when the aneurysm is sufficiently surrounded by bony structures (e.g., foramen transversarium of the cervical spine) to hold these embolic materials in position. In the chronic setting, the fibrosis of the pseudoaneurysm wall has taken place, which may allow direct embolization with parent artery preservation. The risks of endovascular aneurysm therapy have been well-documented and include aneurysm rupture during embolization, thromboembolic phenomenon, stroke due to intolerance of major vessel occlusion, and transient cranial nerve deficits from mass effect. The risk of the proposed embolization procedure must be tailored to the risk of the underlying condition to the patient. Arteriovenous Malformations An AVM is an abnormal network of arteriovenous connections without the normal intervening capillary bed. It can be found throughout the body and is a common vascular malformation in the central nervous system.42 It is discovered with one-seventh the frequency of intracranial

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aneurysms.43 This congenital condition can be seen at any age, but symptoms arise most commonly in the third decade.44 Intraparenchymal hemorrhage represents the most catastrophic form of presentation, may be accompanied by intraventricular or subarachnoid hemorrhage, and carries a 10% mortality rate and 30% morbidity rate. The risk of hemorrhage is estimated at 1% to 3% per year, but each hemorrhage augments this risk.44,45 Other common presenting symptoms are seizures and headaches. AVMs located in the occipital lobe have a particular association with migraine headaches. Progressive neurologic deterioration, seen in a minority of patients in the absence of hemorrhage, is thought to result from either venous hypertension or “steal” of blood supply to the AVM from normal brain tissue. Rarely, posterior fossa AVMs can present with neurotologic symptoms, including vertigo, diminished hearing, trigeminal neuralgia, and hemifacial spasmic46 (Fig. 24-3). Pulsatile tinnitus is distinctly unusual. These symptoms are often related to the venous drainage pattern of the AVM rather than to the location of the AVM nidus itself. As a result of long-standing high flow and elevated pressure, AVM draining veins may become enlarged, tortuous, restricted, or thrombosed and may impinge on cranial nerves as they exit the brainstem. CT scanning will delineate the AVM as a serpiginous tangle of contrast-enhancing tubular structures, representing the AVM nidus. Routine spin-echo MRI sequences will show a similar pattern, with signal dropout, or “flow void” within the AVM due to fast-flowing blood. Newer flowsensitive MRI sequences will demonstrate the AVM as high signal, confirming the presence of flow within the lesion. Enlarged feeding arteries and draining veins enter and exit this nidus. The relationship of the AVM to adjacent normal structures is more easily identified on MRI because of improved differentiation of soft tissue structures and lack of artifacts in the posterior fossa normally seen on CT. Acute hemorrhage is better evaluated with CT, and subacute/chronic hemorrhage on MRI. Angiography remains essential to confirm the diagnosis, search for risk factors for hemorrhage, and plan therapy. Feeding arteries are often multiple and enlarged due to increased flow,47 and each must be demonstrated angiographically. Primary supply is derived from pial arteries (e.g., anterior, middle, or posterior cerebral artery branches), but dural branches may be recruited secondarily and are thought to have the capacity to produce headache by affecting the highly innervated dura. The angioarchitecture of the nidus is seen only on angiography, and aneurysms arising from feeding arteries or within the nidus can be delineated. Irregular, restricted patterns of venous drainage may represent increased risk of hemorrhage, by increasing pressure within the AVM nidus. The treatment of choice is complete surgical resection. This cannot always be achieved with acceptable morbidity rates, and surgeons have devised pretherapeutic grading systems to evaluate such risks.48 Alternatively, stereotactic radiosurgery can provide effective therapy for smaller AVMs with unacceptable surgical risk. In either case, embolization undertaken as prior adjunctive therapy can improve the efficacy of the primary treatment.49 The surgeon is assisted

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A

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B

Figure 24-1. Fusiform petrous internal carotid artery aneurysm in a 14-year-old girl with a pulsatile retrotympanic mass and severe unilateral headaches. A, Transaxial noncontrast CT scan shows expansion of the petrous portion of the right carotid canal by a fusiform internal carotid aneurysm with erosion of the petrous bone (arrow). B, Transaxial long TR (repetition time)/TE (echo time) MRI scan (TR 2800/TE 80), rostral to (A), shows expansion of the petrous carotid canal by the aneurysm with inhomogeneous signal (arrow). This mixed signal represents turbulent flow within this portion of the aneurysm and possibly some surrounding thrombus. Lateral (C), and anteroposterior (D) angiographic views, right internal carotid artery injection confirm the presence of an irregular, partially thrombosed fusiform aneurysm extending from the distal cervical segment to the proximal cavernous segment of the internal carotid artery. Continued

C

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E Figure 24-1, cont’d. E, Plain skull film, lateral view, shows two oval embolization balloons filled with radiopaque metrizamide. These balloons have been placed into the IAC proximal and distal to the aneurysm to provide occlusion of the artery and aneurysm.

D by improved visibility and reduced operative blood loss and operating room time,50 and the radiotherapist by diminished flow in a smaller target.51 Occasionally, embolization alone is curative or provides palliation in large AVMs that produce neurologic deficits related to cerebral steal phenomenon or effects of abnormal venous drainage.46 The first AVM embolization was performed by direct catheterization of the common carotid artery and deposition of embolic spheres that flowed preferentially to the AVM.52 Presently, the embolization procedure uses a No. 2 French microcatheter, which can be superselectively navigated into an AVM feeding artery. These microcatheters are of two general types: steerable or flowdirected. A general anesthetic is used most often to eliminate patient motion during the delicate embolization, but in some circumstances the patient may be treated under IV sedation alone, allowing the possibility of selective tolerance testing using Amytal Sodium. Embolic materials in common use include particulate emboli

(PVA particles),53 liquid adhesives54,55(N-butyl cyanoacrylate), ethanol, and acrylic spheres. In AVMs with large fistulous connections, embolic platinum coils,56 silk suture segments, or even detachable balloons57 can be deposited at the fistula site. Complications of endovascular AVM therapy include AVM rupture, perforation of a feeding artery,58 and stroke from inadvertent embolization of normal arteries. Improved catheter technology and advances in angiographic imaging capabilities can reduce these risks, but do not substitute for the skill and judgment of the experienced interventional neuroradiologist. Dural Arteriovenous Fistulas A dural arteriovenous fistula (DAVF) is an acquired arteryto-vein shunt in the dura mater without an intervening malformation or nidus. This usually occurs along one of the dural venous sinuses draining the brain. It differs from an AVM in location (dural rather than intraparenchymal),

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C Figure 24-2. Traumatic internal carotid artery pseudoaneurysm in a 62-yearold man presented emergently with active arterial bleeding from the mouth, hoarseness, and tongue and palatal deviation. He had undergone attempted transoral biopsy of a calcified retropharyngeal mass 2 days earlier and had a remote childhood history of tonsillectomy without complication. Lateral (A), and anteroposterior (B) angiographic views of a left internal carotid artery injection, show a giant, bilobed pseudoaneurysm of the cervical segment of the internal carotid artery projecting anteromedially toward the oropharynx. The anteroposterior view was obtained during manual compression of the contralateral (right) common carotid artery to assess patency of the anterior communicating artery and cross-flow between the hemispheres, important information in consideration of carotid occlusion as treatment for the false aneurysm. C, Left internal carotid artery injection, high-magnification anteroposterior angiographic view, shows the pseudoaneurysm originating from a tonsillar loop of the internal carotid artery (arrows). D, Plain skull film, lateral view, after balloon occlusion of the left internal carotid artery, shows two contrast-filled detachable silicone balloons (black arrows) placed proximal to the heavily calcified pseudoaneurysm (white arrows).

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Figure 24-3. Cerebellar AVM in a 58-year-old man presenting with right hemifacial spasm, pulsatile tinnitus, and intermittent dizziness. A, Coronal MRI scan (TR 600/TE 20) shows an AVM nidus (arrow) in the right cerebellar hemisphere, along with feeding arteries and draining veins (foci of signal void). B, Transaxial MRI scan (TR 2800/TE 80) shows vessels in the cerebellopontine angles (open black arrows) abutting the internal auditory canals (white arrows). The AVM nidus is not present on this image. Continued

cause (acquired rather than congenital),59 morphology (lack of AVM nidus), and arterial supply (dural rather than pial). The majority of these lesions arise spontaneously, although there are associations with trauma60 and a history of venous sinus thrombosis, infection, and hormonal changes.41 The specific genesis of the condition is unclear, although it is speculated that small arteriovenous connections arise in the wall of a thrombosed dural sinus, which progress to form the DAVF. Alternatively, venous sinus thrombosis is a known sequela of DAVFs,61 raising the question of which pathologic state, thrombosis or arteriovenous shunting, precedes the other. Djindjian62 classified DAVFs according to pattern of venous drainage and presented the first large series of patients treated with embolization therapy. DAVFs occur in certain locations with some frequency, including the transverse sigmoid sinus, cavernous sinus (also termed indirect carotid cavernous fistulas),63,64 tentorium, ethmoidal groove,65 vein of Galen area,66,67 superior sagittal sinus, marginal sinus (foramen magnum), and petrosal sinuses.68 Symptoms depend heavily on location and routes of venous drainage,69 with the exception of pulsatile tinnitus,70–72 which is seen in the majority of DAVFs, especially if the venous drainage from the fistula involves a petrosal sinus. A bruit is classically auscultated by the physician and characterized as loud, harsh, and of variable high pitch. A small subpopulation of infants73 and children generally exhibit more arteriovenous shunting than their adult counterparts and may also experience high-output congestive heart failure, cortical atrophy, and a poorer prognosis.41 The major characteristic of a DAVF that directs its therapy is the pattern of venous drainage.62 This also has a direct bearing on symptomatology. A DAVF may drain exclusively into the affected venous sinus in an antegrade

direction. This drainage route may become inadequate if the arterialized inflow overwhelms the drainage capabilities of the sinus or if venous stenosis or restriction develops. In this instance, venous outflow may be reversed and drain to the contralateral transverse sinus, or retrogade into cortical/parenchymal veins. This type of aberrant venous drainage places the patient at significant risk for cerebral hemorrhage or infarction, which may be the initial symptom, especially if stenoses or varices develop in these cortical veins (Figs. 24-4 and 24-5). The character of the pulsatile tinnitus may change, becoming softer or even disappearing. Such a phenomenon may herald the development of cortical venous drainage as the dominant sinus undergoes thrombosis.41 As experience with this phenomenon has accrued, indications for urgent therapy have been identified,74,75 including hemorrhage, cortical venous drainage, visual loss, and raised intraocular pressure. DAVFs involving the cavernous sinus variably produce pulsatile tinnitus, proptosis, chemosis, orbital pain, ophthalmoplegia (cranial nerves III, IV, VI), decreased visual acuity (cranial nerve II), and raised intraocular pressure. Most patients present to an ophthalmologist, but if the superior ophthalmic vein is occluded, the patient may experience only pulsatile tinnitus without ophthalmologic symptoms. DAVFs involving the transverse, sigmoid, and petrosal sinuses can present more insidiously. Patients with these types of DAVFs typically experience pulsatile tinnitus without a vascular tympanic mass on otoscopy76,77 and sometimes headache, otalgia, or lower cranial nerve deficits (Fig. 24-6), but lack of more specific symptoms often hinders the diagnosis. In Halbach’s series of 28 patients with transverse or sigmoid sinus DAVFs, 18 presented with pulsatile tinnitus and another 8 with intracerebral, subarachnoid, or subdural hemorrhage.78

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Figure 24-3, cont’d. Early arterial (C) and venous (D) angiographic phases of a left vertebral artery injection, anteroposterior views, show the right cerebellar hemisphere AVM supplied primarily by the enlarged right AICA (C, open arrow). Several large serpiginous draining veins traverse the cerebellum (D). E, Arterial angiographic phase, left vertebral artery injection, Townes view, after embolization of the AVM with polyvinyl alcohol particles. Note absent opacification of the previously seen AICA. Residual AVM is supplied by the right superior cerebellar artery (SCA). The patient’s hemifacial spasm, pulsatile tinnitus, and dizziness abated completely.

E DAVFs involving the ethmoidal groove, tentorium, and vein of Galen often present catastrophically with hemorrhage because development of cortical venous drainage frequently precedes development of other symptoms. Cross-sectional imaging can assist in the diagnosis of a DAVF, but CT and MRI should not be used as a screening measure because of their relative lack of sensitivity. DAVFs without veno-occlusive disease may demonstrate

an entirely normal magnetic resonance appearance.79 Patients who have developed veno-occlusive changes show dilated vessels representing cortical venous drainage, without a focal parenchymal AVM nidus, differentiating DAVFs from AVMs. Major sinus thrombosis may also be evident. Complications of veno-occlusive disease, such as hemorrhage or infarction, are well demonstrated on MRI.

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Figure 24-4. Complex transverse sinus DAVF, treated with particulate embolization and surgery, in a 68-year-old woman presenting with cerebellar hemorrhage with several-month history of dizziness and nausea with acute worsening, new left facial numbness and mild weakness, and gait instability with falling to the left. A, Gadolinium–DTPA-enhanced transaxial MRI scan (TR 600/TE 20), performed after symptom onset but before acute worsening, shows left cerebellar hemisphere swelling and enhancement, with several foci of signal void representing abnormal vessels. No discreet arteriovenous malformation nidus is seen. B, Transaxial MRI scan (TR 2800/TE 80), performed in the same plane as (A) several days after abrupt symptom worsening, shows a new left cerebellar hemorrhage. A central dark area (deoxyhemoglobin) is surrounded by high-signal edema. C, Left internal carotid artery injection, anteroposterior view, venous angiographic phase, shows absent normal venous drainage to the left transverse sinus with opacification of the right transverse sinus (arrows) only. Arterial (D) and magnified venous (E) angiographic phases of a left external carotid injection, lateral views, show a transverse sinus DAVF supplied by several transmastoid perforating branches (D, small arrows) of the occipital artery and by posterior division of the middle meningeal artery (D, curved arrow). These feeding arteries were catheterized superselectively and embolized. Continued

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G Figure 24-4, cont’d. The isolated segment of transverse sinus (open arrows) drains only to multiple cerebellar veins (E) and demonstrates no normal antegrade venous drainage. F, Left vertebral artery injection, lateral angiographic view, also shows the DAVF (open arrows) supplied by posterior meningeal artery (curved arrow). G, Selective left posterior meningeal artery (black curved arrow) injection, lateral angiographic view, opacifies the affected isolated left transverse sinus (large open arrows). Note contrast reflux into left vertebral artery (curved open arrows). The microcatheter was navigated to a more distal position in the posterior meningeal artery prior to embolization to avoid reflux of embolic material into the vertebral artery. Left vertebral artery (H) and left external carotid artery (I) injections, lateral angiographic views, after embolization of occipital, middle meningeal, and posterior meningeal artery supply, show no residual DAVF. The patient subsequently underwent craniotomy and surgical occlusion of the affected transverse sinus to remove the possibility of future recanalization of the DAVF. She has recovered fully from her hemorrhage.

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Figure 24-5. Foramen magnum DAVF, treated by liquid adhesive embolization in a 30-year-old man presenting with acute onset of severe headache and nausea followed by coma. A, Noncontrast transaxial CT scan shows a large acute left cerebellar hematoma with midline shift and rupture into the displaced fourth ventricle (arrow). B, Left vertebral artery injection, lateral angiographic view, shows faint opacification of a pseudoaneurysm (curved open arrow) supplied by a muscular branch of the vertebral artery (black arrow). Continued

Subselective angiography is necessary for diagnosis and should be performed even when CT or MRI is normal when a DAVF is suspected clinically. This will allow confirmation of the exact location of the DAVF, visualization of all feeding arteries, assessment of the venous drainage including sinus occlusion and cortical venous outflow, and examination of patency of important dural-pial artery anastomoses. Because dural arteries provide arterial input and can originate from many sources, the angiogram should specifically include injection of the internal carotid (meningohypophyseal and inferolateral trunks), external carotid, vertebral (posterior meningeal and muscular branches), ascending pharyngeal, occipital, and middle meningeal arteries.41 Supply may be bilateral: depending on expected shunt location, the appropriate contralateral arteries must be examined (i.e., both vertebral arteries in a torcular DAVF; both middle meningeal arteries in a superior sagittal sinus DAVF.) In considering therapeutic options, it is useful to remember that DAVFs are dynamic lesions. A DAVF may be considered a benign disease in the absence of venoocclusive disease, visual loss, or elevated intraocular pressure. Under such conditions, conservative therapy is indicated. A small percentage of DAVFs undergo spontaneous regression without therapy or following diagnostic angiography. Assisted thrombosis of such benign fistulas can also be achieved using carotid–jugular compression therapy, especially in cavernous sinus DAVFs.80 The patient uses the contralateral fingertips to manually compress the common carotid artery and internal jugular vein simultaneously for

a period not to exceed 30 seconds, up to three times per hour. This results in static blood flow at the fistula site due to the combination of reduced inflow and outflow. This maneuver is contraindicated with atherosclerotic carotid bifurcation disease, cortical venous drainage, high-flow fistulas, DAVF-associated visual loss or elevated intraocular pressure, or in children. Just as DAVFs may regress spontaneously, progression can produce veno-occlusive changes and cortical venous drainage resulting in cerebral hemorrhage or infarction, underscoring the dynamic nature of this process. Endovascular therapy has become the treatment of choice in DAVFs to prevent such sequelae. Transarterial approaches allow navigation of microcatheters through feeding arteries as close to the fistula site as possible. The goal of embolization is to obliterate the fistula site, since proximal feeding artery occlusion will not cause thrombosis of the DAVF, but will encourage collateral supply to the fistula and will preclude future use of the embolized artery as a potential route for embolization. Embolic material that traverses the shunt and produces only venous occlusion causes redirection of venous outflow and possible aggravation of cortical venous flow without reducing arterialized inflow. Liquid adhesive agents (N-butyl cyanoacrylate) are ideal when there is minimal risk of embolizing normal dural arteries because they allow less chance of recanalization. However, particulate agents (PVA particles) are technically easier to use and may be selected when increased risk of normal artery embolization is present, despite the greater possibility of recanalization. Preembolization provocative testing with 2% cardiac lidocaine may help

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Figure 24-5, cont’d. C, Left external carotid injection, lateral angiographic view, shows a DAVF at the foramen magnum supplied by the ascending pharyngeal artery (closed arrows). The pseudoaneurysm opacifies (curved open arrow) and is the likely source of the hemorrhage. D, Superselective left ascending pharyngeal artery (straight black arrows) injection, lateral angiographic view, shows the fistula site at the foramen magnum supplied by branches of the neuromeningeal division of the ascending pharyngeal artery. Restricted early venous drainage to the cerebellum is seen (straight open arrowhead), along with the pseudoaneurysm (curved open arrow). Note opacification of the odontoid artery (curved black arrow) which can anastomose with the vertebral artery. To avoid reflux of embolic material into this artery and possible brainstem or posterior fossa stroke, the microcatheter in the ascending pharyngeal artery was advanced to the fistula site, and liquid adhesive embolization was performed. E, Postembolization left external carotid injection, lateral angiographic projection, shows no residual DAVF or pseudoaneurysm.

E determine the embolization risk in a particular artery and assist the choice of embolic agent. Often, a series of staged embolizations will permit access to certain feeding arteries that were initially too small to permit catheter passage for embolization, by allowing them to enlarge. The severity of veno-occlusive changes will direct whether conservative or aggressive management is pursued. Despite the best efforts at transarterial embolization, some DAVFs may remain patent. Others may have no adequate arterial access because of prior embolization or surgical ligation of feeding arteries. Transarterial embolization may be hazardous in still others because of crucial territory supply from adjacent arteries. In these instances, transvenous catheterization and embolization may provide safe occlusion at the fistula site. Embolization of veins away from the fistula site will only raise venous

pressure and aggravate symptoms. Cavernous sinus DAVFs lend themselves particularly well to this technique.63 From a transfemoral venipuncture, a microcatheter system is navigated through the internal jugular vein and inferior petrosal sinus (IPS) to the cavernous sinus. Embolic materials in frequent use include platinum coils56 and silk suture. Frequently, the IPS will permit catheter passage even if it fails to opacify on preembolization angiography. Other transvenous routes to the cavernous sinus include external jugular to angular to superior ophthalmic vein, and from the contralateral cavernous sinus across the sellar veins. Transverse sigmoid sinus DAVFs have also been treated successfully using the transvenous approach.78,81 Embolization of the diseased sinus itself is achieved by placement of a series of platinum or steel coils to occlude the fistula. A normal sinus with

Diagnostic and Therapeutic Angiography

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Figure 24-6. Inferior petrosal sinus DAVF, treated by balloon and coil embolization in a 47-year-old man with a 5-year history of tongue weakness and hemiatrophy and pulsatile tinnitus. He subsequently developed hoarseness and palatal deviation. A, Contrast-enhanced transaxial CT scan shows right tongue hemiatrophy and low density fatty replacement (arrows) with deviation of the oral cavity to the affected side. B, Right common carotid artery injection, lateral angiographic view, shows an inferior petrosal sinus DAVF supplied by a markedly enlarged ascending pharyngeal artery with drainage through a varix to the internal jugular vein (open curved arrow). The fistula site is identified (long straight arrow). C, Selective right ascending pharyngeal artery injection, lateral magnified angiographic view, shows the fistula more clearly. A detachable silicone balloon was flow-directed through the ascending pharyngeal artery and was detached at the fistula site. Continued

C

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F Figure 24-6, cont’d. D, Postembolization right common carotid artery injection, lateral angiographic view, shows the detachable embolization balloon (outlined by arrows) and no residual fistula supply from the ascending pharyngeal artery. E, Right vertebral artery injection, lateral angiographic view, shows residual supply to the fistula from a cervical muscular branch (long straight arrows) with faint opacification of the internal jugular vein (open curved arrow). A microcatheter was navigated through this muscular branch to the varix at the fistula site, and platinum coil embolization of the fistula site and feeding muscular branch was performed. F, Postembolization right vertebral artery injection, lateral angiographic view, shows multiple platinum coils in the varix at the fistula site (large arrow) and in the feeding muscular branch (small arrow), without residual arteriovenous shunting.

Diagnostic and Therapeutic Angiography

antegrade flow, without cortical venous reflux, should not be considered for this technique, as this type of DAVF is low-risk and other sinus drainage routes may be inadequate for normal venous drainage, if the affected sinus is closed. Surgical obliteration of the DAVF may be necessary when neither transarterial nor transvenous embolization can be performed. This is particularly true in ethmoidal DAVFs65 occurring along the floor of the anterior cranial fossa, which present with frontal lobe hemorrhage or subarachnoid hemorrhage. Other DAVFs are termed “complex”82,83 because they require a combination of endovascular and surgical techniques for cure. This combined approach is reserved for DAVFs likely to produce hemorrhage or neurologic deficits from veno-occlusive disease and has been effective in transverse/sigmoid and deep venous DAVFs. After embolization, certain clinical sequelae are expected. They include transient headache, disappearance of pulsatile tinnitus, and transient ophthalmoplegia in cavernous sinus DAVFs. True endovascular complications are uncommon and include stroke or cranial nerve deficits from inadvertent embolization of crucial normal arteries or occlusion of normal venous drainage patterns, hemorrhage from occlusion of normal veins or perforation of subarachnoid veins or dural sinuses, and visual loss from iatrogenic restriction of the superior ophthalmic vein without closure of the DAVF. Due to the great number of skull base collateral pathways, complexity of vascular anatomy, and variety of technical materials available, such surgical complications can be limited only by training and experience. Extracranial Arteriovenous Fistulas Acquired arteriovenous fistulas involving direct major artery-to-vein shunts may also occur in expected locations in and around the skull base, not involving dura. Characteristic types include direct carotid–cavernous, vertebral, and scalp arteriovenous fistulas. Most of these fistulas result from direct traumatic injury to the affected artery and subsequent fistula formation with an adjacent vein. Although symptoms differ with location, the classical presentation includes pulsatile tinnitus and an objective bruit. Direct Carotid–Cavernous Fistulas Direct carotid–cavernous fistulas (CCFs) represent acquired communications between the cavernous portion of the ICA and its surrounding cavernous venous sinus. A tear in the ICA causes arterialized inflow into the cavernous sinus, which must direct this high pressure to other draining veins. This entity differs from the cavernous sinus dural AVF (indirect carotid–cavernous fistula) in that the latter is composed of numerous small shunts in the wall of the cavernous sinus from small dural internal or external carotid branches, although similar symptoms may result. Common venous drainage pathways from the cavernous sinus include inferior and superior petrosal sinuses, superior and inferior ophthalmic veins, pterygoid venous plexus, sphenoparietal sinus (to cerebral veins), and contralateral cavernous sinus across the sella. Several of these venous routes must drain in a retrograde direction to

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decompress the cavernous sinus. Trauma is by far the most common cause. Because the cavernous segment of the ICA is fixed by dura at the skull base, it is susceptible to injury from skull base fracture.84 Nontraumatic CCFs result from ruptured cavernous carotid aneurysms or may occur spontaneously in association with fibromuscular dysplasia, Ehlers-Danlos syndrome,85 or neurofibromatosis.41 As with DAVFs, symptoms depend on routes of venous drainage, but pulsatile tinnitus is present in the overwhelming majority of patients. One can often auscultate a bruit over the temporal bone, mastoid region, or eye. Retrograde drainage through an enlarged superior ophthalmic vein may produce proptosis, chemosis, orbital pain, ophthalmoplegia, trigeminal pain or numbness, visual loss, and raised intraocular pressure to variable degrees depending on patency of other venous outflow pathways. Retrograde drainage through the sphenoparietal sinus to cortical veins places the patient at risk for intracerebral or subarachnoid hemorrhage or infarction. The contralateral eye may become involved if venous drainage crosses the sella to pressurize the contralateral cavernous sinus. Drainage along the petrous bone (inferior and superior petrosal sinuses) most often produces pulsatile tinnitus. The diagnosis of CCF is made clinically and confirmed angiographically, but cross-sectional imaging may assist the evaluation of these patients. CT is best suited to demonstrate skull base fractures, especially using bone reconstruction algorithms. CT or MRI may reveal dilatation of the cavernous sinus, proptosis, enlargement of the superior ophthalmic vein, cortical venous drainage, or infarction or hemorrhage in the brain. Angiography is necessary to delineate the CCF and its venous drainage pathways. The angiographer must be vigilant in identifying trauma-related injuries to other arteries, such as dissection, pseudoaneurysm formation, or a second fistula. Depending on the clinical scenario, both internal and external carotid arteries should be studied angiographically. Specific angiographic maneuvers use manual compression of the ipsilateral common carotid artery while injecting the vertebral artery (Huber’s maneuver)86 or ipsilateral ICA (Mehringer’s maneuver)87 to aid in identifying the exact site of the fistula in the cavernous carotid. High flow necessitates a fast filming rate. Surgical therapies have been supplanted by transarterial balloon embolization, the treatment of choice.88–90 From a transfemoral approach, a detachable balloon is directed through the ICA to the fistula site. Fistula flow allows entry of the balloon through the defect in the ICA into the cavernous sinus, where it is inflated and detached to close the CCF and preserve patency in the ICA91 (Fig. 24-7). This procedure has achieved closure of the CCF in almost all cases, with a residual ICA patency rate of 90%.84 A pseudoaneurysm may develop at the site of injury after embolization, which rarely requires additional therapy due to production of cranial nerve palsies (III, IV, V1, or VI). Embolic or ischemic complications are unusual, but can be caused by premature detachment and distal migration of a deflated balloon or intolerance of carotid occlusion. Care must be taken to avoid occlusion of the ICA proximal to the fistula site, as this will increase retrograde arterial steal to the fistula from the supraclinoid ICA and preclude further endovascular therapy.

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Figure 24-7. Direct CCF in a 30-year-old man with pulsatile tinnitus and mild unilateral proptosis and chemosis. A, Left internal carotid artery (solid curved arrows) injection, lateral angiographic view, shows a direct CCF with arteriovenous shunting across the fistula site (long arrow) and early opacification of the cavernous sinus (large open arrowhead). Retrograde venous drainage opacifies the enlarged superior ophthalmic vein (open curved arrows) and cortical veins (small solid arrows), placing this patient at risk for visual decline and cerebral hemorrhage. B, Left IAC injection, lateral angiographic view, with ipsilateral common carotid artery manual compression proximal to the catheter tip (Mehringer’s maneuver87) defines the fistula site (long arrow) more clearly. Early filling of the cavernous sinus (open arrow) and its venous drainage pathways is seen. C, Plain skull film, lateral view, during balloon embolization. The detachable balloon is inflated with contrast, and is not yet detached from its catheter. D, Postembolization left ICA injection, lateral angiographic view, shows no residual fistula. The balloon has been detached within the cavernous sinus allowing patency of the ICA. A small residual pseudoaneurysm (arrow) demarcates the previous fistula site.

Vertebral Fistulas Vertebral fistulas represent acquired abnormal arteriovenous shunting from the extracranial vertebral artery to adjacent veins. Penetrating trauma, especially knife and gunshot wounds, is the most common cause by far. Clinical symptoms and signs include pulsatile tinnitus (especially with more distal lesions), expanding hematoma, neck pain, progressive vertebrobasilar ischemia from arterial steal, and various cerebral and spinal cord neurologic deficits associated with venous hypertension, mechanical compression, or subarachnoid hemorrhage. Angiography will define the exact site of the fistula and route of venous drainage. Arterial steal can be confirmed, if present, by injection of the contralateral vertebral artery and observation for retrograde opacification of the affected vertebral artery from the vertebrobasilar junction to the fistula site. Complete transection of the vertebral artery with retraction of the severed stumps is difficult to assess prior

to treatment, as retrograde arterial steal distally in the affected vertebral artery may not allow its opacification from ipsilateral proximal vertebral artery injection. As with CCFs, transarterial balloon embolization has become the primary therapy.91–94 One or more detachable balloons can be navigated through the vertebral artery tear into the receiving vein and inflated to close the fistula (Fig. 24-8). The angiographer must avoid producing a normal perfusion pressure breakthrough (NPPB) phenomenon as a result of the treatment. Abrupt restoration of cerebral blood flow immediately after closure of a highflow vertebral fistula of long duration with arterial steal can overwhelm the ability of the cerebral vasculature to compensate, as it may have lost its autoregulatory capacity. This could theoretically result in intracerebral hemorrhage or malignant cerebral edema.95 Gradual occlusion of the fistula using staged procedures will limit such catastrophic complications.

Diagnostic and Therapeutic Angiography

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Scalp AVFs are often associated with a large varix (cirsoid aneurysm). Most often traumatic, abnormal connections from superficial temporal, occipital, and posterior auricular branches of the external carotid artery to dilated, irregular scalp veins may produce loud pulsatile tinnitus, cosmetic deformity, headache, or scalp necrosis.96 Surgical methods of treatment required extensive excision, risking significant operative blood loss and recurrence of the fistula from collateral supply, which limited the effectiveness of this form of therapy. Endovascular approaches have been used as surgical adjuncts and alone as definitive therapy. After superselective bilateral arteriography has delineated the fistula site and pattern of venous drainage, transarterial, transvenous, or direct varix puncture with embolization of the fistula site can be curative. Selection of embolic material depends on proximity of the catheter to the exact fistula site, caliber of vessels, rate of flow, and location. Liquid adhesive agents are the most permanent, but care must be taken to avoid scalp necrosis from occlusion of normal arteries. Platinum and steel coils, PVA particles, silk suture, absolute alcohol, and detachable balloons have also been used. Atherosclerosis

C Figure 24-8. Vertebral fistula in a 23-year-old man with pulsatile tinnitus after a shotgun wound to the left neck. A, Left vertebral artery injection, anteroposterior angiographic view, shows a high-flow vertebral fistula with multiple draining veins. Antegrade flow in the left vertebral artery (curved open arrows) is seen proximal to the fistula site. A shrapnel fragment (black arrow) is shown for orientation. B, Right vertebral artery injection, anteroposterior angiographic view, shows antegrade flow in the right vertebral artery (black curved arrow) with angiographic steal seen as retrograde flow in the distal left vertebral artery (open curved arrow) to the fistula site (large black arrow). The shrapnel fragment is again shown (smallblack arrow). C, Postembolization left vertebral artery injection, high-magnification anteroposterior angiographic view, shows antegrade flow in the artery (long arrow) without residual arteriovenous shunting. A single balloon was detached across the fistula site, now demarcated by a small residual pseudoaneurysm (large arrow) adjacent to the shrapnel fragment (small arrow).

Atherosclerosis is a major cause of morbidity and death in developed countries. It is the major cause of arterial occlusive disease (thrombosis and embolism), which is responsible for 80% of cerebral strokes.97 It frequently involves the common carotid artery bifurcation, ICA origin and siphon, vertebral artery origin, and basilar trunk. Formation of atheromatous plaque is accompanied by gradual stenosis, thrombotic occlusion, calcification, ulceration, and embolism. Tortuosity and dilatation can be associated findings as well, common in the basilar artery (dolichoectasia), which can produce trigeminal neuralgia or hemifacial spasm.98 Although patients present classically with episodes of cerebral ischemia or infarction, many patients demonstrate an audible bruit over the affected artery. Rarely, this is perceived by the patient as pulsatile tinnitus. Carotid duplex examination, which includes ultrasound visualization of the carotid bifurcation and Doppler measurement of blood velocity, is an effective noninvasive screening tool. Although advances in magnetic resonance angiography (MRA) and computerized tomographic angiography (CTA) have improved spatial resolution and have allowed better estimation of the degree of stenosis caused by a given lesion, conventional angiography remains the standard for evaluation of atherosclerotic carotid and vertebral arterial occlusive disease. Antiplatelet medications and endarterectomy remain treatment staples, although transarterial balloon angioplasty99–102 and carotid stenting103–106 have emerged as alternative treatments for clinically and hemodynamically significant atherosclerotic lesions. These endovascular treatments are especially helpful in more distal surgically inaccessible locations, in patients who have undergone prior neck irradiation, and in recurrent stenoses. Fibromuscular Dysplasia Fibromuscular dysplasia (FMD), also called fibromuscular hyperplasia or fibromuscular disease, is an idiopathic

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stenotic condition of large arteries97 most often seen in middle-aged women. Stenosis develops from overgrowth of muscular and fibrous tissue in the arterial wall. Originally identified in renal arteries, the cervical portions of the internal carotid and vertebral arteries are common disease sites. Symptomatic FMD most often presents as cerebrovascular insufficiency, but pulsatile tinnitus has been reported.107,108 Patients with FMD are prone to arterial dissection, AVFs,109 and aneurysm formation. Indeed, we have encountered a middle-aged woman, previously treated with carotid occlusion for a cavernous segment ICA aneurysm, who later presented with pulsatile tinnitus attributed to FMD in the contralateral cervical ICA (Fig. 24-9). Angiography is necessary for the diagnosis and classically demonstrates a long-segment “string-of-beads” appearance, with variable stenoses. Endarterectomy or surgical revascularization has been the mainstay of therapy in symptomatic FMD, but successful reports of balloon angioplasty100,110 and stent placement in selected cases

encourage further investigation and may provide a promising primary therapy. Normal Variants Aberrant Petrous Internal Carotid Artery An aberrant petrous ICA is a rare anatomic variant wherein the petrous portion of the ICA can take an anomalous course through the middle ear cavity and may present with pulsatile tinnitus or conductive hearing loss as a retrotympanic mass, simulating a glomus tympanicum tumor.111–114 During embryogenesis, the dorsal and ventral aortas are connected by a series of four arches. Further modification occurs both by anastomosis and by arterial regression. Abnormal development of the third aortic arch can result in agenesis of the cervical segment of the ICA. Collateral supply is derived from a primitive ascending pharyngeal artery that courses through the tympanic cavity. This artery has been labeled the “aberrant” ICA.113,115 Prior to the advent of CT, angiography was necessary to avoid the potential catastrophic consequences of performing surgery or biopsy of the suspected lesion, which could result in stroke or exsanguinating hemorrhage. Angiographically, the aberrant ICA ascends in a more lateral position than usual (Fig. 24-10) and takes a sharp turn anteriorly within the middle ear. Currently, this diagnosis is made on transaxial and coronal CT scans, which show absence of the normal vertical segment of the carotid canal, lack of a bony covering at the lateral aspect of the horizontal petrous carotid canal, and enlargement and ectasia of this canal. A rounded soft tissue mass in the medial aspect of the middle ear is continuous with the petrous carotid canal.112 MRI appears less sensitive than CT in the detection of this condition,76,77 although MRA may be diagnostic. Persistent Stapedial Artery A persistent stapedial artery is a rare variant in which the usual embryonic regression of the proximal stapedial artery fails to occur. Initially a continuation of the hyoid branch of the ICA, the stapedial artery becomes annexed by the developing external carotid system and regresses proximally at the level of the stapes. The distal remnant of the stapedial artery corresponds to the middle meningeal artery. If this regression fails to occur, the stapedial artery remains as a branch of the petrous segment of the ICA coursing through the stapes and turning anterosuperiorly to become the middle meningeal artery.113,114 Aberrant Jugular Bulb

Figure 24-9. FMD in a 58-year-old woman with pulsatile tinnitus. Left common carotid artery injection, anteroposterior angiographic view, shows alternating areas of dilitation and stenosis (“string-of-beads” appearance) in the cervical segment of the internal carotid artery (arrows) indicative of FMD. No other cause for pulsatile tinnitus was found.

A high, or aberrant, jugular bulb represents exposure of the bulb to the middle ear cavity due to a congenital or acquired dehiscence of the normal bony jugular plate (Fig. 24-11). This condition can variably produce conductive hearing loss and presents as a bluish middle ear mass.116 CT has supplanted angiography as the method of diagnosis, exhibiting a defect in the anterolateral aspect of the jugular foramen allowing protrusion of the jugular bulb into the middle ear cavity.76,117 Smooth, regular erosion of the jugular foramen permits differentiation of this condition from glomus tumor.112 As with an aberrant

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Figure 24-11. Aberrant jugular bulb. Left internal jugular venogram, anteroposterior projection, shows absence of a portion of the bony jugular plate allowing the jugular bulb to protrude into the middle ear cavity superiorly (arrows). (Case courtesy of William P. Dillon, M.D.)

A

petrous ICA, radiographic evaluation prior to surgery will avoid the potential for massive bleeding.76,112,116 Pulsatile tinnitus secondary to enlarged jugular bulb (“megabulb”) without bony or other vascular abnormalities has also been described.118 Mechanical Compression of the Jugular Vein Mechanical compression of the jugular vein has been seen angiographically with ipsilateral head turning, thought to result from compression of the adjacent sternocleidomastoid,116 or with contralateral head turning, thought to result from compression of a transverse process. Although this phenomenon has been seen in patients presenting with subjective pulsatile tinnitus, it has also been seen in normal individuals, and the clinical consequences of this observed phenomenon are unclear.

Tumors Jugulotympanic Glomus Tumors

B Figure 24-10. Aberrant pertous internal carotid artery. Longstanding pulsatile tinnitus. A, Transaxial CT scan shows a rounded soft tissue mass representing the internal carotid artery in the medial aspect of the left middle ear cavity (arrows) continuous with its slender petrous segment anteromedially. B, Left common carotid artery injection, anteroposterior angiographic view, shows the unusual lateral course (arrow) and sharp angulation of the aberrant ICA within the middle ear cavity. (Case courtesy of William P. Dillon, M.D.)

Glomus tumors (paragangliomas, chemodectomas) are highly vascular, slow-growing, generally benign tumors arising from paraganglionic glomic tissue. This tissue is composed of cells that have the capacity to detect chemical changes, such as alterations in oxygen and carbon dioxide concentration and pH changes, in arterial blood. These cells are derivatives of nonchromaffin paraganglions of neuroectodermal origin and have secretory capacity as well (catecholamines, serotonin). Glomus tumors can be found at any adult age and have a female predilection.119–122 The most common sites are the temporal bone (jugular and tympanic), carotid body, and vagus nerve.123,124 They are also seen with increased frequency at higher altitudes. Five percent of glomus tumors can secrete vasoactive hormones. Patients with episodic hypertension, diaphoresis, headache, flushing, anxiety, or palpitations may harbor glomus tumors that produce catecholamines or serotonin. Hypertensive crises may be sporadic or precipitated by massage, surgical manipulation, or angiography.125 Analysis

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of these functional tumors may yield elevated serum, urine, or tumor values of catecholamines, norepinephrine, or homovanillic acid. Patients considered for angiography or embolization should undergo screening for urine vanillylmandelic acid (VMA) or 5-hydroxyindoleacetic acid (5-HIAA), breakdown products of the vasoactive substances. Prophylactic alpha blockade (phentolamine, phenoxybenzamine) should precede angiography in patients with evidence of elevated catecholamines. Antihypertensive agents (nitroprusside,126 labetalol) should be readily available during the procedure. Additionally, posttherapy hypotension can develop due to baseline circulatory volume constriction coupled with a precipitous drop in circulating catecholamines. Presenting clinical symptoms depend on tumor location.127 Glomus jugulare tumors present with the jugular foramen syndrome consisting of palsies of cranial nerves IX–XI (difficulty speaking or swallowing, hoarseness, trapezius and sternocleidomastoid weakness). Retroauricular pain may be noted, but subtle pulsatile tinnitus may be overlooked initially. With tumor growth, tongue deviation (involvement of cranial nerve XII), jugular bulb occlusion by the tumor mass, or vertigo and hearing loss may ensue. Very large tumors may produce cerebellar compression or raised intracranial pressure. Glomus tympanicum tumors classically present with unilateral pulsatile tinnitus, which may be accompanied by conductive hearing loss or peripheral facial nerve palsy (occurring acutely in 30% of cases128). Situated on the cochlear promontory, the tumor may appear as a purple-red mass behind the tympanic membrane on otoscopy and produce otorrhagia. Medial invasion to the inner ear can produce vertigo and sensorineural deafness. Posterior invasion can produce lower cranial nerve deficits, as with a primary glomus jugulare tumor. Finally, these tumors may be multifocal or multicompartmental and can be seen clinically, pathologically, and angiographically.129 Initial diagnostic radiologic evaluation should consist of CT or MRI. The benefit of CT lies in its ability to evaluate bone erosion with optimal resolution.76,77,130 Glomus jugulare tumors erode the jugular foramen initially, whereas glomus tympanicum tumors appear as a tuft of enhancing tissue eroding the cochlear promontory.112 A characteristic feature of glomus tumors is the pattern of simultaneous local extension along canals and vessels.131 MRI offers the ease of multiplanar imaging and can evaluate differences among soft tissue structures well, but is less effective evaluating subtle bony changes. Diagnostic angiography remains an effective method of evaluating glomus tumors preoperatively and assessing arterial supply and ability to carry out preoperative embolization, degree of vascularity, encasement of major arteries, degree of arteriovenous shunting, presence of major venous sinus occlusion by tumor, multicompartmentalization or multifocality of tumor, confirmation of the expected diagnosis, and exclusion of other vascular skull base processes mimicking glomus tumors. Classical angiographic features include enlargement of feeding arteries, intense tumor stain, and arteriovenous shunting. These tumors may be supplied by a single enlarged artery or by multiple feeders, depending on tumor size and number of compartments, which can be separate from one

another.129 When evaluating a glomus tumor, angiography must include injection of ascending pharyngeal, occipital, posterior auricular, middle meningeal, and internal maxillary branches of the external carotid artery. Internal carotid and vertebral arteries also give rise to dural branches that can supply the tumor. Tumors invading intradurally may parasitize pial supply including anterior and posterior inferior cerebellar arteries.41 Occasionally, angiography will reveal an unsuspected additional glomus tumor. The ascending pharyngeal artery (particularly its inferior tympanic branch132) nearly always supplies jugulotympanic glomus tumors, as it gives off branches that supply normal structures in these locations. As such, it is postulated that bilateral ascending pharyngeal artery injections can effectively diagnose all jugulotympanic glomus tumors.41 The stylomastoid artery, which normally supplies the descending portion of the facial nerve, can arise from the occipital, posterior meningeal, or posterior division of the middle meningeal arteries and can supply glomus tumors extending posterolaterally. Tumors extending superiorly will involve the middle meningeal artery. Embolization is performed as a preoperative adjunct to limit surgical blood loss (Figs. 24-12 and 24-13). Its efficacy has been demonstrated by many authors.41,133,134 Supraselective catheterization of a feeding artery is followed by high-resolution arteriography. Functional testing of cranial nerves with 2% cardiac lidocaine (10–20 mg) may be helpful. PVA particles 300 μm or larger can saturate the tumor bed and generally avoid cranial nerve deficits. Vigilance will allow detection of anastomoses with intracranial arteries, such as connections between the occipital artery or odontoid branch of ascending pharyngeal artery with the vertebral artery. Particular care is necessary to preserve the neuromeningeal branch of the ascending pharyngeal artery (cranial nerves IX–XI) and the stylomastoid artery (facial nerve). Embolization of pial supply is difficult to achieve safely.41 Among the limited complications arising from the large number of embolization procedures performed to treat glomus tumors are transient facial nerve palsy, extravasation of contrast related to high-pressure injection of the embolic agent, and palsies involving cranial nerves IX–XI. These last are related particularly to liquid adhesive embolization of the neuromeningeal branch of the ascending pharyngeal artery.41 Meningiomas Meningiomas are common benign extraaxial tumors of the meninges covering the brain.135 These tumors are thought to have arisen from cells that form arachnoid villi, which serve to reabsorb cerebrospinal fluid from the cerebral cisterns into the venous sinuses. As such these tumors are found in locations where the arachnoid villi are most plentiful, along the dura lining the venous sinuses of the brain and skull base. Specific presenting symptoms depend on tumor location and size. Common locations include parasagittal and lateral cerebral convexity (most common sites), sphenoid wing, petrous ridge, cerebellopontine angle (CPA), tenorium, foramen magnum, orbit, cavernous sinus, or rarely in sites without dural attachments (intraventricular, sylvian

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B A

Figure 24-12. Glomus jugulare tumor in a 47-year-old man with pulsatile tinnitus. A, Transaxial MRI scan (TR 750/TE35) with gadolinium-DTPA enhancement, shows an enhancing mass in the left jugular foramen (arrow). Transaxial (B) and coronal (C) CT scans, windowed to optimize visualization of bone, show enlargement of the jugular foramen with erosion of its lateral bony margins (closed arrows). The tissue mass has permeated bone and extends into the middle ear (C, white arrow). Continued

C fissure). Because arachnoid cell rests may be found in the jugular foramen, internal auditory canal, geniculate ganglion area, and along the lesser and greater superficial petrosal nerves,136 meningiomas arising from these cells may present with neurotologic symptoms, including conductive hearing loss (temporal bone, middle ear), sensorineural hearing loss and vestibular symptoms (internal auditory canal, simulating an acoustic neuroma), tinnitus, and facial nerve palsy (CPA), or hoarseness, cough, dysphagia, difficulty speaking and handling secretions, and trapezius weakness (jugular foramen).137

A number of histologic subtypes have been described,138 including syncytial, transitional, fibroblastic, angioblastic, and malignant varieties, depending on the predominant cell type.139 There is a correlation between incidence of meningioma and a history of prior irradiation, with a latent period of 5 to 25 years.140 CT and MRI have supplanted plain skull radiography in the initial diagnostic evaluation of meningiomas. CT scanning will show a well-circumscribed extraaxial mass relatively isodense or hyperdense compared with normal brain tissue on noncontrast images; these enhance brightly with

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D

E

Figure 24-12, cont’d. D, Left external carotid artery (ECA) injection, lateral angiographic view, shows a highly vascular mass in the jugular foramen region, characteristic of a glomus tumor. Supply is derived from ascending pharyngeal (open curved arrow), posterior auricular (large closed curved arrow), and occipital transmastoid perforating branch (small closed curved arrow) arteries. Early retrograde opacification of the sigmoid sinus (long straight arrow) indicates arteriovenous shunting through the tumor. E, Superselective left ascending pharyngeal artery (posterior branch) injection, lateral angiographic view, shows dense tumor blush. This was followed by provocative testing and particulate embolization. F, Left external carotid artery injection, lateral angiographic view performed after embolization of all three ECA feeding arteries, shows no residual tumor opacification. The tumor was successfully resected the following day.

F administration of IV contrast.131 MRI scanning with administration of gadolinium–DTPA allows more facile tumor evaluation in multiple planes, which is especially helpful for evaluating the dural attachment of the tumor and patency of dural sinuses. Meningiomas are typically vascular tumors, as would be expected of tumors arising from the vascular dura. Additionally, meningiomas receive their blood supply primarily from dural arteries, especially from external carotid branches.141 Depending on tumor location, arterial supply is derived predominately from middle meningeal, accessory meningeal, ascending pharyngeal, or occipital transmastoid perforating branches of the external carotid artery and may be bilateral, especially in a midline tumor. Superselective catheterization of these branches is important for excluding

each as a supply source because a global common carotid or even external carotid injection may visualize these arteries inadequately. Dural arteries from the internal carotid (meningohypophyseal trunk, inferolateral trunk, ethmoidal branches of ophthalmic artery) and vertebral (posterior meningeal) arteries may also supply the tumor. As a meningioma grows, it parasitizes pial branches, which supply small twiglike branches to the periphery of the tumor. Another characteristic feature of meningiomas is the angiographic staining pattern: uniform radial arrangement of tiny tumor vessels in a well-defined round tumor. Opacification begins in the arterial phase, augments, and persists into the venous phase without washout (Fig. 24-14). Cerebral venography has a limited role in the evaluation of meningiomas. Confirmation or exclusion of dural sinus

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Figure 24-13. Glomus jugulare tumor in a 53-year old woman with loud pulsatile tinnitus and headaches. She underwent staged preoperative particulate embolization followed by complete surgical resection. A, Transaxial MRI scan (TR 600/TE 20) with gadolinium–DTPA enhancement, shows subtle increased signal in the left jugular bulb (arrow). B, Transaxial contrast-enhanced CT scan confirms the presence of an enhancing mass in the left jugular bulb (arrow). Transaxial (C) and coronal (D) CT scans, windowed to optimize visualization of bone, show enlargement of the left jugular foramen and erosion of the lateral cortex (white arrows). Continued

patency, which may be questionable on other imaging studies, can be made. This assessment is important for the surgeon because the tumor and occluded adjacent sinus can be resected without danger of venous infarction, whereas a patent sinus should be preserved. This is especially true of the dominant (usually the right) transverse sinus and posterior two-thirds of the superior sagittal sinus. Delineation of the exact site of sinus tumor invasion

by venography is superior to that of arteriography. Finally, venous pressure gradients across a sinus partially obstructed by a meningioma can be measured,12 and sinus test occlusion performed to assess tolerance of surgical resection of the tumor and adjacent sinus. The goal of therapy for meningiomas is complete eradication of the tumor. This is best achieved by complete surgical resection, when possible. Not all meningiomas are

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E

F

G Figure 24-13, cont’d. E, Left ECA injection, lateral angiographic view, shows a highly vascular ill-defined mass (black arrow) in the region of the jugular foramen, characteristic of a glomus tumor. Arteriovenous shunting to the sigmoid sinus (small open arrows) and internal jugular vein (open curved arrow) is seen. Superselective catheterization of: occipital (F) posterior auricular (G) and middle meningeal (H) arteries prior to embolization, lateral angiographic views, shows dramatic tumor blush and AV shunting. Continued

vascular, and some authors have questioned the benefit of preoperative embolization in meningiomas with feeding arteries easily accessible to the surgeon.142 However, preoperative devascularization of the microvascular tumor bed by embolization143,144 provides the following advantages: diminution of surgical blood loss and operative time, improvement of visibility for the surgeon, allowing the surgeon to amputate a portion of the tumor devascularized by embolization, and control of arterial flow in surgically inaccessible tumor feeders (especially at the skull base).

H

Advances in technology, including improved spatial resolution of digital subtraction “road-mapping” angiographic systems and development of softer steerable or flow-directed microcatheters, have provided the angiographer with safer supraselective access to tumor vascularity. However, experience with endovascular techniques is necessary to avoid the many pitfalls associated with these procedures. Prior to embolization, the patient is given corticosteroids to reduce the immediate risk of tumor swelling after embolization, and a sublingual calcium

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K

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channel blocker or topical nitropaste (or both) to reduce the incidence of arterial spasm, sometimes encountered during catheterization of external carotid branches. Arteries of the skull base supplying meningiomas may also supply critical normal structures or provide collaterals to the intracranial circulation. The angiographer must be aware of this and carry out effective evaluation to protect against this prior to embolization. The ascending pharyngeal artery, often providing supply to meningiomas of the skull base, gives off a neuromeningeal division supplying cranial nerves IX–XI and sometimes XII. It also gives rise to the odontoid artery, which anastomoses with the vertebral artery. Inadvertent embolization could result in ipsilateral vocal cord paralysis, inability to adequately handle oral secretions, palatal or tongue deviation, and stroke involving the brainstem or posterior fossa. The occipital artery also anastomoses with the vertebral artery as it enters the foramen magnum, which may be impossible to visualize without superselective angiography. The middle meningeal artery can anastomose with the cavernous portion of the ICA via the inferolateral trunk or can give rise to a meningolacrimal artery, which traverses the sphenoid bone through the canal of Hyrtl to supply the retina. This vessel may provide the entire retinal supply or a portion thereof. Inadvertent embolization could result in central retinal artery embolism and monocular blindness. The stylomastoid artery supplying the peripheral facial nerve can arise from the occipital, posterior auricular, or middle meningeal arteries. The accessory meningeal artery can supply cranial nerves III, IV, and VI. The distal internal maxillary artery can anastomose with the ICA via the artery of foramen rotundum or vidian artery. Several techniques have been developed to reduce complications of inadvertent embolization. Once the microcatheter has been navigated into the artery to be embolized, it is directed as close to the tumor as possible without causing spasm or complete flow arrest, to avoid potential normal branches arising more proximally. Supraselective angiography using high resolution is performed to visualize normal arteries or collaterals to the vertebral or internal carotid arteries. Supraselective angiography of the middle meningeal artery requires centering the angiographic film over the orbit, specifically to exclude the presence of a meningolacrimal artery. Provocative testing by injecting 2% cardiac lidocaine (10 to 20 mg) may result in temporary cranial nerve deficit revealing unsuspected supply via the artery considered for embolization, requiring more distal placement of the microcatheter before embolization or withdrawal of the catheter from that artery without embolization. Selection of the appropriate embolic agent depends on the goal of embolization. Because embolization is a preoperative adjunct in this setting, safe embolization without the need for a permanent embolic agent is best achieved with the

Figure 24-13, cont’d. I, Left vertebral artery injection, lateral angiographic view, shows tumor opacification from several branches including the posterior meningeal artery (arrow). J, Left posterior meningeal artery injection, lateral angiographic view, shows abundant tumor supply, embolized with particles. The catheter tip is marked (arrow). K, Left PICA injection, lateral angiographic view, shows tumor supply from small branches. Embolization is precluded because of supply to normal distal PICA (arrow).

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Figure 24-14. Recurrent clivus meningioma in a 35-year-old man with a remote childhood history of a brain tumor treated by radiation. He has undergone prior craniotomy for resection of multiple meningiomas. He now presents with hearing loss, generalized weakness, and gait instability. He underwent preoperative particulate embolization followed by surgical debulking of the tumor. A, Transaxial contrast-enhanced CT scan shows a vascular mass on the clivus displacing the brainstem posteriorly. B, Transaxial MRI scan (TR 2500/TE 40) shows the high-signal clival mass invading the left porus acousticus and encasing the displaced left vertebral artery (arrow). C, Sagittal MRI scan (TR 600/TE 20) with gadolinium–DTPA enhancement shows posterior displacement of the brainstem and encased basilar artery (arrows) by the enhancing extraaxial clival mass. D, Coronal MRI scan (TR 600/TE 20) with gadolinium–DTPA enhancement shows the mass abutting the internal auditory canals (arrows). Continued

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F E

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Figure 24-14, cont’d. E, Right vertebral artery injection, lateral angiographic view, shows marked posterior displacement of the basilar artery (arrows) by the mass and mild diminished caliber of its inferior portion consistent with tumor encasement. F, Right ICA injection, lateral angiographic view, shows tumor supply from the meningohypophyseal trunk (arrow). The relatively small tumor supply, difficult catheterization, and risk of reflux of embolic material into the ICA do not warrant an attempt at embolization of this branch. G, Right ECA injection, lateral angiographic view, shows abundant tumor blush supplied by the ascending pharyngeal artery (arrow). H, Superselective right ascending pharyngeal artery injection, lateral angiographic view prior to embolization, shows tumor supply and reflux of contrast via the odontoid artery to opacify the right vertebral artery (arrows). Extreme care during embolization must be taken to avoid high pressure injections which could reflux embolic material in the same manner.

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use of particulate agents. The smallest available PVA particles (measuring 50 to 200 μm), Gelfoam powder, or small acrylic spheres will penetrate well into the tumor bed, but risk permeating normal branches of similar size that are too small to resolve well on angiography, particularly at the base of the skull where the dense petrous bone will hinder optimal radiography. Large particles may result in proximal occlusion of the artery without adequate tumor penetration. Therefore, an intermediate size particle (250 to 500 μm) may achieve the desired result with less risk to small normal branches. Liquid adhesive agents (e.g., N-butyl cyanoacrylate) need not be used in this setting, as their permanence is unnecessary and they will easily permeate small normal branches below the resolution capacity of current angiographic systems. Vigilance must be maintained to avoid reflux of embolic material into normal proximal branches by overly vigorous embolization. Pial meningioma supply is generally not embolized preoperatively, as pial branches provide only a small percentage of tumor vascularity, and the risk of embolization is greater than that of dural artery embolization. A postembolization control angiogram is performed to document adequate results. Despite the many potential pitfalls of meningioma embolization, the complication rate is very small in experienced hands.41,142,145,146 Berenstein reports 3 permanent (monocular blindness, stroke) and 5 transient (facial nerve) neurologic deficits in 185 patients.41 Two cases of subarachnoid hemorrhage have been encountered.41,145 Trismus, resulting from internal maxillary artery branch occlusion, was more prevalent prior to the introduction of microcatheters.142 Schwannomas Schwannomas, 90% of which occur in the CPA, are benign extraaxial tumors arising from the cranial nerve sheaths, which are formed of Schwann cells.112,139 Usually solitary, multiple schwannomas are characteristic of neurofibromatosis, and bilateral acoustic schwannomas are the hallmark of the central form of neurofibromatosis, or NF2.147,148 Sensory cranial nerves are overwhelmingly involved. These tumors are generally seen in middle-aged individuals and have a predilection for females. Association with head and neck irradiation during childhood has been postulated.149 The so-called acoustic schwannoma is by far the most common site of tumor origin. Ninety percent of these tumors arise in the superior division of the intracanalicular vestibular nerve. The trigeminal nerve is the next most frequent site of origin.112 Schwannomas in other locations are most often manifestations of neurofibromatosis. The facial nerve, although infrequently a tumor site, is the most commonly affected motor nerve.139 Generally, schwannomas are firm, encapsulated tumors that may contain cysts. As the tumor grows, it may become lobulated, increase in vascularity,150 or develop arachnoid adhesions that may result in arachnoid cysts.151 Clinical presentation depends on the size and site of origin of the tumor. Acoustic schwannomas initially present with tinnitus and progressive, high-frequency neurosensory

hearing loss due to cochlear nerve compression. Although most acoustic schwannomas arise in the vestibular nerve sheath, vertigo, disequilibrium, and dizziness are less common. Similarly, the facial nerve, which shares the internal auditory canal with its cochlear and vestibular eighth nerve counterparts, is affected infrequently,151,152 possibly because motor fibers are less sensitive to local effects of compression than sensory fibers. Tumor enlargement into the CPA and posterior fossa can compress the cerebellum producing ataxia, compress the brainstem or exiting cranial nerves (most commonly the trigeminal nerve), or result in obstructive hydrocephalus or raised intracranial pressure.110 Schwannomas arising in the trigeminal nerve sheath present with facial paresthesias and hypesthesia, but may become quite large in the absence of such symptoms.120 Schwannomas of cranial nerves IX to XI can produce the jugular foramen syndrome (difficulty speaking and swallowing, hoarseness, and trapezius and sternocleidomastoid paralysis) due to the intimate anatomic arrangement of these three cranial nerves. CT scanning demonstrates an extraaxial, well-circumscribed tumor eroding the involved canal and may enhance variably with IV contrast administration. More recently, MRI has supplanted CT in the primary evaluation of schwannomas, especially acoustic schwannomas, because of superior intrinsic soft tissue contrast differences, lack of artifacts produced on CT by density differences at air-bone or soft tissue-bone interfaces, and ease of multiplanar image acquisition. Small intracanalicular acoustic schwannomas can be detected easily on MRI and are best evaluated on gadolinium–DTPA-enhanced short TR (repetition-time) images obtained in both transaxial and coronal planes. Several angiographic features of schwannomas assist in differentiating them from meningiomas, which have a similar angiographic appearance. Schwannomas have been described as hypervascular in up to 68% of cases,41 especially in larger tumors or in the rare childhood case,153 but feeding arteries are generally of normal or minimally enlarged caliber, and tumor stain, when present, is less dense than that of a meningioma.154,155 No arteriovenous shunting occurs, but a network of capsular veins may encircle the tumor. The most suggestive angiographic finding is the presence of multiple small puddles of contrast that persist into the venous phase.156 Arterial supply can be predicted from tumor location and may arise from external carotid branches or from the anterior (AICA) or posterior (PICA) inferior cerebellar arteries in cases of acoustic schwannomas.155 Preoperative embolization has been shown to be efficacious in treating vascular schwannomas153,156 by reducing tumor blood supply and easing surgical resection, as with meningiomas. Embolization techniques are also similar. Use of intermediate-sized PVA particles (300 μm) in selected branches of the external carotid artery can effect adequate tumor devascularization while safely avoiding cranial nerve deficits, especially if undertaken after provocative lidocaine testing. Pial artery embolization should be reserved for very large vascular schwannomas, as the risk of producing neurologic deficit from embolization of the PICA (Wallenberg’s syndrome) or AICA (vertigo, diminished hearing) is

Diagnostic and Therapeutic Angiography

considerably greater than with external carotid branch embolization. Although no large body of experience with embolization of schwannomas has been compiled, smaller series suggest minimal risk in experienced hands.156 Miscellaneous Tumors Malignant Skull Base Tumors Endovascular therapy can provide palliation or adjunctive therapy for surgery in vascular primary or secondary malignant skull base tumors. Angiography will assess the vascularity of the mass, and particulate embolization will permit tumor necrosis, decreased mass effect,41 and reduced arterial inflow. As with other vascular tumors, this will allow safer surgical resection or biopsy with reduced chance of significant hemorrhage. In palliative cases, such embolization can reduce the frequency of spontaneous bleeding and diminish pain.41 Properly sized particulate emboli are most suitable because they provide the greatest permeation of the vascular tumor bed with the least risk of side effects. Additionally, ICA test occlusion with measurement of arterial pressures distal to the occlusion balloon will enable the skull base surgeon to determine whether the patient can tolerate carotid occlusion should this become necessary during surgery. If permanent carotid occlusion is deemed mandatory for safe and successful skull base tumor resection, this can be carried out in the angiography suite following test occlusion.3 One must adhere to the policy of vigorous volume expansion and strict limitation of activity following carotid occlusion to avoid hemispheric ischemia. The anesthesiology team should be apprised of the need to avoid episodes of hypotension during the subsequent operation for the same reason. Hemangioblastomas Posterior fossa hemangioblastomas are highly vascular intraaxial tumors primarily supplied by pial arteries, but may demonstrate dural arterial supply and meningeal invasion especially in large or recurrent tumors.157 Such tumors can produce lower cranial nerve palsies. Surgical resection can be aided by preoperative embolization to produce tumor necrosis and reduce blood flow. Risk of embolization is greater than with many other types of tumor because of the apparent fragility of tumor arterioles, which can lead to parenchymal or subarachnoid hemorrhage during embolization. Juvenile Angiofibromas Juvenile angiofibromas (JAFs) are benign vascular tumors arising in the pterygopalatine fossa in pubescent males, usually presenting with epistaxis and nasal obstruction.158 Large JAFs with posterior extension may come to the attention of the neurotologist because of secondary hearing loss.159 Transarterial particulate embolization, usually involving the ascending pharyngeal and internal maxillary arteries has become the standard of care in preoperative devascularization.160 Because a high degree of correlation exists between the angiographic tumor blush and actual tumor boundary, this feature can be used to determine tumor extent before therapy and to assess efficacy of embolization.41

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CONCLUSION Diagnostic angiography plays an essential role in the evaluation of vascular abnormalities and tumors presenting to the skull base surgeon. Additionally, embolization of these abnormalities has become an accepted form of therapy, broadening the treatment options for both the surgeon and the patient. Further technical developments and experience will permit an expanded role of endovascular therapy by well-trained individuals who have mastered endovascular techniques and who are aware of their capabilities and limitations.

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25

Outline Auditory Neuropathy Introduction Incidence Etiology Pathophysiology Clinical Presentation Audiometric Findings Peripheral Neuropathy Vestibular Function Evaluation Medical Evaluation Audiology Evaluation Treatment Options Future Directions Sarcoidosis Introduction Incidence Etiology

Chapter

Auditory Neuropathy, Sarcoidosis, Siderosis, and Idiopathic Pachymeningitis

Histopathology Pathophysiology Clinical Presentation Evaluation Audiology Diagnostic Tests Cerebrospinal Fluid Findings Imaging Treatment Outcomes Superficial Siderosis of the Central Nervous System Introduction Incidence Etiology Pathophysiology Pathology Clinical Presentation

History and Physical Exam Audiology CSF Findings Imaging Treatment Outcomes Idiopathic Hypertrophic Pachymeningitis Introduction Incidence and Etiology Histopathology Clinical Presentation Evaluation Imaging Treatment Outcomes

AUDITORY NEUROPATHY Introduction Auditory neuropathy (AN) is a term used to describe patients with a hearing disorder characterized by (1) a bilateral pure tone sensorineural hearing loss (SNHL); (2) absent or severely abnormal auditory brainstem responses (ABR) beginning at wave I, suggesting impairment of function of afferent neural transmission; (3) preserved otoacoustic emissions (OAEs) and cochlear microphonics (CMs), suggesting normal cochlear outer hair cell function; and (4) normal imaging studies (Table 25-1).1–5 Although AN has only been recently described, the condition is not new.6–8 AN was difficult to recognize in the past because tests to distinguish disorders of the cochlear receptors from those of the auditory nerve were not routinely performed.

Incidence Data regarding the incidence of AN in children is gradually accumulating due to widespread institution of infant hearing screening programs. There are no data for adults. In a study from Australia the incidence of AN presenting in infancy was found to be 0.23% of the general population. Of the 5199 infants who underwent screening, 109 had an abnormal ABR (2.09%). Of these, 12 had present OAEs or CMs, consistent with the diagnosis of

Angela D. Martin, MD Colin L. W. Driscoll, MD

AN. Although the overall number of patients with AN in the general population appears small, one in nine infants found to have a permanent hearing deficit met the criteria for AN.3 Park and Lee found that 6% of patients with bilateral severe to profound hearing loss had present otoacoustic emissions.9 Among patients with AN, there appears to be no gender preference.10 The identification of AN in older children and adults is complicated by the fact that the OAEs are sometimes lost and therefore the disorder cannot be distinguished from other types of SNHL.

Etiology The causes of AN are currently being investigated and appear to be diverse. In approximately 50% of patients AN has no defined cause. Genetic factors have been identified and appear to account for the disorder in ≈40% of patients with AN. Other associated causes, including toxic-metabolic, infectious, and immunologic factors that account for ≈10% of patients.10 In infants AN has been associated with neonatal hyperbilirubinemia,11,12 hypoxia, congenital infection, and prematurity.3,13 It may occur as part of a generalized metabolic, toxic, or inflammatory neuropathy, as seen with diabetes,14 uremia,15 or exposures to cisplatin, which appears to selectively damage inner hair cells.16 AN has been diagnosed in patients with Friedreich’s ataxia,17 in patients with a hereditary motor and sensory neuropathy (HMSN)18–20 and Charcot-Marie-Tooth 471

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TABLE 25-1. Main Features of Auditory Neuropathy Clinical Findings Difficulty understanding speech, particularly in background noise Normal physical exam, except for hearing loss

Audiometric Findings Bilateral pure tone sensorineural hearing loss Preserved otoacoustic emissions and cochlear microphonic Absent or severely abnormal ABR Impaired word recognition score out of proportion to degree of hearing loss

Imaging Findings Normal CT and MRI ABR, auditory brainstem response; CT, computed tomography; MRI, magnetic resonance imaging.

disease,21 or as an isolated and sporadic event.22 A genetic mutation of the PMP22 gene in Charcot-Marie-Tooth disease,23 as well as a mutation mapped to 8q24 in some Bulgarian and Italian Gypsy families with AN have been identified.19

Pathophysiology The site of the pathology causing the findings of absent ABRs and preserved OAEs and CMs in AN has yet to be discovered. It has been suggested that the disorder may occur at the level of the inner hair cells, the synapse between the inner hair cells and the eighth nerve, the ganglion neurons, the nerve fibers, or any combination of these.4 Along the auditory nerve, the site of pathology may be the myelin sheath or the neuron (axon and dendrite).10 Other authors have hypothesized that the normal synchronous activity of the auditory nerve is disrupted, which may be secondary to a demyelinating process, leading to temporal and speech-processing deficits, without necessarily affecting the amplification function of the inner ear.4,24,25 An increase in body temperature has been associated with marked worsening of hearing in some patients with AN.26 Starr noted that heat sensitivity is common among patients with multiple sclerosis and that this worsening in hearing in patients with AN may represent a conduction block secondary to a myelin disorder.10 Chinchillas with carboplatin-induced lesions of the inner hair cells (IHCs) and type I neurons demonstrated similar characteristics to patients with AN.27 Temporal bone findings in patients with Friedreich’s ataxia revealed a pronounced loss of nerve fibers and spiral ganglion cells, increasing from base to apex, with preservation of the outer hair cells.28 Hyperbilirubinemia has been implicated but because this is a common occurrence after birth it is difficult to know if there is a causal relationship.

Clinical Presentation AN has been diagnosed in all ages from newborns to adults. A study of 67 patients with AN by Starr and colleagues found that children under the age of 10 years account for the majority of the population with AN (≈75%), whereas adolescents and adults account for the minority (≈25%). They suggest that the reason for the

discrepancy may be secondary to the more widespread use of OAEs and ABRs in the evaluation of hearing loss in infants and children than in adults. Furthermore, ≈20% of the children with AN currently being followed have been found to lose their OAEs over time. AN in adult patients who have subsequently lost their OAEs would therefore be underdiagnosed.10 Infants with AN usually present when abnormal ABRs and preserved OAEs are found during routine infant screening. In older children and adults, the clinical presentation is typically that of a gradual hearing loss. These patients report extreme difficulty understanding speech, especially when using the telephone or in noisy environments. Many are dependent on lip reading. Some patients report fluctuations in hearing over time. It is not uncommon for them to be accused of malingering or for their hearing disorder to be mistaken for a behavioral problem. It can be confusing for older children and young adults and the surrounding friends and family because the hearing can be quite satisfactory in quite environments but very poor in other settings. Audiometric Findings Hearing loss ranges from mild to profound, and there is no characteristic audiometric pattern. Patients with AN often have difficulty providing consistent responses during testing and demonstrate test-retest variability. Starr and colleagues reported that 31% have a hearing loss of 35 dB or less, 39% have between a 35- and 70-dB loss, and 30% have a greater than 70-dB loss. Thresholds remain constant over time in ≈40% of patients, fluctuate in 30%, and worsen in ≈15%.10 Impaired word discrimination is disproportionate to pure tone loss. The audiogram reveals a flat configuration in 41%, an upsloping pattern consistent with a low-frequency loss in 29%, an irregular “saw tooth” pattern in 9%, a U-shaped pattern in 5%, tentshaped loss in 5%, and a downsloping pattern in 11% (Fig. 25-1).10 ABRs are either absent or severely abnormal in all cases (Fig. 25-2). A few patients with preserved components (wave V with or without wave III) have been identified when the stimulus rate was slowed.10 In these cases, wave V was of prolonged latency and decreased amplitude, and wave III was of abnormal morphology. The differences in ABRs suggest that the loss of neural synchrony is variable among patients with AN secondary to different causal and physiologic factors.10 Stapedial reflexes are absent in all but a few patients with AN. Normal distortion product and transient evoked otoacoustic emissions (DPOAE, TEOAEs) or CMs are present at initial examination. Increased amplitude of CMs has been observed in patients with AN who are younger than 10 years compared with normal subjects.1,19 In one study increased amplitude of CMs was observed in 50% of patients.10 The significance of this finding is currently unknown. There have also been reports of loss of OAEs on future testing with preservation of CMs,2,11 with a 20% incidence reported in a recent study.10 The reason for this finding is also currently unknown, but may represent a primary disorder of the outer hair cells (OHCs) or damage to the OHCs from hearing aid use or middle ear disorders.

Auditory Neuropathy, Sarcoidosis, Siderosis, and Idiopathic Pachymeningitis

a generalized neuropathic process that expresses itself as patients get older.

dB hearing level

Auditory Neuropathy :10 0 10 20 30 40 50 60 70 80 90 100 110 120

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1,000 2,000 4,000 8,000 1,500 3,000 6,000

Figure 25-1. Audiogram from an adult patient with bilateral auditory neuropathy. Note the characteristic marked variation in thresholds at different frequencies, saw-toothed pattern. This variation makes testing her difficult and when younger she was thought to be malingering. Also note, despite good pure tone thresholds her word recognition scores are poor.

Peripheral Neuropathy Usually at the time of presentation, patients are otherwise neurologically normal. However, Starr and colleagues identified a peripheral neuropathy in a significant number of patients with AN. They found no evidence of a peripheral neuropathy in children younger than 5 years, whereas 80% of patients examined after age 15 years showed both clinical and nerve conduction evidence of a peripheral neuropathy.10 Larger population-based studies will be needed to clarify the relationship between AN and other peripheral neuropathies. AN may occur alone or as part of

Patients typically have no vestibular symptoms. Abnormal caloric tests have been identified in asymptomatic patients with AN who tended to be older and have a concomitant peripheral neuropathy.29 There have also been a few reports of abnormal vestibular function tests in older patients with AN who had vestibular symptoms, but no evidence of a peripheral neuropathy.30 This may represent a neuropathy of the vestibular nerves as part of a generalized neuropathic process or as an isolated eighth nerve process.

Evaluation Medical Evaluation Because too little is known about the pathophysiology of AN, the evaluation is largely the same as that for patients with other types of SNHL. Regardless of other testing (e.g., syphilis, autoimmune tests), in all adults with AN we recommend a magnetic resonance imaging (MRI) scan and consultation with a neurologist in order to identify any concomitant peripheral neuropathy or other associated neurologic disorder. In addition to a complete neurologic exam, patients may undergo nerve conduction studies looking for an absence or slowing of nerve conduction velocities as well as a diminished amplitude of the compound action potential. In patients for whom there is a high suspicion of a peripheral neuropathy, a sural nerve biopsy is recommended to confirm the diagnosis. Our current philosophy when evaluating a child with hearing loss is to be thorough in our efforts to determine the cause and to search for evidence of a syndromic disorder.

Accepted: LD05 Fsp :180.00 :100.00 :200.00 :100.00 Rejected: 0

Cursor 1L: 4.80 Cursor 2L: :0.74

Diff Diff

5.54 ms 0.04 uV

Stimulus artifact Rarefaction clicks

Figure 25-2. ABR obtained with clicks presented at 90-dB hearing loss to the right ear of the same patient presented in Figure 25-1. The ABR demonstrates the presence of a phase reversing cochlear microphonic and no other identifiable waveforms. The absence of a repeatable waveform beyond the cochlea is suggestive of neural dyssynchrony.

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The core medical team in our practice consists of an otolaryngologist, geneticist, ophthalmologist, and pediatrician. Evaluation by a pediatric neurologist has not been a routine part of our evaluation because of the rarity of a peripheral neuropathy at a young age but is considered on an individual basis. Because these children may develop other neuropathies later in life, a neurology appointment at some point seems reasonable. Laboratory work typically consists of an ECG, thyroid function test, urinalysis, glucose, and an MRI or computed tomography (CT) scan of the head. Genetic screening for abnormalities in the Connexin-26 gene is encouraged and performed in most cases. Our evaluation procedure continues to evolve, and with advances in genetic screening over the next several years we will continue to alter our routine to minimize the number of tests obtained. Audiology Evaluation Accurate audiometric testing is critical to making the diagnosis, and the knowledge and abilities of an experienced audiologist are invaluable. In addition to standard audiometric tests and age-appropriate speech perception tests, otoacoustic emissions are obtained and followed over time. Evoked potentials always include an ABR in which we record phase-reversing clicks or tone bursts in order to identify the cochlear microphonic. Middle (MLR) and late (LLR) latency responses may also be recorded. For adults, the Hearing In Noise sentence Testing (HINT) is quite beneficial in delineating the difficulty that patients have in different listening situations. Lastly, although most patients are asymptomatic with regard to vestibular function, abnormalities of vestibular caloric stimulation have been identified. Therefore, it may be appropriate for patients to undergo vestibular testing to identify baseline function.

Treatment Options Treatment options for children with AN include intensive speech and language therapy, hearing aids, or cochlear implantation. From the time that AN was first reported in the literature, clinicians have questioned whether it was wise to consider amplification with hearing aids or cochlear implants,3,11,17,18,22 There was concern that amplification would cause further injury to the cochlea and that cochlear implants would not work because the hearing loss was due to a problem with the nerve. In an effort to not injure the outer hair cells, hearing aids were often fitted using a low-gain and wide-dynamic-range compression strategy. The hearing aids were usually tolerated, but because the gain was low they seldom provided any benefit. The trend now is to fit the hearing aids to the behavioral audiogram according to accepted rules and assess auditory skill development. Most children will tolerate the aids but many will not demonstrate adequate progress in acquisition of speech and language skills. For those who do show progress, amplification is the treatment of choice. Adults with mild or moderate losses often reject hearing aids, stating that “the sound is louder but I still can’t understand the words.” It is likely that the children who fail to progress with hearing aids are having the same problem. Despite some early reports of poor outcomes, cochlear implantation has now been shown to be a viable option for

patients with AN.31,32 A recent review at our institution of 10 children with AN compared with a matched group with hearing loss from other causes showed no difference in performance after cochlear implantation (unpublished data). Evoked intraoperative and postoperative potentials (EABR) and electrical compound action potentials (ECAP) demonstrate the ability of the cochlear implant to restore neural synchrony. We have had similar favorable results in adults.

Future Directions The following factors vary among patients with AN: cause, age of onset, presence or absence of a peripheral neuropathy, degree of hearing loss, differences in physiological measures of auditory function (ABRs, OAEs/CMs), and differences in treatment outcomes. As more is learned about AN, it will become more evident whether this is truly a single disorder or many different ones that share a few common features. Routine use of nerve conduction studies in patients with AN will help to identify the rate of a peripheral nerve disorder in this population. Genetic studies may identify a common link in hereditary cases of AN. Long-term outcomes of AN patients with cochlear implants will shed light on the effectiveness of this treatment. Our understanding of AN is evolving, with many questions still to be answered.

SARCOIDOSIS Introduction Sarcoidosis is a chronic systemic granulomatous disease of unknown origin. It is characterized by the presence of noncaseating granulomas that can affect any organ system of the body. Although it most commonly affects the pulmonary, ocular, dermatologic, and lymphatic systems, the central nervous system (CNS) may also be affected.33 CNS symptoms include hearing loss or vertigo (or both). Other otolaryngologic manifestations of sarcoidosis include involvement of the salivary gland (uveoparotid fever), the larynx (most often supraglottic), nasal cavity and nasopharynx (mucous membrane lesions, septal perforation), and neck (cervical adenopathy).34,35

Incidence The overall incidence of sarcoidosis is 40 per 100,000.36 Neurosarcoidosis occurs is approximately 5% to 10% of cases.37,38 The cranial nerve (CN) most commonly affected is the facial nerve, presenting with unilateral or bilateral facial paralysis with a good prognosis for spontaneous recovery.37,39–41 Lesions of the optic, trigeminal, and vestibulocochlear nerves are fairly common. Symptoms include optic neuritis/atrophy (CN II) and unilateral sensory loss of the face (CN V).41,42 Sarcoidosis of the eighth nerve presenting with hearing loss or vertigo is often associated with other cranial neuropathies. Isolated eighth nerve involvement is rare.35 Whereas the overall incidence of hearing loss among cases of sarcoidosis is ≈0.5%,43 in cases of neurosarcoidosis it occurs in 10% to 20% of cases.36 Cranial nerves less commonly involved

Auditory Neuropathy, Sarcoidosis, Siderosis, and Idiopathic Pachymeningitis

may cause symptoms of dysphagia and hoarseness (IX, X), anosmia (I), and disturbances of ocular movements (III, IV, VI).42

Etiology Despite advances in the understanding of sarcoidosis, a specific cause has not been identified. Human leukocyte antigen (HLA) studies show a higher prevalence of the disease among first-generation relatives of patients with sarcoidosis, suggesting a genetic factor.44 The current theory suggests that a combination of environmental factors and a genetically susceptible individual is most likely responsible for the induction of the disease.36

Histopathology The typical histopathologic features of sarcoidosis include noncaseating granulomas consisting of epithelioid cells surrounded by mature lymphocytes (Fig. 25-3). Other cells that are often present include giant cells, both Langerhans’ and foreign body types. The inflammatory process is associated with an increase in activated T cells and macrophages, initiating an immune response with the release of interferon-γ, interleukin-2, other cytokines, and proinflammatory factors.36 The diagnosis of tuberculosis is excluded by the absence of central caseation and acid-fast bacilli.45

Pathophysiology Autopsy findings of the temporal bone in a patient with sarcoidosis and neurosensory deafness revealed a striking perivascular lymphocytic infiltration of the eighth nerve, resulting in myelin and axonal degeneration. Within the inner ear, degeneration was evident in the cochlear and labyrinthine neuroepithelium and stria vascularis.45 It has been hypothesized that the neurosensory deafness and vestibular dysfunction in sarcoidosis begins as a reversible neuropathy. With the persistence of the inflammatory response, fibrotic changes occur, resulting in irreversible tissue damage.36,46

In neurosarcoidosis, a predilection for the basal leptomeninges is evident and often presents as granulomatous meningitis affecting the hypothalamus, third ventricle, pituitary, and cranial nerves. Less commonly, neurosarcoidosis presents as a mass lesion. Sarcoid granulomas occurring at the cerebellopontine angle (CPA) have been reported.35,46–53 In one of these cases, the CPA lesion was the only clinical finding, and the sarcoid granuloma was mistaken for a meningioma and treated surgically.47

Clinical Presentation The clinical presentation of hearing loss with sarcoidosis is quite variable. Often involvement of the eighth nerve occurs with other symptoms or cranial neuropathies, including uveitis, hilar adenopathy, and facial paralysis.35,54 Isolated cases of hearing loss have been reported as the presenting symptom of sarcoidosis.35,47,55 The hearing loss may be fluctuating55,56 or of sudden onset.35,53,54,57 Other symptoms include tinnitus, vertigo, or disequilibrium with a positive Romberg test and hypoactive calorics.53,54 Depending on the site of the lesion(s), the hearing loss may be unilateral or bilateral. Typically the hearing loss is sensorineural, although cases of a conductive loss have been reported secondary to nasopharyngeal granulomas obstructing the eustachian tube.52 Systemic symptoms include fever, malaise, weight loss, and night sweats. The age of presentation of neurosarcoidosis is typically young adulthood between ages 30 and 44 years,37,39–41,58 although there have been reports in children.59 The differential diagnosis of hearing loss in the setting of neurosarcoidosis includes syphilis, multiple sclerosis, Cogan’s syndrome, Vogt-Kyoanagi-Harada disease, endolymphatic hydrops, other granulomatous diseases including tuberculosis and Lyme disease, CPA tumors, and AIDS.42,56

Evaluation In patients presenting with a unilateral or asymmetric fluctuating or sudden-onset hearing loss, the diagnosis of sarcoidosis should be included in the differential diagnosis.

Figure 25-3. In tumefactive sarcoidosis, the disease presents as a dural-based meningioma-like mass. Histologically, the typical feature is the presence of numerous nonnecrotizing granulomas, composed of epithelioid histiocytes and multinucleated giant cells. A, Hematoxylin-eosin stain at low power; B, High power view.

A

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B

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Initial work-up includes a thorough history with a detailed review of systems, inquiring about fatigue, weight loss, changes in vision, and so on. Physical examination should include a general exam, including assessment of the skin, as well as complete otolaryngologic and neurologic evaluations. Facial nerve function should be documented. Due to the high incidence of associated ocular findings, most often uveitis, patients who are suspected of having sarcoidosis should undergo ophthalmologic evaluation. Audiology Audiometric testing includes pure tone audiometry, word recognition, stapedial reflexes (usually absent), tympanometry, and ABR (often absent or abnormal). If patients have associated vestibular symptoms, electronystagmography should be performed. Diagnostic Tests The criteria for the diagnosis of neurosarcoidosis include a clinical picture compatible with the disease, typical radiologic findings, and histologic evidence of noncaseating granulomas. Plain film chest radiograph is performed to search for hilar adenopathy and pulmonary infiltrates, which are present in ≈90% of patients at some time during the course of their disease.38 Biopsy specimens may be obtained from any involved tissue in the body. If pulmonary involvement is evident, the diagnosis may be obtained by transbronchial or mediastinoscopic biopsy or bronchoalveolar lavage (BAL).36 Fine-needle aspiration can give an accurate diagnosis when taken from involved lymph nodes or salivary glands.60 If no specific lesions are identified, a random lip biopsy of minor salivary glands may confirm the diagnosis in 40% to 50% of patients with hilar adenopathy.61 Serologic testing, although nonspecific, should be obtained to support the diagnosis of sarcoidosis. Tests include CBC (leukopenia, anemia, thrombocytopenia), electrolytes (elevated blood urea nitrogen [BUN] and creatinine), serum calcium (hypercalcemia), liver function tests (elevated AST, ALT, Alk Phos), sedimentation rate (elevated), and angiotensin I-converting enzyme (ACE, elevated) (Table 25-2). ACE levels are often elevated in sarcoidosis and thought to be specific for this disease, but increased levels are also seen in patients with leprosy, Gaucher’s disease, liver disease, diabetes mellitus, hyperthyroidism, systemic infection, and malignancy.61,62 Purified protein derivative (PPD) and appropriate skin tests should be performed to rule out anergy, which occurs in ≈25% of patients. Cerebrospinal Fluid Findings Cerebrospinal fluid (CSF) findings in neurosarcoidosis are nonspecific. However, up to 80% of patients with neurosarcoidosis show some CSF abnormalities.37 Abnormalities include mononuclear pleocytosis, increased protein, elevated CSF pressure and low glucose levels. Increased CSF ACE occurs in ≈50% of patients with neurosarcoidosis. Levels tend to fall with treatment and correlate with the activity of the disease42; however, Ferriby and coworkers found no correlation between blood or CSF ACE and

TABLE 25-2. Laboratory Findings Supportive of the Diagnosis of Sarcoidosis ACE ↑ WBCs ↓ Hemoglobin ↓ Platelets ↓ BUN and creatinine ↑ Serum calcium ↑ Liver function tests ↑ ESR ↑ ACE, angiotensin I-converting enzyme ; BUN, blood urea nitrogen; ESR, erythrocyte sedimentation rate; WBCs, white blood cells.

clinical outcome.63 Increased immunoglobulin G (IgG) index and oligoclonal bands have been reported, suggesting that intrathecal immunoglobulin synthesis is increased.39,41 Elevated CD4:CD8 ratios of CSF lymphocytes have been reported,64 as have elevations in lysozyme and β-2-microglobulin.42 Imaging MRI with gadolinium is the imaging study of choice. The granulomatous lesions will enhance on T1 images with gadolinium. MRIs performed without contrast may miss the diagnosis of sarcoidosis.49 Lesions are usually well defined, slightly hyperdense, and homogenously enhancing.42 Some lesions are quite large (Fig. 25-4), whereas others may be very subtle. MRI is also helpful for monitoring the response of CNS lesions to treatment.51 A lack of vascularity of sarcoid granulomas is seen on angiography.47 CT scanning is typically less sensitive but may reveal a large mass as shown in Figure 25-4. Gallium-67 scanning can identify sites of inflammation and may be useful in identifying asymptomatic lesions that can be accessed for directed biopsy. Although the test can be positive in any inflammatory or neoplastic lesions, the identification of pulmonary lesions is relatively specific for sarcoidosis.65

Treatment Systemic steroids are the cornerstone of treatment for sarcoidosis and neurosarcoidosis. Typically larger doses of steroids are used with neurosarcoidosis, that is, 60 to 80 mg methylprednisolone daily.42 Dosages should be tapered carefully. In patients in whom corticosteroids may be contraindicated, other agents including methotrexate, azathioprine, cyclosporine, chloroquine, hydroxychloroquine, radiation, and other immunosuppressive drugs have been used.66 In cases of acute hydrocephalus, expanding mass lesions, and progressively worsening neurologic deficit secondary to increased intracranial pressure unresponsive to medical treatment, surgical intervention is recommended for decompression.38,42

Outcomes The hearing loss often improves with the initiation of steroids. However, it may also be relapsing or chronically progressing. The prognosis for patients with

Auditory Neuropathy, Sarcoidosis, Siderosis, and Idiopathic Pachymeningitis

A

477

B

Figure 25-4. Axial (A) and coronal (B) T1-weighted MRI scans with gadolinium demonstrate an enhancing petroclival lesion that was initially felt to be a large meningioma. Axial CT scan (C) with contrast shows the same homogeneously enhancing, noncalcified lesion.

C neurosarcoidosis is poorer than for patients with sarcoidosis without neurologic involvement. Patients with cranial neuropathies and aseptic meningitis tend to do better, with a greater than 90% recovery or improvement compared with those with other neurologic manifestations, especially parenchymal disease, who tend to have a prolonged course with significant morbidity.63 The mortality rate of neurosarcoidosis is between 5% and 15%.40,41,64

SUPERFICIAL SIDEROSIS OF THE CENTRAL NERVOUS SYSTEM Introduction Superficial siderosis of the CNS is a rare, but potentially fatal, cause of SNHL.67 The disorder is caused by deposition of hemosiderin in the CNS secondary to recurrent or persistent bleeding into the subarachnoid space.68–70 In the

past the diagnosis was officially made only at autopsy,67 whereas today the diagnosis is almost always made with MRI. The cardinal clinical features of superficial siderosis are progressive SNHL and cerebellar ataxia.68

Incidence The incidence of superficial siderosis of the CNS is unknown. A review article by Fearnley and colleagues in 1995 revealed that only 87 cases have been reported in the world literature.68 With the advent of MRI, the diagnosis can be made more readily and even detect presymptomatic cases. In one series, MRI findings consistent with the diagnosis of superficial siderosis were found in 0.15% of 8843 consecutive MR studies. Eighty-five percent of these patients reported no symptoms.71 Superficial siderosis can occur in any age group, with age of onset ranging between 14 and 77 years. Males are typically more commonly affected than females (3:1).68

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Etiology

Clinical Presentation

The cause of superficial siderosis of the CNS is persistent or recurrent bleeding into the subarachnoid space, leading to a deposition of hemosiderin in the CNS. In a review series of 63 patients, the bleeding site was identified in 54% of cases, whereas in 46% of patients the source of bleeding remained unknown.68 In the cases in which the site of bleeding was identified, the source was found to be due to dural pathology (CSF cavity lesion or cervical root lesion) in 47% of patients; a vascular tumor (ependymoma, oligodendroglioma, and astrocytoma) in 35%; and a vascular abnormality (arteriovenous malformation or aneurysm) in 18% of patients.68 Systemic iron overloaded conditions, such as hemachromatosis, do not typically lead to iron excess in the CNS due to the blood-brain barrier for iron.72

Prior to the onset of symptoms there is reported to be a presymptomatic phase, in which superficial siderosis is present, but not sufficient to cause symptoms. This phase ranges from 4 months to 30 years, with a mean of 15 years.68 Clinically superficial siderosis of the CNS presents as a distinct syndrome characterized by progressive SNHL (95%), cerebellar ataxia (88%), and pyramidal signs (76%). The pyramidal signs range from mild symptoms, such as hyperreflexia, to severe symptoms of paraparesis and quadriparesis. Other symptoms include dementia (24%), bladder disturbance (24%), anosmia (17%), anisocoria (10%), and sensory signs (13%) (Table 25-3).68 The most common feature of superficial siderosis is bilateral progressive SNHL, with the high frequencies being more severely affected.68 The hearing loss may be asymmetric and is typically retrocochlear, supported by absence of stapedial reflexes and abnormal brainstem evoked potentials.68 Takasaki and coworkers suggest that there may also be damage to the cochlea due to the elevation of the detective threshold of CM and no response on DPOAE in one patient.80 It is possible that damage to the organ of Corti could occur by way of a patent cochlear aqueduct.81 One case of a sudden bilateral profound hearing loss occurring at the time of a subarachnoid hemorrhage has been reported.82 Vestibular function has been evaluated and reported in only a few patients with superficial siderosis. In all of the patients evaluated, the vestibulo-ocular reflex is absent or diminished.77,83 Symptoms of vertigo and unsteadiness reported by patients probably have a combination of vestibular and cerebellar components.

Pathophysiology In superficial siderosis of the CNS, hemosiderin deposition is primarily seen in areas bathed by circulating CSF, including the cerebellum, brainstem, and eighth nerve. Chronic exposure of blood to the CSF leads to the breakdown of hemoglobin into ferritin and hemosiderin, which accumulates in the microglia.73 Immunohistochemical staining has shown that selective siderosis of the cerebellum and eighth nerve is due to the biosynthesis of ferritin in the microglia of these tissues.74 It has been postulated that ferritin synthesis is neuroprotective by binding the iron released into the CSF by the red cells and that tissue damage occurs only after this reserve has been exhausted.75 A characteristic finding of superficial siderosis involving the cranial nerves is preferential staining to the proximal (glial) segments versus the distal (Schwann cell) segments.74 The eighth nerve, unlike the adjacent facial nerve, retains its glial sheath up to the internal auditory canal (IAC). This long glial segment makes the eighth nerve particularly susceptible, resulting in a greater chance of hemosiderin deposition and chance of axonal damage. In addition, the location of the eighth nerve in the pontine cistern exposes the nerve not only to a large pool of CSF, but also a greater flow of CSF.68 Cranial nerve I is also affected for similar reasons, and it is speculated that anosmia is underreported in association with siderosis.68

History and Physical Exam Patients presenting with SNHL with or without ataxia should undergo a complete history and physical exam, including a neurologic evaluation. Questions related to history of head trauma recently or in the past, headaches, change in sense of smell or vision, and symptoms of imbalance should be included. During the otolaryngologic exam, the patient’s sense of smell should be tested. Audiology

Pathology Gross pathology of superficial siderosis reveals characteristic light-brown staining of diffusely thickened and fibrotic leptomeninges.76 The eighth nerve, and to a lesser extent, cranial nerves I and II, are typically darkly pigmented secondary to a dense accumulation of hemosiderin often associated with demyelination and atrophy.74 Hemosiderin deposition in the tissues, revealed by staining with Prussian blue, is associated with demyelination, neuronal loss, reactive gliosis, and the appearance of intracellular rounded eosinophilic ovoid bodies.77,78 Ovoid bodies represent degenerated axonal swellings caused by heme-iron complexes, which catalyze lipid peroxidase reactions, resulting in a local oxidative effect and neuroaxonal dystrophy.79

Audiometric testing includes pure tone audiometry, word recognition, and stapedial reflexes. Further testing may include ABRs or OAEs (or both). Vestibular testing should be considered if patients report imbalance or vertigo. TABLE 25-3. Key Clinical Features of Superficial Siderosis Progressive sensorineural hearing loss (95%) Cerebellar ataxia (88%) Pyramidal signs (hyperreflexia, paraparesis, quadriparesis) (76%) Dementia (24%) Bladder disturbance (24%) Anosmia (17%) Anisocoria (10%)

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479

Cerebrospinal Fluid Findings The main CSF findings are hemorrhage and xanthochromia. Other features include elevated iron, red blood cell, and ferritin levels, as well as the presence of erythrophages and siderophages.68 A review of CSF findings in 48 patients with superficial siderosis revealed hemorrhage in 20 patients and xanthochromia in 16. In a small percentage of patients, the CSF may be normal. In these cases it may be necessary to repeat the CSF examination.68 Imaging A suggestive clinical picture and CSF findings, along with diagnostic MRI findings can confirm the diagnosis of superficial siderosis of the CNS. MRI findings are pathognomonic for superficial siderosis and MRI is currently the gold standard for diagnosis, preventing the need for biopsy (Table 25-4). T1-weighted images appear normal. T2-weighted images reveal a characteristic marginal hypointensity of the brainstem, cerebrum, cerebellum, and eighth nerve (Fig. 25-5A, B). The hypointensity is due to the paramagnetic effect of iron, which leads to the induction of local heterogeneous magnetic field gradients with shortened relaxation times, promoting signal voids in the MRI.68,84 CT is not useful for the diagnosis of superficial siderosis,85 although it may show atrophy of the cerebrum and cerebellum. When an MRI of the head does not localize a site of bleeding intracranially, further evaluation should include MRI of the spine in search of a spinal cord lesion. If negative, magnetic resonance angiography (MRA) or conventional angiography may be performed to exclude a vascular lesion.69

A

Treatment Treatment of superficial siderosis consists of identification and surgical control or endovascular treatment of suspected bleeding sites.67,68 There is currently no evidence that chelating agents, such as deferoxamine, or antioxidants, such as vitamin E, affect the progression of the disorder.68 The hearing loss is typically managed with hearing aids. Cochlear implant use has been successful in one reported case in a patient with a bilateral profound hearing loss who no longer benefited from hearing aids.81

Outcome Superficial siderosis is a chronic illness. Once diagnosed, patients may become bed-bound secondary to cerebellar ataxia or a myelopathic syndrome. Even after surgical intervention to stop the bleeding, it may still take several years before the effectiveness of surgery is known. Also, it

TABLE 25-4. Key MRI Findings in Superficial Siderosis T1-weighted images: Appear normal T2-weighted images: Marginal hypointensity of brainstem, cerebrum, cerebellum

B Figure 25-5. Superficial siderosis. Axial T2-weighted MRI scans revealing characteristic marginal hypointensity around the brainstem (A) and cerebellum (B) due to the paramagnetic effect of deposited iron.

is currently unknown whether the disease continues to progress after the bleeding has been stopped. In most cases, the disease is ultimately fatal, although it may progress slowly over several decades. The mean survival of reported cases is 11 years.68

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IDIOPATHIC HYPERTROPHIC PACHYMENINGITIS Introduction First described by Naffziger and Stern in 1949, idiopathic hypertrophic pachymeningitis (IHCP) is a rare fibrosing inflammatory process characterized by marked thickening of the dura.86 The site of dural involvement can be subdivided into intracranial, spinal, and craniospinal, with the intracranial form being rarer than the spinal form. The most common intracranial symptoms are headache, cranial nerve palsies, and ataxia. Presenting symptoms may include hearing loss and tinnitus or vertigo. IHCP is a diagnosis of exclusion, since other clinical entities can produce thickening of the meninges. The diagnosis is made with biopsy and supported with characteristic MRI findings.

(less than 60 mm H2O) that occurs without an inciting event, such as trauma or lumbar puncture. The clinical course of SIH, unlike IHCP, is typically benign.93

Histopathology Gross pathology of IHCP reveals an immensely thickened and fibrotic dura. Histologic features are characterized by a chronic nonspecific inflammatory infiltrate of lymphocytes, plasma cells, and histiocytes (Fig. 25-6).89,91 Granulomas may or may not be present.88 Chronic infectious and neoplastic processes are absent. It has been theorized that the symptoms of headache and cranial neuropathies are secondary to nerve encasement and ischemia due to the chronic inflammation and fibrosis of the dura.88-90 Fibrosis may also cause occlusion of the venous sinuses.94

Clinical Presentation

Incidence and Etiology The incidence and cause of IHCP are currently unknown. Early reports of pachymeningitis were typically attributed to syphilis or tuberculosis. Today, however, most reported cases are idiopathic.87 The age at presentation in reported cases ranges from 20 to 78 years, with a mean age of 51 years. The incidence is equal in males and females.87,88 The three main known causes of IHCP are sarcoidosis, tuberculosis, and syphilis.89–91 Other infectious causes include fungi and viruses, including human T-cell lymphoma virus-1 (HTLV-1).92 Autoimmune causes include rheumatoid arthritis, Wegener’s granulomatosis, polyarteritis nodosa, and multifocal fibrosclerosis.91 Neoplastic processes include lymphoma, plasmacytoma, meningioma, and metastatic prostate cancer.89 IHCP has also been associated with spontaneous intracranial hypotension93 and dialysis.90 Spontaneous intracranial hypotension (SIH) is a rare syndrome associated with low intracranial pressure

The clinical presentation of IHCP is extremely variable and depends on the site of involvement of the dura. The most common symptoms are a subacute or chronic localized headache and single or multiple cranial neuropathies. A review of 33 cases in the literature by Parney revealed that the most commonly affected cranial nerve is the eighth followed by the second cranial nerve.87 Symptoms include asymmetrical SNHL, tinnitus, and vertigo. The hearing loss may be sudden in onset.95 Symptoms also include ataxia. In a review of their series, Hatano and colleagues divided IHCP into two main sites of involvement: (1) cavernous sinus to superior orbital fissure involvement, affecting cranial nerves III, IV, V, and VI, and (2) falcotentorial to posterior fossa dural involvement, involving cranial nerves V, VII, VIII, IX, and X.89 IHCP has also been associated with the Tolosa-Hunt syndrome (painful ophthalmoplegia), optic neuropathy, and diabetes insipidus.89

Pathology

Giant cell Intense inflammation

Figure 25-6. Histopathology slide showing a chronic nonspecific inflammatory infiltrate of lymphocytes, plasma cells, and histiocytes.

Granuloma & Necrosis

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Evaluation To make the diagnosis of IHCP, known causes of pachymeningitis must be ruled out (Table 25-5). Appropriate work-up includes plain film chest radiograph, PPD skin test, and CSF serology and culture. Serologic tests include reactive protein reagent (RPR), ACE, rheumatoid factor (RF), antinuclear antibody (ANA), and antineutrophil cytoplasmic antibodies (C-ANCA). Nonspecific findings in patients with IHCP include an elevated erythrocyte sedimentation rate (ESR) in the majority of patients, as well as an elevated CSF protein.87 Dural biopsy is necessary to exclude known causes of pachymeningitis and obtain the diagnosis of IHCP. In patients in whom tuberculosis is suspected, but routine tests are negative, use of polymerase chain reaction (PCR) on CSF or biopsy specimen may be helpful.91 Imaging MRI with contrast is necessary to support the diagnosis. IHCP lesions appear isointense or hypointense relative to brain on T1-weighted images and hypointense with or without a thin margin of hyperintensity on T2-weighted images. Lesions show intense dural enhancement with gadolinium (Fig. 25-7A, B).89,96 Lesions that are more localized may mimic a meningioma.97 Screening studies, such as noncontrast fast-spin echo T2-weighted images used for acoustic tumors, may miss the diagnosis.95 CT with and without contrast often reveals thickening of the dura.94

A

Treatment Management of IHCP involves corticosteroid therapy, which has been effective in relieving symptoms and halting the progression of the disease.90,91 Symptoms may recur or progress, however, despite treatment.88,89 Hatano and colleagues89 and Bang and coworkers93 reported that linear lesions, which have diffuse enhancement of the meninges, might have a better response to corticosteroids than nodular lesions, which have a localized enhancement and thickening of the meninges. High-dose pulse steroid therapy may help to reduce side effects that occur with daily steroid administration.89 Immunosuppressive agents, such as azathioprine, used mainly to taper corticosteroids, have shown early promising results, but long-term follow-up is still needed.91 Radiotherapy has not been proven to be effective.89,91 Surgical excision is necessary to make the diagnosis of IHCP. In certain circumstances, such as involvement of the optic canal and superior orbital fissure, surgical decompression may be necessary to help alleviate symptoms.88,89 TABLE 25-5. Known Causes of Pachymeningitis Infectious Autoimmune Neoplastic Other

Tuberculosis, syphilis, fungal, HTLV-1 Rheumatoid arthritis, Wegener’s granulomatosis, polyarteritis nodosa, multifocal fibrosclerosis Lymphoma, plasmacytoma, meningioma, metastatic prostate cancer Sarcoidosis, spontaneous intracranial hypotension, dialysis

HTLV-1, human T-cell lymphoma virus type I.

B Figure 25-7. Gadolinium-enhanced coronal (A) and axial (B) T1-weighted MRI scans depicting the intense dural enhancement and thickening seen with pachymeningitis.

In cases with a positive PPD, but negative histologic exam and cultures for tuberculosis (TB), a trial of anti-TB medications may be warranted.87

Outcomes Although the number of reported cases of IHCP has recently increased with the advent of MRI, there is still much to learn with regard to cause, incidence, treatment,

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and long-term outcomes. Reported cases of IHCP reveal a chronic clinical course. Patients may improve initially, but many relapse and become steroid-dependent. Often the disease progresses despite treatment.93,98 Otolaryngologists should be aware that IHCP may present early as an asymmetrical SNHL alone or with associated symptoms and that screening procedures, such as fast spin-echo T2weighted MRI, may miss the diagnosis.

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21. Berlin CI, Hood LJ, Hurley A, Wen H: Contralateral suppression of otoacoustic emissions: An index of the function of the medial olivocochlear system. Otolaryngol Head Neck Surg 110:3–21, 1994. 22. Sheykholeslami K, Kaga K, Kaga M: An isolated and sporadic auditory neuropathy (auditory nerve disease): Report of five patients. J Laryngol Otol 115:530–534, 2001. 23. Kovach MJ, Lin JP, Boyadjiev S, et al: A unique point mutation in the PMP22 gene is associated with Charcot-Marie-Tooth disease and deafness. Am J Hum Genet 64:1580–1593, 1999. 24. Kraus N, Bradlow AR, Cheatham MA, et al: Consequences of neural asynchrony: A Case of auditory neuropathy. J Assoc Res Otolaryngol 1:33–45, 2000. 25. Zeng FG, Oba S, Garde S, et al: Temporal and speech processing deficits in auditory neuropathy. Neuroreport 10:3429–35, 1999. 26. Starr A, Sininger Y, Winter M, et al: Transient deafness due to temperature-sensitive auditory neuropathy. Ear Hear 19:169–79, 1998. 27. Salvi RJ, Wang J, Ding D, et al: Auditory deprivation of the central auditory system resulting from selective inner hair cell loss: Animal model of auditory neuropathy. Scandinavian Audiology 51:1–12, 1999. 28. Spoendlin H: Optic and cochleovestibular degenerations in hereditary ataxias. Brain 97:41–48, 1974. 29. Fujikawa S, Starr A: Vestibular neuropathy accompanying auditory and peripheral neuropathies. Arch Otolaryngol Head Neck Surg 126:1453–1456, 2000. 30. Sheykholeslami K, Kaga K, Murofushi T, Hughes DW: Vestibular function in auditory neuropathy. Acta Otolaryngol 120:849–854, 2000. 31. Trautwein PG, Sininger YS, Nelson R: Cochlear implantation of auditory neuropathy. J Am Acad Audiol 11:309–315, 2000. 32. Shallop JK, Peterson A, Facer GW, et al: Cochlear implants in five cases of auditory neuropathy: Postoperative findings and progress. Laryngoscope 111:555–562, 2001. 33. Lazarus AA: Sarcoidosis. Otolaryngol Clin N Am 15:621–631, 1982. 34. Hybels RL, Rice DH: Neuro-otologic manifestations of sarcoidosis. Laryngoscope 86:1873–1878, 1976. 35. Souliere CR, Kava CR, Barrs DM, Bell AF: Sudden hearing loss as the sole manifestation of neurosarcoidosis. Otolaryngol Head Neck Surg 105:376–81,1991. 36. Gullapalli D, Phillips LH: Neurologic manifestations of sarcoidosis. Neurologic Clin 20:59–83, 2002. 37. Stern BJ, Krumholz A, Johns CJ, et al: Sarcoidosis and its neurological manifestations. Arch Neurol 42:909–917, 1985. 38. Sharma OP, Sharma AM: Sarcoidosis of the nervous system. A clinical approach. Arch Intern Med 151:1317–1321, 1991. 39. Delaney P: Neurologic manifestations in sarcoidosis: review of the literature with a report of 23 cases. Ann Intern Med 87:336–345, 1977. 40. Chapelon C, Ziza JM, Piette JC, et al: Neurosarcoidosis: signs, course and treatment in 35 confirmed cases. Medicine 69:261–276, 1990. 41. Oksanen V: Neurosarcoidosis: Clinical presentations and course in 50 patients. Acta Neurologica Scandinavica 73:283–290, 1986. 42. Oksanen V: Neurosarcoidosis. Sarcoidosis 11:76–79, 1994. 43. Moine A, Frachet B, Van Den Abbeele T, et al: Surdite et sarcoidose. Ann Oto-Laryngol (Paris) 107:469–73, 1990. 44. Gardner J, Kennedy HG, Hamlin A: HLA associations in sarcoidosis: A study of two ethnic groups. Thorax 39:19–24, 1984. 45. Babin RW, Liu C, Aschenbrener C: Histopathology of neurosensory deafness in sarcoidosis. Ann Otol Rhinol Laryngol 93:389–393, 1984. 46. Babu VS, Eisen H, Pataki K: Sarcoidosis of the central nervous system. J Comput Assist Tomogr 3:396–397, 1979. 47. Elias WJ, Lanzino G, Reitmeyer M, Jane JA: Solitary sarcoid granuloma of the cerebellopontine angle: a case report. Surg Neurol 51:185–90, 1999. 48. Clark WC, Acker JD, Dohan FC, Robertson JH: Presentation of central nervous system sarcoidosis as intracranial tumors. J Neurosurg 63:851–6, 1985. 49. Seltzer S, Mark AS, Atlas SW: CNS sarcoidosis: Evaluation with contrast-enhanced MR imaging. AJNR 12:1227–1233, 1991.

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50. Sherman JL, Stern BJ: Sarcoidosis of the CNS: comparison of unenhanced and enhanced MR images. AJNR 11:915–923, 1990. 51. Lexa FJ, Grossman RI: MR of sarcoidosis in the head and spine: Spectrum of manifestations and radiographic response to steroid therapy. AJNR 15:973–982, 1994. 52. Sugisaki K, Miyazaki E, Fukami T, et al: A case of sarcoidosis presenting as multiple pulmonary nodules, nasopharyngeal and cerebellopontine tumors. Sarcoidosis Vasc Diffuse Lung Dis 17:82–85, 2000. 53. O’Reilly BJ, Burrows EH: VIIIth cranial nerve involvement in sarcoidosis. J Laryngol Otol 109:1089–1093, 1995. 54. Majumdar B, Crowther J: Hearing loss in sarcoidosis. J Laryngol Otol 97:635–639, 1983. 55. Brihaye P, Halama AR: Fluctuating hearing loss in sarcoidosis. Acta Oto-Rhino-Laryngologica Belgica 47:23–26, 1993. 56. Jahrsdoerfer RA, Thompson EG, Johns MM, Cantrell RW: Sarcoidosis and fluctuating hearing loss. Ann Otol Rhinol Laryngol 90:161–163, 1981. 57. Sugaya F, Shijubo N, Takahashi H, Abe S: Sudden hearing loss as the initial manifestation of neurosarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 13:54–56, 1996. 58. Pentland B, Mitchell DJ, Cull RE, Ford MJ: Central nervous system sarcoidosis. QJ Med 220:457–465, 1985. 59. Vaphiades MS, Eggenberger E: Childhood sarcoidosis. J Neuroophthalmol 18:99–101, 1998. 60. Smith Frable MA, Frable WJ: Fine-needle aspiration biopsy: Efficacy in the diagnosis of head and neck sarcoidosis. Laryngoscope 94:1281–1283, 1984. 61. Dash GI, Kimmelman CP: Head and neck manifestations of sarcoidosis. Laryngoscope 98:50–53, 1988. 62. Leiberman J (ed.): Angiotensin-converting enzyme (ACE) and serum lysozyme in sarcoidosis. In: Sarcoidosis. Orlando, FL, Grune and Stratton, pp 145–159, 1985. 63. Ferriby D, de Seze J, Stojkovic T, et al: Long-term follow-up of neurosarcoidosis. Neurology 57:927–929, 2001. 64. Stern BJ, Griffin DE, Luke RA: Neurosarcoidosis: Cerebrospinal fluid lymphocyte subpopulations. Neurology 37:878–881, 1987. 65. Israel HL, Albertine KH, Park CH: Whole body gallium-67 scanning in pulmonary and extrapulmonary sarcoidosis. Ann N Y Acad Sci 465:1182–1186, 1991. 66. Sharma OP: Effectiveness of chloroquine and hydroxychloroquine in treating selected patients with sarcoidosis with neurological involvement. Arch Neurol 55:1248–1254, 1998. 67. Pribitkin EA, Rondinella L, Rosenberg SI, Yousem DM: Superficial siderosis of the central nervous system: An underdiagnosed cause of sensorineural hearing loss and ataxia. Am J Otol 15:415–418, 1994. 68. Fearnley JM, Stevens JM, Rudge P: Superficial siderosis of the central nervous system. Brain 118:1051–1066, 1995. 69. Hsu WC, Loevner LA, Forman MS, Thaler ER: Superficial siderosis of the CNS associated with multiple cavernous malformations. AJNR 20:1245–1248, 1999. 70. Castelli ML, Husband A: Superficial siderosis of the central nervous system: an underestimated cause of hearing loss. J Laryngol Otol 111:60–62, 1997. 71. Offenbacher H, Fazekas F, Schmidt R, et al: Superficial siderosis of the central nervous system. MRI findings and clinical significance. Neuroradiology 38:S51–S56, 1996. 72. Koeppen AH, Hurwitz CG, Dearborn RG, et al: Experimental superficial siderosis of the central nervous system: biochemical correlates. J Neurosurg Sci 112:38–45, 1992. 73. Koeppen AH, Dickson AC, Chu RC, Thach RE: The pathogenesis of superficial siderosis of the central nervous system. Ann Neurol 34:646–653, 1993. 74. Koeppen AH, Dentinger MP: Brain hemosiderin and superficial siderosis of the central nervous system. J Neuropath Exp Neurol 47:249–270, 1988.

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75. Koeppen AH, Borke RC: Experimental superficial siderosis of the central nervous system. Morphological observations. J Neuropathol Exp Neurol 50:579–594, 1991. 76. Hughes JT, Oppenheimer DR: Superficial siderosis of the central nervous system. Acta Neuropathol (Berl) 13:56–74, 1969. 77. Resvesz T, Earl CT: Superficial siderosis of the central nervous system presenting with longstanding deafness. J R Soc Med 81:479–481, 1988. 78. Koeppen AH, Barron KD: Superficial siderosis of the central nervous system: A histological, histochemical, and chemical study. J Neuropathol Exp Neurol 30:448–467, 1971. 79. Sadeh M, Sandbach U: Neuraxonal dystrophy and hemosiderin in the central nervous system. Ann Neurol 7:286–287, 1980. 80. Takasaki K, Tankaka F, Shigeno K, et al: Superficial siderosis of the central nervous system. A case report on examination by ECoG and DPOAE. ORL 62:270–273, 2000. 81. Irving RM, Graham JM: Cochlear implantation in superficial siderosis. J Laryngol Otol 110:1151–1153, 1996. 82. Kott E, Bechar M, Bornstein B, et al: Superficial hemosiderosis of the central nervous system. Acta Neurochir (Wien) 14:287–298, 1966. 83. Stevens I, Petersen D, Grodd W, et al: Superficial siderosis of the central nervous system. A 37 year follow-up of a case and review of the literature. Eur Arch Psychiatry Clin Neurosci 241:57–60, 1991. 84. Bryant RG, Marill K, Blackmore C, Francis L: Magnetic relaxation in blood and blood clots. Magn Reson Med 13:133–144, 1990. 85. Uchino A, Aibe H, Itoh H, et al: Superficial siderosis of the central nervous system. Its MRI manifestations. Clinical Imaging 21:241–245, 1997. 86. Naffziger HC, Stern WE: Chronic pachymeningitis: Report of a case and review of the literature. Arch Neurol Psychiatry 62:383–411, 1949. 87. Parney IF, Johnson E, Allen PB: Idiopathic cranial hypertrophic pachymeningitis responsive to antituberculous therapy: case report. Neurosurgery 41:965–971, 1997. 88. Mamelak AN, Kelly WM, Davis RL: Idiopathic hypertrophic cranial pachymeningitis: Report of three cases. J Neurosurg 79:270–276, 1993. 89. Hatano N, Behari S, Nagatani T, et al: Idiopathic hypertrophic cranial pachymeningitis: Clinicoradiological spectrum and therapeutic options. Neurosurgery 45:1336–1347, 1999. 90. Goyal M, Malik NK, Mishra NK, Gaikwad SB: Idiopathic hypertrophic pachymeningitis: Spectrum of the disease. Neuroradiology 39:619–623, 1997. 91. Dumont AS, Clark AW, Sevick RJ, Myles ST: Idiopathic hypertrophic pachymeningitis: A report of two patients and review of the literature. Can J Neurol Sci 27:333–340, 2000. 92. Kawano Y, Kira J: Chronic hypertrophic cranial pachymeningitis associated with HTLV-1 infection. J Neurol Neurosurg Psychiatry 59:435–437, 1995. 93. Bang OY, Kim DI, Yoon SR, Choi IS: Idiopathic hypertrophic pachymeningeal lesions: Correlation between clinical patterns and neuroimaging characteristics. Eur Neurol 39:49–56, 1998. 94. Martin N, Masson C, Henin D, et al: Hypertrophic cranial pachymeningitis: assessment with CT and MR imaging. AJNR 10: 477–484, 1989. 95. Ramirez A, Hegarty JL, Jackler RK: Hypertrophic pachymeningitis: An unusual case of hearing loss. Paper presented at the American Academy of Otolaryngology Annual Meeting, Sep 1, 2001. 96. Friedman DP, Flanders AE: Enhanced MR imaging of hypertrophic pachymeningitis. AJR 169:1425–1428, 1997. 97. Deprez M, Born J, Hauwaert C, et al: Idiopathic hypertrophic cranial pachymeningitis mimicking multiple meningiomas: A case report and review of the literature. Acta Neuropathol (Berl) 94: 385–389, 1997. 98. Masson C, Henin D, Hauw JJ, et al: Cranial pachymeningitis of unknown origin: A study of seven cases. Neurology 43:1329–1334, 1993.

Chapter

26 Joel A. Goebel, MD, FACS Gerard Gianoli, BSE, MD

Vestibular Neuritis Outline Introduction Historical Background Pathophysiology Clinical Features

INTRODUCTION Vestibular neuritis (VN) is a clinical diagnosis made in cases presenting with severe vertigo, nausea, and vomiting in the absence of significant hearing loss or central nervous system signs. Throughout the years, numerous names have been used for this clinical picture, including epidemic vertigo, neurolabyrinthitis epidemica, acute labyrinthitis, vestibular paralysis, and vestibular neuronitis. As the name implies, VN is thought to be caused by an inflammatory condition of the vestibular nerve, although the exact cause of the inflammation remains speculative. Even though the clinical picture can be variable, certain key features in the patient history and, to a lesser extent, the examination and laboratory findings makes this diagnosis possible. In the following sections, we will explore the historical background of VN and the evolution of thought regarding its pathophysiology and then discuss the main features of the history, examination and laboratory findings. We will then present current therapeutic options based on recent evidence regarding anatomic considerations and probable viral causes. Emphasis is placed on controversial issues such as the exact nature of viral involvement, single versus recurrent attacks, and the cause of selective superior versus inferior vestibular nerve involvement.

HISTORICAL BACKGROUND The first case of what might today be called VN was reported in the literature in 1909 by Ruttin.1 In 1952, Dix and Hallpike reported 100 cases with either single or multiple attacks of vertigo without hearing loss and commented that canal paresis with caloric irrigation was unilateral in 47% and bilateral in 53% of the cases. They mentioned that all symptoms ceased within a few years after diagnosis.2 Harrison (1962) studied 67 patients and noted recurrent attacks up to seven years later in 29 patients.3 Lumio and Aho (1965) followed 27 patients for at least 6 months and noted that all patients showed complete recovery or only mild unsteadiness.4 Boffi (1965) 484

Diagnosis Treatment Prognosis Future Directions

studied 85 cases and postulated a relationship between VN and paroxysmal positional nystagmus.5 In 1956, a landmark article appeared by Lindsay and Hemenway describing seven cases of acute vertigo without hearing loss and the accompanying histopathologic findings.6 In all seven cases, severe positional vertigo developed after the initial prolonged attack and varying degrees of superior vestibular nerve, lateral and superior canal ampulla, and utricle damage was found with sparing of the inferior vestibular nerve and posterior canal ampulla. Although they postulated vascular occlusion of the anterior vestibular artery as the probable cause in one case, no direct evidence of occlusion was noted and a viral cause was included in their differential diagnosis. Schuknecht (1962) studied these cases and four additional patients and postulated that the positional vertigo was caused by loosened otoconia from the damaged utricle stimulating the intact posterior canal ampulla.7 From these two papers, it was suspected that, regardless of cause, V N was a selective degenerative process that spared the inferior vestibular nerve, posterior canal ampulla, and saccule. In 1981, Schuknecht and Kitamura described temporal bone findings in patients with VN.8 In certain cases, selective superior vestibular nerve atrophy was seen without end-organ degeneration. In other cases, however, both neural and end-organ atrophy were found (Fig. 26-1). No evidence of arteriolar thrombus or intralabyrinthine hemorrhage was seen. They concluded that VN preferentially damaged the superior vestibular nerve and corresponding end-organs without offering a plausible explanation for this selectivity. Furthermore, a viral cause was suspected in this disorder, but no definitive direct evidence was noted on histopathologic examination. The presence of a latent viral infection in VN had been suspected for many years before recent electron microscopic techniques and polymerase chain reaction (PCR) amplification became available. As noted earlier, Schuknecht and Kitamura felt that the lack of vascular injury in their specimens and a similarity in labyrinthine and neural injury in three of their cases to a case of herpes zoster

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affects the superior vestibular nerve and related labyrinthine receptors.

PATHOPHYSIOLOGY Total atrophy of ampullary nerve fibers

Atrophy of crista

Normal ampullary Normal crista nerve fibers Figure 26-1. Photomicrographs through sections of the superior vestibular nerve and lateral semicircular canal ampulla in a patient with right vestibular neuronitis. A, Right ear shows severe atrophic changes in both the nerve and crista ampullaris. B, Left ear demonstrates normal nerve and end-organ architecture. (Reprinted with permission from Schuknecht HF, Kitamura K. Vestibular neuronitis. Ann Otol Rhinol Laryngol 78(Suppl):1–19, 1981.)

oticus described by Zajtchuk and colleagues was suggestive for a viral cause.9 Friedman and House described an abundance of lipofuscin inclusion bodies in Scarpa’s ganglion cells in a case of clinical VN and felt that this may represent a “wear and tear” phenomenon following a viral infection.10 In similar fashion, Baloh and coworkers described Scarpa’s ganglion cell loss in a patient with clinical vestibular neuritis and felt the changes were consistent with viral infection even though electron microscopy or immunohistochemistry failed to demonstrate evidence of viral particles.11 However, Furata and colleagues reported 6 of 10 temporal bones of patients with VN had herpes simplex virus (HSV) particles identified by PCR.12 Arbusow and coworkers studied evidence of HSV-1 infection in both Scarpa’a ganglion and the geniculate ganglion and found widespread distribution of the viral elements throughout both ganglia. According to their study, serologic evidence of primary exposure by HSV-1 can be found in more than 80% of the adult population and has been identified in Scarpa’s ganglion in 60% of temporal bone specimens by PCR.13 Historically, the evidence seems to support a viral etiology for VN although by the strictest definition a cause and effect relationship has not been established. As noted in the histopathologic studies of VN, a predilection for superior vestibular nerve or related endorgan structures is fascinating. Even the early observations of Schuknecht and Kitamura that benign positional vertigo frequently occurs following VN suggests that posterior semicircular canal function is intact on the involved side. Indeed, Fetter and colleagues used multiple-axis rotational measurements of the vestibulo-ocular reflex (VOR) in patients with a clinical history of VN to show that ipsilateral posterior canal function was intact while lateral and anterior canal function on the same side were variably reduced.14 In some instances, however, either all canal function or, rarely, only posterior canal function is affected. In most cases, however, it appears that VN

Since the diagnosis of vestibular neuritis is clinical rather than pathologic, the pathophysiology is speculative. Lindsay and Hemenway thought the explanation for the vertigo without hearing loss in their seven patients was occlusion of the anterior vestibular artery, which supplies the superior and lateral semicircular canal ampullae, utricular macula, and the superior vestibular nerve itself. Later, however, Schucknecht hypothesized that the insult was most likely viral due to the pattern of hair cell loss and fibrosis and the lack of any arterial or venous occlusion seen on temporal bone microscopic examination. Subsequent reports have supported the presence of viral particles in Scarpa’s ganglion in temporal bones of patients with and without a clinical history of VN but have failed to definitively prove that these viral particles are the cause of the clinical picture rather than a coincidental bystander. There is, however, enough compelling immunohistochemical evidence in support of viral ganglionitis (especially HSV-1) as the cause of VN to make it the leading hypothesis. Two puzzling observations about VN require further investigation—that is, (1) why the superior vestibular nerve and its end-organs are more often affected than the inferior vestibular nerve, posterior canal, and saccule and (2) why the amount of histologic injury varies widely from case to case. One theory states that VN is caused by a selective viral ganglionitis that only affects superior vestibular nerve cells.15 However, because no anatomic barrier exists within the ganglion to prevent viral spread between cells, this explanation seems unrealistic Arbusow and coworkers proposed a dual innervation of the posterior canal ampullae via separate bony channels to explain sparing of posterior canal function. Recently, Goebel and colleagues and Gianoli and coworkers proposed anatomic differences in the length, trabeculation, and arteriolar channels between the superior and inferior vestibular nerve bony paths to explain selective superior nerve and end-organ injury.16 Both studies confirmed a longer, narrower, more trabeculated bony path for the superior vestibular nerve compared with either the inferior vestibular or singular nerves in normal temporal bones (Fig. 26-2). They hypothesized that VN causes neural edema and subsequent entrapment and possible ischemia of the superior more than inferior nerve and endorgan structures. This theory also accounts for milder cases with more complete recovery of function (no permanent ischemic changes) and more severe cases with loss of canal and otolith function. It must be noted, however, that no study to date has documented definitive evidence of vascular compromise.

CLINICAL FEATURES Typically, vestibular neuritis begins with an abrupt onset of vertigo accompanied by nausea and vomiting. In some instances, the onset of the attack is less dramatic with an

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A

B Figure 26-2. Photomicrographs of sections through the labyrinth and internal auditory canal in a normal temporal bone specimen. A, Superior vestibular nerve and canal. A denotes lateral semicircular canal crista, B superior vestibular nerve, C arteriole of superior vestibular nerve, and D reticulated bony canal. Note the length and degree of bony trabeculations. B, Singular nerve and canal. A marks the singular nerve, B the reticulations in the canal, C the arteriole within the canal, and D posterior canal ampulla. Note the shorter course and looser trabeculation compared with part A. (Reprinted with permission from Goebel J, O’Mara W, Gianoli G. Anatomic considerations in vestibular neuritis. Otol Neurotol 22:512–518, 2001.)

antecedent period of vague dizziness and nausea. Many times the initial episode awakens the patient at night or is first noticed when they get out of bed. The vertigo may wax and wane but is present in all head positions. Most patients feel better lying flat and still, although some prefer to sit upright during the episodes. In all cases, head movement exacerbates the vertigo and nausea. Sometimes there is a history of upper respiratory infection or even influenza preceding the attack, but this is not a predictable historical finding. What is remarkable, however, is the absence of auditory or central nervous system signs and symptoms. In a minority of cases, unilateral tinnitus may be present and audiometry may document a high-frequency hearing loss. There is no loss of consciousness, memory loss, or motor or sensory deficits that might be seen in brainstem ischemia or infarction. The time course

of the initial vertiginous episode is typically hours up to a day in duration. Although the onset of VN is more predictable, the chronic course of the disease is more variable. In most cases, the initial episode will resolve, and the patient experiences dysequilibrium while ambulating and momentary dizziness with rapid head turns lasting up to 3 months after the initial attack. However, some patients experience repeated episodes of severe vertigo much like the initial episode although the intensity and duration is usually less than the first spell. One theory for the recurrent episodes proposed by Gacek and Gacek is reactivation of a latent viral ganglionitis secondary to another viral infection or stress.15 In all instances, the episodes of vertigo diminish or disappear but the residual dysequilibrium persists to a greater or lesser extent. The variability in recovery is due to a combination of the extent of end-organ damage and the ability of the central nervous system to compensate for the loss of peripheral function. If end-organ damage is minimal, persistent dysequilibrium is unlikely. However, significant loss of ipsilateral semicircular canal and utricular function frequently leads to lingering postural instability and disorientation with rapid head movements. A fascinating observation is the apparent association of benign positional vertigo (BPV) following VN in a percentage of cases. This observation was first made by Schucknecht who hypothesized that utricular damage from VN caused loosening of otoconia, which then migrated to the posterior semicircular canal and stimulated the intact posterior canal ampulla.7 Gacek and Gacek proposed an alternative theory of recurrent viral ganglionitis to explain the positional spells.15 In any event, BPV following neuritis is common and is treated with the same canalith repositioning maneuvers used for idiopathic BPV.

DIAGNOSIS The diagnosis of VN is made by a typical history and exclusion of other causes of sudden loss of unilateral vestibular input. At times, the diagnosis of VN is difficult because many other recurrent vestibular pathologies can mimic VN at their onset. For example, the initial episode of Ménière’s disease, perilymphatic fistula, or vestibular migraine can all be indistinguishable from VN if there are no auditory findings with the first episode. Over time, however, these entities can usually be identified by the natural course and progression of the disease. In general, VN is typically a single severe episode of vertigo without involvement of the auditory system, whereas the other entities tend to be recurrent vestibulopathies and may have auditory involvement at some point as the disease progresses. However, some cases of VN involve recurrent bouts of vertigo and can only be distinguished from other causes by the lack of hearing loss or any central nervous system signs or symptoms after a thorough investigation. The typical history of VN includes the abrupt onset of severe rotary vertigo associated with nausea, vomiting, and diaphoresis. There are typically no auditory symptoms to localize the lesion. There may be a history of a prior cold or upper respiratory infection in the days or weeks prior to the onset of the acute vertigo. During the attack, the

Vestibular Neuritis

patient prefers to sit or lie perfectly still to minimize nausea. There should be no neurologic symptoms, such as blurred or double vision, dysarthria, dysphagia, or alterations in consciousness. Vomiting is common and may be severe enough to require hospitalization and intravenous fluids. Very often the patient will be convinced that he is having a stroke or a heart attack, precipitating a visit to the emergency room. The length of the initial vertigo spell is usually a few hours with a lingering disequilibrium for days to weeks. During the recovery phase, the patient usually notes symptoms brought on mainly by quick head movements, particularly to the affected side. The patient may feel off balance for several months after the incident and in some cases may have symptoms persist for years. Additionally, it is not uncommon for patients to develop BPPV after a bout of VN. Physical examination during the acute phase of VN will demonstrate a brisk horizontal-rotary nystagmus with the fast phase beating to the uninvolved side, implying involvement of semicircular canals in both the horizontal and vertical planes. Removal of fixation by using Frenzel lenses intensifies the nystagmus. An otherwise normal neurologic exam and the ability to stand unassisted without lateropulsion is important in distinguishing VN from an acute cerebellar hemorrhage or infarct. Imaging studies are usually normal, but high-resolution MRI with gadolinium may show enhancement of the eighth cranial nerve. Oculographic studies are usually not indicated during the initial episode but may demonstrate either unilateral or bilateral caloric reduction and a lingering nystagmus without fixation. If the extent of vestibular injury is substantial, the patient may exhibit refixation saccades on unilateral head thrust toward the affected ear even months to years following the initial episode. In most cases, the patient with VN experiences a single episode of vertigo lasting up to a day and recovers completely over a few weeks. Some cases with documented severe vestibular loss may experience poor compensation and lingering dysequilibrium. Finally, in a few cases of suspected VN the vertigo attacks recur although usually in diminishing intensity. The key features of VN and common vestibular disorders in the differential diagnosis are listed in Table 26-1.

TREATMENT Medical management of VN can be divided into acute treatment, chronic treatment, and treatment of concomitant

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BPPV. The conventional treatment of acute-onset VN is supportive care—antiemetics, hydration, and judicious use of vestibular-suppressant medications. In mild cases, meclizine 25 mg PO tid is sufficient, whereas severe cases may benefit more from diazepam either orally or parenterally to suppress vertigo and nausea. Inpatient admission may be justified in some cases due to the severity of vomiting and dehydration. Although vestibular suppressants may benefit the patient during the acute phase of the disease, long-term use of these medications may actually delay central compensation by masking ongoing symptoms. Consequently, tapering of vestibular suppressants should be done as soon as possible after the onset of VN—usually within a week. There is also some evidence that early use of corticosteroids in VN may reduce the intensity and duration of the vertigo and may actually improve overall recovery of function.17 Finally, since VN is felt to be viral in origin, there is a theoretical basis for using antiviral agents early in the disease process although no studies have confirmed their efficacy. Chronic treatment of VN should start soon after the diagnosis is made. Vestibular rehabilitation therapy with or without assistance of a therapist should begin once the patient has been stabilized to help speed central compensation. Exercises that reinforce the vestibulo-ocular reflex and ambulation should be encouraged. Vestibular-suppressant medications should be tapered to prevent symptom masking during central compensation. Most patients will note significant improvement in their symptoms within the first several weeks. However, some symptoms may persist for many months and in some severe cases indefinitely. Persistent symptoms may include disequilibrium with fast head movement, particularly when turning to the affected side. As noted earlier, the appearance of BPPV following the initial episode of VN is not uncommon. Treatment of concomitant BPPV is probably best delayed until the patient has resolved the most severe symptoms of VN. Canalith repositioning with the Epley or Semont maneuvers usually suffice as treatment. Treatment of concomitant BPPV is mandatory to enhance the patient’s chances for full central compensation. Once satisfactory central compensation has occurred, some patients may exhibit “decompensation.” Typically when patients are fatigued or under physical or emotional stress they may exhibit an exacerbation of movementinduced disequilibrium. This will resolve when the fatigue or physical/emotional stress has resolved. Vestibular exercises may mitigate these symptoms. Vestibular suppressants

TABLE 26-1. Comparison of Vestibular Neuritis with Other Common Labyrinthine Disorders

Onset Duration Intensity Hearing loss Recurrence Treatment

Vestibular Neuritis

Labyrinthitis

Ménière’s Disease

BPPV

Acoustic Neuroma

Abrupt Hours Severe None Possible Suppressants Steroids

Abrupt Hours Severe Severe None Suppressants Steroids

Variable Minutes Variable Variable Yes Suppressants Diet, diuretic

Abrupt Seconds Variable None Yes CRP

Slow Days Mild Variable Possible Surgery Observation Gamma RT

BPPV, benign paroxysmal positioning vertigo; CRP, Canalith Repositioning Procedure; RT, Radiation Therapy.

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usually do not help and may exacerbate these symptoms. A Dix-Hallpike exam should be performed during these episodes to ensure these symptoms are not secondary to BPPV.

PROGNOSIS In most cases, VN is a benign self-limited process with an excellent prognosis once the patient recovers from the initial attack. Recovery of balance is generally complete, and alteration of lifestyle is not necessary. In some cases, however, lingering disequilibrium is disturbing and requires ongoing exercise therapy and modification of daily activities. If BPPV develops, it may be recurrent, and repositioning maneuvers may be needed from time to time. Finally, in a few instances, recurrent vertigo attacks develop and require suppressant therapy.

FUTURE DIRECTIONS As the cause and pathophysiology of VN becomes more clearly known, interventional therapy will be aimed at reducing the ultimate amount of injury to the vestibular nerve and end-organ. Clinical trials are necessary to determine the utility of corticosteroid and antiviral therapy early in the course of the disease. Specific virus identification in Scarpa’s ganglion and end-organ tissues in cases of VN will enhance our understanding of whether direct cellular injury or indirect neural and end-organ damage secondary to edema and ischemia is the mechanism of injury.

REFERENCES 1. Ruttin B: Zur Differentialdiagnose der Labyrinth-u. Hornervekrankungen. Z Ohrenheilkd 57:327–331, 1909.

2. Dix M, Hallpike C: The pathology, symptomatology and diagnosis of certain disorders of the vestibular system. Ann Otol 61:987–1016, 1952. 3. Harrison M: Epidemic vertigo-vestibular neuronitis: A clinical study. Brain 85:613–620, 1962. 4. Lumio J, Aho J: Vestibular neuronitis. Ann Otol Rhinol Laryngol 74:264–270. 1965. 5. Boffi A: Positional nystagmus and vertigo in vestibular neuronitis. Laryngoscope 75:484–490, 1965. 6. Lindsay JR, Hemenway WG: Postural vertigo due to unilateral partial vestibular loss. Ann Otol 65:692–708, 1956. 7. Schuknecht HF: Positional vertigo: Clinical and experimental observations. Trans Am Acad Opthalmol Otolaryngol 66:319–331, 1962. 8. Schuknecht HF, Kitamura K: Vestibular neuronitis. Ann Otol Rhinol Laryngol 78(Suppl):1–19, 1981. 9. Zajtchuk JT, Matz GJ, Lindsay JR: Temporal bone pathology in herpes oticus. Ann Otol Rhinol Laryngol 81:331–339, 1972. 10. Friedmann I, House W: Vestibular neuronitis—Electron microscopy of Scarpa’s ganglion. J Laryngol Otol 94:877–883, 1980. 11. Baloh RW, Lopez I, Ishiyama A, et al: Vestibular neuritis: Clinicalpathologic correlation. Otolaryngol Head Neck Surg 114:586–592, 1996. 12. Furata Y, Takasu T, Fukada S, et al: Latent herpes simplex virus type I in human vestibular ganglia. Acta Otolaryngol (Stockh) 519 (Suppl):93–96, 1995. 13. Arbusow V, Schulz P, Strupp M, et al: Distribution of herpes simplex virus type I in human geniculate ganglia; Implications for vestibular neuritis. Ann Neurol 46:416–419, 1999. 14. Fetter M, Dichgans J: Vestibular neuritis spares the inferior division of the vestibular nerve. Brain 119:755–763, 1996. 15. Gacek R, Gacek M: The three faces of vestibular ganglionitis. Ann Otol Rhinol Laryngol 111:103–114, 2002. 16. Goebel J, O’Mara W, Gianoli G: Anatomic considerations in vestibular neuritis. Otol Neurotol 22:512–518, 2001. 17. Kitahara T, Okumura S, Takeda N, et al: Effects of steroid therapy on long-term canal prognosis and activity in the daily life of vestibular neuronitis patients. Nippon Jibiinkoka Gakkai Kaiho 104: 1059–106, 2001.

27

Outline Introduction Epidemiology Microbiology Pathophysiology and Histopathology Signs and Symptoms

Chapter

Otologic and Neurotologic Sequelae of Meningitis

Other Neurologic Abnormalities Testing Treatment Conclusion

Alexis H. Jackman, MD David R. Edelstein, MD

INTRODUCTION

EPIDEMIOLOGY

Meningitis is a major cause of sensorineural hearing loss in both the pediatric and adult populations. Despite recent advancements in its prevention, diagnosis, and treatment, it is still associated with significant neurologic morbidities and mortality. Meningitis remains a major cause of sensorineural hearing loss.1–3 The effect of meningitis on hearing is primarily a direct effect of infection in the inner ear, but compromise of any structures along the auditory pathway of the central nervous system may also play a role. The importance of understanding the disease process is critical to the neurotologist since cochlear implantation has assumed a prominent role in the treatment of postmeningitic sensorineural hearing loss.4 Although the incidence of bacterial meningitis has significantly decreased since the implementation of conjugate Haemophilus influenzae type b vaccine, other forms of bacterial meningitis are still prevalent and are associated with high rates of deafness. Rates of hearing loss have been reported in up to 40% of children with meningitis.2,5,6 Also, as the number of immunocompromised individuals continues to increase, deafness associated with viral and fungal meningitis are increasing in prevalence. The influence of meningitis on speech and language are amplified in prelingually deafened children. A major problem associated with postmeningitic hearing loss is the difficulty of identifying the condition in a young child. Optimum diagnosis and treatment of meningitis continues to change with medical advancements. Once meningitis is diagnosed, the choice of antibiotics becomes a critical decision for the physician and family. In addition, the adjunctive use of steroids continues to be hotly debated. Identification of hearing loss can lead to earlier intervention, such as hearing aid selection and cochlear implantation. Since the degree of cochlear pathology at the time of surgery has surgical and prognostic implications for patients who receive cochlear implants, early coordination with a cochlear implant team is essential if there is a profound bilateral hearing loss.

The development and widespread use of H. influenzae type b vaccine has greatly altered epidemiologic patterns of meningitis. Consequently, the epidemiology of postmeningitic hearing loss reflects this change, yet its impact remains. Wolff and Brown noted in a 1987 study that 9% of children enrolled in special education programs suffered from hearing loss–associated meningitis.3 Presently, meningitis-associated hearing loss is a common indication for cochlear implantation.7 Several types of meningitis exist and the probability of developing a sensorineural hearing loss can often be predicted based the etiology of the disease. Hearing loss is most often attributed to the bacterial form of the disease. Furthermore, the probability of developing a sensorineural hearing loss has been shown to differ among bacterial organisms, Streptococcus pneumoniae having the highest reported incidence of hearing loss.8 Although fungal meningitis rarely occurs, it has been reported to have as high as 43% chance of causing significant hearing loss; whereas, viral meningitis, the most common form of meningitis, is associated with a low rate of hearing loss.9–11 The reported incidence of hearing loss associated with bacterial meningitis has varied over the past 40 years. A major retrospective study in 1978 by Nadol reported that 6% of the 547 participants exhibited hearing loss after meningitis.11 Whereas, Rosenhall and Kankkunen in 1981 reported 30% of the 270 participants developed hearing loss after meningitis.12 A recent meta-analysis of 45 studies with a total of 4920 cases of pediatric meningitis reported hearing loss in 11% of patients, with a severe to profound sensorineural hearing loss of 5%.13 Other studies have reported the percentage of significant hearing loss due to meningitis to be as low as 6% and as high as 40% (Table 27-1). This variation in incidence has been attributed to several factors such as biases in the data collection, sample size, geographic location, and screening for effects of ototoxic medication. 489

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TABLE 27-1. Studies of Incidence of Hearing Loss following Meningitis Date

Author*

1962 1969 1976 1977 1977 1978 1978 1979 1979 1979 1980 1981 1981 1981 1982 1983 1984 1984 1984 1984 1984 1985 1985 1985 1986 1988 1988 1988 1989 1990 1990 1990 1990

Kresky1 Sproles76 Feigin20 Lindenberg57 Jones77 Nadol11 Raivio Keane19 Habib91 Nylen78 Berlow74 Finitzo-Hieber6 Kotagal79 Rosenhall12 Feldman80 Munoz81 Dodge53 Guiscafre41 Kaplan82 Vienny48 MacDonald62 Borkowski46 Baldwin5 Lin83 Edwards84 Lebel59 Dawson86 Smyth87 Lebel & McCracken88 Pomeroy et al89 Schaad et al70 Snedeker91 Taylor et al92

Hearing loss can be defined only among meningitis survivors. Despite advances in treatment, there is still a significant incidence of mortality. A study from Bowman Gray showed the death rate to be 12% in patients with acute meningitis and 31% in a smaller group with chronic meningitis.14 In 1995, the case fatality rate for bacterial meningitis in the United States ranged from 6% for H. influenzae to 21% for S. pneumoniae (Table 27-2).15 In contrast, a recent Canadian study of acute bacterial meningitis in adults in 2000 reported a mortality rate of 18%. In this study, the highest meningitis-related mortality was seen with Listeria monocytogenes of 40% followed by a rate 24% with S. pneumoniae.16 There is a strong possibility that this subgroup would have experienced a high incidence of hearing loss and other neurologic sequelae if these patients had survived.

Cases

Hearing Loss (%)

155 33 50 82 47 547 131 100 775 83 47 86 41 270 44 70 185 236 37 51 34 94 20 58 86 176 145 15 333 191 114 113 97

6 12 6 18 6 6 (12% bacterial, 4% fungal, 0% viral) 22 6 6 18 11 37 12 30 17 31 10 16 (5% chronic) 11 21 (10% chronic) 15 18 40 33 8 26 10 17 14 10 10 11 8

Another reason for possible underreporting of meningitisrelated hearing loss is unidentified unilateral hearing loss. The incidence of unilateral and bilateral meningitis has also varied in several studies. Henneford and Lindsay reported a 5% incidence of bilateral hearing loss versus Nadol’s reporting a 77% incidence of bilateral hearing loss.11,17 This loss often remains undetected unless the affected ear or the contralateral ear undergoes additional otologic insult that necessitates hearing testing. The effect of the patient’s age on the incidence of meningitis-associated hearing loss is also debated. Twentyone percent of children older than 2.5 years exhibited a sensorineural hearing loss compared with only 5% of children younger than 2.5 years.11 Similarly, Vernon reported a high incidence of multiple neurologic sequelae in addition to deafness among children younger than 18 months old

TABLE 27-2. Causes of 248 Cases of Bacterial Meningitis in 1995 and Overall Cases Fatality Rate According to Organism Organism H. influenzae S. pneumoniae N. meningitides Group B streptococcus L. monocytogenes

No. Cases Reported 18 117 62 31 20

Percentage of Total 7 47 25 12 8

From Schuchat A, et al: Bacterial meningitis in the United States in 1995. N Engl J Med 337:970, 1997.

Incidence 0.2 1.1 0.6 0.3 0.2

Case Fatality Rate (%) 6 21 3 7 15

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who contracted meningitis.2 However, Ozdamar, Kraus, and Stein found a lack of statistical significance to age or prematurity on the probability of developing a hearing loss after meningitis.18 There is some question as to the correlation of sex with the incidence of hearing loss. Keane and colleagues, for example, reported a male preponderance of 1.4 to 1 in the younger than 1 age group.19 Similarly, in Vernon’s classic study boys outnumber the girls 82 to 32.2 Feigin and colleagues also reported a male-to-female ratio of 62% to 38%.20 In contrast, however, Nadol, Ozdamar, and others have not confirmed this sex distribution, nor has any other researcher proposed a convincing explanation for such a sex-related pattern of hearing loss.11,21

organism, making it now the fourth most common cause of meningitis in adults.25 Its prevalence among patients who have deficits in cell-related immunity, such as in patients with human immune deficiency syndrome or hematologic abnormalities, has been noted.26,27 As the number of immunocompromised individuals increases, more cases of viral and fungal meningitis and meningitis-related hearing loss are being reported. Postviral meningitis–associated hearing loss, although not as common as bacterial-associated hearing loss, does occur. The neurotropic nature of viruses such as herpes simplex and human immunodeficiency virus (HIV) are well known and their presence in the cochlea and the eighth cranial nerve has been demonstrated.28

MICROBIOLOGY

PATHOPHYSIOLOGY AND HISTOPATHOLOGY

Meningitis may be caused by many bacterial and fungal organisms as well as by several viral strains. Historically, meningitis was a disease of infancy and childhood and was most commonly due to bacterial organisms such as H. influenzae and S. pneumoniae. Other well-known causes of bacterial meningitis include Neisseria meningitidis, L. monocytogenes, Staphylococcus aureus, and group B streptococcus. The relative importance of different pathogens among various age groups continues to be seen in population studies, but the predominance of various organisms within these groups has changed in the recent past. Twenty years ago, H. influenzae type b (HiB) meningitis developed in 1 in 200 children younger than 5 years and accounted for 70% of bacterial meningitis in this age group.22 In December 1987, HiB conjugate vaccines were licensed for routine use. Its widespread use in preschoolage children has lead to dramatic declines in diseases caused by HiB, reportedly up to 94%, and the hope for eradication of the disease due to HiB now seems an attainable goal.23 Consequently, infants and children, the group HiB most affected, are no longer the age groups most commonly associated with meningitis and meningitisrelated hearing loss. In a multistate surveillance study of bacterial meningitis in 1995, the median age of patients with bacterial meningitis had risen from 15 months in 1986 to 25 years, and S. pneumoniae replaced H. influenzae as the most common pathogen. The most prevalent pathogen in neonatal meningitis remained Streptococcus agalactiae (group B streptococcus). However, in infants 1 to 23 months old, S. pneumoniae and N. meningitidis have replaced H. influenzae as the predominant organism in this age group, accounting for 45% and 31% of cases, respectively. N. meningitidis has also replaced H. influenzae as the most common pathogen in the 2 to 18 years age group and N. meningitidis was reported to cause of 59% cases in this age group. In the over 19 age group, S. pneumoniae was the most common bacteria (62% of cases).15 It is also important to consider less common causes of meningitis, which may have a regional or seasonal occurrence such as Lyme neuroborreliosis.24 Neuroborreliosis presenting as encephalitis or meningitis is more common in the European form of this disease. The incidence of L. monocytogenes is increasing in incidence with up to 12.5% of adult cases caused by this

The most prevalent etiology of hearing loss associated with meningitis results from an inflammatory labyrinthitis initiated by an infectious pathogen via the cochlear aqueduct. The inflammatory infiltrate is then replaced by fibrous tissue and cellular debris, and subsequently, neoossification within the cochlea occurs. The end result, termed cochlear ossificans or labyrinthitis ossificans, is the pathological hallmark of meningitis-related sensorineural hearing loss. Several authors have reported on histopathologic changes in the temporal bone after meningitis. Schuknecht presented seven cases of pneumococcal meningitis that caused a variety of pathologic findings including widespread inflammation of the pneumatized spaces of the temporal bone, large pacchionian bodies in the posterior cranial fossa extending into the mastoid, and a suppurative labyrinthitis with pus in the cochlear aqueduct and vestibule.29 Igarashi described destruction of the stria vascularis and massive hemorrhage in the cochlear duct. He postulated that primary bacterial endolymphatic involvement could occur not only in suppurative labyrinthitis but also in the serous form via destruction of local vessels. He highlighted the presence of large amounts of inflammatory cells along all the nerves of the internal auditory canal. Inflammation was noted in the spiral ganglion cells, the loose perivascular tissue, the modiolus, and directly in the endolymphatic space via Reissner’s membrane or the basement membrane.30,31 Keithley and Harris demonstrated the sequential cellular changes in the cochlea in response to a viral pathogen in animal models. Lymphocytes, macrophages, and polymorphonuclear cells and other inflammatory cells entered the cochlea and caused variable degrees of structural damage, although hair cells were identified. Later changes in the cochlea included fibrotic tissue, blood vessels, and ectopic bone, which was shown to persist even after the viral particles were cleared.32 Similar cellular changes have been seen in response to bacterial meningitis in an animal model using S. pneumoniae. Evidence for bacterial spread via the cochlear aqueduct in meningitis was also demonstrated as the most intense inflammatory response and greatest amount of ossification occurred in the scala tympani of the basal turn of the cochlea, where the cochlear aqueduct joins the cochlea.33 Temporal bone studies using

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electron microscopy and immunohistochemistry of HIV were preformed by Roland and colleagues. Fibrotic changes in the spiral lamina, basilar membrane, and external spiral ligament were demonstrated as well as budding viral particles.28 Other causes of hearing loss can occur anywhere along the neural peripheral and central auditory pathway. Septic emboli can be transmitted via the vertebrobasilar system and arrest end organ blood flow to the cochlea. Leichenger reported on a case of deafness in the presence of meningococcemia without evidence of meningitis, demonstrating the potential effect of septicemia on the cochlea.34,35 Also, there may be a local neuritis of the eighth cranial nerve as it runs in the internal auditory canal with an inflammatory infiltrate interrupting neuronal impulse transmission. Hearing loss from central auditory pathway dysfunction can result from local edema or leukocytic infiltration in the auditory pathway or cortex. Brainstem dysfunction following meningitis is a known cause of multiple neurologic disorders associated with meningitis and is postulated to result from increased intracranial pressure or hydrocephalus. The pressure in the ventricles may promote prolongation of waves I to V on auditory brainstem response (ABR) testing. Additionally, seizures associated with meningeal irritation and fever and associated hypoxia can also predispose these patients to hearing loss. Another possible route of spread for meningitis-related hearing loss is from the middle ear following otitis media via the round or oval window depending on which site had the predominant degree of inflammatory infiltrate.36,37 Children with congenital malformations of the inner ear, such as Mondini’s dysplasia, may be predisposed to meningitis following middle ear infection. Congenital abnormalities of the inner ear may be associated with cerebrospinal fluid leakage by pathologic interconnections via the internal auditory canal, the cochlear aqueduct, the oval window, or the round window.38,39 Meningitis is a known complication of temporal bone fractures. The callus formation at the fracture site is not replaced by bone and provides infectious pathogens a pathway to the central nervous system (CNS). Once in the CNS, pathogenic spread to the cochlea can occur via the cochlear aqueduct or via bony defects between the CNS and the inner ear, resulting in an inflammatory response and sensorineural hearing loss. Three cases from the Temporal Bone Collection of the House Ear Clinic help to demonstrate the effects of bacterial meningitis on the inner ear. The first case involved a young adult who developed meningitis as a result of a skull fracture. He presented with mastoiditis in one ear, which spread to the contralateral inner ear via the CNS as a result of meningitis. Figures 27-1 through 27-4 demonstrate the purulent accumulation in the cochlea and stria vascularis. The second case was of a young woman who died of a brain abscess as a complication of chronic otitis media. Figure 27-5 shows the contralateral ear and cellular infiltration of the internal auditory canal and scala media. The third case involved a 66-year-old man who also died from meningitis. Figures 27-6 and 27-7 show pus cells in the ganglion tissue and nervous infiltration by inflammatory cells. The timing and degree of labyrinthitis ossificans are unpredictable and vary from case to case. Auditory involvement has been reported to occur usually in the first 24 to

Figure 27-1. Temporal bone specimen of a patient with meningitis shows an inflammatory infiltrate in the scala vestibuli and scala media especially in the basal turn.

48 hours, although delayed hearing loss can occur.40,41 It has been theorized that the reason for the initial hearing loss may be local inflammation or immediate vasospasm. Reports of long-term or delayed hearing loss following meningitis may be due to either slow disruption of cochlear hair cells or degeneration of the brainstem.42

SIGNS AND SYMPTOMS Physicians are faced with three diagnostic pictures involving meningitis. First is the patient with otitis media who develops lethargy, headaches, nausea, and severe otalgia. In this case, the physician is already attuned to the many possibilities of hearing loss. Second are the patients with meningitis who need a complete otolaryngologic workup to determine the cause or source of infection. Third is the child with meningitis with a nonotologic cause or no known cause who needs a thorough hearing and age-appropriate vestibular evaluation and follow-up. Children with otitis media should be monitored for the development of not only mastoiditis but also such other

Figure 27-2. Photomicrograph is taken at 55 power near the round window at the exit of the cochlear aqueduct showing pus cells filling the aqueduct and extending into the basal turn of the cochlea. (From Schuchat A, et al: Bacterial meningitis in the United States in 1995. N Engl J Med 337:970, 1997.)

Otologic and Neurotologic Sequelae of Meningitis

Figure 27-3. A larger view of the anterior basal turn showing pus in the two scalae. (From Gary N, Powers N, Todd JK: Clinical identification and comparative prognosis of high-risk patients with H. influenzae meningitis. Am J Dis Child 143:307, 1989.)

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Figure 27-5. Pus in the internal auditory canal. There are some fibrotic changes and inflammatory cells in the scala media.

intracranial complications as meningitis, brain abscess, otic hydrocephalus, lateral sinus thrombosis, and subdural abscess. The common symptoms of meningitis include stiff neck, abnormal vision (blurring and diplopia), tremor, ataxia, and seizures. Common signs that should be investigated include papilledema, dysmetria, hemianopsia, abnormal eye movements, abnormal Romberg and gait, and other neurologic abnormalities.43 In a paper from the Children’s Hospital of Denver, a system called the Herson-Todd scoring method was devised to predict hearing loss in certain high-risk patients with meningitis due to H. influenzae (see Table 27-3). The criteria included coma, hypothermia, seizures, shock, age, cerebrospinal fluid (CSF) white blood cell count, hemoglobin CSF glucose, and symptoms lasting more than 3 days. Outcome parameters included cognitive, motor, clinical, speech, hearing, and visual factors.44,45 All of these factors should be documented in the patient’s record. The most common type of hearing loss following meningitis is a sensorineural loss, although a conductive component may be present initially due to concurrent

middle ear disease. Ozdamar, Kraus, and Stein found that 64% of patients with meningitis had normal or borderline hearing, 16% had a conductive loss, and 22% had a sensorineural hearing loss.18 Predictably, conductive hearing loss was largely related to the presence of otitis media. A correlation analysis revealed the presence of a sensorineural hearing loss to be statistically related to both the pathogen involved and a hospitalization longer than 14 days. Similarly, Borkowski and colleagues reported on a group of 94 children with meningitis in which 44% had normal hearing, 18% had a sensorineural hearing loss, 17% had a conductive hearing loss, 11% had mixed losses, 9% had retrocochlear pathology, and 1% were identified as other or unknown.46 Fluctuating and delayed hearing loss have both been described by Rosenhall and Kankkunen.12 In a series of 327 patients followed for 3 years, Trolle found no cases of fluctuating hearing.47 However, in a series of 236 patients followed for 6 months, Guiscafre and colleagues found 28 patients with fluctuations in their sensorineural hearing loss.41 Vienny and colleagues also found in their series that 68% of the patients had normal hearing, 22% had transient

Figure 27-4. High-power view of the organ of Corti demonstrating its disintegration as well as some changes in the stria vascularis.

Figure 27-6. Pus in Rosenthal’s canal and in the perilymph of the scala vestibuli. The inflammatory cells are scattered among the ganglion cells and in the adjacent tissue.

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NEUROTOLOGIC MANIFESTATIONS OF NEUROLOGIC DISEASE

Figure 27-7. This auditory nerve has been invaded by many purulent cells.

changes, and only 10% had early and persistent hearing loss.48 Similar findings have been recorded by several other authors.18 Rosenhall and Kankkunen reported cases of delayed hearing loss after a normal hearing interval between 6 and 12 months.12 Several configurations of hearing loss have been reported. In Brookhauser’s series, 53% of the children with meningitis had a sensorineural hearing loss, of which 83% had a bilateral profound hearing loss, 14% had a moderate hearing loss, and 3% had a mild hearing loss. In the better hearing ear, there was fairly even distribution of sharply sloping flat, through-shaped, and rising hearing.49 In Vernon’s classic work on prematurity and deafness, he compared the various causes of deafness and found meningitis to result in the largest average level of hearing loss (93 dB) compared with such other causes as genetics (88 dB), prematurity (83 dB), rubella (82 dB), and kernicterus (76 dB).2

OTHER NEUROLOGIC ABNORMALITIES Before the introduction of antibiotics, up to 60% of the children with meningitis developed either brain damage or some other form of serious neurologic dysfunction.1 Since the 1950s, the incidence of neurologic sequelae after meningitis has ranged from 10% to 30%.50 The major neurologic sequelae include retardation, seizures, and TABLE 27-3. Scoring System for Prediction of Morbidity in H. Influenzae Meningitis Factor at Admission Severe coma Hypothermia Seizures Shock Age <12 months CSF white blood cell count <1000 × 10/L Hemoglobin <110 g/L CSF glucose <1.1 mmol/L Symptoms persisting >3 days

Points 3 2 2 1 1 1 1 0.5 0.5

From Gary N, Powers N, Todd JK: Clinical identification and comparative prognosis of high-risk patients with H. influenzae meningitis. Am J Dis Child 143:307, 1989.

ataxia. One of the challenges facing the clinician is to identify these problems systematically in order to better focus on treatment and rehabilitation. Historically the number of serious neurologic problems experienced after recovery from meningitis was large. In Trolle’s study from 1920 to 1945, he identified a prechemotherapy rate of 54% (41% of these neurologic sequelae were severe), which dropped to 50% after the early introduction of sulfonamides and penicillin (17% severe).47 Similarly, in studies from the late 1940s and early 1950s, Crook, Smith, and others identified a 12% to 19% incidence of serious neurologic sequelae.51,52 In 1963, Dodge and Swartz presented a series in which 44% of the patients with H. influenzae meningitis experienced seizures, 12% went into profound coma, and 18% developed ocular movement dysfunction, and some died from cerebral edema.53 Nadol reported that 21% of meningitis survivors had at least one nonotologic neurologic complication.11 Seizures are a common problem in patients who have meningitis with rates of up to 31%. Seizures included both generalized and focal and several patients experienced prolonged episodes of status epilepticus.53 Ataxia and other symptoms of vestibular dysfunction have also been described as a both short- and long-term sequelae of meningitis. Farmer in 1945 reported on unilateral and bilateral vestibular involvement in children with meningococcal meningitis.54 Schwartz reported several children who had ataxia before treatment and two who developed ataxia without other vestibular abnormalities.55 The ataxia was most likely cerebellar. Some of these patients could have also developed ataxia due to use of streptomycin. In one series, eight children with postmeningitic ataxia were reported. Of the seven children who were tested, electronystagmography was abnormal in three, and all of the children had a gradual improvement in their ataxia.56 Lindberg and colleagues reported that 12% of the 82 children in their study developed temporary ataxia.57 Several other cranial neuropathies have been reported. Dodge and Swartz best described the many focal signs of cerebral dysfunction. Among the 147 cases in their study were 3 cases of dysphagia, 8 cases of disconjugate gaze, 3 cases of visual defects, 10 episodes of hemiparesis, and 6 cases of paraplegia. Many of these complications may be due to multiple factors including heightened intracranial pressure, generalized cerebral swelling, and purulent material in the ventricles and subarachnoid space.53 Meningitis is also a leading cause of brain damage in children. In early studies, major neurologic sequelae were reported to affect between 15% and 71% of meningitis patients. The percentage of deafness associated with other major neurologic problems was reported by Vernon to be as high as 28%. These associated problems included cerebral palsy, aphasia, mental retardation, and emotional disturbances. The prevalence of multiple disturbances was as high as 38%. He reported that children younger than 1 year were most susceptible to these sequelae and that 35% of postmeningitic deaf children had an IQ level lower than 90.2 Sell and colleagues in 1971 attempted to study two groups of children: one with meningitis and a second matched pair or a near-age sibling. They found that based on several test methods, the postmeningitic child had a greater chance of having a low IQ and other psychological sequelae.58

Otologic and Neurotologic Sequelae of Meningitis

TESTING Patients with meningitis usually undergo many tests during their hospital stay. The normal workup includes a physical examination, lumbar puncture, multiple blood tests, and a basic neurologic and infectious disease review. In a recent study of adult bacterial meningitis in 100 patients, Huessein and colleagues found almost all patients (97%) presented with fever higher than 37.7°C, 87% of patients had nuchal rigidity, and 51% had a decreased level of consciousness.16 Radiographs and magnetic resonance imaging (MRI) may help to identify the source of infection and possible intracranial complications. However, computed tomography (CT) scans do not yield additional information useful in prognosticating the outcome of the disease.59 Hearing tests should be performed as soon as the patient has been stabilized. Unfortunately, audiograms are often delayed to end of the hospitalization because of the needs of these sick children in the intensive care unit. Follow-up audiograms are just as important as the initial studies. Tests should be performed promptly if there is a questionable hearing loss. After hospital discharge, hearing tests should be repeated every 3 to 6 months until hearing has stabilized because both delayed deterioration and recovery of hearing are possible.12 One challenge of otologists is assessing the neonatal or infant patient with meningitis who needs a hearing evaluation. Although traditional cribigrams and play audiometry offer good screening tools, they are rough tests and do not localize the side of loss and can miss significant fluctuations in hearing. In 1971, Jewett and Williston suggested the use of ABR testing as a major advance in testing young children or patients with serious neurologic damage who would not comply with the usual audiometric protocols.60 Thresholds in the higher frequencies are similar in the traditional clickspecific ABR. In these tests, wave 1 may be used to monitor the integrity of the auditory nerve with the remaining waves monitoring the brainstem auditory pathway. Absolute latencies, interwave latencies, and latency shifts can be used to identify cochlear pathology, hypoxic encephalopathy, intracranial hemorrhages, demyelination, and other brainstem abnormalities.61,62 Several authors have used ABR tests to monitor hearing loss in their patients with meningitis. In 1981, FinitzoHieber, Simhardi, and Hieber demonstrated the importance of using ABR by identifying 14% more children suffering from unilateral hearing loss following meningitis than would have been identified by standard audiometric techniques.6 Similarly, by using ABR, Ozdamar, Kraus, and Stein were able to identify hearing abnormalities in 37% of children included in the 1983 study. Of this group, 15% had conductive hearing loss and 22% had sensorineural hearing loss (10% had brainstem neuropathology).18 In 1984, Vienny and colleagues studied 51 children prospectively with ABR; 69% had normal recordings, 22% showed transient abnormalities, and 9% had persistent auditory pathology.48 MacDonald and Feinstein in 1984 found a 62% agreement between standard conditioned orienting response testing (COR) and ABR. They concluded that ABR was more effective than COR for testing infants younger than 6 months, children with significant handicaps, and patients with unilateral hearing loss. They

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recommended that ABR tests be performed either when the child is recovering or at least 1 week following the beginning of the antibiotic therapy.62 One limitation of traditional click-stimulus ABR is an inability to identify hearing loss in the low- or middle-range frequencies. In 1988, Brookhauser, Auslander, and Meskan highlighted this conflict. They noted that postmeningitic hearing loss could have a “wide array of audiometric configurations,” not all of which could be easily outlined by ABR.49 Frequency-specific ABR and pure tone audiograms become critical in these patients. They also emphasized the importance of the audiologist’s impressions regarding the test reliability in determining the type of test and repetition of testing necessary per patient. Newer techniques using otoacoustic emission testing may also be helpful with the young or uncooperative child or infant. If the patient has been identified as a potential cochlear implant candidate, additional radiographic testing is usually requested. Although high-resolution computed tomography (HRCT) is traditionally used in cochlear implantation, a high-resolution fast spin-echo T2-weighted MRI scan of the temporal bone has been shown to be advantageous in postmeningitic patients for its ability to detect cochlear fibrosis, which can be undetected by HRCT.63 Therefore, a temporal bone MRI is often part of the preoperative workup in postmeningitic patients.

TREATMENT Children with meningitis may present with either a mild febrile illness with neck stiffness or a profound illness with seizures, coma, and disseminated intravascular coagulation. Both groups need aggressive treatment and intensive care monitoring after the diagnosis is made. Since the introduction of antibiotics, the principal debate regarding the treatment of meningitis has concerned the choice of antibiotics and the possible use of steroids in diminishing complications. Fluid management and frequent neurologic evaluations are also essential. The first priority in the treatment of meningitis is the initiation of antimicrobial therapy, which usually begins with empiric therapy until Gram stain and culture results are available. Decisions regarding empiric therapy are based on probable types of organisms and their known patterns of antibacterial resistance as well as on factors that affect the bactericidal activity of an antibiotic in the cerebrospinal fluid. Optimal antibiotic therapy requires that the drug have a bactericidal effect in the cerebrospinal fluid because specific antibody and complement factors are frequently absent in this immunologically deficient site. Major factors that influence bactericidal activity in the CSF include degree of CNS penetration, concentration in the CNS, and the antibiotic’s intrinsic activity. The advantages of third-generation cephalosporins include their increased antibacterial activity, increased CSF penetration, and expanded spectrum against β-lactamase organisms and gram-negative enteric bacilli as well as a reduced toxicity compared with chloramphenicol and aminoglycosides. The age of the patient as well the health status and immunization records of the patient will direct the clinician toward the most likely organisms. For example, for a

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nonimmunized 3-year-old child, antibiotic coverage should be obtained for H. influenzae, N. meningitidis, and S. pneumoniae. In the case of a 50-year-old patient receiving cytotoxic chemotherapy for leukemia, treatment should include coverage for Listeria and gram-negative organisms as well as for S. pneumoniae. After identification of the probable causative organism, knowledge of current patterns of antimicrobial resistance is critical. A worldwide increase in antimicrobial resistance strains of S. pneumoniae has been documented. Resistance of S. pneumoniae is mediated by alterations in penicillinbinding proteins involved in the synthesis of bacterial cell walls.64 In a 10-month surveillance study of S. pneumoniae in Atlanta, Georgia, in 1994, 25% of patients with invasive pneumococcal infection were resistant to penicillin and 9% of those were also resistant to cefotaxime.65 Presently, S. pneumoniae remains sensitive to vancomycin, which is the recommended therapy with presumed antibiotic resistance S. pneumoniae. If H. influenzae is suspected, the high prevalence of β-lactamase-resistant strains require empiric treatment with a third-generation cephalosporin such as cefotaxime. Fortunately, most strains of N. meningitidis are sensitive to ampicillin, although isolates with penicillinbinding proteins have been identified in the United States, Europe, and South Africa.66–68 In these cases, a second- or third-generation cephalosporin can be used. The interval between the first signs of meningitis and the beginning of antibiotic therapy may affect the clinical and audiologic outcomes. Nadol reported that for children who suffered no hearing loss, the average time to treatment was 32 hours compared with 47 hours for those who sustained a hearing loss.11 Others have confirmed his result, including Vienny and colleagues, who found that most hearing loss associated with meningitis occurs early in the course of the disease.48,69 A recent study compared the audiologic outcomes of cefuroxime and ceftriaxone in order to elucidate if the time to CSF sterilization had any effects on hearing. The group, which received ceftriaxone, which is known to more rapidly sterilize CSF, was found to have a 17% less frequent moderate to profound hearing loss than the cefuroxime group.70 However, Dodge and colleagues pointed out in 1984 that it can be difficult to determine the time when meningitis begins.69 Although early antibiotic intervention is a priority in the treatment of any infection, the literature on the relationship of the timing of treatment of meningitis with long-term results remains controversial. Adjuncts to antibiotic treatment of meningitis have been a focus of widespread study and speculation. In Dodge and Swartz’s landmark work in 1963, they suggested the use of high-dose corticosteroids to decrease the high CSF pressure associated with meningitis.53 Other actions of steroids in meningitis include decreasing brain edema, decreasing prostaglandin concentrations, and inhibiting arachidonic acid formation. It may also reduce the concentration of lactate and protein and increase glucose in the CSF. Several case reports of glucocorticoid therapy were presented with good results. In 1969, two independent studies by DeLemos and Haggerty and Belsey, Hoffpauir, and Smith failed to show beneficial effects of steroids on the outcome of meningitis.71,72 In this study the incidence of long-term neurologic effects was high among the patients

who received steroids. Unfortunately, hearing was not monitored as an outcome parameter. Eden and Cummings in 1978 and Berlow and colleagues in 1980 reported the possibility of reversing the hearing loss of patients with meningitis if they are treated with steroids.73,74 The best study of this subject was undertaken by Leben and colleagues in 1988 when two double-blind placebo-controlled trials in children with bacterial meningitis were performed. In one study cefuroxime was used and in the second ceftriaxone was used and both were combined with either a placebo or steroid. Lebel and colleagues found that the patients who were treated with steroids had less moderate or severe bilateral hearing loss than the placebo group. Fifteen percent of the patients in the placebo group had bilateral sensorineural hearing loss compared with only 3% of the recipients of dexamethosone.59 Gary, Powers, and Todd in 1989 reported that children with high Henson-Todd scores who were given steroids had a better outcome than those who did not receive steroids.14 Once culture and sensitivity results are available, therapeutic treatment can be tailored to these results, but it is also essential to try to identify the underlying cause of the meningitis. The otolaryngologist should not lose sight of his or her role in identifying middle ear effusions or other possible otologic causes. In many patients, particularly children, the underlying cause may be an upper respiratory infection or a middle ear infection. Rapid drainage and culturing of these sources will help both to relieve the inciting infection and to identify the pertinent organisms and their sensitivities. Patients with mastoiditis should undergo a complete mastoidectomy once antibiotics have been started and the patient is considered stable. In some individuals, HRCT scanning of the temporal bone may detect a congenital cochlear abnormality or a traumatic break in the bony barriers between the cerebrospinal space and the environment. Unfortunately, the otologic cause of meningitis often goes unrecognized. Gower and McGuirt found, for example, that only 22% of patients with a CNS complication of ear disease had a complete otologic evaluation.75

CONCLUSION Meningitis remains a serious cause of hearing loss and other neurologic disorders. Advances in the antibiotic development over the last 40 years have diminished the incidence of the disease and lessened the chance of death. Over the last 15 years, the greatest advance in reducing the prevalence of meningitis has come from the new vaccines. Nevertheless, the incidence of temporary and permanent hearing loss remains high in these patients, and cochlear implantation remains the treatment of choice for many patients with severe to profound hearing loss. Otologists often observe meningitis as a result of otitis media. Early recognition of signs of meningismus and prompt intervention with antibiotics and steroids may alleviate or lessen long-term neurologic sequelae. Every patient should have a full otolaryngologic and audiologic evaluation in addition to medical and neurologic workups. Close follow-up collaboration among the otologist, implant team, and medical teams provides the best care and outcome in patients with meningitis-related hearing loss.

Otologic and Neurotologic Sequelae of Meningitis

REFERENCES 1. Kresky B, Buchbinder S, Greenberg IM: The incidence of neurological residua in children after recovery from bacterial meningitis. Arch Pediatr 79:63, 1962. 2. Vernon M: Meningitis and deafness: The problem, its physical, audiological, psychological, and educational manifestations in deaf children. Laryngoscope 77:1856, 1967. 3. Wolff AB, Brown SC: Demographics of meningitis-induced hearing impairment: Implications for immunization of children against Hemophilus influenzae type b. Am Ann Deaf 132:26, 1987. 4. Quagliarello VJ, Scheld WM: Drug therapy: Treatment of bacterial meningitis. N Engl J Med 336:708, 1997. 5. Baldwin RL, Sweitzer RS, Friend DB: Meningitis and sensorineural hearing loss. Laryngoscope 95:802, 1985. 6. Finitzo-Hieber T, Simhardi R, Hieber JP: Abnormalities of the auditory brainstem response in post-meningitic infants and children. Int J Pediatr Otorhinolaryngol 3:275, 1981. 7. Telian SA, Zimmerman-Phillips S, Kilney PR: Successful revision of failed cochlear implants in severe labyrinthitis ossificans. Am J Otol 17:53, 1996. 8. Eisenberg LS, Luxford WM, Becker TS, House WF: Electrical stimulation of the auditory system in children deafened by meningitis. Otolaryngol Head Neck Surg 92:700, 1984. 9. Adair CV, Gauld RL, Smadel JE: Aseptic meningitis, a disease of diverse etiology: Clinical and etiologic studies of 854 cases. Ann Int Med 39:675, 1953. 10. Adams RD, Kublik CS, Bonner FJ: The clinical and pathological aspects of influenzal meningitis. Arch Pediatr 65:354, 1948. 11. Nadol JB Jr: Hearing loss as a sequela of meningitis. Laryngoscope 88:739, 1978. 12. Rosenhall U, Kankkunen A: Hearing alterations following meningitis: 2. Variable hearing. Ear Hear 2:170, 1981. 13. Baraff LJ, Lee SI, Schriger DL: Outcomes of bacterial meningitis in children: A meta-analysis. Pediatr Infect Dis J 12:389, 1993. 14. Gary N, Powers N, Todd JK: Clinical identification and comparative prognosis of high-risk patients with Haemophilus influenzae meningitis. Am J Dis Child 143:307, 1989. 15. Schachat A, Robinson K, Wenger JD, et al: Bacterial meningitis in the United States in 1995. N Engl J Med 337:970, 1997. 16. Hussein AS, Shafran SD: Acute bacterial meningitis in adults: A 12-year review. Medicine 79:360, 2000. 17. Henneford GE, Lindsay JR: Deaf-mutism due to meningogenic labyrinthus. Laryngoscope 78:251, 1968. 18. Ozdamar O, Kraus N, Stein L: Auditory brainstem responses in infants recovering from bacterial meningitis. Arch Otolaryngol 109:13, 1983. 19. Keane WM, et al: Meningitis and hearing loss in children. Arch Otolaryngol 105:39, 1979. 20. Feigin RD, et al: Prospective evaluation of treatment of hemophilus influenzae meningitis. J Pediatr 88:542, 1976. 21. Ozdamar O, Kraus N: Auditory brainstem response in infants recovering from bacterial meningitis: Neurologic assessment. Arch Neurol 40:499, 1983. 22. Cochi SL, Broome CV, Hightower AW: Immunization of US children with Hemophilus influenzae type B polysaccharide vaccine: A cost-effectiveness model of strategy assessment. JAMA 253:251, 1985. 23. Adams WG, Deaver KA, Cochi SL, et al: Decline of childhood Haemophilus influenzae type b (Hib) disease in the HiB vaccine era. JAMA 269:221, 1993. 24. Christen HJ: Lyme neuroborreliosis in children. Ann Med 28:235, 1996. 25. Schwartz B, Robinson ZK, Wegner JD, et al: Bacterial meningitis in the United Stated in 1995. N Engl J Med 337:970, 1997. 26. Lorber B: Listeriosis. Clin Infect Dis 24:1, 1997. 27. Mylonakis E, Hohmann EL, Calderwood SB: Central nervous system infection with Listeria monocytogenes: 33 years’ experience at

28. 29. 30.

31. 32. 33. 34. 35. 36. 37.

38. 39. 40.

41.

42. 43. 44. 45. 46. 47. 48.

49. 50. 51. 52. 53.

54. 55. 56. 57.

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a general hospital and review of 776 episodes from the literature. Medicine 77:313, 1998. Roland JT, Alexiades G, Jackman AH, et al: Cochlear Implantation in HIV infected patients. Otol Neurotol 24(6):892, 2003. Schuknecht HF: The ear in pneumococcal meningitis. Ann Otol 80:397, 1971. Igarashi M, Schuknecht HF: Pneumococcic otitis media, meningitis, and labyrinthitis, a human temporal bone report. Arch Otolaryngol 76:126, 1962. Igarashi M, et al: Temporal bone findings in pneumococcal meningitis. Arch Otolaryngol 99:79, 1974. Keithley EM, Harris JP: Late sequelae of cochlear infection. Laryngoscope 106:341, 1996. Bhatt S, Halpin C, Hsu W, et al: Hearing loss and pneumococcal meningitis: An animal model. Laryngoscope 101:1285, 1991. Leibman EP, et al: Hearing improvement following meningitis deafness. Arch Otolaryngol 90:92, 1969. Leichenberg H, Abelson SM: Deafness associated with meningococcemia. Arch Otolaryngol 26:306, 1937. Paparella MM, Sugiura S: The pathology of suppurative labyrinthitis. Ann Otol Rhinol Laryngol 76:554, 1967. Suzuki, C, Sando I, Fagan JJ, et al: Histopathological features of cochlear implant and otogenic meningitis in Mondini dysplasia. Arch Otolaryngol Head Neck Surg 124:462, 1998. Ohlms LA, et al: Recurrent meningitis and Mondini dysplasia. Arch Otolaryngol Head Neck Surg 116:608, 1990. Parisier SC, Birken E: Recurrent meningitis secondary to idiopathic oval window CSF leak. Laryngoscope 86:1, 1976. Yuan-ch’eng T, Juei-hua L, Yin-hsiang H: Meningitis and deafness: Report of 337 cases of deafness due to cerebrospinal meningitis. Chinese Med J 81:127, 1962. Guiscafre H, et al: Reversible hearing loss after meningitis: Prospective assessment using auditory evoked responses. Ann Otol Rhinol Laryngol 93:229, 1984. Silkes ED, Chabot J: Progressive hearing loss following Haemophilus influenzae meningitis. Int J Ped Oto 9:249, 1985. Powell KR: Meningitis. In Hoekelman RA, et al (eds.): Primary Pediatric Care, 2nd ed. St. Louis, Mosby Year Book, 1992, p 1352. Gantz B, McCabe B, Tyler R: Use of cochlear implants in obstructed and obliterated cochleas. Otolaryngol Head Neck Surg 98:72, 1988. Herson VC, Todd JK: Prediction of morbidity in hemophilus influenzae meningitis. Pediatrics 59:35, 1977. Borkowski WJ, et al: Cerebrospinal fluid parameters and auditory brainstem responses following meningitis. Pediatr Neurol 1:134, 1985. Trolle E: Defective hearing after meningococcal meningitis. Acta Otolaryngol 38:384, 1950. Vienny H, et al: Early diagnosis and evolution of deafness in childhood bacterial meningitis: A study using brainstem auditory evoked potentials. Pediatrics 73:579, 1984. Brookhauser PE, Auslander MC, Meskan ME: The pattern and stability of postmeningitic deafness. Laryngoscope 98:940, 1988. Hutchison PA, Kovacs MC: The sequelae of acute purulent meningitis in childhood. Can Med Ass J 89:158,1963. Crook WG, Clanton R, Hodes HL: Hemophilus influenzae meningitis. Pediatrics 4:643, 1949. Smith ES: Purulent meningitis in infants and children: A review of 409 cases. J Pediatr 45:425, 1954. Dodge PR, Swartz MN: Bacterial meningitis: A review of selected aspects II. Special neurologic problems, postmeningitis complications and clinicopathological correlations. N Engl J Med 272:954, 1963. Farmer TW: Neurologic complications during meningococcic meningitis treated with sulfonamide drugs. Arch Int Med 76:201, 1945. Schwartz JF: Ataxia in bacterial meningitis. Neurology 22:1071, 1972. Kaplan SL, et al: Ataxia and deafness in children due to bacterial meningitis. Pediatrics 68:8, 1981. Lindenberg J, et al: Long-term outcome of hemophilus influenzae meningitis related to antibiotic treatment. Pediatrics 60:1, 1977.

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58. Sell SHW, et al: Psychological sequelae to bacterial meningitis: Two controlled studies. Pediatrics 49:212, 1972. 59. Lebel MH, et al: Dexamethasone therapy for bacterial meningitis results of double-blind, placebo-controlled trials. N Engl J Med 319:964, 1988. 60. Jewett DL, Williston JS: Auditory-evoked far fields averaged from scalp of humans. Brain 94:681, 1971. 61. Jerger J: Prediction of sensorineural hearing level from the brain stem evoked response. Arch Otolaryngol 104:456, 1978. 62. MacDonald JT, Feinstein S: Hearing loss following Hemophilus influenzae meningitis in infancy: Diagnosis by evoked response audiometry. Arch Neurol 41:1058, 1984. 63. Arriaga MA, Carrier D: MRI and clinical decisions in cochlear implantation. Am J Otol 17:547, 1996. 64. Coffey TJ, Daniels M, McDougal LK, et al: Genetic analysis of clinical isolates of Streptococcus pneumoniae with high-level resistance to expanded-spectrum cephalosporins. Antimicrob Agents Chemother 39:1306, 1995. 65. Hofmann J, Cetron MS, Farley MM, et al: The prevalence of drugresistant Streptococcus pneumoniae in Atlanta. N Engl J Med 333:481, 1995. 66. Van Esso D, Fontanals D, Uriz S, et al: Neisseria meningitides strains with decreased susceptibility to penicillin. Pediatr Infect Dis J 6:438, 1987. 67. Seaz-Nieto JA, Lujan R, Berron S, et al: Epidemiology and molecular basis of penicillin-resistant Neisseria meningitides in Spain: A 5-year history (1985–1989). Clin Infect Dis 14:394, 1992. 68. Woods CR, Smith AL, Wasilauskas BL, et al: Invasive disease caused by Neisseria meningitides relatively resistant to penicillin in North Carolina. J Infect Dis 170:453, 1994. 69. Dodge PR, et al: Prospective evaluation of hearing impairment as a sequelae of cute bacterial meningitis. N Engl J Med 311:869, 1984. 70. Schaad UB, Suter S, Gianella-Borradori A, et al: A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children. N Engl J Med 322:141, 1990. 71. Belsey MA, Hoffpauir CW, Smith MHD: Dexamethasone in the treatment of acute bacterial meningitis: The effect of study design on the interpretation of results. Pediatrics 44:503, 1969. 72. DeLemos RA, Haggerty RJ: Corticosteroids as an adjunct to treatment in bacterial meningitis: A controlled clinical trial. Pediatrics 44:30, 1969. 73. Eden AR, Cummings FR: Sudden bilateral hearing loss and meningitis in adults. J Otolaryngol 7:304, 1978. 74. Berlow SJ, et al: Bacterial meningitis and sensorineural hearing loss: A prospective investigation. Laryngoscope 90:1445, 1980.

75. Gower D, McGuirt WF: Intracranial complications of acute and chronic infectious ear disease: A problem still with us. Laryngoscope 93:1028, 1983. 76. Sproles ET, et al: Meningitis due to Hemophilus influenzae: Longterm sequelae. J Pediatr 75:782, 1969. 77. Jones FE, Hanson DR: H. influenzae meningitis treated with ampicillin or chloramphenicol, and subsequent hearing loss. Develop Med Child Neurol 19:593, 1977. 78. Nylen O, Rosenhall U: Hemophilus influenzae meningitis and hearing. Int J Pediatr Oto 1:97, 1979. 79. Kotagal S, et al: Auditory evoked potentials in bacterial meningitis. Arch Neurol 38:693, 1981. 80. Feldman WE, et al: Relation of concentrations of Haemophilus influenzae type b in cerebrospinal fluid to late sequelae of patients with meningitis. J Pediatr 100:209, 1982. 81. Munoz O, et al: Hearing loss after Hemophilus influenzae meningitis: Follow-up study with auditory brainstem potentials. Ann Otol Rhinol Laryngol 92:272, 1983. 82. Kaplan SL, et al: Onset of hearing loss in children with bacterial meningitis. Pediatrics 73:575, 1984. 83. Lin TY, et al: Seven days of ceftriaxone therapy is as effective as ten days’ treatment for bacterial meningitis. JAMA 253:3559, 1985. 84. Edwards MS, Baker CJ: Complications and sequelae of meningococcal infections in children. J Pediatr 99:540, 1981. 85. Lebel MH, et al: Magnetic resonance imaging and dexamethasone therapy for bacterial meningitis. Am J Dis Child 143:301, 1989. 86. Dawson KP, Abott GD, Mogridge N: Bacterial meningitis in childhood: A 13-year review. NZ Med J 107:758, 1988. 87. Smyth V, et al: Audiological management in the recovery phase of bacterial meningitis. Int J Pediatr 75:782, 1969. 88. Lebel MH, McCracken GH: Delayed cerebrospinal fluid sterilization and adverse outcome of bacterial meningitis in infants and children. Pediatrics 83:16, 1989. 89. Pomeroy SL, Homes SJ, Dodge PR, Feigin RD: Seizures and other neurologic sequelae of bacterial meningitis in children. N Engl J Med 323:1651, 1990. 90. Habib RB, et al: Hearing impairment in meningococcal meningitis. Scand J Infect Dis 11:121, 1979. 91. Snedeker JD, Kaplan SL, Dodge PR, et al: Subdural effusion and its relationship with neurologic sequelae of bacterial meningitis in infancy: A prospective study. Pediatrics 86(2):163, 1990. 92. Taylor HG, Mills EL, Ciampi A, et al: The sequelae of haemophilus influenzae meningitis in school-age children. N Engl J Med 323(24): 1657, 1990.

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Outline Introduction Epidemiology Pathology and Pathophysiology of Multiple Sclerosis Clinical Features Internuclear Ophthalmoplegia Vestibular Manifestations of Multiple Sclerosis Auditory Manifestations of Multiple Sclerosis Acoustic Reflex

Chapter

Demyelinating Diseases

Auditory Evoked Responses Facial Weakness Speech Disorders in Multiple Sclerosis Visual Evoked Potentials Other Ophthalmologic Manifestations Other Cranial Nerves Radiologic Imaging of Multiple Sclerosis Formal Diagnosis Management

INTRODUCTION This review will focus on multiple sclerosis (MS), the most common demyelinating disorder and the one most often encountered by the otolarygologist, neurotologist, and audiologist (Table 28-1). MS is a disorder whose demyelinating effects on the central nervous system (CNS) are disseminated in space and time in 85% to 90% of patients on presentation. Because the brainstem is commonly affected, otologists and neurotologists are often called on to assist in various ways in the diagnosis and management of MS. MS may be suspected on the basis of findings from routine evaluation of dizziness, hearing loss, or cranial nerve symptoms. A patient may be referred to help determine whether early or mild brainstem findings on examination or testing support the diagnosis of MS in combination with other findings. A question may arise whether a new symptom in a patient with an established diagnosis of MS is due to the disease or to an unrelated, peripheral cause. Otologists and neurotologists may be asked to treat dysequilibrium, facial palsy, hemifacial spasm, or another symptom, and to provide rehabilitation of hearing loss.

EPIDEMIOLOGY The female to male preponderance of definite MS is 1.5 to 2:1.1,2 The onset is typically from ages 20 to 40. Onset before puberty is rare. The prevalence of familial MS is approximately 17%, though much less in first-degree relatives. It is more common to have an affected sibling than

Edwin M. Monsell, MD, PhD

a parent or child. MS is primarily a disease of persons of northern European racial background. It is seen least often in Asians and native African blacks and with intermediate frequency in African Americans.1,3 The prevalence increases geographically as latitude increases. In the United States, the 37th parallel seems to be a divider between a zone of higher prevalence (50 to 150/100,000) to the north and a zone of lower prevalence (10/100,000) to the south.3 (In the United States the 37th parallel is approximately described by a line connecting the cities of San Francisco, St. Louis, and Washington, D.C.) There seems to be an increase in relative risk for those who moved north, but the magnitude of this increase appears less than the corresponding decrease found in those who moved south. The greatest reduction in risk occurs among those who moved south before the age of 9 years. Some reduction occurs among those who moved south between the ages of 15 and 19 years (Table 28-2).3,4

PATHOLOGY AND PATHOPHYSIOLOGY OF MULTIPLE SCLEROSIS The literature on the pathogenesis of MS is voluminous, contradictory, and controversial. Theories of genetic, viral, autoimmune, and multifactorial causation have been proposed.5 Interruption of the blood-brain barrier has been invoked as an important early event in the causal sequence, as has inflammation.6 Because of its high lipid content, normal myelin is hydrophobic. However, the breakdown products in active 499

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TABLE 28-1. Classification of Demyelinating Diseases I. Primary diseases of myelin A. Multiple sclerosis B. Devic’s disease C. Schilder’s disease D. Balo’s sclerosis II. “Allergic” group (perivenous encephalomyelitis) A. Postviral B. Postvaccinal C. Antirabies immunization D. Acute hemorrhagic leucoencephalitis III. Infections A. Subacute sclerosing panencephalitis (measles virus) B. Progressive multifocal leucoencephalitis (papova virus) IV. Toxic/Metabolic A. Carbon monoxide, postanoxic B. Diphtheria toxin C. Lead D. Organic mercury E. Triethyl tin F. Edema G. Methotrexate V. Nutritional A. Vitamin B12 deficiency B. Marchifava-Bignami syndrome C. Central pontine myelinolysis VI. Heredofamilial system degenerations A. Familial spastic paraplegia B. Hereditary ataxias C. Leber’s disease From Hallpike JF: Clinical aspects of multiple sclerosis. In Hallpike JF, Adams CWM, Tourtellotte WW (eds.): Multiple Sclerosis: Pathology, Diagnosis, and Management. Baltimore, Williams & Wilkins, 1983.

MS lesions become hydrophilic, resulting in increased signal brightness on T2-weighted magnetic resonance images (MRI). An acute MS plaque provokes a healing response that results in varying degrees of remyelination and gliosis (scarring). MS exerts its primary effect by disrupting the myelin sheath, which functions normally to increase the rate of transmission of action potentials in nerve axons. Temporary conduction blockade may occur in demyelinated fibers when rates of stimulation exceed the refractory period of axons. Action potentials in groups of fibers may lose the synchrony of firing, possibly accounting for the abnormality of auditory brainstem responses in MS. Axonal dysfunction, damage, or transection may also be present.7 The effects of MS lesions may be accentuated by increased body temperature.6 Evidence that MS is heightened by trauma is generally discounted.8 The number and loci of lesions vary considerably among patients, causing variable patterns of findings. Though

MS can occur in any part of the CNS, most lesions are in the white matter, producing sensory, cerebellar, and upper motor neuron effects (weakness, hypertonia, and hyperreflexia). The cerebrum, spinal cord, and ocular pathways are commonly affected. There is a predilection for periventricular regions. The presence of “silent” (subclinical) disease, variations in methods of clinical observation, and variations in the performance and interpretation of tests cause differing rates of abnormal findings in reported series.

CLINICAL FEATURES MS is a chronic, relapsing disorder of youth and middle life. The clinical course is variable and difficult to predict, ranging from “benign,” almost asymptomatic, MS to “malignant,” fulminant MS. Neurologic deficits may be sudden in onset, slowly progressive, or subclinical. Most MS patients experience early remissions and relapses, subsequently deteriorating into a chronic progressive course with advancing disability.9–11 More than 70% of younger patients present with a series of relapses and remissions associated with complete or relative recovery following each early episode (relapsing-remitting MS). Increasing deficits are seen in many patients with repeated episodes. As many as 80% to 90% will eventually develop a progressive course (secondary progressive MS). Other patients with MS (more commonly older male patients) demonstrate a chronic, progressive course from the onset (primary progressive MS). This pattern is associated with early disability and a poor prognosis (Table 28-3). The severity of the clinical course can be roughly estimated at presentation (Table 28-4). Approximately 20% of patients follow a benign course.11,12 The benign course is typical of the youngest patients.13 Life span and physical activity may be normal. If the first symptoms of MS are followed by 5 or more years of remission, the course is more likely to continue to be benign.12,13 A malignant course is seen in 5% to 10% of patients and usually occurs in younger patients.10 Many severe relapses occur during the first year, followed by early chronic, progressive deterioration. Patients are severely disabled or dead within a few years of the first symptoms. Cerebral and cerebellar symptoms dominate, though effects are widespread. Progressive cerebellar ataxia and intention

TABLE 28-3. Effect of Degree of Disability on Survival TABLE 28-2. High-Risk Factors in Multiple Sclerosis

Disability

Racial background Sex Age Residence before age 15 years Family history of MS

Walks unaided Walks with one stick Walks with two sticks Can just stand Able to sit Bedridden

Caucasian, North European, British Isles Female 20 to 40 years Above 37th parallel Sibs > parents > others

MS, multiple sclerosis. From Paty DW, Poser CM: Clinical symptoms and signs of multiple sclerosis. In Poser CM (ed.): The Diagnosis of multiple Sclerosis. New York, Thieme-Stratton, 1984.

% Dying within 10 Years 7 21 34 49 64 84

From Hyllested K: Lethality, duration and mortality of disseminated sclerosis in Denmark. Acta Psychiatr Neurol Scand 36:553–563, 1961.

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A

B

C

D

Figure 28-2. Axial MRI scans from a 29-year-old man. He presented with a 1-year history of constant lightheadedness and motion intolerance increasing as the day goes on. His past history included an episode of transient visual loss in the left eye and an episode of tingling of the left leg. Physical examination revealed spontaneous left-beating nystagmus that was accentuated on left lateral gaze, rigidity of the right upper and lower extremities, and hyperreflexia in the right ankle. Arrows indicate MS plaques. A, Cerebral cortex with ovoid periventricular lesion (T2 image). B and C, Brainstem with lesion in deep cerebellar nuclei (T2 images). D, T1 image with gadolinium enhancement showing a small plaque in the brainstem, representing an active MS lesion. Used with the permission of the author.

and vague dizziness, are common in MS (see Table 28-5 and Fig. 28-2).20–22 Acute vertigo is an initial complaint in only 3% to 7% of MS cases.16,22 Dysequilibrium is probably due to abnormalities in cerebellar, spinal cord, somatosensory, and motor control mechanisms as well as vestibular function.

Completely normal electronystagmography has been reported in no more than 12% of cases.23,24 The most common findings are abnormal visually induced eye movements (saccade test, smooth pursuit test, optokinetic nystagmus test), positional nystagmus, and hyperactive caloric responses.17,20

Demyelinating Diseases

Although MS lesions of the peripheral vestibular apparatus have not been reported, unilateral caloric weakness occurs in approximately 7% of patients, presumably due to plaques encroaching on the vestibular nuclei. Hyperexcitable caloric responses have been noted in up to 44% of individuals with MS, apparently due to a loss of cerebellar suppressant activity on caloric responses.20,23–25 Failure of fixation suppression has been reported in up to 47% of MS patients.20,23 Both hyperexcitablity and failure of fixation suppression are related to MS lesions in cerebellar pathways. “Dysrhythmia” of caloric responses in 8% to 34% of MS individuals is an artifact that arises from recording from both eyes simultaneously when INO is present.20,23 As a form of INO, it is a reliable indicator of MS.22 Pathologic nystagmus has been reported in 18% to 63% of cases, most commonly horizontal gaze nystagmus, reflecting the frequent occurrence of cerebellar involvement in MS.26 Vertical nystagmus is not uncommon, but rarely occurs apart from the horizontal form. Pendular nystagmus is a severe cerebellar sign and is prevalent in approximately 4% of MS patients late in their disease.27 Monocular nystagmus should suggest the diagnosis of MS. Abnormal saccade latency, velocity, and accuracy have been reported in 30% to 95% of patients.28,29 Optokinetic nystagmus may be disrupted or asymmetrical, and abnormality of smooth pursuit has been reported in 40% to 78% of MS patients.20,30 Smooth pursuit is usually normal in pure peripheral vestibular disorders. When the smooth pursuit mechanism is not functioning, tracking is saccadic. Saccadic tracking may occur from the effects of sedative medication, inadequate alerting during testing, fatigue, age, or poor visual acuity. Rotational testing of the vestibulo-ocular reflex and dynamic posturography have been used only infrequently in MS. There is evidence that posturography may be more sensitive than electronystagmography in detecting extravestibular abnormalities in posture control mechanisms and may serve as a useful guide for balance therapy, though further study is necessary.31,32

AUDITORY MANIFESTATIONS OF MULTIPLE SCLEROSIS Hearing loss and tinnitus are not common complaints in MS (see Table 28-5). There is no evidence that the prevalence of hearing loss is different from the rate in the general population.33 It has been reported that MS can cause sudden sensorineural hearing loss, though apparently does so rarely (Fig. 28-3).33–37 Sudden sensorineural hearing loss due to MS has retrocochlear features and has a good prognosis for recovery.34 The presence of abnormal auditory brainstem responses38 or normal evoked otoacoustic emissions may identify a central cause of the loss.39 Reports of insidious, chronic sensorineural hearing loss in MS vary widely, and not many studies were controlled for age or sex. One report indicated that 59% of MS patients had hearing loss compared with 27% in a control group, though this high an incidence has not been confirmed in other studies.40 No consistent pattern of pure

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Figure 28-3. T2-weighted axial MRI scan from a 31-year-old man presenting with sudden sensorineural hearing loss. There were no other clinical findings corroborating the diagnosis of MS, but the CSF demonstrated an elevated IgG index and oligoclonal bands. The arrow indicates an MS plaque in the low pons anterior to the fourth ventricle on the side opposite the sudden hearing loss. Used with the permission of the author.

tone slope in acute or chronic hearing loss associated with MS has emerged.20,21 Standard clinical speech audiometry (speech reception threshold and word recognition) reveals few abnormalities in MS.17,20,40 Poor speech discrimination scores relative to pure tone thresholds may be consistent with a CNS lesion (or acoustic neuroma); however, reported rates in MS are typically low, 3% to 7%.20 Although results of traditional audiometric tests are usually normal in MS, tests requiring response to a sustained stimulus, discrimination of speech in noise, and binaural masking tests are commonly abnormal.20 Abnormal word recognition in a noisy environment has been reported in 14% to 36% of cases.17,20,41 Recent evidence has suggested that some MS patients have a reduced ability to detect small shifts in tone frequency, but retain the ability to detect small differences in intensity.42 Additional audiometric measures that have been found to be abnormal in MS include the synthetic sentence identification test, some of the dichotic speech tests (staggered spondaic word test, dichotic sentence identification test, dichotic digits test), the rapid alternating speech perception test, and low-pass filtered speech.33

ACOUSTIC REFLEX In the normal acoustic reflex, the stapedius muscle contracts bilaterally when a loud tone is presented to the ear. The afferent limb of the reflex involves the auditory nerve and the ventral cochlear nucleus, which in turn stimulates the medial superior olivary nucleus bilaterally. The efferent limb reaches the facial motor nuclei bilaterally; these send motor twigs to the stapedius muscles

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bilaterally. Ipsilateral stimulation is more effective than contralateral, and binaural stimulation is more effective than monaural. Several measurements of the acoustic reflex may be made. In standard clinical testing, the reflex thresholds are recorded through an impedance bridge or otoadmittance meter. Adaptation, or “decay” of the acoustic reflex is defined as the loss of half or more of the reflex amplitude within the first 5 seconds of a 10-second stimulation period at 10 dB above the reflex threshold. Adaptation is normal at high frequencies, but abnormal at 500 or 1000 Hz. Positive acoustic reflex decay occurs in retrocochlear disorders such as acoustic neuroma. Between 13% and 69% of MS patients have been reported to display abnormal results for acoustic reflex thresholds elicited by pure tone stimuli.43–45 Bilaterally absent acoustic reflexes have been noted in 20% of MS cases.46 In one review of 40 MS patients, elevated or absent reflex thresholds were found in all subjects with hearing loss.47 Reflex amplitude and, to a lesser extent, latency measures were more sensitive markers for MS (75%) than threshold measures (23%) in 122 subjects with MS48; however, measures of acoustic reflex rise time and latency of onset are apparently not sensitive enough to detect otherwise asymptomatic MS.49 These studies demonstrate that subclinical abnormalities are variably present in the brainstem of MS patients. Suprathreshold measures of the acoustic reflex have not become established for routine clinical use in MS.

AUDITORY EVOKED RESPONSES The detection of subclinical disease in the brainstem by evoked potential testing can be valuable in the diagnosis of MS. The auditory brainstem response (ABR) is elicited by the application of acoustic click stimuli to the ear and recorded as far-field responses from the scalp within the first 10 to 15 msec of the stimulus onset.50 It is now assumed that the generators of waves I and II reflect cochlear and auditory nerve activity and that waves III to VI arise from several sites within the central auditory pathways.51 The asynchronous firing of impulses through the auditory brainstem in MS would be expected to result in abnormal ABR. The ABR has been found to be abnormal in up to 83% of cases of MS.52,53 Clinically manifest and even clinically silent MS plaques may yield alterations in ABR waves I to V, such as prolonged interwave latencies, higher amplitude of earlier than later waves in the response, absent waves, and poor replicability.17,52–54 Nevertheless, the ABR has not been accepted as a means of demonstrating “dissemination in space” under new diagnostic criteria (see Table 28-9).13 Latency values may show a bimodal distribution, with modes associated with either normal latency or markedly abnormal latency in the range of 4 or more standard deviations above normal values.53 One interpretation of this finding is that neural conduction through the auditory brainstem may be normal if there is no lesion, but even a small lesion can cause a marked impairment of conduction.53 Latency increases may be more indicative of MS than changes in wave amplitude.55 It is unclear whether increases in stimulus rate can enhance latency changes in

MS patients.54,56 Some effects of stimulus rate may depend on the polarity of the click stimulus.57 The middle latency response (MLR) occurs approximately 30 msec after the onset of the stimulus, and the late vertex response (LVR) consists of two peaks occurring normally at 90 and 180 msec, respectively, after the stimulus. Abnormal MLRs and LVRs have been reported in brainstem lesions, central auditory processing disorder, developmental dysphasia, acoustic neuroma, and some central disorders.58–60 These late potentials are less likely to be abnormal in MS than is the ABR, though there is evidence that the addition of the MLR, but not the LVR, to the ABR can increase the diagnostic yield in MS.61 Direct comparisons of multimodality evoked potentials have found that visual evoked responses (VERs) are more sensitive (66%) for definite MS, followed by somatosensory evoked responses (23%), followed by ABR (18%).62,63 Multimodality testing is more sensitive than any modality alone, over 85%. The diagnostic yield of evoked potentials drops when they are needed most, that is, in probable and possible MS.64 Due to the many clinical and technical variables, evoked potential testing has not become established in clinical settings to follow the progress of MS or its response to treatment.

FACIAL WEAKNESS Facial weakness is infrequently a presenting symptom of MS.15,65 Given that MS is a central nervous system disease, it may be assumed that facial motor pathology in MS is due to upper or lower motor neuron disease within the CNS. The location of the lesion is usually the brainstem.65 Approximately 15% of individuals with MS eventually develop some degree of facial weakness (see Table 28-5). The most common manifestation is mild paresis in the lower division of the face. The appearance of facial weakness in a patient with established MS should not be assumed to be due to the MS, because of the high general incidence of idiopathic facial palsy (Bell’s palsy) and other causes of facial paralysis. For example, in the author’s experience, bilateral acoustic neuromas were found by MRI in a patient with established MS who developed unilateral facial weakness. Hemifacial spasm has also been reported in MS and is associated with the presence of a plaque involving the ipsilateral facial nucleus.66 Facial myokymia, which may occur in any or all divisions of the facial nerve, consists of flickering and undulation of the facial muscles. It is caused by rhythmic discharge in individual muscle fascicles and single motor units rather than entire muscle groups. Facial myokymia is more often associated with MS than is hemifacial spasm.66,67 The two entities may be distinguished by electromyography and may coexist rarely.66

SPEECH DISORDERS IN MULTIPLE SCLEROSIS Dysarthria, one of the symptoms comprising Charcot’s triad (dysarthria, intention tremor, and nystagmus), may be caused by paresis or incoordination of speech musculature.68

Demyelinating Diseases

The triad is classic in MS, but rarely occurs early in the disease.9 Dysarthria should be distinguished from disorders of higher centers, such as apraxia of speech and aphasia.69 Darley documented 59% of MS individuals with normal speech, 28% with abnormal speech of minimal severity, and 13% with abnormal speech of greater severity. The various speech deviations included impaired loudness control and harshness (77%), defective articulation (46%), impaired emphasis (39%), impaired pitch control (37%), hypernasality (24%), inappropriate pitch level (24%), and breathiness (22%). These defects are presumed to be due to the effects of MS plaques on the lower cranial nerve nuclei and motor control pathways. Lesions of the supranuclear corticobulbar tracts are associated with pseudobulbar palsy.70

VISUAL EVOKED POTENTIALS This sensory evoked potential modality can detect both clinically apparent and subclinical damage to the optic nerve, tract, and radiations.71,72 Abnormal visual evoked potential (VEP) findings have been reported in 57% to 100% of MS patients.71–73 The number of clinically silent lesions disclosed by VEP is considerable, ranging from 8% to 24% of MS cases.72,73 Thus, VEPs are more sensitive indicators of MS than is the ABR and remain abnormal in more than 90% of cases.

OTHER OPHTHALMOLOGIC MANIFESTATIONS Visual disturbances have been reported in 55% to 77% of MS patients.74,75 Optic neuritis, often presenting as a central scotoma, is the most common visual manifestation of MS. Scotomata may evolve over hours to days into a visual defect of any size, including complete blindness. Usually the scotomata resolve over a few weeks or months with a minimal residual visual deficit, though effects are permanent in some cases. Optic neuritis affects red and green color perception and occurs to varying degrees in 31% to 55% of MS cases.72,74,75 Swelling of the optic disc may occur if a demyelinating lesion is located anteriorly. Other ophthalmologic manifestations of MS include: anisocoria, Horner’s syndrome, oculomotor defects, and abnormalities of visual psychophysical tests.

OTHER CRANIAL NERVES Loss of taste and dysgeusia have been reported in 8% to 17% of MS cases.76,77 Changes in smell, which are more difficult to assess, have been reported in up to 68%.78 Facial numbness is an initial complaint in 2% to 3% of individuals with MS.15,76 Hyperpathia may precede hypoesthesia. Isolated persistent facial numbness is unlikely to be due to MS. Trigeminal neuralgia is rare in MS, occurring in only 1% to 2% of patients.15,16 Among patients with trigeminal neuralgia the incidence of MS is approximately 3%.79 It is rare to observe paralysis of the

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motor division of the trigeminal nerve in MS; however, when it occurs in a young person, it may be the first symptom of MS.

RADIOLOGIC IMAGING OF MULTIPLE SCLEROSIS T2-weighted MRI is currently the most sensitive imaging modality for the detection of MS plaques in the brainstem, whereas fluid-attenuated inversion recovery (FLAIR) sequences are more sensitive for lesions in the cerebral hemispheres. The sensitivity and specificity of MRI in MS vary in different series with stage of disease, technique, and test interpretation. Additional variables include the regional pattern of dissemination of the disease, the duration of disease, the age of plaques, and the region of the CNS being studied by MRI. Sensitivity and specificity may be enhanced with the addition of T1-weighted sequences.80 Gadolinium contrast material can cross the broken blood-brain barrier of active MS lesions, resulting in enhancement within the plaque.80–82 Sensitivity and specificity are less in subtentorial regions than in supratentorial regions, particularly when clinically probable and possible MS are considered. In one study MRI was 60% sensitive in infratentorial regions in clinically definite MS and 33% in clinically probable MS, whereas the corresponding results for supratentorial regions were 97% and 82%, respectively.80 The most common associations of lesions with high signal intensity on T2-weighted MRI are with normal aging and with white matter ischemic lesions.82 The prevalence of nonspecific incidental white matter changes is as high as 20% among healthy individuals, higher among hypertensives, and from 30% to 100% in demented persons.80 Lesions that enhance on T2-weighted sequences may also be found in neurosarcoidosis, Lyme disease, granulomatous angiitis of the CNS, connective tissue disorders, subcortical atherosclerotic encephalopathy, vasculitides, acute disseminated encephalomyelitis, subacute sclerosing panencephalitis, autoimmune disease, central pontine myelinolysis, vitamin B12 deficiency, tumors and tumor-like lesions, and other demyelinating and dysmyelinating diseases.82,83 Many of the bright lesions in these disorders can be distinguished from lesions due to MS. Superatentorial MS lesions are characteristically wider in the transverse diameter than the coronal diameter due to the orientation of fiber tracts. Vascular lesions do not characteristically have this ovoid shape. Although T2-weighted bright lesions may be low in specificity as isolated findings, they are quite specific for MS in the context of clinical findings and abnormal CSF studies. This specificity is further enhanced if lesions are periventricular.80–82 Lesions in infratentorial regions or the corpus callosum are worrisome. The extent of MS lesions seen on MRI does not correspond well to the duration or clinical severity of MS. The majority of lesions identified on MRI are not associated with symptoms. Meaningful comparisons between the sensitivity of MRI and other laboratory investigations are difficult to make because of the number of variables involved, though with current technology MRI appears to be more sensitive than evoked potential testing.84–86

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TABLE 28-6. Differential Diagnosis of Multiple Sclerosis I. Diseases causing multiple lesions A. SLE B. Primary Sjögren’s syndrome C. Polyarteritis nodosa D. AIDS E. Acute disseminated encephalomyelitis F. Lyme disease G. Cerebrovascular disease II. Systematised diseases A. Hereditary spinocerebellar ataxia B. Subacute combined degeneration of the spinal cord C. Leukodystrophy III. Single lesions of the CNS with a relapsing/remitting course A. Intracranial meningioma during pregnancy B. Glioma of brainstem C. Extramedullary tumors in region of foramen magnum D. Primary cerebral lymphoma E. Arteriovenous malformations involving brainstem F. Tumors involving spinal cord IV. Single lesions with a progressive course A. Cervical spondylotic myelopathy B. The chiari malformation V. Monosymptomatic presentation: Note: 45% of MS patients A. Visual failure, i.e., optic neuritis B. Diplopia, i.e., internuclear ophthalmoplegia C. Vertigo: Note: as an initial symptom of MS, this is indistinguishable from an episode of vestibular neuronitis; however, the course is generally shorter with MS. D. Sensory symptoms VI. Nonorganic Symptoms AIDS, acquired immunodeficiency syndrome; CNS, central nervous system; MS, multiple sclerosis; SLE, systemic lupus erythematosus. From Matthews WB, Compston A, Allen IV, Matyn CN: McAlpine’s Multiple Sclerosis, 2nd ed. New York, Churchill Livingstone, 1991.

FORMAL DIAGNOSIS MS remains a clinical diagnosis and has an extensive differential diagnosis (Table 28-6).76,87 Although the diagnosis of MS may be clear on presentation, in mild or uncertain cases, years may be required to establish it. The variable natural history of MS has made necessary the development of diagnostic criteria for clinical and research purposes consistent with the dynamics of the disease (Tables 28-7 through 28-9). Bladder hypertonia, bowel or sexual dysfunction, and the hot bath test can be used to support the diagnosis on clinical grounds.88 Recently, more emphasis has been placed on the use of MRI and laboratory tests in diagnosis (see Table 28-9). CSF immunologic studies are abnormal in up to 90% of cases. No single CSF study is confirmatory of MS. These studies are of less clinical value than evoked potentials or imaging.87 In one study at least one component of a test battery consisting of visual evoked potentials, somatosensory evoked potentials, and CSF studies was positive in 100% of definite, 95% of probable, and 80% of possible MS cases.1

TABLE 28-7. Rose Criteria for the Clinical Diagnosis of Multiple Sclerosis, 1976 I. Clinically definite multiple sclerosis A. Relapsing and remitting course with at least two bouts separated by no less than one month; or B. Slow or stepwise progressive course extending over at least 6 months. C. Documented neurologic signs attributable to more than one site of predominantly white matter central nervous system pathology. D. Onset of symptoms usually between ages of 10 and 50. E. No better neurologic explanation. II. Probable multiple sclerosis A. History of relapsing and remitting symptoms but without documentation of signs and presenting with only one neurologic sign commonly asscociated with multiple sclerosis, or B. A documented single bout of symptoms with signs of mulifocal white matter disease with good recovery and followed by variable symptoms and signs. C. No better neurologic explanation. III. Possible multiple sclerosis A. History of relapsing and remitting symptoms without documentation of signs, or B. Objective neurologic signs insufficient to establish more than one site of central nervous system white matter pathology. C. No better neurologic explanation. From Rose AS, Ellison GW, Myers LW, Tourtellotte WW: Criteria for the clinical diagnosis of multiple sclerosis. Neurology 26:20–22, 1976.

Two immunomodulators are well established in the treatment of MS, glatiramer acetate,90 and interferon beta-1.91 In clinical trials most other agents were not demonstrated to be effective, or toxicity was unacceptable. The diagnosis of MS and overall management should be the responsibility of a trained and experienced physician, who will usually be a neurologist. Otolarygologists and neurotologists have important supporting roles in patient evaluation and treatment. The management of balance disorders may require vestibular testing, counseling, and rehabilitation. Hearing evaluation and rehabilitation, including the use of amplification, may be appropriate. Reasonable physical activities such as walking to help maintain balance function are recommended along with precautions to avoid falls. Muscle strengthening may improve gait and balance function, but weak muscles can be strained by overuse. Stretching exercises are often

TABLE 28-8. Clinically Definite MS—Schumacher Criteria, 1965 1. 2. 3. 4.

MANAGEMENT

Neurologic examination reveals objective abnormalities of CNS function. Examination or history indicates involvement of two or more parts of CNS. CNS disease predominantly reflects white matter involvement. Involvement of CNS follows one or two patterns. a. Two or more episodes, each lasting at least 24 hours and a month or more apart b. Slow or stepwise progression of signs and symptoms over at least 6 months. 5. Patient 10–50 years old at onset. 6. Signs and symptoms cannot be explained better by an other disease process.

The rate of publication on the medical treatment of MS has tripled since the first edition of this book.89 Corticosteroids are often used to treat acute relapses.

CNS, central nervous system; MS, multiple sclerosis. From Schumacher GA, Beebe G, Kibler RE, et al: Problems of experimental trials of therapy in multiple sclerosis: Report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis. Ann N Y Acad Sci 12:552–568, 1965.

Demyelinating Diseases

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TABLE 28-9. Diagnostic Criteria, International Panel, McDonald, 2001 Clinical Presentation

Additional Data Needed for MS Diagnosis

Two or more attacks; objective clinical evidence of two or more lesions Two or more attacks; objective clinical evidence of one lesion

None

One attack; objective clinical evidence of two or more lesions One attack; objective clinical evidence of one lesion (monosymptomatic presentation; clinically isolated syndrome)

Insidious neurologic progression suggestive of MS

Dissemination in space, demonstrated by MRI or Two or more MRI-detected lesions consistent with MS plus positive CSF or Await further clinical attack implicating a different site Dissemination in time, demonstrated by MRI or Second clinical attack Dissemination in space, demonstrated by MRI or Two or more MRI-detected lesions consistent with MS plus positive CSF and Dissemination in time, demonstrated by MRI or Second clinical attack Positive CSF and Dissemination in space, demonstrated by (1) Nine or more T2-weighted lesions in brain or (2) two or more lesions in spinal cord, or (3) four to eight brain plus one spinal cord lesion or Abnormal VEP associated with four to eight brain lesions, or with fewer than four brain lesions plus one spinal cord lesion demonstrated by MRI and Dissemination in time, demonstrated by MRI or Continued progression for 1 year

CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; MS, multiple sclerosis; VEP, visual evoked potential. See original source for qualifications, footnote, and explanatory material. From McDonald W, Compston A, Edan G, et al: Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127, 2001.

helpful in states of hypertonia, but should be properly supervised. Appropriate counseling and involvement in support groups for the patient and family are important (National Multiple Sclerosis Society, 733 Third Avenue, New York, NY 10017, http://www.nmss.org.)

REFERENCES 1. Achejon ED: Epidemiology of multiple sclerosis. Br Med Bull 33, 1977. 2. Hogancamp WE, Rodriguez M, Weinshenker BG: The epidemiology of multiple sclerosis. Mayo Clin Proc 72:871–878, 1997. 3. Paty D, Ebers G, Wonnacott T: Prognostic markers in multiple sclerosis. In Kuroiwa Y, Kurland LT (eds.): Multiple Sclerosis East and West. Basel, Switzerland, Karger, 1982, pp 56–63. 4. Detels R, Visscher BR, Haile RW, et al: Multiple sclerosis and age at migration. Am J Epidemiol 108:386–393, 1978. 5. Weinshenker B: Natural history of multiple sclerosis. Ann Neurol 36:S6–S11, 1994. 6. Poser CM: Exacerbations, activity, and progression in multiple sclerosis. Arch Neurol 37:471–474, 1980. 7. Bruck W, Lucchinetti C, Lassmann H: The pathology of primary progressive multiple sclerosis. Mult Scler 8:93–97, 2002. 8. Corcoran M: An unhappy coincidence between multiple sclerosis and trauma? Lancet 359:726, 2002.

9. Paty DW, Poser CM: Clinical symptoms and signs of multiple sclerosis. In Poser CM (ed.): The Diagnosis of Multiple Sclerosis. New York, Thieme-Stratton, 1984. 10. Weinshenker BG: The natural history of multiple sclerosis: Update 1998. Semin Neurol 18:301–307, 1998. 11. Wingerchuk DM, Weinshenker BG: The natural history of multiple sclerosis: Implications for trial design. Curr Opin Neurol 12: 345–349, 1999. 12. Mackey R, Hirano A: Forms of benign multiple sclerosis. Report of two “clinically silent” cases discovered at autopsy. Arch Neurol 17:588–600, 1967. 13. McDonald W, Compston A, Edan G, et al: Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 50: 121–127, 2001. 14. Stenager E, Knudsen L, Jensen K: Psychiatric and cognitive aspects of multiple sclerosis. Semin Neurol 10:254–261, 1990. 15. Muller R: Studies on disseminated sclerosis with special reference to symptomatology, course and prognosis. Acta Med Scand 133:1–124, 1949. 16. Kahana E, Leibowitz U, Alter M: Brainstem and cranial nerve involvement in multiple sclerosis. Acta Neurol Scand 49:269–279, 1973. 17. Dayal VS, Tarantino L, Swisher LP: Neuro-otologic studies in multiple sclerosis. Laryngoscope 76:1798–1809, 1966. 18. Siroky A, Krejcova H, Vymazal J: The early diagnosis of multiple sclerosis by monocular registration of evoked nystagmus. Acta Neurol Scand 49:205–214, 1973.

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19. Reulen JP, Sanders EA, Hogenhuis LA: Eye movement disorders in multiple sclerosis and optic neuritis. Brain 106:121–140, 1983. 20. Noffsinger D, Olsen WO, Carhart R, et al: Auditory and vestibular aberrations in multiple sclerosis. Acta Otolaryngol (Suppl) 303:1–63, 1972. 21. Grénman R: Involvement of the audiovestibular system in multiple sclerosis. An otoneurologic and audiologic study. Acta Otolaryngol (Suppl) 420:1–95, 1985. 22. Herrera WG: Vestibular and other balance disorders in multiple sclerosis. Differential diagnosis of disequilibrium and topognostic localization. Neurol Clin N Am 8:407–420, 1990. 23. Aantaa E, Riekkinen PJ, Frey HJ: Electronystagmographic findings in multiple sclerosis. Acta Otolaryngol 75:1–5, 1973. 24. Bruner M, Chila R, Maurer K: Audiometrie und vestibularisuntersuchungen bei MS patienten. Laryngol Rhinol 56:80–87, 1997. 25. Barghuti J: Observations on the neuro-otologic diagnosis of early multiple sclerosis. Rev Laryngol Otol Rhinol (Bord) 100:137–149, 1979. 26. Nylen CO: Positional nystagmus. J Laryngol Otol 64:295–318, 1950. 27. Aschoff JC: Acquired pendular nystagmus with oscillopsia in multiple sclerosis: A sign of cerebellar nuclei disease. J Neurol Neurosurg Psychiatry 37:570–577, 1974. 28. Ochs AL, Hoyt WF, Stark L, Patchman MA: Saccadic initiation time in multiple sclerosis. Ann Neurol 4:578–579, 1978. 29. Mastaglia FL, Black JL, Collins DW: Quantitative studies of saccadic and pursuit eye movements in multiple sclerosis. Brain 102:817–834, 1979. 30. von Noorden GK, Preziosi TJ: Eye movement recordings in neurological disorders. Arch Ophthalmol 76:162–171, 1966. 31. Shepard NT, Telian SA, Smith-Wheelock M: Balance disorders in multiple sclerosis: Assessment and rehabilitation. Semin Hear 11:292–305, 1990. 32. Monsell E, Furman JM, Herdman S, et al: Technology assessment: Computerized dynamic platform posturography. Otolaryngol Head Neck Surg 117:394–398, 1997. 33. Stach BA, Delgado-Vilches G, Smith-Farach S: Hearing loss in multiple sclerosis. Semin Hear 11:221–230, 1990. 34. Barratt HJ, Miller D, Rudge P: The site of the lesion causing deafness in multiple sclerosis. Scand Audiol 17:67–71, 1988. 35. Shea JJ III, Brackmann DE: Multiple sclerosis manifesting as sudden hearing loss. Otolaryngol Head Neck Surg 97:335–338, 1987. 36. Schweitzer VG, Shepard N: Sudden hearing loss: An uncommon manifestation of multiple sclerosis. Otolaryngol Head Neck Surg 100:327–332, 1989. 37. Franklin DJ, Coker NJ, Jenkins HA: Sudden sensorineural hearing loss as a presentation of multiple sclerosis. Arch Otolaryngol Head Neck Surg 115:41–45, 1989. 38. Furman JM, Durrant JD, Hirsch WL: Eighth nerve signs in a case of multiple sclerosis. Am J Otolaryngol 10:376–381, 1989. 39. Robinette MS, Facer GW: Evoked otoacoustic emissions in differential diagnosis: A case report. Otolaryngol Head Neck Surg 105:120–123, 1991. 40. Dayal VS, Swisher LP: Pure tone thresholds in multiple sclerosis. A further study. Laryngoscope 77:2169–2177, 1967. 41. Olsen WO, Noffsinger D, Kurdziel S: Speech discrimination in quiet and in white noise by patients with peripheral and central lesions. Acta Otolaryngol 80:375–382, 1975. 42. Quine DB, Regan D, Beverley KI, Murray TJ: Patients with multiple sclerosis experience hearing loss specifically for shifts of tone frequency. Arch Neurol 41:506–508, 1984. 43. Colletti V: Stapedius reflex abnormalities in multiple sclerosis. Audiology 14:63–71, 1975. 44. Hess K: Stapedius reflex in multiple sclerosis. J Neurol Neurosurg Psychiatry 42:331–337, 1979. 45. Hannley M, Jerger JF, Rivera VM: Relationships among auditory brain stem responses, masking level differences and the acoustic reflex in multiple sclerosis. Audiology 22:20–33, 1983.

46. Bosatra A, Russolo M, Poli P: Oscilloscopic analysis of the stapedius muscle reflex in brain stem lesions. Arch Otolaryngol 102:284–285, 1976. 47. Lennhardt E: Übersichten Hurstorungen bei Multipel Sclerose. Hals-Nasen-Ohrenheilkunde 23:101–108, 1975. 48. Jerger J, Oliver TA, Rivera V, Stach BA: Abnormalities of the acoustic reflex in multiple sclerosis. Am J Otolaryngol 7:163–176, 1986. 49. Wiegand DA, Poch NE: The acoustic reflex in patients with asymptomatic multiple sclerosis. Am J Otolaryngol 9:210–216, 1988. 50. Jewett DL, Williston JS: Auditory-evoked far fields averaged from the scalp of humans. Brain 94:681–696, 1971. 51. Moore JK: The human auditory brain stem as a generator of auditory evoked potentials. Hear Res 29:33–43, 1987. 52. Jerger JF, Oliver TA, Chmiel RA, Rivera VM: Patterns of auditory abnormality in multiple sclerosis. Audiology 25:193–209, 1986. 53. Hall JW (ed.): Neurodiagnosis: Central nervous system. In: Handbook of Auditory Evoked Potentials. Boston, Allyn and Bacon, 1992. 54. Chiappa KH, Harrison JL, Brooks EB, Young RR: Brainstem auditory evoked responses in 200 patients with multiple sclerosis. Ann Neurol 7:135–143, 1980. 55. Stockard JJ, Stockard JE, Sharbrough FW: Brainstem auditory evoked potentials in neurology: Methodology, interpretation, clinical application. In Aminoff MJ (ed.): Electrodiagnosis in Clinical Neurology. New York, Churchill Livingstone, 1980, pp 370–413. 56. Robinson K, Rudge P: Abnormalities of the auditory evoked potentials in patients with multiple sclerosis. Brain 100 Pt 1:19–40, 1977. 57. Jacobson JT, Jacobson GP: The auditory brainstem response in multiple sclerosis. Semin Hear 11:248–264, 1990. 58. Fifer RC, Sierra-Irizarry B: Clinical applications of the auditory middle latency response. Am J Otol (Suppl) 9:47–56, 1988. 59. Harker LA, Backoff P: Middle latency electric auditory responses in patients with acoustic neuroma. Otolaryngol Head Neck Surg 89:131–136, 1981. 60. Robinson K, Rudge P: The use of the auditory evoked potential in the diagnosis of multiple sclerosis. J Neurol Sci 45:235–244, 1980. 61. Djupesland G, Tvete O, Stein R, Bachen NI: A comparison between auditory and visual evoked responses in multiple sclerosis. Scand Audiol (Suppl) 13:135–137, 1981. 62. Stach BA, Hudson M: Middle and late auditory evoked potentials in multiple sclerosis. Semin Hear 11:265–275, 1990. 63. Deltenre P, Van Nechel C, Strul S, Ketelaer P: A five-year prospective study on the value of multimodal evoked potentials and blink reflex, as an aid to the diagnosis of suspected multiple sclerosis. In Nodar RH, Barber C (eds.): Evoked Potentials II: The Second International Evoked Potentials Symposium. Boston, Butterworth, 1984, pp 603–608. 64. Chiappa KH: Pattern shift visual, brainstem auditory, and shortlatency somatosensory evoked potentials in multiple sclerosis. Neurology 30:110–123, 1980. 65. Commins D, Chen J: Multiple sclerosis: A consideration in acute cranial nerve palsies. Am J Otol 18:590–595, 1997. 66. Telischi FF, Grobman LR, Sheremata WA, et al: Hemifacial spasm. Occurrence in multiple sclerosis. Arch Otolaryngol Head Neck Surg 117:554–556, 1991. 67. Anderman F, Cosgrove JB, Lloyd-Smith DL, et al: Facial myokymia in multiple sclerosis. Brain 84:31–44, 1961. 68. Charcot JM: Lectures on the Diseases of the Nervous System. London, New Sydenham Society, 1877, p 339. 69. Darley FL, Aronson AE, Brown JR: Differential diagnostic patterns of dysarthria. J Speech Hear Res 12:246–269, 1969. 70. Darley FL, Brown JR, Goldstein NP: Dysarthria in multiple sclerosis. J Speech Hear Res 15:229–245, 1972. 71. Clifford-Jones RE, Clarke GP, Mayles P: Crossed acoustic response combined with visual and somatosensory evoked responses in the diagnosis of multiple sclerosis. J Neurol Neurosurg Psychiatry 42:749–752, 1979.

Demyelinating Diseases

72. Nikoskelainen E, Falck B: Do visual evoked potentials give relevant information to the neuro-ophthalmological examination in optic nerve lesions? Acta Neurol Scand 66:42–57, 1982. 73. Deltenre P, Vercruysse A, van Nechel C, et al: Early diagnosis of multiple sclerosis by combined multimodal evoked potentials: Results and practical considerations. J Biomed Eng 1:17–21, 1979. 74. Asselman P, Chadwick DW, Marsden DC: Visual evoked responses in the diagnosis and management of patients suspected of multiple sclerosis. Brain 98:261–282, 1975. 75. Lowitzsch K, Kuhnt U, Sakmann C, et al: Visual pattern evoked responses and blink reflexes in assessment of MS diagnosis. A clinical study of 135 multiple sclerosis/pathol. J Neurol 213:17–32, 1976. 76. McAlpine D: The problem of diagnosis. In McAlpine D, Lumsden CE, Acheson ED (eds.): Multiple Sclerosis: A Reappraisal, 2nd ed. Edinburgh, Churchill Livingstone, 1972, pp 83–307. 77. Rollin H: Geschmacksstorungen bei Multipel Sclerose. Laryngol Rhinol 55:678–681, 1976. 78. Ansari K: Olfaction in multiple sclerosis. Neurology 14:138–145, 1976. 79. Rivera V: The nature of multiple sclerosis. Semin Hear 10:207–220, 1990. 80. Yetkin F: Multiple sclerosis: Specificity of MR for diagnosis. Radiology 178:447–451, 1991. 81. Nesbit GM, Forbes GS, Scheithauer BW, et al: Multiple sclerosis: Histopathologic and MR and/or CT correlation in 37 cases at biopsy and three cases at autopsy. Radiology 180:467–474, 1991. 82. Wallace CJ, Seland TP, Fong TC: Multiple sclerosis: the impact of MR imaging. Am J Roentgenol 158:849–857, 1992. 83. Byrne JV, Kendall BE, Kingsley DP, Moseley IF: Lesions of the brain stem: Assessment by magnetic resonance imaging. Neuroradiology 31:129–133, 1989. 84. Sola P, Scarpa M, Faglioni P, et al: Diagnostic investigations in MS: Which is the most sensitive? Acta Neurol Scand 80:394–399, 1989.

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85. Bone G, Ladurner G, Artmann W, Bsteh C: Correlations between clinical and magnetic resonance imaging findings in multiple sclerosis. Eur Neurol 28:212–216, 1988. 86. Paty DW, Oger JJ, Kastrukoff LF et al: MRI in the diagnosis of MS: A prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology 38:180–185, 1988. 87. Hallpike JF: Clinical aspects of multiple sclerosis. In Hallpike JF, Adams CWM, Tourtellotte WW (eds.): Multiple Sclerosis: Pathology, Diagnosis, and Management. Baltimore, Williams & Wilkins, 1983. 88. Poser CM, Paty DW, Scheinberg L, et al: New diagnostic criteria for multiple sclerosis: Guidelines for research protocols. Ann Neurol 13:227–231, 1983. 89. Hohlfeld R, Wiendl H: The ups and downs of multiple sclerosis therapeutics. Ann Neurol 49:281–284, 2001. 90. Comi G, Filippi M, Wolinsky J: European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance image-measured disease activity and burden in patients with relapsing multiple sclerosis. Ann Neurol 49:297, 2001. 91. Paty DW, Li D: Interferon beta-1b is effective in relapsingremitting multiple sclerosis II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43:662–667, 1993. 92. Hyllested K: Lethality, duration and mortality of disseminated sclerosis in Denmark. Acta Psychiatrica Neurol Scand 36:553–563, 1961. 93. Matthews WB, Compston A, Allen IV, Matyn CN: McAlpine’s Multiple Sclerosis, 2nd ed. New York, Churchill Livingstone, 1991. 94. Rose AS, Ellison GW, Myers LW, Tourtellotte WW: Criteria for the clinical diagnosis of multiple sclerosis. Neurology 26:20–22, 1976. 95. Schumacher GA, Beebe G, Kibler RE, et al: Problems of experimental trials of therapy in multiple sclerosis: Report by the panel on evaluation of experimental trials of therapy in multiple sclerosis. Ann N Y Acad Sci 12:552–568, 1965.

Chapter

29 Lee A. Harker, MD

Migraine Outline Introduction Etiology and Pathogenesis Migraine and Neuro-otologic Disorders Benign Paroxysmal Positional Vertigo Benign Recurrent Vertigo Ménière’s Disease Familial Episodic Ataxia Transient Ischemic Attacks Stroke Neurotologic Symptoms Vertigo

Motion Sickness Auditory Symptoms Migraine Types Associated with Neurotologic Symptoms Migraine with Aura Basilar Migraine Migraine Aura without Headache Management Management of Headaches Management of Vestibular Symptoms Summary

INTRODUCTION

ETIOLOGY AND PATHOGENESIS

Migraine affects 28 million Americans, approximately 18% of women and 6% of men. After puberty the prevalence is much higher in women than men, is highest between ages 30 and 45 years in both sexes, and varies inversely with household income (Figure 29-1).1,2 It occurs in two principal forms: migraine without aura and migraine with aura. Although most patients with migraine have no symptoms related to an aura, slightly more than 30% experience aura on some occasions.3 Migraine headaches are a major cause of work absenteeism and decreased work productivity. But despite its pervasiveness and its associated disability, migraine is underrecognized and undertreated. It is estimated that almost 4 million individuals who meet the diagnostic criteria for migraine4,5 (Table 29-1) are diagnosed with sinus or tension-type headache but not with migraine.6 Of significance to otolaryngologists, vertigo and abnormal sensitivity to motion are frequently associated with migraine, and they also can be severe enough to cause absence from work and disability. These facts are grossly underappreciated by general physicians evaluating and treating patients with migraine, and by otolaryngologists evaluating and treating patients with vestibular symptoms. This chapter discusses migraine from the perspective of the otolaryngologist and reviews the etiology and pathogenesis of migraine, discusses the relationship of migraine to other neurotologic disorders, reviews the neurotologic symptoms associated with migraine and the types of migraine that evoke those symptoms, and discusses current management.

Migraine is not caused by a primary vascular event as had been previously thought.4 It is best understood as a primary disorder of the brain, a form of neurovascular headache in which neural events result in the dilation of blood vessels, which, in turn, results in pain and further nerve activation. In all probability, the basic biologic problem is dysfunction of an ion channel in the aminergic brainstem or diencephalic nuclei that normally modulates sensory input and exerts neural influences on cranial vessels.4 The migraine aura reflects a neural dysfunction, spreading depression, that is followed by vasoconstriction and oligemia. Spreading depression is actually a wave of neuronal excitation that travels over the cerebral cortex at a rate of approximately 3 mm/min that is followed by a prolonged depression of cortical neuronal activity.7,8 In patients with typical scintillating scotoma, this process begins at the center of the visual cortex, propagates to the periphery within 10 to 15 minutes and returns to normal within another 10 to 15 minutes. This wave of cortical spreading depression is responsible for the neurologic symptoms of the aura. It is followed by a period of hypovolemia representing a 20% to 30% reduction in cortical blood flow that persists for 2 to 6 hours. During this time period the patient suffers from headache but has no focal neurologic deficits. The mechanisms underlying the pathogenesis of pain in migraine are not fully understood, but key factors include the cranial blood vessels, the trigeminal innervation of blood vessels, and reflex connections of the trigeminal

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patients with familial hemiplegic migraine,10 linking that cellular mechanism with at least one form of migraine. It is common to have several members of the same family affected with migraine, and it is possible that similar gene abnormalities may be involved in other forms of migraine.

MIGRAINE AND NEURO-OTOLOGIC DISORDERS Benign Paroxysmal Positional Vertigo

Figure 29-1. Correlation of low income and high incidence of migraines. (From Stewart WF, Lipton RB, Celentrano DD, et al: Prevalence of migraine headache in the United States: Relation to age, income, race, and other sociodemographic factors. JAMA 267:64–69, 1992.)

system with the cranial parasympathetic outflow.4 The brain itself is essentially insensate, but pain can be generated by large cranial vessels, proximal intracranial vessels, or by the dura matter. The ophthalmic division of the trigeminal nerve innervates the vessels, and branches of the second cervical nerve roots innervate the structures of the posterior fossa. Stimulation of the trigeminal system causes release of vasoactive neuropeptides including calcitonin gene-related peptide. Levels of this peptide are consistently elevated during migraine headaches with or without aura and are reduced when sumatriptan successfully ameliorates migraine headaches. Voltage-gated calcium channels mediate the entry of calcium into the cell. The opening and closing of these channels are controlled by changes in voltage across the cell membrane. The gradient between intracellular and extracellular calcium controls neurotransmitter release, neuronal excitation, and many other neuronal functions.9 Mutations in one such gene have been identified in TABLE 29-1. Modified Diagnostic Criteria for Migraine Migraine is defined as episodic attacks of headache lasting 4 to 72 hours With two of the following symptoms: Unilateral pain Throbbing Aggravation on movement Pain of moderate or severe intensity And one of the following symptoms: Nausea or vomiting Photophobia or phonophobia

Baloh and colleagues reviewed the records of 247 consecutive patients who met strict criteria for the diagnosis of benign paroxysmal positional vertigo (BPPV) over a 5-year period.11 Each patient completed a detailed questionnaire and then was interviewed and examined. Criteria of the International Headache Society (IHS) were used for the diagnosis of migraine. In 31 of the patients it seems unlikely that migraine was involved in the pathophysiology because in 21 patients BPPV occurred secondary to head trauma and in 10 it began in the immediate postoperative period following a variety of different operations. In the remaining 216 patients no cause was identified. The incidence of migraine was three times greater in the large group of patients with no identifiable trigger than in the 31 patients who had an obvious cause. The age of onset of BPPV in those patients with BPPV but without migraine was skewed toward the older ages with a peak in the eighth decade, but when BPPV and migraine coexisted, the age of onset of BPPV was distributed rather evenly over multiple decades. Nearly half of the patients with onset of BPPV before age 50 had migraine, whereas only 15% of the patients with onset after age 50 had migraine. Baloh postulated that vasospasm of the labyrinthine arteries could be responsible for BPPV in migraine patients, because vasospasm is a well-documented phenomenon with migraine, and BPPV is a well-documented sequela to ischemic changes of the inner ear. The ischemia is postulated to cause the otoconia responsible for the BPPV symptoms to be released from the macular membrane.

Benign Recurrent Vertigo Recurring spells of vertigo unassociated with any auditory or neurologic symptoms are a very common reason patients are referred to both otolaryngologists and neurologists. In 1979 Slater described a series of patients who experienced recurrent vertigo lasting a few minutes to as long as 3 or 4 days and coined the term benign recurrent vertigo.12 Most were women, and their episodes were more common before or at the beginning of their menstrual periods and often awakened them in the morning. They were asymptomatic between spells. Many had a personal or strong family history of migraine. Basser had previously described recurrent vertigo in a group of young children and called the condition benign paroxysmal vertigo of childhood.12 The children exhibited all the features of severe vertigo unassociated with auditory or

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neurologic symptoms. The spells were brief and the children acted perfectly normal again after their cessation. The condition would frequently begin before age 4, recur for a few years, and spontaneously remit, although sometimes it persisted into adulthood. Patients with histories and symptoms similar to these often receive different diagnoses in different locations and clinics. Leliever and Barber13 described a group of patients with recurrent isolated vertigo without auditory or clinical neurologic abnormalities lasting 5 minutes to 24 hours and named the condition recurrent vestibulopathy. The mean age of onset of symptoms was 37 years, significantly younger than that for a comparable, larger group of patients with unilateral Ménière’s disease seen during the same period. Migraine was said to be present in 3% of the Ménière’s group and 7% of the recurrent vestibulopathy group. Both figures are well below current prevalence numbers for migraine in the general population, and the study predated the development of the IHS criteria. Over a mean follow-up period of 3.5 years, the diagnosis was changed to unilateral Ménière’s disease in only 10% of this group of patients. Vestibular Ménière’s disease is another diagnosis given to patients who experience recurrent vertigo that lasts for a few minutes to a few hours, but who have no associated auditory or neurologic symptoms. Although the American Academy of Otolaryngology—Head and Neck Surgery Committee on Hearing and Equilibrium discarded the diagnostic terms cochlear Ménière’s disease and vestibular Ménière’s disease in 1985, some continue to use them.14 Baloh and his colleagues have studied patients diagnosed with benign recurrent vertigo (BRV) who had vertiginous episodes that lasted minutes to hours, or occasionally a few days and whose attacks were commonly triggered by emotional stress, sleep deprivation, and the beginning of menstrual periods.12 There was a female preponderance of more than 2 to 1, and most patients with BRV also had migraine headaches even though the headaches often occurred independent of the episodic vertigo. They studied 24 patients with BRV who also reported a history of similar vertiginous spells in some family members. All patients underwent extensive evaluation to rule out other causes of vertigo, and none had hearing loss or other auditory features of Ménière’s disease. All were interviewed regarding a personal and family history of vertigo and migraine, and completed the standardized questionnaire, which was also sent to all relatives who agreed to participate. The IHS criteria for the diagnosis of migraine were used. Response rates were quite good; in addition to the 24 probands, 111 firstdegree relatives (parents, siblings, children), 110 other relatives (uncles, aunts, and cousins), and 43 unrelated spouses participated in the study. Twenty of the 24 probands were female, and 20 met the IHS diagnostic criteria for migraine. Nearly 40% of all of the relatives who completed the questionnaire reported spontaneous recurrent attacks of vertigo. By contrast, only 1 of 43 unrelated spouses reported a history of benign recurrent vertigo. Fifty percent of relatives met the diagnostic criteria for migraine. Baloh postulated that the high prevalence of benign recurrent vertigo and migraine in these groups suggests autosomal-dominant transmission

of a migraine vertigo syndrome with decreased penetrance in humans.12 The important clinical point of the study is that patients who present with disabling recurrent vertigo without neurologic or auditory signs and symptoms also are likely to have migraine, and the disabling vestibular symptoms can often be ameliorated or eliminated by prophylactic migraine medications (see Management section).

Ménière’s Disease Ménière’s disease is difficult to clinically distinguish from migraine. Both conditions lack a definitive diagnostic test and rely instead on clinical diagnostic criteria, those of the American Academy of Otolaryngology—Head and Neck Surgery and the IHS. But patients with Ménière’s disease also have auditory symptoms and signs, and there are no neurologic symptoms and signs associated with the spells. Because the pathophysiology of Ménière’s disease is restricted to the cochlea, it cannot be responsible for any associated positive or negative visual phenomena or proprioceptive symptoms, so their presence during spells of vertigo rules out the diagnosis of Ménière’s disease. Similarly, although it is possible for central nervous system pathophysiology to result in fluctuating sensorineural hearing loss and other auditory symptoms, it is exceedingly uncommon.

Familial Episodic Ataxia The familial episodic ataxias are rare dominantly inherited diseases characterized by dramatic episodes of ataxia.15 Both sexes are equally affected. Episodic ataxia type 1 (EA-1) patients are usually children who exhibit brief episodes of ataxia triggered by exercise, startle, or emotional upset that have a duration of seconds to a few minutes. Aura-like symptoms are common, including a feeling of weakness or falling, dizziness, and blurring of vision. The ataxia involves the trunk and extremities and speech is slurred. In between episodes of ataxia, muscle rippling (myokymia) is frequently clinically evident in the periorbital region and the fingers or can be detected with electromyography. The ataxia episodes associated with EA-1 frequently diminish as the child becomes older and may completely disappear later in life. Patient with episodic ataxia type 2 (EA-2) have ataxia episodes that last for hours, and one-third of the patients exhibit spontaneous vertical nystagmus, particularly downbeat nystagmus, between spells. The episodes vary from pure ataxia to a combinations of symptoms that usually includes vertigo, nausea, and vomiting. As with EA-1, episodes are triggered by exercise and emotional stress and often they are dramatically relieved by acetazolamide. About half of the patients with EA-2 also have migraine headaches, and there is a genetic association between the two disorders. Mutations at the same locus on chromosome 19p have been demonstrated for both diseases.16

Transient Ischemic Attacks Differentiating migraine with aura from transient ischemic attacks (TIAs) is clinically very important and sometimes

Migraine

difficult especially if there have only been one or two sensory episodes. Repeated identical self-limited attacks occurring over weeks to months suggests migrainous aura, but there may be other clues evident along the way. Symptoms of the aura usually develop gradually and consecutively over a 5- to 20-minute period and then subside, whereas TIA symptoms usually develop more rapidly and frequently simultaneously. Blumenthal17 stresses that the visual symptoms of TIA are usually negative phenomena presenting as a black or blank visual loss such as amaurosis fugax or hemianopic scotoma. In contrast, the visual sensations in migraine aura usually include positive phenomenon such as scintillations or fortification spectra as well as negative phenomena such as scotomata.

Stroke Without question, individuals with migraine are at higher risk for ischemic stroke than those without migraine.18 The association is highest in those who have migraine with aura, but the risk probably extends to those who have migraine without aura and to children with migraine. This risk is increased in those under age 40 years, and by the use of oral contraceptive agents and smoking. Patients with migraine should not smoke. Women with migraine should not use combined oral contraceptive pills, including those with low estrogen, even if no other risk factors for stroke exist.18 Vertigo can also be a manifestation of cerebrovascular disease, and since the circulation to the inner ear arises from the vertebrobasilar system, either central or peripheral vascular insufficiency can be responsible. Infarctions of the vestibulocerebellar pathways in the most dorsolateral portion of the rostral medulla and bilateral cerebellar infarctions in the distribution of the posterior inferior cerebellar artery have been described in patients who exhibited only gait ataxia and acute vertigo without other symptoms suggestive of Wallenberg’s syndrome.15 Otolaryngologists must be aware that isolated vertigo can be a manifestation of posterior fossa infarction and should suspect it in elderly patients and those with cerebrovascular risk factors.

NEUROTOLOGIC SYMPTOMS Vertigo At least 25% of all patients with migraine experience vertigo.19,20 The episodes can constitute all or part of a migraine aura, can occur spontaneously and seem to be unrelated to any migraine headaches, or can develop in response to motion of the individual or the individual’s surrounding environment. In some patients 10- to 15-minute episodes of vertigo precede a migraine headache as a prodrome and are sometimes or always sequentially associated with other symptoms of the aura, most commonly scintillations or numbness and tingling. However, the vertiginous spells do not always precede the headaches as a prodrome. In Kayan and Hood’s 53 patients with both symptoms, vertigo immediately preceded the headache in only 15%, whereas

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it occurred sometime during the headache in 47% and in the headache-free interval in 36%.20 Spontaneous vertigo attacks in patients with migraine can last as little as 5 minutes or as long as 3 to 6 days but commonly last from 30 minutes to 2 hours. The spells of each patient usually have a similar duration. Generally, the spells are severe and evoke pallor, diaphoresis, nausea, and commonly vomiting. Cutrer and Baloh21 propose two different mechanisms for the production of dizziness with migraine. They believe that vertiginous episodes lasting minutes to 2 hours that are temporally associated with headaches are due to the spreading wave of depression or transient vasospasm (or both), as are the other aura phenomena. When vertigo and motion sickness last for days, with or without headache, Cutrer and Baloh postulate that neuroactive peptides are released into peripheral and central vestibular structures and cause an increased baseline firing rate of primary afferent neurons and increased sensitivity to motion.

Motion Sickness Several authors have noted a close relationship between migraine and motion sickness. In a classic study of 9000 Swedish schoolchildren, Bille22 matched children with clearly established migraine to a similar group without migraine. Severe motion sickness was present in 49% of the children with migraine and only 10% of the control group. Barabas, Matthews, and Ferrari studied motion sickness in 60 children with migraine and three similarly sized control groups.23 They defined motion sickness as three or more episodes in which an otherwise normal appearing child vomited during or immediately after an automobile ride. Forty-five percent of the children with migraine had motion sickness compared with 5% to 7% of the three control groups. In adults, Baloh19 reported twothirds of migraine patients to be motion-sensitive. Kayan and Hood reported the association in more than 50% of their 200 unselected migraine adults,20 and Kuritzky noted motion sickness to be more prevalent in patients who had migraine with aura than in those without aura.24 Within the large number of migraine patients who have motion sickness exists a subset of patients who have such severe motion sickness that it significantly restricts their life. They limit their head motion to an absolute minimum, plan their day’s activities to minimize movement, and rest several times during the day, remaining motionless for a half hour or so until symptoms abate. If they cannot avoid continuous motion, the queasiness proceeds to nausea and imbalance, vertigo, emesis, and a migraine headache.

Auditory Symptoms Hearing loss and tinnitus are much less common than vestibular symptoms in migraine. However, in the small subset of patients with basilar migraine, a fluctuating low-frequency sensorineural hearing loss identical to that seen in Ménière’s disease is found in more than half of affected individuals.25 Phonophobia (and photophobia) is extremely common and helps differentiate migraine from nonmigraine headache.

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MIGRAINE TYPES ASSOCIATED WITH NEUROTOLOGIC SYMPTOMS Migraine with Aura In the IHS classification, aura denotes the occurrence of any or all of the neurologic manifestations experienced as a result of migraine whenever they occur and does not represent the time period in relation to the headache in which these symptoms occur.5 The IHS describes migraine with aura as an: idiopathic recurring disorder manifesting with attacks of neurological symptoms unequivocally localizable to cerebral cortex or brain stem, usually gradually developed over 5-20 minutes and usually lasting less than 60 minutes. Headache, nausea, or photophobia usually follow neurological aura symptoms directly or after a free interval of less than an hour. The headache usually lasts 4-72 hours, but may be completely absent.5

Visual symptoms are by far the most common component of the migraine aura, and the most common visual phenomena are (1) scotomata, or blind spots, (2) teichopsia or fortification spectra (a zigzag pattern in the visual field resembling a fort), and (3) flashing of lights (photopsia) or colored lights. Bartleson3 has provided a clear concise summary and states that the visual symptoms: … usually affect both eyes simultaneously but can affect one eye alone. The patient may experience negative phenomena only and describe hemianopia and quadrantanopia, complete blindness, tunnel vision, asymmetric field deficits, monocular blindness, altitudinal defects, or one or more scotoma. More frequently, positive phenomena occur and consist of stars, sparks, unformed flashes of light (photopsia), simple and complex geometric patterns, or jagged zigzags of light (teichopsia or fortification spectra). These visual hallucinations are usually white but can be any color. They are typically present with the eyes open or closed. The slowly evolving images have a shimmering, flickering quality. The positive and negative visual phenomena are frequently combined and the term scintillating scotoma is used. The patient may report wavy lines like heat off pavement or as though looking through rain covered glass …

The most common sequence is the slow onset of bilateral central scotomata or luminous phenomena that move slowly in an arc to the periphery of one visual field. The leading edge is a zigzag of light followed by moving geometric patterns, which in turn leave behind expanding homonymous scotomata. (Author’s note—compare this description with the discussion of pathophysiology.) Paresthesias present as a numbness, tingling, or both, and affect the face, upper or lower extremities, or occasionally the trunk. According to Fisher26 “a reliable sign of migrainous paresthesias is the ‘march’ of numbness as it gradually spreads over the face or fingers and hand and migrates from face to limb or vice versa or crosses to the face and hand on the opposite side.” These paresthesias are not the result of hyperventilation but rather reflect the effects of spreading depression (see Etiology and Pathogenesis section). Vertigo can also constitute part of the migraine aura, but the frequency with which this occurs is unknown. Five to fifteen minutes of vertigo are followed by a typical migraine

headache. The vestibular aura may precede only some and not all of a patient’s headaches, and visual scintillations or numbness and tingling may be part of the aura as well.

Basilar Migraine Bickerstaff27 described a subset of migraine in which the aura symptoms reflected ischemia in the distribution of the basilar artery. The majority of Bickerstaff’s patients were adolescent girls in whom the migraine attacks often occurred premenstrually. The clinical picture also can include stupor, loss of consciousness, neurotologic symptoms, and extreme postictal fatigue. To establish the diagnosis of basilar migraine, the episodes must contain two or more of the following symptoms5: • Visual symptoms in both temporal and nasal fields of both eyes • Dysarthria • Vertigo • Tinnitus • Decreased hearing • Diplopia • Ataxia • Bilateral paresthesia • Bilateral pareses • Decreased level of consciousness These symptoms reflects dysfunction of the involved neural structures, including the brainstem, cerebellum, cranial nerve nuclei, and occipital lobe cortex.

Migraine Aura without Headache This category of migraine is confusing to many physicians and patients alike. Often, neither group even considers migraine as a possible cause for vertigo when the headache and the vertigo occur at different times or when the vertigo is much more distressing to the patient than the headaches. Whitty28 reported a series of patients who experienced symptoms typically seen during a migraine aura, but who had no headaches with their symptoms. Some of the patients had the same aura symptoms earlier in life associated with migraine headaches, and some developed typical migraine headaches later in life in association with their aura. Other patients experienced the aura symptoms alone on some occasions and together with a typical migraine headache on other occasions. Others have described similar patients and used the terms migraine equivalent or migraine accompaniments.26 The key to the diagnosis is the history of repeated episodes in which neurotologic symptoms coexist with symptoms typical of a migraine aura. A past history of migraine, motion sickness, premenstrual clustering of attacks, headaches associated with some of the attacks, or a family history of migraine are frequently present in these patients.

MANAGEMENT Management of the neurotologic symptoms of migraine is made difficult by at least three problems. First, as

Migraine

mentioned above, migraine is underdiagnosed and the neurotologists may not suspect it as the cause of the patient’s symptoms. Second, much of the general migraine literature ignores any reference to neurotologic symptoms associated with migraine, and concentrates on the headaches or the other neurologic symptoms of the aura. Third, there is almost no clinical research evaluating treatment of the neurotologic symptoms associated with migraine.

Management of Headaches It is necessary to first review management of the headache. Strategies typically include (1) lifestyle changes and the identification and avoidance of specific triggers, (2) treatment of the acute headache, and (3) prophylactic therapy. In many patients with migraine, the brain does not seem to tolerate the peaks and troughs of life very well. Regular sleep, regular meals, exercise, and avoidance of peaks of stress and troughs of relaxation can help reduce the occurrence of episodes.4 In some patients, barometric pressure changes or excessive exposure to motion (especially in children) regularly initiate migraine headaches. Many women recognize that their migraine attacks are more predictable and more severe around menstruation, underscoring the influences of hormonal changes. Although it sometimes requires a personal headache and diet diary, many patients are able to report a spectrum of migraine triggers that that can initiate their attacks. For some patients, certain forms of alcohol, such as red wine, beer, or champagne are common inciters; in other individuals headaches are stimulated by caffeine, cured meats, monosodium glutamate, aspartame, strong cheeses, yogurt, or pickled foods. Finally, external sensory stimuli such as cigar smoke, certain bath oils, perfumes, or visual sensory stimuli from bright lights or repeated striped or geometric patterns can provoke attacks.17 In all these situations, careful attention to the investigation, identification, and subsequent elimination of the offending stimuli can dramatically reduce the frequency of migraine headaches. Since the introduction of sumatriptan in 1992, the triptans have become the mainstay of symptomatic or abortive treatment for moderate to severe migraine headaches. Today at least five triptans are available for prescription and, although oral, nasal, intramuscular, and suppository forms of administration are available, 80% of the prescriptions are for oral use. The cost, efficacy, and side effects differences are reviewed elsewhere,4,29 but all the triptans are very effective in ameliorating the pain of a migraine headache. However, they are not able to terminate an attack, and the headache recurs in 25% to 40% of patients with long-lasting migraine attacks. Nearly 25% of all patients do not respond to any of the triptans. Another problem is that with frequent migraines, repeated use of the triptans decreases the time interval between migraine attacks, and drug-induced headaches result. Furthermore, all triptans exhibit vasoconstrictive action and are contraindicated in patients with ischemic heart disease, uncontrolled hypertension, cerebrovascular disease, and in pregnancy. There are other management strategies for the

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treatment of acute migraine headaches, but these are beyond the scope of this chapter.4 Migraine prophylaxis is recommended for patients who experience three or more attacks per month, whose attacks are incapacitating and impair normal activities, who cannot tolerate or are not helped by abortive therapy, who cannot psychologically cope with attacks, and who have certain other special situations.30 Drugs commonly used for migraine prophylaxis include beta-blocking agents, calcium channel-blocking agents, antidepressants, anticonvulsants, and others. The benefit of prophylactic treatment by beta blockers was detected incidentally in migraine patients being treated for hypertension or angina pectoris. Propranolol is the most effective of these. Meta-analysis of 53 studies including 2403 patients treated with 160 mg of propranolol versus a reference substance or placebo yielded a 44% reduction in migraine activity when daily headache recordings were used to assess outcome, and 65% reduction in migraine activity when clinical ratings of improvement in global patient reports were used.29 The dropout rate due to side effects was 5.3%. Although calcium channel blockers such as verapamil and nimodipine are touted by some, others regard them as only marginally effective or ineffective.29 The antidepressant amitriptyline is an effective migraine prophylactic agent, even in children. Side effects usually necessitate initiating treatment with a subtherapeutic dose and gradually increasing the dosage over a period of several weeks until an effective therapeutic level is achieved. The carbonic anhydrase inhibitor acetazolamide was originally developed as an antiepilepsy drug. In addition to its diuretic effects, it slightly acidifies blood and tissue including the brain. It produces dramatic benefit in patients with familial EA-2 and familial hemiplegic migraine who exhibit mutations in the same calcium channel gene necessary for both central and peripheral neurotransmission. That gene is expressed throughout the brain but is particularly prominent in the cerebellum and is also heavily expressed in the neuromuscular junction where it tightly couples with neurotransmitter release.16 Several controlled clinical studies have documented the prophylactic effectiveness of valproic acid in preventing migraine headaches, but adverse effects resulted in suspension of treatment in up to 20% of patients in different studies. Rarely hepatitis, pancreatitis, and significant platelet effects occur, and the drug has significant risk of teratogenicity.30 There is no evidence that valproic acid mitigates vestibular symptoms accompanying migraine. Another interesting approach to migraine prophylaxis is the use of botulinum toxin (Botox) injections into the neck or scalp. The mechanism by which botulinum toxin works to prevent migraine headaches is unknown, but it is probably unrelated to Botox’s known effect on muscle relaxation. Although not yet approved for use in migraine, several case studies and trials have demonstrated safety and efficacy, and the effects after pericranial injections can last 3 or more months.31,32 No data indicate whether Botox injections eliminate or improve vestibular symptoms associated with migraine.

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Management of Vestibular Symptoms Vestibular symptoms associated with migraine can be managed symptomatically, can be treated prophylactically, or can be managed with vestibular rehabilitation therapy. Patients in whom personal or environmental motion initiates migraine episodes routinely curtail their own head movement to avoid the evoked imbalance, nausea, and progression to vertigo. These patients will avoid turning their head when the physician or nurse enters the room and will react unfavorably if the examining chair is turned quickly. In such individuals, mild vestibular suppression (e.g., with diazepam 2 mg every 4 to 6 hours as needed) is often quite helpful if prophylactic measures are ineffective (see later discussion). Management of the acute severe vestibular episode associated with migraine is supportive. If oral agents can be used, that is, if there is no emesis, low dosages of benzodiazepine drugs such as diazepam are helpful. The administration of antiemetic agents such as metoclopramide (Reglan) that increase gastric motility can facilitate the absorption of the primary drug and thus help ameliorate the attack. Promethazine (25 or 50 mg orally or by suppository) has both antivertiginous and antiemetic properties and is also recommended. When the associated vestibular symptoms are incapacitating, prophylaxis is appropriate. No controlled clinical trials have documented beneficial effects of drugs, but in the author’s experience propranolol often dramatically eliminates spontaneous spells of vertigo in these patients and greatly ameliorates the abnormal sensitivity to motion they experience. The effective dose is usually 80 to 120 mg a day in two divided doses. Monitoring resting pulse for bradycardia is essential, and fatigue and reduced energy are sometimes observed. The drug is contraindicated in patients with asthma. Beneficial effects may not be apparent for the first 2 to 3 weeks of therapy. Several patients taking acetazolamide 250 mg bid have had similar, sometimes dramatic improvements in spontaneous vertigo and motion sensitivity associated with migraine. Baloh believes the drugs beneficial effect results from its altering the pH within the cerebellum, thus stabilizing the mutated calcium channel.16 All patients taking acetazolamide notice that carbonated beverages taste terrible, and up to 20% experience episodic acral or facial paresthesias lasting up to 30 minutes. The paresthesias become shorter in duration and less frequent over a few months. Long-term therapy increases the risk of renal calculi, but this risk can be reduced by drinking citrus juices. Because of cross-reactivity, the drug should not be given to patients allergic to sulfa preparations. The antiepileptic drug lamotrigine has not been used to treat vestibular symptoms in migraine, but perhaps it should be studied. Although it has been shown to be ineffective in preventing migraine headaches, it is very effective in treating the aura associated with migraine.30 It blocks voltage-sensitive sodium channels, leading to inhibition of the neuronal release of glutamate and aspartate, which are essential to spreading depression. Vestibular rehabilitation therapy has been recommended for use in migraine patients. However, since

most migraineurs with disabling symptoms suffer from abnormal sensitivity to motion, it seems counterintuitive to recommend as therapy an exercise program based on repetitive motion. One is reminded of the early therapeutic efforts at treating BPPV with exercises designed to bring on the symptoms.

SUMMARY Migraine is common and often is disabling, both because of headaches and because of associated vertigo and motion sensitivity. It is related to benign paroxysmal positional vertigo, benign recurrent vertigo (sometimes diagnosed as recurrent vestibulopathy, vestibular Ménière’s disease, or benign paroxysmal vertigo), and familial episodic ataxia. Understanding of the etiology and pathophysiology is improving, but there is a disturbing lack of awareness of the association of vestibular symptoms in patients with migraine by most nonotolaryngologists treating migraine patients, and no research studies have evaluated drug effectiveness in treating vestibular symptoms associated with migraine. However, empiric evidence suggests that effective treatment is available, and the great majority of patients with severe or disabling vestibular symptoms can be very effectively treated without surgery.

REFERENCES 1. Lipton RB, Diamond S, Reed M, et al: Migraine diagnosis and treatment: Results from the American Migraine Study II. Headache 41:638–645, 2001. 2. Stewart WF, Lipton RB, Celentrano DD, et al: Prevalence of migraine headache in the United States: Relation to age, income, race, and other sociodemographic factors. JAMA 267:64–69, 1992. 3. Bartleson JD: Transient and persistent neurological manifestations of migraine. Stroke 15:383, 1984. 4. Goadsby PJ, Lipton RB, Ferrari MD: Migraine—Current understanding and treatment. N Engl J Med 346(4):257–270, 2002. 5. Headache Classification Committee of the International Headache Society: Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8(Suppl 7):1–96, 1988. 6. Diamond ML: The role of concomitant headache types and nonheadache co-morbidities in the underdiagnosis of migraine. Neurol 58(Suppl 6):S3–S10, 2002. 7. Lauritzen M: Cortical spreading depression in migraine. Cephalalgia 21:757–760, 2001. 8. Spierings ELH: Mechanisms of migraine and action of antimigraine medications. Headache 85(4):943–958, 2001. 9. Edvinsson L: Aspects on the pathophysiology of migraine and cluster headache. Pharmacol Toxicol 89:65–73, 2001. 10. Ophoff RA, Terwindt MN, Vergouve R, et al: Familial hemiplegic migraine and episodic ataxia type 2 are caused by mutation in the Ca2+ channel gene CACNL1A4. Cell 87:543–552, 1996. 11. Ishiyama A, Jacobsen KM, Baloh RW: Migraine and benign positional vertigo. Ann Otol Rhin Laryngol 109:377–380, 2000. 12. Oh AK, Lee H, Jen JC, et al: Familial benign recurrent vertigo. Am J Med Genetics 100:287–291, 2001. 13. Leliever WC, Barber HO: Recurrent vestibulopathy. Laryngoscope 91:1–6, 1981. 14. Pearson BW, Brackmann DE: Committee on Hearing and Equilibrium Guidelines for Reporting Treatment Results in Ménière’s Disease. Otolaryngol Head Neck Surg 93:579–581, 1985.

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15. Baloh RW: Episodic vertigo: Central nervous system causes. Curr Opin Neurol 155:17–21, 2002. 16. Baloh RW, Jen JC: Genetics of familial episodic vertigo and ataxia. Ann NY Acad Sci 956:338–345, 2002. 17. Blumenthal HJ, Rapoport AM: The clinical spectrum of migraine. Headache 85(4):897–909, 2001. 18. Tietjen GE: The relationship of migraine and stroke. Neuroepidemiology 19:13–19, 2000. 19. Baloh RW: Neurotology of migraine. Headache 37(10):615–621, 1997. 20. Kayan A, Hood JD: Neuro-otological manifestations of migraine. Brain 107:1123–1142, 1984. 21. Cutrer FM, Baloh RW: Migraine-associated dizziness. Headache 31:300–304, 1992. 22. Bille BS: Migraine in school children. Acta Paediatr Scand 51(Suppl 135): 1–151, 1962. 23. Barabas G, Matthews WS, Ferrari M: Childhood migraine and motion sickness. Pediatrics 72:188, 1983.

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24. Kuritzky A, Zergler DK, Hassanein R: Vertigo, motion sickness and migraine. Headache 21:227, 1981. 25. Olsson JE: Neurotologic findings in basilar migraine. Laryngoscope 101:1–41, 1991. 26. Fisher CM: Late-life migraine accompaniments as a cause of unexplained transient ischemic attacks. J Can Sci Neurol 7(1):9–17, 1980. 27. Bickerstaff ER: Basilar artery migraine. Lancet 1:15–17, 1961. 28. Whitty CWM: Migraine without headache. Lancet 2:283–285, 1967. 30. Diener HC, Limmroth V: Advances in pharmacological treatment of migraine. Exp Opin 10(10):1831–1845, 2001. 30. Krymchantowski AV, Bigal ME, Moreira PF: New and emerging prophylactic agents for migraine. CNS Drugs 16 (9):611–634, 2002. 31. Gobel H, Heinze A, Heinze-Kuhn K, et al: Evidence-based medicine: Botulinum toxin A in migraine and tension-type headache. J Neurol 248(Suppl 1):I/34–I/38, 2001. 32. Silberstein SD: Review of botulinum toxin type A and its clinical significance in migraine headache. Exp Opin 2(10):1649–1654, 2001.

Chapter

30 Nancy M. Young, MD John Grant, MD

T

Seizure Disorders Outline Diagnosis and Evaluation Management of Seizures Management of Status Epilepticus Neurotogenic Manifestations of Seizure Disorders

he neurotologist may encounter seizure for a number of reasons. First, it is a very common disorder. It is estimated that 10% of the general population will experience at least one seizure and that 4% of persons who live until age 80 will have a chronic seizure disorder.1 Second, seizure activity can produce symptoms of vestibular and auditory disease that need to be recognized as central and not peripheral. Third, surgeons who diagnose and operate on lesions in the cranial vault need to understand the significance and treatment of seizures. Pain is a symptom of peripheral nerve irritation. Analogously, a seizure is a symptom of irritation of the brain. A seizure occurs secondary to excessive neuronal discharge in the cerebral cortex. It results in transient impairment of sensation, movement, consciousness, or memory. Epileptic seizures are classified according to clinical and electroencephalographic (EEG) findings (Table 30-1). Seizures are either partial or generalized depending on whether clinical or EEG data demonstrate the area of onset as limited to a part of the brain in one hemisphere or beginning simultaneously in both hemispheres. Therefore, the onset of partial seizures is by definition focal. They are further subclassified depending on whether consciousness is impaired. If partial seizures occur without impairment of consciousness, they are classified by whether symptoms are sensorimotor, autonomic, or psychic. In contrast, the onset of generalized seizures involves both hemispheres and lapses of consciousness always occur. Generalized seizures can be nonconvulsive or convulsive. Absences are nonconvulsive generalized seizures. Petit mal epilepsy consists of typical brief absences. In contrast, convulsive generalized seizures are characterized by major motor events. For example, tonic-clonic generalized seizures (previously referred to as grand mal) begin with extension of the extremities followed by synchronous jerking movements. Single seizures can occur and recur as a normal response of brain tissue to physiologic stress. These seizures are often referred to as reactive. They can be caused by sleep deprivation, alcohol or sedative withdrawal, and reversible 518

Vestibular Seizures Vestibular Vertigo in Children Vestibulogenic Seizures Audiogenic Seizures Summary

or irreversible toximetabolic processes, which include hyponatremia, hypocalcemia, hepatic encephalopathy, and hypoxia. Epilepsy refers to a chronic condition in which there are recurrent seizures of cerebral origin. This term implies that a chronic underlying neurologic problem is present. Classification of epilepsy (Table 30-2) depends on age of onset, whether the seizures are partial or generalized, and whether the etiology is idiopathic or acquired. Some authors reserve the term epilepsy for patients who have idiopathic recurrent seizures. Seizure disorder is a more general term for chronic recurrent seizure, regardless of etiology.

DIAGNOSIS AND EVALUATION Seizures need to be considered in the diagnosis of any patient with a history of a lapse or alteration of consciousness, memory, sensation, or movement. A blackout is a common presentation of seizures and many other disorders. The differential diagnosis of blackout includes a number of disorders including syncopal episodes secondary to cardiac function or poor cerebral circulation, head trauma or concussion, transient ischemic attacks (TIAs), and vertebrobasilar migraine. Patients being initially evaluated for loss of consciousness of unknown etiology often undergo testing to determine whether cardiac syncope versus an epileptic seizure has occurred. Unusual and subtle presentations of recurrent seizures can include a history of “daydreaming” episodes, frequent automobile accidents, bed wetting, or aphasic or dysphasic episodes. Of special importance to the neurologist is the fact that vertigo can occur secondary to seizure activity. A careful history is critical to the diagnosis of seizure disorders. Descriptions of any prodrome, aura (initial signs and symptoms), and the ictus (the event itself ), and postictal events are critical. An aura consists of abnormal sensation of motion, thought, or movement. It signifies a partial

Seizure Disorders

TABLE 30-1. International Classification of Epileptic Seizures I. Partial (focal, local) seizures A. Simple partial seizures 1. With motor signs 2. With somatosensory or special sensory symptoms 3. With autonomic symptoms or signs 4. With psychic symptoms B. Complex partial seizures 1. Simple partial onset followed by impairment of consciousness 2. With impairment of consciousness at onset C. Partial seizures evolving to secondarily generalized seizures 1. Simple partial seizures evolving to generalized seizures 2. Complex partial seizures evolving to generalized seizures 3. Simple partial seizures evolving to complex partial seizures II. Generalized seizures (convulsive or nonconvulsive) A. Absence seizures 1. Typical absences 2. Atypical absences B. Myoclonic seizures C. Clonic seizures D. Tonic seizures E. Tonic-clonic seizures F. Atonic seizures (astatic seizures) III. Unclassified epileptic seizures From: Commission on Classification and Terminology of the International League Against Epilepsy: Proposal for Revised Clinical and Electroencephalographic Classification of Epileptic Seizures. Epilepsia 22:489–501, 1981.

seizure even if a generalized seizure follows as a result of spread of discharge from the initial focus. A patient is able to describe the seizure and the events that follow only if a purely sensorimotor partial seizure has occurred. It is much more common, however, that seizures involve alterations of consciousness or memory that necessitate the account of a reliable witness. Generalized tonic-clonic seizures should not be remembered by the patient unless they are due to malingering or hysteria.2 The physical examination may provide information regarding possible seizure etiology. Patients with neurocutaneous syndromes such as tuberosclerosis or SturgeWeber syndrome may have characteristic skin findings in addition to cerebral lesions. Papilledema and other signs of increased intracranial pressure are important as well as evidence of meningeal signs. Any sensory or motor asymmetry may point to the site of the structural lesion. Seizure occurs as an initial symptom in 15% of brain tumor patients.3 However, their occurrence depends greatly on tumor location. Tumors in or near the sensorimotor cortex are more likely to cause seizure. The presentation of tumors of the cerebellopontine angle (CPA) is not associated with seizure. In House’s initial series of 500 patients with acoustic tumors, seizure was not a reported symptom.4 In terms of surgical management of CPA tumors, chronic seizures can occur in patients who have undergone procedures that include a transtentorial approach in order to expose the temporal lobe widely.5,6 Cabral, King, and Scott7 reported that 22% of 45 patients with large tumors who underwent a combined translabyrinthine and transtentorial approach developed chronic seizures and required treatment with antiepileptic drugs. In contrast, the occurrence of chronic seizures has

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not been reported as a consequence of acoustic tumor removal via the translabyrinthine, middle fossa, or posterior fossa approaches, all of which involve less manipulation of the temporal lobe. So although the potential for a seizure disorder to develop is always present during surgery adjacent to or within the brain, it is more likely to occur when manipulation is traumatic or protracted. In any patient with new onset of a seizure disorder or recurrence of previously controlled seizures, a thorough examination must be done to look for an underlying etiology and potentially treatable cause. The most important aspect of investigation is obtaining a detailed history in order to determine whether the episode was, indeed, consistent with a seizure and whether there have been recurrent episodes. In children with a family history of seizures, it may not be necessary to perform additional studies.8 The most common causes of seizures are age related. In childhood, typical causes include perinatal asphyxia or trauma, congenital malformations, and toximetabolic disorders. In adolescents, trauma and neoplasms predominate. In older adults, stroke, tumor, and degenerative diseases are most frequently the underlying problem. Many drugs are known to precipitate seizures. They include many common agents, some of which are often prescribed by otolaryngologists. Examples include antihistamines, sympathomimetics, and prednisone (in the setting of hypocalcemia). General and local anesthetics, narcotic analgesics, and iodinated contrast agents (such as metrizamide) are also agents reported to cause seizures.9 Laboratory tests to be considered include studies of hepatorenal function, glucose, calcium, magnesium, and electrolytes, complete blood count (CBC) with platelets, erythrocyte sedimentation rate (ESR), and serologic and immunologic studies. The occurrence of seizures secondary to hyponatremia must be kept in mind in any patient undergoing a surgical procedure. Hyponatremia in headinjured patients is not uncommon, especially in children, and usually presents as a seizure.10 Some patients secrete inappropriate levels of antidiuretic hormone (ADH) during the postoperative period, which can lead to intractable seizures.11 Selected patients may need to undergo a lumbar puncture so that cerebrospinal fluid (CSF) can be sent for protein, glucose, culture, and serology for syphilis. Neuroimaging studies are often essential to the workup of seizure disorders. Magnetic resonance imaging (MRI) and, in some cases, functional MRI have replaced computed tomography as the neuroimaging modality of choice. EEG is one of the few diagnostic tests that is sensitive to abnormalities of brain function as opposed to structure. The use of EEG is important to confirm the clinical diagnosis of seizure and to assist in classification. Most EEG laboratories use procedures to provoke seizure activity in order to increase diagnostic yield. These procedures can include hyperventilation, photic stimulation, sleep deprivation, and use of pharmacologic agents. It is important to realize that a normal interictal EEG does not exclude a seizure disorder. Nor does an abnormal EEG necessarily confirm the diagnosis of seizure disorder. When there is doubt about the diagnosis, 24-hour video EEG monitoring is useful.

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TABLE 30-2. International Classification of Epilepsies and Epileptic Syndromes 1. Localization-related (focal, local, partial) epilepsies and syndromes 1.1 Idiopathic with age-related onset At present, two syndromes are established, but more may be identified in the future: benign childhood epilepsy with centrotemporal spikes and childhood epilepsy with occipital paroxysms 1.2 Symptomatic This category compromises syndromes of great individual variability, which will mainly be based on anatomic localization, clinical features, seizure types, and etiologic factors (if known). 2. Generalized epilepsies and syndromes 2.1 Idiopathic, with age-related onset, listed in order of age Benign neonatal familial convulsions Benign neonatal convulsions Benign myoclonic epilepsy in infancy Childhood absence epilepsy (pyknolepsy) Juvenile absence epilepsy Juvenile myoclonic epilepsy (impulsive petit mal) Epilepsy with grand mal seizures on awakening Other generalized idiopathic epilepsies, if they do not belong to one of the above syndromes, can still be classified as generalized idiopathic epilepsies. 2.2 Idiopathic and/or symptomatic, in order of age of appearance West syndrome (infantile spasms, Blitz-Nick, and Salaam Krampfe) Lennox-Gastaut syndrome Epilepsy with myoclonic-astatic seizures Epilepsy with myoclonic absences 2.3 Symptomatic 2.3.1 Nonspecific etiology Early myoclonic encephalopathy 2.3.2 Specific syndromes Epileptic seizures may complicate many disease states Included under this heading are diseases in which seizures are a presenting or predominant feature. 3. Epilepsies and syndromes undetermined as to whether they are focal or generalized 3.1 With both generalized and focal seizures Neonatal seizures Severe myoclonic epilepsy in infancy Epilepsy with continuous spike-waves during slow wave sleep Acquired epileptic aphasia (Landau-Kleffner syndrome) 3.2 Without unequivocal generalized or focal features This heading covers all cases where clinical and EEG findings do not permit classification as clearly generalized or location-related, such as in many cases of sleep grand mal. 4. Special syndromes 4.1 Situation-related seizures Febrile convulsions Seizures related to other identifiable situations such as stress, hormonal changes, drugs, alcohol, or sleep deprivation 4.2 Isolated, apparently unprovoked epileptic events 4.3 Epilepsies characterized by specific modes of seizure precipitation 4.4 Chronic progressive epilepsia partialis continua of childhood From: Commission on Classification and Terminology of the International League Against Epilepsy: Proposal for Revised Clinical and Electroencephalographic Classification of Epileptic Seizures. Epilepsia 22:489–501, 1981.

MANAGEMENT OF SEIZURES It is of utmost importance that any patient who has a seizure disorder be fully evaluated for the presence of a treatable underlying cause. It must be remembered that seizure is simply a symptom of brain dysfunction and not a disease entity in itself. The diagnosis of “idiopathic epilepsy” is a diagnosis of exclusion analogous to the diagnosis of Bell’s palsy in patients with facial nerve paralysis. If an underlying disease is found, then in some cases treatment with an antiepileptic drug (AED) may not be required. Patients with an idiopathic seizure disorder or one due to a known lesion that cannot be corrected need to have their seizures medically controlled. There are many AEDs, all of which nonspecifically increase the brain’s seizure threshold. Often this effect is accomplished by influences on ionic mechanisms critical to membrane excitability. The choice of AED depends on the classification

of the seizure disorder and the number of possible side effects. In general, the drug of choice for partial and generalized convulsive seizures is carbamazepine (Tegretol) and the drug of choice for absence of seizures is ethosuximide (Zarontin). These two AEDs have good efficacy and low incidence of unacceptable side effects. If these agents are unsuccessful, then alternative single agents should be used. Adding drugs (polytherapy) can be tried in refractory patients but is not highly successful.1 Because many newer agents are available in only oral form, Dilantin and phenobarbital are still useful anticonvulsants in the surgical population. Intravenous phosphenytoin is a safer formulation of Dilantin and is usually preferred. The most common reason for failure of monotherapy is failure to achieve appropriate drug levels.12 Common side effects of AEDs include sedation, behavioral changes, tremor, vertigo, diplopia, nystagmus, and ataxia.13 Thus, it is important to realize that a patient with a

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sensation, which can occur before and between episodes of generalized seizures.17 Vestibular seizures are defined as seizures that are simple or complex partial sensory seizures in which the overriding symptom is vertigo. Patients with vestibular seizures experience vertigo or disequilibrium, which is often associated with body or head and eye rotation with or without nystagmus. If nystagmus occurs, its direction and that of measurable body motion can be the same. This finding is in contrast to peripheral vestibular syndromes in which the direction of nystagmus and body fall are opposite, because the latter occurs on the basis of vestibulospinal compensation.18 A history of associated symptoms helps to distinguish a central versus peripheral site of origin of vertigo. Patients with vestibular epilepsy would not be expected to have positional vertigo or associated hearing loss. They would be likely to have associated symptoms of temporal lobe dysfunction. However, these symptoms may go undetected unless specifically sought. Phenomena suspicious of temporal lobe origin include auditory hallucinations, which may range from simple tinnitus to hearing words or sentences. Alterations of consciousness may occur. For example, the patient may describe himself or herself as being in a dreamlike state during attacks. Because of the importance of the temporal lobe in a perceptual integration, the patient may complain of a disorder of time perception. Time may rush by or stand still during the episode. A feeling of déjà vu or depersonalization may also be described.19 Kogeorgos, Scott, and Swash20 reported 30 patients with vestibular seizures. These patients had a mean age at onset of 25 years and represented less than 1% of the author’s population of seizure patients. They had intermittent brief episodes of disequilibrium. Almost half experienced rotational vertigo. Almost a quarter of the patients in the study had a history of the occurrence of more generalized seizures. Nearly half had a history of brief alterations in consciousness (absences or other features suggestive of temporal lobe epilepsy). EEG evaluations demonstrated a posterior temporal lobe focus in the vast majority of patients. Almost all responded well to AEDs. Note that vestibular epilepsy and a peripheral vestibular problem can both exist by chance or can be a result of a common etiologic factor such as head trauma or vascular disease. The suspicion of vestibular epilepsy requires evaluation in an EEG laboratory. If the diagnosis is confirmed, then the search for an underlying cause of the cerebral dysfunction must be performed. If no treatable cause is found, then an AED can be used. If medical therapy fails, then surgical therapy remains an option.

Vestibular Vertigo in Children Vestibular seizure is an important diagnosis to consider in children who have vertigo. Vertigo is not as common a complaint nor as well studied in children as in adults. In adults it is more commonly due to peripheral disease. In children, central disease must be strongly considered. Eviatar and Eviatar21 evaluated 50 children who were referred to a neurology clinic with a chief complaint of vertigo. A high incidence of central vertigo (42 of 50 patients) was found. Vestibular seizure was the diagnosis in the majority of children (25 of 42). Age of onset ranged between 3 and 18 years.

Vestibular vertigo in children can be suspected by the presence of a positive family history of seizures. A careful history will elicit that at least some episodes of vertigo are associated with focal or generalized seizure phenomena such as an alteration or loss of consciousness, facial or extremity twitching, inability to speak, or progression of the attack to an obvious tonic-clonic generalized seizure. The differential diagnosis of vertigo in children includes cerebellar and brainstem tumors, benign postural vertigo (BPV) of childhood, perilymph fistula, labyrinthitis, posttraumatic vertigo, otitis media, vestibular neuronitis, and endolymphatic hydrops. BPV is an important cause of episodic vertigo in children that does not occur in adults. Its onset occurs when the child is between 1 and 4 years old. The child experiences sudden episodic vertigo without headache or change in consciousness. The disease is self-limited; it resolves in months or years. BPV is thought to be a migraine equivalent and therefore occurs secondary to a cerebral vasomotor disorder. Approximately 50% of affected children develop migraines as adults.18,22 Children with vertigo may require careful workup by both a neurologist and an otolaryngologist. Even if obvious peripheral disease is found by the otolaryngologist, this could be coincidental to the occurrence of vertigo. In children the presence of an underlying central disorder such as vestibular epilepsy or brain tumor must be considered.

Vestibulogenic Seizures Vestibular seizures need to be distinguished from a rare phenomenon known as vestibulogenic seizures. This term refers to seizures evoked by stimulation of the labyrinth. The term vestibulogenic was initially applied to seizures by Berhman and Wyke.23 Based on experimental and clinical data, they theorized that the mechanism of initiation is abnormal activation of the reticular system of the brainstem secondary to caloric or rotary stimulation of the labyrinth. Vertigo occurs and is usually followed by generalized tonic-clonic convulsions with loss of consciousness. Most authors believe that vestibulogenic seizures are extremely rare.24 However, a small number of welldocumented cases of vestibulogenic seizure exist.24,25

Audiogenic Seizures Auditory stimuli can precipitate seizure activity in rare patients. These patients have an unusual form of reflex epilepsy. Reflex epilepsy refers to seizures precipitated by a specific sensory stimulus. The most commonly reported audiogenic seizures are induced by sudden loud noises. Musicogenic seizures occur less commonly. Certain notes or themes precipitate events in these patients.1,26,27 Patients with audiogenic seizures have not been described as having a history of hearing impairment. In contrast, many of the animal models that are known to be susceptible to audiogenic seizures have been shown to have elevated auditory thresholds. Correlation between degree of loss and susceptibility to and severity of audiogenic seizures has been reported in the epilepsyprone rat.28

Seizure Disorders

SUMMARY The neurotologist can encounter seizures in a variety of ways. They may be the underlying cause of symptoms that bring the patient to a physician’s office or the result of medical and surgical management of other conditions. Seizures are of special interest to the neurotologist in that they need to be considered in the differential diagnosis of complaints of vestibular and auditory dysfunction.

REFERENCES 1. Engel J Jr (ed.): Seizures and Epilepsy. Philadelphia, FA Davis, 1989. 2. Earnest MP (ed.): Neurologic Emergencies. New York, Churchill Livingstone, 1983. 3. Grossman RG (ed.): Principles of Neurosurgery. New York, Raven Press, 1991. 4. House WF, Luetje CM (eds.): Acoustic Tumors, vol 1. Baltimore, University Park Press, 1979. 5. King T, Morrison A: Translabyrinthine and transtentorial removal of acoustic nerve tumors. J Neurosurg 52:210–216, 1980. 6. Morrison A, King T: Experiences with translabyrinthine-transtentorial approach to the cerebellopontine angle. J Neurosurg 38:382–390, 1972. 7. Cabral R, King T, Scott D: Incidence of postoperative epilepsy after a transtentorial approach to acoustic nerve tumors. J Neurol Neurosurg Psychiatr 39:663–665, 1976. 8. Tuxhorn I, Holthausen H, Boenigk H (eds.): Paediatric epilepsy syndromes and their surgical treatment. London, England, John Libbey, 1997. 9. Messing RO, Closson RG, Simon RP: Drug-induced seizures: A 10 year experience. Neurology 34:1582–1586, 1984. 10. Lüders HO (ed.): Epilepsy Surgery. New York, Raven Press, 1992. 11. Ketterer T, Gacek R: Convulsions secondary to hyponatremia associated with labyrinthectomy. Arch Otolaryngol Head Neck Surg 115:387–388, 1989.

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12. Temkin NR, Dikmen SS, Wilensky AJ, et al: A randomized, doubleblind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med 323(8):497–502, 1990. 13. Pellock JM: Efficacy and adverse effects of antiepileptic drugs. Pediatr Clin North Am 35:435–448, 1989. 14. Barber HO, Stockwell CW: Manual of Electronystagmography. St. Louis, CV Mosby, 1980. 15. Wiebe S, Blume WT, Girvin JP, Eliasziw M: Effectiveness and efficiency of surgery for temporal lobe epilepsy study group: A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 345(5):311–318, 2001. 16. Currie S, Heathfield KWG, Henson RA, Scott DF: Clinical course and prognosis of temporal lobe epilepsy. A survey of 666 patients. Brain 94:173–190, 1971. 17. Hughes JR, Drachman DA: Dizziness, epilepsy and the EEG. Dis Nerv System 38:431–435, 1977. 18. Brandt T (ed.): Vertigo. Its Multisensory Syndromes. London, Springer-Verlag, 1991. 19. Williams DJ: Central vertigo. Proc R Soc Med 60:961–964, 1967. 20. Kogeorgos J, Scott DF, Swash M: Epileptic dizziness. Br Med J 282:687–689, 1981. 21. Eviatar L, Eviatar A: Vertigo in children: Differential diagnosis and treatment. Pediatrics 59:833–838, 1977. 22. Blayney AW, Colman BH: Dizziness in childhood. Clin Otolaryngol 9:77–85, 1984. 23. Behrman S, Wyke BD: Vestibulogenic seizures. A consideration of vertiginous seizures with particular reference to convulsions produced by stimulation of labyrinthine receptors. Brain 81:529–541, 1958. 24. Barac B: Vertiginous epileptic attacks and so-called “vestibulogenic seizures.” Epilepsia 9:137–144, 1968. 25. Tartara A, Manni R, Mira E, Mevio E: Polygraphic study of vestibular stimulation in epileptic patients. Rev EEG Neurophysiol 14:227–234, 1984. 26. Danbe JR: Sensory precipitated seizures: A review. J Neurol Ment Dis 141:524, 1965. 27. Mello DH: Precipitating factors in epilepsy. J Neurol Ment Dis 12:800–802, 1970. 28. Faingold CL, Walsh EJ, Maxwell JK, Randall ME: Audiogenic seizure severity and hearing deficits in the genetically epilepsy-prone rat. Exper Neurol 108:55–60, 1990.

Increased Intracranial Pressure Outline Douglas A. Chen, MD

J. Diaz Day, MD

Cerebrospinal Fluid Dynamics Cerebrospinal Fluid and lis Relationship to the Inner Ear Hydrocephalus with Elevated Cerebrospinal Fluid Pressure

igns and symptoms of increased intracranial pressure may be the features that send a patient to the neurotologist. Furthermore, most neurotologic procedures subject patients to the possible complication of increased intracranial pressure. A working knowledge of this topic is essential to the neurotologist. Intracranial pressure is determined by the contents within the volume-constant cranial vault, largely brain tissue, blood, and spinal fluid. 1 This concept is known as the Monro-Kellie doctrine. To maintain a constant pressure, if one component changes, one or both of the other two must change to compensate. Changes in blood and spinal fluid volume, therefore, lead to changes in intracranial pressure. Acute changes in intracranial pressure are compensated for by changes in venous and cerebrospinal fluid (CSF) volume up to a certain point beyond which intracranial pressure is increased. The pressure-volume relationships are nonlinear and are a function of CSF pressure. In most instances, intracranial pressure is reflected accurately through CSF pressure measurements. Manifestations of increased intracranial pressure in adults classically include headaches, nausea, vomiting, abducens nerve palsies, and papilledema. Papilledema may initially occur without visual deficits, but blurred vision, central scotoma, and "graying out" episodes suggest the end stages that lead to permanent visual damage. Abducens nerve weakness and diplopia may be present as a result of generalized increased intracranial pressure without a localized intracranial lesion. Headaches classically occur in the morning, but can occur any time. If severe enough, nausea and vomiting may relieve the headaches, presumably secondary to the hyperventilation that accompanies vomiting. This results in hypercapnea, which causes vasoconstriction, reducing the blood volume component according to the Monro-Kellie doctrine. Increased intracranial pressure may be a manifestation of hydrocephalus. Hydrocephalus in the most literal sense means "water head" and refers to an excessive accumulation of CSF intracranially. This excessive accumulation

S

524

Normal-Pressure HydrocephalUS Pseudotumor Cerebri Conclusion

usually takes place in the ventricular system from an imbalance between production and reabsorption. Numerous adjectives are used in conjunction with the term hydrocephalus. Communicating and noncommunicating refer to the presence or absence, respectively, of free flow of fluid from the ventricular system to both the lumbar and cerebral hemisphere subarachnoid space. Obstructive hydrocephalus implies an obstruction of CSF flow anywhere along its path and is the most common type. Acute and chronic hydrocephalus describe the time course over which excessive CSF accumulates, acute accumulation taking place over days and chronic over months to years. Patients with acute hydrocephalus tend to be dramatically symptomatic, whereas those with chronic hydrocephalus tend to exhibit more subtle signs and symptoms of elevated pressure. In chronic cases, neurologic signs and symptoms may exist that are not obvious, especially if they have occurred over a long time. Arrested hydrocephalus refers to a cessation of whatever factors initially led to hydrocephalus. Active hydrocephalus implies progressive ventriculomegaly or increased intracranial pressure. Benign intracranial hypertension, or pseudotumor cerebri, is a syndrome of increased intracranial pressure without apparent intracranial mass or ventriculomegaly. The term otitic hydrocephalus refers to the condition of benign intracranial hypertension secondary to an infectious process of the ear. Otitic hydrocephalus is consequently a misnomer, because by definition the ventricles are of normal size.' Horowitz suggested otogenic intracranial hypertension as a preferable name.' The hypertension is a phenomenon of venous outflow obstruction, causing increased intracranial pressure.

CEREBROSPINAL FLUID DYNAMICS CSF is produced at a rate of approximately 500 mL/day in adults and children. Production is an energy-dependent process. It takes place via a sodium pump on the apical

Increased Intracranial Pressure

surface of the choroidal epithelium, which transports sodium into the ventricles. Water then flows passively. Multiple factors, including drugs, can influence the production rate." A classic example is the carbonic anhydrase inhibitor, acetazolamide, which can decrease production of CSF by as much as 50% to 60%. Acetazolamide taken orally achieves a peak plasma level 1 hour after ingestion and is effective for 8 to 12 hours.' Given intravenously its peak effect occurs in 15 minutes and is effective 4 to 5 hours.? Few hydrocephalic states result from overproduction of CSF, with exceptions such as hypersecretion from a choroid plexus papilloma or villous hypertrophy.o'' CSF production may also occur in the brain parenchyma, but control is poorly understood." The choroid plexus is located primarily in the floor of the lateral ventricles and roofs of the third and fourth ventricles. Fluid leaves the lateral ventricles through the foramen of Munro, traverses the third ventricle, and reaches the fourth ventricle by way of the cerebral aqueduct (aqueduct of Sylvius). Fluid passes from the fourth ventricle through the foramina of Magendie and Luschka into the subarachnoid space. Several pockets of CSF exist at the base of the brain in the subarachnoid space known as cisterns. The largest is the cisterna magna located between the inferior surface of the cerebellum and the medulla (Fig. 31-1). Spinal fluid diffuses upward from the basal areas of the brain over the cerebral hemispheres. Absorption of spinal fluid into the venous system takes place primarily via the arachnoid villi mostly in the walls of the superior sagittal sinus and transverse sinuses.l'' Alternative routes of CSF absorption may exist. Substantial drainage occurs via the lymphatics of the nasal mucosa via the peri olfactory and optic nerve sheath in animals." Body of Lateral Ventricle

Arachnoid

Controversy exists as to whether the brain itself can absorb spinal fluid. The argument centers on the periventricular edema seen in acute hydrocephalus and whether this results from pressure-dependent transependymal migration of CSF or from active absorption. I I The pressure gradient between the ventricular system and the subarachnoid space is referred to as the transmantie pressure. The precise mechanism by which fluid passes into the sagittal sinus through the arachnoid villi is unclear but depends on a positive transmantle pressure gradient. Obstruction of the superior sagittal sinus results in elevated transmantle pressure and subsequent hydrocephalus.F

CEREBROSPINAL FLUID AND ITS RELATIONSHIP TO THE INNER EAR The inner ear is connected to the intracranial space via two aqueducts, the cochlear and vestibular. The cochlear aqueduct originates on the medial wall of the scala tympani near the round window membrane and terminates on the upper border of the jugular fossa in the petrous portion of the temporal bone. It is often filled with fibrous tissue.!' In lower animal species and frequently in human adult temporal bones, anatomically patent cochlear aqueducts can be found.?,14,ls Physiologic patency of the cochlear aqueduct is believed to be poor or nonexistent in most cases. The vestibular aqueduct originates in the scala vestibuli near the elliptical recess and passes into the posterior cranial fossa midway between the internal auditory canal and the sigmoid sinus.l ' The vestibular aqueduct transmits an artery, vein, and the endolymphatic duct, which dilates to Villi Sagittal Sinus

Sub Arachnoid Space

Third Ventricle

Figure 31-1. Formation, flow, and absorption of CSF.

Foramen of Munro (Interventricular Foramen)

...o~l-rr

Fourth Ventricle

Temporal Horn Aqueduct of Sylvius (Cerebral Aqueduct) Foramen of Luschka (Lateral Foramen)

Foramen of Magendie (Medial Foramen)

t

525

Cisterna Magna

526

NEUROTOLOGIC MANIFESTATIONS OF NEUROLOGIC DISEASE

form the endolymphatic sac on the dura mater of the posterior fossa. Maintenance of labyrinthine fluid pressure equilibrium in relationship to CSF has been proposed by Allen and widely accepted by other authors.lf-" He theorized that increased intracranial CSF pressure exerted on the endolymphatic sac and then to the endolymph were balanced by increases in the perilymph transmitted from the CSF via the cochlear aqueduct. However, recent animal experiments indicate that the endolymphatic sac is incapable or has limited capability of transmitting pressure changes from the CSF. In contrast, the cochlear aqueduct, if physiologically patent, is capable of transmitting changes in CSF pressure without dampening effects." Furthermore, pressure gradients as small as 2 to 5 mm H 20 between endolymph and perilymph have been postulated to cause inner ear membrane ruptures. I? Thus, if the cochlear aqueduct is large and physiologically patent, the inner ear may be susceptible to damage from sudden extreme variations of CSF pressure. 18 Clinically, reports of both auditory and vestibular symptoms coexisting with hydrocephalus occur in adult and pediatric literature. Barlas and colleagues'? reported two cases of fluctuating hearing loss and vertigo as the presenting symptoms in aqueductal stenosis and hydrocephalus. Symptoms in both patients were relieved by ventricular shunts. Loppenen and coworkers/? described audiologic findings of shunt-treated hydrocephalus in children. Eighteen of 47 shunt-treated hydrocephalic children had a high-frequency sensorineural hearing loss. The majority of these cases had only very mild losses, with hearing thresholds between 20 and 30 dB at 4, 6, and 8 kHz. Edwards and colleagues/! described auditory brainstem response audiometry in 16 neonatal hydrocephalus patients but felt the findings were more a reflection of a neurologic condition than peripheral hearing loss.

Idiopathic causes of hydrocephalus also make up a significant portion. Cerebellopontine angle tumors obstructing the fourth ventricle, such as an acoustic neuroma, account for only 2 % of all cases of obstructive hydrocephalus (Figs. 31-2 and 31-3). Increased intracranial pressure following neurologic surgery occurs occasionally and can be transient or prolonged. The cause can be cerebral edema or hydrocephalus. It is most common with large tumors and cases that have been complicated by excessive brain retraction, meningitis, and significant contamination of the CSF pathways with blood. Blood can block the absorptive capacities of the arachnoid villi. 25 It can also produce an obliterative meningeal inflammatory response, as can surgical exposure of the posterior fossa." Clinical manifestations ofhydrocephalus include headache, nausea, vomiting, ataxia, urinary incontinence, and visual disturbance. The headaches tend to occur in the morning and are usually bifrontal. As symptoms progress, they may occur in the evening and progress into the neck. Nausea and vomiting usually relieve the headaches. Ataxia is usually truncal. A wide-based, unsteady gait may also be present. Visual disturbances include decreased visual acuity, central scotoma, and diplopia. Momentary episodes of "graying vision" in both eyes are important signs of serious optic nerve and retina ischemia secondary to increased intracranial pressure. Papilledema and abducens nerve palsy are nonlocalizing signs, but are indicative of increased intracranial pressure.

HYDROCEPHALUS WITH ELEVATED CEREBROSPINAL FLUID PRESSURE Virtually all hydrocephalus associated with increased CSF pressure is secondary to obstruction. Any pathology obstructing the free flow of CSF from its origin in the ventricles to its site of absorption can cause hydrocephalus.F The most common cause in adults is subarachnoid hemorrhage either from aneurysm rupture or secondary to trauma. Like other causes such as meningitis, in cases of subarachnoid hemorrhage mechanical obstruction is produced by obliteration of the subarachnoid pathways over the convexity: As red cell lysis occurs, scarring of arachnoid villi leads to decreased absorption and hydrocephalus. Repeated or chronic subarachnoid blood can also cause neurotologic symptoms without hydrocephalus by chronic hemosiderin deposition in the central nervous system (CNS). Superficial siderosis of the CNS can result in cerebellar ataxia and progressive sensorineural hearing loss, as well as motor deficits and dementia.P Magnetic resonance imaging (MRI) findings are characteristic. T2-weighted images show marked hypointensity of the pial and arachnoid membranes.i"

Figure 31-2. Axial MRI with a large petroclival meningioma distorting the brainstem and fourth ventricle.

Increased Intracranial Pressure

Figure 31-3. Coronal image of the same tumorwith moderate hydrocephalus of the lateral and third ventricles aswell as the temporal horns.

The diagnosis of hydrocephalus is generally made with a computed tomographic (CT) scan. Contrast agents should be used so any underlying process can be established. Making the diagnosis by CT scan can be problematic. The first difficulty is deciding whether the ventricles are truly enlarged. The second difficulty is deciding, if they are enlarged, whether the enlargement is a result of brain atrophy or hydrocephalus. Temporal horn dilatation, "rounding of the third ventricle," and periventricular edema are all fairly reliable signs of true hydrocephalus. MRI is also useful in evaluating hydrocephalus and its underlying cause. An advantage of MRI is its ability to assess the flow of CSF in the cerebral aqueduct.i" In the hydrocephalic state, CSF flow signal void in the cerebral aqueduct is more prominent due to pulsatile CSF motion, which is thought to be a reflection of increased ventricular compliance." Despite CT and MRI, spinal puncture has remained a valued diagnostic technique in CNS diseases. Its utility in the setting of hydrocephalus is limited to patients with normal-pressure hydrocephalus as a provocative tool. Drainage of CSF in this setting may result in temporary alteration of symptoms, thus predicting a favorable outcome from shunting the CSF. Otherwise, in patients with elevated pressure secondary to hydrocephalus, the procedure is ill-advised. The normal CSF pressure/? in adults in the lateral recumbent position is less than 180 mm H 20. Merrit and

527

Fremont-Smith'? found a range between 70 and 180 mm H 20 in 971 patients. Massermarr'! found a mean CSF pressure of 148 mm H 20 in 824 patients. In neonates and children, it can be considerably less.'? The Queckenstedt test examines the patency of the subarachnoid space, but is seldom used today.32 In this test, lumbar CSF pressure is measured when applying pressure to the major venous outflow of the head. In normal CSF circulation through the subarachnoid space, compression of the jugular vein for 10 seconds increases CSF pressure in the head. This increased pressure in return will be reflected in the lumbar spinal fluid pressure by an increase of 150 to 300 mm H 20 . 3D On release of venous compression, the spinal fluid pressure returns to normal levels in 10 seconds. When the subarachnoid space is obstructed or when the venous outflow system is obstructed, spinal fluid response to jugular vein compression and release is delayed or absent. As alluded to earlier, lumbar puncture can be dangerous in the face of increased intracranial pressure. Under these conditions, the procedure may lead to uncus herniation through the tentorial incisura or the cerebellar tonsils through the foramen magnum.P A less serious complication of lumbar puncture is spinal epidural, subdural, or subarachnoid hemorrhage. Usually this passes, with local pain as the only complication; however, the occurrence of paralysis or sphincter disturbance demands prompt drainage.l" The most common complication, but least serious, is a postspinal tap headache, which last hours to several days. This complication is caused by continued leakage of CSF into the paraspinal soft tissues leading to failure to replenish the normal CSF volume. Typically this is relieved by the patient lying down for a period of time. Rarely, a blood patch is necessary to seal the dural puncture site and halt further leakage of CSF. If high-pressure hydrocephalus results from an obstructing mass lesion, treatment is centered around removal of the mass or shunt placement, with the former becoming increasingly advocated. A shunt drains CSF to a body cavity, such as the peritoneal or pleural, or a vein. Preoperative shunting before definitive removal of an intracranial mass has been advocated, and the results appear to be similar to those from centers that do not shunt preoperatively." If a shunt is not used preoperatively, the patient must be followed closely after surgery and be prepared for a shunt later. There are several common types of shunts. Ventricular shunts are usually inserted into the frontal horn of the lateral ventricle. Alternatively, the catheter is inserted into the lateral ventricle via an occipital trajectory. A catheter connecting the ventricle is buried subcutaneously and terminates in the peritoneal or pleural cavity (Fig. 31-4). Alternatively, the catheter may be directed into the common facial vein and subsequently to the atrium, the so-called ventriculoatrial shunt (Fig. 31-5). The lumboperitoneal shunt drains fluid from the lumbar subarachnoid space to the peritoneum (Fig. 31-6). This shunt is indicated in cases of communicating hydrocephalus. A lumboperitoneal shunt is ill advised if hydrocephalus is noncommunicating because of the higher risk of tonsillar herniation. All shunts have a valve system that regulates pressure and prevents retrograde flow.

528

NEUROTOLOGIC MANIFESTATIONS OF NEUROLOGIC DISEASE

Burr Hole approximately 6cm above and 3cm to right of Occipital Protuberance

Catheter tip in Ant. Horn of R. Lateral Ventricle 11-12 em from Burr Hole

Figure 31-4. Ventriculoperitoneal shunt.

/

./---------

/

Catheter brought through subcutaneous tunnel over chest and R, side of neek

I

-0"

"I .;, I

~IF'"

Catheter anchored

~,: - - to the Peritoneum

j~ 18 to 20 em

Temporary ventricular drainage into an external closed system, a ventriculostomy, can be done under local anesthesia in the intensive care unit. This technique is common in cases of hydrocephalus, trauma, stroke, and subarachnoid hemorrhage. Placement of the catheter allows for drainage of CSF and monitoring the intracranial pressure. Complications of shunts include infection, shunt malfunction, chronic subdural collections, and seizure.l? Shunt infections are especially common in infants. Peritoneal shunt malfunction may be the only manifestation, and CSF cultures should be obtained from the catheter on removal or replacement. If a shunt becomes infected antibiotics are administered. However, removal of the entire shunt, with temporary placement of a ventriculostomy, is necessary until the infection resolves. Progressive ventricular enlargement despite shunt placement is typically a sign of shunt malfunction. Ventricles will usually begin to diminish in size within a week after shunt placement, which is the best indicator of shunt patency. In normal-pressure hydrocephalus, ventricles may remain large despite good shunt function. A shunt tap will test the patency of the catheter; however, risk of infection exists. Inability to withdraw fluid from the ventricular reservoir indicates ventricular catheter

tI

obstruction, and shunt reVISIOn is indicated. Several radionuclide methods for determining shunt patency and flow have been described but have met with variable success. Radionuclide shunt evaluation determines the clearance of radioisotope from the ventricular reservoir into the catheter and has been found to vary greatly depending on the various components of the system. 37,38 Chronic subdural collections occur most commonly in normal-pressure hydrocephalus. This complication is uncommon in high-pressure hydrocephalus.'? The mechanism is thought to be secondary to negative intracranial pressure that results in tearing of bridging veins or leakage around the ventricular catheter into the subdural space.f Most subdural collections will not enlarge; however, when they do, replacement with a higher pressure valve is usually necessary."

NORMAL-PRESSURE HYDROCEPHALUS Ventricular enlargement in the face of normal CSF pressure may present a confusing clinical picture. This situation may occur in association with neurodegenerative diseases, such a Alzheimer's disease and cortical atrophy causing an "ex vacio" hydrocephalus. This scenario must be

Increased Intracranial Pressure

529

Catheter tip in Ant. Horn of R, Lateral Ventricle 5-6 cm from Burr Hole

Figure 31·5. Ventriculoatrial shunt.

Catheter enters through Common Facial Vein

0=~acava

(

J.\ distinguished from normal-pressure hydrocephalus, which is a syndrome clinically defined by the classic triad of gait disturbance, dementia, and urinary incontinence. It was described by Hakim and Adamsf in 1965 and then by Adams and colleaguesf and has been referred to as the Hakim, or Hakim-Adams, syndrome. A number of conditions that precede the syndrome have been identified." Most can be related to some low-grade obstructive flow phenomenon, such as subarachnoid hemorrhage, tumor, meningitis, or previous intracranial surgery. High-pressure and normal-pressure hydrocephalus probably represent a spectrum of the same disease process with different outcomes. The mechanism by which hydrocephalus occurs in the face of normal CSF pressures remains controversial. Symon and Dorsch suggested that these patients have episodically raised intracranial pressure, especially at night, which may not manifest on one lumbar puncture.t" Similarly, Di Rocco and coworkerst' postulated that CSF pulse pressure with normal mean pressure in the ventricular system could be responsible for increasing ventricular size. Hakim and Adarnsf suggested that according to Laplace's law, the increased ventricular size represents increased force on the ventricular wall despite normal CSF pressure. Several explanations, which involve primarily brain parenchyma, have been proposed. Extensive atherosclerotic changes in brains of patients with normalpressure hydrocephalus at postmortem have been observed; however, they were not compared with controls.t'v" The triad of gait disturbance, memory loss, and urinary incontinence are the chief clinical features of normal-pressure

hydrocephalus. The gait disorder is usually characterized by a broad-based shuffling with short steps." The patient often reports imbalance when standing or sitting associated with a history of falling."? The severity of recent memory loss can vary greatly. A general degradation of mental faculties, which the family may report as lethargy, apathy, or attention, and concentration difficulties may occur. CT and MRI should show large ventricles, and a lumbar puncture may be performed to establish CSF pressures. Pressure should be less than 180 mm H 20 and protein, sugar levels, and cell count should also be normal. The clinical response of normal-pressure hydrocephalus to shunting is mild improvement in approximately twothirds of patients and significant improvement in one-third; however, the range varies from 33% to 85% showing significant improvement.t-!' The wide variation in results probably reflects differences in patient selection criteria and evaluation of the shunt response. Many investigators have tried to prognosticate about who will benefit from shunting. Certain factors have been associated with favorable shunt results, with evidence of altered CSF dynamics being the underlying theme. Overnight, a CSF pressure of more than 180 mm H 20 was associated with better shunt results.V Improvement after lumbar puncture is akin to a therapeutic trial of temporary shunting and has also been associated with good shunt results.t" Lumboventricular perfusion is the measurement of CSF absorption capacities and has had good predictive value.P Factors that have been of little importance when considering shunting include atrophy on CT scan,

530

NEUROTOLOGIC MANIFESTATIONS OF NEUROLOGIC DISEASE

ANTERIOR VIEW

I ~ Spinious process O;;;:;;:~\l~~6~~;

Figure 31-6. Lumboperitoneal shunt.

Catheter Tunneled Subcutaneously to right upper Quadrant

L4 ~~~4=-::,......~'--- 1-inch incision

over L3 and L4 down to Lumbodorsal fascia

\ radionuclide cisternography, cerebral blood flow measurements, and certain electroencephalographic patterns.50

PSEUDOTUMOR CEREBRI Pseudotumor cerebri, or benign intracranial hypertension, is a syndrome of increased intracranial pressure without apparent intracranial mass. The presenting signs and symptoms include headache and blurred vision, and it has a predilection for young obese females.54 Diplopia and nausea can occur but are less frequent symptoms. Pulsatile tinnitus, hearing loss, and vertigo have been described as being associated with it and can be the presenting symptoms.55 The tinnitus can usually be auscultated, and light digital occlusion of the ipsilateral internal jugular vein usually will improve the tinnitus and low-frequency sensorineural hearing loss.56 Papilledema is invariably present on physical exam. Sixth nerve palsies may also occur. Causal factors associated with pseudotumor cerebri have been identified as pregnancy, vitamin A disturbances, drugs, anemia, arteriovenous malformations, and sinus obstruction.57 The pathophysiology remains poorly understood, but the underlying mechanism appears to be defective CSF absorption leading to interstitial brain edema. This theory has been supported by human studies linking pseudotumor cerebri to increased resistance to absorption of CSF, probably at the level of the arachnoid villi of the superior sagittal sinuses. 58,59 Why this should lead to interstitial edema instead of hydrocephalus is unclear. The resistance to reabsorption is probably secondary to venous hypertension.

J

The pathophysiology of hearing loss in patients with increased intracranial pressure has been attributed to transmission of increased pressure via the cochlear aqueduct to the perilymph or stretching of the central ascending auditory pathways.60,61 An alternative hypothesis was proposed by Sismanis and colleagues.55 They postulated that when a venous hum is present in pseudotumor cerebri, it produces a "pseudosensorineural" hearing loss from the masking of the low frequencies.l' The electronystagmography findings of patients with pseudotumor cerebri were described by Kaaber and Zilstorff.f with decreased caloric response being the most common finding. Neurologic imaging is important to rule out underlying intracranial mass. Ventricular size is usually normal, although reports of slightly large or small ventricles do exist. Lumbar puncture is essential to confirm the diagnosis of elevated CSF pressures. Angiography may be indicated in cases where AVM or sinus occlusion is suspected. The treatment of pseudotumor cerebri is directed at the underlying cause, if any can be found, such as anemia or obesity. Direct management of the intracranial pressure with serial lumbar punctures, acetazolamide, diuretics, and steroids has been used.v' Lumboperitoneal shunting has been advocated in cases refractory to medical management. 51,64 Continued care by an ophthalmologist until intracranial pressures are reduced is also necessary to minimize the possibility of permanent visual loss from papilledema. Otitic hydrocephalus, despite its name, is actually a form of pseudotumor cerebri.v' It is the least common of the intracranial complications of otitis media, and only infrequent case reports exist in modern literature. The largest

Increased Intracranial Pressure

series consists of a literature review of 44 cases by Foley.'" Most cases were associated with lateral sinus thrombosis or perisinus abscess, but not all. The increased intracranial pressure is most likely related to obstructed venous flow from the head. The presenting signs and symptoms are the same as for pseudotumor cerebri in association with recent or ongoing ear disease. It is most commonly seen in children and adoIescents." CT will detect the ear disease but will also rule out intracranial lesions. Imaging of the venous system via angiography or magnetic resonance venography is critical to establish the status of the sinuses. Lumbar puncture should reveal elevated pressure but is otherwise normal.v? Treatment consists of managing increased intracranial pressure to prevent permanent visual deficits. If steroids and diuretics are of little benefit, serial lumbar punctures as a temporizing measure or a shunt procedure are indicated. The mainstay of treatment of the ear disease consists of mastoidectomy and antibiotics.

CONCLUSION In summary, increased intracranial pressure is primarily a neurologic problem; however, ear signs and symptoms can be the presenting manifestations of hydrocephalus or benign intracranial hypertension. Neurotologic procedures also can be complicated by hydrocephalus. Thus a working knowledge of this topic should be in the armamentarium of every neurotologist.

REFERENCES 1. Marmarou A, Shulman K, La Morgese]: Compartmental analysis of compliance and outflow resistance of the cerebrospinal fluid system. J Neurosurg 43:523-534, 1975. 2. Symonds CP: Otitic hydrocephalus. Neurobiology 6:681-685, 1956. 3. Horowitz S: Otogenic intracranial hypertension. ] Laryngol Otol 63:363-381, 1949. 4. McComb ]G: Recent research into the nature of cerebrospinal fluid formation and absorption.] Neurosurg 59:369-383,1983. 5. Hossie RD et al: Quantitation of acetazolamide in plasma by high performance liquid chromatography.] Pharm Sci 69:348-349, 1980. 6. Berkowitz RR et al: Handbook for prescribing medications during pregnancy. Boston, Little, Brown and Co., 1981. 7. Eisenberg HM, McComb ]G, Lorenzo AV: Cerebrospinal fluid overproduction and hydrocephalus associated with choroid plexus papilloma.] Neurosurg 40:381-385,1974. 8. Welch K et al: Congenital hydrocephalus due to villous hyperttophy on the telencephalic choroid plexuses.] Neurosurg 59:172-175, 1983. 9. Chapman PH: Hydrocephalus in childhood. In Youmans]R (ed.): Neurological Survey. Philadelphia, WE Saunders, 1990. 10. Welch K, Friedman V: The cerebrospinal fluid valves. Brain 83:454-469, 1960. 11. Mori K et aI: Periventricular lucency in hydrocephalus on computerized tomography. Surg Neurol 8:837-840, 1970. 12. Black P: Idiopathic normal pressure hydrocephalus. Results of shunting in 62 patients.] Neurosurg 52:371-377,1980. 13. Anson B et al: The vestibular and cochlear aqueducts: The variational anatomy in the adult human ear. Laryngoscope 75:1203-1223, 1965. 14. Carlborg B, Farmer F: Transmission of cerebrospinal fluid pressure via the cochlear aqueduct and endolymphatic sac. Am ] Otol 4:273-282, 1983.

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15. Wlodyka ]: Studies on cochlear aqueduct patency. Ann Otol Rhinol Laryngol 87:22-28, 1978. 16. Allen CWo Endolymphatic sac and cochlear aqueduct. Arch Otolaryngol 79:322-327, 1964. 17. Henriksson, N, Gleisner L, ]ohanssan G: Experimental pressure variations in the membranous labyrinth of the frog. Acta Otolaryngol 61:281-291, 1966. 18. Allen CW: Fluid flow in cochlear aqueduct and cochlea hydrodynamic consideration in perilymph fistula, stapes gusher, and secondary endolymphatic hydrops. Am] Otol 8:319-321, 1987. 19. Barlas 0 et al: Adult aqueductal stenosis presenting with fluctuating hearing loss and vertigo.] Neurosurg 59:703-705, 1983 20. Lopponen H et al: Audiological findings of shunt treated hydrocephalus in children. Int] Pediatr Otorhinolaryngol 18:21-30, 1989. 21. Edwards CC, Smith A, Pictor TW: Auditory brainstem response audiometry in neonatal hydrocephalus. ] Otolaryngol Suppl 14:40-46, 1985. 22. Katzman R: Low pressure hydrocephalus. In \VilIs EE (eds.): Dementia. Philadelphia, FA Davis, 1977. 23. Revesz T, Earl C], Barnard TO: Superficial siderosis of the central nervous system presenting with longstanding deafness. ]R Soc Med 81:479-481, 1988. 24. Kwartler ]A, De La Cruz A, Lo WWM: Superficial siderosis of the central nervous system. Ann Otol Rhinol Laryngol 100:249-250, 1991. 25. Ellington E, Margolis G: Block of arachnoid villus by subarachnoid hemorrhage.] Neurosurg 30:651-657,1967. 26. Stein BM, Tenner MS, Fraser RAR: Hydrocephalus following removal of cerebellar astrocytoma in children. ] Neurosurg 36:763-768, 1972. 27. Sherman ]L, Citrin CN: Magnetic resonance demonstration of normal CSF flow. Am] Neuroradiol 7:3-7,1986. 28. Bradley WG, Kortmann KE, Burgoyne R: Flowing cerebrospinal fluid in normal hydrocephalic states: Appearance on MR imaging. Radiology 159:611-616, 1986. 29. Gillian 0 et al: Normal cerebrospinal fluid pressure.] Neurosurg 40:587-593, 1973. 30. Merrit HH, Fremont-Smith F: The Cerebrospinal Fluid. Philadelphia, WE Saunders, 1937. 31. Masserman ]H: Cerebral spinal fluid hydrodynamics: IV Clinical experimental studies. Arch Neurol Psychiat 32:523-553, 1934. 32. Queckensredr H: Zur Diagnose der Riickenmarkkopression. Deutch 2 Nervenheilk 15:325-333,1916. 33. Gochwald F: Cerebrospinal fluid. In Hount R (ed.): Clinical Neurology. Philadelphia, Lippincott, 1990. 34. Masdeu J, Breuer AC, Schoene WC: Spinal subarachnoid hematomas: Clue to a source of bleeding in traumatic lumbar puncture. Neurology 29:872-876, 1979. 35. McLarin RLL: On the use of precraniotomy shunting in the management of posterior fossa tumors in children: A cooperative study. Concepts Pediatr Neurosurg 6:1-5,1985. 36. Ojemann RG, Black McL P: Hydrocephalus in adults. In Youmanns ]R (ed.): Neurological Surgery. Philadelphia, WE Saunders, 1990. 37. Chervu Shanta, et al: Quantitative evaluation of cerebrospinal fluid shunt flow,] Nucl Med 25:91-95, 1984. 38. Harbert ]C, et al: Radionuclide tests of cerebrospinal fluid shunt patency. ] Nucl Med 25:112-114,1984. 39. Udcarhely GB, et al: Results and complications in 55 shunted patients with normal pressure hydrocephalus. Surg Neurol 3:271-275, 1975. 40. McCullough DC, Fox]L: Negative intracranial pressure in adults with shunts and its relationship to the production of subdural hematoma.] Neurosurg 40:372-375, 1974. 41. Black P, Ojemann TG, Tzouras A: Cerebrospinal fluid shunts for dementia, gait disturbance and incontinence. Clin Neurosurg 32:632-656,1985. 42. Hakim S, Adams RD: The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure.

Increased Intracranial Pressure

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Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci 2:307-327, 1965. Adams RD, et al: Symptomatic occult hydrocephalus with "normal" cerebrospinal fluid pressure. A treatable syndrome. N Engl J Med 273:117-126,1965. Symon L, Dorsch NWC: Use of long-term intracranial pressure measurement to assess hydrocephalic patients prior to shunt surgery. J Neurosurg 42:258-273, 1975. Di Rocco C, et al: Communicating hydrocephalus induced by mechanical increased amplitude of the intraventricular cerebrospinal pressure: Experimental studies. Exp Neurol 59:40-52, 1978. Ernst MP, et al: Normal pressure hydrocephalus and hypertensive cerebrovascular disease. Arch Neurol 31:262-266, 1974. Hakim S, Modi SM: Normal pressure hydrocephalus and hypertensive cerebrovascular disease. Dis Nerd SST 38:918-921, 1977. Knutsson E, Lying-Tunll U: Gait apraxia in normal pressure hydrocephalus: Patterns of movement and muscle actuation. Neurology 35:155-160,1985. Chawla JC, Woodward J: Motor disorders in "normal pressure hydrocephalus," Br Med J 1:485-486, 1972. Black P, Connor E: Chronic increased intracranial pressure. In Asbury A, McKhann G, McDonald W (eds.): Diseases of the Nervous System, vol 2. Philadelphia, Ardmore Medical Books, 1986. Hughes CPo Adult idiopathic communication hydrocephalus with and without shunting. J Neurol Neurosurg Psychiat 41:961-971, 1978. Symon L, Hinzpeter T: The enigma of normal pressure hydrocephalus: Tests to select patients for surgery and to predict shunt function. Clin Neurosurg 24:285-315,1977. Borgesen SE, Gjerris F: The predictive value of conductance to outflow of cerebrospinal fluid in normal pressure hydrocephalus. Brain 105:65-86, 1982

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54. Weisberg LR: Benign intracranial hypertension. Medicine 54:197-207,1975. 55. Sismanis A et al: Otologic symptoms and findings of the pseudotumor cerebri syndrome. Head Neck Surg 93:398-402, 1985. 56. Sismanis A, Butts F, Hughes G: Objective tinnitus in benign intracranial hypertension: An update. Laryngoscope 100:33-36, 1990. 57. Fishman RA (ed.): Benign intracranial hypertension. In: Cerebrospinal Fluid in Diseases of the Nervous System. Philadelphia, WE Saunders, 1980. 58. Jammy P, et al: Benign intracranial hypertension and disorders of CSFcirculation. SurgNeuroI15:168-174, 1981. 59. Sklar FH, et al: Cerebrospinal fluid dynamics in patients with pseudotumor cerebri. Neurosurgery 5:208-216, 1979. 60. Best RLL: Perilymph hypertension and the indirect measurement of cochlear pressure. Laryngoscope 91:1706-1713,1981. 61. Tandon PN, et al: Auditory function in raised intracranial pressure. J Neuro Sci 15:455-467, 1973. 62. Kaaber E, Zilstroff K: Vestibular function in benign intracranial hypertension. Clin OtolaryngoI3:183-188m 1978. 63. Jefferson A, Clark J: Treatment of benign intracranial hypertension by dehydrating agents with particular reference to the measurement of the blind spot area as a means of recording improvement. J Neurol Neurosurg Psychiat 39:627-639, 1976 64. Sismanis A: Otologic manifestations of benign intracranial hypertension: Diagnosis and management. Laryngoscope 97(Suppl) 42:1-17, 1987. 65. Lenz RP, Graeme MA: Otitic hydrocephalus. Laryngoscope 94:1451-1454,1984. 66. Foley J: Benign forms of intracranial hypertension-"toxic" and "otitic" hydrocephalus. Brain 78(1):1-41,1955. 67. Greer M: Pseudotumor cerebri. In Youmans JR (ed.): Neurological Surgery. Philadelphia, WE Saunders, 1990.

32

Outline Introduction Structural Changes with Aging Alterations in Vestibular Function with Aging Presbystasis Evaluation Vertebrobasilar Insufficiency

Chapter

Vertigo, Dysequilibrium, and Imbalance with Aging

Labyrinthine Disorders Other Otologic and Neurotologic Disorders Cervical Vertigo Systemic Disorders Treatment and Rehabilitation of Vestibular Dysfunction

Anil K. Lalwani, MD

INTRODUCTION

STRUCTURAL CHANGES WITH AGING

Vestibular dysfunction is common in the elderly, with reported prevalence of vertigo, dysequilibrium, or imbalance to be as high as 47% in men and 61% in women older than age 70.1–3 Dizziness is the most common presenting symptom in those 75 years and older seen in an office practice.4,5 The incidence of falls in individuals older than age 65 is between 20% and 40% in those living at home.2,6–10 It is twice as frequent for the institutionalized elderly.11,12 By age 80, one in three people will have suffered a fall associated with significant morbidity. Vestibular symptoms precede these falls in more than half of the patients. These falls are associated with significant morbidity and mortality and constitute one of the leading causes of death in the elderly.13 Spatial orientation and balance is achieved through the complex integration of visual, proprioceptive, somatosensory, and vestibular information in the central nervous system. The visual oculomotor reflexes interact with the vestibulo-ocular reflex to produce a stable visual field necessary to maintain orientation. Posture is maintained through the interaction of the collicovestibular and spinovestibular reflexes, segmental stretch reflexes, and several exteroceptive sensory systems such as touch and temperature. The processing and integration of these various sensory and motor input in the brain allows for orientation, balance, maintenance of posture, and locomotion. The aging brain is less efficient at processing the variety of mechanosensory inputs and effecting an appropriate motor response to maintain perfect balance. This is likely due to structural and physiologic alterations associated with aging.

The vestibular system, like other organ systems, undergoes degenerative changes with aging, resulting in variable functional disability. The specialized neural cells of the mammalian vestibular system are nonmitotic and thus cannot undergo replication and renewal. During the course of a lifetime, DNA transcription errors and insoluble pigments accumulate, and protein synthesis becomes increasingly inefficient. Additionally, environmental and external factors such as noise trauma, physical trauma, ototoxic substances, and medications also contribute to senescence. Degenerative changes (Table 32-1) and atrophy have been noted throughout the vestibular apparatus, including the otoconia, vestibular epithelium, vestibular nerve, Scarpa’s ganglion, and cerebellum.14–19 In the utricle and saccule, statoconia progressively demineralize and fragment, resulting in decreased responsiveness to gravity and to linear acceleration.20 The migration of degenerated otoconial debris into the dependent ampulla of the posterior semicircular canal may result in positional balance disturbances (cupulolithiasis or benign paroxysmal positional vertigo).21 In the sensory epithelia, inclusion bodies, lipofuscin, and vacuoles accumulate. In addition, cell shrinkage and atrophy and replacement of hair cells with scar formation occur.22,23 After age 70, the number of hair cells in the maculae of otolith organs decreases by 20%, and the cristae of the semicircular canals decreases by 40%.24 The cell loss begins at about age 40.25 The type I hair cells are affected more than type II hair cells. The reduction in the number of cells in the Scarpa’s ganglion as well as the number of vestibular nerve fibers parallels the loss of sensory epithelia.26 By age 60, the 533

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NEUROTOLOGIC MANIFESTATIONS OF NEUROLOGIC DISEASE

TABLE 32-1. Structural Changes in the Vestibular Apparatus with Aging Otoconia Vestibular epithelium

Vestibular nerve Scarpa’s ganglion Vestibular nuclei Cerebellum

Demineralization Fragmentation Migration Inclusion bodies Vacuoles Lipofuscin accumulation Hair cell loss and atrophy (type 1 > type II) Decrease in number of fibers Decrease in number of ganglion cells Alterations in synaptic bars Lipofuscin accumulation Axonal degeneration Membrane invaginations Loss of Purkinje cell Decreased axodendritic synapses Reduction in size of cerebellar vermis Lipofuscin accumulation Rodlike inclusions Other inclusion bodies

number of ganglion cells in the Scarpa’s ganglion is reduced.27 Examination of the vestibular nerve synapses has demonstrated alterations in the synaptic bars in people 40 years of age and older.25 Beginning at age 50, there is loss of nerve fibers between the vestibule and the Scarpa’s ganglion. Compared with those 35 years of age or younger, the number of nerve fibers in specimens 75 years and older is reduced by 37%.28 The greatest loss occurs among the thick myelinated fibers of the cristae, resulting in decrease in the neuronal condition velocity with age. Hair cell degeneration likely precedes vestibular neuronal degeneration.27 The effect of aging on the vestibular nuclei are less well understood. Studies of other brainstem nuclei have failed to demonstrate significant age-related decline in neuronal cell populations.23 Lipofuscin accumulation in the vestibular nuclei, similar to that seen in the hair cells, has been observed. In the lateral vestibular nucleus of rats, membrane invagination and axonal degeneration has been noted.29 In the cerebellum, there is loss of Purkinje’s cells beginning in the fifth decade. Ellis30 reported a 38% decline in the number of Purkinje cells in the cerebellar cortex of five adults age 62 to 100 years compared with younger population. Hall and colleagues31 noted a 25% reduction in Purkinje cell population in the cerebellum with aging, with most rapid neuronal loss occurring after 60 years of age. The Purkinje cell loss is highly variable among individuals, with some individual in their nineties retaining nearly normal number of cells. Glick and Bondareff32 have documented a 24% decrease with age in axodendritic synapses in the rat cerebellar vermis paralleling cerebellar neuronal cell loss. Raz and coworkers,33 using magnetic resonance imaging, have demonstrated a significant reduction in the total area of the cerebellar vermis. As in the peripheral sensory epithelia and the vestibular nucleus, lipofuscin, rodlike nuclear inclusions, and other inclusion bodies have been observed to accumulate with age in the cerebellum.34,35 Other ultrastructural changes associated with aging include a decreased amount of Nissl substance in the perikaryon, loss of demarcation between the nucleus and cytoplasm, and paler nucleoli.34,35 The clinical significance of these changes is unclear.23

ALTERATIONS IN VESTIBULAR FUNCTION WITH AGING Vestibular testing of the elderly has demonstrated quantifiable functional decline with age. A variety of testing modalities are available, including physical examination, electronystagmography, rotational testing, and posturography. The physical exam may assess the eye movements, note the presence or absence of nystagmus, perform postural testing, and evaluate gait. Potvin36 has demonstrated decline in all postural tests with age, the most sensitive of which was the inability of the elderly male to stand on one leg with the eyes closed. Electronystagmography is a graduated series of evaluations of the vestibular and vestibuloocular system that includes caloric responses. It can be useful in establishing the degree of vestibular function in an ear, determining the side of pathology, and differentiating central from peripheral diseases. After age 70, the elderly exhibit a decline in caloric response, which peaks between the ages of 50 to 70.37 Studies of the vestibulo-ocular reflex in the elderly have shown decreased sensitivity and shorter time constants over a wide range of frequencies of rotational stimuli.38,39 Posturography is a relatively new method for studying the ability of the subject to maintain balance with changing visual and somatosensory input. The relative energy required to maintain balance on the posturography test increases linearly with age until age 70. The elderly also have larger sway excursions on balance platforms in posturography.40 Further, Teasdale and colleagues41 have shown that visual deficits along with platform disruption has a much greater effect on posture than platform alteration in isolation. This and other work have highlighted the increased reliance on visual cues on maintenance of balance in the elderly.42,43 In addition, the posture is also negatively affected by decreased sensation and muscle weakness in the lower extremities and increased reaction time.43–45 Rotational testing is available to evaluate the vestibulo-ocular reflex. In the elderly, there is significant decrease in gain in the vestibulo-ocular reflex to different rotatory stimuli.46,47 Overall, aging affects the vestibular, visual, and proprioceptive information available for central processing, as well as the ability of the central nervous system to process the sensory information and effect motor response.

PRESBYSTASIS Dysequilibrium of aging, or presbystasis, a term coined by Belal and Glorig, is a common diagnosis in elderly patients evaluated for dizziness.48 Its cause is multifactorial and is related to the structural and physiologic deterioration of the vestibular apparatus associated with normal aging as discussed earlier.49,50 Presbystasis is the vestibular counterpart to presbycusis, the hearing loss associated with aging of the auditory system. It is a diagnosis of exclusion and not a specific pathologic diagnosis. In their original study of 740 patients older than age 65 presenting with dizziness, 79% of the patients were diagnosed with presbystasis following clinical evaluation.48 A specific cause for dizziness was found only in 21% of the 740 patients. However, with

Vertigo, Dysequilibrium, and Imbalance with Aging

better and more complete testing of the vestibular and balance function, including electronystagmography, posturography, and rotational testing, the ability to assign a specific pathologic diagnosis has improved.23,51 In their review of 116 patients, 70 years and older, evaluated for persistent dizziness, Sloane and coworkers23 were able to identify the specific cause in 85% of their cases. A variety of vestibular disorders have been identified in the elderly, including benign positional vertigo, Ménière’s disease, unilateral or bilateral vestibular deficits of various causes, defective central nervous system adaptation to vestibular injuries, cervical vertigo, cereberovascular disease, and vertebrobasilar insufficiency, among others (Table 32-2).52 Therefore it is imperative that a careful and complete clinical evaluation be performed in the assessment of an older adult with vestibular symptoms prior to assigning the nonspecific diagnosis of presbystasis.

EVALUATION Thorough vestibular evaluation begins with a complete history, general physical, and specialized neurotologic examination (Table 32-3). Dizziness is an all-encompassing TABLE 32-2. Causes of Vertigo or Dizziness in the Elderly Otologic

Neurotologic

Cardiovascular

Neurologic

Hematologic Vascular

Metabolic

Other

Benign paroxysmal positional vertigo Cholesteatoma Labyrinthitis Ménière’s disease Perilymph fistula Osseous dysplasia of temporal bone Otosclerosis Ototoxic/vestibulotoxic drugs Syphilis Vestibular neuronitis Cerebellopontine angle tumors Acoustic neuroma Arachnoid cyst Lipoma Meningioma Metastatic tumors Aortic stenosis Carotid sinus hypersensitivity Dysrhythmia Postural hypotension Epilepsy Multiple sclerosis Parkinson’s disease Psychogenic disorders Syncope Anemia Hyperviscosity syndrome Autommune vasculitis Carotid artery stenosis Cerebellar ischemia Subclavian steal syndrome Vertebrobasilar insufficiency Wallenberg’s syndrome Diabetes mellitus Hyperventilation Hyperglycemia Hypoglycemia Cervical vertigo Head injury Side effect of medications

535

term employed by the patient and may include vertigo, dysequilibrium, or imbalance. The diagnostic evaluation and management differs markedly depending on the exact nature of dizziness. Therefore, it is imperative for the physician to determine the true nature of patient’s symptoms. Vertigo is the cardinal symptom of vestibular disease and is usually described as a rotatory sensation. However, it may take the form of any illusion of movement, such as rocking, ground rolling, tilting, or a sense of falling forward or backward. Dysequilibrium is a sense of discoordination with erect posture or during a purposeful movement. Although vertigo is usually episodic, dysequilibrium is typically continuous. The term imbalance implies an orthopedic (e.g., hip disease) or neurologic (e.g., hemiparesis) problem. Dizziness may also be used to denote a lightheaded feeling, as in postural hypotension or hypoglycemia, or to indicate an inability to concentrate. The exact nature of dizziness, the time course, and the associated symptoms are of great differential value and should be elicited.53–55 Short-lived episodes of vertigo associated with nausea and vomiting are classically associated with peripheral labyrinthine pathology. Likewise, the illusion of movement of self or the environment is highly suggestive of labyrinthine dysfunction. Acute rotational vertigo lasting several days with slow recovery is characteristic of acute viral, vascular, or traumatic labyrinthitis. Rotational vertigo lasting less than a minute is usually due to benign positional vertigo. Unsteadiness of insidious onset, lightheadedness, and faintness are more likely due to medical or neurologic disease. The sensation of dysequilibrium is usually chronic. Vertigo associated with hearing loss is consistent with peripheral end-organ pathology, whereas involvement of other cranial nuclei is more characteristic of central pathology. A full medical history and examination are essential in evaluation of dizziness.56 Specifically, history of diabetes, hypertension, coronary artery disease, peripheral vascular disease, and any neurologic disease should be elicited. List of current medications should be reviewed. Table 32-4 lists some of the common medications associated with balance symptoms. Supine and standing blood pressure are useful in excluding orthostatic hypotension. Sadly, the skills and knowledge of health care personnel in accurately detecting orthostatic hypotension is lacking and large differences in measurement techniques has lead to underdiagnosis.57 Therefore, it is critical that standardized measurement techniques are implemented to better diagnose this common problem in the elderly associated with balance disturbance. Absence or presence of nystagmus should be TABLE 32-3. Evaluation of Vertigo Complete clinical and medical history General physical examination Otologic and neurotologic examination Complete audiometry Internal medicine, neurology, or other consultation as necessary Additional examinations: Electronystagmography Posturography Rotational testing Computerized tomography Magnetic resonance imaging

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NEUROTOLOGIC MANIFESTATIONS OF NEUROLOGIC DISEASE

TABLE 32-4. Common Medication Associated with Balance Symptoms Anticholinergics Anticonvulsants Antihypertensives Antineoplastic drugs Dopamine agonists H2 blockers Ototoxic drugs Sedatives Tricyclic antidepressants Vasodilators

Scopolamine, promethazine, amitriptyline, meclizine Phenytoin, carbamazepine, phenothiazines, chlorpromazine Furosemide, propranolol, terazosin Cisplatin L-Dopa/carbidopa Cimetidine Gentamicin Barbiturates, benzodiazepines Nortriptyline Isosorbide, nifedipine

noted in the examination of extraocular movements. Otoscopic examination, to rule out middle ear disease and cholesteatoma, should always be performed. Examination of gait, rapid alternating movement test, finger-to-nose testing, and heel-to-knee test are useful in assessing cerebellar function. Complete audiometry should be obtained to evaluate auditory function. Further examinations may include electronystagmography, posturography, rotational testing, computerized tomography, and magnetic resonance imaging. When cardiac or another medical cause is suspected, a complete evaluation by an internist should be obtained.

VERTEBROBASILAR INSUFFICIENCY Vertebrobasilar insufficiency is an important cause of vertigo and dysequilibrium in the elderly because it supplies both the peripheral and central components of vestibular system.58 It usually results from arteriosclerosis with insufficient collateral circulation, but may also be due to compression of vertebral arteries by cervical spondylosis, postural hypotension, or the subclavian steal syndrome. The classic clinical presentation of vertebrobasilar ischemia includes vertigo with head motion (especially looking up), dysarthria, numbness of the face, hemiparesis, headache, and diplopia. Less frequently, visual disturbances, including oscillopsia, field defects, transient blindness, cerebellar ataxia, dysphagia, and drop attacks may occur, reflecting ischemia of the brainstem and cerebellum. Vertigo or dysequilibrium may occur without other neurologic signs or symptoms. A definitive diagnosis may be established by four-vessel cerebral angiography, but is seldom indicated. Magnetic resonance angiography, a noninvasive imaging modality, will likely play an increasingly important role in the diagnosis of vertebrobasilar disease. Presently, there is no effective medical or surgical treatment for vertebrobasilar insufficiency, although rehabilitative measures may be beneficial in the amelioration of the vestibular symptoms.

LABYRINTHINE DISORDERS A host of peripheral vestibular disorders may cause vertigo, including benign paroxysmal positional vertigo

(BPPV) or cupulolithiasis, labyrinthitis, vestibular neuronitis, Ménière’s syndrome, labyrinthine concussion due to trauma, and perilymph fistula among others. In younger patients BPPV is usually secondary to trauma, whereas in the elderly it is usually a result of degenerative processes.21,59 The patient complains of intermittent, irregular episodes of vertigo precipitated by rapid head motion, particularly when turning over in bed or with neck extension. Vertigo is of short duration usually lasting less than a minute. The Hallpike maneuver, the brisk positioning of the patient’s head backward and sideways with the test ear positioned down, performed during electronystagmography is diagnostic. In a patient with BPPV, the maneuver elicits a geotropic verticorotatory nystagmus with a latency of a few seconds and lasting less than a minute. The intensity of the rotatory nystagmus is reduced on subsequent testing. Vestibular suppressant medications are of limited usefulness, except during periods of exacerbation. The severity of symptoms may diminish with repetition due to habituation. Patients usually respond to vestibular exercises and spontaneous resolution occurs within a year in most cases.60 In persistent cases, singular neurectomy may be curative.61 Ménière’s syndrome is characterized by episodic severe vertigo, fluctuating sensorineural hearing loss, tinnitus, and ear fullness. Pathologically, there is distension of the endolymphatic system throughout the inner ear, presumably due to dysfunction of the endolymphatic sac. Other specific causes of endolymphatic hydrops include bacterial, viral, immunologic, and syphilitic labyrinthitis. The clinical course is highly variable, with clusters of severe episodes interspersed with periods of remission of variable duration. Vertigo may last from 30 minutes to several hours and is usually associated with nausea and vomiting. A feeling of being off-balance or of unsteadiness may persist for several days with subsequent recovery until the next episode. The patient may complain of worsening hearing loss and tinnitus that may precede the acute attack of vertigo. Management may include a low-salt diet, diuretics, vasodilators, vestibular suppressants, and occasionally surgery to decompress the endolymphatic system. Acute labyrinthitis, which most probably results from a viral infection of the inner ear, causes both severe vertigo and hearing loss. Typically, it runs its course over a period of 1 to 2 weeks, although residual hearing loss and periodic recurrence of vertigo are frequent sequelae. In the elderly, the recovery may be incomplete and prolonged over several months. Vestibular neuronitis also presents with vertigo similar to labyrinthitis, but is unaccompanied by auditory symptoms. Electronystagmography demonstrates unilateral reduced caloric response.

OTHER OTOLOGIC AND NEUROTOLOGIC DISORDERS Middle ear disease such as acute otitis media can present with vertigo in the young and the elderly. Cholesteatoma may cause dizziness due to serous or bacterial labyrinthitis or direct erosion of the semicircular canals. Perilymphatic fistula resulting from chronic otitis media, cholesteatoma, or trauma can present with episodic vertigo. Ototoxicity

Vertigo, Dysequilibrium, and Imbalance with Aging

secondary to aminoglycoside therapy is more common in the elderly and is frequently associated with simultaneous diuretic therapy or diminished renal function.62 Acoustic neuroma, also called vestibular schwannoma, the most common tumor of the cerebellopontine angle, presents with unilateral hearing loss, tinnitus, and vertigo or dysequilibrium. Selesnick and Jackler63 found that nearly half of the patients complained of dysequilibrium that was directly correlated to the size of the tumor. Vertigo, present in 19% of their patients, was more common in smaller tumors. Other symptoms of acoustic neuroma include facial nerve dysfunction, and other cranial neuropathies, facial hypesthesia, headache, and cerebellar dysfunction. Audiogram usually reveals a unilateral, asymmetrical, sensorineural hearing loss with poor speech discrimination. Gadolinium-enhanced magnetic resonance imaging is the study of choice and is capable of identifying tumors millimeters in size. Surgical removal is curative. Other tumors of the cerebellopontine angle include meningioma, epidermoid, arachnoid cyst, lipoma, and metastatic tumor, among others.64 Clinically, they mimic an acoustic neuroma and may present with dizziness.

CERVICAL VERTIGO Vertigo occurring with neck motion is defined as cervical vertigo. The exact cause of this disorder is controversial. Possible explanations include altered spinovestibular input, vertebrobasilar ischemia due to compression by osteophytes, and irritation of the vertebral sympathetic plexus due to cervical spondylosis.65–67 The aortic arch syndrome and subclavian steal syndrome may also cause cervical vertigo. Cervical spine films are not helpful due to the large prevalence of asymptomatic osteoarthritic disease in the elderly. Neck exercises and proper posture may be of help in relieving the symptoms.

SYSTEMIC DISORDERS A plethora of systemic disorders may affect equilibrium and balance in the elderly, including cardiovascular disease (hypertension, arrhythmia, ischemic heart disease, hyperactive carotid sinus reflex, postural hypotension), cerebrovascular disease, peripheral vascular disease, neurologic disorders (Parkinson’s disease, dementia, epilepsy, vitamin B12 deficiency), visual impairment, metabolic disease (diabetes, thyroid disorder), and musculoskeletal problems.51 Therapeutic drugs are frequently responsible for dysequilibrium and postural instability, especially the antihypertensive, antidepressant, psychotropic, and sedativehypnotic classes.68

TREATMENT AND REHABILITATION OF VESTIBULAR DYSFUNCTION Many different drugs have been tried for the symptomatic relief of vertigo. In most common use are the antihistamines, sedative-hypnotics, and anticholinergics. Vestibular

537

suppressants should be used to lessen the unpleasant sensation and to alleviate vegetative symptoms such as nausea and vomiting. However, they should only be used for a short duration of 1 to 2 weeks, because they adversely affect the process of central compensation following acute vestibular disease. In acute severe vertigo, diazepam, 2.5 to 5 mg intravenously, may abate an attack. Relief from nausea and vomiting usually requires an antiemetic delivered intramuscularly or by rectal suppository (e.g., prochlorperazine, 10 mg intramuscularly, or 25 mg rectally every 6 hours). Antihistamines may be used for less severe vertigo. Examples include meclizine or dimenhydrinate, 25 to 50 mg orally every 6 hours. Transdermal scopolamine, which is in widespread use for the suppression of motion sickness, is also useful in the management of vertigo. In the elderly, however, anticholinergic therapy is frequently complicated by mental confusion and urinary obstruction, the latter especially in males. The use of transdermal scopolamine may also be limited due to side effects of dry mouth and blurred vision and is contraindicated in glaucoma patients. Therapeutic effect with fewer side effects may be achieved by cutting the patch in half or even to one-quarter size. Careful handwashing after handling the patches is necessary to prevent inadvertent eye contact with resultant prolonged pupillary dilatation and possible acute narrow-angle glaucoma. Therapy with a combination of pharmacologic agents may be efficacious when single-drug therapy has been ineffective. Once nausea and vomiting have resolved, exercise should be encouraged to enhance central compensation following peripheral labyrinthine dysfunction. Physical activity is the single most important element in functional recovery after acute labyrinthine dysfunction.69,70 Patients should be instructed to repeatedly perform maneuvers that provoke vertigo—up to the point of nausea or fatigue—in an effort to habituate them. Many patients find vestibular exercise programs (e.g., Cawthorne’s exercises) helpful.71 A formal physical therapy program designed to identify and correct maladaptive compensation strategies may also prove beneficial to patients with a central or peripheral vertigo. The benefit from vestibular rehabilitative therapy is not significantly influenced by the age of the patient72 but may be negatively affected by the presence of multiple causal factors. Subjective and objective benefit with vestibular rehabilitation is seen in patients with balance disturbance associated with migraine headache.73 Surgical intervention may be helpful in selected patients who continue to have disabling symptoms despite a prolonged and varied course of medical therapy. Surgical therapy may include sectioning of the vestibular nerve in a hearing ear or a labyrinthectomy in a deaf ear.74

REFERENCES 1. Droller H, Pemberton J: Vertigo in a random sample of elderly people living in their homes. J Laryngol 67:689–695, 1953. 2. Sheldon JH: The social medicine of old age. London, Oxford University Press, 1948. 3. Sixt E, Landahl S: Postural disturbances in a 75-year-old population: I. Prevalence and functional consequences. Age Ageing 16:393–398, 1987.

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4. Hale WE, Perkins LL, May FE, et al: Symptom prevalence in the elderly. J Am Geriatr Soc 34:333–340, 1986. 5. Sloane P, George L, Blazer D: Dizziness in a community elderly population. J Am Geriatr Soc 37:101–108, 1989. 6. Droller H: Falls among elderly people living at home. Geriatrics 10:239–244, 1955. 7. Overstall PW: Falls in the elderly—epidemiology, etiology, and management. In Isaacs B (ed.): Recent advances in geriatric medicine. New York, Churchill Livingstone, 1978. 8. Overstall PW: Falls. In Pathy MSJ (ed.): Principles and Practice of Geriatric Medicine, 2nd ed. New York, John Wiley & Sons, 1991. 9. Perry BC: Falls among the aged living in a high-rise apartment. J Family Pract 14:1069–1073, 1982. 10. Prudham D, Evans JG: Factors associated with falls in the elderly: A community study. Age Ageing 10:141–146, 1981. 11. Gryfe CI, Amiers A, Ashley MJ: A longitudinal study of falls in an elderly population. I. Incidence and morbidity. Age Ageing 6:201–210, 1977. 12. Tinetti ME: Factors associated with serious injury during falls by ambulatory nursing home residents. J Am Geriatr Soc 35:644–648, 1987. 13. Barber HO, Blakley BW: Ataxia of the elderly. In Goldstein JC, Kashima HK, Koopmann CF Jr (eds.): Geriatric Otolaryngology. Philadelphia, BC Decker, 1989. 14. Anderson RG, Meyerhoff WL: Otologic manifestation of aging. Otolaryngol Clin N Am 15(2):353–370, 1982. 15. Babin RW, Harker LA: The vestibular system in the elderly. Otolaryngol Clin N Am 15(2):387–393, 1982. 16. Engstrom H, Ades HW, Engstrom B, et al: Structural changes in the vestibular epithelia in elderly monkeys and humans. Adv Otorhinolaryngol 22:93–110, 1977. 17. Gleeson M, Felix H: A comparative study of the effect of age on the human cochlear and vestibular neuroepithelia. Acta Otolaryngol (Stockh) Suppl 436:103–109, 1987. 18. Kennedy R, Clemis JD: The geriatric auditory and vestibular systems. Otolaryngol Clin N Am 23:1075–1082, 1990. 19. Nadol JB Jr, Schuknecht HF: The pathology of peripheral vestibular disorders in the elderly. Ear Nose Throat J 68:930–933, 1989. 20. Ross MD, Johnsson LG, Peacor D, Allard LF: Observations on normal and degenerating human otoconia. Ann Otorhinolaryngol 85:310–326, 1976. 21. Schuknecht HF: Cupulolithiasis. Arch Otolaryngol 90:765–778, 1969. 22. Rosenhall U, Rubin W: Degenerative changes in the human vestibular sensory epithelia. Acta Otolaryngol 79:67–80, 1975. 23. Sloane PD, Baloh RW, Honrubia V: The vestibular system in the elderly: Clinical implications. Am J Otolaryngol 10:422–429, 1989. 24. Rosenhall U: Degenerative patterns in the aging human vestibular neuroepithelia. Acta Otolaryngol 76:208–228, 1973. 25. Engstrom H, Bergstrom B, Rosenhall U: Vestibular sensory epithelial. Arch Otolaryngol 100:411–418, 1974. 26. Fujii M, Goto N, Kikuchi K: Nerve fiber analysis and the aging process of the vestibulocochlear nerve. Ann Otorhinolaryngol 99:863–870, 1990. 27. Richter E: Quantitative study of human Scarpa’s ganglion and vestibular sensory epithelia. Acta Otolaryngol 90:199–208, 1980. 28. Bergstrom B: Morphology of the vestibular nerve. II. The number of myelinated vestibular nerve fibers in man at various ages. Acta Otolaryngol 76:173–179, 1973. 29. Johnson JE, Miquel J: Fine structural changes in the lateral vestibular nucleus of aging rats. Mech Ageing Dev 3:203–224, 1974. 30. Ellis RS: A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on functional localization. J Comp Neurol 30:229–252, 1919. 31. Hall TC, Miller AKH, Corsellis JAN: Variation in the human Purkinje cell population according to age and sex. Neuropathol Appl Neurobiol 1:267–292, 1975. 32. Glick R, Bondareff W: Loss of synapses in the cerebellar cortex of the senescent rat. J Gerontol 34:818–822, 1979.

33. Raz N, Torres IJ, Spencer WD, et al: Age-related regional differences in cerebellar vermis observed in vivo. Arch Neurol 49:412–416, 1992. 34. Brizzee KR, Klara P, Johnson SE: Changes in microanatomy, neurocytology and fine structure with aging. In Ordy JM, Brizzee KR (eds.): Neurobiology of Aging: An Interdisciplinary Life-Span Approach. New York, Plenum, 1975. 35. Nosal G: Neuronal involution during ageing, ultrastructural study in the rat cerebellum. Mech Ageing Dev 10:295–314, 1979. 36. Potvin AR, Syndulko K, Tourellotte WW, et al: Human neurologic function and the aging process. J Am Geriatr Soc 28:1–9, 1980. 37. Oosterveld WJ: Changes in vestibular function with increasing age. In Hinchcliffe R (ed.): Hearing and Balance in the Elderly. Edinburgh, Churchill Livingstone, 1983. 38. Rosenhall U, Bjokman G, Pedersen K, et al: Oculomotor tests in different age groups. In Grapham MD, Kemink JL (eds.): The Vestibular System: Neurophysiologic and Clinical Research. New York, Raven, 1987. 39. Stefansson S, Imoto T: Age-related changes in optokinetic and rotational tests. Am J Otol 7:193–196, 1986. 40. Era P, Heikkinen E: Postural sway during standing and unexpected disturbance of balance in random samples of men of different ages. J Gerontol 40:287–295, 1985. 41. Teasdale N, Stelmach GE, Breunig A: Postural sway characteristics of the elderly under normal and altered visual and support surface conditions. J Gerontol 46:B238–B244, 1991. 42. Simoneau GG, Leibowitz HW, Ulbrecht JS, et al: The effects of visual factors and head orientation on postural steadiness in women 55 to 70 years of age. J Gerontol 47:M151–M158, 1992. 43. Manchester D, Woollacott M, Zederbauer-Hylton N, Marin O: Visual, vestibular and somatosensory contributions to balance control in the older adult. J Gerontol 44:M118–M127, 1989. 44. Horak FB, Shupert CL, Mirka A: Components of postural dyscontrol in the elderly. Neurobiol Ageing 10:727–738, 1989. 45. Lord SR, Clark RD, Webster IW: Postural stability and associated physiological factors in a population of aged persons. J Gerontol 46:M69–M76, 1991. 46. Mulch G, Petermann W: Influence of age on results of vestibular function tests. Ann Otol 88(Suppl 56):1–17, 1979. 47. Ura M, Pfaltz R, Allum JHJ: The effect of age on the visuo- and vestibulo-ocular reflexes of elderly patients with vertigo. Acta Otolaryngol (Stockh) 481(Suppl):399–402, 1991. 48. Belal A Jr, Glorig A: Dysequilibrium of ageing (presbystasis). J Laryngol Otol 100:1037–1041, 1986. 49. Koopmann CF Jr: Otolaryngologic (head and neck) problems in the elderly. Med Clin N Am 75:1373–1388, 1991. 50. Linthicum FH Jr: Presbyastasis. In Goldstein JC, Kashima HK, Koopmann CF Jr (eds.): Geriatric Otolaryngology. Philadelphia, BC Decker, 1989. 51. Jenkins HA, Furman JM, Gulya AJ, et al: Dysequilibrium of ageing. Otolaryngol Head Neck Surg 100:272–281, 1989. 52. Maclennan WJ: Dizziness. In Evans JG, Williams TF (eds.): Oxford Textbook of Geriatric Medicine. Oxford, Oxford University Press, 1992. 53. Baloh RW: Dizziness in older people. J Am Geriatr Soc 40:713–721, 1992. 54. Luxon LM: Disorders of the vestibular system. In Pathy MSJ (ed.): Principles and Practice of Geriatric Medicine, 2nd ed. New York, John Wiley & Sons, 1991. 55. Luxon LM: Disturbances of balance in the elderly. Br J Hosp Med 45:22–26, 1991. 56. Cohen NL: The dizzy patient—Update on vestibular disorders. Med Clin N Am 75:1251–1260, 1991. 57. Vloet LC, Smits R, Frederiks CM, et al: Evaluation of skills and knowledge on orthostatic blood pressure measurements in elderly patients. Age Ageing 31(3):211–216, 2002. 58. Ausman JI, Shrontz CE, Pearce JE, et al: Vertebrobasilar insufficiency—A review. Arch Neurol 42:803–808, 1985.

Vertigo, Dysequilibrium, and Imbalance with Aging

59. Bloom J, Katsarkas A: Paroxysmal positional vertigo in the elderly. J Otolaryngol 18:96–98, 1989. 60. Norre ME, Beckers A: Vestibular habituation training for positional vertigo in elderly patients. Arch Gerontol Geriatr 8:117–122, 1989. 61. Gacek RR: Singular neurectomy for cupulolithiasis. In Nomura Y (ed.): Hearing Loss and Dizziness. Tokyo, Igaku-Shoin, 1985. 62. Baciewicz AM, Sokos DR, Cowan RI: Aminoglycoside-associated nephrotoxicity in the elderly. Ann Pharmacother 37:182–186, 2003. 63. Selesnick SH, Jackler RK: Clinical manifestations and audiologic diagnosis of acoustic neuromas. Otolaryngol Clin N Am 25:521–551, 1992. 64. Lalwani AK: Meningiomas, epidermoids, and other nonacoustic tumors of the cerebellopontine angle. Otolaryngol Clin N Am 25:707–728, 1992. 65. Barre HJ: Sur un syndrome sympathique cervical posterieure et sa cause frequente l’arthrite cervicale. Rev Neurol 33:1246–1252, 1926. 66. Sheehan S, Bauer RB, Meyer JS: Vertebral artery compression in cervical spondylosis. Neurology 10:968–986, 1960.

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67. Wyke B: Cervical articular contributions to posture and gait: Their reaction to senile dysequilibrium. Age Ageing 8:251–258, 1979. 68. Mhoon E: Otology. In Cassel CK, Riesenberg DE, Sorensen LB, Walsh JR (eds.): Geriatric Medicine. New York, Springer-Verlag, 1990. 69. Herdman SJ: Exercise strategies for vestibular disorders. Ear Nose Throat J 68:961–964, 1989. 70. Norre ME, Forrez G, Beckers A: Vestibular dysfunction causing instability in aged patients. Acta Otolaryngol (Stockh) 104:50–55, 1987. 71. Dix MR: The rationale and technique of head exercises in the treatment of vertigo. Acta Otorhinolaryngol 33:370–384, 1979. 72. Whitney SL, Wrisley DM, Marchetti GF, Furman JM: The effect of age on vestibular rehabilitation outcomes. Laryngoscope 112(10):1785–90, 2002. 73. Wrisley DM, Whitney SL, Furman JM: Vestibular rehabilitation outcomes in patients with a history of migraine. Otol Neurotol 23(4):483–487, 2002. 74. Gacek RR, Ham R: A clinical approach to the management of geriatric dysequilibrium. Ear Nose Throat J 68:958–960, 1989.

Chapter

33 Mark J. Syms, MD

Cervical Proprioceptive Dysfunction Outline Introduction Definition Cervical Proprioceptive Function Clinical Evidence

INTRODUCTION A sense of balance is obtained through integration of three sensory systems—visual, vestibular, and somatosensory. The sensory information is redundant, which allows the loss, or decreased input, of one sense to be compensated for, in part, by input from the other two sensory systems. When the information from two sensory sources conflict, disorientation and vertigo results. The intensity of the disorientation and vertigo is a function of the magnitude of the sensory mismatch.

DEFINITION Cervical vertigo, a controversial term that has been commonly used in the literature,1 was introduced by Ryan and Cope2 to describe a condition affecting four patients with vertigo and common neck complaints. Neck afferents not only assist in coordination of the eye, head, and body, but also influence spatial orientation and posture. On this basis, it is argued that stimulation or lesions of the neck proprioceptive system could result in vertigo. The skeptics question the existence of cervical vertigo for two reasons.3 First, there is no reliable clinical test for the syndrome and a typical time course for the condition has not been established. Second, reliable and well-established signs and tests can establish a convincing alternative diagnosis in about 90% of patients presenting with vertigo.

CERVICAL PROPRIOCEPTIVE FUNCTION The neck enables rotation of the head independently of the trunk. In order to maintain a stabile position, the vestibular input has to be complemented with neck proprioceptive input.4 There is considerable experimental evidence from animal studies demonstrating neck and vestibular signals converge and interact in the brain.5–8 Anatomic studies have identified links between the cervical 540

Differential Diagnosis Treatment Conclusion

spine receptors and the vestibular nuclei.9,10 Large populations of receptors have been found in the neck muscle in close proximity to the facet joints of the cervical spine.11 Various reflexes have been demonstrated between the neck and vestibular and ocular systems. The vestibulocollic reflex (VCR) is mediated by vestibulospinal projections.12 The function of the VCR is to stabilize the head in space by means of neck muscle movements. The VCR operates in conjunction with the cervicocollic reflex (CCR), which employs proprioceptive information from the neck to stabilize the head on the body.13 In 1906 Bárány was the first to observe, in rabbits, coordinated deviations of the eyes toward the direction of trunk movements when the head was held stationary in space.14 Later, the cervico-ocular reflex (COR) was demonstrated in normal human subjects and found to contribute to visual stabilization.15 It is thought that neck joint receptors rather than muscle spindles are the primary source of neck afferents involved in the COR.16,17 The body employs these reflexes to maintain position of the head in space. Any perturbations of the information or interruptions of the reflexes could potentially lead to a proprioceptive disorder.

CLINICAL EVIDENCE Despite the evidence demonstrating cervical contribution to proprioception, skeptics argue that no reliable tests exist.3 The presence of nystagmus with neck movement is not diagnostic of a cervical proprioceptive disorder. Cervical nystagmus has been found in subjects without the complaint of vertigo.18 Since neck control is the product of input of multiple systems, isolation of the cervical region as the source of the “dizziness” is impossible with simple postural maneuvers.3 Animal experiments have demonstrated that surgical deafferentation of C1–3 in squirrel monkeys19 and in the cat20 caused ataxia. Additionally, injection of local anesthesia in the suboccipital region caused ataxia in rhesus monkeys.21 When suboccipital anesthesia is performed in humans,

Cervical Proprioceptive Dysfunction

transient increased ipsilateral and decreased contralateral extensor muscle tone results with a tendency to fall, and a deviation of gait and past-pointing toward the injected side occurs.3 Based on this evidence, the characteristics of cervical proprioceptive dysfunction is likely to be a sensation of numbness or floating with ataxia of stance and gait. The relative contribution of the neck afferents to the vestibular nuclei is small compared with the major, direct input from the labyrinth and the indirect input from the visual system.22 The work of De Jong and colleagues did demonstrate vertigo when C2–3 were anesthetized.21 However, it has been demonstrated that lesions involving the neck afferents in primates compensate rapidly.23 This rapid compensation would make chronic dysequilibrium or vertigo difficult to explain on the basis of disruption of cervical structures. Despite the inability to clearly define the cause and time course of cervical proprioceptive disorders, certainly cervical dysfunction can contribute to dizziness. After whiplash injuries, dizziness/vertigo is reported to be one of the most frequent, distressing, and persistent symptoms (Table 33-1). Since dizziness is very common with whiplash injuries, the controversy surrounding cervical vertigo is understandable given the economic and legal ramifications of injuries resulting in whiplash.

Skeptics of the existence of cervical vertigo argue the symptoms of cervical vertigo have an alternative explanation.24 Brandt argues that well-established signs and tests can provide a convincing alternative diagnosis in about 90% of patients presenting with vertigo.3 Prior to making the diagnosis of cervical vertigo, alternative causes need to be excluded (Table 33-2). Others argue that cervical vertigo is very common. Karlberg and colleagues evaluated 65 patients and found 22 of the patients had dizziness of cervical origin.25 Despite the controversy surrounding the definition and existence of cervical vertigo, vertigo with a cervical component surely exists. In the context of a thorough neurotologic examination, clinicians can recognize that cervical disorders are a component of the dizziness a patient is experiencing and should attempt to address the cervical disorder with the hope of improving the symptoms.

TREATMENT Cervical physical therapy has been reported to be very successful in the resolution of vertigo attributed to cervical dysfunction. Galm and colleagues reported on a group of 50 patients who presented with symptoms of dizziness.26 TABLE 33-1. Dizziness/Vertigo after Head Injury

Linthicum and Rand27 Glaser Procter et al28

Number of Patients 30 70 32

TABLE 33-2. Differential Diagnosis of Cervical Vertigo Disorder

Assumed Mechanism

Labyrinthine Benign paroxysmal positional vertigo Post-traumatic otolith vertigo Perilymph fistula

Canalotolithiasis, cupulolithiasis Dislodged otoconia, causing unequal heavy load of macula Floating labyrinth

Vestibular Nerve Unilateral vestibular failure Bilateral vestibular failure Vestibular paroxysmia Nerve compression by cerebellopontine angle mass

Cross coupling effects with acute vestibular tone imbalance Defective vestibulo-ocular reflex Neurovascular cross compression Conduction block or ectopic discharges

Ocular Motor Extraocular eye muscle or gaze paresis Central vestibular: Central positional nystagmus/vertigo Migraine without aura Migraine with aura (basilar migraine, vestibular migraine) Vestibulocerebellar ataxia

Inappropriate vestibulo-ocular reflex Cerebellar disinhibition Motion sickness due to sensory hyperexcitiability Spreading depression involving vestibular structures Vestibulocerebellar dysfunction

Vascular

DIFFERENTIAL DIAGNOSIS

Author

541

Incidence (%) 90 40 50

Luxon L: Posttraumatic vertigo. In Baloh R, Halmagyi G (eds.): Disorders of the Vestibular System. New York, Oxford University Press, 1996, pp 381–395.

Rotational vertebral artery occlusion Carotid sinus syndrome Intoxication: Positional alcohol nystagmus/vertigo Drugs (e.g., antiepileptics)

Ischemic depolarisation Global cerebral ischemia Cerebellar and specific gravity differential between cupula and endolymph Cerebellar and ocular motor

From Brandt T, Bronstein AM: Cervical vertigo. J Neurol Neurosurg Psychiatry 71(1):8–12, 2001.

Each patient underwent a neurologic and otolaryngologic examination to rule out other causes of the vertigo. The patients underwent a chiropractic evaluation, which demonstrated dysfunction of the upper cervical spine in 31 (62%) of the 50 patients. The remaining 19 (38%) patients did not show signs of upper cervical dysfunction. All of the patients underwent extensive outpatient physical therapy for 3 months and were followed up 2 weeks after the end of the therapy. If the patient’s vertigo was not resolved, the patients underwent another 3 months of physical therapy and were reevaluated 2 weeks after the completion of the physical therapy. In the group with cervical dysfunction, the vertigo was improved in 16 of 31 patients after the first 3 months of therapy. None of the 19 patients without cervical dysfunction had improvement of their vertigo. After the second 3 months of physical therapy, 24 (77.4%) of the 31 patients reported improved vertigo symptoms. The remaining seven reported no improvement. Of the group without cervical dysfunction, only five patients (26.3%) reported any improvement of the vertigo symptoms. Similarly, Karlberg and associates reported that physiotherapy in patients with dizziness of a suspected cervical origin significantly reduced the neck pain and intensity and the frequency of the dizziness.25 Even skeptics of the existence of cervical vertigo acknowledge that vertigo

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can be accompanied by cervical pain and associated with head injury or whiplash injury and that in some cases it improves dramatically with physiotherapy.1

CONCLUSION Cervical vertigo is a controversial entity. Despite the controversy, vertigo with a cervical component surely exists. Clinicians should perform a thorough neurotologic examination and recognize if a cervical disorder is a component of the dizziness a patient is experiencing. If a cervical proprioceptive disorder is thought to contribute to the dizziness, the patient should be referred for physiotherapy to address the cervical disorder.

REFERENCES 1. Brandt T: Cervical vertigo—Reality or fiction? Audiol Neurootol 1(4):187–196, 1995. 2. Ryan G, Cope S: Cervical vertigo. Lancet 2:1355–1358, 1955. 3. Brandt T: Vertigo: Its Multisensory Syndromes. New York, Springer-Verlag, 1991, pp 277–288. 4. Roberts TD: Reflex balance. Nature 244(5412):156–158, 1973. 5. Fredrickson JM, Schwarz D, Kornhuber HH: Convergence and interaction of vestibular and deep somatic afferents upon neurons in the vestibular nuclei of the cat. Acta Otolaryngol 61(1):168–188, 1966. 6. Boyle R, Pompeiano O: Convergence and interaction of neck and macular vestibular inputs on vestibulospinal neurons. J Neurophysiol 45(5):852–868, 1981. 7. Rubin AM, Liedgren SR, Odkvist LM, et al: Labyrinthine and somatosensory convergence upon vestibulospinal neurons. Acta Otolaryngol 86(3–4):251–259, 1978. 8. Kasper J, Schor RH, Wilson VJ: Response of vestibular neurons to head rotations in vertical planes. II. Response to neck stimulation and vestibular-neck interaction. J Neurophysiol 60(5):1765–1778, 1988. 9. Bankoul S, Neuhuber WL: A direct projection from the medial vestibular nucleus to the cervical spinal dorsal horn of the rat, as demonstrated by anterograde and retrograde tracing. Anat Embryol (Berl) 185(1):77–85, 1992. 10. Neuhuber WL, Zenker W: Central distribution of cervical primary afferents in the rat, with emphasis on proprioceptive projections to vestibular, perihypoglossal, and upper thoracic spinal nuclei. J Comp Neurol 280(2):231–253, 1989.

11. Dutia MB: The muscles and joints of the neck: their specialisation and role in head movement. Prog Neurobiol 37(2):165–178, 1991. 12. Peterson B, Baker J, Perlmutter S, Iwamoto Y: Neuronal substrates of spatial transformations in vestibuloocular and vestibulocollic reflexes. In Cohen B, Tomko D, Guerdy F (eds.): Sensing and Controlling Motion: Vestibular and Sensorimotor Function. New York, New York Academy of Sciences, 1992, pp 485–499. 13. Peterson B, Goldberg J, Bilotto G, Fuller F: Cervicocollic reflex: Its dynamic properties and interactions with vestibular reflexes. J Neurophysiol 54:90–109, 1985. 14. Bárány R: Augenbewegegungen durch Thoraxbewegungen ausgelöst. Zbl Pysiol 20:298–302, 1906. 15. Barnes GR, Forbat LN: Cervical and vestibular afferent control of oculomotor response in man. Acta Otolaryngol 88(1–2):79–87, 1979. 16. Biemond A, De Jong JM: On cervical nystagmus and related disorders. Brain 92(2):437–458, 1969. 17. McCouch G, Deering I, Ling T: Location of receptors for tonic neck reflexes. J Neurophysiol 14:191–195, 1951. 18. Norre ME, Forrez G, Stevens A, Beckers A: Cervical vertigo diagnosed by posturography? Preliminary report. Acta Otorhinolaryngol Belg 41(4):574–581, 1987. 19. Igarashi M, Alford BR, Watanabe T, Maxian PM: Role of neck proprioceptors for the maintenance of dynamic bodily equilibrium in the squirrel monkey. Laryngoscope 79(10):1713–1727, 1969. 20. Manzoni D, Pompeiano O, Stampacchia G: Cervical control of posture and movements. Brain Res 169(3):615–619, 1979. 21. De Jong PT, de Jong JM, Cohen B, Jongkees LB: Ataxia and nystagmus induced by injection of local anesthetics in the Neck. Ann Neurol 1(3):240–246, 1977. 22. Luxon L: Posttraumatic Vertigo. In Baloh R, Halmagyi G (eds.): Disorders of the Vestibular System. New York, Oxford University Press, 1996, pp 381–395. 23. Baloh R, Honrubia V: Clinical Neurophysiology of the Vestibular System. Philadelphia, FA Davis, 1990. 24. Brandt T, Bronstein AM: Cervical vertigo. J Neurol Neurosurg Psychiatry 71(1):8–12, 2001. 25. Karlberg M, Magnusson M, Johansson R: Effects of restrained cervical mobility on voluntary eye movements and postural control. Acta Otolaryngol 111(4):664–670, 1991. 26. Galm R, Rittmeister M, Schmitt E: Vertigo in patients with cervical spine dysfunction. Eur Spine J 7(1):55–58, 1998. 27. Linthicum F, Rand C: Neuro-otological observations in concussion of the brain. Arch Otolaryngol 13:785–821, 1931. 28. Procter B, Gurdjian E, Webertser J: The ear in head trauma. Laryngoscope 66:16–61, 1956.

34

Outline Paraneoplastic Syndromes Generated by Neurotologic Tumors Paraneoplastic Syndromes from Disorders Associated with Neurotologic Tumors Paraneoplastic Syndromes Associated with Carcinoma Summary

T

he concept that cancers could evoke remote effects was first articulated by Guichard in 1956 when he referred to the polyneuritis seen in patients with known cancer as a paraneoplastic syndrome (PNS).1 Fundamentally, a PNS describes an “association of symptoms and signs not directly related to the site or local manifestations of a malignant tumor or its metastases.”1 Although the term is most appropriately used when referring to the remote effects of cancerous lesions, for the purpose of discussion in this chapter it is expanded to encompass the remote effects of benign tumors as well. PNSs are of significance to neurotologists for they may be generated by tumors managed by neurotologists, they may be generated by neoplasms occurring in association with disorders managed by neurotologists, or they may give rise to auditory and vestibular dysfunction requiring neurotologic evaluation and management. In addition, a PNS provides a unique vantage point from which to observe the basic biology of the tumor cell involved.

PARANEOPLASTIC SYNDROMES GENERATED BY NEUROTOLOGIC TUMORS The chief cells of paraganglions and paragangliomas (glomus tumors) are of neural crest origin and are constituents of the diffuse neuroendocrine system (DNES) (Table 34-1).2,3 Cells of the DNES, although seemingly disparate in nature, are linked by shared cytochemical and ultrastructural features, particularly with regard to their capacity to synthesize, store (in osmiophilic granules), and secrete physiologically active products, for example, amines and neuropeptides,4 which variably function as neurotransmitters, neurohormones, hormones, and parahormones.4 The chief cells of paragangliomas have a demonstrated capacity for catecholamine synthesis and secretion.5–9 The metabolism of tyrosine, key in the generation of catecholamines, is illustrated in Table 34-2.10 Only the adrenal medulla, heart, and brain possess the enzyme

Chapter

Paraneoplastic Disorders

A. Julianna Gulya, MD, FACS

phenylethanolamine-N-methyltransferase; thus, in paragangliomas dopamine and norepinephrine are produced.9,11 Tryptophan metabolism results in the production of the indole amine serotonin (5-hydroxytryptamine) (Table 34-3),10 a capacity within the repertoire of human glomus cells, as evidenced by their serotonin immunoreactivity.12–15 In addition, the chief cells of paragangliomas have been documented to contain a wide variety of neuropeptides (Table 34-4), enzymes, and other proteins typical of, although not entirely specific for, members of the DNES.13 Neuron-specific enolase (NSE), chromogranin, and leuenkephalin in particular serve as markers for chief cells, and sustentacular cell markers include S-100 protein, glial fibrillary acidic protein (GFAP),13 and nerve growth factor receptor. The clinical consequences of amine production by paragangliomas are manifested in the PNS of the “functional” tumor. Although, as pointed out by Batasakis,16 “nearly all” of these tumors “demonstrate intracellular catecholamines,” only 1% to 3% actually give rise to the hypertension, headaches, excessive perspiration, tremor, palpitations, pallor, nausea, anxiety, flushing, epigastric or chest pain, and weight loss related to elevation of serum norepinephrine and possibly dopamine.9 The disparity between potential and actual catecholamine-related symptomatology is generally attributed to the requirement for a four- to fivefold elevation of serum norepinephrine for the development of symptoms.9 Tumor burden in and of itself does not appear to predict whether or not a tumor will be “functional.”17 Ultrastructural and immunocytochemical analyses18 have suggested that functional tumor cells, in contrast to those of nonfunctional tumors, have larger secretory granules (220 to 280 nm vs. 100 to 180 nm), contain numerous dilated mitochondria) profiles (indicative of metabolic activity), and express at least two of the antigens enkephalin, neuropeptide Y, or tyrosine hydroxylase. The carcinoid syndrome, consisting of “episodic cutaneous flushing, cyanosis, abdominal cramps, diarrhea, and valvular heart disease (and less commonly asthma and arthropathy),”19 has been related to elevated serum levels of serotonin. Farrior and associates20 presented one 543

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TABLE 34-1. Cells of the DNES

TABLE 34-3. Tryptophan Metabolism TRYPTOPHAN

Pituitary chief cells Pancreatic islet cells Thyroid C-cells Paraganglion chief cells Adrenal medulla cells Parathyroid chief cells* Lung endocrine (Feyrter) cells Gastrointestinal argyrophil and enterochromaffin cells *Debated. DNES, diffuse neuroendocrine system. Adapted from Bolande RP: The neurocristopathies: A unifying concept of disease arising in neural crest maldevelopment., Human Pathol 5:409–429, 1974.

Tryptophan hydroxylase 5-HYDROXYTRYPTOPHAN Decarboxylation SEROTONIN (5-Hydroxytryptamine) Data from Diem K, Lentner C: Scientific Tables, 7th ed. Ardsley, NY, Geigy Pharmaceuticals, 1970.

paraganglioma (jugulare) in which carcinoid-like symptomatology resolved with resection of the tumor, providing circumstantial evidence for the association of paragangliomas with yet another type of PNS. More convincingly, Galan and colleagues21 reported the development of hypotension, bradycardia, and bronchospasm with intraoperative manipulation of a glomus tympanicum tumor that had been associated preoperatively with elevated urinary 5-hydroxyindoleacetic acid (5-HIAA), the urinary metabolite of serotonin. Within 5 minutes of the administration of intravenous octreotide, the bronchospasm and the hemodynamic changes resolved, and by the fifth postoperative day the patient’s urinary 5-HIAA dropped to nearly normal. The neuropeptides found within paraganglioma cells, both chief and sustentacular, remain of uncertain significance. Investigations have focused on the possibility that neuropeptides give rise to PNS(s),22 that they prognosticate tumor behavior,23 or that they can be used for tumor localization.24 In the course of caring for patients who had undergone infratemporal fossa removal of paragangliomas, members of the Otology Group noted postoperative ileus, acalculous cholecystitis, and pancreatitis not seemingly related to the surgical procedure nor the patients’ past medical

histories. In an attempt to determine whether neuropeptide secretion by the paragangliomas precipitated such symptomatology, routine serum screening of paraganglioma and other skull base tumor patients for vasoactive intestinal polypeptide, cholecystokinin (CCK), somatostatin, pepsinogen I, human pancreatic polypeptide, and thyroid-releasing hormone was undertaken. The degree of postoperative ileus was then contrasted to the preoperative serum levels of these neuropeptides, as well as to sacrifice of the vagus nerve. In a review of 25 cases (19 paragangliomas and 6 nonglomus tumors) it became evident that vagus nerve sacrifice was not a determinant factor in postoperative ileus. Interestingly enough, serum CCK levels in patients with paragangliomas were significantly higher ( p < 0.05) than those of nonparaganglioma patients, and the patients with more than 3 days of postoperative ileus had preoperative CCK levels approximately twice that of patients with postoperative ileus of briefer duration.22 A major difficulty in drawing firm conclusions from these data is the wide variability in normal CCK serum levels; nonetheless, further investigation appears warranted, especially of the tracking serum neuropeptide levels postoperatively. A few reports of anemia, usually normochromic/normocytic, were associated with metastatic paragangliomas.25–28

TABLE 34-2. Tyrosine Metabolism

TABLE 34-4. Immunohistochemical Markers for Paragangliomas

TYROSINE

Chief Cells Tyrosine hydroxylase DOPA Dopa decarboxylase DOPAMINE Dopamine hydroxylase NOREPINEPHRINE Phenylethanolamine-N-Methyltransferase

Catecholamines Norepinephrine Dopamine Serotonin Neuron-specific enolase Chromogranins Synaptophysin Neurofilaments

Sustentacular Cells S-100 protein Glial fibrillary acidic protein Nerve growth factor receptor Neuropeptides Enkephalins

Pancreatic polypeptide Somatostatin Gastrin Calcitonin Neuropeptide Y Corticotropin Vasoactive intestinal polypeptide Bombesin Neurotensin Insulin Glucagon Substance P Cholecystokinin Alpha melanocyte stimulating hormone

EPINEPHRINE Data from Diem K and Lentner C: Scientific Tables, 7th ed. Ardsley, NY, Geigy Pharmaceuticals, 1970.

Data from Kliewer KE, Cochran AJ: A review of the histology, ultrastructure, immunohistology, and molecular biology of extra-adrenal paragangliomas. Arch Pathol Lab Med 113:1209–1218, 1989.

Paraneoplastic Disorders

Two patients with nonmetastatic, cervical paragangliomas experienced normalization of reduced hematocrits subsequent to tumor removal.27,29 Interference with production of, or enhanced destruction of, erythropoietin are mechanisms proposed by Schwartz and Israel26 based on their finding of depressed erythropoietin levels in a patient with metastatic paraganglioma. The precise mechanism of such an “antierythropoietic effect,” if it truly exists, has yet to be determined. Linnoila and colleagues23 conducted immunohistochemical analyses of 99 human adrenal and extra-adrenal paragangliomas for neuron-specific enolase and a total of 10 neuropeptides. They found that malignant paragangliomas, that is, those with “proven regional or distant metastases,” were positive for only an average of two neuropeptides per tumor, in contrast to the benign tumors, which were positive for an average of five neuropeptides per tumor. They suggested that there was a “definite relationship between expression of neuropeptides and the biologic behavior of these paragangliomas.”23 Lamberts and associates24 reported on the utility of 123 Ilabeled Tyr3-octreotide (a somatostatin analogue) in visualizing some tumors, including paragangliomas, with somatostatin receptors. Of the 20 paraganglioma patients scanned, 10 jugulotympanic, 9 carotid, and 10 vagal paragangliomas were detected. Scanning missed small tumors (less than 5 mm)—one carotid body and one tympanic paraganglioma. Scintigraphy with 111In-diethylenetriaminepentaacetic acid octreotide (indium-111-pentretreotide) is able to reveal tumors of at least 1 cm and perhaps as small as even 0.5 cm30 and may aid in the differentiation of paraganglioma versus neuroma, meningioma, radionecrosis, and postoperative scar from recurrent paraganglioma. Octreotide may have some utility in the treatment of unresectable or recurrent paragangliomas. In one report,31 octreotide therapy for up to 35 months was associated with either no tumor growth or reduced tumor volume as visualized by magnetic resonance imaging; side effects of the therapy were mild, consisting largely of fatty stool.

PARANEOPLASTIC SYNDROMES FROM DISORDERS ASSOCIATED WITH NEUROTOLOGIC TUMORS PNSs may arise from tumors occurring in conjunction with disorders managed by the neurotologist; such situations are exemplified by the occurrence of additional nonparaganglioma tumors with paragangliomas, as well as with neurofibromatosis. Paragangliomas have long been recognized for their propensity to manifest associated lesions; approximately 10% of nonfamilial jugulotympanic paragangliomas will exhibit another tumor of the paraganglioma type.32–34 In addition, pheochromocytomas,35,36 papillary thyroid carcinoma,37 medullary carcinoma of the thyroid,38 and parathyroid adenoma9 have been reported in association with paragangliomas. Kennedy and Nager38 pointed out a potential relationship between the occurrence of paragangliomas (tympanic)

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with multiple endocrine neoplasia II (MEN II—Sipple’s syndrome), an autosomal-dominant, familial disease consisting of pheochromocytomas, medullary carcinoma of the thyroid, and parathyroid hyperplasia. A familial tendency has been described for paragangliomas, typified by autosomal-dominant transmission and an exaggeration in the tendency for multiple para-gangliomas,39,40 occurring in 25% to 50% of the cases39–42 and also perhaps in the occurrence of associated lesions.39 Thus, regardless of the functional status of the paraganglioma that brings the patient to the attention of the neurotologist, it is possible for an associated lesion to give rise to the symptomatology of a PNS. It is important to recognize that elevated serum epinephrine levels in a patient with a paraganglioma mandate a thorough investigation for a concurrent pheochromocytoma, because, as discussed earlier, paragangliomas cannot metabolize norepinephrine to epinephrine. Patients with neurofibromatosis (von Recklinghausen’s disease, NF1) also tend to manifest associated lesions. For example, they have a 10-fold greater incidence of pheochromocytoma than the general population.43 The occurrence of parathyroid adenoma in NF1 has been speculated to represent a variant of MEN IIb, that is, the MEN II that occurs in patients with diffuse ganglioneuromatosis of the alimentary tract, mucosal neuromas, and often a marfanoid habitus.44 Griffiths and colleagues45,46 have even suggested that the triad of NF1, pheochromocytomas, and duodenal carcinoid constitutes a specific multiple endocrine neoplasia syndrome, which they labeled MEN IIIa. Terminology can cause confusion, for MEN IIb also has been referred to as MEN III.44 Thus in managing neurofibromatosis the neurotologist must be cognizant of the possibility of an associated lesion with functional potential and may consider endocrinology consultation for appropriate diagnosis and treatment. Finally, neurofibromatosis has been associated with pheochromocytomas, a paraganglioma (jugulare), and multiple pulmonary paraganglioma,43 as well as with a vagal paraganglioma.3 Although such an association may merely be a chance event, it may be more reasonable to consider all of these lesions as reflecting an abnormality of neural crest derivatives, or, as stated by Bolande,3 a neurocristopathy. As defined by Bolande,3 a neurocristopathy is a condition with roots in aberrant neural crest development. Isolated paragangliomas, pheochromocytomas, and carcinoid tumors are some examples of what Bolande categorized as simple neurocristopathies, or single, localized pathologic processes. Complex neurocristopathies or neurocristopathic syndromes include such entities as von Recklinghausen’s disease and the multiple endocrine neoplasia disorders, which are typified by a vast array of possible combinations of the simple neurocristopathies. In fact, von Recklinghausen’s disease, because it can potentially involve a wide range of neurocutaneous and neuroendocrine disorders, is considered the prototype of the complex neurocristopathies.3 Thus it is perhaps more useful in terms of extending our knowledge of the basic biology of the paraganglioma not merely to dismiss associations with other neural crest disorders as random events, but to consider them as clues

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to the existence of neurocristopathic syndromes, in which paragangliomas represent only one manifestation.

PARANEOPLASTIC SYNDROMES ASSOCIATED WITH CARCINOMA Certain PNSs associated with malignancies rarely will encompass auditory or vestibular symptomatology leading to neurotologic consultation. Despite their rarity, such PNSs are of significance because they provide a unique perspective on the biology, not only of the underlying cancer,47 but also of the auditory and vestibular systems. Substantial progress, accelerated by advances in immunochemistry and immunohistochemistry, has been made in elucidating the operative mechanisms of two PNSs of potential relevance to neurotologists, namely, paraneoplastic encephalomyelitis (PEM) and paraneoplastic cerebellar degeneration (PCD). PEM describes a group of neurologic PNSs sharing inflammatory changes in neural tissue, especially perivascular round cell infiltrates, microglial activation and neuronal loss,48,49 and an autoimmune pathogenesis.50 A small-cell lung carcinoma (SCLC) is the underlying malignancy in the majority of cases.51 The various types of PEM, namely, cerebral encephalitis, brainstem encephalitis, cerebellar encephalitis, subacute myelitis, and dorsal root ganglionitis, are distinguished according to predominant anatomic site of the lesion. Clinical application of this nosology is confronted with the reality of considerable overlap among the various types.51 The brainstem form of PEM manifests the hallmark inflammatory neuronal destruction, especially in the medulla,51 that commonly involves the vestibular brainstem nuclei and uncommonly affects the cochlear nuclei.51 In addition, cranial nerve motor nuclei, such as XII and X may be affected,51 and in the pons, the cranial nerve nuclei involved include VI and VII.51 Sudden unilateral sensorineural hearing loss has been documented well in only one case of brainstem encephalitis.52 McGill52 found diffuse cochlear neuronal loss in the spiral ganglion as well as in the dorsal and ventral cochlear nuclei and peripheral vestibular structures ipsilateral to the side of a sudden sensorineural hearing loss in a 54-year-old female whose underlying SCLC was detected only on autopsy. Such diffuse neuronal loss is not characteristic of viral sudden sensorineural hearing loss.53,54 Márquez and coworkers55 reported the development of a bilateral, rapidly-progressive sensorineural hearing loss associated with gait instability in a 50-year-old man who was subsequently found to have lung carcinoma with antiHu antibodies (see following discussion). Unfortunately, an autopsy was not performed. PCD describes the subacute cerebellar degeneration seen in patients with carcinoma (especially of the ovaries, breast, and lung [SCLC]) and lymphoma.56 Histopathologically, inflammatory and noninflammatory variants occur,57 and although the exact relationship of the two forms is uncertain,50 they both share the finding of a diffuse loss of Purkinje cells. Patients with PCD manifest progressive pancerebellar dysfunction, particularly truncal and appendicular ataxia, nystagmus, dysarthria, and diplopia.2,57-59 Abrupt-onset

vertigo or ataxia may be the initial symptoms of PCD,57 and although concurrent hearing loss has been reported,59,60 no histopathologic correlates have been reported. The appropriate diagnosis of PEM and PCD is of significance because the onset of either PNS may precede the diagnosis of the underlying malignancy.61 Nonspecific clues for PEM are sudden hearing loss occurring in a patient older than 50 years in association with diffuse neurologic symptoms. PCD is part of the differential diagnosis of sudden-onset or progressive vertigo and ataxia, particularly in a middle-aged female. Both PEM and PCD can manifest the cerebrospinal fluid (CSF) findings of pleocytosis with lymphocytic predominance, an elevated protein count, oligoclonal bands, and an elevated IgG level.50,51 More specific tests have been developed for the diagnosis of PEM and PCD, as discussed later. The preponderance of evidence favors an autoimmune pathogenesis for both PEM and PCD. The foundation of the autoimmune hypothesis is that the cancer patient produces antibodies that react with antigens displayed by the tumor; the antibodies may or may not have an adverse effect on tumor growth,62,63 but they do react with antigens of specific neural cells, causing their dysfunction or death.63 Certainly, in the case of PEM, such a hypothesis appears feasible because the cells of origin of SCLC, Kulchitsky cells of the lung, are members of the DNES and can express a variety of neuronal differentiation antigens.64–67 Further support for the autoimmune hypothesis has come with the identification of the antibodies anti-Hu and anti-Yo being relatively restricted to patients with PEM and PCD, respectively.50,68–70 Anti-Hu reacts with 35- to 36-kilodalton nucleoproteins expressed only by brain tissue, for example, the neurons of the nuclei of the brain (including the vestibular and cochlear nuclei), and dorsal root and gasserian ganglion neurons, as well as SCLC tissue. The nuclear staining observed immunohistochemically with anti-Hu spares the nucleolus and is not observed with satellite, Schwann, or non-neural cells.62,71 Anti-Hu has been detected in the blood and CSF72,73 and has also been eluted from tumor (SCLC) and brain tissue of patients with PEM.74 The antibody may be taken up from the blood by central nervous system (CNS) neurons in a process that involves endocytosis and retrograde axonal transport,75 or from the CSF, which is linked to intrathecal anti-Hu production.72 Copy DNA (cDNA) clones have been isolated from both normal brain tissue76 and SCLC tissue,77 which code for the Hu antigen. A quantitative assay for anti-Hu sera has been developed that uses the fusion protein encoded by these cDNA clones.76 The target of the anti-Hu antibody is a family of neuron-specific RNA-binding proteins (Hu).78 It is thought that “antibody mediated disruption of the Hu RNA-binding activity might lead to neuronal death,”78 but the mechanism remains unclear. Anti-Yo is the anti-Purkinje cell antibody found in the serum and79 CSF72,80 of women with gynecologic or breast cancer and PCD.69 Immunofluorescent study of anti-Yo reveals a coarsely granular fluorescence of the cytoplasm,69 which by immunoelectron microscopy81 is correlated to binding to the endoplasmic reticulum (Nissl substance) and Golgi complexes of Purkinje cells. Two groups of proteins (cerebellar degeneration–related [CDR] proteins)—one with

Paraneoplastic Disorders

a relative molecular weight of 62 to 64 kilodaltons (CDR 62) and one with a relative molecular weight of 34 to 38 kilodaltons (CDR 34)—are recognized by anti-Yo; CDR 62 accounts for the majority of the reactivity.82 Both CDR 34 and CDR 62 are also expressed in the tumor tissues of women with PCD, and anti-Yo, similar to anti-Hu, is produced in the CSF,72,73 from which it is extracted by the Purkinje cells.83,84 CDR 62 is thought to function in the regulation of gene expression85—and if interfered with by anti-Yo could prove lethal to the host Purkinje cell. A sensitive and specific assay for anti-Yo sera has been developed that utilizes the fusion protein produced by a cDNA clone, which encodes the CDR 62 antigen.85,86 Currently it is thought that the protein target of the anti-Yo antibody is a neuronal signal transduction protein.78 The mechanism whereby anti-Yo antibodies cause Purkinje cell death is not yet determined, although Tanaka and colleagues87 theorize that cytotoxic T lymphocytes may be involved. Thus, for both PEM and PCD, the autoimmune, or antionconeural (since the tumor is not really “self”), mechanism82 appears to be operational. Antibodies, anti-Hu and anti-Yo, have been demonstrated in the serum and CSF of patients with PEM and PCD, respectively, which react with the neural tissue and the tumor of patients with PNS.

SUMMARY PNSs, or the remote effects of neoplasia, are of practical significance to the neurotologist in terms of patient diagnostic evaluation and perioperative management, and of theoretic importance in leading to a better understanding of neurotologic tumors and cochleovestibular system biology.

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35

Outline Development of the Vestibular System Diagnostic Evaluation History Physical Examination Testing Developmental Effects of Vestibular Dysfunction Congenital and Hereditary Hearing Loss Congenital Anomalies Specific Disease Entities: Peripheral Otitis Media and Complications of Otitis Media Benign Paroxysmal Vertigo of Childhood Ménière’s Disease Trauma

D

Chapter

Dizziness in Childhood

Perilymphatic Fistula Vestibular Neuronitis Labyrinthitis and Meningitis Specific Disease Entities: Central Migraine Vertiginous Seizures Tumors Neurosyphilis Congenital Nystagmus Ataxia Familial Ataxia Multiple Sclerosis Other Disease Entities Metabolic/Systemic Disease Toxic Functional Summary

izziness is both frightening to the child and worrisome for the parents. As in adults, the symptoms of dizziness, giddiness, unsteadiness, and imbalance can arise from a variety of body systems. True rotational vertigo generally implies a disorder of the vestibular system and its relationship to the appropriate proprioceptive and visual systems. A team approach, involving neurotologist, neurologist, pediatrician, ophthalmologist, and audiologist/neurophysiologist provides the best chance for an accurate diagnosis and effective treatment. Although the neurotologist is generally consulted about how the vestibular system contributes to the child’s problem, he or she should be familiar with the associated pathways and disorders relating the vestibular system to other systems that may play a part in the dizziness. The clinical presentation of vertigo and ataxia in the pediatric age group may resemble that of the adult, but the differential diagnoses in the two groups are different. Many relatively common disorders that produce dizziness in adults are rarely seen in children. The neurologic and vestibular systems mature during childhood, which results in different interpretations of physical findings in children and adults. The vestibular system is one of the first central nervous system (CNS) projections to begin functioning in infancy. As in adults, the history and physical examination are the basis for the majority of diagnoses, with assorted diagnostic tests used for confirmation.

Fred F. Telischi, MEE, MD Grayson K. Rodgers, MD Thomas J. Balkany, MD

Vestibular symptoms as a chief complaint in the pediatric patient population are uncommon. Series reported in the literature are small. Fried1 found 14 out of 2088 patients in 12 months claiming dizziness as the chief complaint. Eviatar and Eviatar2 reported 24 patients with vertigo from a pediatric neurology clinic of 5000. The University of Nebraska experience published by Beddoe3 included 22 cases of dizziness or vertigo in children from 1960 to 1974.

DEVELOPMENT OF THE VESTIBULAR SYSTEM Although postural changes occur prenatally,4 the neural interconnections among the visual, cerebellar, labyrinthine, proprioceptive, and peripheral neuromuscular systems are incompletely developed at birth.2 Myelination of the various pathways occurs after birth.5 Vestibular pathways myelinate earlier (by 16 weeks) than pyramidal tracts (by 24 months). Peripheral labyrinthine functions, however, appear to be even more advanced. When an embryo reaches the size of 8 mm, the otocyst differentiates into a wider dorsal (vestibular) portion and a narrow ventral (cochlear) portion. The endolymphatic 553

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duct can be recognized on the medial aspect of the otocyst at this stage. When the embryo reaches 14 mm (6 weeks), pouches are formed on the vestibular portion of otocyst that will eventually give rise to the semicircular canals. At 20 mm (7 weeks), the vestibule divides into the utricle and saccule. When the embryo has reached a 30-mm size (8 weeks), the inner ear nearly resembles the adult form. Although the anatomic pathways may be developed in utero6,7 vestibulo-ocular reflexes and the Moro response cannot be elicited until birth.4 Woollacott and colleagues8 summarized the current understanding of the development of balance and posture in humans. Children appear to rely more on visual sensory information than vestibular and proprioceptive between 18 months and 3 years of age, during which time they acquire locomotor skills. Vision becomes especially important at transition periods when the child progresses to the next milestone of mobility (e.g., between crawling and standing). At school age (4 to 6 years), integration of visual, vestibular, and somatosensory information appears to expand and become more sophisticated, perhaps reflecting functional changes in the nervous system connections. With further maturation comes greater control reflected by more efficient use of postural muscles.

DIAGNOSTIC EVALUATION Disorders of the peripheral vestibular system and labyrinth are usually reflected by tangible symptoms and signs such as the sensation of spinning or movement, actual falling, constitutional symptoms (nausea, vomiting, sweating), and abnormal eye movements. Other symptomatology related to the vestibular system also occurs, but may result from disorders in the cerebellar, CNS, metabolic, and hemodynamic systems, as well as being caused by exogenous substances. Ataxia indicates poor coordination and encompasses a wide range of disorders. Gait ataxia refers to incoordination of ambulation. Walking is a highly complex skill dependent on proper functioning of a number of neuromuscular structures and pathways. The neurovestibular evaluation of the pediatric patient includes a history, neurotologic exam, general neurologic survey, and indicated testing and imaging. Emphasis should be placed on the team approach even though referral to all specialties may not be needed in every case.

History Historical information provides the most important data on the diagnosis and treatment of many dizzy patients. Benign paroxysmal vertigo, for example, represents a diagnosis made almost solely by history. Unfortunately, in the pediatric population the history may be incomplete. Perseverance frequently is rewarded with important facts obtained not only from parents but more frequently than expected from the child. Obviously the age of the patient determines the quantity and quality of information. In younger children and infants, parental observation constitutes the history. As myelinization proceeds during the first months and years of life, the infant progresses through

various developmental milestones. Significant delays of motor function occur in children with bilateral vestibular dysfunction.9 When physical activity is delayed or abnormal, vestibular disorders should be included in the differential diagnosis. Parents should be specifically questioned about abnormal movements, especially of the head and neck. Nystagmus or unusual eye movements may be noted by the parents. Loss of consciousness or alteration of behavior suggests seizure activity. When the child can communicate either with the physician or with the parents, the character of the dizziness should be elucidated. True vertigo, the sensation of movement of the surroundings or self, is distinguished from feelings of lightheadedness, faintness, floating, or “just not being right.” Children may recognize the sensation produced by calorics or rotation testing as equal to their own symptoms of dizziness. Vertigo arouses suspicion of a peripheral vestibular disorder, whereas dizziness suggests dysfunction in other systems such as cardiovascular, respiratory, hematologic, or psychoneurologic. Episode vertigo with constitutional symptoms suggests peripheral vestibular dysfunction. Hearing loss, tinnitus, and aural fullness/ pressure further localize the problems to the inner ear. Vertigo that lasts more than 12 hours suggests a cause central to the vestibular nerve. Falling, difficulty ambulating with eyes closed, or difficulty ambulating in the dark suggests bilaterally decreased vestibular function. Difficulty walking under normal conditions does not usually accompany isolated stable peripheral vestibular disease. Finally, a thorough but directed past medical history should be obtained, including but not limited to perinatal problems, medications, prior otologic disease and hearing loss, use of alcohol and illicit drugs, and neuromuscular problems. Parents and the patient may be questioned regarding the degree of disability caused by the vestibular symptoms. Contrast the child who continues to play and attend school with one fearful of leaving the house lest the dizziness cause physical or emotional damage.

Physical Examination The neurotologic exam of the dizzy child includes a complete head and neck examination, general neurologic survey, and specific neurovestibular testing. Many clues can be obtained by observing the child before and during the physician encounter. Otoscopy identifies inflammatory processes of the ear and mastoid. Use of the pneumatic otoscope may elicit a positive fistula test (see the section on Perilymphatic Fistula). A complete cranial nerve assessment should be performed. Tuning forks identify the presence and character of hearing loss and confirm audiometry. With a child sufficiently mature, Romberg, tandem or augmented Romberg, and tandem gait testing are performed. Eye movements should be observed. Normally, a few beats of nystagmus can be seen on extreme lateral gaze. Pathologic spontaneous nystagmus may be observed occasionally, but specific measures usually are necessary to elicit the finding. Frenzel lenses eliminate the patient’s ability to extinguish peripherally induced nystagmus by visual fixation. The Dix-Hallpike maneuver can elicit positionally

Dizziness in Childhood

provoked nystagmus. Generally, positionally provoked, fatigable nystagmus with a several-second latency accompanies a peripheral vestibular lesion, and nonfatiguable nystagmus without latency accompanies a CNS cause. Reflexes specific to neurovestibular function are present and can be tested in infants as described by Eviatar.10 Appropriate tone and movement of the cervical musculature indicate that input from the vestibular end-organ and cervical proprioceptive receptors exists. Abnormal posturing of the neck in an infant may indicate a vestibular problem. The vertical acceleration test qualitatively measures response in the extremities to gravitational acceleration sensed by the otolithic organs.2 While holding the infant in his or her arms with the head well supported, the examiner abruptly lowers the patient toward the floor. A normal response is abduction and extension of the upper extremities and an embracing posture. Semicircular canal response can be identified by rotating the upright infant with neck flexed 30 degrees. A doll’s eye response is elicited in the newborn. Nystagmus with the fast component in the direction of rotation appears at 2 to 3 weeks. Vestibular dysfunction also may be identified by examining the righting response. This reflex involves the child extending the arm to prevent falling in the direction of applied force or tilt. The response presents at 6 months and becomes voluntarily inhibited after 2 to 4 years of age. The test should be performed with the eyes closed to eliminate visual input, which isolates the vestibular component of the reflex. A patient with vestibular dysfunction will not exhibit the reflex and may fall in the direction of tilt. Similar righting tests can be performed in various positions until the age when the child can cooperate with the Romberg and other tests. A stepping test has been described in which the child steps in place over a grid with eyes closed and arms outstretched.11 The angle and distance of displacement are compared with that of normal subjects. Patients with unilateral lesions rotate greater than 45 degrees toward the affected side, whereas patients with bilateral lesions display forward or backward displacement of greater than 20 inches. Detailed cerebellar and gait examination may be indicated when the history does not suggest vestibular disorder or when the patient’s complaints focus on ambulation.12 Information from physical findings regarding the location of dysfunction causing ataxia may help differentiate vestibular, proprioceptive, and cerebellar causes. Problems in the vestibular system usually become exacerbated with the eyes closed, whereas cerebellar dysfunction may appear or worsen during visual fixation. Proprioceptive losses may mimic the other two in some respects but are usually discovered during position testing of the lower extremities. Neurologic consultation is indicated in these circumstances.

Testing Hearing evaluation in dizzy children becomes especially important when considering the 49% to 95% estimates of vestibular abnormalities in children with congenital and acquired hearing impairments.13,14 An audiologist experienced in testing children will employ a variety of tests

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based on age and disposition, including behavioral audiometry using pure tone and speech tests, play and startle localization, evoked auditory brainstem response (ABR), otoacoustic emissions, and others. Children with sensorineural hearing loss (SNHL) are at risk for vestibular hypofunction. Phillips and Backous have published a comprehensive, detailed review of vestibular testing in children.15 The remainder of this section outlines available tests. Electronystagmography (ENG), rotational chair testing, and posturography may be used in evaluating dizziness in children. Electrical recording of nystagmus can be performed even in young children. Caloric-induced nystagmus in children may be slower and more erratic than that in adults due to their developing/myelinating nervous system. Ice water may be necessary to measure vestibular dysfunction adequately. Rotation testing stimulates both labyrinths and may be an appropriate alternative for children who cannot cooperate for calorics or when calorics cannot be measured. Atretic or abnormal external auditory canals and perforations of the tympanic membrane are contraindications to open system ENG testing. Patients with bilateral vestibular weakness may demonstrate some response by rotation when calorics are negative. Rotary chair testing may be more sensitive than calorics for identifying very early bilateral weakness. Infants can be held in their parent’s lap for testing. Cyr and coworkers16 developed modifications of ENG and harmonic rotation for screening pediatric patients for vestibular hypofunction and asymmetry. By 6 weeks, the majority of normal infants demonstrate nystagmus to caloric or rotary stimulation.17 It must be remembered, however, that vestibulo-ocular response testing primarily examines only horizontal semicircular canal function and that these tests may not reflect the fluctuating nature of many pediatric vestibular disorders. Static and dynamic posturography examine the interaction of the vestibular system with the visual, proprioceptive, and other systems involved in maintaining balance. Posturography can be performed in children old enough to cooperate and, in fact, can be treated as a game. Information similar to that in adults is obtained, although results must be compared with size- and age-matched normals.18 Normal children younger than 4 to 6 years often fall in the sensory conflict situations (posturography conditions 3 to 6), which makes this test inaccurate at present for that age group.19 Tests of vestibular sensory organization and postural sway strategies have been standardized to normal children so that abnormal responses can be identified.18,20 These examinations aid physical therapists in designing vestibular and balance exercise programs for patients. They cannot as yet, however, reliably localize pathology and they demonstrate low sensitivity and specificity for the disorders of balance in children. ABR can be used as a screen for retrocochlear pathology and in infants when behavioral response audiometry cannot be performed. However, Brookhouser and colleagues21 demonstrated a lack of correlation between abnormal ABR and abnormal vestibular testing. Prolonged vestibular symptoms or signs of central dysfunction are evaluated with computerized tomographic (CT) scanning or magnetic resonance imaging (MRI). CT is preferred when

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temporal bone structures are presumed to be involved such as in chronic ear disease, skull base pathology, and congenital abnormalities. MRI provides excellent detail of soft tissues of the brain and CNS. Neurology consultation may order electroencephalography (EEG) when seizure activity is suspected.

DEVELOPMENTAL EFFECTS OF VESTIBULAR DYSFUNCTION A variety of developmental delays have been attributed to disorders of vestibular function as reviewed by Horak and coworkers.22 Reported disabilities usually result from bilateral vestibular dysfunction and include impairments of learning, postural coordination, motor skills, and developmental milestones. Children gradually compensate for many of the postural problems and by the time they become teenagers demonstrate no postural disturbances in everyday situations compared with normals.23–25 Vestibular testing, particularly posturography, will identify balance problems. Compensation is encouraged by vigorous physical education and, when required, by formal vestibular therapy.

Congenital and Hereditary Hearing Loss Many congenital and hereditary hearing losses are accompanied by vestibular deficits.26,27 Usher’s type I and Waardenburg’s syndromes are notable for the relatively common occurrence of vestibular abnormalities. Newborn hearing screening is identifying hearing loss at younger ages, and some type of vestibular assessment should be performed in these children. This can vary from an office neurotologic exam to more sophisticated testing. According to the clinical circumstances, children with audiovestibular dysfunction typically seek help because of hearing loss and rarely list imbalance as a chief complaint. The reader is referred to the chapter on pediatric auditory disorders (Chapter 36) for more detail regarding hearing loss.

Congenital Anomalies Temporal bone development anomalies often involve the vestibular apparatus. These anomalies may affect the membranous labyrinth only or the bony and membranous labyrinths together. The former must be diagnosed by histopathology, but the latter can be seen radiographically due to the bony malformation. Jackler and colleagues28 have shown that this distinction can provide a classification with clinical relevance and can be further broken down into more specific subtypes. These conditions are usually considered in terms of congenital SNHL, although children may have associated vestibular deficits that can manifest clinically. Children born without vestibular function will not experience vertigo because this is a static lesion. Although fine aspects of balance may be lacking, these children will compensate well with their somatosensory and visual systems. Vestibular symptoms may occur in patients who have vestibular function and a dynamic lesion. The enlarged vestibular aqueduct as an isolated anomaly has received some attention in the literature. Jackler and De La Cruz29

found many children with symptoms of incoordination and imbalance, whereas in adults episodic vertigo was more common. Endolymphatic sac surgery, done mainly to stabilize hearing, was complicated by a high rate of hearing loss in patients with an enlarged vestibular aqueduct, and no benefit could be shown in other congenital malformations. Sac surgery is therefore not recommended for these patients.30

SPECIFIC DISEASE ENTITIES: PERIPHERAL Otitis Media and Complications of Otitis Media Middle ear disease is, of course, extremely common in children. Acute and chronic otitis media are commonly seen from infancy to adulthood. Although most of these patients present with pain, drainage, or hearing loss, dizziness may accompany the spectrum of this disease. Serous otitis media (otitis media with effusion) can produce ill-defined balance disturbances manifesting as a delayed ability to walk, clumsiness, running into things, and so on.31 Clearing the middle ear fluid, either medically or surgically, rapidly resolves imbalance due to this cause. The mechanism by which the dizziness is produced is unclear, but one hypothesis is that negative middle ear pressure causes displacement of the round window membrane and subsequent movement of the perilymph in a susceptible individual.32 When active infection is evident in the middle ear, serous labyrinthitis can occur, which produces vertigo and SNHL. Transmission of toxic substances across the round window membrane presumably creates a serous labyrinthitis. Treatment is aimed at resolution of the infection of the middle ear with antibiotics and middle ear drainage. Steroid therapy may play a role in decreasing inflammation. Suppurative labyrinthitis as a complication of otitis media is a very rare, but extremely serious situation. Here, bacteria gain access to the perilymphatic space and produce a purulent inner ear infection. The route of bacterial spread may be from the middle ear through a fistula in the otic capsule or, more commonly, from the meninges and cerebrospinal fluid (CSF) through the cochlear aqueduct or internal auditory canal. Patients with bacterial labyrinthitis are seriously ill and have severe auditory and vestibular impairment compared with patients with serous labyrinthitis. Management is directed at controlling the underlying infection in either the middle ear/mastoid or the CSF.1,33 Cholesteatoma, acquired or (less commonly) congenital, can erode into the otic capsule, producing a labyrinthine fistula. The horizontal semicircular canal is the most common site for this destruction to occur, but other areas can be involved. Cholesteatoma at this stage is generally easily seen on otoscopy. Pneumatic fistula testing will produce symptoms in most cases and increase suspicion of the diagnosis. Audiometry may demonstrate SNHL in addition to the expected conductive component. CT scanning should suggest the erosive process and allows for appropriate preoperative planning. Surgical management of a fistula is quite individualized and depends on a number of factors, such as hearing in the diseased ear, hearing in the

Dizziness in Childhood

contralateral ear, size of the mastoid, and experience of the surgeon.34

Benign Paroxysmal Vertigo of Childhood Basser35 described benign paroxysmal vertigo (BPV) of children in 1964. Including their own cases, Finkelhor and Harker36 in 1987 counted 113 cases reported in the literature. Age of onset has been reported37 between 2 and 12 years of age, the majority before age 6. This disorder should be distinguished from benign paroxysmal positional vertigo, which is rare in the pediatric population, but common in adults. The typical pattern involves the sudden onset of vertigo lasting from seconds to a minute. Nausea and vomiting may or may not be associated with the episode. The child usually becomes frightened and clutches the nearest object in an apparent attempt to prevent falling. Observant parents will note unusual eye movements suggestive of nystagmus. The child remains completely lucid with no alteration in consciousness. Fenichel38 first suggested an association between BPV and migraine headache in children in 1967. Parker39 reported an overall incidence of 43% for family history positive for migraine among series of BPV patients reported in the English language literature. He also calculated a 13% incidence of subsequent development of migraine along with other symptoms associated with migraine, such as cyclic vomiting, recurrent abdominal pain, scotomata, and photophobia. A history of motion intolerance is a common finding. Headache provocation tests that made use of nitroglycerin,40 histamine, and fenfluramine37 resulted in headache or vertigo (or both) in 12 out of 12 and 10 out of 15 patients with BPV, respectively. Paroxysmal torticollis of infancy (PTI) also has been reported to precede BPV.41,42 PTI and BPV may represent early manifestations of the full migraine complex, progressing from one to the other as the nervous system develops. The International Headache Society now places BPV, PTI, and cyclic vomiting in the migraine family.43 Because these patients are rarely at the doctor’s office during attacks, audiometry and vestibular testing generally are normal. Eighty-nine percent of 90 cases reviewed in the literature had normal caloric responses.39 Abnormalities on ENG, when present, are subtle and transitory. Earlier reports demonstrated abnormal ENG results (primarily with respect to calorics), whereas more recent series have shown normal ENG findings.35,44 EEG has demonstrated mild abnormalities in wave patterns in a few patients with family history or other symptoms suggestive of seizure activity, but generally has been normal in BPV patients.36,37 Imaging studies have been uniformly normal. The natural history of BPV is one of spontaneous remission of vertiginous episodes prior to the teenage years. As already noted, some patients resolve their vertigo only to develop migraine. The important aspects of treatment include ruling out other treatable conditions and reassurance and counseling regarding possible later development of migraine. Antiseizure medication has not been useful,

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although some patients have been noted to improve on antimigraine regimens.37,40 The efficacy of pharmacologic therapy remains unclear, given the natural spontaneous remission.

Ménière’s Disease Episodic vertigo, fluctuating hearing, and low-pitched tinnitus were described in 1861 by Prosper Ménière as a disorder localized to the labyrinth. Harrison and Haftalin45 noted that 75% of cases occur between 30 and 60 years of age. The first case reported of Ménière’s disease in a child (6 years old) was by Crowe46 in 1938. Since that time, only a small number of reports of this entity in children have appeared.47 Sade and Yaniv48 outlined three cases of Ménière’s occurring in infants having episodes of vomiting. Specific review of pediatric Ménière’s disease has been published by Rodgers and Telischi.49 The diagnosis of Ménière’s disease is clinical and relies heavily on the history. In the pediatric population, it will likely be difficult to elicit the classic history, especially in children younger than age 10 years. Therefore, a certain index of suspicion must be kept for this disorder. Once hearing loss has been documented, the differential diagnosis of vertigo and hearing loss includes physical and acoustic trauma, spontaneous perilymphatic fistula, allergy, inner ear malformation (e.g., Mondini’s), cerebellopontine angle tumor, hypothyroidism, syphilis, and adrenal pituitary insufficiency in addition to Ménière’s disease. The diagnostic evaluation in such patients should include basic and impedance audiometry that is age-appropriate, ABRs, ENG, electrocochleography, and detailed CT scanning of the temporal bones. Serologic syphilis testing, thyroid function studies, glucose tolerance testing, adrenocorticotropic hormone-stimulated cortisol levels, and allergy testing in selected cases should be obtained. Filipo and Barbara50 found glycerol testing particularly helpful in this age group for whom histories often lack important details. They had a positive test in four of five children with suspected Ménière’s disease. Once a diagnosis is made, treatment is the same as for adults. Diuretic therapy is the mainstay of the therapeutic regimen along with dietary modification (e.g., low sodium and decreased caffeine).

Trauma This section is limited to closed-head trauma and whiplash-type injuries as causes of dizziness and vertigo. Eviatar and coworkers51 categorized post-traumatic vestibular symptoms without hearing loss into “labyrinthine concussion, whiplash syndrome, vertiginous seizures, migraine and post-traumatic neuroses.” Temporal bone fracture and perilymphatic fistula also can be caused by blunt injuries and result in dizziness or vertigo along with hearing loss. Loss of consciousness at the time of trauma may or may not be associated with all of these disorders. Labyrinthine concussion is the name given to the symptom complex similar to BPV that occurs after head trauma with no detectable fracture or injury to the labyrinth. Patients typically develop vertigo and imbalance immediately after the injury that persists for several days. As these

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symptoms resolve during the first week, patients are left with residual positional vertigo, which can persist for weeks to months. Episodes of positional vertigo last seconds to a few minutes and may be associated with nausea. Hearing loss and tinnitus are not typical complaints. Dislodged particulate debris trapped in the semicircular canals (posterior canal most commonly) causes these symptoms, and treatment with partial repositioning maneuvers is usually effective. Vestibular exercises can be helpful as well. Audiometry may reveal mild SNHL, although more commonly shows no change in thresholds. ENG demonstrates positional nystagmus and, less often, canal paresis. Rotary chair and posturography are helpful for severe injuries resulting in bilateral vestibular paresis. Whiplash injuries, in addition to head trauma, can result in positional vestibular symptoms. Hearing generally is normal although some patients complain of tinnitus. Physical examination and ENG may elicit positional nystagmus. Audiometry is normal. A cervical collar may be prescribed to splint the neck and minimize discomfort. Vestibular habituation exercises may be designed to promote compensation to rapid head movements. Vestibular suppressants and muscle relaxants are helpful initially but not on an ongoing basis. Even severe symptoms generally resolve during a period of weeks to months. In some patients, no diagnosis matches the symptoms. The physical examination is normal. Some patients may exhibit nonspecific abnormalities on ENG or even ABR. Eviatar and coworkers51 termed this nonspecific post-traumatic dizziness. They postulated brainstem injury, psychosomatic disorder, or secondary gain associated with litigation as causes. Patients whose symptoms resolve spontaneously during a period of weeks to months, not in association with lawsuit settlements, are more likely to have an organic basis for their symptoms than those whose complaints are protracted and less specific. Closed-head trauma can produce other conditions manifested by dizziness or vertigo, such as perilymphatic fistula, temporal bone fracture, and trauma-induced migraine or seizures. These are described in detail in other sections of this chapter or other chapters.

Perilymphatic Fistula Perilymphatic fistulae are fluid connections between inner and middle ear spaces. Many aspects of the diagnosis and management, indeed even the existence, of this disorder are controversal.52,53 Perilymphatic leaks unrelated to prior otologic surgery were reported initially in 1968.54 Theories of their pathogenesis have been well described. Individual predisposition, congenitally weak areas in the temporal bone, patent cochlear aqueduct, and other anatomic explanations have been proposed to account for the failure to contain the perilymph subjected to pressure differential with respect to the CSF or ambient pressure. Perilymph leaks can result in vertigo, ataxia, disequilibrium, and nonspecific dizziness symptoms. The most common symptom is SNHL. Tinnitus occurs less commonly. Any combination of vestibular and auditory complaints have been reported, either stable or fluctuating over time.55

Antecedent trauma, physical exertion, or barotrauma are reported by some patients. Supance and Bluestone56 documented such a history in 6 of 22 (27%) patients with surgically confirmed leaks. No symptoms are pathognomic for fistula, but some of the following historical findings should heighten the index of suspicion: 1. No other obvious diagnosis to explain the symptoms 2. Antecedent trauma blunt or penetrating to the temporal bone, physical straining/Valsalva’s maneuver, barotrauma (atmospheric changes or internally induced such as violent sneezing/coughing and playing wind instruments) 3. Hearing loss associated with trauma, sudden, fluctuating, and progressive 4. Vertigo or dizziness occurring with straining or position changes 5. History of recurrent, unexplained meningitis 6. Vestibular symptoms brought on or magnified during exposure to loud sounds (Tullio’s phenomenon) 7. Congenital anomalies or syndromes involving the head and neck Physical examination may be completely normal. Occasionally, perilymph in the middle ear masquerades as serous otitis media. Position changes may elicit peripheraltype nystagmus, or the patient may exhibit spontaneous nystagmus. Gross ataxia or abnormalities in Romberg/ tandem gait testing may be present. Congenital deformities should be noted. The fistula test is not accurate but has been reported to be more specific (50%) than sensitive (35%) in children.56 This test is based on acute changes in middle ear pressure transmitted via a fistula to the inner ear, causing vertigo and nystagmus. Properly performed, a good seal is obtained in the external auditory canal while positive and negative pressures of 200 to 300 mm H2O are induced acutely, maintained for 5 to 10 seconds, and repeated several times. Although the sensation of vertigo suggests the diagnosis, a positive result requires the eliciting of nystagmus or a change in the magnitude of spontaneous nystagmus. Eye movements may be visually documented with Frenzel glasses and a pneumatic otoscope in the office, or ENG can be employed with independence/admittance instrumentation. ENG may be normal or abnormal. Positional testing and platform posturography have been reported to be abnormal more frequently than have oculomotor screening, calorics, and rotation tests in children with confirmed leaks.56 Pure tone and electrical audiometry commonly reveal SNHL. CT remains the best modality for imaging temporal bone structures and should be undertaken when labyrinthine fistula is suspected. More than half of children with surgically confirmed fistulas exhibit abnormal temporal bone tomography. Mondini’s and other inner ear deformities are the most common abnormalities identified. Still, the only way to definitely identify a leak remains operative exploration. Even at surgery, with Valsalva’s maneuvers, there may be questionable fluid accumulation and the timing of exploration may not correspond with perilymph flow from an intermittent leak. Analysis of any identified fluid for β2-transferrin held promise, but has not been uniformly helpful.57

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Treatment in cases of acute barotrauma in otherwise normal patients may begin with bedrest with head elevation and avoidance of Valsalva’s maneuvers for several days. Significant or progressive hearing loss or persistent vertigo mandates surgical exploration. This involves an exploratory tympanotomy with exposure similar to that for a stapedectomy. Oval and round window areas should be fully visible. The anterior aspect of the oval window is the most common site of leak. Careful suctioning and diligent observation with Valsalva’s maneuver may identify small leaks. Abnormalities in the ossicles, oval window niche, or round window are commonly identified. Many surgeons will reinforce the oval and round window areas with fibroconnective tissue grafts even if a specific leak is not seen due to the vagaries of diagnosis.

Vestibular Neuronitis Vestibular neuronitis usually occurs in children older than 10 years and follows a clinical course similar to but milder than that seen in adults.33,44,58,59 Vertigo occurs suddenly and may last 1 or 2 days with nausea and vomiting. A period of imbalance and ataxia may follow for several weeks. It commonly accompanies or follows a viral illness and may be diagnosed as gastroenteritis or a similar disorder. Intermittent episodes of vertigo may occur, decreasing in severity during the ensuing week. Vestibular neuronitis is not associated with changes in hearing. As in adults, ENG frequently demonstrates unilateral decreased caloric response. Vestibular suppressants can be employed temporarily for symptomatic treatment, but ultimately this is a self-limited disorder.

Labyrinthitis and Meningitis The presence of hearing loss accompanying the acute onset of severe vertigo, nausea, vomiting, and fever heralds labyrinthitis. The cause may be viral or bacterial. Labyrinthitis may be classified as serous, suppurative, or chronic.60 Acute or chronic ear infections can result in toxins and noxious enzymes entering the inner ear.61 Viral infection presumably invades the membranous labyrinth via a hematogenous route. Suppurative labyrinthitis involves bacterial entry into and infection of the perilymphatic space. This may occur via a bony fistula of the otic capsule or infected CSF through the internal auditory canal or cochlear aqueduct. The diagnosis is suggested by noting the acute onset of severe vertigo with either sudden or progressive hearing loss. Signs and symptoms of otologic disease or meningitis support the diagnosis. A careful fistula test should be performed. Audiometry and vestibular tests will demonstrate hypofunction of one or both labyrinths. Bilateral involvement suggests meningogenic spread; unilateral suggests otologic. Management is directed at controlling the underlying infection. Viral and serous labyrinthitis leave mild inner ear dysfunction, and suppurative disease results in severe auditory and vestibular hypofunction. Vertigo following meningitis in children may be the effect of scar traction on the meninges surrounding the vestibular nerve or a direct postinflammatory effect on the labyrinth or vestibular nerve.31 Vestibular exercises and time generally result in resolution of symptoms.

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SPECIFIC DISEASE ENTITIES: CENTRAL Migraine Migraine is generally believed to be a vascular disorder associated with vasospasm of vessels supplying the CNS, which produces neurologic symptoms, followed by vasodilation of extracranial vessels, hence producing headaches. A wide spectrum of symptomatology can occur from this process.39 An array of symptoms may be produced by the vasospastic phase while headache, if any, symptoms occur during the vasodilation phase. Also, the time course between the phases can vary widely, and the phases can occur independently. Migraine precursors, variants, or equivalents signify the vasospastic phase and can manifest as vertigo.62 Consider migraine in the differential diagnosis for children experiencing episodic vertigo without auditory symptoms. As previously noted, BPV of childhood and PTI are thought to be manifestations of migraine. The diagnosis of migraine is one of elimination. Other otologic or neurologic diseases should be excluded prior to a diagnosis of migraine. A history of repeated episodes with recovery between spells is suggestive. A detailed family history must be obtained because a history for migraine is often present. This history should include questioning of family members that may have had BPV of childhood or PTI. Migraine associated vertigo may be treated similarly to adult disease in conjunction in consultation with pediatric colleagues. Johnson has contributed a very thorough review of migraine-related dizziness.63

Vertiginous Seizures Changes in cognitive function and alteration or loss of consciousness accompanying vertigo suggest seizure activity. Vertigo may be a manifestation of the ictal phenomenon (vertiginous seizures), or the abnormal vestibular activity may stimulate convulsion (vestibulogenic seizures). Vertigo or dizziness not uncommonly occur as an aura preceding a generalized seizure. Vertigo is the sole or primary symptom in vertiginous seizures. The differentiation between this entity and other varieties of paroxysmal vertigo is made by identifying altered mental status and abnormal sleep-deprived EEG. Imaging and vestibular testing will be normal but are usually indicated to rule out other disorders. Vestibulogenic seizures are a rare form of sensory epilepsy. Altered afferent vestibular stimuli or abnormal central processing of robust peripheral input lead to generalized epileptic activity via the reticular activating system in the brainstem and thalamocortical pathways. Simultaneous ENG and EEG recording during caloric stimulation will reveal abnormalities. Anticonvulsants are the primary treatment for both of these types of seizures.

Tumors Tumors involving the CNS at the brainstem and above may cause vertigo. Posterior fossa tumors constitute almost two-thirds of brain tumors in children.64 Intrinsic cerebellar and brainstem lesions make up the majority of

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those in the cerebellopontine angle. Medulloblastomas, astrocytomas, gliomas, hematomas, and inflammatory masses can cause mass effect on nearby vestibular structures. A high index of suspicion is sometimes necessary to diagnose these lesions. The combination of vertigo with hearing loss, other cranial nerve palsies, ataxia, or seizures warrants a vigorous diagnostic work-up that includes imaging. Signs of increased intracranial pressure, such as headache, vomiting, and papilledema, also require a search for a mass lesion. MRI with gadolinium contrast provides detailed images of the soft tissue structures in the CNS. CT scans are best for identifying changes in bony structures such as those caused by tumors in the skull base.

Neurosyphilis Neurosyphilis is known to be a cause of true vertigo as well as other forms of dizziness in childhood. The spirochete Treponema pallidum may infect any portion of the vestibular system as well as the cochlea, eighth nerve, and central auditory and vestibular pathways. The onset of dizziness in childhood due to neurosyphilis is often accompanied and overshadowed by bilateral symmetrical profound hearing loss. The audiogram may show a flat configuration with disproportionately poor speech discrimination. Vestibular symptoms occur more commonly in congenital and late syphilis than in early acquired syphilis. These symptoms may vary from mild imbalance to severe attacks of vertigo lasting days.65 Symptoms on occasion may be indistinguishable from Ménière’s disease and consist of episodic vertigo, fluctuating SNHL, and tinnitus.66,67

Congenital Nystagmus Congenital nystagmus is characterized by horizontal, conjugate jerky oscillations of the eyes.68 The abnormal eye movements occur at birth or during infancy.69 Dizziness, vertigo, and oscillopsia are notably absent. These children generally have good vision although they may adopt compensatory head posturing to compensate for visual changes during periods of nystagmus. This form of nystagmus increases during fixation and decreases during eye closure or convergence. Treatment involves reassurance and monitoring of vision.

Ataxia Ataxia implies impaired coordination. The causes of ataxia are protean and affect any aspect of muscular activity.70 We discuss those entities that manifest vertigo/dizziness as part of the symptomatology and primarily involve gait or balance disturbances in children. Familial Ataxia Familial ataxias may be inherited in a dominant, recessive, or sex-linked fashion. Up to one-third of patients with recessive disease do not fit current diagnostic classifications of familial ataxia. Dominant recurrent (periodic) ataxia is characterized by childhood onset with episodic imbalance and vertigo.71,72 Nystagmus and ataxia are observed during

attacks, but interim examination is normal. In contrast to many of the recessive ataxias, this dominantly inherited disorder does not appear to involve significant progressive neurologic or systemic impairment. A defect in pyruvate metabolism has been postulated as the cause, leading to cerebellar atrophy observable by MRI.73,74 Griggs and colleagues74 and later others reported clinical response to acetazolamide.71,75 Among a number of forms of recessive ataxia, Friedreich’s ataxia ranks as the most common.72 This disorder affects many organ systems, beginning with spinocerebellar degeneration of the CNS. The cause remains unknown. Gait ataxia or scoliosis develops during childhood or early adolescence. Other neurologic findings include dysarthria, loss of position and vibratory sense in the lower extremities, muscle atrophy, and areflexia. Eighth nerve and cochlear nucleus degeneration with preservation of the end organ lead to hearing loss and vestibular hypofunction.76 Visual loss from optic atrophy and diabetes occur in less than half of patients. Most patients die from the complications of hypertrophic cardiomyopathy. No effective treatment exists. A number of other inherited ataxias exist that are beyond the scope of this chapter. Treatable varieties include Refsum’s disease, Wilson’s disease, Hartnup disease, Bassen-Kornzweig syndrome, urea cycle, and multiple carboxylase enzyme deficiencies.

Multiple Sclerosis Multiple sclerosis (MS) is uncommon in childhood, but up to 10% of cases may present in the pediatric population. As in adults, dizziness can occur if a focus of demyelination (plaque) involves the vestibular system.77 Molteni78 reported 14 cases of MS in the children. Four (20%) had vertigo as the presenting symptom. The possibility of MS increases if other neurologic symptoms such as visual disturbance or gait disturbance are present. The diagnosis may only become clear as time passes and other symptoms develop. MRI of the brain may show the sclerotic plaques. Visual evoked potentials and analysis of spinal fluid may be helpful in the diagnosis. Treatment of acute exacerbations with steroids is often effective.

OTHER DISEASE ENTITIES Metabolic/Systemic Disease Imbalance and lightheadedness may be the result of certain systemic conditions. Anemia and vasovagal reactions are common causes of dizziness. Congenital heart disease and arrhythmias also may present with vestibular complaints. Hypoglycemia is another consideration and symptoms should have a relationship to food intake. Adrenal insufficiency, dysautonomia, and thyroid disease all are other uncommon systemic causes of dizziness. A careful history and physical examination will often lead to clues that point to a need for further work-up. Where indicated, a battery of blood tests can be pursued to rule out these disorders.

Dizziness in Childhood

Toxic Many medications can produce dizziness as a side effect. Therefore, a review of medications is always required, and, where appropriate, elimination or substitution may determine if a drug is causing the symptoms. Anticonvulsants such as phenytoin and carbamazepine as well as various vasoactive medicines are common offenders. Patients who experience dizziness taking these medications should have blood drug levels checked. Another consideration is of illicit drugs. This may be more likely in the teenage population. Urine screening can help in this matter. Other considerations include vestibulotoxic medications. Aminoglycosides are by far the most common in this category. A history of severe infection treated with intravenous antibiotics should prompt an investigation into which medications were used. Topical application of aminoglycoside-containing drops to the middle ear can result in vestibulotoxicity via round window absorption. An audiogram, otoacoustic emissions measurement, and ENG will reveal deficits in these cases. Other medications that can be toxic to the vestibular system include loop diuretics, quinine, and some cancer chemotherapeutic drugs.

Functional Although not usually seen in very young children, the school-age child may manifest a number of functional symptoms that not uncommonly include dizziness.2,31 Underlying the symptom can be anxiety, behavior disturbance, depression, difficulty with social adaptation, and hyperventilation. Dizziness rarely occurs as an isolated symptom in these cases, which adds to the confusion. Particular attention must be given to the history, which should include the social and family dynamics. These cases often become clearer if the physician is able to sort out this portion of the history. All laboratory testing is normal as is the physical examination. Treatment is directed at resolving the underlying problem through appropriate counseling.

SUMMARY As in adult patients, dizziness in children is a complex problem that may be difficult to diagnose. Making matters more difficult is the limited history possible from the patient. Parents are helpful, but they are not the ones with the symptoms and as such can only provide limited and indirect information. The examination and laboratory evaluation of the vestibular system, as well as imaging in selected cases, can help to solidify a diagnosis. This chapter has provided an outline and discussion of disorders that can produce dizziness in children. An understanding of these diseases helps to provide a framework of knowledge with which each individual case can be compared. With a systematic approach, these challenging cases can be solved.

REFERENCES 1. Fried MP: The evaluation of dizziness in children. Laryngoscope 90:1548–1560, 1980. 2. Eviatar L, Eviatar A: Vertigo in children: differential diagnosis and treatment. Pediatrics 59(6):833–838, 1977.

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3. Beddoe GM: Vertigo in childhood. Otolaryngol Clin North Am 10:139–144, 1977. 4. Prechtl HFR: Prenatal motor development. In Wade M, Whiting H (eds.): Motor Development in Children: Aspects of Coordination and Control. Boston, Martinus Nijhoff, 1986, pp 53–64. 5. Anson BJ: Developmental anatomy of the ear. In Paparella MM, Shumrick DA (eds.): Otolaryngology. Philadelphia, WB Saunders, 1973. 6. Gessel A, Amatruda CS: The embryology of behavior: The beginning of the human mind. New York, Harper & Row, 1945. 7. Hamilton WJ, Mossman HW: Human embryology: Prenatal development of form and function, 4th ed. Cambridge, England, Hoffer, 1972. 8. Woollacott MH, Shumway-Cook A, Williams HG: The development of posture and balance control in children. In Woollacott MH, Shumway-Cook A (eds.): Development of Posture and Gait Across the Life Span. Columbia, SC, University of South Carolina Press, 1989, pp 77–96. 9. Cyr D: The vestibular system: Pediatric considerations. Semen Hear 4(1):33–45, 1983. 10. Eviatar L: Vertigo. In Swaiman KF (ed.): Pediatric Neurology: Principles and Practice. St. Louis, Mosby, 1989. 11. Fukuda T: The labyrinth and ataxia. Japan J Clin Med 29(8):1848–1851, 1971. 12. Swaiman KF: Gait impairment. In Swaiman KF (ed.): Pediatric Neurology: Principles and Practice. St. Louis, Mosby, 1989. 13. Rosenblut B, Goldstein R, Landon WM: Vestibular responses of some deaf and spastic children. Ann Otol Rhinol Laryngol 60:747–755, 1960. 14. Sanberg L, Terkildsen K: Caloric tests in deaf children. Arch Otolaryngol 81:350–354, 1965. 15. Phillips JO, Backous DD: Evaluation of vestibular function in young children. Otolaryngol Clin North Am 35:765–790, 2002. 16. Cyr D, Brookhouser P, Valente M, Grossman A: Vestibular evaluation of infants and preschool children. Otolaryngol Head and Neck Surg 93:463–468, 1985. 17. Mitchell T, Cambon K: Vestibular response in the neonate and infant. Arch Otolaryngol 90(5):556–557, 1969. 18. Horak FB, Nashner LM: Central programming of postural movements: Adaptation to altered support-surface configurations. J Neurophysiol 55(6):1369–1381, 1986. 19. Forssberg H, Nashner LM: Ontogenetic development of postural control in man: Adaptation to support and visual conditions during stance. J Neurosci 2(5):545–552, 1982. 20. Shumway-Cook A, Woollacott MH: Dynamics of postural control in the child with Down syndrome. Phys Therapy 65(9):1315–1322, 1985. 21. Brookhouser PE, Cyr DG, Peters JE, Schulte LE: Correlates of vestibular evaluation results during the first year of life. Laryngoscope 101:687–694, 1991. 22. Horak FB, Shumway-Cook A, Crowe TK, Black FO: Vestibular function and motor proficiency of children with impaired hearing, or with learning disability and motor impairments. Devel Med Child Neurol 30(1):64–79, 1987. 23. Brunt D, Broadhead GD: Motor proficiency traits of deaf children. Res Q Exercises Sport 53:236–238, 1982. 24. Butterfield SA: Gross motor profiles of deaf children. Percept Mot Skills 62:68–72, 1986. 25. Enbom H, Magnusson M, Phykko I: Postural compensation in children with congenital or early acquired bilateral vestibular loss. Ann Otol Rhinol Laryngol 100:472–478, 1991. 26. Konigsmark BW: Genetic hearing loss with no associated abnormalities: A review. J Speech Hear Disord 37:89–99, 1972. 27. Konigsmark BW, Gorlin RJ: Genetic and Metabolic Deafness. Philadelphia, WB Saunders, 1976. 28. Jackler RK, Luxford WM, House WF: Congenital malformations of the inner ear: A classification based on embryogenesis. Laryngoscope 97(40):2–14, 1987.

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29. Jackler RK, De La Cruz A: The large vestibular aqueduct syndrome. Laryngoscope 99:1238–1243, 1989. 30. Jackler RK, Brackmann DE, Luxford WM, Monsell EM: Endolymphatic sac surgery in congenital malformations of the inner ear. Laryngoscope 98:698–704, 1988. 31. Balkany TJ, Finkel RS: The dizzy child. Ear Hear 7(3):138–142, 1986. 32. Blayney AW, Colman BH: Dizziness in childhood. Clin Otolaryngol 9:77–85, 1984. 33. Frederic MW: Central vertigo. Otolaryngol Clin North Am 6(1):267–285, 1973. 34. Sheehy JL, Brackmann DE: Cholesteatoma surgery: Management of the labyrinthine fistula—A report of 97 cases. Laryngoscope 59:78–87, 1979. 35. Basser LS: Benign paroxysmal vertigo of childhood (a variety of vestibular neuronitis). Brain 87:141–152, 1964. 36. Finkelhor BK, Harker LA: Benign paroxysmal vertigo of childhood. Laryngoscope 97:1161–1163, 1987. 37. Lanzi G, et al: Benign paroxysmal vertigo in childhood: A longitudinal study. Headache 26:494–497, 1986. 38. Fenichel GM: Migraine as a cause of benign paroxysmal vertigo of childhood. J Pediatr 71:114–115, 1967. 39. Parker W: Migraine and the vestibular system in childhood and adolescence. Am J Otol 10:364–371, 1989. 40. Curatolo P, Sciarretta A: Benign paroxysmal vertigo and migraine. Devel Med Child Neurol 29:405–406, 1987. 41. Dunn DW, Snyder CH: Benign paroxysmal vertigo of childhood. Am J Dis Child 130:1099–1100, 1976. 42. Eeg-Olofsson O, Odkvist L, Lindskog U, Andersson B: Benign paroxysmal vertigo in childhood. Acta Otolaryngol 93:283–289, 1982. 43. Headache Classification Committee of the International Headache Society: Classification and Diagnostic Criteria for Headache Disorders, Cranial Neuralgias and Facial Pain. Cephalgia (Suppl) 8:1–96, 1988. 44. Koenigsberger MR, Chutorian AM, Gold AP, Chievy MS: Benign paroxysmal vertigo in childhood. Heurology 20:1108–1113, 1970. 45. Harrison MS, Haftalin L: Ménière’s Disease. Springfield, IL, Charles C Thomas, 1938. 46. Crowe SJ: Ménière’s disease: Study based on examinations made before and after intracranial division of the vestibular nerve. Medicine 17:1–36, 1938. 47. Mahmud MR, et al: Vestibular Nerve Section in a child with Intractable Ménière’s Disease. Int J Pediatr Otorhinolaryngol 64(1):61–64, 2002. 48. Sade J, Yaniv E: Unrecognized infantile Ménière’s disease. Am J Otol 2:196–197, 1981. 49. Rodgers GK, Telischi FF: Ménière’s disease in children. Otolaryngol Clin North Am 30(6):1101–1104, 1997. 50. Filipo R, Barbara M: Juvenile Ménière’s disease. J Laryngol Otol 99:193–196, 1985. 51. Eviatar L, Bergtraum M, Randel RM: Post-traumatic vertigo in children: A diagnostic approach. Pediatr Neurol 2(2):61–66, 1986. 52. Parnes LP, McCabe BF: Perilymph fistula: An important cause of deafness and dizziness in children. Pediatrics 80(4):524–528, 1987. 53. Vartiainen E, Nuutinen J, Karjalainen S, Nykanen K: Perilymph fistula—A diagnostic dilemma. J Laryngol Otol 105:270–273, 1991. 54. Fee GA: Traumatic perilymphatic fistulas. Arch Otolaryngol 88:477–480, 1968.

55. Healy GB, Friedman JM, Strong MS: Vestibular and auditory findings of perilymphatic fistula: A review of 40 cases. Trans Am Acad Opth Otol 82:44–49, 1976. 56. Supance JS, Bluestone CD: Perilymph fistulas in infants and children. Otolaryngol Head Neck Surg 91:663–671, 1983. 57. Rauch SD: Transferrin microheterogeneity in human perilymph. Laryngoscope 110(4):545–52, 2000. 58. Shirabe S: Vestibular neuronitis in childhood. Acta Otolaryngol Suppl (Stockh) 458:120–122, 1988. 59. Rabe EF: Recurrent paroxysmal nonepileptic disorders. Curr Probl Pediatr Adolesc Health Care 4(8):1–31, 1974. 60. Schuknecht HF: Pathology of the Ear. Cambridge, MA, Harvard University Press, 1974. 61. Paprella MM, Goycoolen MV, Meyerhoff WL: Inner ear pathology and otitis media: A review. Ann Otol Rhinol Laryngol 89(3):249, 1980. 62. Watson P, Steele JC: Paroxysmal disequilibrium in the migraine syndrome of childhood. Arch Otolaryngol 99:177–179, 1971. 63. Johnson GD: Medical management of migraine related dizziness and vertigo. Laryngoscope 180(Suppl):1–28, 1998. 64. Cohen ME, Duffner PK: Current therapy in childhood brain tumors. Neurol Clin 3(1):147–164, 1985. 65. Darmsteadt GL, Harris JP: Luetic hearing loss: Clinical presentation, diagnosis and treatment. Am J Otol 10:410–421, 1979. 66. Becker G: Late syphilitic hearing loss: A diagnostic and therapeutic dilemma. Laryngoscope 89:1273–1288, 1979. 67. Durham K, et al: Clinical manifestations of otological syphilis. J Otolaryngol 13(3):175–179, 1984. 68. Dell’Osso LF, Daroff RB: Congenital nystagmus waveform and foveation strategy. Doc Ophthalmol 39:55–182, 1975. 69. Reineche RD, Guo S, Goldstein HP: Waveform evolution in infantile nystagmus: An electroculographic study of 35 cases. Binocul Vis Strabismus Q 3:191–202, 1988. 70. Stumpf DA: Diseases of the brainstem and cerebellum. In Swaiman KF (ed.): Pediatric Neurology: Principles and Practice. St. Louis, Mosby, 1989. 71. Hankey GJ, Gubbay SS: Familial periodic ataxia. Med J Australia 150(5):277–278, 1989. 72. Tibbles JA, Camfield PR, Cron CC, Farrel D: Dominant recurrent ataxia and vertigo of childhood. Pediatr Neurol 2(1):35–38, 1986. 73. Vighetto A, Froment JC, Trillet M, Aimard G: Magnetic resonance imaging in familial paroxysmal ataxia. Arch Neurol 45(5):547–549, 1988. 74. Griggs RC, Moxley RT III, Lafrance RA, McQuillen J: Hereditary paroxysmal ataxia: Response to acetazolamide. Neurology 28(12):1259–1264, 1978. 75. Bouchard JP, Roberge C, van Gelder NM, Barbeau A: Familial periodic ataxia responsive to acetazolamide. Can J Neurol Sci (4 Suppl) 11:550–553, 1984. 76. Spoendlin H: Optic cochleovestibular degenerations in hereditary ataxias. II. Temporal bone pathology in two cases of Friedreich’s ataxia with vestibulo-cochlear disorders. Brain 97(1): 41–48, 1974. 77. Busis SN: Vertigo. In Bluestone CO, Stoll SE (eds.): Pediatric Otolaryngology. Philadelphia, WB Saunders, 1983, pp 261–270. 78. Molteni RA: Vertigo as a presenting symptom of multiple sclerosis in childhood. Am J Dis Child 131:553–554, 1977.

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Outline Development of the Central Auditory System Introduction Anatomic Development Spiral Ganglion Cells General Aspects of Central Auditory System Development Cochlear Nucleus Superior Olivary Complex Lateral Lemniscal Nuclei Inferior Colliculus Medial Geniculate Body Auditory Cortex Myelination Functional Development of the Central Auditory System Behavioral Responses to Sound Hearing by the Human Fetus Postnatal Development of Auditory Competence Methodology Neonatal Period (Birth to 28 days)

Chapter

Central Auditory System Development and Disorders

Infancy (28 days to 2 years) and Early Childhood Central Auditory Testing Influence of Environmental Factors on the Developing Central Auditory System Abnormal Central Auditory System Development Conductive Hearing Loss: Effects of Deprivation of Sound Input Human Studies Animal Studies Sensorineural Hearing Loss: Effects of Deafferentation Animal Studies Human Studies Reintroduction of Activity by Electrical Stimulation in the Deaf Subject: Cochlear Implant Pathology of the Central Auditory System

DEVELOPMENT OF THE CENTRAL AUDITORY SYSTEM Introduction The human, unlike most nonprimate mammalian species, is born with highly developed auditory sensitivity. Complete maturation of auditory processing capabilities takes place over the first year of life, and, to a lesser extent, perhaps for the first several years. The recent refinement of techniques to assess behaviorally the auditory processing skills in the infant have added to our understanding of auditory development. Such measures can be correlated with anatomic, physiologic, and behavioral data from animal studies to gain a more complete understanding of the developmental process. Animals such as the cat and various rodents have been extensively used for these investigations. As altricial animals, the period of most rapid maturational change is after birth and, hence, unlike the human, readily accessible for study.

Debara L. Tucci, MD Edwin W Rubel, PhD

An appreciation of the process of auditory development is important not only for an understanding of the normal auditory system, but also for the impact of hearing loss on this system. In this chapter on the development of the central auditory system, we are concerned with the wellreferenced but little understood mechanisms of neural plasticity, which presumably allow the child to adapt to changes in auditory input. These mechanisms for adaptation have become particularly important when considering clinical issues such as the timing and aggressiveness of medical and surgical treatment of conditions that produce hearing loss in children. We will first discuss our understanding of central auditory system (CAS) development as revealed in human and animal studies of auditory system anatomy, physiology, and behavior. We then review the literature pertaining to changes in the system that occur in response to decreased auditory input and attempt to draw general conclusions that may be applied to clinical situations. Central auditory system pathology is reviewed at the end of the chapter. 563

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ANATOMIC DEVELOPMENT The following section provides a brief review of developmental auditory system anatomy. For further information the reader is referred to discussions of the subject by Rubel1 and Brugge.2

Spiral Ganglion Cells Embryologic development of the vertebrate inner ear has been described by Yntema,3,4 Rubel,1 and Van De Water.5 Yntema3 described two overlapping waves of inductive activity during inner ear development—a mesodermal followed by a neural influence. Briefly, the chordamesoderm is thought to induce determination of the cephalic ectoderm to form the otic field. This ectoderm thickens to become the otic placode, which invaginates to become the otic cup. Later, under the inducing influence of the adjacent neural tube, this tissue further differentiates into the otocyst. First-order neurons are derived solely from the otic placode, without contribution from the adjacent neural crest.6,7 Studies in chick embryos have demonstrated the presence of auditory and vestibular ganglion cells as a common ganglionic mass during the otocyst stage.8,9 Cells in the medial portion of this mass are later identifiable as cochlear ganglion cells. These cells are bipolar early in development, and central axons penetrate the marginal layer of the medulla before peripheral processes enter the cochlear epithelium. The possible role of neural induction in hair cell differentiation was investigated by Corwin and Cotanche.10 The authors found that transplanted denervated embryonic chicken ears developed phenotypically normal cochlear hair cells, a finding that allowed them to reject the hypothesis that neural connections are necessary for normal hair cell development. Cochlear nucleus (CN) neurons and cochlear hair cells may play a trophic role in the survival of ganglion cells11 or the direction of axonal growth.

maturation gradient is preserved in cochlear nerve projections to the dorsal cochlear nucleus (DCN).14 However, no such gradient was identified for second-order neurons in any division of the CN.15 A tonotopic order has been identified in most mature nuclei of the CAS including the CN (see Altman and Bayer16 for a review). In nuclei with demonstrated cytogenetic gradients (exceptions include the CN, the medial superior olivary nucleus, and the ventral nucleus of the lateral lemniscus), a relationship can be identified between time of origin and tonotopic gradient. In these nuclei, cells produced first are located in the highfrequency response area of the nucleus. Exceptions to this rule are the dorsal nucleus of the lateral lemniscus and the medial trapezoid nucleus, where the gradient is reversed. Several spatiotemporal gradients have been demonstrated in the developing chick auditory system, including cell loss and nuclear volume increases17 and dendritic absorption18 in CN, and dendritic growth in third-order neurons.19 We now consider whether lower order neurons are capable of imposing a topographic organization on successively higher structures of the CAS. Specifically, we can determine if successively higher nuclei are generated in a sequence that allows for developmental influence by

General Aspects of Central Auditory System Development Temporal ordering of neuron generation in the CAS is of interest for two reasons. First, it has been suggested (see later discussion) that the order of appearance of neurons may correlate with the tonotopic organization evident in adult auditory nuclei. Second, it is conceivable that brainstem nuclei influence the differentiation of neurons in sequentially higher auditory processing centers. Most investigators, however, agree with the assertion of Ramon y Cajal12 that primary central pathways are formed and develop function well in advance of cochlear function.1 For the most part, CAS structures develop concurrently, and there is little evidence that they influence each other substantially during early maturation. A series of studies by Altman and Bayer indicate a correlation between the time of origin of neurons in most nuclei of the CAS and the tonotopic organization found in the mature system. Ruben13 identified a frequency-specific developmental gradient for spiral ganglion cells (SGCs), with basal cells produced first (Fig. 36-1). A similar

Figure 36-1. Position of labeled SGCs within the mature cochlea. Gestation day is the day of injection of the tritiated thymidine. Note that earliest labeled cells are in the basal segment of the cochlea. (Reprinted with permission from Ruben RJ: Development of the inner ear of the mouse: A radioautographic study of terminal mitoses. Acta Otolaryngol 220(Suppl): 1–44, 1967, p 30.)

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lower centers. Comprehensive studies of time of origin of CAS nuclei have been performed using autoradiographic techniques with radioactive thymidine labeling of mitotic cells in the mouse, chick, and rat. Based on dating of time of origin, neurons of the lower brainstem and inferior colliculus are generated in a caudorostral sequence. However, the majority of medial geniculate neurons are generated several days before those of the inferior colliculus. In addition, thalamocortical fibers may be present by the time that medial geniculate structure is evident.16 It appears, therefore, that the topographic organization of the SGCs is not imposed sequentially on higher centers to the level of the cortex, although segmental influences may exist. However, certain aspects of neuronal maturation may occur sequentially, as Morest20 has suggested that dendritic differentiation in several mammalian species proceeds centripetally. For the following discussion, the reader is referred to Figures 36-2 through 36-4 for schematic diagrams of the mature central auditory system.

Cochlear Nucleus The CN complex, which includes the anteroventral and posteroventral as well as the dorsal cochlear nucleus Figure 36-3. Connections of the intermediate brainstem pathway (solid lines) and monaural brainstem pathway (dotted line). As in Figure 36-2, only projections from one side are shown. Forebrain auditory pathways are dashed. Abbreviations as in Figure 36-2. (Reprinted with permission from Rubel EW, Dobie RA: The auditory system: Central auditory pathways. In Patton H, Fuchs A, Hille B, Scher A, Steiner R [eds]: Textbook of Physiology. Philadelphia, WB Saunders, 1989, p 390.)

Figure 36-2. Binaural auditory pathways in the brainstem illustrated for the left CN. The connections from the other cochlear nucleus would form a mirror image. AVCN, anteroventral cochlear nucleus; DCN, dorsal cochlear nucleus; DLL, dorsal nucleus of the lateral lemniscus; IC, inferior colliculus; LSO, lateral superior olive; MG, medial geniculate nucleus; MNTB, medial nucleus of the trapezoid body; MSO, medial superior olive; PVCN, posteroventral cochlear nucleus; VLL, ventral nucleus of the lateral lemniscus. (Reprinted with permission from Rubel EW, Dobie RA: The auditory system: Central auditory pathways. In Patton H, Fuchs A, Hille B, Scher A, Steiner R [eds]: Textbook of Physiology. Philadelphia, WB Saunders, 1989, p 388.)

(AVCN, PVCN, and DCN), is derived primarily from the rhombic lip at the midrostrocaudal level of the brainstem; it has been suggested that at least the granule cells of the DCN may derive, along with the cerebellum, from the germinal trigone of the recess of the fourth ventricle.21 In the human embryo, the CN root is present in the medulla by the eighth week.22 Human brainstem nuclei are apparent at about 6 to 7 weeks.1 Cellular development was emphasized in a comprehensive study of the postnatal maturation of the cat CN.15 Large cells were found to originate first, followed by medium and then small-size cells, confirming a general rule of cellular development also observed by Pierce23 and Altman and Bayer.21 However, certain large cells mature very slowly, particularly the large spherical (“bushy”) cells of AVCN, which reach only 70% to 75% of their adult size by 12 weeks. The octopus cell of PVCN is the first large cell to reach adult morphology (3 to 4 weeks) and size (6 to 8 weeks).24 All cells of the CN were found to demonstrate rapid growth during the first month and slower growth thereafter. Webster and Webster25 note that in the mouse, the most rapid period of neuron growth takes place between postnatal days 3 and 12, before the onset of auditory function. J. Moore26 has investigated neuron soma development in prenatal human tissue as well as in the early postnatal rat. Cellular development in human CN tissue at 20 weeks’ gestational age is similar to that of the rat at birth. In both

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interactions. On the other hand, Parks and colleagues18,33–35 have shown that many of the normal developmental events in CN proceed unaltered in the absence of AN input (see later discussion of afferent influences). Development of DCN is prolonged compared with that of VCN. Fusiform cells of DCN are not fully mature by electron microscope criteria until the fourth postnatal month in the cat. Unlike AVCN, DCN neurons receive a large variety of inputs from several descending sources and have a complex network of intranuclear connections. These facts may explain the lengthy maturation period. For example, eight types of synaptic endings were found to mature in a systematic manner, with the earliest synapses formed by fibers originating close to the nucleus.36

Superior Olivary Complex

Figure 36-4. The major descending auditory pathways for one side of the brain. Abbreviations as in Figure 36-2. (Reprinted with permission from Rubel EW, Dobie RA: The auditory system: Central auditory pathways. In Patton H, Fuchs A, Hille B, Scher A, Steiner R [eds]: Textbook of Physiology. Philadelphia, WB Saunders, 1989, p 391.)

species, cells are numerous and demonstrate a high nuclearto-cytoplasmic ratio. Morphology similar to adults is achieved by 30 weeks’ gestation in the human and by 21 days postnatal in the rat, when neuropil as well as cellular cytoplasm is significantly increased. Studies of human tissue have relied primarily on classical cell body (Nissl) and myelin stains, and little information on the intricate complexities of dendritic, axonal, and astrocyte processes is available. Auditory nerve (AN) axons connect in a highly specific fashion with large spherical (“bushy”) cells of AVCN in a specialized synapse, the end-bulb of Held. Only one to three AN axons contact each spherical cell in the AVCN. End-bulbs are evident in the 2-day-old kitten; at this time the endings appear as irregular spoon-shaped swellings. By 45 days of age, nearly all cells exhibit characteristic adult-like endings with highly branched terminal arborizations, which appear to envelop the postsynaptic cell body.27 The early development of this highly elaborated cellular contact may serve to decrease the probability of multicellular input to the large spherical cell. Some evidence suggests that these developing second-order neurons may be transiently innervated by four or more auditory nerve fibers.28 However, the slight overproliferation of fibers requires a small amount of “pruning” to arrive at the mature configuration, synaptic connections formed early in development are typically maintained.29,30 Jhaveri and Morest31,32 demonstrated that morphologic changes in the end-bulbs are accompanied by parallel changes in their spherical cell targets in the chick, possibly reflecting developmental

The superior olivary complex (SOC) comprises several nuclei that occupy the ventral region of the pons. The primary regions contributing axons to the more cephalad auditory regions are the lateral superior olivary nucleus (LSO), the medial superior olivary nucleus (MSO), and the medial nucleus of the trapezoid body (MNTB). In addition, a series of so-called periolivary nuclei are equally important and issue descending inputs to the olivary nuclei, CN complex, and cochlea. Neurons of the SOC probably arise from the dorsal aspect of the medullary epithelium in the region of the rhombic lip and migrate a considerable distance to their final location in the ventral brainstem.37 Developmental changes in the primary olivary regions largely mirror those observed in the CN.

Lateral Lemniscal Nuclei Information on the developmental anatomy of the lateral lemniscal nuclei is lacking. The only information available is that reported by Altman and Bayer,16 discussed earlier, on the time of origin of this nuclear group.

Inferior Colliculus Virtually all ascending (lemniscal) and descending auditory pathways synapse in the inferior colliculus (IC). The convergence of input from numerous sources makes this structure critical for processing auditory information. Several schema have been devised to subdivide the IC. All include the central nucleus (CNIC), which is the most highly organized and frequently studied nucleus within this structure. Other divisions include the cortex and paracentral nuclei, according to one classification.38 The human IC is identifiable in the 3.7-cm (approximately 3 months’ gestation) fetus.39 The three main subdivisions of the IC are readily identified in the kitten at birth, and evidence suggests that the CNIC develops first.40 In CNIC laminae formed by neurons and afferent axons correspond to isofrequency contours. This highly organized pattern is evident early in development. In fact, neurons destined to form the IC demonstrate distinct proliferative gradients (rostrocaudal, lateromedial, and ventrodorsal), so that neurons generated at a certain time will have a characteristic distribution throughout the adult nucleus. This is in contrast to the superior colliculus,

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which develops concurrently and demonstrates no obvious spatiotemporal gradients.41 All neuronal cell types are present at birth in the cat CNIC.42 Several changes have been documented over the first month of life, including an increase in soma size25; decrease in extracellular space43; increase in lipid content44; and changes in dendritic length, morphology, and orientation.42,45,46 Adult patterns of connectivity to other CAS structures are present by postnatal day 7 in the rat.47 Some fibers originating in CN and SOC are present in the CNIC at birth, whereas the first projections from auditory cortex (AC) are identified on postnatal day 3.48 Dendritic maturational changes, not confined to the CAS, include an increase in length, loss of hairy or filiform processes, and a decrease in number (or complete loss) of dendritic spines.42

Medial Geniculate Body The medial geniculate body (MGB) comprises three main subdivisions—ventral, dorsal, and medial—each with component nuclei. The relatively early development of this diencephalic structure is recognized in the human embryo. The MGB can be defined in the 29- to 30-mm embryo (≈8.5 weeks), before the IC is identifiable.39,49 Nuclear organization is evident in the 6-month-old (16 to 21 cm) fetus.49 Most investigators believe that the MGB forms from dorsal thalamus (also see Stroer50), which is dependent on the presence of the telencephalon for normal differentiation.51

Auditory Cortex The AC is, like other CAS structures, comprises several divisions defined by morphologic and functional criteria. The organization of the auditory cortex of the cat has been described by Wong.52 AI, or primary auditory cortex, is a laminated, tonotopically organized structure. It is surrounded by subregions that either are tonotopically organized (A, anterior auditory cortex; P, posterior auditory cortex; VP, ventral posterior auditory cortex) or demonstrate no apparent tonotopicity (AII, secondary auditory cortex; DP, dorsoposterior area; V, ventral auditory area; T, temporal area). The columnar organization characteristic of cerebral cortex is most highly developed in AI. Functional properties organized according to binaural interaction columns and tonotopicity exist concurrently over the spatial map of this subregion. Moore and Guan53 and Moore54 recently described the maturation of the human auditory cortex through documentation of neurofilament proliferation in specimens ranging in age from 16 weeks of gestation to 27 years of age. Neurofilament proliferation reflects axon maturation in terms of increase in diameter, myelin sheath development, and increase in conduction velocity, and can be used to document patterns of connectivity and general brain maturation. During the perinatal period, between the third trimester and fourth postnatal month, mature axons are present only in the most superficial layer of the cortex, with no connections to areas outside the cortex. In early childhood, the first thalamocortical afferents are identified,

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and after age 5 years axons that connect the cerebral hemispheres are evident. By age 11 to 12 years the density of cortical axons approximates that of adults. Moore correlates cortical maturation with advancing auditory processing abilities, beginning in infancy when most abilities reflect brainstem function to late childhood and adolescence when more complex auditory skills are perfected, such as speech perception in noise and complex binaural processing.

Myelination In contrast to the late development of myelination in the auditory cortex, brainstem auditory axons develop an adult-like content of neurofilaments between the 16th and 28th weeks of gestation,55 and myelination of the axons first occurs between the 26th and 28th weeks.56 There is no evidence for centripetal axonal maturation in the human brainstem; the brainstem auditory pathway matures as a unit, rather than sequentially from lower centers to higher. Latency of auditory brainstem response (ABR) waveforms decreases significantly with increasing age.57–60 This change has been attributed by numerous investigators to progressive myelination of CAS pathways.44,59,60 Walsh and colleagues61 have quantitatively investigated myelination of the CAS of the cat. They compared rate and timing of maturation of axons and ABR latency and amplitude.62 Interestingly, they found that the rate of myelination does not correlate highly with either ABR latency decline or amplitude growth during the postnatal period in the kitten. Fibers of the AN, trapezoid, and inferior brachium have acquired only roughly half of the adult myelin sheath by the time the ABR latency and amplitude have achieved adult values (Figs. 36-5 and 36-6). The authors suggest that changes in ABR waveforms occur as a result of a combination of developmental processes, including myelination and synaptic maturation. Moore and coworkers63 further discuss factors that interact to produce developmental maturation reflected in the ABR. Based on their structural knowledge of brainstem development, they constructed a model that allows separate analysis of the ABR components of axonal conduction time and synaptic delay. These two components have different maturational time courses—although synaptic maturation proceeds until age 3 years, axonal conduction time is mature at birth. Because the brainstem auditory pathways continue to lengthen postnatally, they surmise that conduction velocity must also continue to increase. This may be due both to increasing thickness of the myelin sheath and increasing axon diameter.

FUNCTIONAL DEVELOPMENT OF THE CENTRAL AUDITORY SYSTEM Functional capabilities of the CAS may be defined either in physiologic or behavioral terms. Although physiologic methods can sometimes be more objective, precise, and less dependent on the motor system development and “state” of the organism, behavioral measures have the advantage of reflecting the animal’s ability to respond to the acoustic

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A

B

Figure 36-5. A, Distributions of the number of myelin lamellae investing auditory nerve axons, trapezoidal fibers, and fibers within the brachium of the inferior colliculus are shown for several postnatal ages for the cat. B, Average number of myelin lamellae investing myelinated axons for the three axonal populations in (A) are plotted as a function of postnatal age. (From Walsh EJ, McGee J: Development of auditory coding in the central nervous system: Implications for in utero hearing. Semin Perinatol 14:281–293, 1990, p 291. Modified from unpublished abstract data.)

environment in a meaningful way. Recent advances in techniques of behavioral assessment have greatly increased the objectivity of these measures and added to our understanding of human infant auditory processing. A wealth of data are available to detail the physiologic development of animal species. Many of these studies use precocial species, or those with immature hearing ability at birth, so that the early events of hearing development can be studied. In this chapter, we focus on developmental hearing milestones that can be measured in the human. Physiologic developmental studies are summarized by Rubel,1 Brugge,2 Sanes and Rubel,64 and Walsh and McGee,65 and the reader is referred to these sources for discussions of the physiologic development of the CAS.

BEHAVIORAL RESPONSES TO SOUND Hearing by the Human Fetus The human auditory system is well developed structurally by the third trimester. Furthermore, as discussed later, behavioral studies of auditory skills of the neonate reveal the presence of discrimination capabilities that require perception of complex auditory cues. The existence of these skills so early in life has led some investigators to suggest that the auditory experience of the fetus may facilitate,

or even be required for normal functional auditory system development. Until the advent within the past decade of sophisticated means of measuring sound transmission through the abdominal and uterine wall, it was believed that what little sound reached the fetus was largely masked by internal noise.66 More recent studies have used the hydrophone, rather than the standard microphones, to measure attenuation of external sound in humans67,68 and sheep.69–72 For low-frequency signals, at or below 250 Hz, reduction in sound pressure levels is less than 5 dB. Above 250 Hz, attenuation increased at a rate of about 6 dB per octave up to approximately 4000 Hz, where the average attenuation was 20 to 25 dB. Results obtained in sheep were similar to those obtained in humans, supporting the use of the sheep as a model for in utero sound transmission studies. In addition, a hydrophone can be implanted surgically in the sheep prior to delivery, whereas in the human the location of implantation is less accurate and requires taking measurements with the amnion ruptured. Intrauterine basal noise is dominated by low frequencies. Highest intensities are measured at frequencies below 32 Hz, to which the human auditory system is not responsive. Measurements obtained by Querleu and colleagues73 suggest that basal noise is of sufficiently low level that external sounds are not masked. Their A-weighted sound

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Figure 36-6. Comparison between myelination of the auditory nerve (expressed as percent of the adult average number of lamellae per axon) and normalized ABR latency and amplitudes for wave I as illustrated. Latencies are expressed as percent of adult values, and amplitude as percent of maximum. (From Walsh EJ, McGee J: The development of function in the auditory periphery. In Altschuler RA, Hoffman DW, Bobbin RP [eds]: Neurobiology of Hearing: The Cochlea. New York, Raven Press, 1986, p 254.)

pressure level measurements of internal noise were 28 dB. (The A-weighted scale excludes the lowest frequencies, see Green74). Voices emerged above the basal noise level by 8 to 12 dB for exterior voices and 24 dB for the mother’s voice. Independent observers asked to repeat what they could hear from an interuterine recording of male and female speakers (including the mother) were able to correctly reproduce 30% of the phonemes, regardless of the source. Although the mother’s voice was louder, it was not better perceived, presumably because of greater distortion of the internally transmitted sound. Transmission of sound into the interuterine environment is meaningful only if the fetus is capable of perceiving the stimulus. Investigators attempting to measure fetal hearing have used a variety of unconditioned responses, such as body movements, heart rate changes, and eye blink responses. Such measures are primarily startle responses to sound and are subject to rapid habituation with repetitive stimulation.75 The earliest eye blink responses to noise bursts can be elicited in the 25th gestational week, and consistent eye blink, heart rate, and motor responses are measured from the seventh month of pregnancy.76,77 Studies by Lecanuet and coworkers78 have demonstrated response (cardiac deceleration) to stimuli of 90 to 100 dB sound pressure level ex utero.

Postnatal Development of Auditory Competence Methodology Psychoacoustic tests must be designed to optimize the acoustic stimulus control of the subject and the adaptiveness of the task to the behavioral repertoire of the subject.75 Different response strategies will be most effective at different points along the developmental timeline; herein lies the challenge to investigators interested in development of auditory competence. Unconditioned

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responses used most often for neonatal testing, including the registration of limb and body movements, heart rate changes, and eye blink responses, provide less precise information than obtained by use of the conditioning procedures applied in children 3 months and older. Newer methods for detecting auditory responses in infants use “observer-based” strategies (observer-based psychoacoustic procedure, or OPP). In these procedures, an observer judges not whether the infants responded but whether a signal occurred, using the infant’s behavior as the only basis for the judgment.79 This test strategy is more objective and more sensitive in assessing auditory abilities in this age group than other methods of assessment. After age 5 to 6 years, children can be evaluated using routine audiometric testing techniques. Interpretation of developmental studies must take into account the accuracy of the method of evaluation. Clearly, development of nonsensory processes such as memory and attention may confound interpretation of experimental results, particularly for infants and young children. Thus, it is useful to use varied experimental strategies to address each question of human auditory system development. Postnatal hearing development is well summarized by Werner.79 Neonatal Period (Birth to 28 days) The newborn is able to discriminate a number of the elements of speech, including voiced versus unvoiced consonants, consonants by place of articulation, and several vowel pairs, by about 2 months of age (see Querleu et al.73 for review). DeCasper and Fifer80 determined that 3-day-old neonates consistently respond preferentially to their mothers’ voices. Responses rely at least partially on intonation patterns, as there is no preference for the mother’s voice when text is read backwards.81 The neonate is also able to localize the origin of a sound.82,83 Interestingly, this behavior is more difficult to elicit in 1- to 2-month-olds, but reappears around 3 to 4 months of age.84 This developmental pattern is thought to reflect a difficulty in organization of auditory space and coordination with appropriate motor behavior. When the head-orienting response reappears, it is accompanied by visual search; this may represent the beginning of true spatial hearing.84 A number of studies have shown a substantial improvement in pure tone thresholds in quiet in the first 6 months of life. Thresholds of 2- to 5-week-old infants have been measured as 40 to 50 dB greater than those of adults across frequency (500, 1000, 4000 Hz85). By 3 months of age the gap has narrowed to about 20 dB.86 Thresholds appear to be poorest initially at high frequencies, relative to adult thresholds, and demonstrate the most improvement during the first 6 months of life. Infancy (28 days to 2 years) and Early Childhood Absolute Sensitivity and Intensity Discrimination As reported by Werner,79 the available evidence suggests that, in quiet, detection thresholds at 6 months are 10 to 15 dB higher than those of adults and that thresholds are not

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adult-like through the entire frequency range of hearing until at least 10 years of age. Although responses are initially most adult-like in the low frequencies, high-frequency responsiveness improves more rapidly, so that the adult values are first achieved in the high frequencies. The trend toward earliest development of low-frequency hearing parallels that seen in the physiologic studies87 and behavioral studies of hearing in animals.88 Low-frequency threshold elevation is reported as late as 10 to 18 years of age (Fig. 36-7).89–91 Frequency Resolution Frequency resolution capabilities are among the earliest to mature. Werner and Bargones92 report that frequency resolution is adult-like at all but the highest frequencies by 6 months of age. Psychophysical data obtained from children have indicated that frequency resolution continues to improve until at least age 4 years93,94 and may continue to improve as late as age 12.90,95 Temporal Resolution Animal studies of physiologic response development have revealed that temporal response properties are the last of the “simple” auditory system coding mechanisms to reach maturity. Accordingly, one might expect that behavioral measures of temporal processing would reflect this prolonged developmental time course. Although absolute sensitivity and frequency resolution is nearly mature by 6 months, temporal resolution continues to mature after 6 months of age. The developmental time course of temporal processing is difficult to assess independently because of dependence on intensity coding. One common

measure of temporal processing is gap detection. Studies of gap detection report that this ability doesn’t reach maturity until about age 5,96 but it is possible that stimulus duration and adaptation effects influence this measure. Using one technique designed to separate the effects of intensity and temporal processing, Levi and Werner97 suggest that infants may have mature temporal resolution, but immaturity of intensity processing contributes to the experimental findings that reflect apparent deficits in temporal processing. It is possible that threshold, frequency resolution, and temporal resolution are all nearly mature within the first couple of years of life and that development of intensity coding lags behind, mature by some measures by about 5 years of age. Spatial Hearing Clifton84 summarized the ability of infants to respond to auditory spatial cues. Sensitivity to binaural time cues is well developed in 4-month-olds; development of binaural intensity cues has not been studied. Investigations of minimal audible angle (MAA) have reported that 6-month-olds can discriminate a change in sound location of 12 to 19 degrees off-midline. Gradual improvement is noted to 18 months (6 degrees). Performance of 5-years-olds is similar to that of adults, who can detect an MAA of 1 degree. The “precedence effect” aids in localizing a sound by suppression of echoes, or reflections from surrounding surfaces. Clifton84 presents evidence that development of this ability is delayed in infants compared with their ability to localize single-source sounds. Infants younger than 4 months do not demonstrate a precedence effect (cannot inhibit the echo), and thus are unable to accurately localize the source of the sound. The ability to discriminate auditory distance reflects the infant’s ability to integrate a representation of space and object location in space. Clifton and colleagues84 have shown that a 6-month-old will reach correctly for an unseen, sounding object when presented within reach. When the object was beyond reach, infants typically did not attempt to grasp it. Clifton and colleagues84 demonstrated that 6-month-old infants can use sound to identify an object. Infants were able to correctly reach for an object (response differentiated by bimanual grasp vs. one-handed reach) identified by a learned associated sound. Thus, 6-month-old infants are capable of evaluating and responding to environmental events through an integration of cognitive functioning, motor activity, and auditory information.

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Figure 36-7. Absolute thresholds as a function of age for five octave-band noises. Individual exponential decay functions have been fit to the data at each frequency. (From Trehub SE, Schneider BA, Morrongiello BA, Thorpe LA: Auditory sensitivity in school-age children. J Exp Child Psychol 46:273–285, 1988, p 278.)

Keith (see Chapter 17, Central Auditory Testing) has defined an auditory processing disorder as the inability or impaired ability, in the setting of normal intelligence and hearing sensitivity, to attend to, discriminate, recognize, remember, or comprehend information presented to the auditory system. Although efforts have been made to tailor tests of central auditory function to young children, behavioral assessments are difficult in children younger

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than 6 years of age, and normative data are often lacking. A thorough discussion of behavioral assessment of central auditory function is provided by Keith in Chapter 17 of this text. The reader is also referred to the discussion by Musiek and Baran.98 Many of the shortcomings of behavioral testing in this age group can theoretically be circumvented by the use of carefully administered and interpreted electrophysiologic tests for evaluation of central auditory processing skills. Interpretation of many of these responses is poorly understood. However, recent advances in the understanding of middle latency and late responses may lead to improved clinical utility. A comprehensive review of the electrophysiologic tests of central auditory system function is provided by Kraus and McGee.99 Responses to sound are classified by latency into early, middle, and late waveforms. The ABR, the development of which was discussed earlier, consists of seven peaks, all occurring within 15 msec of signal onset. Studies of Moller and Jannetta100,101 suggest that waveforms are generated at sites from the peripheral AN to the IC. The ABR provides a highly reliable indication of auditory function in subjects of all ages and shows predictable changes in neurologically impaired systems.102–104 The middle latency response (MLR) comprises a series of waveforms (Na, Pa, Pl, and TP41) that occur between 10 and 60 msec after stimulus onset. Generator sites include auditory pathway structures central to the IC (“primary pathway”) as well as structures outside this pathway, such as the so-called reticular activating system, and nonprimary divisions of the auditory thalamocortical pathways, which process multisensory stimuli (“nonprimary pathway”). The MLR derives from multiple sources that mature at different developmental rates and are variously affected by anesthetics and sleep state. Whereas the ABR is developmentally mature by 18 months of age, the MLR exhibits a much longer developmental time course; the primary cortical generator is likely mature by age 10 to 12 years, but the nonprimary areas may not be fully mature until early adulthood. McGee and Kraus105 suggest that this extended developmental process may account for the relatively late development of selective auditory attention. The MLR has been used in pediatric populations primarily to assess low-frequency hearing thresholds that are not easily measured with the traditional ABR.106 One problem with this application has been the lability of the response in the pediatric population, particularly in sleeping children. Problems of recording this response in children may be circumvented by targeting response measurements made during favorable sleep stages as described by McGee and colleagues.107 Late auditory evoked potentials occur after 70 msec and reflect primarily responses of structures central to the brainstem. In general, these responses are less stimulusdependent and more state-dependent and, thus, variable. Although certain of the late response waveforms are well defined and useful as clinical entities, others are much more variable and controversial. Some of the more welldocumented responses include the N1–P2 complex (P1, N1, P2, N2), present at a latency range of 50–300 msec. All are elicited by a stimulus train of repetitive identical tonal or

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click stimuli. Other late responses occur in response to speech stimuli, with total durations out to 700 msec. Kurtzberg and colleagues108,109 described a series of cortical auditory evoked potentials (CAEPs) in response to speech stimuli that show an orderly sequence of maturation until adult-like responses are achieved at about age 2. Patients with various brain lesions have been shown to have abnormal late potentials, and attention of some investigators has focused on the use of these responses for identification of neurologic disease (see Kraus and colleagues110). Another set of late responses is elicited only in reaction to a deviant or unexpected stimulus inserted into a repetitive identical stimulus train, presented in an “oddball” paradigm. Some of these responses include the mismatch negativity response (MMN), P300, and the cortical discriminative response (CDR).110 The MMN is a robust response that, unlike other cortical potentials, appears to be mature in school-age children.111 It is passively elicited from nonattending subjects, in response to stimulus pairs (such as /da/ and /ga/) that are at or above behavioral discrimination threshold. Stimulus pairs may be within or across phonemic boundaries. The MMN is thought to originate from the auditory cortex, with contributions from auditory thalamus and hippocampus.112–115 Thus, it may be useful for evaluation of central auditory processing skills such as auditory shortterm memory, stimulus detection in background “noise,” temporal processing, or speech discrimination. It also may be useful for evaluation of children with attention deficit disorders.111 Another potentially exciting use of the MMN is in evaluation of speech discrimination in cochlear implant recipients, particularly children with limited auditory processing skills.116 The P300, originally described by Sutton and coworkers,117 is also elicited by an oddball paradigm. P3a can be elicited in nonattending subjects, but the P3b component requires active discrimination of the stimulus by the subject. Multiple subcortical as well as cortical sites are thought to contribute to the response (see Kraus and McGee99 for a review). Definitive norms have not been established for the P300 because of great intersubject variability in latency and amplitude. For this reason, the P300 may be more useful as a measure of changes over time in one individual subject (i.e., recovery from injury, response to treatment, etc.). It has been suggested that the P300 correlates more with global cognitive function than with any specific disorder.118 Speech evoked CAEPs and CDRs have been investigated by Kurtzberg and colleagues108,109 in clinical populations. They studied infants identified to be at risk for language disorders based on low birth weight or perinatal asphyxia and discovered a high incidence of abnormal speech-elicited responses. On follow-up, children with abnormal responses in the neonatal period were later found to have deficiencies of language-processing skills. The authors concluded that the abnormal CAEPs and CDRs were meaningful predictors of later language performance. Finally, the N400 (latency 400 msec) is elicited only in response to a stimulus that presents a semantic incongruity (e.g., “I am going to walk the house”). It is elicited, as is the P300, by auditory, visual, and sign language stimuli.119 Generators of the N400 have not been identified, but it is

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assumed that since many modalities can be involved in the response that it is generated from many areas of the brain. Some abnormalities of the N400 have been identified in language-impaired children.99

INFLUENCE OF ENVIRONMENTAL FACTORS ON THE DEVELOPING CENTRAL AUDITORY SYSTEM Abnormal Central Auditory System Development Abnormalities of CAS development may occur as a result of direct insult by disease processes affecting the brain (see later section on Pathology of CAS) or secondary to pathology of the peripheral auditory system. Numerous studies describe the often profound effects of afferent manipulation on the developing CAS. Conversely, effects on the mature auditory system are usually modest or nonexistant. Investigators have described a sensitive, or developmental, period during which abnormal experience can adversely influence development, and a more protracted critical period during which normal afferent input appears to be necessary to affect normal CAS development. However, rather than being confined to discrete periods, the dependence of neuronal integrity on afferent activity seems to decline gradually with age. Despite an ability to define for various species and experimental conditions the time of maximal sensitivity to afferent manipulations, the cellular mechanisms that affect the response to environmental manipulation in the developing animal have yet to be delineated. Disruption of afferent input to the CAS may be separated, at least theoretically, into one of two types of insults (Fig. 36-8). These are usually termed deprivation and deafferentation, based on the nature of the manipulation intended by the experimenter. Deprivation describes a manipulation that decreases sound transmission through the outer or middle ear system, producing a conductive hearing loss. Blockage of sound transmission results in a decrease in sound-evoked activity in the CAS, but may have little short-term effect on spontaneous activity of these neurons.120,121 Effects of purely conductive pathology on CAS anatomy and function are often subtle, but appear to involve the entire CAS, in particular the CN.122–125 Deprivation of sound input may be unilateral or bilateral; if unilateral, development of binaural processing strategies may be affected. Another type of experimentally induced deprivation is interference with patterned activity. For example, introduction of a repetitive environmental sound can deprive the CAS of the pattern of neuronal discharges evoked by a normal acoustic environment and can disrupt the acquisition of central auditory-processing capabilities.126,127 The second type of insult, deafferentation, occurs with the partial or total destruction of the peripheral end-organ. The lesion produces a sensorineural hearing loss and invariably results in diminution or elimination of all input—spontaneous as well as sound-evoked—to the CAS. Deafferentation results in degenerative changes that proceed sequentially to more central structures. CAS pathology is usually much more marked than is the case of sound

Figure 36-8. Sites of manipulations of the peripheral auditory system represented on a section through the human ear (schematic from Pickles 1988). 1, pinna removal; 2, ear plug; 3, tympanic membrane puncture; 4, ossicular disarticulation or removal; 5, application of pharmacologic substances to the cochlea; 6, round or oval window puncture; 7, cochlea removal or destruction. (Reprinted with permission from Moore DR: Developmental plasticity of the brainstem and midbrain auditory nuclei. In Romand R (ed): Development of the Auditory and Vestibular Systems 2. Amsterdam, Elsevier, 1992, p 299. Modified from Rubel and Parks, 1988.)

deprivation with an intact end-organ. It should be emphasized, however, that a meaningful interpretation of deprivation and deafferentation experiments requires rigorous quantification of the effect of the manipulation on the pattern and amount of activity in the CAS.30,120

Conductive Hearing Loss: Effects of Deprivation of Sound Input Human Studies Physicians initially assumed that because the conductive hearing loss (CHL) typically associated with otitis media may be mild, unilateral, and fluctuating, the functional consequences were likely to be minimal. As early as the 1960s, however, it was noted that children with a history of repeated episodes of otitis media with hearing loss lagged behind their normal-hearing peers in measures of language development and educational achievement. These early studies lacked many of the necessary features of a welldesigned investigation of clinical outcomes, and critical commentary took issue with the conclusions of these investigators.128–131 Nevertheless, these early investigations nearly universally reported a negative effect of hearing loss on development. By the late 1980s several research groups initiated experimentally sound prospective studies of sufficiently large numbers of subjects to draw statistically valid conclusions about the consequences of CHL on hearing, as well as on more global measures of speech, language, cognition, behavior, and educational achievement. Some of the most compelling evidence of long-standing deficits in individuals with chronic CHL comes from studies that assess performance on specific auditory processing tasks. Hall, Pillsbury, and colleagues,132–134 and others135,136

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have used the masking level difference (MLD) to assess the ability of subjects with a history of CHL to process binaural information in the presence of noise. The MLD measures the subjects’ ability to use binaural difference cues of time and amplitude introduced during the test by changing the phase of the signal presented to the two ears. MLDs are significantly smaller in children with a history of CHL than in age-matched control children. In a study population that was selected for placement of middle ear ventilation tubes, the abnormality in MLDs noted prior to tube placement, in the presence of hearing loss, persisted in approximately half of the children after hearing thresholds were normal.133 Interestingly, Pillsbury and colleagues132 commented that postsurgical MLDs were most likely to be abnormal in subjects who had experienced asymmetrical hearing losses, although this was not confirmed in their later studies. ABRs have been studied in subjects who have normal hearing and a history of CHL.137–139 All three studies reported an increase in latency to waves III and V of the ABR and an increase in interwave latencies. Binaural interaction was assessed by subtracting binaural from summed monaural waveforms and was significantly diminished in normal subjects and subjects with a history of otitis media with effusion. Prospective investigations have examined the effect of otitis media with effusion and CHL on development of speech and language skills and on behavior and cognition. Vernon-Feagans140 noted risk factors that may affect language and attention outcomes. Her model predicts that, in the presence of an environment that facilitates communication, children develop normal speech, language, and behavior. In less optimal situations, language skills develop poorly, and a lack of attentive behavior complicates language processing. Children in the latter group with a history of hearing loss from otitis media may tend to “tune-out” language and attend to less auditory parts of the environment. Such children have a more difficult time with complex listening tasks such as comprehending extended discourse in conversation, storytelling, or extended topic elaboration, such as they might encounter in a school setting. Therefore, prompt and aggressive management of childhood medical conditions associated with hearing loss seems well advised. Such interventions are not always implemented, secondary to lack of knowledge of the implications of such impairment and to controversy regarding the most cost-effective method of medical management of disease.141,142 The above-mentioned studies provide compelling evidence that changes in central auditory processing abilities persist long after hearing loss resolves in children with a history of conductive impairment. The existence of long-term alterations in processing of auditory signals could imply that hearing loss in early life is associated with structural or functional modifications in the CAS. Very little is known about the specific structural and functional changes that occur in response to this impairment, and the mechanisms of these neuronal changes are even less well understood. The need to effectively manage hearing loss in children is one ultimate goal that drives our need to understand the factors, such as duration of impairment and effect of developmental stage, which influence the

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consequences of CHL and the potential for reversal of any CAS changes. Animal Studies Anatomic Effects of Conductive Hearing Loss Animal models of CHL have been developed and give us some insight into the CAS consequences of conductive impairment. These studies must be interpreted with consideration of the species studied, the developmental stage at which the experiment is conducted, species-specific characteristics such as the frequency range of hearing, and the effect of the manipulation used on activity in the auditory nerve and CAS. A valid model of CHL requires that the manipulation used to create the hearing loss damage only the sound-conducting mechanism of the middle ear and not the inner ear. Results of studies in which concomitant sensorineural hearing loss has been inflicted are confounded by the associated degenerative changes typically observed following cochlear damage (see later discussion). A number of investigations, mostly in rats and mice, have documented that CHL or other forms of auditory deprivation (e.g., sound isolation) introduced during a “critical period” of auditory development result in smaller than normal brainstem nuclei and neurons,143–152 and other structural changes.149,153,154 Webster145 documented that sound amplification introduced during the critical period of auditory development in the mouse decreases the atrophy of the CN in mice with external canal atresia and CHL. Subcutaneous administration of a neurotrophic agent, monosialoganglioside, significantly ameliorates CHL-induced atrophy of spiral ganglion cells and neurons of the VCN.155 Tucci and coworkers124,125 identified marked changes in CAS neuronal activity using the 2-deoxyglucose method, as well as changes in capacity for oxidative metabolism in gerbils with unilateral conductive hearing impairment. Investigations in chick,123 monkey,156 and ferret122 failed to demonstrate changes in cross-sectional area of brainstem neurons following conductive impairment. Thus, species differences do appear to be important in assessing the effect of CHL. However, it is likely that other structural or functional modifications occur, particularly if the loss is asymmetrical or unilateral. For example, in the ferret, Moore and colleagues122 found, despite the lack of change in neuron area in the CN, a significant change in the projection from the CN opposite the affected ear to the ipsilateral IC following unilateral conductive impairment. This change may occur secondary to the newly introduced asymmetry of peripheral input with the unilateral hearing impairment (see following section). Evidence that Unilateral Conductive Impairment May Affect the Symmetry of Central Auditory System Projections As discussed earlier, unilateral conductive impairment has been found in one experimental paradigm to change the symmetry of projections from the CN to IC. It has also been argued that compensatory changes occur in brainstem neurons of the CN opposite an ear with CHL.

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Coleman and O’Connor151 reported that the mean neuron area in the spherical cell region of the rostral AVCN decreased in the CN ipsilateral to a conductive hearing impairment but increased in the contralateral CN. Tucci and coworkers124 reported a similar effect on their measure of oxidative metabolism in the gerbil with a unilateral CHL. Some evidence suggests that the symmetry of input between the two ears may be important in establishing and maintaining neuronal projections. Killackey and Ryugo154 reported that the laminated structure of the central nucleus of the IC in the rat is altered following unilateral but not bilateral ear canal closure. Studies by Knudsen and colleagues in the barn owl157 reveal evidence of reorganization of a binaurally innervated nucleus of the CAS and altered localization cues following unilateral conductive impairment secondary to an earplug placed during a critical period in development. Physiologic Responses to Conductive Hearing Loss Studies of physiologic responses from the auditory cortex158 (cat) or inferior colliculus159,160 (rat) in animals with unilateral ear canal atresias imposed at an early stage in development show abnormal responses to binaural stimulation. This apparent inability to appropriately integrate auditory input from the two ears following unilateral ear canal occlusion may reflect physiologic changes that could be associated with structural abnormalities noted in the animal studies discussed earlier. Auditory processing abnormalities noted in children with a history of CHL, such as problems with localization136 and use of binaural cues for signal detection in noise,133 may reflect similar changes in the human central auditory system. Although monaural CHL decreases the level of acoustic stimulation that reaches the inner ear, it does not entirely deprive the ear of patterned input. Several investigators have examined the effect of restriction of auditory experience on CAS development. It has been hypothesized29,126,127 that response properties of the CAS may be fine-tuned through selective elimination of synapses during development. Evidence from studies such as Jackson and Parks28 shows that immature CAS neurons may receive a slight overabundance of excitatory inputs. Although which factors influence the final synaptic configuration is unknown, it is possible that activity, both spontaneous and evoked, influences the establishment of mature synaptic anatomy. If this is the case and a diversity of auditory experience is necessary for normal maturation, it is possible that restriction of auditory experience could result in postsynaptic cells manifesting a larger than normal receptive field and poorer frequency resolution secondary to failure to eliminate inappropriate inputs during development. Sanes and Constantine-Paton126,127 tested this hypothesis by raising mice in the presence of a repetitive click stimulus. Clicks were demonstrated to entrain a large portion of primary afferents in both the AN and IC during the developmental period. The investigators demonstrated that single-unit tuning curves to tone pip stimuli obtained from recording in the central nucleus of the IC were less sharp (poorer frequency resolution) for click-reared than for normal control animals. The authors concluded that normal temporal patterns of neural activity help to structure synapses in the developing auditory system.

From the foregoing data, it appears that experience with a normal acoustic environment may influence cellular response properties of the CAS. The full range of effect of altered experience is probably not appreciated at this time. Certainly, binaural integration is influenced by asymmetrical acoustic input. Refinements in our ability to study these properties in the nervous system are necessary to determine if other complex integrative capacities are influenced as well. Whether a sensitive period exists during which these abilities must develop or be lost forever is unclear. Several of the previously cited studies seem to suggest that certain capabilities are never achieved if hearing loss is allowed to persist during the developmental period. The obvious question raised to the otologic surgeon is that of the urgency of correcting a CHL in the young child. Agreement is widespread that aggressive intervention is warranted for treatment of recalcitrant middle ear effusion with tympanostomy tubes for prevention of repeated infections and correction of CHL. However, less of a consensus is achieved on the issue of correction of other types of CHL in children, particularly when the loss is unilateral. Bone conduction hearing aids provide reasonable levels of amplification, but compliance is a problem, and identical signals are presented to both ears, thus eliminating cues for binaural hearing.161 A treatment decision must be based in part on the needs of the child, the wishes of the parents, and the likelihood of achieving normal hearing with surgical intervention (i.e., in the case of congenital atresia).

Sensorineural Hearing Loss: Effects of Deafferentation Animal Studies In contrast to the little-understood effects of conductive impairment on the CAS, the repercussions of sensorineural hearing loss (SNHL) is well documented, and investigators are developing an increasingly sophisticated understanding of the mechanisms of CAS changes following sensorineural impairment. Transneuronal degenerative effects of endorgan damage include changes in neuronal and synaptic morphology,162–164 dendritic morphology,165,166 protein synthesis,167 and metabolic activity.168–173 Changes are most marked in young developing animals, and maximum susceptibility is confined to a “critical period” in development.174–178 Neuronal changes are generally greatest in the VCN, which receives its primary afferent input from the ipsilateral ear. However, changes are also seen in more central structures, including the ipsilateral LSO and contralateral MNTB in young gerbils179,180 and ferrets.181,182 Morphologic changes similar to those seen following deafferentation (destruction of the auditory end-organ) can be produced by pharmacologic blockade of auditory nerve activity. Tetrodotoxin (TTX), when applied at the round window, immediately and reversibly eliminates auditory nerve action potential.177,183–186 Presynaptic action potentials regulate protein synthesis in secondorder auditory neurons of the chick brainstem.183 Born and Rubel183 examined the effect of a perilymph injection of TTX on numbers and size of neurons in nucleus magnocellularis (the avian equivalent of the AVCN in mammals)

Central Auditory System Development and Disorders

and on incorporation of 3H leucine using autoradiography. Short-term effects (1.5 hours) of TTX were very similar to changes seen after deafferentation,167,187 but by 24 hours after injection—as the reversible effects of TTX dissipated—these changes reverted to normal. Similarly, TTX application produces reversible cell size changes in the CN of the gerbil.186 Synaptic activation is essential for maintenance of normal cell metabolism, as antidromic activation of neurons via electrical stimulation of axons in a brain slice preparation did not enhance protein synthesis.184 These studies of afferent manipulation suggest that the activity of auditory afferents regulates the metabolism and morphology of neurons in the CAS. The early changes observed following deafferentation (either anatomic or pharmacologic) appear to be due to a reduction in activitydependent interactions between presynaptic and postsynaptic cells.186 Studies in chicks have shown that second-order auditory system neurons rely on eighth nerve activity-dependent activation of a metabotropic glutamate receptor to maintain physiologic intracellular calcium. Loss of intracellular calcium is thought to contribute to the early stages of neural degeneration and cell death.188 The balance of input from afferent projections to binaurally innervated nuclei may influence structure and function in the CAS. Kitzes and colleagues studied the effects of unilateral cochlea removal in the neonatal gerbil on patterns of connectivity and physiologic responses (see Kitzes189 for review). Projections from the VCN, which in the normal gerbil innervate the ipsilateral LSO, the contralateral MNTB (via the ventral acoustic stria), and both the ipsilateral and contralateral MSO, are altered after neonatal cochlear ablation. Labeling experiments showed aberrant projections from the unoperated side to the contralateral LSO, the ipsilateral MNTB, and both MSO. It has been suggested that these abnormal patterns of connectivity may occur because of lack of inhibition or competition from the projections of the lesioned side, implying that such interactions are important for normal development of innervation patterns.189 Further studies in the neonatal gerbil190 demonstrated changes in the patterns of connectivity between the CN and IC, with an increase in the ipsilateral CN–IC projection on the side opposite cochlear ablation, and a decrease in the CN–IC projection on the side of the ablation. These results again suggest that an interaction of binaural inputs may influence the final configuration of innervation patterns for this CAS structure. Investigation of physiologic responses obtained by stimulation of the unoperated ear in neonatally ablated gerbils revealed larger responses from the ipsilateral IC than was observed in normal animals or those ablated as adults, indicating functionality of this enhanced projection from the ipsilateral ear.191 Similar effects were noted on recorded responses from auditory cortex ipsilateral to the nonoperated ear of neonatally cochlear ablated cats.192 Another study of auditory cortex plasticity investigated the tonotopic organization of auditory cortex contralateral to a partial unilateral cochlear lesion in the guinea pig.193 Immediately after restricted peripheral lesion, neurons in the region of cortex in which the damaged portion of the cochlea is normally represented undergoes a change in tonotopicity such that neuron characteristic frequencies (CFs) are shifted outside the frequency range of the lesion.

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Thresholds for these neurons are initially grossly elevated compared with thresholds for normal neurons in this region, but over time neurons in this region develop near normal thresholds at the new CFs. This progression suggests that the representation of frequencies above and below the lesion is expanded. Similar results have been reported by Harrison and coworkers194 for the newborn kitten and by Schwaber and colleagues195 for the adult macaque monkey. Furthermore, studies by Recanzone and coworkers196 in the adult owl monkey and Bakin and Weinberger197 in the guinea pig have demonstrated that cortical responses can be changed in response to behavioral conditioning in the absence of a peripheral lesion, thus demonstrating exceptional functional plasticity. The functional significance of this reorganization has yet to be understood. As pointed out by Schwaber and coworkers,195 such findings raise questions about the utility of reintroduction of auditory stimuli after the onset of hearing loss, either with a hearing aid or a cochlear implant. However, it appears likely, although not proven, that the extreme plasticity of cortical organization would allow further reorganization to accommodate the reintroduction of activity. Mutant strains of animals with congenitally determined lesions of the organ of Corti provide another means of assessing degenerative changes and may offer useful models for studying genetic CHL in human subjects. In this case, deafferentation is generally gradual and bilateral. However, unlike the case of cochlear ablation, findings may be confounded by genetic defects in central structures, so that all observed degenerative changes may not be secondary to peripheral destruction. In the deaf white cat, for example, degenerative changes have been observed in auditory brainstem nuclei prior to the time when changes are noted in SGCs.198 One of the most widely cited studies is that of West and Harrison199 in the deaf white cat. Pathologic alterations observed for this species occur postnatally, from the 5th to 21st day after birth. The authors demonstrated severe atrophy of the organ of Corti, although SGCs of the two animals studied were largely normal in appearance. Despite the normal ganglion cell population, the volume of medullary nuclei and soma areas in these nuclei were decreased compared with normal animals, much like the results of Powell and Erulkar162 discussed earlier. Thus, central degenerative changes may be primary rather than secondary to SGC degeneration and loss of activity. The authors provide an excellent summary of work on congenitally deaf animal models published before the date of their study. More recent work in the deafness mutant (dn/dn) mouse highlights physiologic changes in central structures.200,201 Horner and Bock201 studied IC unit responses to electrical stimulation of the periphery and discovered that, at least by certain measures, responses measured from congenitally deaf animals were more robust than those of the normal-hearing control animals. They found a preponderance of multispike single-unit responses in contrast to the single-spike responses more often observed in the control animals. Similar observations have been made in animals genetically susceptible to audiogenic seizures202 and noiseinduced hearing loss.203 The maximum number of evoked

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spikes in response to stimulation was greater in mutant animals, and the group mean threshold of response was lower in mutant than control animals. Peak-to-peak amplitudes of responses recorded in the IC were also greater in mutant mice.200 The absence of spontaneous activity in this mutant was confirmed (in 6- to 7-month-old animals) using the 2-deoxyglucose method.204 Human Studies Investigations of the effects of deafferentation in the human CAS are quite limited. Moore and colleagues205 reported their analysis of brainstem specimens from seven deaf and six normal-hearing control subjects. Neuron areas in a restricted location in the PVCN were correlated inversely with length of period of deafness, so that the patients with the longest period of deafness prior to death tended to have the smallest cell size. Furthermore, consistent with the foregoing discussion, the two congenitally deaf patients in this sample were found to have the most severe degenerative changes. They also reported a positive correlation between cell size and spiral ganglion cell number. Therefore, even though these populations of SGCs were receiving no or little afferent stimulation, their presence appeared to affect the population of second-order neurons. This raises the possibility that, although shortterm studies of spontaneous activity following cochlear lesion demonstrate dramatic loss of activity in the CN, long-term evaluation may reveal some level of activity in the auditory nerve that may partially sustain more central structures. Liberman and Kiang206 studied spontaneous discharge rates of auditory nerve fibers in cats 4 to 8 weeks after noise trauma. Although the majority of fibers determined to be unresponsive to sound demonstrated no spontaneous activity, low spontaneous discharge rates were recorded in many fibers. Those unresponsive units that were found to have spontaneous activity had abnormal patterns of activity, typically bursts separated by long periods of silence. Wu and Moore207 developed three-dimensional reconstructions of the CN complex in normal-hearing and deaf subjects, including two patients with acoustic neuromas. Their findings in normal-hearing subjects were consistent with the report of Konigsmark and Murphy208 that showed a continuous decline in nuclear volume with increasing age. Interestingly, in the deaf subjects, all over age 60 at the time of death, there was a less marked decline in nuclear volume, secondary to gliosis and replacement of much of the neuropil by glial processes. Thus, the authors conclude that nuclear volume is not a good correlate of sensory loss in humans. Reintroduction of Activity by Electrical Stimulation in the Deaf Subject: Cochlear Implant Human Studies Given the apparent relationship between auditory nerve activity and integrity of the CAS system structures, it has been suggested that the reintroduction of electrical stimulation of the auditory nerve, as via a cochlear implant, might provide sufficient stimulation to either maintain

these central structures or, if instituted immediately after the onset of deafness, prevent degenerative changes from occurring. However, the limited histologic material available from human subjects who received a cochlear implant prior to their death demonstrates no consistent effect of chronic electrical stimulation on CAS anatomy. This statement is based on the temporal bone histopathologic studies by Linthicum and coworkers209 and the studies of brainstem tissue conducted by Moore and colleagues205 cited earlier. Linthicum and colleagues209 quantitatively evaluated the number of SGCs in 22 temporal bones from 13 cochlear implant patients. Contrary to what might be expected, SGC population did not appear to correlate with patient performance with the implant; in fact, satisfactory performance was achieved with as few as 3212 ganglion cells, or slightly greater than a tenth of the usual population of approximately 30,000. Interestingly, the duration of electrical stimulation, which ranged from 9 months to 14 years (mean 5 years) had no effect on the number of ganglion cells. Of the seven specimens from bilaterally deaf subjects analyzed by Moore and colleagues,205 four subjects had been implanted unilaterally with either a single- or multichannel cochlear implant. In no subject was there a significant increase in ganglion cell number or PVCN cell area on the side of the brain ipsilateral to the implanted cochlea (J. Moore26). Duration of stimulation for the four subjects prior to their death was 7 months, 9 months, 2 years, and 23 years, respectively. The last subject, however, never responded to stimulation with the implant, and on temporal bone histology was found to have no surviving ganglion cells. Thus, stimulation of this population was very limited. Another way to examine plasticity is through functional measures of implant performance. Although more global measures are evaluated, and many potential confounding variables are present, performance as a function of factors such as length of deafness or duration of stimulation may provide some insight into the ability of the CAS to use newly available auditory information. Early studies210,211 reported that, for children and adults, age of onset of deafness, length of total auditory deprivation, and age at implantation are all important factors in predicting postimplant performance. Longitudinal studies of implanted deaf children show significant gains in speech production and language acquisition in the implanted children relative to their matched nonimplanted peers.212–214 Best results are obtained with early implantation, particularly before age 3.215 Such results would seem to imply that electrical stimulation instituted soon after the onset of profound deafness is more effective in stimulating auditory pathways than stimulation begun after progressive degenerative changes have taken place. Animal Studies Several animal studies have addressed the questions raised in the foregoing discussion about auditory system plasticity in response to the reintroduction of electrical activity by means of a cochlear implant. Most investigators have concluded that electrical stimulation instituted soon after deafening results in an increase in SGC density ipsilateral to the stimulated ear. More central effects of stimulation are less clearly demonstrated.

Central Auditory System Development and Disorders

Measures of metabolic function have shown increased activity following deafening and subsequent chronic electrical stimulation. Wong-Riley and colleagues216 used the cytochrome oxidase technique to determine if brainstem auditory pathways in the cat would demonstrate evidence of return of function after 5 to 6 months of deafness. Levels of cytochrome oxidase increased to nearly control levels after 1 month of electrical stimulation. Although sample size was small (n = 2), they demonstrated return of function in a previously deficient system. El-Kashlan and coworkers217 also reported evidence of metabolic activity in the CAS following prolonged deafferentation using the 2-deoxyglucose technique. They demonstrated response to electrical stimulation of the CN through at least 16 weeks after deafening. Chouard and colleagues218 presented early evidence that implantation and stimulation may prevent degenerative changes following cochlear damage in the guinea pig CN. Lousteau,219 noting Chouard’s results, first demonstrated that the early introduction of electrical intracochlear stimulation in young guinea pigs deafened with systemic kanamycin and ethacrynic acid affected a significant increase in spiral ganglion cell density compared with the nonstimulated ear. Modest amounts of stimulation were used in this study—animals were stimulated at 100 μA for 1 hour daily, 6 days a week for a 45-day period. Hartshorn and coworkers220 also assessed SGC survival in ototoxically deafened guinea pigs stimulated at various current levels for a 9-week period, 2 hours per day, 5 days per week. SGC survival was significantly enhanced for cells in the basal turn of the cochlea only. Leake and colleagues221 reported a similar pattern of enhanced survival of SGCs only in the basal cochlear region following chronic intracochlear stimulation in four cats (Fig. 36-9). In this investigation, newborn kittens were ototoxically deafened, unilaterally implanted (age 9 to 17 weeks) and chronically stimulated at 6 dB above electrically evoked ABR thresholds for 1 hour per day for 1 to 3 months. No differences in SGC density

Figure 36-9. Pooled data for eight neonatally deafened cats that were implanted and chronically stimulated at 2 dB above threshold for periods of about 3 months. For each cochlear sector the mean spiral ganglion cell density and standard errors are shown for the stimulated and control specimens. The mean ganglion cell density averaged over all segments was significantly higher in the stimulated cochleas than in the control specimens. (From Leake PA, Snyder RL, Hradek FT, Rebscher SJ: Chronic intracochlear electrical stimulation in neonatally deafened cats: Effects of intensity and stimulating electrode location. Hear Res 64:99–117, p 107.)

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between the stimulated and nonstimulated side were observed in two kittens that received only 4 weeks of stimulation, or in implanted nonstimulated control animals. Analysis of SGC area revealed no effect of stimulation. In a follow-up study using the same animals, Lustig and coworkers222 reported that, although ototoxic deafening resulted in a 20% to 26% reduction in AVCN spherical cell size compared with the normal cat, intracochlear stimulation was associated with a 7% increase in ipsilateral AVCN spherical cell area. No changes were seen in nuclear volume or AVCN cell density following stimulation. Matsushima and colleagues223 deafened four cats at age 37 to 40 days with a one-time dose of ototoxic drugs, implanted an intracochlear electrode array at age 70 to 80 days, and delivered electrical stimulation unilaterally beginning 10 days after surgery. Animals were stimulated 16 hours per day for a total of 3 to 4 months. An automated image analysis system was used to measure all cells in the CN, so the chance of sampling error was greatly reduced. Cell area in AVCN was significantly greater ipsilateral to the stimulated ear. However, mean cell areas for the stimulated AVCN were still less than reported for normal-hearing cats.15,224 Thus, more robust effects were obtained in studies with a longer duration of stimulation and a more complete sampling of AVCN neurons. An alternative explanation for the failure of electrical stimulation to completely reverse the CAS effects of deafness may involve the nature of the stimulus used in these studies. Although the repetitive stimuli delivered chronically in the cited studies may replicate the effects of spontaneous activity in these structures, they allow for no simulation of evoked activity or for any alteration in the pattern of activity. Snyder and coworkers225 evaluated frequency resolution of responses in the IC of cats that underwent chronic electrical stimulation as described for the experiments of Leake and colleagues.221 The CNIC is characterized by a well-organized spatial tonotopic gradient that is not altered by deafness or chronic electrical stimulation.226 Spatial “tuning curves” were generated from single and multiunit data by determining the threshold for an electrical stimulus generated by a particular intracochlear electrode pair at all levels in an CNIC electrode penetration. Results in chronically stimulated deaf cats were compared with results in deaf implanted, nonstimulated cats. Although tuning curves obtained from deaf nonstimulated cats were similar to those obtained from normal animals, spatial tuning curves obtained from chronically stimulated animals were significantly broader, indicating that the volume of CNIC stimulated by activation of an electrode pair appears to be significantly expanded, or less finely tuned. As discussed earlier, Sanes and Constantine-Paton126,127 also demonstrated broader CNIC tuning curves in click-reared mice. Snyder and colleagues226 also reported on temporal properties of neurons in the IC of deafened nonstimulated, deafened stimulated, and normal cats. Chronic stimulation was found to increase the response threshold back toward normal (compared with deaf nonstimulated animals); decrease the average response latency of neurons in the IC; and substantially increase the frequency of occurrence, amplitude, and latency of long latency responses. The

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finding, similar to that reported by Horner and Bock201 of lower response thresholds in deaf nonstimulated animals is paradoxical, as it occurs coincident with a decrease in the SGC population. One possible explanation is that the disappearance of myelinated fibers from the habenula and bony spiral lamina provides a preferential path for excitation of remaining neural elements, allowing stimulation of SGCs at lower current levels. Secondly, lower thresholds may be secondary to denervation supersensitivity to auditory nerve excitation. Interestingly, thresholds increase toward normal following chronic electrical stimulation. Based on these findings, the authors suggest that low thresholds to electrical stimulation may not accurately predict numbers of surviving neural elements in cochlear implant patients.226 In summary, although steady progress is observed in patients following cochlear implantation, particularly when performed early after the onset of deafness, investigators have not been able to document irrefutably that the reintroduction of chronic electrical activity substantially alters central auditory pathways in deaf animals. It is likely that a multitude of factors must be accounted for to document alterations in CAS anatomy. Changes in the pattern, type, level, duration, and intracochlear location of stimulation are likely to be important, as is the method of data analysis.

PATHOLOGY OF THE CENTRAL AUDITORY SYSTEM Pathologic conditions associated with CAS abnormalities during the developmental period include the following: chromosomal aberrations, skeletal CNS deformities, certain forms of hereditary deafness, congenital and neonatal infections, metabolic disorders, and storage diseases such as leukodystrophies.227–229 In many cases, central findings are incompletely documented, and their significance often disputed. Primary CAS pathology is most clearly documented for two metabolic disorders: anoxia and hyperbilirubinemia. Morphologic studies of the CNS have documented structural abnormalities in patients with Down syndrome (trisomy 21), Edwards’ syndrome (trisomy 18), and Patau’s syndrome (trisomy 13). Gandolfi and coworkers230 reported several abnormalities in the VCN in Down syndrome, including reduced cell number, cell density, and nuclear volume. Abnormalities of the VCN were also noted in Edwards’ syndrome, and abnormalities of auditory cortical neurons noted in Edwards’ and Patau’s syndromes. In all cases, overall brain development is retarded.229 Skeletal and structural abnormalities associated with Arnold-Chiari malformation and Klippel-Feil syndrome can result in compression and kinking of the eighth cranial nerve. In Arnold-Chiari malformation the CN can be compressed,227 and compression of blood vessels can lead to brainstem ischemic changes.231 Hearing loss is reported in patients with this disorder, in percentages ranging from 12% to 44%.232 Rydell and Pulec232 report that 20% of 29 patients studied had both vestibular and auditory symptoms. The hearing loss can be asymmetrical and progressive,233 and surgical decompression has been reported to halt the progression of hearing loss.234

Although CNS abnormalities and mental retardation have been reported for a few syndromes associated with early-onset deafness, including Cockayne’s syndrome (retinitis pigmentosa, dwarfism, microcephaly, premature senility, photosensitive dermatitis), Sylvester’s disease (optic atrophy, ataxia), and Norrie’s disease (oculoacousticocerebral degeneration), evidence of auditory pathway degenerative changes has been demonstrated only for Cockayne’s syndrome.229 Studies have documented loss of peripheral sensory cells, loss of over half of the spiral ganglion cell population, and degenerative changes in auditory nuclei, presumed secondary to transneuronal degeneration.235,236 Auditory dysfunction has been well documented for patients with Friedrich’s ataxia, a disorder of spinocerebellar degeneration. Abnormalities have been noted in the VCN, medullary striae, and superior olive.237–239 Van Bogaert and Martin238 provide a comprehensive summary of previously published literature on auditory system involvement in this disorder. Reports of CAS pathology are difficult to interpret because of the paucity of data on the integrity of the peripheral auditory system. Spoendlin240 reported that, in two patients with Friedrich’s ataxia, the organ of Corti was essentially intact, but severe degenerative changes were noted in more central structures. Satya-Murti and colleagues241 performed audiometric tests and brainstem auditory evoked potentials on four patients with Friedrich’s ataxia who had no subjective hearing impairment. Behavioral audiometry revealed a mild to severe bilateral SNHL in all subjects, with no consistent configuration. Three of the four patients demonstrated “rollover,” or a decrease in speech recognition scores with increasing word intensity. ABRs for all four subjects were markedly abnormal, with no identifiable waveforms. The authors argue based on their findings that the primary lesion producing auditory dysfunction in these patients is spiral ganglion cell degeneration. Intrauterine and early-onset infections are rarely associated with CAS abnormalities. Congenital deafness resulting from maternal rubella results primarily from cochlear destruction. However, Rorke and Spiro242 documented cerebral lesions in these patients, although not specifically in CAS pathways. Extensive degenerative changes were noted in association with vascular lesions, confined primarily to the deep white matter and nuclei. Ames and coworkers243 identified central auditory processing deficits in children demonstrated to have congenital rubella. In a sample of 118 affected children, 50% were found to have central auditory impairment. Of these, none were diagnosed as mentally retarded, and 30 patients had no concomitant peripheral auditory system abnormalities. Cytomegalovirus infections cause CNS abnormalities in approximately half of affected cases. Abnormalities include microcephaly, seizures, mental retardation, and deafness.143,244 Again, inner ear involvement and CNS degenerative changes have been documented, but abnormalities of CAS pathways have not been investigated.229 Several postnatal infections have been documented to have CAS involvement.228 Bacterial meningitis usually produces hearing impairment by labyrinthine destruction.245 However, the infection may spread to involve the eighth nerve and spiral ganglion cells. Cerebral arteritis may produce focal brain lesions, particularly in the infant.245

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Meningoencephalitis due to Listeria monocytogenes or tuberculosis may involve the CAS,229 although this pathology has not been demonstrated in children. Syphilis involves both the peripheral and central auditory system. Severe demyelination and degeneration of the CN may occur.228 Hearing impairment has been demonstrated in patients with storage diseases, particularly those that involve white matter degeneration, or leukodystrophies.229 Ochs and colleagues246 identified abnormalities in the ABRs of 10 patients with various leukodystrophies, including poor waveform morphology and increased interwave latencies. Abnormalities were presumed to be secondary to the severe demyelination associated with these diseases. The ABR was also studied in an infant with Gaucher’s disease. Progressive deterioration of waveforms was noted. Postmortem pathology revealed no abnormalities of the central auditory pathways, however.247 Anoxic encephalopathy is one of the major causes of hearing loss of central origin; this insult is typically associated with a bilateral high-frequency sensorineural deficit.248 Although the inner ear and spiral ganglion cells are relatively immune to the effects of anoxia, the CAS, particularly the CN, is severely affected.228 Hall249 studied brain and temporal bone specimens from 39 patients with neonatal anoxia. Although temporal bone specimens were essentially normal, severe degenerative changes were noted in the CN complex. Cell loss ranged from 20% to 45% in the VCN, and up to 66% in the DCN. Less marked changes were observed in the IC. Degree of cell loss appeared to correlate with length of the hypoxic period. The vulnerability of the CN to anoxic-related injury is attributed to the relatively high metabolic rate of this region. Some investigators have attributed the CAS injury produced by hyperbilirubinemia to the effects of hypoxia, produced by hemolysis and intracapillary sludging of erythrocytes.228 It is likely, however, that several factors influence the development of bilirubin encephalopathy. For example, anoxia during the perinatal period may result in acidosis, which may increase cellular uptake of bilirubin (discussed by Conlee and Shapiro250). Ahdab-Barmada and Moossy251 described different patterns of CNS abnormalities observed with kernicterus and anoxic/hypoxic injury. Evidence presented by MacDonald and coworkers252,253 suggests that bilirubin neurotoxicity may act through glutaminergic excitotoxicity in the hippocampus, and Conlee and Shapiro250 argue that a similar mechanism may contribute to CAS toxicity, particularly in AVCN and MNTB. Crabtree and Gerrard254 presented the first evidence of an association between kernicterus and SNHL. A typically high-frequency loss was identified in 80% of 20 cases tested. Early audiometric studies reported results consistent with cochlear pathology.255 However, more recent ABR studies have documented evidence of brainstem pathology, a finding more consistent with reported anatomic findings. Although inner ear pathology has been reported in association with hyperbilirubinemia,256 most investigators have failed to document cochlear abnormalities.228,257,258 Instead, extensive degenerative changes have been reported in the CAS, particularly in the CN.228,257 ABR abnormalities have been reported in neonates with hyperbilirubinemia.259–261 Nwaesei and coworkers260

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recorded ABRs in nine full-term infants before and after exchange transfusion for hyperbilirubinemia (mean concentration 22.3 mg/dL), and noted significant improvement in waveform morphology, latency, and amplitudes following transfusion. The homozygote jaundiced ( jj) Gunn rat, which lacks the hepatic enzyme glucuronyl transferase necessary to conjugate bilirubin, has been used as a model for human bilirubin encephalopathy. Shapiro and colleagues250,262–265 have documented abnormalities of ABR waveforms and auditory brainstem morphology in this species. In order to accentuate neuropathologic abnormalities, brain bilirubin concentration was artificially raised in heterozygotic (Nj) and homozygotic Gunn rats by the administration of sulfadimethoxine, an albumin-binding drug that increases free bilirubin levels. Increased latencies were demonstrated for waves II and III of the ABR, as well as the I–II and I–III interwave latencies, following administration of sulfadimethoxine to jj rats only.262 As with transfusiontreated neonates,260 abnormalities were reversed after treatment, which in this case consisted of administration of albumin (to bind bilirubin). ABR abnormalities were found to correlate in severity with degenerative changes in the CN.264 Anatomic analysis of brainstems of sulfa-treated jj rats revealed a significant decrease in CN volume, AVCN spherical cell area, and area of principal cells in the nucleus of the trapezoid body, as compared with treated heterozygotes. The authors suggest that these two cell groups are uniquely targeted in bilirubin toxicity, possibly through a neurotoxic mechanism related to presumed glutaminergic inputs.250 Auditory neuropathy, a disorder first described by Starr and colleagues,266,267 is characterized by hearing loss for pure tones, impaired word discrimination out of proportion to pure tone hearing loss, absent or abnormal ABRs, and normal outer hair cell function as measured by otoacoustic emissions and cochlear microphonic.268 Causes of this condition have not been determined; some patients have an apparently isolated auditory abnormality, and others are diagnosed with a variety of disease processes, including Charcot-Marie-Tooth disease, hyperbilirubinemia, Friedreich’s ataxia, multiple sclerosis,268,269 and severe neonatal illness.270 Sites of involvement may include the cochlea (central to the outer hair cells), the auditory nerve, and the auditory pathways of the brainstem, or all of these structures. In cases of delayed auditory maturation function may improve over time; however, if the auditory neuropathy is a manifestation of a generalized neurologic condition, function may deteriorate.269,271

REFERENCES 1. Rubel EW: Ontogeny of structure and function in the vertebrate auditory system. In Jacobson M (ed.): Handbook of Sensory Physiology, vol IX: Development of Sensory Systems. New York, Springer-Verlag, 1978. 2. Brugge JF: Development of the lower brain stem auditory nuclei. In Romand R, Marty R (eds.): Development of Auditory and Vestibular Systems. New York, Academic Press, 1983, pp 89–120. 3. Yntema DL: An analysis of induction of the ear from foreign ectoderm in the salamander embryo. J Exp Zool 113:211–243, 1950.

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189. Kitzes LM: The role of binaural innervation in the development of the auditory brainstem. In Ruben RJ, Van De Water TR, Rubel EW (eds.): The Biology of Change in Otolaryngology: Proceedings of the Symposium of the 9th Midwinter Research Meeting of the Association for Research in Otolaryngology, February 1986, New York, Elsevier Science, 1986. 190. Nordeen KW, Killackey HP, Kitzes LM: Ascending projections to the inferior colliculus following unilateral cochlear ablation in the neonatal gerbil, Meriones unguiculatus. J Comp Neurol 214: 144–153, 1983. 191. Kitzes LM, Semple MN: Single-unit responses in the inferior colliculus: Effects of neonatal unilateral cochlear ablation. J Neurophysiol 53:1483–1500, 1985. 192. Reale RA, Brugge JF, Chan JCK: Maps of auditory cortex in cats reared after unilateral cochlear ablation in the neonatal period. Dev Brain Res 34:281–290, 1987. 193. Robertson D, Irvine DRF: Plasticity of frequency organization in auditory cortex of guinea pigs with partial unilateral deafness. J Comp Neurol 282:456–471, 1989. 194. Harrison RV, Nagasawa A, Smith DW, et al: Reorganization of auditory cortex after neonatal high frequency cochlear hearing loss. Hear Res 54:11–19, 1991. 195. Schwaber MK, Garraghty PE, Kaas JH: Neuroplasticity of the adult primate auditory cortex following cochlear hearing loss. Am J Otol 14:252–258, 1993. 196. Recanzone GH, Schreiner CE, Hradek GT, et al: Functional reorganization of the primary auditory cortex in adult owl monkeys parallel improvements in performance at an auditory frequency discrimination task. Soc Neurosci Abst 17:534, 1991. 197. Bakin JS, Weinberger NM: Classical conditioning induces CSspecific receptive field plasticity in the auditory cortex of the guinea pig. Brain Res 536:271–286, 1990. 198. Schwartz I, Higa J: Correlated studies of the ear and brainstem in the deaf white cat: Changes in the spiral ganglion and the medial superior olivary nucleus. Acta Otolarynol 93:9–18, 1982. 199. West CD, Harrison JM: Transneuronal cell atrophy in the congenitally deaf white cat. J Comp Neurol 151:377–398, 1973. 200. Steel KP, Bock GR: Electrically-evoked responses in animals with progressive spiral ganglion degeneration. Hear Res 15:59–67, 1984. 201. Horner EC, Bock GR: Inferior colliculus single unit responses to peripheral electrical stimulation in normal and congenitally deaf mice. Dev Brain Res 15:33–43, 1984. 202. Willott JF: Comparison of response properties of inferior colliculus neurons of two inbred mouse strains differing in susceptibility to audiogenic seizures. J Neurophysiol 45:35–47, 1981. 203. Willott JF, Shao-Ming L: Noise induced hearing loss can alter neural coding and increase excitability in the central nervous system. Science 216:1331–1332, 1981. 204. Durham D, Rubel EW, Steel KP: Cochlear ablation in deafness mutant mice: 2-deoxyglucose analysis suggest no spontaneous activity of cochlear origin. Hear Res 43:39–46, 1989. 205. Moore JK, Niparko JK, Linthicum FH: Changes in the central auditory pathway in deafness. Paper presented at the 126th Annual Meeting of the American Otological Society, April 17, 1993, Los Angeles. 206. Liberman MC, Kiang NYS: Acoustic trauma in cats: Cochlear pathology and auditory-nerve activity. Acta Otolaryngol (Suppl) 358:1–63, 1978. 207. Wu BJ-C, Moore JK: Human cochlear nuclei: Shape and volume in normal and deaf subjects. Assoc Res Otolaryngol 15:54, 1992. 208. Konigsmark BW, Murphy EA: Volume of the ventral cochlear nucleus in man: Its relationship to neuronal population and age. J Neuropath Exp Neurol 31:304–316, 1972. 209. Linthicum FH, Fayad J, Otto SR, et al: Cochlear implant histopathology. Am J Otol 12:245–311, 1991. 210. Kileny PK, Zimmerman-Phillips S, Kemink JL, Schmaltz SP: Effects of preoperative electrical stimulability and historical factors

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on performance with multichannel cochlear implant. Ann Otol Rhinol Laryngol 100:563, 1991. Staller SJ, Beiter AL, Brimacombe JA, et al: Pediatric performance with the nucleus 22-channel cochlear implant system. Am J Otol (Suppl) 12:126–136, 1991. Robbins AM, Svirsky M, Kirk KI: Children with implants can speak, but can they communicate? Otolaryngol Head Neck Surg 117:155–160, 1997. Brackett D, Zara CV: Communication outcomes related to early implantation. Am J Otol 19(4):453–60, 1998. Franz DC: Pediatric performance with the Med-El COMBI 40+ cochlear implant system. Ann Otol Rhinol Laryngol 111:66–68, 2002. Kirk KI, Miyamoto RT, Lento CL, et al: Effects of age at implantation in young children. Ann Otol Rhinol, Laryngol S189:69–73, 2002. Wong-Riley MTT, Walsh SM, Leake-Jones PA, Merzenich MM: Maintenance of neuronal activity by electrical stimulation of unilaterally deafened cats demonstrable with cytochrome oxidase technique. Ann Otol Rhinol Laryngol (Suppl 82) 90:30–32, 1981. El-Kashlan HK, Noorily AD, Niparko JK, Miller JM: Metabolic activity of the central auditory structures following prolonged deafferentation. Laryngoscope 103:399–405, 1993. Chouard CH, Meyer B, Josset P, Buche JF: The effect of the acoustic nerve chronic electrical stimulation upon guinea pig cochlear nucleus development. Acta Otolaryngol 95:639–645, 1983. Lousteau RJ: Increased spiral ganglion cell survival in electrically stimulated, deafened guinea pig cochleae. Laryngoscope 97:836–842, 1987. Hartshorn DO, Miller JM, Altschuler RA: Protective effect of electrical stimulation in the deafened guinea pig. Otolaryngol Head Neck Surg 104:311–319, 1991. Leake PA, Hradek GT, Rebscher SJ, Snyder RL: Chronic intracochlear electrical stimulation induces selective survival of spiral ganglion neurons in neonatally deafened cats. Hear Res 54: 251–271, 1991. Lustig LR, Leake PA, Snyder RL, Rebscher SJ: The consequences of neonatal deafening and chronic intracochlear stimulation on the cochlear nucleus. Assoc Res Otolaryngol Abstr 15:55, 1992. Matsushima J-I, Shepherd RK, Seldon HL, et al: Electrical stimulation of the auditory nerve in deaf kittens: Effects on cochlear nucleus morphology. Hear Res 56:133–142, 1991. Cant NB, Morest DK: The structural basis for stimulus coding in the cochlear nucleus of the cat. In Berlin C (ed.): Hearing Sciences: Recent Advances. San Diego, College-Hill Press, 1984. Snyder RL, Rebscher SJ, Cao K, et al: Chronic intracochlear electrical stimulation in the neonatally deafened cat. I. Expansion of central representation. Hear Res 50:7–34, 1990. Snyder RL, Rebscher SJ, Leake PA, et al: Chronic intracochlear electrical stimulation in the neonatally deafened cat II. Temporal properties of neurons in the inferior colliculus. Hear Res 56:246–264, 1991. Dublin WB. Fundamentals of Sensorineural Auditory Pathology. Springfield, IL, Charles C Thomas, 1976. Dublin WB: Central auditory pathology. Otolaryngol Head Neck Surg (Suppl) 95:363–424, 1986. Horoupian DS: Pathology of the central auditory pathways and cochlear nerve. In Alberti PW, Ruben RJ (eds.): Otologic Medicine and Surgery. New York, Churchill Livingstone, 1988. Gandolfi A, Horoupian DS, DeTeresa RM: Pathology of the auditory system in autosomal trisomies with morphometric and quantitative study of the ventral cochlear nucleus. J Neurol Sci 51:43–50, 1981. Sieben RL, Hamida MB, Shulman K: Multiple cranial nerve deficits associated with Arnold-Chiari malformation. Neurology 21:673–681, 1971. Rydell RE, Pulec JL: Arnold-Chiari malformation: Neurootologic symptoms. Arch Otolaryngol 94:8–12, 1971.

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233. Hendrix RA, Bacon CK, Sclafani AP: Chiari-1 malformation associated with asymmetric sensorineural hearing loss. J Otolaryngol 21:102–107, 1992. 234. Johnson GD, Harbaugh RE, Lenz SB: Surgical decompression of Chiari I malformation for isolated progressive sensorineural hearing loss. Am J Otol 15(5):634–638, 1994. 235. Gandolfi A, Horoupian D, Rapin I, et al: Deafness in Cockayne’s syndrome: Morphological, morphometric, and quantitative study of the auditory pathway. Ann Neurol 15:135–143, 1984. 236. Horoupian DS: Pathology of the auditory pathway in hereditary sensory neuropathy and deafness—(HSAN I). J Neuropath Exp Neurol 46:386, 1987. 237. Urich H, Norman RM, Lloyd OC: Suprasegmental lesions in Friedreich’s ataxia. Conf Neurol 6:360–371, 1957. 238. Van Bogaert L, Martin L: Optic and cochleovestibular degenerations in the hereditary ataxias I. Clinico-pathological and genetic aspects. Brain 97:15–40, 1974. 239. Oppenheimer DR: Brain lesions in Friedreich’s ataxia. Can J Neurol Sci 6:173–l76, 1979. 240. Spoendlin H: Optic and cochleovestibular degenerations in hereditary ataxias II. Temporal bone pathology in two cases of Friedreich’s ataxia with vestibulo-cochlear disorders. Brain 97:41–48, 1974. 241. Satya-Murti S, Cacace A, Hanson P: Auditory dysfunction in Friedreich ataxia: Result of spiral ganglion degeneration. Neurology 30:1047–1053, 1980. 242. Rorke LB, Spiro AJ: Cerebral lesions in congenital rubella syndrome. J Pediatr 70:243–255, 1967. 243. Ames MD, Plotkin SA, Winchester RA, Atkins TE: Central auditory imperception: A significant factor in congenital rubella deafness. JAMA 213:419–421, 1970. 244. McCracken GH, Shinefield HR, Cobb K, et al: Congenital cytomegalic inclusion disease: A longitudinal study of 20 patients. Am J Dis Child 117:522–539, 1969. 245. Igarashi M, Saito R, Alford B, et al: Temporal bone findings in pneumococcal meningitis. Arch Otolaryngol 99:79–83, 1974. 246. Ochs R, Markland ON, DeMyer WE: Brainstem auditory evoked responses in leukodystrophies. Neurol 29:1089–1093, 1979. 247. Kaga M, Azuma Ch., Imamura T, Murakami T: Auditory brain stem response (ABR) in infantile Gaucher’s disease. Neuropediatrics 13:207–210, 1982. 248. Flottorp G, Morley DE, Skatvedt M: The localization of hearing impairment in athetoids. Acta Otolaryngol 48:404–414, 1957. 249. Hall JG: The cochlea and cochlear nuclei in neonatal asphyxia: A histological study. Acta Otolaryngol (Suppl) 194:1–93, 1964. 250. Conlee JW, Shapiro SM: Morphological changes in the cochlear nucleus and nucleus of the trapezoid body in Gunn rat pups. Hear Res 57:23–30, 1991. 251. Ahbab-Barmada M, Moossy J: The neuropathology of kernicterus in the premature neonate: Diagnostic problems. J Neuropath Exp Neurol 43:45–56, 1984. 252. McDonald JW, Shapiro SM, Silverstein FS, Johnston MV: Excitatory amino acid neurotransmitter systems contribute to the

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pathophysiology of bilirubin encephalopathy. Ann Neurol 28:413, 1990. McDonald JW, Shapiro SM, Silverstein FS, Johnston MV: Hyperbilirubinemia is associated with a state of hypersensitivity to excitotoxic amino acid in brain. Soc Neurosci Abst 16:1123, 1990. Crabtree N, Gerrard J: Perceptive deafness associated with severe neonatal jaundice: A report of sixteen cases. J Laryngol Otol 64:482–506, 1950. Matkin ND, Carhart R: Auditory profiles associated with Rh incompatibility. Arch Otolaryngol 84:502–513, 1966. Kelemen G: Erythroblastosis fetalis: Pathologic report on the hearing organs of a newborn infant. AMA Arch Otolaryngol 63:392–398, 1956. Dublin WB: Neurologic lesions of erythroblastosis fetalis in relation to nuclear deafness. Am J Clin Path 21:935–939, 1951. Gerrard J: Nuclear jaundice and deafness. J Laryngol Otol 66:39–46, 1952. Perlman M, Fainmesser P, Sohmer H, et al: Auditory nerve brainstem evoked responses in hyperbilirubinemic neonates. Pediatr 72:658–664, 1983. Nwaesei C, VanAerde J, Boyden M, Perlman M: Changes in auditory brainstem responses in hyperbilirubinemic infants before and after exchange transfusion. Pediatr 74:800–803, 1984. Lenhardt ML, McArtor R, Bryant B: Effects of neonatal hyperbilirubinemia on the brainstem electric response. J Pediatr 104:281–284, 1984. Shapiro SM: Acute brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide. Pediatr Res 23:306–310, 1988. Shapiro SM: Binaural effects in brainstem auditory evoked potentials of jaundiced Gunn rats. Hear Res 53:41–48, 1991. Shapiro SM, Conlee JW: Brainstem auditory evoked potentials correlate with morphological changes in Gunn rat pups. Hear Res 57:16–22, 1991. Shapiro SM, Hecox KE: Development of brainstem auditory evoked potentials in heterozygous and homozygous jaundiced Gunn rats. Dev Brain Res 41:147–157, 1988. Starr A. McPherson D, Patterson J, et al: Absence of both auditory evoked potentials and auditory percepts dependent on timing cues. Brain 114:1157–1180, 1991. Starr A, Picton TW, Sininger Y, et al: Auditory Neuropathy. Brain 119:741–753, 1996. Doyle KJ, Sininger Y, Starr A: Auditory neuropathy in childhood: Laryngoscope 108(9):1374–1377, 1998. Berlin CI, Bordelon J, St. John P, et al: Reversing click polarity may uncover auditory neuropathy in infants. Ear Hear 19(1):37–47, 1998. Deltenre P, Mansbach AL, Bozet C, et al: Auditory neuropathy: a report on three cases with early onsets and major neonatal illnesses. Electroencephalogr Clin Neurophysiol 104(1):17–22, 1997. Stein LK, Tremblay K, Pasternak J, et al: Auditory brainstem neuropathy and elevated bilirubin levels. Semin Hear 17:197–213, 1996.

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Outline Cochlear Physiology and Sensorineural Hearing Loss Noise-Induced Hearing Loss Presbycusis Ototoxicity Aminoglycosides Cisplatin and Carboplatin Loop Diuretics Salicylate and Quinine Topical Otic Preparations Chemical Teratogens Monitoring during Ototoxic Drug Administration Idiopathic Sudden Sensorineural Hearing Loss Temporal Bone Trauma Temporal Bone Fracture Perilymphatic Fistula Diving Barotrauma Infectious Causes of Cochlear Hearing Loss Meningitis Congenital Infections

Chapter

Cochlear Hearing Loss

Adult-Onset Acquired Syphilis Human Immunodeficiency Virus Sequelae of Acute and Chronic Otitis Media Poststapedectomy Sensorineural Hearing Loss Congenital Hearing Loss Congenital Anomalies of the Inner Ear Membranous Labyrinth Malformations with a Normal Otic Capsule Membranous Labyrinth Malformations with Otic Capsule Malformations Genetic Metabolic Cochlear Hearing Loss Otic Capsule Bony Diseases Autoimmune Hearing Loss

COCHLEAR PHYSIOLOGY AND SENSORINEURAL HEARING LOSS Hearing allows us to be conscious of what is going on around us. It is always working to warn us of danger. Most important, hearing permits communication. Hearing loss affects 28 million Americans (1 out of every 10 people). The isolation from society that occurs with hearing loss can lead people to depression and behavioral problems. Understanding the pathophysiology of hearing loss necessitates an understanding of the mechanism of sound transduction in the cochlea. The cochlea acts as both a passive filter and an active filter. The passive filtering properties create a tonotopic distribution of the frequency spectrum along the length of the cochlea, based on the inverse relationship between the mass and the stiffness of the basilar membrane. The basilar membrane is narrow and stiff at the base of the cochlea, which corresponds to high-frequency tuning. At the apex of the cochlea, the basilar membrane is wider and less stiff, which corresponds to low-frequency tuning. Thus, each point along the basilar membrane has a characteristic frequency to which it is tuned.

John S. Oghalai, MD

Active filtering properties are found only in the mammalian cochlea. A positive feedback loop locally amplifies sound vibrations at each characteristic frequency along the basilar membrane. This cochlear amplifier dramatically increases cochlear sensitivity (the ability to hear quiet sounds) and improves frequency selectivity (the ability to distinguish between adjacent frequencies). Outer hair cell electromotility (discussed below) is the source of the active filtering of the mammalian cochlea. The organ of Corti is a highly organized structure (Fig. 37-1). There are a single row of inner hair cells and three rows of outer hair cells. These cells run the length of the cochlea and are positioned on top of the basilar membrane by supporting cells. There are tight junctions between the apex of the hair cells and the surrounding supporting cells, which form the barrier between the endolymph and the perilymph (the reticular lamina). Movement of the stapes footplate at a certain frequency produces a traveling wave that maximally vibrates the section of the organ of Corti tuned to that frequency. This leads to sharing forces between the hair cells and the tectorial membrane, which deflects stereocilia and depolarizes hair cells. 589

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Additionally, inner hair cell and supporting cell damage begins.10 When hair cells die, a permanent hearing loss results because mammalian cochlear hair cells do not regenerate. With extremely loud noise trauma, such as from a blast injury, there is widespread fracture of the tight junctions between cells in the organ of Corti, as well as damage to Reissner’s membrane, the basilar membrane, and the pillar cells. This can lead to mixing of endolymph and perilymph, resulting in a severe sensorineural hearing loss. Other evidence of cochlear trauma secondary to noise exposure is changes in the terminals of cranial nerve VIII. There can be swelling of dendritic terminals at the inner hair cell junction, as well as high densities of synaptic vesicles in efferent nerve terminals on the outer hair cells. Following a noise exposure that leads to loss of outer and inner hair cells, there is retrograde degeneration of VIIIth nerve fibers. The interaction between ototoxic drugs and noise is important. Administration of a low dose of cisplatin to laboratory animals may cause no hearing loss and only minimal hair cell damage. When the same dose of drug is delivered in concert with a mild noise exposure, however, the animal may show dramatic hair cell loss and hearing threshold shifts.11 The pathophysiology of this potentiation is unclear. In contrast, loop diuretics, which cause reversible threshold shifts due to loss of the endolymphatic potential, and salicylate, which inhibits outer hair cell electromotility, do not potentiate noiseinduced hearing loss.12 An interesting conundrum in the investigation of patients with acoustic trauma is a large intersubject variability to noise-induced hearing loss. Patients can be characterized as having “tough” ears or “tender” ears based on their susceptibility.13 Although one protective mechanism against noise damage is the middle-ear muscular reflex, efferent olivocochlear projections from the brainstem to the outer hair cells also may affect a person’s susceptibility to noiseinduced hearing loss. Animal studies have demonstrated that cutting the efferent fibers to the ear reduces the intersubject variability to noise trauma.14 Efferent fibers probably work to reduce cochlear trauma during noise exposure by becoming activated in the presence of loud noise. In this way, loud noise acts to hyperpolarize the outer hair cells, reduce their electromotile response, and turn down the gain of the cochlear amplifier.

PRESBYCUSIS Presbycusis is defined as progressive sensorineural hearing loss associated with aging. Several major studies have shown the epidemiology of presbycusis. The U.K. National Study of Hearing Disorders in 1995 involved more than 48,000 patients.15 Twenty percent of patients had hearing impairments greater than 25 dB, 75% of these being older than 60 years. This large cross-sectional study demonstrates that the majority of sensorineural hearing loss occurs in the elderly. Longitudinal studies of hearing loss accounting for age, sex, and noise exposure history demonstrate that 97% of subjects experienced a decrease in hearing over time.16 Patients younger than 55 years

lost hearing at an average rate of 3 dB per decade, and patients 55 years and older lost hearing at a rate of 9 dB per decade. Thus, hearing declines gradually in the majority of the population and the rate of decline accelerates over time. The pathophysiology of presbycusis appears to be predominantly a peripheral phenomenon (i.e., cochlear and spiral ganglion degeneration). Although there is clearly a generalized degeneration of the central nervous system during aging, there is significant evidence against a central lesion being the main contributor to presbycusis. Although few, some elderly people have normal pure tone average and word recognition scores, which suggests that CNS atrophy does not cause hearing loss.17 Physiologic studies concur in that otoacoustic emissions diminish with age, lending evidence toward the hypothesis of presbycusis being associated with peripheral degeneration.18 The best designed studies have been performed by Schuknecht.19–21 By correlating pure tone audiometry and temporal bone histologic findings in patients with presbycusis, four types of presbycusis can be defined: sensory (hair cell loss), neural (spiral ganglion cell loss), metabolic or strial (loss of the stria vascularis), and mechanical (change in the mechanical stiffness of the cochlear duct with aging). Sensory presbycusis has histologic findings of lipofuscin deposition in hair cells and loss of hair cell stereocilia. Neural presbycusis has a reduction in the number of spiral ganglion neurons. About 2100 out of 35,000 spiral ganglion neurons are lost every decade.20,21 Clinically significant sensorineural hearing loss develops only after about 50% of the neurons are lost.20,21 Metabolic presbycusis has histologic findings that demonstrate a thinning of the stria vascularis.19–21 This presumably diminishes the endolymphatic potential. Mechanical presbycusis (cochlear conductive) is thought to be due to a change in the mass and stiffness of the cochlear duct and basilar membrane. However, no clear histologic abnormality has been identified. Animal models for presbycusis have been developed by maintaining animals in quiet environments as they age. Serial histologic and electrophysiologic studies can then be performed on the cohort. Studies in the chinchilla demonstrate that inner hair cells degenerate at a rate of about 0.29% per year and outer hair cells degenerate at a rate of 1% per year.22 There is also mild strial and spiral ganglion atrophy. Studies involving the Mongolian gerbil have been mixed. Some investigators have found that a majority of age-related changes occur at the hair cell level, with the stria vascularis and spiral ganglion being spared.23 Others have found the opposite.24,25 Laboratory data about the interaction of noise and age are sparse. Because of the large variability in age-related hearing loss, it is often difficult to distinguish the influences of noise and age. However, aged animals and young animals appear to be equally susceptible to noise.24 The etiology of presbycusis is unclear. Studies with the Framingham cohort show no association between hypertension or cardiovascular disease and presbycusis.26,27 Additionally, atherosclerosis, hypercholesterolemia, and hyperlipidemia do not appear to be associated with presbycusis.18 Another potential etiology of presbycusis is related to repeated exposure to low-intensity noise, not

Cochlear Hearing Loss

loud enough to produce temporary threshold shifts. Constant sound exposure causes an increase in calcium in the hair cells and spiral ganglion cells. A high rate of calcium influx could lead to cell toxicity and possibly cell death. The association of noise and presbycusis has been carefully studied by comparing cross-sectional studies of noise-exposed and nonnoise-exposed populations. Nonnoise-exposed populations include the Mabaan tribe from the Sudan, the Todas tribe in South India, and islanders in North Scotland. The nonnoise-exposed populations had significantly greater preservation of hearing into old age than did subjects from noisy industrial centers.28–30 Finally, a genetic explanation for presbycusis has been sought. Although multiple genes have been identified with congenital hearing loss, no specific genes have been associated with human presbycusis. It is possible that mitochondrial gene mutations that result in progressively lower production of adenosine triphosphate (ATP) lead to hearing loss. Spiral ganglion, stria vascularis, and hair cells have large energy requirements and may be most affected by this type of mutation. In summary, although an exact etiology for presbycusis has not been identified, many possibilities exist. In all likelihood, a combination of these factors render people susceptible to progressive cochlear degeneration and sensorineural hearing loss associated with aging. Certainly, the genetics and history of noise exposure for any individual play a large role.

OTOTOXICITY Aminoglycosides It is estimated that 6% to 16% of patients who receive aminoglycosides suffer sensorineural hearing loss and an equal percentage suffer some form of vestibular dysfunction. Aminoglycosides have varying degrees of vestibular and cochlear toxicity. The more vestibulotoxic aminoglycosides are streptomycin, tobramycin, and gentamycin, whereas the more cochleotoxic aminoglycosides are kanamycin, neomycin, and amikacin. A multistep hypothesis of aminoglycoside ototoxicity has been proposed.31 The first step is an electrostatic attraction of the positively charged aminoglycoside molecule to the negatively charged hair cell plasma membrane.32 The aminoglycoside is then transported into the cell and binds to phosphatidyl-inositol biphosphate. Toxicity is thought to occur through free radical formation. In the vestibular system, type I hair cells are more prone to aminoglycoside toxicity than type II hair cells.33 In the cochlea, outer hair cells are much more sensitive to aminoglycosides than inner hair cells. Outer hair cell damage first occurs at the base of the cochlea, leading to high-frequency hearing loss. With continued intake of aminoglycosides, the damage progresses down the length of the cochlea, causing low-frequency hearing losses as well.33 Genetic mutations can predispose certain individuals to aminoglycoside ototoxicity. Deafness has even been reported after a single dose. There is a maternal form of inheritance for this susceptibility and genetic mutations in the 12S ribosomal RNA gene in the mitochondrial RNA have been identified. Currently, the two known mutations

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(A155G and D961Cn) account for roughly 17% to 33% of familial aminoglycoside ototoxicity.34 Further mutations have yet to be identified. According to one major study,35 predictors of the development of aminoglycoside ototoxicity include the type of aminoglycoside used, duration of therapy, presence of bacteremia, presence of fever, liver dysfunction, and the serum urea nitrogen/creatinine ratio. Factors that do not predict the development of ototoxicity include the plasma drug level, aminoglycoside type, use of furosemide, diabetes, age, renal function, initial hearing acuity, hematocrit value, and the presence of shock. It should be noted that not all studies agree with all of these findings. Neonates appear to have an increased risk of aminoglycoside ototoxicity.36 Additionally, some data suggest that noise exposure can potentiate aminoglycoside ototoxicity.37 The monitoring of aminoglycoside plasma concentration is an important part of most therapeutic uses of this agent. Aminoglycosides have a low therapeutic index and their bactericidal efficacy is related directly to their peak concentration level (concentration-dependent killing). In contrast, aminoglycoside toxicity is related to the total amount of drug given.38 The pharmacokinetics f aminoglycosides are relatively simple. These drugs are hydrophilic, have low-protein binding, and are excreted renally. Their volume of distribution in the body is roughly that of the extracellular fluid and the clearance is that of the glomerular filtration rate. The half-life of this drug in people with normal renal function is roughly 2.5 hours. However, systemic infections are associated with variable levels of hydration and increased permeability of normal biologic barriers. Therefore, the extracellular fluid volume and the clearance rate may change during therapy.39 Aminoglycoside nephrotoxicity is usually reversible, but ototoxicity is usually irreversible. Although the best dosing regimen for most antibiotics would be to have the concentration of the drug at a constant level above the minimum inhibitor concentration of the bacteria that it is killing, the desired concentration versus time profile for aminoglycosides is that of a high-peak concentration (for increased efficacy) followed by low trough concentration (to prevent accumulation and toxicity). Therefore, a large dose is used. However, the dosing interval is substantially longer than the drug’s half-life. During traditional aminoglycoside therapy (multiple daily doses), it is routine to monitor both a peak and a trough concentration, with the peak concentration reaching roughly 6 to 10 milligrams per liter, and the trough concentration being less than 2 milligrams per liter. Recently, there has been a change to once daily dosing of aminoglycosides with the same total daily dose. Measuring the peak plasma concentration with this regimen can help to identify the actual level of drug being delivered. However, a trough level is not needed in patients with normal renal function because all of the drug should have been excreted after 24 hours. Currently there are no clearly established therapeutic ranges for once-daily dosing39; however, the risk of ototoxicity or vestibular toxicity with this regimen is no higher than that with conventional dosing protocols.40,41 Providing a correct dose of drug to patients with renal impairment and to elderly patients with impaired

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glomerular filtration is crucial because there can be buildup of drug over time. Aminoglycoside ototoxicity is different from aminoglycoside nephrotoxicity in that ototoxicity is not associated with high plasma concentration of drug.42 This may be because the penetration of aminoglycoside into and elimination from the labyrinth is much slower than its corresponding plasma or cerebrospinal fluid concentrations.43,44 However, one similarity between ototoxicity and nephrotoxicity is that similar therapies may protect both the cochlea and the kidney from aminoglycoside toxicity.45 Coadministration of iron chelators and free radical scavengers with aminoglycosides has been shown to reduce hearing loss and nephrotoxicity in animals.46,47 To date, there is no firm evidence to suggest that free radical scavengers reduce aminoglycoside ototoxicity in humans.

Cisplatin and Carboplatin Cisplatin and carboplatin are antineoplastic agents that have permanent high-frequency hearing loss as a frequent side effect. Cisplatin is similar to aminoglycosides in that it is both nephrotoxic and ototoxic, presumably because of the formation of iron-induced free radicals48 and apoptosis.49 Histologically, cisplatin causes outer hair cell degeneration.50,51 The damage starts in the basal turn of the cochlea, producing a high-frequency hearing loss. As the duration of treatment and total dose increase, further hearing loss develops as outer hair cells in the lowerfrequency region of the cochlea become involved.52 Interestingly, carboplatin has similar effects in most mammals; however, in the chinchilla, it appears to cause only extensive inner hair cell damage and little, if any, outer hair cell damage.51 The reason for this is unknown. Younger children seem to be more affected than older patients.53,54 The ototoxicity is enhanced with the concomitant administration of loop diuretics.36

Loop Diuretics The loop diuretics, including furosemide and ethacrynic acid, are direct inhibitors of the Na+-Cl−-K+ cotransport proteins found in both the tubular cells in the loop of Henle and in the cells of the stria vascularis.55 Because the stria vascularis is responsible for maintaining the endolymphatic potential as well as the high potassium level in the endolymph, loss of ionic transport causes reversible hearing loss. With higher and higher doses of loop diuretics, eventual permanent damage can occur; however, this is uncommon. The exact mechanism of the permanent ototoxicity associated with loop diuretics is unclear.

Salicylate and Quinine Salicylate and quinine cause reversible sensorineural hearing loss. This is best characterized with salicylate (a metabolite of aspirin, which is acetylsalicylic acid). Salicylate is known to reversibly block outer hair cell electromotility56 and disrupt membranous structures in the outer hair cell. These effects inhibit the active process in the cochlea responsible for the “cochlear amplifier.” Clinically, this is seen as a reversible moderate sensorineural

hearing loss of roughly 40 dB to 50 dB. The dose of aspirin needed to produce a measurable hearing loss is on the order of 10 to 12 325 mg tablets per day.57 The exact mechanism of quinine ototoxicity is unclear, but is thought to pertain to the disruption of normal outer hair cell functioning. Its effects are also reversible.

Topical Otic Preparations Common topical otic preparations include ototoxic agents such as aminoglycosides, antifungals, and antiseptics (including ethanol and povidone-iodine). Although topical ototoxicity has been demonstrated in abundant experimental studies with animals, information regarding human topical ototoxicity is minimal.58 It appears that ototoxicity occurs during absorption of the drug through the round window membrane, through fissures around the oval window, or through vascular channels. The round window membrane in humans is much thicker than that in the chinchillas and guinea pigs, common animals in studies (40 to 70 microns compared to 10 to 14 microns).59 Additionally, in humans the round window niche is deep and there are often mucosal folds partially covering it, whereas this is not the case in the chinchilla and guinea pig. Finally, humans who are receiving topical otic drops most commonly have chronic otitis media with inflamed middle-ear mucosa, which is thought to have a higher absorbability than uninflamed mucosa and likely reduces the quantity of drug reaching the inner ear. Interestingly, a survey of 2235 otolaryngologists found that 3.4% admitted to having witnessed irreversible cochlear damage as a result of ototoxic antibiotic drops.60 However, there is no demonstrated proof of ototoxicity in human subjects with topical otic preparations used to treat chronic otitis media. Of course, intratympanic gentamicin certainly can cause hearing loss when used to treat vertigo, so clearly the potential for ototoxicity exists. The use of topical fluoroquinolones does not demonstrate any ototoxic effect in laboratory animals61 and is rapidly becoming the drug of first choice for the treatment of chronic otitis media in patients with a perforated tympanic membrane.

Chemical Teratogens Although never available in the United States, even a single dose of thalidomide taken by the mother during a susceptible period of fetal development can produce dramatic fetal defects. Defects in the temporal bone include atresia of the ear canal, sensorineural hearing loss, and paralysis of the facial nerve.62 Findings can include malformation of the cochlea and absent acoustic and vestibular nerves. Ethanol is a highly abused drug throughout the world. Sensorineural hearing loss is associated with fetal alcohol syndrome. Most studies suggest that more than two alcoholic drinks per day by the mother is the threshold for teratogenicity.62 Fetal alcohol syndrome is characterized by a series of neurologic and behavioral aberrations, in addition to craniofacial dysmorphic features. These children have a high incidence of external- and middle-ear abnormalities and a 29% incidence of bilateral sensorineural hearing loss.63

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Isotretinoin is a retinoid used for the treatment of refractory and cystic acne. Taken by pregnant mothers, it can cause severe fetal deformities. These include shortening of the cochlea, a nearly total absence of spiral ganglion cells, and enlargement of the sacculus and utricle.64

Monitoring during Ototoxic Drug Administration There are no universally recognized protocols to monitor patients for early evidence of ototoxicity. Many experts recommend weekly audiograms during the administration of ototoxic medications; however, the major morbidity is actually not hearing loss, but vestibular toxicity. Therefore, even though conventional audiometry is the simplest monitoring technique, it has the disadvantage of not being very sensitive.65 Because most ototoxic agents cause a predominantly high-frequency hearing loss, a more sensitive test might be high-frequency audiometry (above 8 kHz). Additionally, otoacoustic emissions could be measured, but detailed studies as to the sensitivity of otoacoustic emissions when used to screen for ototoxicity have not been performed. Monitoring for vestibular toxicity is limited to serial electronystagmography and rotary chair testing. These tests are almost never performed during the administration of ototoxic medications because of their variability and low sensitivity. In addition, it is very difficult to perform these tests in debilitated patients. Overall, drug-induced ototoxicity can best be prevented by using strategies similar to those used to prevent nephrotoxicity. This involves keeping the patient well hydrated and monitoring the patient’s renal function. If the plasma drug concentration reaches toxic levels, it is important to consider using hemodialysis or peritoneal dialysis to remove the drug rapidly in order to limit toxicity. Although a decrease in creatinine clearance definitely increases the risk of ototoxicity, the literature is unclear as to the importance of avoiding loop diuretics and loud noise exposure during ototoxic medication therapy.

IDIOPATHIC SUDDEN SENSORINEURAL HEARING LOSS Sudden sensorineural hearing loss is defined as a threshold increase of more than 20 dB over at least three contiguous audiometric frequencies occurring within 3 or fewer days. Idiopathic sudden sensorineural hearing loss is a diagnosis of exclusion; other causes of sudden hearing loss must be ruled out. These include cerebellopontine angle tumors,66 autoimmune disease, multiple sclerosis, infectious etiologies,67 intralabyrinthine hemorrhage, and perilymph fistula. Additionally, ototoxicity and noise-induced hearing loss must be considered in the differential diagnosis. Two theories behind the etiology of idiopathic sudden sensorineural hearing loss exist.68 The first is vascular compromise to the inner ear through thrombosis, hemorrhage, or vascular spasm. In support of this hypothesis, the concentration of oxygen in the perilymph from patients with idiopathic sudden sensorineural hearing loss is 30% lower than in controls.69 Also, disturbances in microcirculatory blood flow have been identified in

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patients with idiopathic sudden sensorineural hearing loss.70 The second theory of idiopathic sudden sensorineural hearing loss is viral inflammation of the cochlea and/or auditory nerve. Many patients report having had an upper respiratory syndrome 1 to 2 weeks before onset of their hearing loss. Some patients have seroconverted to a variety of viruses, including influenza B, mumps, measles, rubella, cytomegalovirus, and varicella-zoster. All of these viruses can cause a viral cochleitis.71 Histologic study of temporal bones with idiopathic sudden sensorineural hearing loss demonstrates features consistent with viral infection, including hair cell loss, ganglion cell loss, strial atrophy, and inflammatory cochleitis.72 The prognosis of idiopathic sudden sensorineural hearing loss is highly variable. Overall, untreated patients have a spontaneous recovery rate of about 65% to “functional hearing.”73,74 Recovery, however, appears to depend on the severity and the pattern of the hearing loss. Patients with a predominantly low-frequency loss have the best prognosis for recovery, while those with a high-frequency hearing loss have a worse prognosis. Patients with a flat profound hearing loss across all frequencies have the worst prognosis.73 Although the spontaneous recovery rate is high, the likelihood of recovery declines with time. If a patient is to recover from an idiopathic sudden sensorineural hearing loss, it usually occurs within the first few weeks, and typically no improvement is noted after 1 to 2 months. Luckily, long-term follow-up studies have shown that if improvement does occur, the risk of further hearing loss is low.75 The treatment of sudden sensorineural hearing loss remains confusing and controversial. Countless studies have been performed purporting to have identified the ideal treatment regimen for this disease, only to have a later study report the opposite. The difficulties in analyzing this disease include its rarity, highly variable prognosis, variable time of presentation, and variable severity of hearing loss. Additionally, the spontaneous recovery rate is quite high. Because of this confusion, many physicians manage this disease with many simultaneous treatments, hoping one will work—in other words, a “shotgun” approach. As we move toward evidence-based medicine, it is important to study and characterize this disease further with rigid statistical criteria rather than base our current treatment protocols on anecdotal evidence and hypotheses. The following summaries describe many of the current treatments for idiopathic sudden sensorineural hearing. It is important to note that although statistically significant differences between treated and untreated groups may have been reported, further studies have not backed this up in the majority of cases. Corticosteroid therapy is among the few therapies to treat patients with idiopathic sudden sensorineural hearing loss to have demonstrated effectiveness by randomized, prospective study.76–82 Not all studies agree with this conclusion, however.83,84 The specific action of steroids is based on its anti-inflammatory properties and therefore should be beneficial in infectious, inflammatory, and immune-mediated conditions. A common therapeutic regimen is 80 mg of prednisone per day for 4 days, 60 mg per day for 4 days, 40 mg per day for 4 days, 20 mg per day for 4 days, and then discontinue the prednisone. Some authors have advocated transtympanic administration of the steroid

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in patients who do not improve on oral steroids.85 Antiviral therapy has not been shown to be beneficial in the management of idiopathic sudden sensorineural hearing loss. A recent randomized double-blinded, placebo-controlled, prospective, multicenter clinical trial comparing patients who received prednisone and a placebo to patients who received prednisone with valcyclovir demonstrated that the antiviral medication did not provide any more benefit than steroid therapy alone.86 Treatments to optimize cochlear blood flow include vasodilatory agents (histamine, papaverine, verapamil, etc.) or drugs that decrease blood viscosity (dextran, pentoxifylline, procaine, and heparin). None of these agents appear to offer a significant improvement in hearing recovery over controls.68,87–91 The theory behind using vasodilatory agents can be questioned because these drugs predominantly cause a peripheral vasodilation. Since cerebral blood flow has strong autoregulatory mechanisms, vasodilators may cause a systemic hypotension and actually reduce blood flow from the inner ear. Carbogen inhalation therapy (95% oxygen and 5% carbon dioxide) is one of the few vasodilators that override intracranial autoregulation. Although some studies have demonstrated an improvement in the outcomes of patients with idiopathic sudden sensorineural hearing loss with carbogen,69,92,93 others have demonstrated no improvement.84,94 The efficacy of carbogen remains controversial. A stellate ganglion block is another therapy thought to elicit vasodilation within the inner ear since sympathetic fibers to the inner ear vasculature originate from the stellate ganglion. No study convincingly demonstrates that a stellate ganglion block improves recovery over the natural rate of spontaneous recovery.95,96 Other therapies, including hyperbaric oxygen (to increase cochlear oxygen levels), vitamins (free radical scavengers), gingko biloba, and magnesium have been studied. 97 None of these therapies have shown significant efficacy in the management of idiopathic sudden sensorineural hearing loss.68

TEMPORAL BONE TRAUMA Temporal Bone Fracture Temporal bone fractures represent roughly 20% of skull fractures. Risk factors include being male and younger than 21; more often than others, this population is involved in risky activities that predispose them to blunt head trauma. The most common causes are motor vehicle accidents, falls, bicycle accidents, seizures, and aggravated assaults. Penetrating trauma, predominantly gunshot wounds, are much more damaging to the temporal bone than is blunt trauma. Labyrinthine fractures are common after a gunshot wound to the temporal bone. Blunt trauma to the squamous portion of the temporal bone often results in a longitudinal fracture. Longitudinal fractures follow along the axis of the external auditory canal to the middle-ear space, and then the course anteriorly along the geniculate ganglion and eustachian tube, ending near the foramen lacerum. The otic capsule is spared in a longitudinal temporal bone fracture. In contrast, a blow to the occipital skull often goes through foramen magnum and

results in a transverse fracture of the temporal bone. Transverse fractures course directly across the petrous pyramid, fracturing the otic capsule, and then extend anteriorly along the eustachian tube and geniculate ganglion as well. Longitudinal temporal bone fractures represent 80% and transverse temporal bone fractures represent 20% of temporal bone fractures. Sensorineural hearing loss and vertigo are found in patients who sustain a transverse temporal bone fracture with otic capsule involvement. Audiogram usually demonstrates a complete sensorineural hearing loss in that ear. Clinical examination also reveals the patient to have nystagmus, consistent with a unilateral vestibular deficit. Interestingly, sensorineural hearing loss can be sustained without otic capsule fracture if a labyrinthine concussion occurs. This is thought to involve shearing of the membranes or hair cell stereocilia caused by the rapid acceleration and deceleration forces in the inner ear. Labyrinthine concussion typically manifests as a high-frequency hearing loss.

Perilymphatic Fistula Patients with perilymphatic fistula usually present with disequilibrium and vertigo, although some also have hearing loss, tinnitus, headache, and aural fullness. Patients may state that their symptoms are least intense in the morning but that they worsen progressively during the day. Most important, symptoms become much worse with any type of coughing, sneezing, or straining. Occasionally, altitude change such as going up and down in an airplane or in an elevator can precipitate symptoms. Patients often complain of Tullio’s phenomenon, whereby loud noises precipitate a vertiginous attack. Perilymphatic fistula is difficult to diagnose. The fistula test can be performed by insufflating air into the external auditory canal and observing the patient for evidence of nystagmus. This test is very insensitive, and is positive in only about 50% of patients with a fistula. Additionally, it is not specific because many patients without a fistula experience dysequilibrium during the test. Serial audiometry should demonstrate a fluctuating sensorineural hearing loss. Vestibular testing may demonstrate a unilateral deficit. Nystagmus brought on by straining can be documented with electronystagmographic (ENG) monitoring and evaluation. Computed tomography (CT) is not particularly useful in the identification of a perilymphatic fistula. Its sensitivity is estimated at 20%; however, if a fistula is identified on CT scan, this is obviously highly specific. The only definitive way to make the diagnosis of perilymphatic fistula is surgical exploration with visualization of the leak. Even this is not necessarily definitive because it is quite difficult to verify that small amounts of clear fluid in the middle-ear cavity represent a perilymphatic leak and not serous transudate from the middle-ear mucosa. Fluid suspicious for perilymph can be sampled on a Gelfoam pledget and tested for β2-transferrin testing, a protein found only in cerebrospinal fluid (CSF) and perilymph. The most common etiology of perilymphatic fistula is head trauma. This may be either following a temporal bone fracture involving the otic capsule or with stapes subluxation into the oval window. Barotrauma during scuba diving, a rapid descent in an airplane, an explosion,

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or a difficult childbirth can also cause perilymphatic fistula. Postsurgical perilymphatic fistula is also a wellrecognized entity. This can occur after stapedectomy if the oval window fails to seal appropriately. Poor surgical technique while performing a mastoidectomy can lead to iatrogentic lateral canal fistula. Additionally, an expanding cholesteatoma can erode into the lateral semicircular canal or cochlea, causing a fistula. Finally, patients may present with congenital perilymphatic fistula. These patients typically have stapes footplate anomalies or other temporal bone anomalies identified on CT scan. The superior semicircular canal dehiscence syndrome, with a fistula from the superior canal into the intracranial space, may be identified by CT scan. Fluctuating, but progressive, sensorineural or mixed hearing loss occurs in patients with a perilymph fistula. Also, these patients have progressive dysequilibrium. Since there is a fistula from the middle-ear space to the inner ear, an episode of acute otitis media is worrisome because bacteria in the middle ear can easily enter the inner ear and CSF. This can lead to permanent sensorineural hearing loss or meningitis. Treatment is based on conservative therapy. The patient should be on bedrest with the head elevated for 3 to 6 weeks and take stool softeners, and serial audiograms should be obtained to follow up for evidence of disease progression. If symptoms persist or the sensorineural hearing loss worsens, surgical treatment is indicated. One option is to simply draw blood from the patient’s arm and inject it through the eardrum into the middle-ear space. This blood seal often allows a fistula to heal. Alternatively, a middle-ear exploration can be performed. This is done by a transcanal approach with elevation of the tympanomeatal flap and careful examination of the oval and round windows. If a defect is noted, a graft of fascia or muscle should be laid over the defect. Many surgeons place fascia around both the oval window and the round window even if a fistula is not definitively seen because defects are quite difficult to detect.

Diving Barotrauma Barotrauma during diving most commonly affects the middle ear. It can involve hemorrhage and rupture of the tympanic membrane, along with ossicular chain dislocation. It is associated with a conductive hearing loss and, in most cases, resolves spontaneously with minimal sequelae. In contrast, inner-ear barotrauma can lead to permanent sequelae. There are two types of inner-ear barotrauma: (1) perilymphatic fistula and (2) inner-ear decompression sickness.98,99 Perilymphatic fistula can occur through either the round or oval window because of the pressure gradient between the perilymph of the inner ear and the middle-ear cavity. Symptoms include the acute onset of vertigo, sensorineural hearing loss, tinnitus, nausea, and vomiting. Treatment includes reducing intracranial and perilymphatic pressures by bedrest, elevation of the head of the bed, and the use of stool softeners. If conservative treatment is ineffective, after 1 week surgical exploration of the middle ear can be performed. Inner-ear decompression sickness is caused by the release of nitrogen gas bubbles into the bloodstream and tissues

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during ascent after a prolonged dive. Most divers breathe compressed air, which includes both oxygen and nitrogen, and the partial pressure of these gases increases in the tissues as the dive deepens. Although the oxygen is metabolized during diving, the nitrogen is not and becomes dissolved in the body’s tissues. During rapid ascent, the partial pressure of nitrogen decreases and the dissolved nitrogen is released as bubbles in the bloodstream and other tissues.100 Decompression sickness is classified into types 1 and 2. In type 1 decompression sickness, symptoms are mild and include fatigue or pain in the joints or muscles. Type 2 decompression sickness is more severe, with injury to the lungs, inner ear, and central nervous system. Within the inner ear, nitrogen bubbles can injure the delicate structures either by mechanical disruption of the membranes of the inner ear or through labyrinthine artery occlusion.101 Studies in guinea pigs have shown that the primary damage during hyperbaric exposures includes inner-ear hemorrhage and damage to the cochlear hair cells.102 When a patient is suspected of having inner-ear decompression sickness, the dive profile should be evaluated, including the depth of the dive, the time at the bottom, and the number of earlier dives. All patients with cochleovestibular symptoms after diving should be considered to have type 2 decompression sickness and treated accordingly. This includes the use of 100% oxygen as immediate first aid during transport of the patient to a recompression facility.99 If air transport is required, the patient should be flown at an altitude lower than 1000 feet to reduce symptom exacerbation. The recompression protocol includes initial recompression to 60 feet of salt water with 100% oxygen for 60 minutes, followed by decompression to 30 feet of salt water for two additional periods while breathing a mixture of pure oxygen and air.100 This recompression therapy reduces the size of the bubbles, allowing their resorption and dissipation. Other supportive therapies reported to be useful in the treatment of inner-ear decompression sickness include steroids, diuretics, low-molecular-weight dextran, heparin, and diazepam. Long-term follow-up studies of scuba divers who sustained inner-ear barotrauma and continue to dive against medical advice suggest that no further deterioration of cochleovestibular function occurs after these patients were counseled as to how to equalize middle-ear pressure.103

INFECTIOUS CAUSES OF COCHLEAR HEARING LOSS Meningitis By the age of 3 years, the percentage of children with an acquired hearing impairment out of all those children with bilateral profound deafness is 20%. Of those with acquired impairments, the hearing loss of 90% is due to postmeningitic sequelae.104,105 Persistent sensorineural hearing loss has been documented in 10.3% of 185 infants and children with acute bacterial meningitis.106 The risk of deafness after bacterial meningitis is most frequent following infection with Streptococcus pneumoniae (31.8%) compared

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to Haemophilus influenzae and Neisseria meningitidis (7.5%).104,107 The incidence of bacterial meningitis is dropping because of immunization against Haemophilus influenzae type b.107 There have also been a few documented cases of hearing impairment after viral meningitis, although this appears to be quite rare. Hearing impairment after meningitis can have several causes. Most commonly, a suppurative labyrinthitis occurs during the episode of acute meningitis due to direct spread of the infection from the subarachnoid space to the inner ear via the cochlear aqueduct. This results in destruction of the sensory structures of the inner ear, and no hearing recovery. If only a serous labyrinthitis occurs, partial recovery of hearing is possible. Meningitis can also lead to ischemia of the auditory nerve or brainstem neuron, and result in hearing loss. Finally, sensorineural hearing loss after meningitis can be caused by ototoxicity from the antibiotics used to treat the meningitis, often an aminoglycoside. The administration of steroids to patients with pneumococcal meningitis does not affect the rate of postmeningitic sensorineural hearing loss.108 It is important to get an audiologic assessment on every patient with meningitis. This should start during their first admission to the hospital if possible and should be followed postoperatively. A common sequela of postmeningitic sensorineural hearing loss is labyrinthine ossificans. Presumably, the inflammation in the cochlea leads to a fibrotic reaction, which in time ossifies. This typically happens in the first few months after the meningitis has resolved. Studies have shown that the intense inflammatory response begins around the area of the cochlear aqueduct.109 Earlier, rather than later, cochlear implantation is suggested in patients with postmeningitic deafness because of the difficulty in inserting the cochlear implant in an ossified cochlea.

Congenital Infections Cytomegalovirus (CMV) infection has been found in 0.2% to 2.2% of all newborn children in the United States and is the most common intrauterine infection.107 One-third of pregnant women are serial negative for CMV during pregnancy and about 5% of these women become infected during pregnancy. Of those 5%, one-fourth will transmit the infection to their fetuses. Up to 10% of children with congenital CMV infection demonstrate systemic symptoms at birth and 61% of this group of patients develop sensorineural hearing loss.110 The hearing loss can begin soon after birth but usually progresses over the next 5 years. It may be unilateral or bilateral, and occasionally it fluctuates. It is recommended that children with asymptomatic CMV infections receive regular hearing tests through childhood because of the potential for late-onset sensorineural hearing loss. Herpes simplex infection occurs in roughly 1 in 2500 pregnancies.111 Infections are caused by exposure to the herpes simplex type II virus during delivery. Children with herpes simplex infection, either disseminated or localized, usually present with symptoms within the first 3 weeks of life. All patients with a disseminated presentation of herpes simplex virus (HSV) II infection have sensorineural hearing loss, while 40% of the children with encephalitis and

25% of the children with localized infections present with hearing loss.107 The classic triad of congenital rubella includes congenital heart disease, ocular diseases (cataracts and retinopathy), and sensorineural hearing loss. If the rubella infection occurs in the second or third month of pregnancy, there is a 50% incidence of deafness, although deafness can occur even if the infection occurs late in pregnancy.112 Sixty percent of newborns with congenital rubella have subclinical infections in the neonatal period. However, 71% of these children develop disease manifestations during the next 5 years. Sensorineural hearing loss is the most common manifestation, and it affects 68% to 93% of children with congenital rubella.112 Characteristically, the sensorineural hearing loss is profound and bilateral, affecting all frequencies equally. Since the introduction of the rubella vaccine, congenital rubella infection has become quite rare. The seroconversion rate of pregnant women for toxoplasmosis is roughly 1 in 10,000 and the overall of risk of toxoplasma infection involving the fetus is 33%. At birth, 90% of these babies are asymptomatic; however, late-onset sensorineural hearing loss has been reported in 10% to 15% of these children.113 Because of the increasing prevalence of syphilis in the adult population, the prevalence of congenital syphilis has been increasing in recent years. About 50% of newborns with congenital syphilis are asymptomatic; however, hearing loss is a late manifestation that can occur even after 2 years of age.107 The hearing loss results from active inflammation and scarring within the inner ear. Sensorineural hearing loss can even begin to develop in early adulthood even though the infection initiated in utero. The onset of deafness is usually sudden, bilaterally symmetric, and profound without associated vestibular symptoms. The other common manifestation associated with congenital syphilis is interstitial keratitis, which is noted in about 90% of patients with congenital syphilis. Teens or young adults with late-onset congenital syphilis identified present with Hutchinson triad: sensorineural hearing loss, interstitial keratitis, and notched incisors.

Adult-Onset Acquired Syphilis Primary syphilis occurs initially 1 week to 3 months after inoculation as a chancre on the area of contact. Occasionally, there is large regional lymphadenopathy. The chancre usually heals spontaneously after 2 to 6 weeks and 6 months after this, the patient develops secondary syphilis. Symptoms include widespread mucocutaneous lesions, as well as constitutional symptoms. Thereafter, the untreated patient enters a period of latent subclinical infection. Fifty percent of untreated patients with latent syphilis never develop clinically evident tertiary syphilis. Of those who do develop tertiary syphilis, sensorineural hearing loss is most common in patients with evidence of neurosyphilis (80%).114 Among those with sensorineural hearing loss, there is seldom a history of primary or secondary syphilitic symptoms. Patients can present with either progressive or sudden sensorineural hearing loss, as well as vestibular symptoms. The diagnosis can be made by serologic tests of the plasma, as well as by the visualization of spirochetes in

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the CSF after lumbar puncture. Histopathologic lesions of otosyphilis are identical for congenital and acquired syphilis. This includes an obliterative endarteritis and mononuclear infiltrates with varying degrees of tissue necrosis. In tertiary syphilis, there can also be perivascular round-cell osteitis of the temporal bone, productive periostitis, and gummatous periostitis/osteomyelitis. A gumma is defined histologically as an area of central necrosis with surrounding lymphocytic infiltration and vascular occlusions. Gummatous changes can be found in all of the middle-ear bones but are most frequently identified around the labyrinthine capsule. These findings can result in labyrinthine ossificans. Treatment of this disease is with long-term penicillin therapy.

Human Immunodeficiency Virus Human immunodeficiency virus (HIV) can produce sensorineural hearing loss.115,116 The prevalence of sensorineural hearing loss in this population ranges from less than 1% to 33%.117 Patients with more severe disease have an increased degree of hearing loss. Additionally, antiviral drug therapy may be associated with an increased risk of sensorineural hearing loss.118

Sequelae of Acute and Chronic Otitis Media Sensorineural hearing loss secondary to otitis media can occur under several conditions. It is quite uncommon for recurrent acute otitis media to lead to sensorineural hearing loss. However, acute labyrinthitis can occur during an episode of acute otitis media. Presumably, the causative organism traverses into the spaces of the inner ear via fissures around the oval or round windows. Initially, patients may present with vague symptoms of vertigo and slight symptoms of sensorineural hearing loss. This is thought to be due to the diffusion of toxic inflammatory mediators through the round window membrane into the inner ear. This can progress into serious labyrinthitis if organisms enter the inner ear. A full-blown, suppurative labyrinthitis can result if frank inflammatory exudate forms in the inner ear. As the degree of suppuration worsens, the patient’s chances of permanent sensorineural hearing loss increases dramatically. Labyrinthitis can also occur after a stapedectomy or stapedotomy, presumably by the introduction of bacteria through the fenestra in the oval window. Suppurative labyrinthitis after stapes surgery usually occurs within days of surgery. However, it can occur even after a long delay if a perilymph fistula exists. Sensorineural hearing loss has been demonstrated to occur in patients with chronic otitis media. Several studies have demonstrated a significant difference in hearing between the two ears in patients with unilateral chronic otitis media, both in terms of poor speech discrimination scores and higher bone-conduction thresholds in the ipsilateral ear.119–122 Although the differences are statically significant (changes in speech discrimination scores of 4% and changes in boned-conduction thresholds of 3 to 5 dB), they are minimal and probably have no clinical relevance.123,124 It is unclear why sensorineural hearing loss can develop after chronic otitis media, although presumably

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inflammatory mediators from the middle ear diffused through the round window into the inner ear. Alternatively, the presence of an occult perilymphatic fistula could produce subtle sensorineural hearing loss. Acoustic trauma from repeated loud office suctioning of the ear could produce noise-induced hearing loss. The use of potentially ototoxic topical ear drops in the affected ear could also be responsible. Ear surgery can also cause sensorineural hearing loss because of the exposure to loud drilling noise and ossicular manipulation. Finally, the difference in the ipsilateral bone-conduction threshold may not represent an actual sensorineural hearing loss. Middle-ear mass and stiffness can affect bone-conduction thresholds (similar to the phenomenon of Carhart’s notch in otosclerosis), and patients with unilateral chronic otitis media certainly can have asymmetric middle-ear mechanics.

Poststapedectomy Sensorineural Hearing Loss After stapes surgery, sensorineural hearing loss can develop. This could be due to suppurative labyrinthitis as just discussed. However, if the sensorineural hearing loss or vertigo persist beyond 5 days postoperatively or occur after an initial improvement in hearing, a poststapedectomy granuloma (reparative granuloma) should be suspected. In contrast, mild symptoms occurring within a few days of surgery are consistent with serous labyrinthitis and are relatively common. The incidence of reparative granuloma after a stapedectomy is estimated at 0.1%.125 The incidence of sensorineural hearing loss in reparative granuloma varies from 70% to 100% of patients.126 Histologically, a reparative granuloma is not actually a granuloma. It is a clump of granulation tissue with evidence of chronic inflammation.127 When a reparative granuloma is suspected, a CT scan should be obtained. Evidence of soft tissue in the oval window within the correct time frame after surgery is highly suspicious of reparative granuloma.128 Management of this entity remains controversial and can range from either conservative management with oral steroids to early surgical intervention with delicate removal of the granulation tissue. An MRI is also occasionally useful in that it will demonstrate labyrinthine hemorrhage (bright signal on T1 and T2 without contrast in the labyrinth), a perilymphatic fistula (air bubble in labyrinth), a reparative granuloma, and suppurative labyrinthitis (intense enhancement inner ear with gadolinium contrast).129

CONGENITAL HEARING LOSS Congenital Anomalies of the Inner Ear Overall, about 1 in 1000 children is born with a significant degree of sensorineural hearing loss.130 It is estimated that about 25% of these cases of hearing loss are attributed to identifiable prenatal or postnatal disease or trauma, 18% to undiagnosed genetic factors, 15% to autosomaldominant genetic mutations, 40% to autosomal-recessive genetic mutations, and 2% to sex-linked genetic mutations.131 The hearing loss may not be present at birth,

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but progress during childhood (and so be missed by newborn hearing screening).132,133 Indigent patients are at a higher risk of neonatal hearing loss than the average U.S. population and have a different risk factor profile.134 Malformations of the inner ear occur because of an arrest in normal development during embryogenesis, during the first trimester of pregnancy. This may occur because of a genetic mutation or teratogenesis. At about the fourth week of gestation, the otocyst develops from an invagination of the otic placode. It then differentiates and forms the membranous labyrinth. By the 12th week, the cochlea has fully developed. Chondrification followed by ossification occurs in the second trimester to form the otic capsule. Maturation of the sensory epithelium within the inner ear develops throughout the second trimester of pregnancy and is essentially complete by the 26th week of gestation. The management of a congenital hearing loss is frustrating in that there is little that can be done to alter the progression of the disease. Patients who sustain decrements in hearing may be treated with steroids in an effort to reduce further hearing loss; however, there is little evidence to support the efficacy of this therapy. Patients should be adequately rehabilitated with the use of hearing aids initially and if this does not prove useful, then they should be considered for cochlear implantation. The only absolute contraindications of cochlear implantation in a congenitally dysplastic ear are complete cochlear aplasia or absence of the auditory nerve. Both of these conditions can be diagnosed with the use of high-resolution CT scan of the temporal bone. Additionally, patients with congenital malformations of the inner ear are at a higher risk for CSF leak and meningitis. Families need to be counseled as to the early signs and symptoms of meningitis. Immunization against the common organisms implicated in meningitis should also be considered. Abnormalities of the inner ear can be divided in those in which the membranous labyrinth is abnormal, but the otic capsule is normal, and those in which both are abnormal.135,136 Membranous Labyrinth Malformations with a Normal Otic Capsule Malformations limited to the membranous labyrinth account for about 90% of congenital sensorineural hearing loss. These patients have normal otic capsules and hence cannot be identified by current radiographic techniques. However, it can be safely assumed that all children with congenital sensorineural hearing loss would be found to have abnormalities of their membranous labyrinth if they could be examined histopathologically, unless there is a purely central cause for their hearing loss. Complete membranous labyrinthine dysplasia (BingSiebenmann deformity) is extremely rare and may be associated with cardiac abnormalities. It can be found in the Jervell and Lange-Nielsen syndrome and in Usher’s syndrome.137 Cochleosaccular dysplasia (Scheibe’s deformity) represents the most common inner-ear abnormality that results in hearing loss. This occurs in the phylogenetically newer portion of the inner ear, while the more ancient

semicircular canals and utriculus are normal. It is often inherited as an autosomal-recessive gene and can be found in diseases such as Usher’s syndrome. There is partial or complete aplasia of the organ of Corti with collapse of the scala media. The wall of the sacculus is collapsed onto an atrophic sensory epithelium. Additionally, the stria vascularis is degenerated. Cochlear basal turn dysplasia (Alexander’s deformity) is a limited malformation of the high-frequency region of the cochlea. This condition is related to familial highfrequency sensorineural hearing loss and there is usually sufficient low-frequency hearing to allow good benefit from the use of hearing aids. Membranous Labyrinth Malformations with Otic Capsule Malformations Malformations of the otic capsule can be diagnosed by radiographic imaging. Although thin-cut CT scans are traditionally used, newer fast-spin echo T2-weighted MRI images are also quite good at demonstrating inner-ear anatomy. There is a wide spectrum of hearing disability among this patient population. Although some are completely deaf, most retain some hearing into adult life and have a slowly progressive sensorineural hearing loss. Interestingly, there is a higher risk of sudden hearing loss associated with even minimal head trauma. This is presumably because of latent weaknesses in the membranes of the inner ear or the osseous spiral lamina that are easily damaged, permitting mixture of the endolymph and perilymph. Complete labyrinthine aplasia (Michel’s deafness) is an extremely rare defect in which there is a complete absence of inner-ear structures and, therefore, total deafness. This is likely due to a developmental arrest early in gestation, before the formation of an otocyst. This defect has been seen in association with thalidomide exposure and anencephaly.138 Cochlear aplasia is absence of the cochlea with only semicircular canals present. These are usually deformed as well, however. Cochlear hypoplasia results from an arrest in development at about the sixth week of gestation. The cochlea consists of only a small bud (1 to 3 mm in diameter) protruding from the vestibule. Auditory function is quite variable and may be surprisingly good, considering the small size of the cochlea.139 Incomplete partition (Mondini’s malformation) occurs with an arrest in development at the seventh week of gestation. This is a very common cochlear malformation and it accounts for more than 50% of cochlear deformities. The cochlea is smaller than normal (5 to 6 mm in vertical height instead of the normal 8 to 10 mm). It may possess fewer turns than normal, although this is difficult to quantify by CT scanning. The interscalar septum is partially or completely absent. The severity of hearing loss is quite variable among patients and can range from normal hearing to profound deafness. In the common cavity deformity the cochlea and vestibule are confluent and form an oval space within the otic capsule. Although there may be recognizable segments of the organ of Corti on histologic evaluation of the

Cochlear Hearing Loss

specimen, overall the hair cell population is quite sparse. Hearing is typically poor. Dysplasia of the lateral semicircular canal is a common malformation and is often associated with cochlear malformations as well. The lateral semicircular canal is the most common canal to be affected by dysplasia. During its formation, the lateral semicircular canal is first a confluent broad cystic space contiguous with the vestibule. Then, a bony septum forms in the center (like a donut hole). Deformities range from no septum to a rudimentary septum to a nearly normal septum. There may be reduced caloric responses noted by electronystagmography. Hearing may be normal if the malformation is limited to the vestibular system. This deformity may be associated with Goldenhar’s syndrome.140–142 Semicircular canal aplasia is much less common than semicircular canal dysplasia and is usually associated with cochlear abnormalities. It is presumed to arise as a consequence of failure in the development of the vestibular bud before the sixth week of gestation. Large vestibular aqueduct syndrome is the most common radiographically detectable abnormality of the inner ear.143 The normal diameter of vestibular aqueduct is between 0.4 mm and 1.0 mm (measured between the common crus and the posterior face of the temporal bone). The vestibular aqueduct is said to be enlarged when its diameter exceeds 2.0 mm. Vestibular aqueduct abnormalities often accompany cochlear and vestibular organ abnormalities and are quite commonly seen in conjunction with Mondini’s deformity. Patients with large vestibular aqueduct syndrome usually have a mild sensorineural hearing loss that progressively deteriorates during childhood and early adult life. Forty percent develop profound sensorineural hearing loss. Enlargement of the cochlear aqueduct has been reported; however, most cases demonstrate a wide, funnelshaped opening from the cerebellopontine angle with no evidence of widening of the remainder of the aqueduct. Since the tube narrows to a normal diameter laterally, it is quite possible that the wide medial end is of no consequence. Hence, this entity has not been convincingly demonstrated to be clinically important.129 A wide internal auditory canal is usually of no significance clinically. However, patients with stapes fixation and a wide internal auditory canal may be noted to have a stapes “gusher” during stapes surgery (a CSF leak), particularly if the lateral end of the internal auditory canal (IAC) is widened. In patients with congenital stapes fixation, a CT scan of the temporal bone should be obtained before consideration of surgery to evaluate for this entity. A narrow internal auditory canal may indicate the absence of the VIIIth cranial nerve. This can be crucial during the consideration of cochlear implantation in patients with congenital hearing loss because a diameter of the IAC smaller than 3 mm is a strong predictor of decreased neural population. This finding is a contraindication to cochlear implantation.144

Genetic The identification of genes involved in deafness has made dramatic progress over the last several years. Prior to 1996,

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no nonsyndromic deafness genes had been cloned. To date, 70 loci have been identified as being involved in nonsyndromic deafness and more than 400 distinct syndromes are associated with hearing impairment. However, clearly many more genes remain unidentified. Although singlegene deficits probably account for more than 50% of the cases of congenital hearing loss, the pathophysiology of the genetic contribution to presbycusis has not been defined. Several animal models of genetic deafness have been created, but relatively few of these have been shown to be involved in human deafness. The limited overlap between genes that cause sensorineural hearing loss in mice and humans makes these research endeavors quite challenging. The genetic contribution to sensorineural hearing loss can be associated with several areas in the cochlea. Being unique to the inner ear, the hair cells are the most obvious potential site of involvement. There are several essential molecules for hair cell transduction, which if mutated, will cause hearing loss. These include unconventional myosins found specifically in the hair cell transduction region, including myosins VI, VIIa, and XV. Myosin VIIa mutation is associated with Usher’s syndrome type 1c. These patients are born with congenital hearing loss and develop progressive blindness. Mutations in these myosins lead to abnormal stereocilia anatomy, as well as disorganization of the stereociliary bundle.145–148 Other hair cell genes in which mutations cause deafness include cadherin-related genes (involved in cell-to-cell interactions), aspin (an actin-bundling protein), and Atp2b2 (a calcium pump in the stereocilia).145 Additionally, hair cell synaptic transmission is unique in that very accurate timing information needs to be relayed to the central nervous system. Mutations that disrupt this can cause a sensorineural hearing loss. These include the otoferlin gene (a protein located at the base of inner hair cells involved in synaptic vesicle recycling),149 and mutations in L-type calcium channels (required for calciumdependent exocytosis during synaptic transmission).150 The final site in a hair cell that might be a target for a genetic mutation that produces a hearing loss would be outer hair cell electromotility. The gene for the molecular motor responsible for electromotility has been identified (prestin),1 and there is evidence of patients who are deaf because of amutation in this gene.151 Electromotility is not found in any other cells in the body, so a mutation in this gene causes a limited clinical phenotype (i.e., hearing loss). Other targets in the outer hair cell that could inhibit electromotility include mutations in the exquisitely organized cytoskeleton or in the plasma membrane.2–4 Surprisingly, mutations in other areas of the cochlea are much more clinically relevant than hair cell mutations. Mutations that affect the endolymphatic potential are the most common cause of genetic hearing loss. These include genes important for proper functioning of the stria vascularis or for gap junctions in supporting cells that recycle ions from the hair cells back to the stria vascularis. KCNQ4 encodes a potassium channel found predominantly in outer hair cells that serves as the first step in recycling potassium after transduction. Mutations in this gene cause a dominant progressive hearing loss.152 Mutations in the Kcc4 gene for a potassium-chloride cotransporter protein

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found in supporting cells also causes deafness.73 Connexin genes form gap junction proteins, and mutated gap junction proteins do not permit ion recycling mutations. Mutations in connexin genes are quite frequently involved in human genetic deafness.153–157 The pendrin gene is expressed in the endolymphatic duct and sac, and is mutated in Pendred’s syndrome.158–160 The pendrin protein acts as an iodide-chloride transporter and may be involved in endolymph homeostasis. Finally, defects may occur in the tectorial membrane matrix from mutations in genes encoding alpha tectorin (Tecta), collagen 11A2 (COL 11A2), and otogelin (otog),145 producing ultrastructural deformities of the tectorial membrane and hearing loss.

loss secondary to severe hypoxia is about 1% to 5%. This is a difficult number to estimate because of the multiple comorbid conditions in this complex patient population. The auditory system is very sensitive to hyperbilirubinemia. Damage occurs predominantly to the auditory nerve and brainstem nuclei, producing a sensorineural hearing loss.168 This is usually caused by Rh incompatibility between the mother and infant, although ABO incompatibility can also be the cause. Aggressive treatment of hyperbilirubinemia to lower the plasma levels reduces the risk of sensorineural hearing loss.

METABOLIC COCHLEAR HEARING LOSS

Otosclerosis is a disease of the endochondral otic capsule bone. Although usually this disease presents as a conductive hearing loss secondary to stapes fixation, sensorineural hearing loss can develop in the late stages of this disease. Pathologically, there is replacement of normal compact otic capsule bone by irregular loose or cancellous bone with an increase in the size of the haversion canals, intercellular spaces, and marrow spaces. There is an increase in the vascularity of the involved bone. If this disease involves the otic capsule bone adjacent to the cochlea, sensorineural hearing loss can develop. Although the exact reason for a sensorineural hearing loss is not known, the increased vascularity of the surrounding otic capsule bone may reduce the blood supply to the stria vascularis. Cochlear otosclerosis is described as a pure sensorineural hearing loss in the presence of otosclerosis without conductive hearing loss. This could occur if there is no fixation of the stapes, yet the otic capsule bone around the cochlea is involved with disease. By computed tomography, severe otosclerosis can be seen as lucency around the cochlea (also known as a “double ring” sign). This represents the extensive endochondral demineralization of the otic capsule. Osteogenesis imperfecta encompasses a group of connective tissue disorders with defects in bone formation. There is a high rate of bone turnover and deposition of immature, osteopenic bone that is quite weak and fragile. The most common otologic condition associated with osteogenesis imperfecta is hearing loss. The hearing loss is mixed in 54% of cases, purely conductive in 24%, and sensorineural in 22%. Usually, the hearing loss is noted between the second and third decades of life. Temporal bone CT scan findings in osteogenesis imperfecta are similar to those found in severe cochlear otosclerosis, with lucency of the otic capsule bone surrounding the cochlea. Paget’s disease is another disease of bone that can cause sensorineural hearing loss. Involvement of the otic capsule causes hearing loss in about 50% of sufferers. The initial finding is usually conductive hearing loss due to stapedial ankylosis similar to otosclerosis, although most patients do end up developing sensorineural hearing loss as the otic capsule bone surrounding the cochlea becomes involved. Fibrous dysplasia of the temporal bone may cause a conductive hearing loss by impinging on the ossicular chain or via external auditory canal stenosis. It does not involve the otic capsule. However, compression of the internal auditory canal could occur, with the potential for sensorineural

Renal disease is associated with sensorineural hearing loss. Many enzymatic functions of the kidneys and the stria vascularis are similar. The most important is ion transport. Patients with renal disease can have hearing loss because of disorders of fluid and electrolyte balance. It is possible that altered plasma electrolyte concentrations compromise the ability of the stria vascularis to produce the endolymphatic potential. However, the exact pathophysiology is not known. Additionally, it has been shown that distal renal tubular acidosis, an autosomal-recessive inherited syndrome in which there is an inability of the distal renal tubule to excrete hydrogen ions into the urine, is associated with sensorineural hearing loss at a young age.161,162 Diabetes mellitus is also probably associated with sensorineural hearing loss, although evidence in the literature is conflicting.163,164 The pathologic process is thought to be a microvascular angiopathy with progressive decrease in the functioning of the stria vascularis. Histologically, there has been shown to be thickening in the stria vascluaris similar to vascular changes seen elsewhere in these patients.165 It is also possible that there is an associated primary neuropathy of the auditory nerve. Some evidence suggests that insulin-dependent diabetes and hypertension have synergistic effects that exacerbate the hearing loss.166 Hyperlipidemia and hypercholesterolemia have been shown to be associated with sensorineural hearing loss, but again the literature is conflicting. Presumably, this occurs due to atherosclerotic changes in the vascular supply to the inner ear similar to that seen in other places in the body (i.e., the coronary arteries). Hypothyroidism can lead to sensorineural hearing loss in utero (cretinism). The histologic effects appear to be predominantly cochlear, with atrophy of the stria and degeneration of the spiral ganglion neurons and hair cells of the organ of Corti. Pendred’s syndrome is an inherited autosomal-recessive trait with a deficiency of peroxidase that prevents the organification of iodine (this has also been associated with large vestibular aqueduct syndrome). There is no fixed definition of hypoxia in the newborn; however, this term is typically used when the neonate fails to establish spontaneous regular breathing after birth. Persistent hypoxia can lead to cerebral damage and sensorineural hearing loss. Apoptosis of cells in the organ of Corti and spiral ganglion neurons occurs.167 Retrospective studies suggest that the frequency of sensorineural hearing

OTIC CAPSULE BONY DISEASES

Cochlear Hearing Loss

hearing loss due to impingement of the auditory nerve or labyrinthine artery.

AUTOIMMUNE HEARING LOSS This etiology of cochlear hearing loss is covered in Chapter 40.

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Cochlear Hearing Loss

103. Parell GJ, Becker GD: Inner ear barotrauma in scuba divers. A long-term follow-up after continued diving. Arch Otolaryngol Head Neck Surg 119:455–457, 1993. 104. Fortnum HM: Hearing impairment after bacterial meningitis: A review. Arch Dis Child 67:1128–1133, 1992. 105. Fortnum H, Davis A: Hearing impairment in children after bacterial meningitis: Incidence and resource implications. Br J Audiol 27:43–52, 1993. 106. Dodge PR, Davis H, Feigin RD, et al: Prospective evaluation of hearing impairment as a sequela of acute bacterial meningitis. N Engl J Med 311:869–874, 1984. 107. Roizen NJ: Etiology of hearing loss in children. Nongenetic causes. Pediatr Clin North Am 46:49–64, 1999. 108. Arditi M, Mason EO, Jr, Bradley JS, et al: Three-year multicenter surveillance of pneumococcal meningitis in children: Clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 102:1087–1097, 1998. 109. Blank AL, Davis GL, VanDeWater TR, Ruben RJ: Acute Streptococcus pneumoniae meningogenic labyrinthitis. An experimental guinea pig model and literature review. Arch Otolaryngol Head Neck Surg 120:1342–1346, 1994. 110. Ramsay ME, Miller E, Peckham CS: Outcome of confirmed symptomatic congenital cytomegalovirus infection. Arch Dis Child 66: 1068–1069, 1991. 111. Stagno S, Whitley RJ: Herpesvirus infections of pregnancy. Part II: Herpes simplex virus and varicella-zoster virus infections. N Engl J Med 313:1327–1330, 1985. 112. Freij BJ, South MA, Sever JL: Maternal rubella and the congenital rubella syndrome. Clin Perinatol 15:247–257, 1988. 113. McGee T, Wolters C, Stein L, et al: Absence of sensorineural hearing loss in treated infants and children with congenital toxoplasmosis. Otolaryngol Head Neck Surg 106:75–80, 1992. 114. Darmstadt GL, Harris JP: Luetic hearing loss: Clinical presentation, diagnosis, and treatment. Am J Otolaryngol 10:410–421, 1989. 115. Chandrasekhar SS, Connelly PE, Brahmbhatt SS, et al: Otologic and audiologic evaluation of human immunodeficiency virus–infected patients. Am J Otolaryngol 21:1–9, 2000. 116. Madriz JJ, Herrera G: Human immunodeficiency virus and acquired immune deficiency syndrome AIDS-related hearing disorders. J Am Acad Audiol 6:358–364, 1995. 117. McNaghten AD, Wan PC, Dworkin MS: Prevalence of hearing loss in a cohort of HIV-infected patients. Arch Otolaryngol Head Neck Surg 127:1516–1518, 2001. 118. Marra CM, Wechkin HA, Longstreth WT Jr, et al: Hearing loss and antiretroviral therapy in patients infected with HIV-1. Arch Neurol 54:407–410, 1997. 119. Paparella MM, Morizono T, Le CT, et al: Sensorineural hearing loss in otitis media. Ann Otol Rhinol Laryngol 93:623–629, 1984. 120. Paparella MM, Goycoolea MV, Schachern PA, Sajjadi H: Current clinical and pathological features of round window diseases. Laryngoscope 97:1151–1160, 1987. 121. Noordzij JP, Dodson EE, Ruth RA, et al: Chronic otitis media and sensorineural hearing loss: Is there a clinically significant relation? Am J Otol 16:420–423, 1995. 122. Eisenman DJ, Parisier SC: Is chronic otitis media with cholesteatoma associated with neurosensory hearing loss? Am J Otol 19:20–25, 1998. 123. MacAndie C, O’Reilly BF: Sensorineural hearing loss in chronic otitis media. Clin Otolaryngol 24:220–222, 1999. 124. Dumich PS, Harner SG: Cochlear function in chronic otitis media. Laryngoscope 93:583–586, 1983. 125. Seicshnaydre MA, Sismanis A, Hughes GB: Update of reparative granuloma: Survey of the American Otological Society and the American Neurotology Society. Am J Otol 15:155–160, 1994. 126. Wiet RJ, Harvey SA, Bauer GP: Complications in stapes surgery. Options for prevention and management. Otolaryngol Clin North Am 26:471–490, 1993.

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127. Fenton JE, Turner J, Shirazi A, Fagan PA: Post-stapedectomy reparative granuloma: A misnomer. J Laryngol Otol 110:185–188, 1996. 128. Kosling S, Bootz F: CT and MR imaging after middle ear surgery. Eur J Radiol 40:113–118, 2001. 129. Jackler RK, Hwang PH: Enlargement of the cochlear aqueduct: Fact or fiction? Otolaryngol Head Neck Surg 109:14–25, 1993. 130. Haggard MP, Pullan CR: Staffing and structure for paediatric audiology services in hospital and community units. Br J Audiol 23:99–116, 1989. 131. Steel KP, Brown SD: Genetics of deafness. Curr Opin Neurobiol 6:520–525, 1996. 132. Berrettini S, Ravecca F, Sellari-Franceschini S, et al: Progressive sensorineural hearing loss in childhood. Pediatr Neurol 20:130–136, 1999. 133. Park AH, Kou B, Hotaling A, et al: Clinical course of pediatric congenital inner ear malformations. Laryngoscope 110:1715–1719, 2000. 134. Oghalai JS, Chen L, Brennan ML, et al: Neonatal hearing loss in the indigent. Laryngoscope 112:281–286, 2002. 135. Jackler RK, Luxford WM, House WF: Congenital malformations of the inner ear: A classification based on embryogenesis. Laryngoscope 97:2–14, 1987. 136. Monsell EM, Jackler RK, Motta G, Linthicum FH, Jr: Congenital malformations of the inner ear: Histologic findings in five temporal bones. Laryngoscope 97:18–24, 1987. 137. Friedmann I, Fraser GR, Froggatt P: Pathology of the ear in the cardioauditory syndrome of Jervell and Lange-Nielsen (recessive deafness with electrocardiographic abnormalities). J Laryngol Otol 80:451–470, 1966. 138. Lindsay JR: Profound childhood deafness. Inner ear pathology. Ann Otol Rhinol Laryngol 82(Suppl 5):1–121, 1973. 139. Zheng Y, Schachern PA, Cureoglu S, et al: The shortened cochlea: Its classification and histopathologic features. Int J Pediatr Otorhinolaryngol 63:29–39, 2002. 140. Ceruti S, Stinckens C, Cremers CW, Casselman JW: Temporal bone anomalies in the branchio-oto-renal syndrome: Detailed computed tomographic and magnetic resonance imaging findings. Otol Neurotol 23:200–207, 2002. 141. Scholtz AW, Fish JH 3rd, Kammen-Jolly K, et al: Goldenhar’s syndrome: Congenital hearing deficit of conductive or sensorineural origin? Temporal bone histopathologic study. Otol Neurotol 22:501–505, 2001. 142. Lemmerling MM, Vanzieleghem BD, Mortier GR, et al: Unilateral semicircular canal aplasia in Goldenhar’s syndrome. Am J Neuroradiol 21:1334–1336, 2000. 143. Jackler RK, De la Cruz A: The large vestibular aqueduct syndrome. Laryngoscope 99:1238–1242; discussion 1242–1233, 1989. 144. Shelton C, Luxford WM, Tonokawa LL, et al: The narrow internal auditory canal in children: A contraindication to cochlear implants. Otolaryngol Head Neck Surg 100:227–231, 1989. 145. Steel KP, Kros CJ: A genetic approach to understanding auditory function. Nat Genet 27:143–149, 2001. 146. Self T, Mahony M, Fleming J, et al: Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells. Development 125:557–566, 1998. 147. Probst FJ, Fridell RA, Raphael Y, et al: Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. Science 280:1444–1447, 1998. 148. Richardson GP, Forge A, Kros CJ, et al: A missense mutation in myosin VIIA prevents aminoglycoside accumulation in early postnatal cochlear hair cells. Ann N Y Acad Sci 884:110–124, 1999. 149. Yasunaga S, Grati M, Cohen-Salmon M, et al: A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet 21:363–369, 1999.

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150. Platzer J, Engel J, Schrott-Fischer A, et al: Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels. Cell 102:89–97, 2000. 151. Liu XZ, Ouyang XM, Xia XJ, et al: Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. Hum Mol Genet 12:1155–1162, 2003. 152. Kubisch C, Schroeder BC, Friedrich T, et al: KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 96:437–446, 1999. 153. Kelsell DP, Dunlop J, Stevens HP, et al: Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 387: 80–83, 1997. 154. Xia JH, Liu CY, Tang BS, et al: Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment. Nat Genet 20:370–373, 1998. 155. Liu XZ, Xia XJ, Adams J, et al: Mutations in GJA1 (connexin 43) are associated with non-syndromic autosomal recessive deafness. Hum Mol Genet 10:2945–2951, 2001. 156. Liu XZ, Xia XJ, Xu LR, et al: Mutations in connexin 31 underlie recessive as well as dominant non-syndromic hearing loss. Hum Mol Genet 9:63–67, 2000. 157. Grifa A, Wagner CA, D’Ambrosio L, et al: Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus. Nat Genet 23:16–18, 1999. 158. Li XC, Everett LA, Lalwani AK, et al: A mutation in PDS causes non-syndromic recessive deafness. Nat Genet 18:215–217, 1998. 159. Everett LA, Glaser B, Beck JC, et al: Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 17:411–422, 1997.

160. Wilcox ER, Everett LA, Li XC, et al: The PDS gene, Pendred syndrome and non-syndromic deafness DFNB4. Adv Otorhinolaryngol 56:145–151, 2000. 161. Brown MT, Cunningham MJ, Ingelfinger JR, Becker AN: Progressive sensorineural hearing loss in association with distal renal tubular acidosis. Arch Otolaryngol Head Neck Surg 119:458–460, 1993. 162. McKusick VA: Mendelian Inheritance in Man, 7th ed. Baltimore, Johns Hopkins University Press, 1986. 163. Guillausseau PJ, Massin P, Dubois-LaForgue D, et al: Maternally inherited diabetes and deafness: A multicenter study. Ann Intern Med 134:721–728, 2001. 164. Fowler PD, Jones NS: Diabetes and hearing loss. Clin Otolaryngol 24:3–8, 1999. 165. Smith TL, Raynor E, Prazma J, et al: Insulin-dependent diabetic microangiopathy in the inner ear. Laryngoscope 105:236–240, 1995. 166. Duck SW, Prazma J, Bennett PS, Pillsbury HC: Interaction between hypertension and diabetes mellitus in the pathogenesis of sensorineural hearing loss. Laryngoscope 107:1596–1605, 1997. 167. Cheng AG, Huang T, Stracher A, et al: Calpain inhibitors protect auditory sensory cells from hypoxia and neurotrophin-withdrawal induced apoptosis. Brain Res 850:234–243, 1999. 168. Shapiro SM, Nakamura H: Bilirubin and the auditory system. J Perinatol 21(Suppl 1)S52–S55; discussion S59–S62, 2001. 169. Brownell WE: How the ear works: Nature’s solutions for listening. Volta Rev 99:9–28, 1999. 170. Eatock RA, Rusch A: Developmental changes in the physiology of hair cells. Semin Cell Dev Biol 8:265–275, 1997.

38

Outline Introduction Electronystagmography Eye Movement Recording Equipment Routine Components of Electronystagmography Dix-Hallpike Maneuver Gaze Test Positional Test Bithermal Caloric Test Saccade Test Pursuit Tests Summary Normal Electronystagmography Does Not Rule out Vestibulopathy

Chapter

Electronystagmography and Rotation Tests

Abnormal Electronystagmography Does Not Always Rule in Vestibular Disease as the Cause of Dizziness It Is Important to Test the Patient When Symptomatic if Possible Rotation Chair Test History Rotary Chair Test Clinical Indications for Rotational Chair Testing

Dennis I. Bojrab, MD Vincent B. Ostrowski, MD

INTRODUCTION

ELECTRONYSTAGMOGRAPHY

Vestibular testing should be considered an important tool in the evaluation and management of dizziness. A careful and thorough bedside history and neurotologic examination is key for making an accurate clinical diagnosis in the patient with dizziness. The physician must couple the results of the bedside evaluation with the results of vestibular tests to manage the disorder. In other words, the vestibular tests of electronystagmography (ENG) or rotary chair test (RCT) should not be considered stand-alone diagnostic tests for the patient with dizziness, but instead should be coupled with clinical impressions. It is important to remember that not every patient needs quantitative vestibular testing. Also, other important information provided by the ENG does not involve the vestibular system and may be of value when treating the patient with dizziness. Assessing the integrity of the vestibulo-ocular reflex ( VOR) is an integral part of vestibular testing. The VOR is a reflex that acts at short latency to generate eye movements that compensate for head rotations encountered in daily activity. The VOR preserves clear vision during locomotion to prevent slip of a visual image that is focused on the retina. Measuring the VOR requires stimulation of vestibular system and measurement of the resulting eye movements. There are advantages but also limitations to the current methods of this analysis, which will be discussed in the body of this chapter (Table 38-1).

ENG is a method of monitoring eye movements. For nearly 40 years, it has been widely used in the diagnostic evaluation of dizziness or unsteadiness. The examination consists of a battery of tests collectively referred to as the ENG. This battery was designed to reveal vestibular and nonvestibular functional tests of eye movement abnormalities. The vestibular and ocular systems are connected through the VOR. Patients with peripheral or central balance disorders often exhibit abnormal eye movements that can be measured and recorded. The most common method involves monitoring eye movements using electro-oculography.

Eye Movement Recording Equipment A variety of eye movement recording equipment is currently available. In performing the ENG, the patient’s eye movements are measured relative to head position, which can be achieved in a number of ways: 1. Electro-oculography (depends on the corneoretinal potential) 2. Video-oculography (depends on video camera goggles) 3. Magnetic search coil technique 4. Infrared oculography Electro-oculography ( EOG ) is the most common technique of monitoring eye movements during the ENG and is 607

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TABLE 38-1. Benefit of Electronystagmography and Rotational Chair Testing 1. 2. 3. 4.

Localize a central verses a peripheral lesion. Lateralize the deficit. Offer documentation of clinical examination. Assist in establishing a diagnosis and developing a treatment plan and long-term management.

based on the fact that steady DC potentials—corneoretinal potentials—exist between the corneas and retinas of the eyeballs. These potentials create an electric field in the front of the head that rotates as the eyes rotate in their orbits. The cornea is relatively positively charged in comparison with the retina; thus, an electrical potential exists between the two. This potential is generated by the metabolic activity of the retinal pigment epithelium. The retina is negatively charged relative to the cornea and therefore electrical potential can be measured between the two by means of skin surface electrodes. In neutral position the average potential measured is about 1 mV. Movement of the eyes causes potential changes relative to the skin electrodes. Movement of this electric field produces a roughly linear change in the voltage between electrodes attached to the skin on either side of the eyes. Electrodes placed on the patient’s temples monitor horizontal eye position. Vertical eye position is monitored by electrodes placed above and below one of the patient’s eyes. Some benefits of the EOG surface electrodes are that they are simple and relatively inexpensive. Disadvantages include the inability to monitor ocular torsion, being subject to bioelectric noise from facial muscles and a resolution of about 1 degree/sec while monitoring eye movements (Fig. 38-1). Video-oculography, a technique that has recently become commercially available, involves digital video-recorded eye movements. Videonystagmography (VNG) is a computerbased system that records eye movement under test situations. The eye position is located by detecting the pupil and tracking its center. The internal computer program plots, measures, and analyzes the eye movements under a battery of tests. VNG permits visualization and recording of eye movements that are conveniently stored on a database for retrieval or transfer of data. This is helpful for later study and for teaching of personnel and patients. This technique is easier and quicker than using electrodes with minimal patient preparation, and only one calibration is necessary, speeding the over all test time. Depending on the system, ocular torsion can be measured and video-captured, unlike EOG. Without the bioelectric interference from facial muscles, tracings are clean with no drift as seen with traditional EOG tracings. Monitoring resolution can detect 0.1 degree/sec movements. Blink artifact can be an issue because the eyes must be kept open during testing, and some patients experience claustrophobia and may not tolerate the sensation of confinement. In addition, the test equipment is expensive (Fig. 38-2). The magnetic search coil technique places the patient in a three-dimensional electromagnetic field. The patient wears a soft contact lens in which a wire coil is embedded.

Eye movement effects a change in the magnetic field, and this is recorded. The advantage of this method is that it gives very high-resolution data for all types of eye movements, including torsional nystagmus. Disadvantages of the technique include slight patient discomfort (due to the lens) and the very high cost of the procedure. This procedure has yet to gain widespread acceptance and is rarely used clinically. Infrared oculography is based on the differing reflectance properties of the iris relative to the sclera and the fact that the photocells of the eye remain stationary while the edge of the iris moves with the eye. As a result, the light sensed by the photocells differs according to eye position. The advantage of this technique is that a direct estimate of the eye position as a function of time can be calculated. Disadvantages of this technique include the bulkiness of the equipment, which limits visual stimulation somewhat, and the interference with eyelid motion (e.g., blink), which makes vertical recording difficult at times.

Routine Components of Electronystagmography The ENG test battery generally consists of seven tests. The first four tests are primarily tests of vestibular function, although they sometimes also reveal nonvestibular eye movement abnormalities as well: (1) the Dix-Hallpike maneuver, designed to provoke a nystagmus response in patients with benign positional vertigo, (2) the gaze test, designed to detect nystagmus induced by eccentric gaze, (3) the positional test, designed to determine if different head positions induce or modify nystagmus, and (4) the bithermal caloric test, designed primarily to detect unilateral lesions of the labyrinth or vestibular nerve. The final three tests are tests of nonvestibular eye movements: (5) the saccade test, designed to detect disorders of the saccade eye movement control system, and (6) the tracking test and (7) the optokinetic test, both designed to detect disorders of the pursuit eye movement control system. Although saccade and pursuit eye movements are of secondary interest to those who evaluate dizziness, they are nevertheless routinely tested because abnormalities are occasionally detected in such patients. For many years, eye movements were recorded on strip charts. Recently, ENG has been computerized, permitting efficient storage and easy retrieval of eye movement data and eliminating the cutting and pasting of strip chart recordings. In addition, computerized ENG allows rapid and sophisticated analysis of saccade, tracking, and caloric tests—analyses that could not be done on strip chart recordings.

Dix-Hallpike Maneuver The most frequently employed test for positioning nystagmus is the Dix-Hallpike maneuver. The patient is subjected to two brisk movements, both beginning with the patient in the sitting position. The patient’s head is first turned 45 degrees toward one side. Then the examiner, standing to the side or behind the patient, pulls him briskly backward so that he is lying supine with his head still turned to that side and hanging over the end of the examining table.

Electronystagmography and Rotation Tests

609

A

Figure 38-1. Corneoretinal potential.

B

C

Horizontal Channel right

Vertical Channel up

D

The examiner holds the patient’s head in that position for at least 20 seconds and monitors his eye movements. Then the examiner returns the patient to the sitting position. If a response was elicited, the examiner repeats the same maneuver to determine if it fatigues. Then she performs the maneuver with the patient’s head turned 45 degrees to the other side, and if a response is elicited, repeats the maneuver to determine if it fatigues (Fig. 38-3). During the backward movement, the Dix-Hallpike maneuver normally induces a few beats of nystagmus. After the head has reached the hanging position, normal individuals do not have nystagmus, but some patients with benign positional vertigo display a burst of intense nystagmus—paroxysmal positional nystagmus—that is the

hallmark of the disorder. Paroxysmal positional nystagmus has four distinctive characteristics1,2: 1. It has a delayed onset. Usually an interval of at least a few (2 to 20) seconds elapses after the patient reaches the head-hanging position before the nystagmus begins. 2. It is always transient; that is, it rapidly builds in intensity (crescendos), slowly abates (decrescendos), and finally disappears (within 45 seconds) as the head remains in position. 3. It is always accompanied by vertigo, usually intense, that follows the same time course of the nystagmus. 4. It is usually fatigable; that is, it progressively diminishes in intensity with repetition of the Dix-Hallpike maneuver.

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Figure 38-2. Video-oculography.

D

A

B

Figure 38-3. Dix-Hallpike maneuver and illustration of canalithiasis.

Head tilted back 135 and turned to left 45

Canalithiasis

C

Cupulolithiasis

Electronystagmography and Rotation Tests

The pathophysiology of the response is believed to be due to two types of pathology: canalithiasis and cupulolithiasis, with the former being much more prevalent. In canalithiasis, otoconia or other debris are presumed to be floating freely in the endolymph of one of the canals. If the head is positioned so that the involved canal is vertical and then rotated quickly in the plane of that canal, the otoconia fall to the lowest position in the canal, moving endolymph along with them. This movement of endolymph deflects the cupula of that canal, causing the hair cell stimulation and therefore inducing nystagmus and vertigo. The characteristics of the eye movement response may be explained. The latency of the response is due to inertial drag of the endolymph as the debris falls to the dependent position. The nystagmus response is due to cupula deflection and stimulation. Once the debris settles, the endolymph flow ceases, the cupula goes to the neutral position, and the nystagmus stops (see Fig. 38-3C). Nearly always only one labyrinth is involved, and the response is provoked when the Dix-Hallpike maneuver places the involved labyrinth undermost. Paroxysmal positional nystagmus can be readily appreciated by visual observation with the patient’s eyes open or, better yet, with the patient wearing Frenzel’s lenses in a darkened room. The examiner sees primarily the torsional component of the nystagmus, with counterclockwise fast phases when the right ear is involved and clockwise fast phases when the left ear is involved. In other words the nystagmus seen by the examiner appears to be torsional toward the floor of the downward ear. ENG is useful in documenting the response (Fig. 38-4). ENG is insensitive to the torsional component of the nystagmus, but does record the horizontal and vertical components. The horizontal component generally has fast phases away from the undermost ear, and the vertical component invariably has upward fast phases. Paroxysmal positional nystagmus changes somewhat with the direction of the patient’s gaze. The torsional component is more prominent during gaze toward the undermost ear; the vertical component is more prominent during gaze toward the uppermost ear.

Figure 38-4. Paroxysmal positional nystagmus in response to the Dix-Hallpike maneuver with right ear undermost. Horizontal channel shows left-beating nystagmus, and the vertical channel shows upbeating nystagmus. Upward pen deflection denotes rightward eye movement on horizontal eye position tracing and upward eye movement on vertical eye position tracing.

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TABLE 38-2. Fast Phases

Semicircular Canal Involvement

Upward right torsional Upward left torsional Downward right torsional Downward left torsional

Right posterior canal BPPV Left posterior canal BPPV Right anterior canal BPPV Left anterior canal BPPV

BPPV, benign paroxysmal positioning vertigo.

The Dix-Hallpike maneuver sometimes provokes types of nystagmus response other than the posterior semicircular canal on the downward ear. The examiner may identify the specific canal involved by noting the direction of the fast phases of the abnormal nystagmus with the patient’s eyes looking straight ahead (Table 38-2). Horizontal semicircular canal benign paroxysmal positioning vertigo (BPPV) can be detected with the Dix-Hallpike maneuver. A more effective maneuver involves placing the patient in the supine position, turning the head quickly to the right-ear-down position, and holding it there for at least 30 seconds (or, if nystagmus is provoked, for up to several minutes). The patient’s head is then returned slowly to the supine position; lastly, the head is turned quickly into the left-ear-down position and held there for at least 30 seconds (or, if nystagmus is provoked, for up to several minutes). In patients with horizontal canal BPPV, this maneuver provokes horizontal nystagmus, as described by Baloh and colleagues.3 The nystagmus of horizontal canal BPPV is 1. Geotropic (right beating in the right-ear-down position and left-beating in the left-ear-down position) and often followed by an ageotropic secondary nystagmus 2. Stronger when the ear presumed to be pathologic is undermost 3. Transient (although more persistent than the response of posterior canal BPPV ) 4. Accompanied by vertigo, usually intense, that follows the same time course as the response 5. Not delayed in onset 6. Not fatigable Another abnormal response is downbeat nystagmus, which is exacerbated when the patient is moved to the head-hanging position.4 If downbeat nystagmus is mild, it may be absent when looked for during the gaze or positional tests and appear for the first time in response to the Dix-Hallpike maneuver. Generally it is not accompanied by vertigo. The maneuver may also provoke horizontal positional nystagmus, which, if intense, is accompanied by vertigo. This type of positional nystagmus would also be observed during the positional test. Other types of nystagmus response, generally of central nervous system origin, are rarely provoked by the Dix-Hallpike maneuver. Usually this nystagmus is strictly downbeating without any torsional component. If so, it may be due to an Arnold-Chiari malformation, cerebellar degeneration, or a selective lesion of the cerebellar flocculus. One limitation of the Dix-Hallpike maneuver is that it cannot be performed on patients with cervical spine disease that limits neck extension or back disorders that prohibit rapid positioning of the patient into the headhanging position. In those patients, a sideling Bojrab

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maneuver may be employed. The senior author has been using this technique for over 15 years as his primary technique in elderly patients or patients with significant cervical neck disease. This maneuver allows the same positioning of the posterior semicircular canal as with the Dix-Hallpike maneuver, without the head hanging. With the Bojrab maneuver, the patient is positioned sitting up, facing the examiner. The head is turned to the right 45 degrees, so that the external auricle is perpendicular to the plane of the table. The examiner then holds the head in that position as he briskly lowers the patient onto her shoulder, with the head resting on the table. The position is held for at least 20 seconds while the eye movements are monitored. The patient is then returned to the sitting position. If nystagmus was elicited, the examiner repeats the same maneuver to determine whether the nystagmus is fatigable. The maneuver is then performed on the contralateral side. As with the Dix-Hallpike maneuver, the ear, which is dependent at the time the nystagmus is elicited, is usually the one containing the diseased labyrinth (Fig. 38-5).

Gaze Test The patient’s eye movements are monitored as she fixates while gazing 30 degrees to the right, 30 degrees to the left, 30 degrees up, and 30 degrees down. Some examiners also attempt to monitor eye movements in these gaze positions with visual fixation denied, but the tracing is often difficult to interpret. Young normal individuals rarely have any nystagmus at all while fixating at any of these gaze positions, but many elderly individuals have endpoint nystagmus. This nystagmus is always faint with centripetal slow phases that generally are of equal intensity on right and left gaze.

Figure 38-5. Bojrab maneuver.

The gaze test detects nystagmus from vestibular origin as well as central nervous system origin. An example of one type—upbeat nystagmus—is shown in Figure 38-6. Upbeat nystagmus occurs most commonly as a result of medullary lesions involving vertical vestibular pathways.5 Leigh and Zee describe additional types of central nystagmus seen in the gaze test.6 Barber and Stockwell illustrate ENG tracings of many of these.7 The gaze test may also detect spontaneous nystagmus caused by a unilateral vestibular lesion, although spontaneous nystagmus is better appreciated during the positional test with visual fixation denied.

Positional Test The purpose of the positional test is to determine if different head positions induce or modify vestibular nystagmus. The patient’s eye movements are monitored while his head is in at least four positions: sitting, supine, right ear down, and left ear down. If nystagmus appears or is modified in either of the latter two positions, the patient is tested again while lying on that side to determine if the effect was due to neck rotation. Some examiners also test the patient in the head-hanging position. Eye movements are monitored in each position both with visual fixation permitted (eyes open and fixating on a visual target at center gaze) and with visual fixation denied. Most examiners deny fixation simply by asking the patient to close his eyes, but eye closure may inhibit nystagmus. A better method is to monitor eye movements with eyes open in total darkness. The examiner usually asks the patient to perform a mental task, such as mental arithmetic, when testing with visual fixation denied to maintain mental alertness and thus avoid nystagmus suppression. The most common abnormality seen in the positional test is so-called spontaneous nystagmus (Fig. 38-7). This

Electronystagmography and Rotation Tests

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Figure 38-7. Left-beating spontaneous nystagmus with eyes closed. Upward pen deflection denotes rightward eye movement.

Figure 38-6. Upbeat nystagmus. Upward pen deflection denotes rightward eye movement on horizontal eye position tracings and upward eye movement on vertical eye position tracings.

nystagmus is horizontal-torsional, although ENG is insensitive to the torsional component and only records the horizontal component. It is suppressed by visual fixation, and often suppression is so strong that spontaneous nystagmus is abolished by fixation. Poor fixation suppression indicates a central nervous system lesion involving the pathways responsible for VOR cancellation. Spontaneous nystagmus is a reflection of tonic left-right vestibular asymmetry. It is typically seen after a recent unilateral peripheral vestibular lesion and has fast phases away from the side of the lesion. Sometimes spontaneous nystagmus is seen in the absence of a recent unilateral peripheral lesion, in which case it provides evidence of a vestibular lesion but does not localize it. Spontaneous nystagmus has been defined as nystagmus that is unmodulated by changes in head position and has been distinguished from positional nystagmus, which is modulated by head position changes, but this distinction does not appear to be clinically useful. In fact, tonic horizontal-torsional vestibular nystagmus is occasionally modulated by a change from the sitting to the supine position, and it is

often modulated by changes from the right-ear-down to the supine to the left-ear-down position, as illustrated by the example shown in Figure 38-7. In some cases, the modulation is sometimes so deep that nystagmus even changes in direction, for example, from strongly right-beating in the right-ear-down position, to more weakly right-beating in the supine position, to left-beating in the left-ear-down position. The positional test also detects another variant of positional nystagmus (Fig. 38-8). There is no nystagmus in the sitting or supine positions. Nystagmus beats in one direction in the right-ear-down position and in the opposite direction in the left-ear-down position. Generally strong nystagmus appears when the patient first assumes the position, followed by persistent nystagmus of lower intensity. If the nystagmus is strong enough, the patient experiences vertigo. Like spontaneous nystagmus, this type of positional nystagmus provides evidence of vestibular dysfunction, but is nonlocalizing. Like the Dix-Hallpike maneuver, the positional test occasionally provokes nystagmus of central origin. It also may provoke paroxysmal positional nystagmus if the response has not previously been provoked and fatigued by the Dix-Hallpike maneuver.

Bithermal Caloric Test The bithermal caloric test has proven highly sensitive to unilateral lesions of the peripheral vestibular system, that

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PERIPHERAL AUDIOVESTIBULAR DISORDERS

Figure 38-9. Caloric responses of a patient with a 65% unilateral weakness of the right ear.

caloric stimuli. If both ears are normal, they should produce responses of approximately equal intensity. Therefore the strength of the caloric responses from the two ears is compared. Most examiners use the following formula: (RW + RC) − (LW + LC) × 100 = UW RW + RC + LW + LC

Figure 38-8. Direction-changing positional nystagmus with eyes closed; right-beating with right ear down and left-beating with left ear down. Upward pen deflection denotes rightward eye movement.

is, to unilateral lesions of the labyrinth or vestibular nerve, because it permits the examiner to stimulate each ear separately. Other vestibular test procedures, such as rotation testing and posturography, necessarily involve stimulation of both labyrinths together and therefore permit masking of abnormal responses from one labyrinth by normal responses from the opposite ear. The bithermal caloric test is specifically a test of the integrity of the horizontal semicircular canals and their afferent pathways. The patient is placed in the supine position with her head elevated by 30 degrees to place the horizontal canal in the vertical plane. The standard caloric stimulus consists of 250 mL of water irrigated into the external ear canal within 30 seconds. The temperature of the water is 30°C for the cool irrigation and 44°C for the warm irrigation. Some examiners use air (8 L at 24°C and 50°C within 60 seconds) instead of water as the caloric stimuli. Others use a “closed-loop” system, in which water continuously circulates within a watertight system, which includes a small balloon that inflates in the external ear canal during the irrigation. All three irrigating methods— water, air, and “closed-loop”—yield approximately equivalent stimuli. Caloric stimuli are uncalibrated, that is, stimulus strength varies from person to person depending on the size and shape of the external ear canal and other uncontrollable variables. However the basic assumption of the caloric test is that, for a given individual, the two ears receive equal

RW, RC, LW, and LC are peak slow-phase velocities of the responses to right warm, right cool, left warm, and left cool responses, respectively, and UW is unilateral weakness. The normal limit of +20% to 25% for UW is widely accepted. Figure 38-9 shows the caloric responses of a patient who has a left UW of 65%, which signifies a lesion of the right labyrinth or vestibular nerve. Patients may have both a unilateral weakness and spontaneous nystagmus. This pattern is typical of patients with acute sudden unilateral peripheral vestibular lesions. Such a lesion causes a reduction in the resting input coming from the damaged ear, producing an asymmetry that induces nystagmus with slow phases toward the damaged ear. Figure 38-10 shows the result of a test performed on a patient 3 days after the onset of a right peripheral vestibular lesion. Caloric irrigations provoked no response from the right ear. The patient also had spontaneous nystagmus with rightward slow phases at velocities of about 6 degrees/sec.

Figure 38-10. Caloric responses of a patient with absent caloric responses from the right ear and spontaneous nystagmus with rightward slow phases.

Electronystagmography and Rotation Tests

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TABLE 38-3. Advantages of Caloric Testing 1. 2. 3. 4.

Figure 38-11. Caloric responses of a patient who has no unilateral weakness, but who does have spontaneous nystagmus with rightward slow phases.

Tests for unilateral disease and comparison of sides Results are quantified and are well-defined normal limits Follow patients with known vestibular disease Medical legal documentation

responses to the initial bithermal stimuli. In this case, the test is repeated with ice water (approximately 0°C) irrigations. However, one should keep in mind that the absence of a caloric response does not always imply absent peripheral function, because the stimulus levels are below the level within which the vestibulo-ocular reflex generally functions (Tables 38-3 and 38-4).

Saccade Test This nystagmus created a bias; caloric responses were symmetrical about a new baseline corresponding to the slowphase velocity of this nystagmus. It would be difficult to distinguish between the effects of this bias and a unilateral caloric weakness on the basis of peak slow-phase velocities if only one temperature of irrigant were used in the caloric test. When both warm and cool irrigants—eliciting responses in both directions—are used and then the sum of the two peak responses is used as the measure of response strength of a particular ear, the effects of the bias are canceled and a valid comparison between the two ears is possible. Figure 38-11 shows the caloric responses of a patient who does not have a unilateral caloric weakness, but does have spontaneous nystagmus with rightward slow phases at velocities of about 10 degrees/sec, which creates a new baseline on which the caloric responses are superimposed. The spontaneous nystagmus in this case cannot be attributed to a recent unilateral peripheral vestibular lesion, since the caloric responses of the two ears are equal. A lesion within the central vestibular pathways could have caused it, but other explanations, such as recovery of a previously compensated for peripheral lesion, are also possible. Therefore spontaneous nystagmus that cannot be attributed to a recent unilateral peripheral vestibular lesion must be regarded as nonlocalizing. Although the bithermal caloric test is highly sensitive to unilateral peripheral vestibular lesions, it is relatively insensitive to bilateral lesions. The reason is that the caloric stimulus is uncalibrated. Even though the stimulus at the entrance to the external ear canal is the same for everyone, the amount of stimulus reaching the inner ear varies widely across individuals due to differences in the size and shape of the ear canal and middle ear structures. Therefore, normal limits for absolute response intensity are extremely wide, and bilateral caloric weaknesses must be extreme to fall below them. The usual rule of thumb is that a bilateral weakness exists if caloric responses (warm response plus cool response) of both ears fall below 12 degrees/sec. A bilateral weakness usually indicates bilateral peripheral vestibular lesions.8,9 Central nervous system (CNS) disorders also produce bilateral weaknesses, but other signs of CNS dysfunction usually accompany bilateral weaknesses of CNS origin. Patients with labyrinthine hypofunction may demonstrate reduced or absent caloric

The purpose of the saccade test is to detect abnormalities of saccadic eye movement. The test is performed differently in various laboratories. In one version of the test, the patient’s horizontal eye movements are monitored as she fixates on a computer-controlled visual target that jumps back and forth in the horizontal plane in an unpredictable sequence. The complete sequence consists of 80 target jumps (40 to the right and 40 to the left) with amplitudes ranging from 5 to 25 degrees. After testing, the computer deletes invalid eye movement data, then calculates three values—peak velocity, accuracy, and latency—for each saccade and plots these data in graphic form. Patients may show abnormalities on any of these three measures. Figure 38-12 shows saccade test data of a patient with abnormally slow saccades bilaterally, which are characteristic of many degenerative and metabolic diseases of the central nervous system. Patients may also show abnormalities of saccade accuracy, making saccades that are too small or too large, indicating a lesion of the cerebellar nodulus. They may also show abnormally long saccade latencies, which have been associated with lesion of the frontoparietal cortex.10 Some examiners also monitor vertical eye movements as the patient performs vertical saccades, although the vertical eye movement tracing is often difficult to interpret and well-established normal limits are lacking. Also if the examiner detects internuclear ophthalmoplegia during the pretest eye movement examination, he will monitor eye movements separately for each eye in order to document this abnormality.

Pursuit Tests TABLE 38-4. Limitations of Caloric Testing 1. Caloric stimulus is: poorly controlled poorly tolerated an unnatural way of vestibular stimulation considered to be a very low frequency test of vestibular function 2. Measures relative function, one ear with respect to the opposite ear 3. Measures only lateral semicircular canal function 4. Does not test the dynamic range of the vestibular system (much like testing the auditory system with a single frequency)

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PERIPHERAL AUDIOVESTIBULAR DISORDERS

Figure 38-14. Optokinetic test results of the patient whose tracking test results are shown in Figure 38-13.

Figure 38-12. Saccade test results of a patient with slow saccades bilaterally. Saccade accuracies and latencies are normal.

Two tests of pursuit—the tracking test and the optokinetic test—are commonly performed in the ENG examination. The tracking test is performed in different ways in various laboratories. In one version, the patient’s horizontal eye movements are monitored as he follows a computercontrolled visual target moving in the horizontal plane. The target moves back and forth following a sinusoidal waveform at frequencies from 0.2 to 0.7 Hz. After testing, the computer deletes invalid eye movement data. Then it deletes interpolated saccades, differentiates the eye position signal, calculates the gain of eye velocity with respect to target velocity separately for rightward and leftward tracking at each target frequency, and plots these data. Normal individuals are able to follow the target smoothly in both directions at all target frequencies. Figure 38-13 shows the results of the tracking test in a patient with a unilateral pursuit defect. The patient was unable to follow the leftward-moving target smoothly and instead approximated its motion using successive saccades, producing a stairstep pattern on the eye movement tracing. Tracking of rightward-moving targets was normal.

This patient’s abnormality indicates an asymmetrical CNS lesion involving the pursuit eye-movement control system. The optokinetic test is also performed differently in different laboratories. In one version, the patient’s horizontal eye movements are monitored as she follows a series of visual targets moving first to the right and then to the left. This stimulus provokes nystagmus with slow phases in the direction of target motion, periodically interrupted by fast phases in the opposite direction. The optokinetic test, like the tracking test, is a test of pursuit eye-movement pathways, and the results of the tracking and optokinetic tests agree if task difficulty is the same. In normal individuals, the velocities of nystagmus slow phases approximately match target velocity for both rightward- and leftward-moving targets. Figure 38-14 shows the results of the optokinetic test for the patient whose tracking test results were shown in Figure 38-13. Her optokinetic nystagmus was virtually absent for leftward-moving targets and mildly reduced for rightwardmoving targets.

SUMMARY Although ENG essentially replicates portions of the physical examination, it is an important part of the evaluation of many complaints of dizziness or balance disturbance. ENG testing has a number of advantages: (1) the results of the test are quantified, and the normal limits are well-defined; (2) the bithermal caloric cannot be done as accurately without the precise stimulus control and response quantification provided by ENG; (3) because ENG provides accurate documentation of results, it can be used to follow the patient with known vestibular disease; (4) standardized documentation is helpful in medicolegal and workers’ compensation cases; and (5) it is the only test that tests each ear separately and can give side-of-lesion localizing information.

Normal Electronystagmography Does Not Rule out Vestibulopathy

Figure 38-13. Tracking test results of a patient with an asymmetrical pursuit defect. Upward pen deflection on horizontal eye position tracing denotes rightward eye movement.

Results of ENG testing may fluctuate in concordance with the patient’s disease process. Two of the more common illnesses seen in our patients are BPPV and Ménière’s disease (MD). Both illnesses can be associated with a normal ENG despite “classic” symptoms. For example, on the day of testing a patient with complaints consistent with BPPV, the response may have been fatigued or the disease may have gone into remission. For that patient, the test results may be normal or indicate a unilateral vestibular weakness

Electronystagmography and Rotation Tests

on the suspect side. Nevertheless, we maintain clinical suspicion of BPPV, and we ask the patient to return for retesting on a particularly “dizzy day.” Similarly, the patient suspected of having MD may have a normal ENG early in the course of the illness, and only later, on a particularly “dizzy day,” will the caloric evaluation demonstrate a unilateral peripheral weakness, gaze-evoked nystagmus, or even spontaneous nystagmus. It is important to have patients abstain from taking vestibular suppressant medications (e.g., diazepam) for at least 48 to 72 hours prior to ENG, as this can also be a cause of a “false-negative” test.

Abnormal Electronystagmography Does Not Always Rule in Vestibular Disease as the Cause of Dizziness Some patients may present with dizziness not related to vestibular system dysfunction, for example, syncope or presyncope, vertebral basilar insufficiency, migraineassociated dizziness, multiple sclerosis, ocular dizziness, motion sickness syndrome, or cardiovascular disease. In these patients, a unilateral weakness found on ENG does not necessarily implicate vestibular dysfunction as the cause of their symptoms. The ENG finding may be incidental and must be considered in light of the clinical history and physical examination.

It Is Important to Test the Patient When Symptomatic if Possible The ENG results may change with the course of disease; some patients may be in remission, and others may have their disease escalate later. We therefore try to test patients without medication on the day of their complaint of dizziness if at all possible. ENG testing is an important tool in the management of dizziness. It is by no means a substitute for a thorough neurotologic history and physical examination, and results should be interpreted in light of the clinical evaluation. Those who use ENG testing should have a thorough understanding of how the test is performed, what its components are and the significance of the results. The clinician with a critical eye should always evaluate ENG reports. When used properly, ENG is the single most valuable test currently available in the vestibular laboratory.

ROTATION CHAIR TEST History Rotational tests have been used to evaluate vestibular function for nearly a century. Over the years, various testing methods have been tried, but the one that has proven most useful involves positioning the patient so that the rotational axis is vertical and passes through the center of her head, thus stimulating only her horizontal semicircular canals. Horizontal eye movements are monitored. Rotation tests have been used to evaluate vestibular function for a century. Bárány, in 1907, described an impulsive rotation test in which the subject was brought to a sudden stop after manual rotation of approximately 10 turns within

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20 seconds. The status of the VOR was then evaluated by comparing the duration of the evoked nystagmus. In 1948 Von Egmond and coworkers proposed an elaboration of this test called cupulometry, and the duration of nystagmus in response to a series of velocity steps was measured and plotted as a function of stimulus velocity. The use of the sinusoidal stimuli was introduced with the advent of the torsion swing test. In this test, the subject was seated on a spring-loaded chair that oscillated back and forth when the chair was pressed against the springs and then released. The springs were calibrated so that the chair underwent sinusoidal oscillation at 0.05 Hz. These methods of testing proved to be of limited clinical value due to their insensitivity to common vestibular abnormalities. Rotation testing entered the modern era in the 1960s when methods became available for generating precise, repeatable rotational stimuli and for making quantitative measurements of eye movements. Today, computers control all aspects of rotation testing including stimulus generation, response measurement, and data analysis.

Rotary Chair Test The most widely used rotation test is the so-called slow harmonic acceleration test.11 The patient is seated in a chair mounted on a servo-controlled torque motor enclosed within a light-proof, sound-attenuating booth. The horizontal semicircular canals are in the plane of rotation, and horizontal eye movements are monitored by EOG, the same method used in ENG testing. The patient is tested in total darkness with eyes open while performing mental arithmetic. She undergoes sinusoidal oscillation about a vertical axis at several different frequencies. The exact test protocol varies somewhat among laboratories, but a commonly used procedure employs oscillation frequencies of 0.01, 0.02, 0.04, 0.08, 0.16, 0.32, and 0.64 Hz, with peak angular velocities of 50 degrees/sec at each frequency.12 The patient undergoes multiple cycles of oscillation at each frequency. The relationship between head and eye movement during several cycles of sinusoidal oscillation for a normal individual is shown in Figure 38-15. The oscillation frequency in this example is 0.16 Hz, which is near the middle of the test frequency range. Figure 38-15, top, shows head angular velocity. Figure 38-15, middle, shows horizontal eye position recorded by EOG. The patient has nystagmus with leftward slow phases when her head moves rightward and nystagmus with rightward slow phases when her head moves leftward. As shown in bottom graph of Figure 38-15, the computer then differentiates the eye position signal, removes nystagmus fast phases, and displays slow-phase eye velocity. The computer then compares the head velocity and slow-phase eye velocity and calculates three measurements—phase, gain, and symmetry—for each of the test frequencies. The purpose of the vestibulo-ocular reflex is to produce eye movements that compensate for head movements. If the reflex performs perfectly, the slow-phase eye velocity plot in Figure 38-15, bottom, would have the mirror image of the head velocity plot in Figure 38-15, middle. However compensation is less than perfect. The gain of slow-phase eye velocity signal with respect to head veloc-

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PERIPHERAL AUDIOVESTIBULAR DISORDERS

Figure 38-16. Phase, gain, and asymmetry values in relation to oscillation frequency for a normal person. Note that the eye velocity signal is inverted during analysis, so that a phase angle of 180 degrees is expressed as a phase angle of 0 degrees.

Figure 38-15. Head and eye movement of a normal person during oscillation at 0.16 Hz. Upward pen deflection denotes rightward movement.

ity is only about 0.6. In other words, the eyes do not move quite fast enough during the nystagmus slow phases to compensate entirely for head movements. The relationship between slow-phase eye velocity and head velocity is described by two parameters in addition to gain. The first parameter, phase angle, is a measure of the timing relationship between eye and head velocity. In Figure 38-15, the direction of slow-phase eye velocity is exactly opposite the direction of head velocity at all times; that is, the phase angle is 180 degrees. The second parameter, symmetry, is the ratio of rightward and leftward slow-phase eye velocities. In Figure 38-15, slow-phase eye velocities are roughly equal in the two directions. Figure 38-16 shows graphic plots of phase, gain, and symmetry data (from left to right in the figure) for a normal individual over the entire range of test frequencies. Phase and gain values show the progressive phase lead and gain reduction as oscillation frequency decreases. Symmetry values are approximately zero at all frequencies. At the higher frequency of 0.64 Hz, these relationships are about the same as they are at 0.16 Hz, but when the person is oscillated at progressively lower frequencies of 0.04, and finally 0.01 Hz, these relationships show progressive change. Slow-phase eye velocities exhibit progressively lower gains, and they are no longer exactly opposite in phase, but rather displayed progressively larger phase leads.13 In other words, changes in slow-phase eye velocity occur more and more in advance of head velocity. The slow harmonic acceleration test shows abnormalities primarily at the lowest and at the highest oscillation frequencies. Low frequencies reveal abnormal phase leads and gain reductions. High frequencies reveal asymmetries. Patients with acute unilateral peripheral lesions show the most severe abnormalities. Figure 38-17 shows test results

in a patient who underwent the slow harmonic acceleration test shortly after the sudden onset of severe vertigo. ENG, performed at the same time as rotation testing, showed left-beating spontaneous nystagmus as well as weak caloric responses from the right ear. At the lower oscillation frequencies, this patient displayed progressively greater than normal phase leads, which is thought to be caused by a loss of velocity storage that is normally provided by the central vestibular system to enhance the lowfrequency response of the vestibulo-ocular system.14–16 Loss of velocity storage seems to represent habituation to the strong tonic asymmetry produced by the unilateral peripheral vestibular lesion.17 Loss of velocity storage is not an exclusive feature of unilateral peripheral vestibular lesions. It is seen in a variety of vestibular disorders, both peripheral and central, and has also been observed in normal individuals who have undergone prolonged rotation.18 This patient also has a rightward asymmetry. That is, nystagmus with rightward slow phases is stronger than nystagmus with leftward slow phases. At low oscillation frequencies, the asymmetry is about equal to the slow-phase velocities of the patient’s spontaneous nystagmus with eyes closed; but at higher frequencies, the asymmetry is greater than could be accounted for by the spontaneous nystagmus. This additional asymmetry is thought to be due either to saturation of inhibitory responses of the intact labyrinth during rotation toward the side of the lesion or to an asym-

Figure 38-17. Phase, gain, and asymmetry values in relation to oscillation frequency for a patient with an acute right peripheral vestibular lesion.

Electronystagmography and Rotation Tests

Figure 38-18. Phase, gain, and asymmetry values in relation to oscillation frequency for a patient with a chronic left peripheral vestibular lesion.

metrical loss of velocity storage.19 This response pattern— abnormal low-frequency phase leads and high-frequency asymmetry—is routinely observed in patients with acute unilateral peripheral vestibular loss, and the asymmetry is always toward the side of the loss.20 A second type of abnormality consists solely of abnormally large phase leads at the lower oscillation frequencies. An example is seen in Figure 38-18 from a patient with a left acoustic neuroma. ENG showed a severe left caloric weakness in this patient. The rotation test abnormality seen here is presumed to reflect the same loss of velocity storage that is seen in patients with acute vestibular disorders. The velocity storage loss is persistent, remaining for years following vestibular malfunction although partial recovery nearly always occurs.21,22 The absence of tonic asymmetry in this patient illustrates the effect of vestibular compensation. If a peripheral vestibular lesion develops slowly, as it generally does in a patient with acoustic neuroma, the compensation process is able to rebalance the tonic asymmetry continuously and therefore to prevent the vertigo and spontaneous nystagmus that would otherwise occur. Even when the lesion develops suddenly, as it did in the previous patient with vestibular neuritis, compensation would quickly rebalance the tonic asymmetry over a period of days.23 Thus the response pattern in a patient with an acute lesion like that shown in Figure 38-17 would evolve into a pattern like that shown in Figure 38-18 if the patient were tested after a few weeks. This response pattern—abnormal low-frequency phase leads—is by far the most common abnormality seen in the slow sinusoidal rotation test. Stockwell reported abnormal low-frequency phase leads as the sole abnormality on the slow harmonic acceleration test in 109 of 305 dizzy patients.24 Twenty-seven of these patients showed no abnormalities on ENG—eight with a diagnosis of unilateral Ménière’s disease and the rest scattered across diagnostic categories. Fifty-five of these patients showed evidence of a chronic unilateral peripheral vestibular lesion, that is, a significant unilateral caloric weakness without significant spontaneous nystagmus, and most were diagnosed as having either Ménière’s disease or acoustic neuroma. The caloric weaknesses in these patients were nearly always greater than 50%. Patients with unilateral caloric weaknesses of less than 50% generally did not show abnormal phase leads.

619

Figure 38-19. Phase, gain, and asymmetry values in relation to oscillation frequency for a patient with bilateral absence of caloric responses, showing absent responses at all oscillation frequencies. Phase values were not plotted due to low response gains.

The remaining 27 patients showed various abnormalities on ENG, mostly either evidence of CNS system dysfunction or a combination of abnormalities. The slow harmonic acceleration test also shows abnormalities in patients with bilateral loss of vestibular function. An example is shown in Figure 38-19. This is a patient with total bilateral absence of caloric response of unknown origin. Rotation confirmed the bilateral caloric loss. The patient failed to show a clear nystagmus response at any oscillation frequency. The result shown in Figure 38-19 is actually quite uncommon. Most patients with bilateral absence of caloric response show absent responses or reduced response gains at the lower oscillation frequencies, but normal gains at the highest frequencies. An example is shown in Figure 38-20 from a patient who developed unsteadiness following a course of gentamicin therapy and showed a bilateral absence of caloric response. Baloh and colleagues reported that rotation testing often demonstrates normal vestibular function at high frequencies even when ice water irrigations have failed to provoke a response from either ear.25 In these cases, the results of caloric and rotation tests are not contradictory, since the caloric response is a response to a low-frequency stimulus and therefore should be similar to responses to low-frequency rotational stimuli. However, in

Figure 38-20. Phase, gain, and asymmetry values in relation to oscillation frequency for a patient with bilateral absence of caloric responses, showing normal response gains at the higher frequencies.

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other cases, rotation testing shows normal response gains at all frequencies, despite absent caloric responses, indicating a false-positive caloric test result. Clearly the slow harmonic acceleration test is the procedure of choice in evaluating suspected bilateral loss of vestibular function. The caloric test, even with ice water, does not define the extent of the loss and sometimes yields false-positive results.

Clinical Indications for Rotational Chair Testing RCT stimulates both peripheral vestibular systems simultaneously; however, it may be helpful in determining the site of lesion in certain disorders. Clinicians have made some suggestions as to when chair testing may be helpful in patient evaluation. First, when the ENG is normal and oculomotor results are either normal or observed abnormalities would not invalidate rotational chair results. RCT is used to expand the assessment of peripheral system dysfunction and status of compensation. Second, when the ENG suggests a wellcompensated state, despite the presence of a clinically significant unilateral weakness and active symptomatology. RCT is used to expand the investigation of compensation in a patient with a known lesion site and complaints suggesting poor compensation. Third, when the caloric irrigations are below 10 degrees/sec bilaterally, when caloric irrigations cannot be performed, or when results in the two ears may not be compared reliably because of anatomic variability. RCT is used to verify the presence of and define the extent of a bilateral weakness or to investigate further the relative responsiveness of the peripheral vestibular apparatus in each ear when caloric studies are unreliable or unavailable. Lastly, when a baseline measure is needed to follow the natural history of the patient’s disorder (e.g., possible early Ménière’s disease) or to assess the effectiveness of a particular treatment (such as chemical ablation).

REFERENCES 1. Baloh RW, Honrubia V, Jacobson K: Benign positional vertigo: Clinical and oculographic features in 240 cases. Neurology 37: 371–378, 1987. 2. Baloh RW, Sakata SM, Honrubia V: Benign paroxysmal positional nystagmus. Am J Otolaryngol 1:1–6, 1979. 3. Baloh RW, Jacobson K, Honrubia V: Horizontal semicircular canal variant of benign positional vertigo. Neurology 43(12):2542–2549, 1993. 4. Baloh RB, Spooner JW: Downbeat nystagmus: A type of central vestibular nystagmus. Neurology 31:304–310, 1981. 5. Fisher A, Gresty M, Chambers BR, Rudge P: Primary position up beating nystagmus: A variety of central positional nystagmus. Brain 106:949–964, 1983.

6. Leigh RJ, Zee DS: The Neurology of Eye Movements. Philadelphia, FA Davis, 1991. 7. Barber HO, Stockwell CW: Manual of Electronystagmography, 2nd ed. St. Louis, CV Mosby, 1980. 8. Baloh RW, Jacobson K, Honrubia V: Idiopathic bilateral vestibulopathy. Neurology 39:272–275, 1989. 9. Chambers BR, Mai M, Barber HO: Bilateral vestibular loss, oscillopsia, and the cervico-ocular reflex. Otolaryngol Head Neck Surg 93:403–407, 1985. 10. Leigh RJ, Zee DS: The Neurology of Eye Movements. Philadelphia, FA Davis, 1991. 11. Stockwell CW, Bojrab DI: Background and Technique of Rotational Testing. In Jacobson GP, Newman CW, Kartush JM (eds.): Handbook of Balance Function Testing. St. Louis, Mosby Year Book, 1993, pp 237–248. 12. Shepard NT: Rotational chair testing. In Goebel JA (ed.): Practical Management of the Dizzy Patient. Philadelphia, Lippincott Williams & Wilkins, 2001, pp 129–141. 13. Stockwell CW, Bojrab DI: Interpretation and usefulness of rotational testing. In Jacobson GP, Newman CW, Kartush JM (eds.): Handbook of Balance Function Testing. St. Louis, Mosby Year Book, 1993, pp 237–248. 14. Raphan T, Matsuo V, Cohen B: Velocity storage in the vestibuloocular reflex arc (VOR). Exp Brain Res 35:229–248, 1979. 15. Honrubia V, et al: Vestibulo-ocular reflexes in peripheral labyrinthine lesions: I. Unilateral dysfunction. Am J Otolaryngol 5: 15–26, 1984. 16. Raphan T, Matsuo V, Cohen B: Velocity storage in the vestibuloocular reflex arc. Exp Brain Res 35:229–248, 1979. 17. Honrubia V, et al: Vestibulo-ocular reflexes in peripheral, labyrinthine lesions: I. Unilateral dysfunction. Am J Otolaryngol 5: 15–26, 1984. 18. Baloh RW, Henn V, Jager J: Habituation of the human vestibuloocular reflex by low frequency harmonic acceleration. Am J Otolaryngol 3:235–41, 1982. 19. Honrubia V, et al: Evaluation of rotatory vestibular tests in peripheral labyrinthine lesions. In Honrubia V, Brazier MAB (eds.): Nystagmus and Vertigo. Clinical Approaches to the Patient with Dizziness. New York, Academic Press, 1982, pp 57–78. 20. Stockwell CW, Bojrab DI: Interpretation and usefulness of rotational testing. In Jacobson GP, Newman CW, Kartush JM (eds.): Handbook of Balance Function Testing. St. Louis, Mosby-Year Book, 1993, pp 237–248. 21. Stockwell CW, Bojrab DI: Interpretation and usefulness of rotational testing. In Jacobson GP, Newman CW, Kartush JM (eds.): Handbook of Balance Function Testing. St. Louis, Mosby-Year Book, 1993, pp 237–248. 22. Honrubia V, Jenkins HA, Baloh RW, et al: Vestibulo-ocular reflexes in peripheral labyrinthine lesions: I. Unilateral dysfunction. Am J Otolaryngol 5:15–26, 1984. 23. Halmagyi GM, Curthoys IS: Clinical changes in vestibular function with time after unilateral vestibular loss. In Herdman SJ (ed.): Vestibular Rehabilitation. Philadelphia, FA Davis, 2000, pp 172–194. 24. Stockwell CW: Vestibular function testing: 4-year update. In Cummings CW, et al (eds.): Otolaryngology-Head and Neck Surgery: Update II. St. Louis, Mosby-Year Book, 1989, pp 39–53. 25. Baloh RW, et al: Changes in the human vestibulo-ocular reflex after loss of peripheral sensitivity. Ann Neurol 16:222–228, 1984.

39

Outline Introduction Definitions Reporting Criteria Incidence Clinical Presentations and Natural History Etiology and Pathophysiology Theories of Pathogenesis Anatomic Factors Viral/Immune Theory Allergy Genetics Post-traumatic Hydrops Delayed Hydrops Clinical Evaluation Differential Diagnosis Medical Management Acute Treatment Prophylaxis Diuretics Vasodilators Steroids Allergy Management Gentamicin and Surgical Management

Chapter

Ménière’s Disease

Endolymphatic Sac Surgery Endolymphatic Sac Surgery Technique Vestibular Nerve Section Gentamicin Cochleosacculotomy Cochleosacculotomy Technique Transcanal Labyrinthectomy Transcanal Labyrinthectomy Technique Transmastoid Labyrinthectomy Transmastoid Labyrinthectomy Technique Translabyrinthine Vestibular Nerve Section Translabyrinthine Vestibular Nerve Section Technique Surgery and Hearing Outcomes Surgery and Quality of Life Other Approaches

INTRODUCTION Ménière’s disease (MD) is the idiopathic disorder defined by a symptom complex of episodic vertigo, fluctuating hearing loss, tinnitis, and aural fullness. Its etiology and pathophysiology are incompletely understood. The underlying pathology is thought to be endolymphatic hydrops, and many processes are suspected to share this end point, including viral infection, allergy, and autoimmunity. The treatment of MD remains controversial partly because of the unpredictable nature of the disease with periods of remission and a substantial rate of spontaneous resolution. Empirical medical therapy consists of low-salt diet and diuretic medication, but this approach is unproved. Surgical intervention continues to prompt heated debate. Randomized placebo-controlled trials are very difficult to perform for several reasons: (1) MD lends itself poorly to definition and staging, (2) defining treatment outcomes in a disease largely characterized by subjective symptoms is imprecise, and (3) placebo-controlled trails are unfeasible as long as investigators and patients

Stephanie Moody Antonio, MD Rick Friedman, MD, PhD

object to randomization to a nontreatment or sham treatment control group.1

DEFINITIONS The diagnosis of classical MD is suspected based on the clinical history. People with MD experience incapacitating vertigo, often with nausea and vomiting, typically lasting hours. Dysequilibrium of a more constant nature may persist for 24 to 72 hours after the attack, but it usually resolves completely. Otologic complaints include tinnitis and pressure in the head or ear during vertigo spells. Audiologic evidence of fluctuating low-frequency or progressive sensorineural hearing loss is required to confirm the diagnosis. Tinnitis, hearing loss and aural pressure allow identification of the affected ear. The term cochlear hydrops describes fluctuating low-frequency hearing loss without associated vertigo. Fluctuating low-frequency hearing loss with tinnitis and 621

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aural fullness may precede MD. Eventual development of the full syndrome occurs in 37% to 42% of patients with cochlear symptoms.2 Of patients with definite MD, 40% have purely hearing symptoms prior to the first vertigo attack.3 Patients with severe and long-term MD are at risk of developing Tumarkin otolithic crisis, or drop attacks. These are abrupt attacks of falling after loss of lowerextremity muscle tone without loss of consciousness.4 The incidence is reported as 6% to 7% of patients with MD, although in one report, the incidence was as high as 72%.5 The cause is thought to be a sudden stimulation of the vestibular end organ by a shift of the utricular macula or rupture of inner ear membranes,6 but the exact cause is unknown. This symptom may be secondary to a cardiac, cerebrovascular, or seizure process and these must be ruled out.7 Lermoyez’s syndrome is a variant of MD wherein hearing loss and tinnitis precede an attack of vertigo by days to months, subsiding with the onset of vertigo.8 The pathophysiology is unknown. In one patient with the syndrome whose temporal bones were studied, hydropic changes were limited to the upper basal turn and saccule in contrast to more wide involvement of the cochlea with classic MD.9

REPORTING CRITERIA The Committee on Hearing and Equilibrium of the American Academy of Otolaryngology–Head and Neck Surgery publishes guidelines for defining, reporting, and interpreting results of the treatment of MD.10 (We suggest familiarity and attention to these criteria to anyone reviewing the literature.) Diagnostic criteria for MD are categorized as certain, definite, probable, or possible MD. Certain MD includes definite MD plus histopathologic confirmation. Definite MD is specifically defined as the presence of recurrent, spontaneous episodes of vertigo, documented hearing loss, aural fullness, and tinnitus. Either tinnitus or aural fullness must be present. The vertigo episodes last at least 20 minutes but more commonly for hours, are disabling, and are accompanied by nausea and vomiting. The diagnosis of MD requires at least two definitive spells of 20 minutes or longer. Probable MD is defined by only one episode of vertigo with hearing loss and tinnitus or aural fullness. Possible MD may be used to describe typical episodic vertigo without hearing loss or sensorineural hearing loss with dizziness, but without definitive episodes. Underlying causes for the syndrome (otosclerosis, syphilis, trauma, etc.) are excluded prior to the assumptive designation of idiopathic MD. Specific criteria were outlined by the Committee for Requisite Hearing Loss. When reporting treatment outcomes, the frequency of attacks during the 6 months before treatment should be compared with that of 18 to 24 months after treatment. A numeric scale and a disability scale were suggested (Table 39-1). These scales can be used to evaluate changes as improved, unchanged, or worse. Hearing stage (Table 39-2) can be applied to certain or definite MD. The criteria for the determination that a hearing change is significant are a change of 10 dB or more in pure tone average (PTA) of

TABLE 39-1. Reporting Recommendations for Ménière’s Disease Vertigo Class Class A Class B Class C Class D Class E

Numeric Score* 0 1–40 41–80 81–120 >120

Description Complete control Substantial control Limited control Insignificant control Worse

*Numeric score = 100 × Spells per month in 24 months after treatment. Spells per month in 6 months before treatment.

hearing thresholds at 500, 1000, 2000, and 3000 Hz; or a change in a word recognition score of 15% or more. The worst pretreatment audiogram up to 6 months before treatment is compared with the worst post-treatment audiogram at 18 to 24 months follow-up. Longer follow-up is preferred.10 These guidelines for defining the disease and reporting treatment outcome provide a common reference point for critical assessment of treatment efficacy as reported in the literature. Improved methods to classify and quantify this disease are needed. New clinimetric methods for the study of MD have been developed, including clinical scales of dizziness, hearing loss, and tinnitus. These types of scales may provide valuable insight into the natural history and management of MD since they allow quantification of subjective symptoms. In addition, the disability resulting from these symptoms is influenced by psychological, physical, and social-support structures. Common scales include the Dizziness Handicap Inventory (DHI),11 the Tinnitus Handicap Inventory (THI),12 and the Hearing Handicap Inventory for Adults (HHI).13

INCIDENCE The incidence of MD is difficult to determine because of the character of the disease, with the sometimes subtle onset (cochlear symptoms only), fluctuating symptoms, long periods of remission, and inconsistency in establishing the diagnosis.14 Studies from Sweden and Great Britain estimate the occurrence of MD in those populations as 46 in 100,000 people and 100 in 100,000 people, respectively.15,16 In the population of Rochester, Minnesota, the annual incidence between 1951 and 1980 was 15.3 per 100,000 and the prevalence on January 1, 1980, was 218 per 100,000 population.17 In Finland, the incidence was 4.3 per 100,000 per year in 1992 to 1996 and the prevalence in 1996 was 43 per 100,000.18 The onset of symptoms peaks at 40 to 60 years of age. The disease is uncommon in children.3,19,20 Bilaterality is oft TABLE 39-2. Stages of Ménière’s Disease Stage

Four-Tone Average (dB)

1 2 3 4

≤ 25 26–40 41–70 >70

Ménière’s Disease

debated with reported incidence ranging from 10% to 70%.3 The frequency of bilateral disease increases with time, and at 20 years reached 47% in 161 patients followed in Sweden.21 In Haye and Quist-Hanssen’s longitudinal study of 111 patients and in Green, Blum, and Harner’s study of 108 patients, 37% and 34%, respectively, developed bilateral disease.3,20 Subclinical disease in the asymptomatic ear was observed by Paparella who found that 78.6% of patients with clinically unilateral MD had abnormal audiometric findings in the asymptomatic ear and that 32% had the complete criteria necessary to diagnosis MD in that ear.22 Friedrichs and Thornton used the traveling wave velocity test (based on the stiffness of the basilar membrane) and diagnosed subclinical hydrops in 27% of the contralateral ears in 100 patients with clinically unilateral MD.23

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for 20 years or longer, most have hearing loss of 50 dB or more and all have at least 30 dB of loss.21 Tinnitus and aural fullness are present in the majority of patients in the long term.20 Quality of life measures suggest MD adversely affects daily life.24,25 Symptoms of MD correlate with other medical and psychological complaints such as dysphoria, anxiety, insomnia, and lack of concentration.24 Using the Medical Outcomes Survey-Short Form, Kinney found that patients with MD functioned like patients with minor medical conditions on physical functioning subtests, but more like patients with major medical conditions for vitality, social function, and role limitations, and poorer than patients with major medical conditions for mental health.26

ETIOLOGY AND PATHOPHYSIOLOGY CLINICAL PRESENTATION AND NATURAL HISTORY The typical presentation of MD includes sudden attacks of vertigo with unilateral hearing loss, tinnitus, and aural fullness. The vertigo is incapacitating, often with nausea and vomiting, lasting several hours. It is not uncommon for vertigo to last only minutes or for as long as 24 hours. Dysequilibrium accompanies the vertigo and may persist for 24 to 72 hours after the acute vertigo subsides. Between attacks patients are usually completely asymptomatic, but may describe persistent disequilibrium. Some patients describe a chronic state of dizziness with intermittent superimposed vertigo spells. Patients may also describe positioning vertigo. The attacks may be preceded by an aura consisting of a vague sense of dizziness, aural fullness, tinnitus, or a change in hearing. The attacks may also be sudden and without warning. Associated otologic complaints include hearing loss, tinnitus, and pressure in the head or ear before or during the vertigo attack. All four classical symptoms are often not recognized and may not be present during early disease. Some patients are so distressed by the vertigo that they have not noticed these problems until instructed to record them. Diplacusis can be an early signal and can sometimes be elicited by a thorough history. The frequency of vertigo attacks varies widely with a mean of 6 to 11 episodes per year.21 At worst, episodes can occur 30 times per year.3 Attacks may occur in clusters or on a regular schedule. Periods of remission may last years, only to be followed by recurrence. Spells tend to change in severity over time, becoming more mild; but once again, this is unpredictable, and a long period of time with mild spells may be suddenly ended with a severe spell. Typically, the disease eventually “burns out” with decline and cessation of vertigo and progressive deterioration of hearing. With minimum follow-up of 9 years in 108 patients, Green reported vertigo was completely absent in 54% and decreased in 30%.20 Hearing fluctuates in the early course of disease, but eventually becomes progressively worse, stabilizing at about 50 dB PTA and 50% word discrimination score. Low frequency hearing loss extends to involve high frequencies and the audiogram develops a flat pattern.2 The majority of hearing loss occurs in the first few years of disease.2,21 In patients who have been observed

The etiology and pathophysiology of MD are not known. Some proposed etiologies of “idiopathic” MD are anatomic abnormality, viral infection, autoimmune disease, and allergy. The underlying cause-and-effect relationship of these possible etiologies on the function of the inner ear and endolymphatic system is unknown. One of the most well accepted theories of the pathogenesis of MD is based on the belief that endolymphatic hydrops is the pathological correlate of MD. In this theory, hydrops is caused by mechanical obstruction to endolymphatic flow or by intrinsic malfunction of the endolymphatic system resulting in an overabundance of endolymphatic volume and/or pressure.27 There are many proposed mechanisms that may contribute to aberrations in endolymphatic pressure and volume and endolymphatic sac and duct malfunction. While reading the following discussion on the etiology and pathophysiology of MD, the reader should note that hydrops is not specific to MD and several scientists have raised significant problems with the proposed theories. No alternative theory has been advanced.

Theories of Pathogenesis Theories for the underlying mechanism that results in hydrops include excessive endolymph production, decreased endolymph resorption, fibrosis of the endolymphatic sac or duct, and altered glycoprotein metabolism.28 As a pathologic sign only, hydrops may or maynot be associated with MD symptoms.27 A trigger or other mechanism must therefore provoke an acute change in physiology that results in the symptom complex of MD. The cause of the sudden attacks of vertigo and aural symptoms associated with MD remains unknown. Figure 39-1 is a flowchart of these various factors. Schuknecht developed a theory to explain the acute attacks as well as the progressing hearing loss and dysequilibrium.6 The disease probably begins with a prodromal stage of gradual distention of the endolymphatic system, which may be associated with very few or no symptoms. As the distension progresses, there is thinning and atrophy of the more yielding parts of the membranous labyrinth (Reissner’s membrane and saccular wall), which leads to ruptures and the sudden release into the reduced perilymphatic space of large volumes of endolymph (Fig. 39-2).

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Figure 39-1. Multiple etiological factors might contribute to endolymphatic dysfunction. The exact nature of the mechanisms promoting inner-ear dysfunction is unknown. The pathologic correlate is endolymphatic hydrops. Hydrops can remain asymptomatic or become Ménière’s disease under the influence of a trigger that brings about a sudden devastation in endolymphatic flow, either by rupture of membranes or by sudden release of obstructed longitudinal endolymphatic flow.

Consequently, the sensory and neural structures that are exposed to this potassium-rich (neurotoxic) endolymph are paralyzed, resulting in sudden hearing loss or vertigo. As the biochemical components of the perilymphatic compartment are restored to normal, the symptoms subside. Aided by the collapse of the distended membrane, the rupture heals and the stage is set for a repetition of the process. Progressive hearing loss can be attributed to progressive disturbances in motion mechanics caused by the distorted, dilated, and collapsed membranes (Fig. 39-3) as well as a loss of specialized cell types and alterations in inner ear biochemistry and bioelectric potentials.6

Anatomic Factors

Another theory emphasizes a vital role of the endolymphatic sac. In this theory, described by Gibson and Arenberg,29 a disturbance in longitudinal flow of endolymph (possibly linked to a narrow vestibular aqueduct) from the cochlear duct to the endolymphatic sac results in hydrops. The sac is postulated to actively regulate the flow by maintaining an osmotic gradient and secreting glycoproteins that attract movement of endolymph toward the sac. In addition, the sac may produce saccin, a hormone thought to increase the volume of endolymph, which may promote faster flow. In an ear affected by MD, metabolic debris obstructs longitudinal flow. The sac responds by secreting saccin and glycoproteins and the subsequent increase in flow overcomes the obstruction and clears the duct. The sudden restoration of movement of endolymph results in the sensation of vertigo. In later-stage MD, the sac is no longer able to affect flow of endolymph through an obstructed duct. Vertigo episodes subside but saccin secretion may continue, resulting in worsened hydrops and persistent hearing loss.

Viral/Immune Theory

Anatomic variations in the endolymphatic system may play a role in the development of endolymphatic hydrops. Several studies have documented that the vestibular aqueduct and the external aperture of the vestibular aqueduct are shorter and smaller and the endolymphatic sac and duct are less frequently visualized radiographically, surgically, and pathologically in patients with MD.30–33 Whether this anatomic difference contributes to the pathophysiology of MD is unclear.

One of the most accepted theories of etiology for idiopathic MD is the viral/immune theory.34,35 In this theory, a virus gains access to the inner ear via the middle ear or hematogenously. The initial event might be a direct effect of the viral infection and its inflammatory, immune, and microvascular-mediated injury. Subsequent attacks might not be caused by active virus but by immune-mediated cellular damage to various structures of the inner ear including the stria vascularis, dark cells, and the endolymphatic system. The basis of this theory is that the endolymphatic sac is primarily responsible for the immunodefense of the inner ear.34 An alternative explanation for the recurrent nature of attacks is reactivation of viruses commonly found latent in the vestibular and spiral ganglion cells, resulting in production of new viruses, which can migrate back along axons to the peripheral branches and into the perilymph, where they can cause direct injury or can provoke a local inflammatory reaction.35–37

Ménière’s Disease

625

Semicircular canals Reissners membrane Endolymphatic duct Saccule

Figure 39-2. A, Mechanism of Ménière’s disease, endolymphatic hydrops. Obstruction of the normal pathways of longitudinal flow among the cochlear duct, ductus reuniens, saccule, saccular duct, and endolymphatic duct results in distention of the cochlear duct, saccule, and endolymphatic sac. An enlarged saccule may compress and obstruct the ductus reuniens, saccular duct, and utricular duct. A herniated cochlear duct may obstruct the saccule and ductus reuniens. B, Mechanism of Ménière’s disease, membrane rupture. Release of obstruction by rupture of dilated membranes may lead to reversal of flow with release of excess fluid through the cochlear aqueduct. (Courtesy of Fred Linthicum, Jr., House Ear Institute, Los Angeles.)

Ductus reuniens

A

Cochlear aqueduct

Endolymphatic sac

Semicircular canals Reissners membrane Endolymphatic duct Saccule

Ductus reuniens

B

Cochlear aqueduct

Evidence for the viral theory includes the demonstration of herpes simplex virus (HSV) DNA in the vestibular ganglion and intraosseous endolymphatic sac,38–40 antiviral IgE in the sera of MD patients,41 and elevated anti-HSV IgG in the perilymph of MD patients,36 all with levels greater than controls. The pathologic features of axonal degeneration are thought to be consistent with a viral etiology.35 The importance of the immunologic activity in the pathophysiology of MD is supported by evidence of elevated circulating immune complexes,42 the presence of serum autoantibodies to inner ear antigens greater than in controls and greater than in patients with other otologic conditions,43,44 and evidence that the endolymphatic sac is the source of the inner ear immune response.37,45 Glucocorticoid receptors have been identified in the stria vascularis and may play a role in inner ear fluid homeostasis.46–48 In addition, Adams documented the production of

Endolymphatic sac

cytokines by cells of the spiral ligament.49 A positive clinical response to corticosteroids further supports the role of an immune phenomenon.35,36 Despite this evidence, a direct causal link of HSV or immunological reactivity to MD cannot be definitive.28,50 Studies are needed that further demonstrate a clinical association between MD and HSV or autoimmunity, document virus or immune mediators in inner ear tissues of affected patients, and establish an animal model with similar clinical and pathologic characteristics.51

Allergy Allergy may be another trigger for immune reactions resulting in MD. A significant number of patients with MD report airborne and food allergy.52 Patients treated with desensitization and diet showed a significant

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A

autosomal-dominant mode of inheritance, although an X-linked dominant form has been described.58 Features of familial MD have emerged in the literature. There is a reported association between familial cases of MD and migraine headaches.54,55 Most clinical reports demonstrate similarities in symptom severity and bilaterality in familial and sporadic MD.59,60 Morrison and colleagues, however, have detailed several distinctive features of the familial variant.59 In their series, more females were affected than males, a higher proportion of children and adolescents were affected, and many families displayed vestibular symptoms only. Based on the variability of inheritance and phenotypic expression noted in the literature, familial MD is likely a genetically heterogeneous disorder. Several observations have been made that not only suggest a genetic basis in some cases, but also present a possible mechanism for their molecular characterization. An association between MD and immune response genes has been identified.61,62 These findings are consistent with the clinical observation of a coincidence of MD and immune and allergic disease. The pathogenesis in these cases might be explained by a genetic predisposition to the identification and processing of certain immunogens, which affect endolymphatic homeostasis either directly or indirectly.

Post-traumatic Hydrops

B Figure 39-3. A, Membrane ruptures. Cochlea with diffuse hydrops (A). Rupture of Reissner’s membrane healed, but the thin membrane is now distended and collapsed against the spiral ligament (B). The saccular membrane is dilated and fused to the footplate of stapes (C). B, Rupture outpouching. Rupture of ampullary wall (*) with collapse of healed membrane filling ampulla (arrows). (Courtesy of Fred Linthicum, Jr., House Ear Institute, Los Angeles.)

improvement from pretreatment to post-treatment in both allergy and Ménière’s symptoms, including significant reduction in the number and the severity of vertigo.53

Genetics Genetic defects in structural proteins, growth factors or their receptors, ion channels and pumps, or proteins responsible for regulating the developmental cascade of the many genes involved in auditory development can lead to auditory and vestibular dysfunction. The complex processes underlying endolymphatic homeostasis are made possible by the coordinated temporal and spatial expression of many genes during embryonic and adult life. If a defect in one of these “homeostatic” genes were in the germ line, endolymphatic hydrops could be an inherited process. There have been several reports of familial Ménière’s disease in the literature dating back to the first reports by Brown in 1941 and 1949 and followed two decades later by Bernstein in 1965.54,55 Since that time, several reports have citied an incidence between 2.5% and 12%.56,57 The vast majority of these descriptions have suggested an

Post-traumatic MD has been described secondary to head trauma, barotrauma, and surgical trauma. As opposed to symptoms of perilymphatic fistula or vestibular concussion that occur immediately after injury, post-traumatic MD occurs months to years later. The mechanism is unknown, but fistulization of the bony labyrinth, direct injury to the membranous labyrinth, or disruption of the endolymphatic flow have been suggested.63

Delayed Hydrops Delayed hydrops is the new onset of MD symptoms in the setting of a previous severe hearing insult, usually unilateral. The onset of vertigo of Ménière’s type occurs 20 years later and can be either ipsilateral or contralateral. It might include fluctuating hearing loss, tinnitis, and fullness, especially notable in the contralateral cases. The etiology of the preexisting hearing loss can be sudden deafness, head injury, mumps, measles, mastoidectomy, meningitis, and influenza, often occurring during childhood.64,65 Acoustic trauma has also been associated with delayed hydrops.66,67 Pathologic findings of delayed endolymphatic hydrops have been documented by Schuknecht.68

CLINICAL EVALUATION The diagnosis of MD is based on the history and confirmed by the documentation of low-frequency sensorineural hearing loss. Diagnostic testing is desirable to confirm the diagnosis before undertaking destructive treatment procedures and to rule out contralateral asymptomatic disease.69 Despite the introduction of several diagnostic methods, none has yet proved to be the gold standard.69

Ménière’s Disease

Audiometric findings include low-frequency sensorineural hearing loss (occasionally with a mild conductive component), reduced discrimination, and loudness recruitment. In early stages of the disease, hearing loss fluctuates. In later stages, the audiometric pattern becomes flattened with extension of hearing loss to higher frequencies. In some cases, the pattern is “tent-like,” with both low and high frequency hearing loss and a peak at about 2000 Hz. Loudness recruitment, the abnormal growth of perceived loudness with stimulus intensity, was found in all 200 patients with MD in Hallpike’s series.69,70 Otoacoustic emissions have not been helpful in differentiating hydropic from normal ears.71,72 Vestibular testing is difficult to interpret in the presence of a highly variable and fluctuating disease. Although 30% to 50% of patients may show a unilateral weakness, another 25% may have completely normal exams.15,69 Some patients have hyperactive caloric testing.73 One group of authors has suggested that vestibular testing may vary with stage,73 suggesting a progressive dysfunction from hyperactive to normal and finally to reduced responses.74 Electrocochleography has been studied as a technique for identifying hydropic ears, but its clinical role remains unclear. The summating potential tends to be increased in diseased ears, possibly because the basilar membrane is displaced toward the scala tympani.69 A summating potential to action potential ratio more than 0.3 to 0.5 is more common in ears with active MD than in normal ears.69 The sensitivity of the test is low; however, various modifications have been suggested to improve the identification of ears affected by hydrops.69,75,76 The role of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of MD is limited to ruling out vestibular schwannoma or other solid lesion. Nonvisualization of the endolymphatic sac by CT and by MRI has been suggested to correlate with the presence of MD.31,32,77,78 Positive MRI findings have been confirmed during surgery78 and by histology.33 However, MRI does not differentiate an active hydropic ear from the inactive contralateral side.79 In a guinea pig model, standard 1.5-Tesla MRI showed enlargement of the scala media by preferentially enhancing the perilymph over the endolymph, allowing a clear demarcation between the two chambers.80 Gadolinium enhancement of the endolymphatic sac has been documented in a series of patients with auditory and vestibular symptoms.81 Corroborative studies and clinical correlation are needed to further investigate these findings. The continued advancement in imaging technology will no doubt enhance our understanding of MD.

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includes other manifestations of late syphilis, such as interstitial keratitis, cardiovascular disease, and neurologic abnormalities. In otosyphilis, pathologic findings include microgummata, inflammatory osteitis, endarteritis, and degeneration of the neurosensory structures.82,83 Irreversible obstruction of the endolymphatic duct and sac is associated with endolymphatic hydrops and is probably responsible for treatment failures (Fig. 39-4).82 Cogan’s syndrome includes episodic vertigo, hearing loss, and interstitial keratitis or other ocular findings but negative tests for syphilis. Atypical Cogan’s syndrome may include iritis, scleritits, papilledema, or systemic autoimmune disease such as sarcoidosis, rheumatoid arthritis, or Wegener’s granulomatosis. Temporal bone findings include endolymphatic hydrops, degeneration of the cochlear duct and labyrinth, and deposition of new bone.84 Acute vertigo lasting longer than 24 hours with a slow recovery over weeks with hearing loss and tinnitis is consistent with acute labyrinthitis. Vestibular neuritis is characterized by acute vertigo of the same nature without auditory symptoms.85 It can occur as a single episode or be recurrent. Both the single and recurrent types are associated

A

DIFFERENTIAL DIAGNOSIS As defined, MD is idiopathic. However, some cases of endolymphatic hydrops associated with the specific symptom complex (Ménière’s syndrome) are not idiopathic and are associated with syphilis, Paget’s disease, otosclerosis, or autoimmune inner ear disease.82 Congenital or acquired syphilis may produce Ménière’s syndrome. Clinically, the disease is more likely bilateral. Congenital syphilis is associated with Hutchinson’s teeth and interstitial keratitis.82 Late-stage otosyphilis usually

B Figure 39-4. Congenital syphilis. A, Vestibular aqueduct obliterated with inflammatory fibrosis with multinucleated giant cell reaction (A) and inflammatory infiltrate (B). B, Diffuse cochlear hydrops. (Courtesy of Fred Linthicum, Jr., House Ear Institute, Los Angeles.)

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with acute loss of caloric response. In sharp contrast to Ménière’s disease, the vertigo is prolonged and is followed by dysequilibrium that persists for months with slow recovery.85 The histopathology includes atrophy of peripheral vestibular nerve fibers and end organ.85 A viral etiology is suspected.40,85–87 Vascular compression syndrome can be characterized by recurrent disabling vertigo with or without hearing loss. These patients typically complain of disabling motion intolerance including dysequilibrium or vertigo when walking, after quick head movements, and while riding in a car.88–91 McCabe and Gantz reported an erroneous diagnosis of MD in 52% of patients who eventually underwent vascular loop decompression.88 The diagnosis can be made with constructive interference in steady state (CISS) MRI.92 Cerebellopontine angle tumors such as vestibular schwannoma and meningioma can cause symptoms similar to those of MD. Endolymphatic sac tumors in the posterior fossa have been reported to present with Ménière’s-like symptoms.93 Dizziness or hearing loss atypical for MD or otherwise suspicious should be evaluated with gadoliniumenhanced MRI. Migrainous vertigo is a diagnosis based on the presence of episodic vertigo with migraine and/or photophobia, phonophobia, and visual auras. In patients presenting to a neurologic dizziness clinic, 7% were diagnosed with definite migrainous vertigo.94 Vertigo may last longer than that of typical MD, and patients often report a personal or family history of migraine, motion intolerance, and onset of symptoms with visual cues. Hearing loss is uncommon in this group and can help differentiate these patients from those with MD.

MEDICAL MANAGEMENT There is no cure for MD; that is, at this time intervention does not eliminate the underlying cause of disease. The goals of medical management of MD are control and reversal of vestibular and cochlear injury. In light of the etiologic variability and the lack of understanding of the pathophysiology of endolymphatic hydrops, the design and evaluation of specific therapeutic interventions are challenging. The prolonged but the fluctuating nature of the disease and subjective nature of most of its important symptoms make randomized controlled clinical trials extremely difficult to perform. Current treatment strategies are based on anecdotal evidence and personal opinion. Nonetheless, clinicians have noted that medical strategies can control disease in 80% of patients (based on reduced frequency of acute vertigo), although no treatment has been decidedly shown to halt the progression of hearing loss. It is difficult to prove that any intervention is better than natural history alone. Specific goals in the treatment of MD include reduction in the frequency and severity of acute attacks of vertigo and hearing loss, reduction of tinnitis and aural fullness, reduction of progressive hearing loss, and improvement of quality of life.

Acute Treatment Vestibular suppressant and antiemetic medications are generally effective in controlling acute vertigo. Classes of

drugs useful for vertigo include benzodiazepines (diazepam), antihistamines (meclizine, promethazine, diphenhydramine, dimenhydronate), anticholinergics (meclizine, glycopyrrolate), and antidopaminergic (prochlorperazine, droperidol).95 Severe episodes may be treated with courses of oral steroid tapering over 5 to 10 days. In the authors’ experience, steroid burst treatment may lessen the severity of acute vertigo and promote earlier recovery of hearing.

Prophylaxis Several good review articles address long-term medical therapy for MD.2,95–100 Sodium restriction is the foundation of the treatment regimen. It is commonly thought that a low-salt diet will reduce sodium-related volume overload with subsequent redistribution to the endolymphatic space.95,100 The effects are likely more complicated than a simple change of plasma or endolymph sodium level, since a low-salt diet is known to have extremely little influence on the plasma sodium level and sodium levels in dendolymph are near normal in animal models with hydrops.101 Anecdotally, patients have reported acute symptoms after excessive salt intake and a positive response to salt restriction. There are no randomized controlled trials (RCT) to support this impression. Patients should be counseled to limit dietary salt to 2 grams per day.

Diuretics The use of diuretics is based on circumstantial evidence of a positive effect on hearing and vertigo with osmotic agents (glycerol, isosorbide), animal studies, a few nonrandomized studies, and one RCT.95,97 Acetazolamide s recommended because it is thought to inhibit carbonic anhydrase in dark cells and in the stria vascularis, thereby reducing endolymph production. Hydrochlorothiazide and combination hydrochlorothiazide and triamterene are commonly employed, but the mechanism of action is unclear. In a nonrandomized placebo-controlled study, Klockhoff and Lindblom showed a significantly better response of vertigo, hearing loss, and general condition to treatment with hydrochlorothiazide than with placebo.102 Van Deelen and Huizing published the only RCT and used a crossover placebo-controlled design. During 17 weeks of triamterene (Dyazide) treatment, subjects had significantly fewer vestibular complaints, but no reduction in hearing loss or tinnitis.103 Retrospective studies have also supported diet and diuretic therapy.104,105 Inasmuch as the disease fluctuates over time, patients can be weaned from treatment after 6 to 12 symptom-free months; treatment can be reinitiated when needed.

Vasodilators Vasodilators were historically recommended based on the belief that ischemia of the stria vascularis caused MD. Histamine (subcutaneous or sublingual) and betahistine (peroral) acting on H1 and H2 receptors cause capillary dilation.106 The authors found no RCT of histamine therapy. Betahistine (the oral analogue of histamine) has been studied in a few RCTs.107–109 Fraysse and colleagues

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noted a significant reduction in vertigo (in frequency, duration, and severity of attacks) at 60 days of betahistine treatment compared to flunarizine. Cochlear symptoms were also reduced in the group treated with betahistine.108 Schmidt and Huizing found no difference in imbalance between the two groups.107 In a double-blind crossover study reported by Oosterveld, patients had significant reduction of the incidence and severity of dizziness during 6 weeks of beta-histine treatment compared with 6 weeks of placebo treatment. This study included patients with other types of peripheral vertigo, and interestingly, the author’s opinion was that patients with MD responded less than did patients with other vestibular disorders.110 Other vasodilators such as nicotinic acid (50 to 200 mg), vitamin C, bioflavonoid complex, probanthine (15 mg), and diphenhydramine (50 mg) can be added, but there is little objective evidence to support their use.95

Steroids Mounting evidence of immune and inflammatory etiology of MD has motivated the investigation of steroids in the long-term management of MD. Although systemic steroid may distribute to the endolymphatic sac, vestibular nuclei, and central nervous system, it does not readily pass the blood-labyrinth barrier, whereas steroid applied to the round window accumulates in the perilymph and endolymph in animal models.111–113 Intratympanic steroid treatment for MD has been suggested as an alternative to surgical or ablative procedures when medical treatment has failed to control vertigo. Shea reported 2-year results after 48 patients with MD were treated with 16 mg of dexamethasone intravenously and 8 mg of dexamethasone intratympanically for 3 consecutive days followed by 3 to 90 days of oral dexamethasone. Of 30 patients, 19 (63.4%) had class A results (see Table 39-1) and 4 (13.3%) had class B results. Hearing was improved or unchanged in 45 or 48 (93.7%) ears based on the 1995 AAOHNS guidelines.113 The study is difficult to interpret because its design was not randomized and not controlled and treatment consisted of three routes of steroid administration. Silverstein and colleagues reported the only randomized controlled trial of intratympanic steroid. Seventeen patients underwent placement of tympanostomy tube and adhesiolysis of the middle ear and were then treated with either intratympanic steroid or placebo for 3 consecutive days. After 3 weeks, a crossover treatment was initiated. No significant difference in hearing or tinnitis was noted, but follow-up was limited and the disease stage was late, suggesting the patients would be unlikely to gain significant hearing benefit from any medication.114 Vertigo was not specifically evaluated in this study. In a nonrandomized prospective study, the rate of substantial or complete vertigo control after intratympanic dexamethasone (applied by the patient through a tympanostomy tube 0.25 mg every other day for 3 months) was 72% at 18 months. However, it was not significantly different than after intratympanic gentamicin or endolymphatic sac decompression.115 Intratympanic steroid may not produce improvement in hearing outcome.115,116 Randomized controlled trials are needed to further investigate the role of intratympanic steroid.

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Allergy Management Allergy management may be indicated in selected patients. Indications for allergy evaluation include bilateral symptoms, symptoms linked to food, seasons, or weather, steroid-responsiveness, or failure to respond to traditional treatment.53 In Derebery’s review53 of 113 patients treated with immunotherapy and/or food elimination/rotation diet, there was a significant reduction in vertigo, tinnitus, and hearing loss compared to pretreatment. Although a statistical comparison was not made because the allergy-treated group had significantly worse symptoms before treatment, the control group (patients who refused allergy treatment) rated their symptoms worse than did the treated patients at the end of the study. This suggests that not only did the treated group show significant improvement, but also they improved to levels that appeared better than the control group. Allergy therapy may include antihistamines, nasal steroid sprays, systemic corticosteroids, immunotherapy, and elimination and/or rotation food diets.117 Immunosuppressive management is closely linked to allergy therapy for immune-mediated MD. Preliminary studies of methotrexate and etanerocept show promise, but must be evaluated further.118–120

GENTAMICIN AND SURGICAL MANAGEMENT For the 10% to 20% of MD patients for whom medical management fails, further intervention may include vestibuloablative or nonablative and hearing preservation or nonpreservation approaches. When considering surgical intervention, it is important to understand that the goal is primarily to eliminate disabling vertigo and improve quality of life, since no surgical treatment has been proved to cure the underlying disease. Ultimate control of progressive hearing loss is ideal, but current strategies have not been proved to significantly alter long-term hearing outcome.

Endolymphatic Sac Surgery Endolymphatic sac surgery (ESS), a nonablative hearing preserving approach, includes decompression and various shunting techniques and was first described by Georges Portmann in 1926.121 It has since been the focus of fervent debate. The authors would direct the reader to examine the extensive literature but note that the only RCTs suggest limited efficacy.122,123 Quaranta and colleagues compared ESS to natural history at 2, 4, and 6 years and found a significant benefit at 2 and 4 years. The benefit did not differ at 6 years, at which time 85% of patients who received ESS and 74% of patients who did not had vertigo control.124 Various nonrandomized studies have reported 50% to 75% vertigo control in.124–128 Many series report ESS results in even higher rates of vertigo control but are uncontrolled.129–135 On the other hand, Jackson and colleagues reported that only 7% of their patients had complete control of vertigo at 2 years.136 Silverstein and colleagues reported no difference in a group of patients who were offered yet declined surgery and those who underwent ESS, both achieving a control rate of 71%

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at 2 years.137 Studies using standardized questionnaires found no difference in patient-scored dizziness after ESS compared to medically treated patients.26,138 The efficacy of the procedure is brought further into question when considering that insertion of a ventilation tube or cortical mastoidectomy alone may reduce vertigo.139,140 Considering the variability of vertigo control in reports of both surgical and nonsurgical management, the substantial spontaneous resolution of vertigo over time, and the lack of RCTs, it is extremely difficult to interpret the literature. Nonetheless, ESS is associated with a low rate of complications. It is commonly used as the first-line surgical treatment for patients with disabling vertigo despite maximal medical treatment because it offers an alternative to surgical procedures with higher risks. Endolymphatic Sac Surgery Technique The procedure is performed under general anesthesia. Intraoperative facial nerve monitoring and perioperative antibiotics are not routinely used. After a routine cortical mastoidectomy, the lateral semicircular canal and the short process of the incus are identified through the mastoid antrum. These two structures are critical landmarks for the identification of the intratemporal facial nerve. The middle fossa plate is identified superiorly and the sigmoid sinus and presigmoid posterior fossa plate posteriorly. The sigmoid sinus is skeletonized, with attention to its anterior aspect. Following the sigmoid medially, bone over the posterior fossa dura is removed. Exposure of the posterior fossa dura is extended toward the jugular bulb and into the retrofacial air cells, allowing a wide decompression over the sac. Air cells over the posterior semicircular canal can be removed to improve visualization, but the canal should not be excessively thinned to avoid a fistula. Staying behind and medial to the posterior semicircular canal and using diamond burrs will protect the vertical facial nerve. The sac is identified by a whitish thickening of the dura extending toward the distal aspect of the sigmoid sinus. An elevator can be used to lift the sac away from the overlying bone to define the operculum and the endolymphatic duct. In contrast to the sac, the dura appears thin and bluish. If a shunt is planned, the sac is carefully entered with a sharp hook or a sharp microblade and the lumen identified by its glistening character. It is important to visualize the shiny, smooth surface of the lumen to avoid creating a false lumen. The lumen is opened wide with a long blunt right-angle hook with specific attention toward the duct. AT-shaped Silastic may be placed to stent the lumen. Potential complications include cerebrospinal fluid (CSF) leak, fenestration of the posterior semicircular canal, labyrinthitis, and facial nerve injury. The rate of complications is less than 1%.

Vestibular Nerve Section Vestibular nerve section (VNS) can be performed via the middle fossa, retrosigmoid, or is a vestibuloablative but hearing preservation approach and retrolabyrinthine approaches. VNS can also be performed after labyrinthectomy as a nonhearing preservation procedure. These surgeries are discussed in Chapter 56.

Gentamicin Chemical labyrinthectomy exploits vestibulotoxic properties of gentamicin. The drug is administered intratympanically via a myringotomy, tympanostomy tube, microwick, or microcatheter. Authors have outlined numerous protocols for drug delivery, each reporting excellent control of vertigo (approximately 90%), but with variability in rates of hearing loss (0% to 50%). Profound hearing loss is less common.141–145 There is no consensus on the ideal dose or protocol for delivery. When comparing protocols for chemical ablation, the method, frequency, and duration of installation and the treatment end point (total nonresponse on ENG, nystagmus, dizziness, or hearing loss) must be considered as important factors in treatment effect and rates of complications such as perforated tympanic membrane and hearing loss. Complete ablation of vestibular function may not be necessary to abolish vertigo attacks, and it may be associated with a higher risk of hearing loss.145 The mechanism of action and the kinetics of transtympanic gentamicin are incompletely understood. There are various theories as to how intratympanic treatment results in ototoxic effects. Gentamicin can enter the inner ear through the round window membrane, the annular ligament, or vascular channels.146 The mechanism of injury is through damage to the dark cells of the crista ampullaris of the semicircular canals, the posterior wall of the utricle, the lateral wall of the crus communes, and the stria vascularis, resulting in a reduced production of endolymph.146,147 Cochlear and vestibular hair cell death has been consistently documented.148 Generally, patients report dizziness and dysequilibrium as vestibular injury takes place. This may persist for a few weeks and can be improved with vestibular rehabilitation exercises. The elderly seem to have greater difficulty with compensation.146 Although titration of dose to effect may reduce the incidence of hearing loss, sudden and profound hearing loss can occur. The cause of this unexpected event is unclear and unpredictable.146 Minor has described a protocol with low risk of hearing loss.145 Gentamicin (40 mg/mL) is buffered with sodium bicarbonate to a pH of 6.4 and a final concentration of 26.7 mg/mL. Phenol is used to anesthetize a small area of the tympanic membrane. The solution is injection using a 27-gauge needle to fill the middle ear (0.3 mL to 0.6 mL). The patient (in a supine position) is instructed to maintain the head turned away from the affected ear and remain in that position for 30 minutes. (Generally, the patient is instructed to avoid swallowing during that time, to reduce loss of medication through the eustachian tube). The patient returns weekly for audiogram and vestibular testing. Treatment is stopped if pure tone thresholds increased by more than 15 dB or if the SDS fell by more than 20%. Observation of spontaneous nystagmus or post–head shake nystagmus with Frenzel glasses indicates termination of therapy. If these criteria are absent, the patient is treated with a second dose of intratympanic gentamicin and reevaluated weekly for further doses until the end point criteria are identified. Using this protocol, Minor reported 91% complete or substantial vertigo control in 34 patients; 21% developed recurrent vertigo 10 to 24 months later, but all responded to additional doses of

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gentamicin. Only one patient (3%) developed profound hearing loss. Long-term hearing outcome based on AAOHNS criteria was better in 36%, unchanged in 32%, and worse in 32%.145 Other authors have found similar results with this protocol.143 Nedzelski and colleagues149 proposed a protocol using the same buffered solution of 26.7 mg/mL gentamicin (0.7 to 0.8 mL) administered through a ventilation tube and attached catheter three times daily for 4 consecutive days. The patient was evaluated for spontaneous and gazeevoked nystagmus, abnormal tandem gait, and hearing loss prior to doses 4, 7, and 10. Treatment was discontinued for abnormal findings. Of 114 patients treated with this protocol and followed at least 24 months, 93.3% had complete or substantial control of vertigo. Hearing was worse in 32.5% at 1 month after treatment and at 2 years improved in 25.9%, unchanged in 50.6%, and worsened in 25.8%; 16.4% of patients suffered profound hearing loss.150 Other authors report good results with a single planned injection followed by repeated injections for recurrent symptoms.142,151 There is no consistent relation between the total dose or the number of injections and the likelihood of profound hearing loss. In animal studies, a wide variation in perilymphatic concentration of drug has been documented and is likely to occur in humans, which may explain the unpredictable, dose-independent incidence of profound hearing loss after intratympanic gentamicin therapy.152 In an attempt to standardize dosage and better define and manipulate the pharmacokinetics of transtympanic gentamicin, microwicks and microcatheters have been studied and may hold promise.153,154 Controlled clinical trials are needed.

Cochleosacculotomy Cochleosacculotomy is a reasonable option for relief of vertigo when general anesthesia is contraindicated. The operation creates an internal shunt by fracturing the osseous spiral lamina and disrupting the cochlear duct. The theoretic permanent fistula between the perilymphatic and endolymphatic spaces may end episodic vertigo by disallowing periodic hydropic episodes. The procedure was developed by Schuknecht based on histologic observations that the membranous labyrinth of patients with MD can spontaneously fistulize, possibly accounting for remissions and arrest of symptoms. In animal studies, fracturedisruption of the osseous spiral lamina and cochlear duct can result in a permanent fistula with minimal impairment of hearing.155 Although some patients may have mild dysequilibrium, cochleosacculotomy does not appear to require prolonged vestibular compensation. Hearing loss is common and may be profound. Cochleosacculotomy Technique The patient is prepared for a transcanal procedure including anesthesia of the external auditory canal. A tympanomeatal flap is elevated. The round window is exposed. A 3-mm right-angle hook is inserted through the round window membrane and guided in the direction of the oval

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window while the pick is held against the lateral wall of the inner ear. Slight resistance will be felt as the pick violates the osseous lamina. The point of the pick will reach the saccule and the footplate of the stapes. Occasionally, a bony overhang at the round window niche interferes with introduction of the pick and can be reduced with a 2-mm diamond burr. Momentary vertigo may result, but usually not, presumably because the vestibular sense organs are not mechanically disturbed, and the endolymph from the fistula drains into the scala tympani rather than into the perilymphatic space of the vestibule. The perforation in the round window is sealed with muscle or perichondrium. The tympanomeatal flap is replaced and secured with Gelfoam, antibiotic ointment, or a small strip of silk cloth. Complications include hearing loss, perforation of the tympanic membrane, facial nerve injury, and perilymphatic fistula.

Transcanal Labyrinthectomy Transcanal labyrinthectomy offers a few advantages over transmastoid labyrinthectomy including shorter operating time and perhaps less risk of CSF leak and facial nerve injury. However, identification and removal of all vestibular end organs may be more difficult and the incidence of incomplete labyrinthectomy may be greater.

Transcanal Labyrinthectomy Technique A transcanal approach is performed through a tympanomeatal flap after routine preparation including canal anesthesia. After raising the flap, a curette is used to remove the bony tympanic annulus. The horizontal segment of the facial nerve, the entire stapes footplate, and the round window niche should all be visualized within the field. The stapedial tendon is sectioned and the stapes and incus are removed. The vestibular end organs are approached by exposing the entire vestibule, either by extending the oval window anteriorly and inferiorly or by removing bone between the oval and round windows. Before aspiration of the vestibule, the utricle should be removed with a 4-mm hook. The utricle may be displaced superiorly if the vestibule is inadvertently aspirated too early. The saccule is destroyed by aspiration of the anterior aspect of the vestibule. The ampulla of the lateral and superior semicircular canals may be approached with blunt dissection with a 4-mm hook that will drop into the ampullary ends of the canals. The posterior canal can be denervated by exposing the posterior ampullary nerve near the posterior aspect of the round window niche. After destruction of the end organs, the vestibule is packed with Gelfoam or a small fat or muscle plug. Some surgeons use gentamicin or streptomycin as irrigation or to soak the Gelfoam in order to ensure complete destruction of the neuroepithelium. The tympanomeatal flap is returned and secured with packing. Postoperatively, patients have acute vestibular dysfunction comparable to the level of preoperative function. Hospitalization for treatment with vestibular suppressants and rehabilitation is necessary. Profound hearing loss results. Complications include CSF leak, incomplete labyrinthectomy (usually because of failure to remove the utricle), and facial nerve injury.

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Transmastoid Labyrinthectomy Transmastoid labyrinthectomy allows a standard access to all neuroepithelium. Generally, it is 95% to 99% successful in obliterating vestibular function. Transmastoid Labyrinthectomy Technique The procedure is performed under general anesthesia with facial nerve monitoring. Perioperative antibiotics are not routinely required. A routine mastoidectomy is performed with identification of the mastoid antrum, lateral semicircular canal, and incus. The descending segment of the facial nerve is identified using the short process of the incus and the lateral semicircular canal as landmarks. The facial recess indicates the lateral position of the facial nerve and the horizontal canal indicates its posterior extent. There is no need to remove bone from the facial nerve. The bony labyrinth is skeletonized by removal of perilabyrinthine air cells and retrofacial air cells. It is helpful to clearly visualize each semicircular canal and the course of the facial nerve before proceeding. A systematic approach to this dissection aids in ensuring all the neuroepithelium is removed while protecting the facial nerve. It is perhaps best to “blue-line” all the canals before entering in order to preserve all the landmarks until the vestibule is entered. Using a medium cutting burr (4 mm or 5 mm), the superior-posterior surface of the lateral canal is blue-lined, then opened. Following the horizontal semicircular canal posteriorly, the posterior canal will be identified. It is best at this point not to open that canal completely, but again skeletonize it so that the common crus and superior semicircular canal are identified first. The superior canal is followed using a circular motion and the ampullated ends of the superior and lateral canal are then opened. Next, the posterior canal is followed inferiorly, medial to the facial nerve, and finally opened along the posterior aspect of the ampullated end. All three canals are carefully dissected with preservation of the medial walls of the superior and lateral semicircular canal ampulla and the inferior wall of the posterior canal ampulla. Just deep to the medial walls of the superior and lateral canal ampulla lies the labyrinthine segment of the facial nerve. Just inferior to the inferior wall of the posterior canal ampulla lies the region of the jugular bulb. The common crus is finally followed medially into the vestibule. The labyrinthine bone (Trautmann’s triangle) is be saucerized, permitting complete opening of the vestibule with a view of the utricle in the elliptical recess and the saccule in the spherical recess. The medial wall of the vestibule is the landmark for the fundus of the internal auditory canal (IAC). At this point all five portions of the neuroepithelium are clearly visualized (the ampulla of three canals, the utricle, and the saccule). Each is removed under high-power microscopy with a fine round knife and suction. The area is inspected for CSF leak and if none is found, the surgical defect can be closed routinely. If a leak is detected, the antrum should be obliterated and the cavity packed with fat.

Translabyrinthine Vestibular Nerve Section Translabyrinthine VNS is a helpful adjunct when labyrinthectomy or VNS fail to relieve vertigo and residual

nerve activity is suspected. This additional step results in preganglionic denervation. Translabyrinthine Vestibular Nerve Section Technique The procedure is performed under general anesthesia with perioperative antibiotics. The labyrinthectomy is completed as described. Further bone removal over the sigmoid sinus and decompression of the sinus may be required for adequate access to the medial aspect of the dissection. Compression of the sigmoid sinus is necessary to obtain the angulated view of the contents of the lateral internal auditory canal. It is helpful to leave an island of bone (Bill’s island) over the sigmoid sinus during this dissection to protect it from injury by the rotating burr and retraction of the suction-irrigator. The bone overlying the posterior cranial fossa dura is progressively removed anterior to the sigmoid sinus. This bone removal extends from the jugular bulb inferiorly to the superior petrosal sinus superiorly. The natural starting point for this dissection is at the vestibule, where the thin bone that separates the fundus of the IAC from the vestibule creates a natural blue-line. It may be sufficient to skeletonize only the lateral half of the IAC, but complete dissection to the porus may be performed. Useful landmarks include a line drawn between the superior semicircular canal ampulla and the sinodural angle and a line drawn posteriorly parallel to the superior line starting at the level of the posterior canal ampulla. Once the IAC is skeletonized, thin bone can be lifted with a right-angle pick. The transverse crest is exposed in the fundus using small diamond burrs. Bill’s bar serves as a bony landmark for the facial nerve, which lies anterior to it. A diamond burr and copious irrigation allow identification of Bill’s bar and the fallopian canal. The dura is opened with a sharp right-angled hook or sickle knife. A 1-mm hook is inserted and Bill’s bar is palpated. Then after sliding posterior to Bill’s bar, the hook is used to avulse the superior vestibular nerve inferiorly. After identification of the plane between the superior vestibular nerve and the facial nerve, small fibers are lysed with sharp or blunt dissection. The inferior vestibular nerve is also avulsed with specific attention to identification and division of the singular nerve (posterior ampullary nerve). Scarpa’s ganglion lies centrally within the IAC. Resection of a 5-mm length of vestibular nerve, medial to the fused portion will include Scarpa’s ganglion and complete the denervation. The surgical site is closed by reapproximating the dura, sealing defects with fat strips, and packing the mastoid with fat. The incision is closed in two layers and a bulky pressure dressing is applied. Complications include CSF leak, facial paralysis, and meningitis.

SURGERY AND HEARING OUTCOMES The current literature on the ESS procedure and other surgical procedures for MD provides conflicting evidence as to the benefits of surgery on attenuating progressive hearing loss. The variability in results is, in no small measure, due to the lack of randomized controlled studies with

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Figure 39-5. Management protocol for suspected Ménière’s disease.

objective outcome data comparing the hearing outcome of surgical procedures to that of MD natural history. The VNS procedure, although highly successful in eliminating vertigo in MD patients, does not appear to have an effect on hearing or other MD symptoms. Hearing loss after VNS follows the expected course of progressive loss associated with MD: About 50% of patients have stabilized or improved hearing and about 50% have worse hearing.156–159 Hearing improvement or stabilization after ESS is supported by several published studies but disputed by others. A frequently quoted paper by Thomsen and colleagues

compared ESS to an active placebo group (simple mastoidectomy).122 The authors reported subjective hearing loss to be “slightly” significantly better in the ESS group than in the placebo group. Objective testing showed no significant difference between the two groups but supported a “tendency” toward better hearing postoperatively in the ESS group, mainly manifested at 250 Hz. When the data were reexamined by Welling and Nagaraja, no significant difference in hearing outcome was found, but the authors suggest “the data seem to favor the active treatment even though statistical significance was not attained.”160 Quaranta compared a control group (patients

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who were offered but declined surgery) to patients after ESS. At 7 to 19 years of follow-up, 65% of patients who declined surgery and 45% of patients who had ESS had stable or improved hearing.124 Goin and colleagues also found no difference in hearing after ESS compared to patients who were offered but declined surgery.161 In various uncontrolled series, objective hearing outcome has been reported to be better or unchanged in 43% to 78% after undergoing ESS.124,125,127,132,161–163

2. 3. 4. 5. 6.

SURGERY AND QUALITY OF LIFE

7.

A review of studies using direct subjective evaluation of tinnitus and aural fullness suggests ESS may ameliorate these symptoms. Improvement in tinnitus has been reported in up to 75% of patients after ESS.127,134 However, the range of improvement has been broad (21% to 75%).123,125,127,133,134,136,162 Quaranta and colleagues reported substantial improvement in tinnitus and aural fullness after ESS compared to patients who declined surgery.124 In studies of tinnitus outcome, between ESS and VNS125,162 and ESS and placebo,123 results were not significantly different. After VNS, tinnitis was improved in 9% to 40%.20,156,159,164–166 Aural fullness is improved in 28% to 79% after ESS and 43% to 64% after VNS.20,125,126,135,136,165,166 Evaluation of self-perceived tinnitus, dizziness, hearing handicap, and quality of life with validated questionnaires provides an additional, possibly quantifiable mechanism to evaluate outcomes. Kinney and colleagues used the DHI, THI, HHI, and the SF-36 to compare treatment outcomes for medically and surgically (20 ESS and 1 VNS) treated patients.26 No significant difference in hearing outcome or disease-specific measures were found among the surgical group compared to the medical treatment groups, but the standard deviations were high, suggesting significant variability within the groups. Smith and Pyle reported pre- and postoperative SF-36 scores for patients who underwent ESS and found that although patients preoperatively scored significantly lower than norms, postoperatively the scores improved to the level of the standardized normative scores.167 Eisenman and colleagues reviewed HHI scores for patients after VNS and labyrinthectomy and reported that both groups had scores suggesting moderate disability with no significant difference between the treatment groups.168

8.

OTHER APPROACHES Low-pulse pressure,169–171 ultrasound,172 cryosurgery173,174 and alternobaric and hyperbaric oxygen therapy175 have been introduced, but evidence to support their use is insufficient. Figure 39-5 shows a management algorithm.

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15. 16. 17.

18. 19. 20.

21. 22. 23.

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25. 26.

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148. Hoffer ME, Kopke RD, Weisskopf P, et al: Microdose gentamicin administration via the round window microcatheter: Results in patients with Ménière’s disease. Ann N Y Acad Sci 942:46, 2001. 149. Nedzelski JM, Chiong CM, Fradet G, et al: Intratympanic gentamicin instillation as treatment of unilateral Ménière’s disease: Update of an ongoing study. Am J Otol 14(3):278, 1993. 150. Kaplan DM, Nedzelski JM, Chen JM, et al: Intratympanic gentamicin for the treatment of unilateral Ménière’s disease. Laryngoscope 110(8):1298, 2000. 151. Harner SG, Driscoll CL, Facer GW, et al: Long-term follow-up of transtympanic gentamicin for Ménière’s syndrome. Otol Neurotol 22(2):210, 2001. 152. Hoffer ME, Allen K, Kopke RD, et al: Transtympanic versus sustained-release administration of gentamicin: Kinetics, morphology, and function. Laryngoscope 111(8):1343, 2001. 153. Hoffer ME, Kopke RD, Weisskopf P, et al: Use of the round window microcatheter in the treatment of Ménière’s disease. Laryngoscope 111(11 Pt 1):2046, 2001. 154. Schoendorf J, Neugebauer P, Michel O: Continuous intratympanic infusion of gentamicin via a microcatheter in Ménière’s disease. Otolaryngol Head Neck Surg 124(2):203, 2001. 155. Schuknecht HF: Cochleosacculotomy for Ménière’s disease: Theory, technique, and results. Laryngoscope 92:853, 1982. 156. Tewary AK, Riley N, Kerr AG: Long-term results of vestibular nerve section. J Laryngol Otol 112(12):1150, 1998. 157. Wazen J, Markowitz A, Donatelle C, et al: Hearing after retrolabyrinthine vestibular neurectomy. Laryngoscope 100(5):477, 1990. 158. Rosenberg SI, Silverstein H, Hoffer ME, et al: Hearing results after posterior fossa vestibular neurectomy. Otolaryngol Head Neck Surg 114(1):32, 1996. 159. Pappas DG Jr, Pappas DG Sr: Vestibular nerve section: LongTerm follow-up. Laryngoscope 107(9):1203, 1997. 160. Welling DB, Nagaraja HN: Endolymphatic mastoid shunt: A reevaluation of efficacy. Otolaryngol Head Neck Surg 122(3):340, 2000. 161. Goin DW, Mischke RE, Esses BA, et al: Hearing results from endolymphatic sac surgery. Am J Otol 13(5):393, 1992. 162. Primrose WJ, Smyth GD, Kerr AG, et al: Vestibular nerve section and saccus decompression: An evaluation of long-term results. J Laryngol Otol 100(7):775, 1986. 163. Quaranta A, Onofri M, Sallustio V, et al: Comparison of long-term hearing results after vestibular neurectomy, endolymphatic mastoid shunt, and medical therapy. Am J Otol 18(4):444, 1997. 164. Moffat DA, Toner JG, Baguley DM, et al: Posterior fossa vestibular neurectomy. J Laryngol Otol 105(12):1002, 1991. 165. McElveen JT Jr, Shelton C, Hitselberger WE, et al: Retrolabyrinthine vestibular neurectomy: A reevaluation. Laryngoscope 98(5):502, 1988. 166. Colletti V, Fiorino FG, Carner M, et al: Vestibular neurectomy and microvascular decompression of the cochlear nerve in Ménière’s disease. Skull Base Surg 4(2):65, 1994. 167. Smith DR, Pyle GM: Outcome-based assessment of endolymphatic sac surgery for Ménière’s disease. Laryngoscope 107(9):1210, 1997. 168. Eisenman DJ, Speers R, Telian SA: Labyrinthectomy versus vestibular neurectomy: Long-term physiologic and clinical outcomes. Otol Neurotol 22(4):539, 2001. 169. Odkvist LM, Arlinger S, Billermark E, et al: Effects of middle ear pressure changes on clinical symptoms in patients with Ménière’s disease: A clinical multicentre placebo-controlled study. Acta Otolaryngol Suppl 543:99, 2000. 170. Densert B, Sass K: Control of symptoms in patients with Ménière’s disease using middle ear pressure applications: Two years followup. Acta Otolaryngol 121(5):616, 2001. 171. Densert B, Densert O, Arlinger S, et al: Immediate effects of middle ear pressure changes on the electrocochleographic recordings

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in patients with Ménière’s disease: A clinical placebo-controlled study. Am J Otol 18(6):726, 1997. 172. Hillerdal M, Friberg U, Svedberg A, et al: Ultrasound treatment of Ménière’s disease. Otolaryngol Clin North Am 27(2):337, 1994. 173. Wolfson RJ: Labyrinthine cryosurgery for Ménière’s disease— present status. Otolaryngol Head Neck Surg 92(2):221, 1984.

174. House WF: Cryosurgical treatment of Ménière’s disease. Arch Otolaryngol 84(6):616, 1966. 175. Fattori B, De Iaco G, Vannucci G, et al: Alternobaric and hyperbaric oxygen therapy in the immediate and long-term treatment of Ménière’s disease. Audiology 35(6):322, 1996.

40

Outline Introduction Autoimmune Inner Ear Disease Clinical Presentation

Chapter

Autoimmune Inner Ear Disease

Diagnosis Immunosuppressive Therapy Conclusions and Future Directions

INTRODUCTION There has long been a notion that the immune system might be capable of damaging the inner ear or eighth cranial nerve, leading to symptoms of hearing loss or dizziness (or both). Some well-documented examples in which systemic autoimmune disease does this include lupus erythematosus, ulcerative colitis, Cogan’s syndrome, and multiple sclerosis. In some inner ear diseases, for example, Ménière’s syndrome and idiopathic sudden sensorineural hearing loss (SNHL), an immune-mediated mechanism has been hypothesized but not demonstrated. One condition, characterized by the clinical presentation of idiopathic, rapidly progressive, bilateral SNHL, has come to be known as autoimmune inner ear disease (AIED). Whether all patients with this presentation have the same underlying pathophysiology and whether that pathophysiology is autoimmune are unknown. However, the disorder is extremely important because it represents one of the medically reversible causes of SNHL.

AUTOIMMUNE INNER EAR DISEASE In 1979, McCabe described 18 patients with idiopathic, rapidly progressive, bilateral SNHL who regained hearing after administration of corticosteroids.1 He theorized an autoimmune cause based on the response to immunosuppressive drugs. The next decade saw proliferation of a host of clinical reports, diagnostic tests, and treatment protocols for this entity, few of which have subsequently been validated. The next significant step toward understanding this disorder came in 1990 when Harris and Sharp reported circulating antibodies against inner ear antigens detected by use of a Western blot technique.2 Four years later Moscicki and coworkers presented the clinical correlation of idiopathic, progressive, bilateral sensorineural

Steven D. Rauch, MD

hearing loss (IPBSNHL) with circulating antibodies against a 68-kD protein antigen present in bovine inner ear and renal extracts.3 They demonstrated that the presence of these antibodies correlated both with activity of disease and steroid responsiveness. Using different experimental approaches, Billings and colleagues and Bloch and coworkers both identified the 68-kD protein antigen as heat shock protein 70 (Hsp70) in 1995.4,5 Hsp70 is a ubiquitous protein found in all living cells. It primarily functions as a molecular chaperone, binding to nascent peptide chains during protein synthesis and aiding in intracellular and transmembrane transport of proteins. It has a peptide binding site that makes it very “sticky”; that is, it tends to bind to other proteins or protein fragments. Since it is unclear why anti-Hsp70 antibodies would specifically damage the ear and since the propensity for Hsp70 to bind other peptides is well documented, it may be that it colocalizes with some other inner ear antigen that is the actual target in IPBSNHL. Another approach to understanding the cause of this disorder was taken by Carey and coworkers. They immunized mice with chick and guinea pig inner ear extracts and created monoclonal antibodies against inner ear cells. One particular antibody, dubbed “KHRI-3,” binds to supporting cells of the organ of Corti, creating a characteristic “wine glass” staining pattern using immunofluorescence.6–12 Infusion of KHRI-3 into live guinea pigs produces hearing loss.7–9 The KHRI-3 antibody also binds to a 68- to 72-kD antigen on Western blot of inner ear extract.6 Sera from some humans with IPBSNHL strongly stained a 68- to 72-kD inner ear antigen immunopreciptated from guinea pig inner ear extract with KHRI-3, and these same patient sera stained organ of Corti supporting cells in a wine glass pattern.13 This is strong evidence that KHRI-3 and human antibodies recognize the same inner ear supporting cell antigen. The target antigen of KHRI-3 has not yet been identified, but it is not Hsp70. 639

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The Western blot assay for circulating antibodies reactive with 68- to 72-kD antigen, whether it is Hsp70 or the inner ear supporting cell antigen target of KHRI-3, is of unproven clinical value. The assay is not standardized, and it has not been widely applied to other inner ear disorders nor to other autoimmune disorders in order to characterize its sensitivity and specificity. Therefore, IPBSNHL remains a clinical diagnosis based on historic and audiometric criteria. Likewise, IPBSNHL is not actually confirmed as an autoimmune disorder. Such confirmation must meet three criteria: (1) identification of antibodies or activated T cells reactive with a “self” protein, (2) identification of a characteristic immune-induced “lesion,” and (3) reproduction of this lesion by introduction of the specific antibodies or activated T cells into a naive host. Until these criteria are met, it is more accurate to refer to this entity by its clinical description (i.e., IPBSNHL) or acknowledge the undefined role of the immune system and call it immune-mediated inner ear disease. However, the popular notion that this is an autoimmune disorder has taken hold, and the condition is now widely referred to as AIED.

CLINICAL PRESENTATION The hallmark of the condition originally described by McCabe was the presence of rapidly progressive SNHL; too fast to be age-related degeneration and too slow to be sudden SNHL. This remains the most salient distinguishing feature of the disorder. Moscicki and colleagues articulated a precise clinical description of AIED (which they called IPBSNHL), which enabled them to minimize heterogeneity in their study population and, ultimately, to correlate this clinical presentation with results of Western blot assays.3 Specifically, they defined the condition as a bilateral SNHL of ≥30 dB at any frequency and evidence of progression in at least one ear on two serial audiograms performed ≤3 months apart; progression being defined as a threshold shift of ≥15 dB at one frequency, 10 dB at two or more consecutive frequencies, or a significant change in discrimination score. A single episode of threshold shift occurring in less than 72 hours and then stabilizing was classified as sudden SNHL and was excluded. Fluctuating hearing loss, however, qualified if progression also occurred according to the previous criteria. This is still the most explicit description of AIED in the literature. Analogous to Ménière’s disease, in the absence of a “gold standard” diagnostic test, adherence to these diagnostic criteria permits comparison of observations and results between different studies. In the paper by Moscicki and colleagues, demographic features, test results, and treatment outcome were reported for 72 patients with IPBSNHL.3 Subsequently, 66 additional cases of possible immune-mediated inner ear disease were studied using Moscicki’s same diagnostic criteria. Five patients were excluded from analysis because they had Cogan’s syndrome, an autoimmune vasculitis characterized by SNHL, vertigo, and interstitial keratitis of the eyes, leaving 61 cases. Results are tabulated in Tables 40-1 and 40-2. Demographic features and trends in the correlation of Western blot assay with steroid response

TABLE 40-1. Clinical Features of 61 Consecutive Patients Evaluated for Possible Autoimmune Inner Ear Disease Clinical Features

n

Male-to-Female Vestibular Symptoms Ménière’s disease Unilateral:Bilateral Other Autoimmune Diagnosis

32:29 30 (49.2%) 13 (21.3%) 5:8 9 (14.8%)

Mean age was 47 years (range: 4–72).

in this group of patients are essentially the same as Moscicki’s original cohort. However, the proportion of patients with positive Western blot assay and the proportion of Western blot-positive patients who responded to steroids are both lower than in Moscicki’s retrospective study. AIED and idiopathic sudden SNHL are two distinct disorders. AIED is far rarer than sudden loss. AIED is by definition bilateral, and sudden hearing loss is virtually always unilateral. Sudden hearing loss develops in ≤72 hours. In contrast, AIED progresses over days to months such that monthly serial audiograms will show continued decline. Sudden hearing loss is an otologic emergency with a treatment of “window” of perhaps 2 to 4 weeks during which a short “burst and taper” of corticosteroids must be administered in order to achieve optimum recovery. AIED is not urgent. Patients with progression over 6 to 12 months can still achieve significant recovery with administration of a long course of high-dose corticosteroids or other immunosuppressive drugs. Throughout the otolaryngology community some cases of SNHL are widely accepted as potentially reversible with corticosteroids. Unfortunately, however, few are aware that these two entities are quite different in cause, presentation, work-up, and management. Hasty administration of a short tapering course of steroids can delay diagnosis of AIED and can confuse interpretation of serologic testing. Approximately half of AIED patients also experience vestibular symptoms (see Table 40-1), including dysequilibrium, motion intolerance, positional vertigo, and episodic whirling vertigo of the Ménière’s type. Approximately 20% of AIED patients have a combination of fluctuating and progressing SNHL and episodic vertigo that meets strict American Academy of Otolaryngology—Head and Neck Surgery diagnostic criteria for Ménière’s disease. Rauch and coworkers14 and Gottschlich and colleagues15 have reported that approximately one-third of classic Ménière’s disease patients have a positive Western blot assay for anti-Hsp70 antibodies. This overlap between TABLE 40-2. Relationship of Western Blot Assay for Anti-Hsp70 Antibodies and Response to Corticosteroid Therapy in 61 Patients with Autoimmune Inner Ear Disease Steroid Response Western Blot

+

−

No Rx

+ − ?

14 5 2

11 12 2

7 8 −

Autoimmune Inner Ear Disease

AIED and Ménière’s disease suggests that a subset of patients falling into both diagnostic categories may share a common pathophysiologic mechanism. AIED can occur in combination with other systemic autoimmune diseases. Nearly 15% of AIED cases have another autoimmune diagnosis (see Table 40-1), such as multiple sclerosis, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis. Though not definitely autoimmune, several other AIED patients listed in Table 40-1 had diabetes or thyroid dysfunction. Some reports of certain human leukocyte antigen (HLA) subtypes showed a correlation with immune-mediated inner ear disease.16 This suggests the possibility of a genetic predisposition to autoimmune disease that may include AIED as well as other systemic disorders.

DIAGNOSIS As noted earlier, the salient feature of AIED is audiometric evidence of progression over days to months. Serial audiometry performed at an interval of ≤3 months is necessary to confirm the diagnosis. When in doubt, monthly audiograms for several months can be helpful. The pattern of hearing loss is highly variable. As yet, no one has described a characteristic pattern of hearing loss. The loss may be high tone, low tone, up- or downsloping, or predominantly affecting discrimination rather than threshold. Exclusion of retrocochlear disease such as multiple sclerosis or acoustic neuroma is mandatory and can be accomplished by evoked response audiometry or gadolinium-enhanced magnetic resonance imaging (MRI). Routine serologic tests in possible AIED patients include complete blood count with differential white count, erythrocyte sedimentation rate (ESR), rheumatoid factor, antinuclear antibody (ANA), C3 and C4 complement levels, and Raji cell assay for circulating immune complexes. Serologic work-up is aimed at detecting evidence of systemic immunologic dysfunction; none of these tests has been shown to correlate with the diagnosis of AIED.

IMMUNOSUPPRESSIVE THERAPY Corticosteroid therapy for AIED has evolved over the last 15 years based on clinical experience. No prospective, randomized clinical trials have yet been conducted to validate this empirical approach. Initial therapy for adults consists of a therapeutic trial of prednisone 60 mg daily for 4 weeks. Pediatric patients receive prednisone 1 mg/kg/day for 4 weeks. Although occasional patients may show a response early in the 4-week period, many do not begin to improve until late in the month, and shorter courses of treatment usually result in relapse. The patient’s hearing is tested at the initiation of therapy and again at 4 weeks. If the threshold has improved by ≥15 dB at one frequency or 10 dB at two or more consecutive frequencies, or if the discrimination is significantly improved, patients are considered steroid responders. The medication is tapered off in 12 days for nonresponders. Responders continue full-dose therapy until monthly audiograms confirm

641

that they have reached a plateau of recovery. The medication is then slowly tapered over 8 weeks to a maintenance dose of 10 to 20 mg every other day. This maintenance dose is continued for a variable length of time. Clinical observation suggests that patients with a total treatment duration of less than 6 months are at increased risk of relapse compared with those treated for 6 months or longer. Patterns of response to corticosteroid therapy vary. Some patients have improvement in threshold, some in discrimination only, and some show benefit to both. Some patients with fluctuation and progression before therapy show stabilization of their hearing without actual improvement. Historically, these cases have been considered nonresponders, but this issue is currently under reassessment. The majority of responders are carried through their slow taper, weaned from steroids, and do well. A subset of AIED patients relapse while tapering or after discontinuing their medication. In some instances retreatment is effective. However, occasionally the hearing loss becomes refractory to corticosteroids. In such cases alternative immunosuppressive drugs are considered. An occasional patient, especially in the pediatric age group, may show steroiddependent hearing loss. In other words, they cannot be weaned below a certain level of steroid dosage without decline in hearing. Such patients often develop unacceptable side effects of chronic steroid administration. Recently, benefit has been observed from combining prednisone with low-dose (15-20 mg/week) methotrexate in these steroid-dependent cases. After several weeks of combined therapy, the prednisone can be tapered and discontinued and the patient maintained on methotrexate alone for an additional 2 to 3 months, at which time the last drug is also successfully discontinued. Corticosteroid therapy has obvious limitations. Longterm administration has risks, including gastritis and ulcers, fluid retention and weight gain, blood pressure lability, altered blood sugar metabolism and diabetes, mood changes or psychiatric problems, sleep disturbance, accelerated cataract formation, and cushingoid habitus. Ischemic necrosis of bone is a rare complication more likely to be seen in cases of prolonged high-dose steroid administration.17 Overall steroid response rate is approximately 60% in AIED patients. Some initial responders become refractory at the time of subsequent relapse. Despite these limitations, corticosteroid therapy remains the mainstay of AIED treatment based on the extensive clinical experience with its use. Alternatives to systemic corticosteroids include methotrexate, etanercept, and cyclophosphamide. Low-dose methotrexate appears to be especially useful as an adjunct in management of steroid-dependent hearing loss. It is the first-line drug of choice for patients unable to take corticosteroids. A low-dose protocol as for rheumatoid arthritis or psoriasis is used. Methotrexate is administered by mouth in three doses given at 12-hour intervals once weekly. The initial dose is 7.5 mg/week (three doses of 2.5 mg). If this is tolerated without toxicity for 2 weeks, the dose is doubled to 15 mg/week. This dose is continued for 6 to 8 weeks as a therapeutic trial. Medication is discontinued in nonresponders; responders are carried on the 15 mg/week dose for 6 months. Potential toxicity includes

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myelosuppression, gastrointestinal upset, oral ulceration, acute pneumonitis, and hepatic fibrosis. This last complication is insidious and generally seen only when methotrexate is given for more than a year. It may be associated with normal liver function tests, and early diagnosis is achieved by liver biopsy. Weekly testing including a complete blood count with differential white count, liver function tests, blood urea nitrogen, creatinine, and urinalysis is recommended to monitor for signs of toxicity. Etanercept, an inhibitor of tumor necrosis factor alpha, has recently been used to treat AIED. Anecdotally, it appears to work well in combination with methotrexate because of its steroid-sparing effect. As seen in rheumatoid arthritis, etanercept alone does not appear nearly as effective. However, neither treatment protocol has been studied systematically. Cyclophosphamide is a potent cytotoxic agent generally used for cancer chemotherapy. It is somewhat selective for B-cell and monocyte-macrophage function.18 Although some advocate its use as a first-line drug,19 the high risk of toxicity makes it a better choice as a salvage drug or treatment of last resort. We have used it in a small number of patients at an initial dose of 1 mg/kg/day orally for 4 to 6 weeks. When no response is apparent, the dose is doubled to 2 mg/kg/day. Responders are treated for 6 to 12 months. Toxicity includes severe myelosuppression, opportunistic infection, hair loss, cystitis, infertility, and increased risk of malignancies. Weekly monitoring of hematologic status is mandatory. Many patients when confronted with the risk of this medication would rather consider cochlear implantation. Intratympanic steroid therapy, systemic IgG injections, and plasmapheresis are possible treatments with sound theoretical justification. Intratympanic steroid therapy is particularly appealing because it is minimally invasive and enables direct application of drug to the affected site with low risk of systemic effects; however, these treatments have not yet been systematically applied in any published series. Determination of the best role for any of these treatment modalities remains to be determined.

CONCLUSIONS AND FUTURE DIRECTIONS The story of AIED from initial description by McCabe to present therapy routines has been presented here as a simple and direct path. That has not been the actual case. It has been a broad and meandering path with significant contributions by many investigators and numerous interesting and important digressions. It is a story that still has far to go. The clinical description of this disorder is confined to its auditory manifestations. However, as noted earlier, 50% of AIED patients have vestibular symptoms. This aspect of the illness has not been well characterized clinically. Just as many AIED patients have exclusively auditory symptoms, an equal number may well have with exclusively vestibular symptoms. Such a presentation has not yet been reported. Little is understood about the underlying pathophysiology of AIED. The very fact of reversible SNHL flies in the face of accepted dogma that SNHL is not medically recoverable. It is interesting to consider what pathophysiologic

mechanism could disable neural signal transduction or transmission in the auditory system yet be reversed months later by anti-inflammatory or immunosuppressive drugs. Solution to this puzzle will come from systematic research into the nature of the humoral and cell-mediated immune response of affected patients. Though the Carey model using KHRI-3 is promising, as yet there is no widely accepted animal model of the AIED phenomenon in which to carry out such research, and human studies progress slowly due to the rarity of the clinical material. This rarity does not diminish the significance of the topic, however. Understanding the mechanism of AIED will provide a new level of insight into the role of systemic and organ-specific immune reactions in disease of the inner ear. The fact that 20% of AIED patients have a clinical presentation overlapping with Ménière’s disease and 33% of Ménière’s disease patients have evidence of antibodies to the 68- to 72-kD antigen by Western blot assay is strong evidence of a shared pathophysiologic mechanism. Though AIED is rare, Ménière’s disease is not. In the United States alone an estimated 125,000 cases are reported yearly. New ways of understanding Ménière’s disease could have great public health benefit. Diagnosis of AIED currently relies on clinical factors alone. As stated earlier, the observation that many AIED patients carry serum antibodies reactive with Hsp70 does not prove that Hsp70 is the actual inner ear target antigen. Hsp70 may carry an epitope shared with the true target antigen or may otherwise colocalize with it biochemically. Despite our poor understanding of AIED pathophysiology, detection of this or other marker antibodies may become clinically useful. The utility of an assay will be greatly enhanced by development of a quantitative measure enabling clinicians to follow antibody titers by serial testing. In addition, estimation of sensitivity and specificity of the assay must be made by its broad application to a wide variety of ear diseases and immunologic disorders. Current therapy of AIED is based on empirical experience over the last 15 years rather than on a clear understanding of the underlying pathophysiology. In the future, therapeutic protocols must be informed by expanding knowledge of the pathophysiology of the disorder. Large multicenter studies are necessary to carefully evaluate the best use of corticosteroids and other immunosuppressive drugs. Consensus must be achieved on the clinical diagnostic criteria and treatment regimens to enable comparison between studies. Even with strict adherence to rigorous methodology, it may take many years to address these questions. For the foreseeable future, AIED will remain one of the most interesting, important, and challenging problems confronting otologists and otologic researchers.

REFERENCES 1. McCabe BF: Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol 88:585, 1979. 2. Harris JP, Sharp PA: Inner ear autoantibodies in patients with rapidly progressive sensorineural hearing loss. Laryngoscope 100:516, 1990. 3. Moscicki RA, San Martin JE, Quintero CH, et al: Specificity of serum antibodies to a 68 kD inner ear antigen in disease associated

Autoimmune Inner Ear Disease

4.

5.

6.

7. 8.

9.

10.

with hearing loss and responsivity to corticosteroid therapy. JAMA 272:611, 1994. Billings PB, Keithley EM, Harris JP: Evidence linking the 68 kilodalton antigen identified in progressive sensorineural hearing loss patient sera with heat shock protein 70. Ann Otol Rhinol Laryngol 104:181, 1995. Bloch DB, San Martin JE, Rauch SD, et al: Serum antibodies to heat shock protein 70 in sensorineural hearing loss. Arch Otolaryngol 121:1167, 1995. Zajic G, Nair TS, Ptok M, et al: Monoclonal antibodies to inner ear antigens: I. Antigens expressed by supporting cells of the guinea pig cochlea. Hear Res 52:59, 1991. Nair TS, Raphael Y, Dolan DF, et al: Monoclonal antibody induced hearing loss. Hear Res 83:101, 1995. Nair TS, Prieskorn DM, Miller JM, et al: In vivo binding and hearing loss after intracochlear infusion of KHRI-3 antibody. Hear Res 107:93, 1997. Nair TS, Prieskorn DM, Miller JM, et al: KHRI-3 monoclonal antibody-induced damage to the inner ear: Antibody staining of nascent scars. Hear Res 129:50, 1999. Ptok M, Nair TS, Altschuler RA, et al: Monoclonal antibodies to inner ear antigens: II. Antigens expressed in sensory cell stereocilia. Hear Res 57:79, 1991.

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11. Ptok M, Carey TE, Altschuler RA: Relationship of monoclonal antibody (KHRI 3 epitope) to cochlear supporting cell microvilli in the guinea pig. Eur Arch Otorhinolaryngol 250:345, 1993. 12. Ptok M, Klein R, Ptok A, et al: Drug therapy of acute inner ear hearing loss in childhood and adolescence. HNO 42:636, 1994. 13. Disher MJ, Ramakrishnan A, Nair TS et al: Human autoantibodies and monoclonal antibody KHRI-3 bind to a phylogenetically conserved inner-ear-supporting cell antigen. Ann N Y Acad Sci 830:253, 1997. 14. Rauch SD, Zurakowski D, Bloch DB, et al: Anti-Hsp70 antibodies in Ménière’s disease. Laryngoscope 110:1516, 2000. 15. Gottschlich S, Billings PB, Keithley EM, et al: Assessment of serum antibodies in patients with rapidly progressive sensorineural hearing loss and Ménière’s disease. Laryngoscope 105:1347, 1995. 16. Cao M-Y, Thonnard J, Deggouj M, et al: HLA Class II-associated genetic susceptibility in idiopathic progressive sensorineural hearing loss. Ann Otol Rhinol Laryngol 105:628, 1996. 17. Zizic TM, Marcoux C, Hungerford DS, et al: Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus. Am J Otol 79:596, 1985. 18. Hadden JW, Smith DL: Immunopharmacology: immunomodulation and immunotherapy. JAMA 268:2964, 1992. 19. McCabe BF: Autoimmune inner ear disease: Therapy. Am J Otol 10:196, 1989.

Chapter

41 Lorne S. Parnes, MD, FRCSC Sumit K. Agrawal, BSc, MD

Benign Paroxysmal Positional Vertigo Outline Introduction and Background Pathophysiology Posterior Canal Benign Paroxysmal Positional Vertigo Lateral Canal Benign Paroxysmal Positional Vertigo Epidemiology Etiology Diagnosis History

INTRODUCTION AND BACKGROUND There is nothing more gratifying for a physician than managing a disorder that is for the most part easily diagnosed, and more important, simply and effectively treated using noninvasive means. Benign paroxysmal positional vertigo (BPPV), the most common affliction of the vestibular labyrinth, is one such disorder. BPPV was first described by Barany1 in 1921. He describes several key manifestations in his clinical description: The attacks only appeared when she lay on her right side. When she did this, there appeared a strong rotatory nystagmus to the right. The attack lasted about thirty seconds and was accompanied by violent vertigo and nausea. If, immediately after the cessation of these symptoms, the head was again turned to the right, no attack occurred, and in order to evoke a new attack in this way, the patient had to lie for some time on her back or on her left side.

Barany mistook the condition as an error in head position encoding by the otoliths because the symptoms seemed to be independent of the positioning maneuver. Dix and Hallpike,2,3 finding histologic evidence of unilateral utricular macular degeneration in a case of BPPV, also mistakenly concluded that the disorder was caused by a lesion in the otolith organ. In 1952, they coined the term benign paroxysmal positional vertigo in their report of 100 patients. The description of the diagnostic nystagmus included (1) brief latency (1 to 5 seconds), (2) rotational nystagmus with the fast component of the superior pole beating toward the affected (undermost) ear, (3) limited duration (5 to 30 seconds), (4) reversal of the induced nystagmus upon returning to the seated position, and (5) fatigability of the response with repetition. In 1969, Schuknecht4 described basophilic cupular deposits in postmortem temporal bones of two patients 644

Diagnostic Maneuvers Subjective vs. Objective Benign Paroxysmal Positional Vertigo Differential Diagnosis Management Nonsurgical Management Vestibular Habituation Therapy Liberatory Maneuver Particle Repositioning Maneuver

Lateral Canal Benign Paroxysmal Positional Vertigo Controversy Factors Affecting Repositioning Maneuvers Surgical Treatment Singular Neurectomy Posterior Semicircular Canal Occlusion Summary

who had manifested benign paroxysmal positional nystagmus. Interestingly, the deposits were found only on the posterior canal cupulae of the presumed affected ears while the cupulae from the other sides were normal. Schuknecht and Ruby5 reported another case and then studied 391 temporal bones from 245 patients without BPPV. They discovered cupular deposits in 149 bones (37%), with small deposits in 125 (32%), medium deposits in 20 (5%), and large deposits in 4 (1%). However, none of these deposits was as large as those found in the three patients with BPPV. Schuknecht4 had initially proposed that loose otoconia from degenerating utricular macula floated in the region of the posterior semicircular canal cupula and caused displacement. He then modified his theory and coined the term cupulolithiasis to represent the findings of attached otoconia to the posterior semicircular canal cupula. He proposed that deposits would render the cupula sensitive to gravity. Ampullifugal deflection of the posterior canal cupula in the provocative head-hanging position was thought to account for the nystagmus seen in posterior canal BPPV. In 1979, Hall and colleagues6 combined these two theories on the basis of the fatigability of the nystagmus. They proposed that BPPV could be caused by deflection of the posterior canal cupula by fixed deposits on the cupula (nonfatigable nystagmus) or by the motion of free-floating particles in the posterior semicircular canal (fatigable nystagmus). Free-floating particles in the semicircular canal has been coined canalithiasis and represents the most common form of BPPV that is diagnosed with the DixHallpike maneuver. Parnes and McClure7 were the first to demonstrate in vivo free-floating endolymph particles in the posterior canal. This intraoperative finding, from two patients with intractable BPPV undergoing posterior semicircular canal

Benign Paroxysmal Positional Vertigo

occlusion surgery, further supported the theory of canalithiasis. A further study by Welling and colleagues8 examined the extracted particles from another patient undergoing canal occlusion surgery under electron microscopy and revealed that the particles were degenerating otoconia.

PATHOPHYSIOLOGY Posterior Canal Benign Paroxysmal Positional Vertigo The vast majority of BPPV cases are of the posterior canal variant. The pathophysiology that causes most posterior canal BPPV cases is thought to be canalithiasis (see Fig. 41-1). This is probably because most free-floating endolymph debris tends to gravitate to the posterior canal, being the most gravity-dependent part of the vestibular labyrinth in both the upright and supine positions. It is important to note that the cupula forms an impermeable barrier across the lumen of the ampulla9 and is located at the shorter, more dependent end of the canal. Therefore, the particles become “trapped” and can exit the posterior canal only through the nonampullated end (the common crus). Agrawal and Parnes10 found obvious free-floating endolymph particles in 30% of ears undergoing surgery for posterior canal BPPV. The mechanism by which canalithiasis causes nystagmus in the posterior semicircular canal was described by Epley.11,12 Particles must accumulate to a “critical mass” in the dependent portion of the posterior semicircular canal. The canalith mass moves to a more dependent position when the orientation of the semicircular canal is modified in the gravitational plane. The resulting drag must overcome the resistance of the endolymph in the semicircular canal and the elasticity of the cupular barrier in order to deflect the cupula. The time taken for this to occur plus the original

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inertia of the particles explains the latency seen during the Dix-Hallpike maneuver. In the head-hanging position, the canalith mass would move away from the cupula to induce ampullifugal cupular deflection. In the vertical canals, deflection produces an excitatory response. This would cause an abrupt onset of vertigo and the typical torsional nystagmus in the plane of the posterior canal. In the left head-hanging position (left posterior canal stimulation), the fast component of the nystagmus beats clockwise as viewed by the examiner. Conversely, the right head-hanging position (right posterior canal stimulation) results in a counterclockwise nystagmus. These nystagmus profiles correlate with the known neuromuscular pathways that arise from stimulation of the posterior canal ampullary nerves in an animal model.13 This nystagmus is of limited duration because the endolymph drag ceases when the canalith mass reaches the limit of descent and the cupula returns to its neutral position. Reversal nystagmus occurs when the patient returns to the upright position; the mass moves in the opposite direction, thus creating a nystagmus in the same plane but opposite direction. The response is fatigable as the particles become dispersed along the canal and become less effective in creating endolymph drag and cupular deflection. Canalithiasis in the posterior canal likely accounts for the majority of BPPV cases. Based on studies at the Portland Otologic Clinic, Epley12 has described two additional mechanisms for which diagnosis and treatment are not yet well defined in the literature. Cupulolithiasis, or “heavy cupula,” refers to particles adherent to or impinging on the cupula. Unlike in canalithiasis, the observed nystagmus in cupulolithiasis is gradual in onset, seldom severe, and persists while the head is in the provocative position. A gradual decline in the nystagmus may occur after 1 to 2 minutes. A third proposed mechanism, known as canalith jam, is thought to be caused by particles creating a blockage in the canal or by particles becoming wedged between the cupula and the adjacent ampulla wall. The resultant nystagmus and vertigo are persistent and unaffected by the patient’s head position. Although testing and possible repositioning treatments have been proposed, these entities need to be studied further.

Lateral Canal Benign Paroxysmal Positional Vertigo cupula

ampulla cupulolithiasis

canalithiasis Figure 41-1. Left inner ear. Depiction of canalithiasis of the posterior canal and cupulolithiasis of the lateral canal. (Reprinted with permission from Parnes LS, Agrawal SK, Atlas J: Diagnosis and management of benign paroxysmal positional vertigo [BPPV]. CMAJ 169:681–693, 2003.).

BPPV most commonly affects the posterior semicircular canal, however, one report suggests that up to 30% of BPPV may be of the horizontal canal variant.14 In our dizziness clinic, the horizontal canal variant accounts for less than 5% of our BPPV cases. However, our findings may be biased by the long wait for an assessment in our clinic (more than 5 months); it has also been our experience that lateral canal BPPV resolves much quicker than posterior canal BPPV. This latter observation is understandable when one considers the orientations of the canals. The posterior canal hangs inferiorly and has its cupular barrier at its shorter, more dependent end. Any debris entering the canal essentially becomes trapped within it. In contrast, the lateral canal slopes upward and has its cupular barrier at the upper end. Therefore, free-floating debris in the lateral canal tends to float back out into the utricle as a result of natural head movements.

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TABLE 41-1. Lateral Canal BPPV Side of Origin and Mechanism Direction of Nystagmus Intensity of Nystagmus Stronger on left side Stronger on right side

Ageotropic Right cupulolithiasis Left cupulolithiasis

Geotropic Left canalithiasis Right canalithiasis

BPPV.22 BPPV most often involves a single semicircular canal, usually posterior, but may involve both posterior and lateral canals in the same inner ear. Posterior canal BPPV may convert to lateral canal BPPV following repositioning maneuvers.23 Head trauma is the most common cause of bilateral posterior canal BPPV.17

ETIOLOGY In lateral canal canalithiasis, particles are most often in the long arm of the canal relatively far from the ampulla.15 If the patient performs a lateral head turn toward the affected ear, the particles will create an ampullipetal endolymph flow, which is stimulatory in the lateral canal. A geotropic nystagmus (fast phase toward the ground) will be present. If the patient turns away from the affected side, the particles will create an inhibitory flow. Although the nystagmus will be in the opposite direction, it will still be geotropic since the patient is now facing the opposite direction. Stimulation of a canal creates a greater response than inhibition of a canal; therefore, the direction of head turn that creates the strongest geotropic nystagmus (i.e., stimulatory response) represents the affected side in lateral canal canalithiasis (Table 41-1). Cupulolithiasis is thought to play a greater role in lateral canal BPPV than in the posterior canal variant. Since particles adhere directly to the cupula, the vertigo is often intense and persists while the head is in the provocative position. When the patient’s head is turned toward the affected ear, the cupula undergoes an (inhibitory) deflection, which causes an apogeotropic nystagmus (fast phase away from the ground). A head turn in the opposite direction creates an ampullipetal (stimulatory) deflection, resulting in a stronger apogeotropic nystagmus. Therefore, turning away from the affected side will create the strongest apogeotropic nystagmus in lateral canal cupulolithiasis (see Table 41-1). Apogeotropic nystagmus is present in about 27% of patients who have lateral canal BPPV.14

EPIDEMIOLOGY BPPV is the most common disorder of the peripheral vestibular system16 and represented 17% of patients in one large dizziness clinic.17 The incidence is likely severely underestimated since most untreated cases of BPPV resolve spontaneously within a few months. Also, most studies do not use a population-based model but determine incidence in patients who either report vertigo as their chief complaint or undergo vestibular testing. Mizukoshi and colleagues18 estimated the incidence to be 10.7 to 17.3 per 100,000 in Japan. Several studies have suggested a higher incidence in women,18–20 but in younger patients and those with post-traumatic BPPV, the incidence in men and women may be equal.17 The age of onset is usually during the fifth through seventh decades of life.18,19,21 The elderly are at an increased risk, and a study of an elderly population undergoing geriatric assessment for non-balancerelated complaints found that 9% had unrecognized

In most cases, BPPV is found in isolation and termed primary or idiopathic BPPV. Rates of primary BPPV have been reported as approximately 50% to 70% of BBPV cases. The most common cause of secondary BPPV is head trauma, which represents 7% to 17% of all BPPV cases.17,19 The blow to the head may cause the release of numerous otoconia into the endolymph, which likely explains why many of these patients suffer from bilateral BPPV.17 Viral neurolabyrinthitis has been implicated in up to 15% of BPPV cases.19 The function of the posterior canal must be preserved to a certain degree in order to be symptomatic from BPPV.24 Ménière’s disease has also been strongly associated with BPPV. There is a large variation in the literature regarding what proportion of patients with BPPV also have Ménière’s disease. One study by Karlberg and colleagues25 reviewed 2847 patients with BPPV and found 16 patients (0.5%) with Ménière’s disease. Another retrospective study examined only 151 patients with BPPV and found that more than 45 patients (31%) had Ménière’s disease.26 However, upon examination of 162 patients with “definite” Ménière’s disease, Gross and colleagues27 found 9 patients (5.5%) to have “certain” posterior canal BPPV. The causative mechanism is not well understood but may be due to hydropically induced damage to the macula of the utricle or by partial obstruction of the membranous labyrinth.27 Recently, migraine headaches have been associated to BPPV. Ishiyama and colleagues28 found that (1) the incidence of migraine was three times greater in patients with primary BPPV than in the general population and (2) patients with migraines had the highest recurrence rate (77%) after successful repositioning. Lempert and colleagues29 found a higher lifetime prevalence of migraine in patients with BPPV (35% vs. 16%). They also found that 83% of patients with BPPV and migraine were women. This may help explain the female preponderance of BPPV in the general population. Since vasospasm is well documented in migraines and BPPV has been associated with ischemic damage to the inner ear,28 vasospasm of the labyrinthine arteries has been suggested as an etiologic mechanism. Recurrent vasospastic ischemia of the utricular otolith could explain the significant recurrence rate of BPPV in patients with migraine.30 Secondary BPPV has also been described after inner ear surgery.26,31,32 Atacan and colleagues31 reviewed 63 stapedectomy cases for BPPV and found 4 patients (6%) who developed BPPV postoperatively. All patients responded to the Epley maneuver. The etiology is thought to be linked to utricular damage during the procedure, leading to the release of otoconia.

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DIAGNOSIS History Patients describe sudden, severe attacks of either horizontal or vertical vertigo precipitated by certain head positions and movements. The most common movements are rolling in bed, extending the neck, and bending forward. Patients can often identify the affected ear by stating the direction of movement that precipitates the majority of the attacks (e.g., rolling in bed to the right, but not the left, precipitates the dizziness that indicates right ear involvement). A study by Kentala and Pyykko33 reported that 80% of patients experience a rotatory vertigo and 47% experience a floating sensation. The attacks of vertigo typically last less than 30 seconds; however, some patients overestimate the duration by several minutes. Reasons for this discrepancy may include the fear associated with the intense vertigo along with the nausea and dysequilibrium that may follow the attack. Patients may go to great lengths to avoid precipitating movements. For this reason, some may not realize that the condition has resolved, as it often does spontaneously over time. Most patients experience several attacks per day (53%) or week (23%).33 Before the development of effective treatments, Schuknecht and Ruby5 had classified the attacks into self-limited, recurrent, or permanent forms. Selflimited BPPV occurs suddenly, resolves in weeks to months, and does not recur. In the recurrent form, patients have multiple recurrent episodes of vertigo interspersed with asymptomatic periods. In the permanent form, vertigo is present without remission longer than 1 year. Chronic balance problems have also been described by BPPV patients, often upon awakening in the morning or after daytime naps.34,35 Although 50% to 70% of BPPV is primary or idiopathic, history should be taken with a view to possible secondary causes of BPPV. These include head trauma, viral labyrinthitis/vestibular neuronitis, Ménière’s disease, migraine headaches, and otologic and nonotologic surgery.

Diagnostic Maneuvers The Dix-Hallpike maneuver to diagnose posterior canal BPPV was first described in 19522 (Fig. 41-2). The patient is seated and positioned such that his or her head will extend over the edge of the table when supine. The head is turned 45º toward the ear being tested and the patient is quickly lowered into the supine position with the head extending below the level of the table. The patient’s head is held in this position and the examiner observes the eyes for nystagmus. The use of Frenzel lenses adds little to the identification of the nystagmus; unlike horizontal nystagmus, rotational nystagmus is not suppressed by visual fixation. The typical nystagmus has a brief latency (1 to 5 seconds) and limited duration (typically less than 30 seconds). It consists of a slight vertical component that is upbeating and a torsional component that has the superior pole of the eye beating toward the affected dependent ear. The direction of the nystagmus reverses when the patient is brought into the upright position and the nystagmus will fatigue with repeated testing. Along with the nystagmus,

A

B Figure 41-2. Dix-Hallpike maneuver. A, The patient is seated and positioned such that her head will extend over the edge of the table when supine. The head is turned 45 degrees toward the ear being tested. B, The patient is quickly lowered into the supine position with her head extending below the level of the table. The patient’s head is held in this position and the examiner observes the eyes for nystagmus. (Reprinted with permission from Parnes LS, Agrawal SK, Atlas J: Diagnosis and management of benign paroxysmal positional vertigo [BPPV]. CMAJ 169:681–693, 2003.)

the patient will describe feeling vertiginous, the intensity of which parallels the nystagmus response. The two posterior canals are tested independently. Superior semicircular canal BPPV is exceedingly rare and is not well described in the literature. The frequency has been reported as only 1% to 3% of BPPV cases.36,37 Since the posterior semicircular canal and contralateral superior semicircular canal lie in the same plane, the Dix-Hallpike maneuver can be used to test for both entities. Therefore, the left Dix-Hallpike will test for the left posterior

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PERIPHERAL AUDIOVESTIBULAR DISORDERS

semicircular canal and right superior semicircular canal. The observed nystagmus, however, will be opposite in both its vertical (downbeating nystagmus) and torsional components (superior pole beating toward the uppermost ear).15 Testing for lateral canal BPPV is done by laying the patient supine and then quickly turning the patient’s head (and body if necessary) laterally toward the side being tested. A purely horizontal nystagmus occurs that is geotropic (fast component toward the lowermost ear) in the majority of cases, but it may be ageotropic (toward the uppermost ear) in 27% of cases.14 Compared with the vertical-torsional nystagmus of posterior canal BPPV, this horizontal nystagmus has a shorter latency and stronger intensity while maintaining the test position, and it is less prone to fatigue.15 Both sides are tested, and the direction of nystagmus coupled with the direction of roll causing the greatest nystagmus intensity often identifies the affected side and the mechanism (see Table 41-1). Overall, history and eye-findings during positional testing are the gold standards for diagnosing BPPV. Additional testing is not normally necessary and since electronystagmography (ENG) does not record torsional eye movements, it adds little in the diagnosis of BPPV. More recently, infrared videography has allowed direct eye observation during the testing maneuvers, but three-dimensional eye movement analysis38 is not common in clinical practice. Rotational-chair testing and posturography have no role in the diagnosis of BPPV. Imaging with CT or MRI scans is unnecessary unless there are atypical or unusual features to the assessment.

Subjective vs. Objective Benign Paroxysmal Positional Vertigo A certain subset of patients may not demonstrate the typical nystagmus during the Dix-Hallpike maneuver but may still experience the classic vertigo during positioning. This has been termed subjective BPPV and several groups have found repositioning maneuvers to be highly effective in this group of patients. Haynes and colleagues,39 Tirelli and colleagues,40 and Weider and colleagues41 found that patients with subjective BPPV treated with various repositioning maneuvers had response rates of 76% to 93% overall. Proposed theories to explain the lack of nystagmus in patients with BPPV during the Dix-Hallpike maneuver include (1) subtle nystagmus missed by the observer, (2) fatigued nystagmus from repeated testing before the maneuver, and (3) a less noxious form of BPPV that elicits vertigo but has an inadequate neural signal to stimulate the vestibulo-ocular pathway.39

Differential Diagnosis Very few conditions can even remotely resemble BPPV. In Ménière’s disease, the vertigo spells are not provoked by position change, and they last much longer (30 minutes to several hours). Furthermore, there is accompanying tinnitus and hearing loss. The vertigo in labyrinthitis or vestibular neuronitis usually persists for days. The vertigo may be aggravated by head movements in any direction, and this needs to be carefully extracted from the history so as not to confuse it with specific position change–evoked vertigo.

As well, the Dix-Hallpike test should not induce the burst of nystagmus seen in BPPV. Very rarely, posterior fossa tumors mimic BPPV, but there are no reports in the literature in which a tumor has perfectly replicated all of the features of a positive Dix-Hallpike maneuver. As mentioned previously, BPPV can be secondary, so as to occur concurrently with, or subsequent to, other inner ear or CNS disorders. Also, being so common, it can often be a coincidental finding with other disorders.

MANAGEMENT Nonsurgical Management The management of BPPV has changed dramatically in the past 20 years as our understanding of the condition has progressed. Traditionally, patients were instructed to avoid positions that induced the vertigo. Medications were prescribed for symptomatic relief, but one double-blind study showed that they were largely ineffective.42 BPPV is self-limited, and most cases resolve within 6 months. As the theories of cupulithiasis and canalithiasis emerged, several noninvasive techniques were developed to correct the condition directly. Vestibular Habituation Therapy In 1980, Brandt and Daroff43 introduced a specific series of positional movements that they believed caused the mechanical loosening and dispersion of otolithic debris from the cupula. The set of exercises were to be done every 3 hours during the day until 2 days after the positional vertigo had resolved. Many believed that these exercises worked through habituated central compensation, but the authors concluded that the time course to the relief of symptoms was too short for this to occur. Brandt and Daroff found that one-third of their patients had an abrupt resolution in symptoms and 66 of their 67 patients had resolution within 3 to 14 days. Although several other studies found excellent initial responses (96% to 100%) to vestibular habituation,44–46 there is a high rate of recurrence (76%).44 The exercises are time-consuming and poorly tolerated by some patients, especially the obese and elderly. Liberatory Maneuver In 1988, Semont and colleagues47 described the liberatory maneuver based on the cupulithiasis theory (Fig. 41-3). It was theorized that this series of rapid changes of head position freed deposits that were attached to the cupula. The maneuver begins with the patient in the sitting position and head turned away from the affected side. The patient is then quickly put into the side-lying position, toward the affected side, with the patient’s head turned up. After approximately 5 minutes, the patient is quickly moved back through the sitting position to the opposite side-lying position with the head now facing down. The patient remains in this second position for 5 to 10 minutes before slowly being brought back to the sitting position. In their large series of 711 patients, Semont and colleagues47 found an 84% response rate after one procedure and a 93% response rate after a second procedure

Benign Paroxysmal Positional Vertigo

2

1 particles in posterior canal

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utricle 3

cupula

Figure 41-3. Liberatory maneuver of Semont. The top panel shows the effect of the maneuver on the canaliths. (Reprinted with permission from Parnes LS, Agrawal SK, Atlas J: Diagnosis and management of benign paroxysmal positional vertigo [BPPV]. CMAJ 169:681–693, 2003.)

1

2

1 week later. Several other studies have had response rates of 52% to 90%39,45,48,49 with recurrence rates of up to 29%.39 There has been no difference in efficacy shown between the liberatory maneuver and particle repositioning maneuver in studies by Herdman and colleagues48 and Cohen and Jerabek.50 The liberatory maneuver is effective but is cumbersome with elderly and obese patients, and it shows no increased efficacy compared with the simple particle repositioning maneuver. Particle Repositioning Maneuver Although he had been teaching his technique for many years, it wasn’t until 1992 that Epley51 first published his report on the canalith repositioning procedure (CRP). It is based on the theory of canalithiasis, which currently is thought to be the mechanism underlying most cases of posterior canal BPPV. This highly successful procedure is done while the patient is sedated and with mechanical vibration to the mastoid bone and it involves moving the patient’s head sequentially through five distinct positions. Epley postulated that the procedure caused otolithic debris to move under the influence of gravity from the posterior semicircular canal into the utricle. Most clinicians today are believed to use a modified version of the CRP. One modified CRP is the particle repositioning maneuver (PRM), which is a three-position maneuver that obviates

3

the need for sedation and mastoid vibration52,53 (Fig. 41-4). To perform the PRM: 1. Place the patient in a sitting position. 2. Move the patient to the head-hanging Dix-Hallpike position of the affected ear. 3. Observe the eyes for “primary stage” nystagmus. 4. Maintain this position for 1 to 2 minutes (position B). 5. The patent’s head is turned 90 degrees to the opposite Dix-Hallpike position while keeping the neck in full extension (position C). 6. Continue to roll the patient another 90 degrees until the head is diagonally opposite to the first Dix-Hallpike position (position D). The change from position B, through C, into D should take no longer than 3 to 5 seconds 7. The eyes should be immediately observed for “secondary-stage” nystagmus. If the particles continue moving in the same ampullifugal direction, that is, through the common crus into the utricle, this secondary-stage nystagmus should beat in the same direction as the primary-stage nystagmus. 8. This position is maintained for 30 to 60 seconds and then the patient is asked to sit up. With a successful maneuver, there should be no nystagmus or vertigo when the patient returns to the sitting position because the particles will have already been repositioned into the utricle.52

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PERIPHERAL AUDIOVESTIBULAR DISORDERS

45° 90°

superior canal D

D utricle cupula particles in posterior canal

A

C

135° 45° 135°

D D

B

D

Figure 41-4. Particle repositioning maneuver. Schema of patient and concurrent movement of posterior and superior semicircular canals and utricle. The patient is undergoing the particle repositioning maneuver in the right ear. A, Patient is seated on table as viewed from the right side. The remaining parts show the sequential head and body positions of a patient lying down viewed from the top. B, Patient in normal Hallpike head-hanging position. Particles gravitate in ampullifugal direction and induce ampullifugal cupular displacement and subsequent counterclockwise rotatory nystagmus (right ear). Position is maintained for 1 to 2 minutes. Head is then rotated toward the opposite side with the neck extended. Head is brought through position C and into position D in a steady motion by rolling the patient onto the opposite lateral side. Particles continue gravitating in ampullifugal direction through common crus into utricle. Eyes are immediately observed for nystagmus. Position is maintained for another 1 to 2 minutes, and then the patient sits up. D, direction of view of labyrinth; dark circle, position of particle conglomerate; open circle, previous position. (Reprinted with permission from Parnes LS, Agrawal SK, Atlas J: Diagnosis and management of benign paroxysmal positional vertigo [BPPV]. CMAJ 169:681–693, 2003.)

Studies that use the repositioning maneuvers are difficult to compare because they vary considerably in the length of follow-up, number of treatment sessions, number of maneuvers per session, use of sedation, and use of mastoid vibration. Table 41-2, adapted from Haynes and colleagues,39 summarizes the efficacy and treatment protocols of many trials. The overall response rates range from 30% to 100% and recurrence rates range from 5% to 30%. Most of the studies presented are case series, however, Lynn and colleagues54 and Steenerson and Cronin46 provide evidence from randomized studies.

The patient is rolled away from the affected ear in 90-degree increments until a full roll is completed. This is believed to move the particles out of the involved canal into the utricle. For less agile patients, Lempert and Tiel-Wilck57 proposed the log roll where the patient is kept supine and only the head is positioned. Here, the patient begins with the head turned completely toward the affected ear. The patient is then rapidly turned away from the affected ear in 90-degree increments for a total of 270 degrees, with the head being held in each position for about 1 minute. Only two patients were in the study, but both were completely relieved of their vertigo.

Lateral Canal BPPV Several positioning techniques to treat lateral canal BPPV have been developed. Perhaps the most simple is the prolonged position maneuver developed by Vannucchi and colleagues.55 In cases involving geotropic nystagmus, the patient lies on his or her side with the affected ear up for 12 hours. They had resolution in greater than 90% of their 35 patients. Six of their patients converted to posterior canal BPPV, but they were successfully treated with repositioning maneuvers. The barrel roll was described by Epley12,56 and involves rolling the patient 360 degrees, supine to supine, keeping the lateral semicircular canal in the earth-vertical plane.

Controversy Despite the excellent results from repositioning maneuvers, there has been some controversy as to whether they have an effect other than for central habituation over time. In 1994, Blakley58 published a trial of 38 patients randomly assigned to the particle repositioning group and the no treatment group. No significant difference was found between the treated and nontreated groups at 1 month, and together, 89% showed some improvement. He concluded that the maneuver was safe but did not provide treatment benefit for BPPV. Buckingham59 examined human temporal bones and attempted to demonstrate the

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TABLE 41-2. Particle Repositioning Maneuver for BPPV Reference

Number of Patients

Success Rate (%)

Recurrence Rate (%)

Treatment Sessions

Treatment Protocol

Postmaneuver Instructions

Mastoid Vibration

Epley51* Epley51† Epley51 Li63 Li63

30 30 14 10 10

80 100 93 30 100

30 NR‡ NR NR NR

Multiple Multiple NR Single Single

Yes Yes Yes Yes Yes

Yes Yes Yes No Yes

Li63 Blakley58 Smouha97 Wolf et al.98 Herdman et al.48 Parnes and Price-Jones52 Weider et al.41 Steenerson and Cronin46 Welling and Barnes99 Harvey et al.100 Lynn et al.54

27 16 27 102 30 34 44 20 25 25 18

92 94 93 93 90 88 88 85 84 68 61

NR NR NR 5 10 17 9 NR NR 20 NR

Single Repeated NR Single Repeated with vibration Single Single Multiple Single Single Multiple Multiple Multiple Multiple Multiple Single

Single Single Multiple Single Single Multiple Multiple Multiple Single Single Single

Yes No No Yes Yes Yes Yes No Yes Yes Yes

Yes No No No No No Yes No No No No

*Parenthetical numbers refer to entries in this chapter’s list of references. † Multiple entries from one reference indicate data extracted from a single study that used different treatments for groups of patients. ‡ Not reported. § Excluding patients lost to follow-up. Table adapted from Haynes DS, et al: Treatment of benign positional vertigo using the Semont maneuver: Efficacy in patients presenting without nystagmus. Laryngoscope 112:796–801, 2002.

possible paths taken by loose otoliths under the influence of gravity in different positions of the head. He found that although loose macular otoliths tend to fall into the lumen of the utricle, they are not returned to their original position in the macula of the utricle, which lies superior in the vestibule. He concluded that a mechanism other than the repositioning of otoliths is responsible for the relief of BPPV seen in repositioning maneuvers. Gacek and Gacek60 have even questioned the entire pathophysiology of BPPV and claim that it is simply a clinical expression of vestibular ganglionitis. This conclusion is, however, based on very weak evidence that involved reviewing 51 temporal bones that contained evidence of ganglion cell degeneration and only 3 of these patients had a history of BPPV. Although most cases of BPPV are self-limited and spontaneously resolve within 6 months, a number of randomized studies have shown that repositioning maneuvers are highly effective. One group in Bangkok performed a 6-month efficacy trial comparing the CRP with no treatment in patients with BPPV.61 At 1 month, vertigo resolution was significantly higher in the CRP group (94%) than in the no treatment group, although this difference was not seen at 3 and 6 months. Lynn and colleagues54 randomized 36 patients to a PRM and placebo treatment group with blind assessment by an audiologist at 1 month. Resolution of vertigo was significantly higher in the PRM group (89%) than in the placebo group (27%). Steenerson and Cronin46 randomly assigned 20 patients into either a PRM or a vestibular habituation group and 20 patients into a no treatment group. At 3 months, all patients in the treatment group were resolved of their symptoms while only 25% of the no treatment group were symptom free.

Factors Affecting Repositioning Maneuvers Number of Maneuvers per Session The literature contains variations regarding how many repositioning maneuvers are performed in each treatment session (see Table 41-2). Some perform a set number of repositioning maneuvers regardless of response.62 However, the majority of groups are divided between performing only one maneuver per clinic visit and performing maneuvers until there is a resolution of nystagmus or excessive patient discomfort. Our objection to repeating the maneuver until there is a negative Dix-Hallpike response is that one cannot know whether the response is abolished because of a successful maneuver or because of fatigued that occurs naturally with repeated testing. From the literature review, there does not appear to be significant differences among these approaches in terms of short-term effectiveness and long-term recurrence. Therefore, in our clinic, repeated maneuvers are reserved for patients who do not demonstrate an ipsidirectional secondary-stage nystagmus or those who have a reverse direction nystagmus at position D30 (see Fig. 41-4). Mastoid Vibration In Epley’s original description of the CRP,51 he used mechanical vibration of the mastoid bone thinking that it would loosen otolithic debris adherent to the membrane of the semicircular canal. In 1995, Li63 randomly assigned 27 patients to receive the PRM with mastoid vibration and 10 patients to receive the PRM without mastoid vibration. He found that the vibration group had a significantly higher rate of improvement in symptoms (92%) than did the nonvibration group (60%).

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These results do not, however, compare well with other published studies (see Table 41-2), in which the majority of authors who did not use mastoid vibration achieved much higher success rates. In 2000, a larger study by Hain and colleagues62 reviewed 44 patients who had the PRM with mastoid vibration and 50 patients who had the PRM without mastoid vibration. There was an overall success rate of 78% with no difference in short-term or long-term outcomes between the two groups. Postmaneuver Instructions Another area of divergence among experts involves the use of activity limitations after repositioning maneuvers. Epley51 asked his patients to remain upright for 48 hours after the CRP. Certain investigators also request that, in addition to remaining upright, their patients avoid lying on their affected side for 7 days. A study by Nuti and colleagues49 examined two sets of patients following the liberatory maneuver. One group of patients was asked to remain upright for 48 hours, while a second group of patients was not given any postmaneuver instructions. These two groups were retrospectively compared and no difference was found in short-term vertigo control. This finding is consistent with an earlier study by Massoud and Ireland,64 who also demonstrated that postliberatory maneuver instructions were not efficacious. Objective vs. Subjective Benign Paroxysmal Positional Vertigo Subjective BPPV refers to the condition of patients with positional vertigo who do not display the classic nystagmus during the Dix-Hallpike maneuver, but who experience the classic vertigo on history and positioning. As previously discussed, several theories have been proposed regarding the pathophysiology of subjective BPPV. Although most studies in the literature include only patients with objective BPPV, it has become clear that repositioning maneuvers in the subjective group is nearly as effective as they are for patients with objective BPPV. Tirelli and colleagues40 prospectively examined two groups of patients: 43 patients with subjective BPPV and 90 patients with objective BPPV, all treated with the PRM. Although the objective BPPV group had a higher complete resolution rate than the subjective BPPV group (90% vs. 60.5%), the subjective BPPV group had 32.5% of patients who partially improved. Therefore, the overall success rate in subjective BPPV patients was 93%, which compares well with the literature on objective BPPV. Haynes and colleagues39 reviewed 127 patients with objective BPPV and 35 patients with subjective BPPV who were all treated with the liberatory maneuver. Similar results were found with no significant difference between the two groups in overall success rate: objective BPPV (91%) versus subjective BPPV (86%). Predicting Success and Recurrence Risk Several studies have attempted to identify variables that would help predict initial short-term success and recurrence risk with repositioning maneuvers. Beynon and colleagues65 followed 51 patients and reported no associations of age, sex, etiology (primary or secondary), or the duration

of symptoms before treatment and success of the PRM. They also found that the presence of recurrent or permanent BPPV before repositioning was not related to recurrence risk after treatment. Macias and colleagues66 followed 259 patients with BPPV and found no significant relationship between either short-term success or recurrence risk and age, sex, etiology (idiopathic or secondary), or the number of repositioning maneuvers performed per treatment visit. It was found, however, that patients with bilateral disease or BPPV in a canal other than the posterior canal required a greater number of treatment sessions until resolution of symptoms. The prospective study of 168 patients using the CRP by Nunez and colleagues67 suggests a recurrence rate of 15% per year, with a 50% recurrence rate of BPPV at 40 months after treatment. There was no significant association between cure or recurrence rate and sex, age, duration of symptoms, presumed cause, or treating physician.

SURGICAL TREATMENT It should be stressed that BPPV, although incapacitating, is a benign disease, and surgery should be reserved for the most intractable or multiply recurrent cases. BPPV often undergoes spontaneous remission within 6 months and is highly amenable to physical therapy and repositioning maneuvers. The practitioner should exclude BPPV of the lateral and superior semicircular canals and accurately assess for secondary causes for BPPV. Furthermore, before the physician considers surgery, the posterior fossa should be imaged to rule out central lesions that might mimic BPPV.68 Singular Neurectomy The singular neurectomy for BPPV was popularized by Gacek69 in the 1970s. It involves a transection of the posterior ampullary nerve in the singular canal. After raising the tympanomeatal flap, the singular canal is approached by drilling inferior to the round window. This puts at risk both the ampulla and vestibule; if either is injured, it may lead to severe vertigo or sensorineural hearing loss. Initial reports by Gacek70 demonstrated high efficacy with complete vertigo resolution in 91.7% of patients. However, there was a 7.3% risk of sensorineural hearing loss with the procedure. Gacek published an update of his personal series in 199571 and decreased the rate of sensorineural hearing loss to 3%. Although safe and reliable in experienced hands, this procedure is technically demanding and has largely been replaced by the simple posterior semicircular canal occlusion.15 Posterior Semicircular Canal Occlusion History It had long been a maxim in otologic surgery that the violation of the labyrinth would result in a “dead ear.” This principle arose in the early days of otologic surgery when surgeons were forced to operate under less than optimal conditions. These included the presence of chronic infection and the difficulty of discerning surgical landmarks because of poor magnification.

Benign Paroxysmal Positional Vertigo

In the early 1960s, Money and Scott72 successfully ablated individual semicircular canals without affecting the response of the other ipsilateral semicircular canals. At least in the cat model, this proved that invasive inner ear surgery did not necessarily result in a “dead ear” under optimal operating conditions. However, although the vestibular labyrinth was spared by individual canal occlusion, the possibility of sensorineural deafness secondary to cochlear damage was not addressed. Several experiments performed in the 1950s had attempted to address this issue. Kristensen73,74 claimed to preserve hearing when performing partial labyrinthectomies in guinea pigs. Unfortunately, hearing was crudely measured using Preyer’s reflexes and the study failed to control for hearing in the nonoperated ear. Wever and colleagues75 used cochlear potentials to determine that partial hearing was preserved after destruction of the lateral semicircular canal in monkeys. The degree of hearing preservation, however, varied a great deal among the subjects. More recently, animal studies by Kobayashi and colleagues76 and Smouha and colleagues77,78 have demonstrated the preservation of cochlear function following the ablation of a semicircular canal. In humans, individual cases of incidental hearing preservation following injury to the lateral semicircular canal have been reported following fenestration surgery for otosclerosis79,80 and chronic otitis media.81–83 It was Parnes and McClure,84 however, who first measured the effect on hearing of posterior semicircular canal occlusion in guinea pigs. Hearing, measured by auditory

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brainstem evoked responses, remained stable for as long as 6 months following canal occlusion.85 This study provided the groundwork for posterior semicircular canal occlusion, the surgical technique now used to treat intractable BPPV in humans. Technique The procedure is performed under general anesthetic and should take no longer than 2 to 3 hours (Fig. 41-5). Using a 5- to 6-cm postauricular incision, the posterior canal is accessed through a mastoidectomy. With the use of an operating microscope and drill, a 1 × 3 mm fenestration is made in the bony posterior canal. Particles can occasionally be seen in the posterior semicircular canal after fenestration. A plug, fashioned from bone dust and fibrinogen glue, is used to occlude the canal. Most patients are hospitalized for 2 to 3 days. Since the occlusion also impairs the normal inner ear physiology, all patients are expected to have postoperative imbalance and dysequilibrium. For most people, the brain adapts to this after a few days to a few weeks, with vestibular physiotherapy hastening this process. A few variations of this technique have been published since the original description. A carbon-dioxide laser has been used to ablate the posterior semicircular canal with promising results in six patients.86,87 The use of an argon laser has been described with a guinea pig model.88 Brantberg and Bergenius89 described successful occlusion of the anterior semicircular canal in a patient with intractable anterior canal BPPV.

Cutting drill

a

Diamond drill b

Posterior canal

A Figure 41-5. Surgical technique of posterior semicircular canal occlusion, right ear. A, Exposing the posterior semicircular canal otic capsule through a standard postauricular transmastoid approach (a). Creating the 1 x 3 mm to 1 x 4 mm endosteal island with small diamond burr (b). Note that the drill-bit size is not to scale. Continued

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a

b 90° Pick

Figure 41-5, cont’d. B, Lifting out the endosteal island with a fine 90-degree pick (a). Magnified lateral view (b). C, Creating the canal plug with two-component fibrinogen glue and mastoid cortex bone chips. Continued

B

A

B Bone chips

Spatula

Plug

C

Benign Paroxysmal Positional Vertigo

a

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Perilymph b

Endolymph

Membranous labyrinth

D

Tisseel glue

Temporalis fascia

E Figure 41-5, cont’d. D, Tamping plug through the fenestra into the canal (a). Cross-section schematic of canal showing intact but occluded membranous canal (b). E, Covering the fenestra and surrounding bone with fascia and glue. (Reprinted with permission from Parnes LS: Update on posterior canal occlusion for benign paroxysmal positional vertigo. Otolaryngol Clin North Am 29:333–342, 1996.)

Results In 2001, Agrawal and Parnes10 published the largest series in the literature of 44 occluded posterior canals in 42 patients. All 44 ears were relieved of BPPV, with only one having a late atypical recurrence. Of the 40 ears with normal preoperative hearing, one had a delayed (3-month) sudden

and permanent profound loss, and one other had a mild loss (20 db). Obvious free-floating endolymph particles were found in 30% of operated ears (Fig. 41-6). Essentially, all cases were followed by an initial 1- to 4-week period of imbalance and motion sensitivity. The average duration of postoperative hospitalization is 2 to

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5 days in uncomplicated cases. Older patients have slower recoveries and require longer hospital stays. The degree of postoperative motion sensitivity usually determines the length of stay. Postoperative vestibular suppressants are discouraged because they tend to prolong the recovery. Patients are given instructions, however, for postoperative vestibular physiotherapy. There have been no late sequelae such as sensorineural hearing loss or tinnitus. Rizvi and Gauthier90 published a case where the patient was not resolved of BPPV following canal occlusion. This was secondary to incomplete occlusion of the canal intraoperatively and the creation of an iatrogenic fistula. This was surgically corrected and the patient’s hearing and vertigo resolved. In addition to the study by Agrawal and Parnes,10 Hawthorne and el-Naggar91 (15 patients), Anthony92 (14 patients), Walsh and colleagues93 (13 patients), Zappia94 (8 patients), Pace-Balzan and Rutka95 (5 patients), and Dingle and colleagues96 (4 patients) have further supported the safety and efficacy of this procedure.

SUMMARY A

Benign paroxysmal positional vertigo presents with a history of brief, episodic, position-provoked vertigo with characteristic findings on Dix-Hallpike testing. Whereas a variety of positional maneuvers have been described, the particle repositioning maneuver is a simple effective treatment for most patients with objective or subjective BPPV. Current evidence does not support the routine use of mastoid vibration with repositioning. Although most investigators are still advising patients to remain upright for 24 to 48 hours after repositioning, recent evidence suggests that this is unnecessary. In addition, the literature is equivocal regarding the ideal number of repositioning maneuvers to perform per treatment session. To date, no factors have been identified to indicate an increased risk of BPPV recurrence after successful repositioning; however, the association between BPPV recurrence and migraine warrants further investigation. For the small group of patients with classic posterior canal BPPV who do not respond to repositioning, posterior canal occlusion is a safe and highly efficacious procedure.

REFERENCES

B Figure 41-6. Sequential computer-regenerated photographs taken from an intraoperative video of a fenestrated posterior semicircular canal. A, Note the single white conglomerate mass in the membranous duct (arrow). B, Note that the mass has fragmented into tiny particles 2 to 3 minutes later, after the membranous duct has been probed (arrow). (Reprinted with permission from Parnes LS, Agrawal SK, Atlas J: Diagnosis and management of benign paroxysmal positional vertigo [BPPV]. CMAJ 169:681–693, 2003.)

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61. Asawavichianginda S, Isipradit P, Snidvongs K, Supiyaphun P: Canalith repositioning for benign paroxysmal positional vertigo: A randomized, controlled trial. Ear Nose Throat J 79:732–734, 736–737, 2000. 62. Hain TC, Helminski JO, Reis IL, Uddin MK: Vibration does not improve results of the canalith repositioning procedure. Arch Otolaryngol Head Neck Surg 126:617, 2000. 63. Li JC: Mastoid oscillation: A critical factor for success in canalith repositioning procedure. Otolaryngol Head Neck Surg 112:670, 1995. 64. Massoud EA, Ireland DJ: Post-treatment instructions in the nonsurgical management of benign paroxysmal positional vertigo. J Otolaryngol 25:121, 1996. 65. Beynon GJ, Baguley DM, da Cruz MJ: Recurrence of symptoms following treatment of posterior semicircular canal benign positional paroxysmal vertigo with a particle repositioning manoeuvre. J Otolaryngol 29:2, 2000. 66. Macias JD, Lambert KM, Massingale S, et al: Variables affecting treatment in benign paroxysmal positional vertigo. Laryngoscope 110:1921, 2000. 67. Nunez RA, Cass SP, Furman JM: Short- and long-term outcomes of canalith repositioning for benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg 122:647, 2000. 68. Dunniway HM, Welling DB: Intracranial tumors mimicking benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg 118:429, 1998. 69. Gacek RR: Further observations on posterior ampullary nerve transection for positional vertigo. Ann Otol Rhinol Laryngol 87:300, 1978. 70. Gacek RR: Singular neurectomy update. Ann Otol Rhinol Laryngol 91:469, 1982. 71. Gacek RR: Technique and results of singular neurectomy for the management of benign paroxysmal positional vertigo. Acta Otolaryngol 115:154, 1995. 72. Money KE, Scott JW: Functions of separate sensory receptors of nonauditory labyrinth of the cat. Am J Physiol 202:1211, 1962. 73. Kristensen HK: Acoustic and vestibular function in guinea-pigs after removal of the membranous external semicircular canal. J Laryngol Otol 66:259, 1952. 74. Kristensen HK: Acoustic-vestibular and histologic examinations in guinea-pigs after interruption of membranous labyrinth in semicircular canals or cochlea. J Laryngol Otol 73:699, 1959. 75. Wever EG, Lempert H, Meltzer PE: The effects of injury to the lateral semicircular canal. Trans Am Acad Ophthalmol Otolaryngol 60:718, 1956. 76. Kobayashi T, Shiga N, Hozawa K, et al: Effect on cochlear potentials of lateral semicircular canal destruction. Arch Otolaryngol Head Neck Surg 117:1292, 1991. 77. Smouha EE, Namdar I, Michaelides EM: Partial labyrinthectomy with hearing preservation: An experimental study in guinea pigs. Otolaryngol Head Neck Surg 114:777, 1996. 78. Smouha EE, Inouye M: Partial labyrinthectomy with hearing preservation: Frequency-specific data using tone-burst auditory brain stem response. Otolaryngol Head Neck Surg 120:146, 1999. 79. Cawthorne T: The effect on hearing in man of removal of the membranous lateral semicircular canal. Acta Otolaryngol Suppl (Stockh) 78:145, 1948.

80. Jongkees LBW: On the function of the labyrinth after destruction of the horizontal semicircular canal. Acta Otolaryngol 38:505, 1950. 81. Palva T, Karja J, Palva A: Immediate and short-term complications of chronic ear surgery. Arch Otolaryngol 102:137, 1976. 82. Jahrsdoerfer RA, Johns ME, Cantrell RW: Labyrinthine trauma during ear surgery. Laryngoscope 88:1589, 1978. 83. Canalis RF, Gussen R, Abemayor E, Andrews J: Surgical trauma to the lateral semicircular canal with preservation of hearing. Laryngoscope 97:575, 1987. 84. Parnes LS, McClure JA: Effect on brainstem auditory evoked responses of posterior semicircular canal occlusion in guinea pigs. J Otolaryngol 14:145, 1985. 85. Parnes LS, McClure JA: Posterior semicircular canal occlusion in the normal hearing ear. Otolaryngol Head Neck Surg 104:52, 1991. 86. Antonelli PJ, Lundy LB, Kartush JM, et al: Mechanical versus CO2 laser occlusion of the posterior semicircular canal in humans. Am J Otol 17:416, 1996. 87. Kartush JM, Sargent EW: Posterior semicircular canal occlusion for benign paroxysmal positional vertigo—CO2 laser-assisted technique: Preliminary results. Laryngoscope 105:268, 1995. 88. Oki S, Nomura Y, Sugio Y, Young YH: Occlusion of the semicircular canal using argon laser. J Clin Laser Med Surg 14:393, 1996. 89. Brantberg K, Bergenius J: Treatment of anterior benign paroxysmal positional vertigo by canal plugging: A case report. Acta Otolaryngol 122:28, 2002. 90. Rizvi SS, Gauthier MG: Unexpected complication of posterior canal occlusion surgery for benign paroxysmal positional vertigo. Otol Neurotol 23:938, 2002. 91. Hawthorne M, el-Naggar M: Fenestration and occlusion of posterior semicircular canal for patients with intractable benign paroxysmal positional vertigo. J Laryngol Otol 108:935, 1994. 92. Anthony PF: Partitioning the labyrinth for benign paroxysmal positional vertigo: Clinical and histologic findings. Am J Otol 14:334, 1993. 93. Walsh RM, Bath AP, Cullen JR, Rutka JA: Long-term results of posterior semicircular canal occlusion for intractable benign paroxysmal positional vertigo. Clin Otolaryngol 24:316, 1999. 94. Zappia JJ: Posterior semicircular canal occlusion for benign paroxysmal positional vertigo. Am J Otol 17:749, 1996. 95. Pace-Balzan A, Rutka JA: Non-ampullary plugging of the posterior semicircular canal for benign paroxysmal positional vertigo. J Laryngol Otol 105:901, 1991. 96. Dingle AF, Hawthorne MR, Kumar BU: Fenestration and occlusion of the posterior semicircular canal for benign positional vertigo. Clin Otolaryngol 17:300, 1992. 97. Smouha EE: Time course of recovery after Epley maneuvers for benign paroxysmal positional vertigo. Laryngoscope 107:187, 1997. 98. Wolf JS, Boyev KP, Manokey BJ, Mattox DE: Success of the modified Epley maneuver in treating benign paroxysmal positional vertigo. Laryngoscope 109:900, 1999. 99. Welling DB, Barnes DE: Particle repositioning maneuver for benign paroxysmal positional vertigo. Laryngoscope 104:946, 1994. 100. Harvey SA, Hain TC, Adamiec LC: Modified liberatory maneuver: Effective treatment for benign paroxysmal positional vertigo. Laryngoscope 104:1206, 1994.

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Outline Introduction Autonomic Dysfunction, Anxiety, and Panic Attacks: Vestibular Circuitry Specific Pharmacotherapy Ménière’s Disease Chemical Labyrinthectomy Preparation of Gentamicin Solution Intratympanic Dexamethasone Otosyphilis

Chapter

Pharmacotherapy for Vestibular Dysfunction

Vestibular Migraine Vertebrobasilar Insufficiency Familial Ataxia Syndrome Psychophysiologic Dizziness Future Perspectives Symptomatic Pharmacotherapy Mechanism of Action Strategy in the Treatment of Vertigo Prophylaxis of Motion Sickness

INTRODUCTION Over the past three decades, the evolution in the diagnosis and management of peripheral and central vestibular disorders has been dramatic. Consequently, it is rare that a patient requires surgical intervention1; however, a clear understanding of the pathophysiology and the scientific basis of medical treatment will help ensure appropriate treatment of these patients. Three peripheral vestibular disorders are commonly encountered by the neurotologist: benign paroxysmal positional vertigo, Ménière’s disease, and vestibular neuronitis (neuritis), and one central disorder that is frequently encountered by the neurotologist (vestibular migraine), therefore the medical management of these disorders will be emphasized. Additional disorders are amenable to medical management, and many of these will also be addressed. Pharmacotherapy of vertigo can be divided into two general categories: specific and symptomatic. Examples of specific therapies include antibiotics for bacterial or syphilitic labyrinthitis, anticoagulants for vertebrobasilar insufficiency, and diuretics for Ménière’s disease. Whenever possible, treatment should be directed at the underlying disorder. In the majority of cases, however, symptomatic treatment is combined with the specific therapy or is the only therapy available (e.g., viral vestibular neuronitis). Common causes and mechanisms of dizziness are outlined in Table 42-1. Tables 42-2 and 42-3 distinguish the common peripheral origins of vertigo from the common central causes.2–4 The diagnosis, pathophysiology, and treatment of most of these disorders are presented throughout several other chapters in this section of the

P. Ashley Wackym, MD, FACS Tammy S. Schumacher-Monfre, MSN, APNP

book, therefore, the focus of this chapter will be on medical management and the scientific rationale for each strategy. The peripheral causes of vestibular dysfunction (see Table 42-2) are presumed to be restricted anatomically to structures associated with the membranous labyrinth, peripheral branches of the vestibular nerve, Scarpa’s ganglion, and the vestibular nerve root. The central causes of vestibular dysfunction, though, compromise central vestibular circuits that mediate vestibular influences on posture (via vestibulospinal and vestibulocollic pathways), control of gaze (via vestibulo-ocular and vestibulocollic pathways), and autonomic functions. However, unlike the peripheral vestibular system, which may be viewed strictly as sensors of linear and angular acceleration of the head, central vestibular pathways are multimodal neural circuits that integrate a variety of sensory and motor signals related to balance, posture, and eye movements. The vestibular nuclei are the primary central target of the vestibular nerve. Other sites that receive primary afferents from the vestibular nerve include several other brainstem nuclei (abducens nucleus, nucleus prepositus hypoglossi, cochlear nuclei [probably from the sacculus], external cuneate nucleus, and reticular formation). Since the vestibular nerve terminates only in the ipsilateral brainstem, integration of information from coplanar pairs of peripheral vestibular end-organs (e.g., left and right lateral canal cristae, left superior and right posterior canal cristae, and left posterior and right superior canal cristae) is mediated by commissural connections. In addition to these vestibular inputs, the vestibular nuclei receive proprioceptive, visual (optic flow), and premotor/motor signals from different of levels of the neuraxis (including cerebral 659

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TABLE 42-1. Common Causes and Mechanisms of Dizziness Symptom

Causes

Mechanisms

Vertigo

Benign positional vertigo, labyrinthitis, vestibular neuronitis, Ménière’s disease, vestibular migraine, otosyphilis, superior semicircular canal dehiscence syndrome, vertebrobasilar insufficiency, multiple sclerosis, brainstem or cerebellar infarction Hyperventilation associated with panic disorders or chronic anxiety, postural hypotension, congestive heart failure, diffuse cerebrovascular disease Ototoxic drugs, peripheral neuropathy, presbystasis, autoimmune inner ear disease, genetic vestibular hair cell loss, cerebellar atrophy, cerebellar infarction, posterior fossa tumors, meningitides New refractive prescription, cataract surgery with lens implant, ototoxic drugs, extraocular muscle dysfunction, multiple sclerosis, cranial nerve III, IV, or VI dysfunction, corneal disease Psychophysiologic dizziness, diabetes mellitus, systemic vasculitis, adverse drug reaction, aging

Imbalance of tonic vestibular signals

Presyncopal lightheadedness Disequilibrium Visual distortion Multisensory dizziness

cortex) that are related to postural and ocular control. One consequence of the polymodal inputs to these circuits may be the ability to use other sensory information to compensate for peripheral vestibular injury. Specific cell groups (or circuits) within the vestibular nuclei then contribute directly to vestibulospinal, vestibulo-ocular, vestibulocollic, and vestibuloautonomic pathways. The activity of each of these functional circuits within the vestibular nuclei is modulated by specific cerebellar circuits in the flocculonodular lobe, the vermis of the posterior lobe, and the anterior lobe. Classical clinical and anatomic evidence indicate that each of these cerebellar regions contribute to different vestibular motor functions. For example, flocculonodular lobe dysfunction has a primary effect on eye movements, whereas anterior lobe degeneration (e.g., alcoholic cerebellar degeneration) predominantly influences postural control. Cerebellar regions related to autonomic control have also been identified (for review see Balaban5). Each of these larger cerebellar regions, though, are subdivided into smaller circuitry units (zones) that appear to directly influence specific vestibular nucleus output pathways. For example, a small region (zone) in the cerebellar flocculus contributes to the control

Diffuse ischemia of the brain Symmetric vestibular loss, proprioceptive loss, cerebellar damage Visual and vestibular input mismatch Integrative dysfunction involving visual, proprioceptive, or vestibular systems

of eye movements in the plane of the horizontal semicircular canal by connections with the vestibular nuclei. The direct cerebellar connections to the vestibular nuclei appear to be important for coordination and continual recalibration of motor responses to vestibular stimulation. Climbing fiber input from the inferior olive appears to play a critical role in these functions. The climbing fibers are believed to provide a sensorimotor error signal to cerebellar Purkinje cells, which may alter the responsiveness of the Purkinje cells to parallel fiber inputs via a mechanism termed long-term depression, to achieve a rapid correction of function. One important feature of central vestibular circuitry is its ability to compensate for peripheral injury. Although the phenomenon is well known, the mechanisms of compensation are poorly understood. The present evidence suggests that behavioral compensation involves synaptic plasticity in both the brainstem and the cerebellum. Two factors in compensation appear to be of particular relevance clinically. First, the stability of the vestibular dysfunction has an obvious influence on the efficacy of compensation. Stable, predictable dysfunction (e.g., vestibular nerve TABLE 42-3. Common Central Causes of Vertigo

TABLE 42-2. Common Peripheral Causes of Vertigo Benign positional vertigo Ménière’s disease Vestibular neuronitis (neuritis) Post-traumatic Endolymphatic hydrops Labyrinthine concussion Drug-induced toxicity Minocycline Phenytoin Quinidine Gentamicin Streptomycin Other Bacterial labyrinthitis Viral labyrinthitis Tumors Otosclerosis Vasculitides

Brainstem lesions Arteriovenous malformation (AVM) Tumor Trauma Demyelinating disease Multiple sclerosis Infarction or ischemia Vestibular migraine Brainstem Cerebellum Vertebrobasilar insufficiency Hereditary disorders Spinocerebellar disease Posterior fossa lesion Acoustic neuroma Meningioma Arachnoid cyst Metastatic tumor Other cerebellopontine angle tumor Arnold-Chiari malformation

Pharmacotherapy for Vestibular Dysfunction

section) provides a baseline of dysfunction as a target for compensation. Conversely, compensation for fluctuating hypoactivity or hyperactivity (e.g., Ménière’s disease) is expected to be ineffective because baseline function is unpredictable or unstable. Second, the functional status of the central nervous system (CNS), due to either agerelated or organic changes, is an important consideration. For example, individuals with preexisting cerebellar damage may show decreased compensatory capability.6

Autonomic Dysfunction, Anxiety, and Panic Attacks: Vestibular Circuitry Every clinician treating patients with vestibular disorders, as well as astronauts experiencing the rapid changes of vestibular input encountered during the various stages of space flight, are well aware of the marked autonomic dysfunction associated with these alterations of vestibular input.7 These signs and symptoms of nausea, vomiting, pallor, as well as changes in respiration and circulation are clinically apparent; however, the basis for these responses has only recently been elucidated via anatomic studies identifying a network of vestibuloautonomic projections in the brainstem of rabbits, rats, and cats.8,9 The finding that vestibular nuclear and secondary visceral projections converge in the parabrachial nucleus (and other brainstem regions) provides important insights into potential neural substrates for phenomena such as respiratory, cardiovascular, and gastrointestinal (emetic) responses to vestibular stimulation, motion sickness, and autonomic responses in altered gravitational environments. In particular, these findings provide a potential neurologic basis for the close relationship between vestibular dysfunction and anxiety disorders with agoraphobia.8 Anxiety, panic attacks, and agoraphobia are also commonly associated with vestibular dysfunction.8 In 1945 Sir Terrence Cawthorne described the terror that patients with acute vestibular injury may experience. Other clinicians have identified specific situations involving changes in spatial orientation that elicit symptoms of anxiety and panic. Levy and O’Leary10 coined the term street neurosis to describe the anxiety that some patients develop after an acute vestibular attack. McCabe11 observed the supermarket syndrome in patients with Ménière’s disease and characterized these patients as experiencing an intolerance to looking back and forth along aisles and up and down shelves. Patients with vestibular deficits who are visually or proprioceptively dependent may have symptoms of imbalance, discomfort, anxiety, or phobic avoidance when in situations with inadequate visual or proprioceptive balance cues. Jacob and colleagues have termed this situational specificity space and motion discomfort. These unpleasant manifestations of discomfort may also be considered as referred signs and symptoms from vestibular pathways to visceral sites and may serve as eliciting or reinforcing stimuli for conditioned avoidance of potentially dangerous situations.12 The diagnostic category space and motion phobia develops when situational distress significantly impairs a patient’s normal activities, particularly by producing avoidance behaviors that reduce vestibular discomfort.4 The neurologic linkage model has been proposed to explain the association of vestibular disorders and autonomic dysfunction, anxiety,

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panic attacks, and agoraphobia.8 The linkage appears to be mediated by (1) ascending vestibular pathways involving the parabrachial nucleus, amygdala, and infralimbic cortex; (2) noradrenergic pathways; and (3) serotonergic pathways. The consequences of this intimate neurologic linkage among vestibular function, autonomic regulation, and affective status are of great practical importance to the clinician. In particular, it is important to consider a multifactorial treatment plan to address the pathogenic mechanisms, obtain symptomatic relief from vertigo and nausea, facilitate vestibular compensation, and address the emergent anxiety and depression of individual patients. The symptomatic pharmacotherapy of vestibular dysfunction is discussed later in this chapter; however, low doses of diazepam (2 mg orally tid PRN), or lorazepam (0.5 mg orally tid PRN) are useful in managing the associated symptoms of autonomic dysfunction, anxiety, panic attacks, and agoraphobia. For symptoms that occur more consistently, clonazepam (0.25 mg bid to tid) should be considered.13,14 Adjunctive techniques such as stress reduction methods, biofeedback, hypnosis, and yoga can likewise prove helpful in reducing these symptoms.

SPECIFIC PHARMACOTHERAPY Specific forms of pharmacotherapy are directed at reversing the proven or presumed pathophysiologic mechanisms responsible for disorders associated with vestibular dysfunction. Examples of such interventional schemes are outlined in Table 42-4.

Ménière’s Disease Medical therapy for Ménière’s disease includes dietary modification, physiotherapy, psychological support, and pharmacologic intervention. Diuretic therapy and salt restriction have long been considered the mainstay of medical intervention for endolymphatic hydrops, based on the assumption that these drugs can affect fluid balance within the inner ear and lead to a depletion of endolymph.15–17 Thiazide diuretics have been a popular form of such specific pharmacotherapy for Ménière’s disease. These agents enhance excretion of sodium, chloride, and water by interfering with absorption of sodium ions across the epithelium of the cortical diluting segment of the nephron. Other electrolyte effects include enhanced potassium, magnesium, phosphate, bromide, and iodide excretion. Long-term therapy produces decreased calcium excretion and hypocalciuria. Prolonged thiazide diuretic therapy can be associated with metabolic alkalosis with hypokalemia and hypochloremia. A potassium-sparing diuretic such as triamterene or spironolactone is often used in conjunction with thiazides to offset potassium loss (e.g., triamterene and hydrochlorothiazide). Thiazides can induce hyperglycemia and exacerbate diabetes mellitus. Other potential adverse reactions include hyperuricemia and orthostatic hypotension. These agents may exacerbate preexisting renal or hepatic insufficiency. Carbonic anhydrase inhibitors (e.g., acetazolamide) decrease sodium-hydrogen exchange in the renal tubule.

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TABLE 42-4. Specific Pharmacotherapy of Vestibular Disorders Peripheral Vestibular Disorders Ménière’s disease Low sodium diet (1–1.5 g Na+/day) Diuretic Triamterene and hydrochlorothiazide (Dyazide) Acetazolamide (Diamox) Hydrochlorothiazide Vasodilator Isosorbide dinitrate Niacin Papaverine Nylidrin Histamine Betahistine Aminoglycosides Gentamicin (transtympanic) Streptomycin (IM or selective perfusion) Steroids Dexamethasone (transtympanic) Otosyphilis Penicillin (IV, IM), Amoxicillin (PO) Doxycycline, Tetracycline, Erythromicin (for penicillin allergy) Steroids Viral neurolabyrinthitis (including vestibular neuronitis) Antiviral agents Acyclovir (Zovirax) Famciclovir (Famvir) Valaciclovir (Valtrex) Steroids Central Vestibular Disorders Vertebrobasilar insufficiency Antiplatelet therapy Aspirin Ticlopidine Pentoxyifylline Anticoagulation (reserve for impending stroke) Heparin Warfarin Postinfarction syndromes Dihydroergocristine, dihydroergocriptine Flunarizine Gangliosides Free radical scavengers 21-Aminosteroids Amphetamine Vestibular Migraine Migraine abortive therapy (not used in basilar artery migraine) Ergotamine tartrate Sumatriptin Migraine prophylaxis Nortriptyline or Imipramine Verelan PM Propranolol (first line agent for children) Neurontin Flunarizine Methysergide Psychophysiologic dizziness (associated with panic attacks) Antidepressants Imipramine Desimpramine Nortriptyline Tranquilizers Alprazolam Diazepam Lorazepam Monoamine oxidase inhibitors Phenelzine Familial ataxia syndromes Acetazolamide (Diamox)

These agents are used to decrease intraocular pressure in patients with glaucoma by reducing the formation of aqueous humor, and the analogy drawn between this disease state and Ménière’s disease has led to the trial of these agents for treatment of endolymphatic hydrops. In addition they are capable of decreasing CSF production by up to 50%. These diuretic agents increase excretion of bicarbonate, sodium, and potassium. Reduction of plasma bicarbonate can produce mild metabolic acidosis with chronic therapy. Rarely, hyperglycemia is exacerbated in patients with diabetes mellitus. Possible adverse effects include nephrocalcinosis, hyperhidrosis, distal paraesthesia, and gastrointestinal disturbance. Lip and distal paraesthesias may resolve with continued use or with decreasing the dosage; however, these symptoms, if tolerated by the patient, do not represent a contraindication to continued use. Particular caution should be taken in prescribing acetazolamide to patients with a previous history of nephrolithiasis, especially if the kidney stones were shown to be calcium oxalate. If a trial of acetazolamide therapy in such a patient is necessary, a 24-hour urine collection should be followed by analysis of calcium, oxalate, and citrate. If the patient demonstrates hypocitruria, which can be a consequence of metabolic acidosis induced by acetazolamide, administration of acetazolamide should be terminated, as hypocitruria can induce calcium oxalate nephrolithiasis. Vasodilators have been used for the treatment of Ménière’s disease, based on the hypothesis that the pathogenesis of endolymphatic hydrops results from ischemia of the stria vascularis. Such agents include niacin, papaverine, nylidrin, isosorbide dinitrate, intravenous (IV) histamine, and the oral histamine agonist betahistine. These agents directly affect vascular smooth muscle, producing vasodilation. Isosorbide dinitrate principally affects the venous system, whereas histamine causes vasodilation of small blood vessels and capillaries. Betahistine has also been shown to exert a direct inhibitory effect on polysynaptic neurons within the vestibular nuclei, independent of changes produced in cerebral blood flow. The most common adverse reactions to these agents include flushing, headache, and hypotension.18,19 The literature contains many anecdotal reports and uncontrolled studies reporting apparent beneficial effects of specific pharmacotherapy in patients suffering from Ménière’s disease. Ruckenstein and colleagues20 critically reviewed this literature in 1991 and concluded that nonspecific vestibular suppressants are the only medications that have been shown to alleviate vertigo associated with Ménière’s disease. Three small double-blind studies showed short-term beneficial effects of betahistine, but this may be secondary to a nonspecific CNS suppression rather that a direct effect on cochlear blood flow, as previously described. Thus, no studies demonstrated definitive beneficial effects of vasodilator therapy in reversing endolymphatic hydrops. Chemical Labyrinthectomy Compliance with medical management (daily sodium restriction to 1500 mg/day plus triamterene hydrochlorothiazide [Dyazide] qd to bid) results in acceptable control of signs and symptoms in most patients15; however,

Pharmacotherapy for Vestibular Dysfunction

approximately 10% of patients reach a point when the symptoms are so severe that an operation or aminoglycoside treatment should be considered.1 Henceforward in this chapter we will consider the aminoglycoside vestibulotoxic treatments to be included under the term chemical labyrinthectomy. When considering vestibular surgery or chemical labyrinthectomy, it is often useful to have the patient with Ménière’s disease consult a dietitian in order to optimize the medical management prior to undertaking this course. From the standpoint of the severity of symptoms the most appropriate group for surgical or chemical labyrinthectomy treatment include patients who cannot work, drive, make secure travel plans, or take care of a family. Candidates may also include those who are managing to carry out these activities only with great effort because they are highly motivated to do so (American Academy of Otolaryngology–Head and Neck Surgery [AAO-HNS] functional levels 4, 5, and 6).21 An endolymphatic sac procedure may be considered in some cases at AAO-HNS functional level 3, whereby no disability or immediate threat of disability is evident, but daily activities are disrupted due to the attacks of vertigo. The overall goal of any treatment of vestibular disorders is to help patients be as functional and comfortable as possible. The operational goals are to control episodic vertigo and to avoid or minimize treatment-associated disequilibrium and hearing loss. The primary technical goal of chemical labyrinthectomy is complete unilateral vestibular ablation.1 The most common difficult problem to manage after any vestibular destructive surgery (vestibular neurectomy, labyrinthectomy, or aminoglycoside treatment) is persistent, troublesome disequilibrium and this complication occurs in 20% of cases.1 Nearly all patients will experience vertigo and disequilibrium immediately after surgical labyrinthectomy or vestibular neurectomy. With aminoglycoside treatments, the disequilibrium begins when the chemical labyrinthectomy effect occurs. This effect typically occurs at least 4 days after the commencement of treatment. Patients report symptoms of acute unilateral peripheral vestibular loss, including an acute sensation of rotational vertigo, imbalance, a tendency to fall toward the affected side, and intolerance to rapid head movement. They usually experience autonomic dysfunction (e.g., nausea and diaphoresis), as well as anxiety and general malaise. These symptoms improve spontaneously such that most patients are able to return to full activities by 6 to 8 weeks after labrinthectomy.1 Patients treated with intramuscular (IM) aminoglycosides or those with a pretreatment contralateral vestibular deficit may also experience oscillopsia. This symptom is a bobbing of the visual field on ambulation. Patients will report that they have trouble reading street signs while driving or riding in a car or difficulty reading labels as they move down the aisle of a store. Oscillopsia is a manifestation of reduction of vestibulo-ocular reflex due to a loss of vestibular sensation. Oscillopsia usually improves in time, possibly due to CNS compensation or tolerance by the patient. In nearly all instances, early postoperative disequilibrium will gradually resolve following ambulation of the patient, and additional treatment is not needed. If disequilibrium

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persists or occurs later following chemical labyrinthectomy, vestibular exercises or formal vestibular rehabilitation are usually helpful in improving balance function and comfort of movement. Interest in intratympanic aminoglycoside (ITAG) has increased in recent years as an alternative to endolymphatic sac surgery and vestibular neurectomy. A key advantage is that ITAG can be a nonsurgical office procedure. Nevertheless, ITAG is, at present, an imprecise treatment, difficult to control, and in at least one current form of drug delivery, appears to be associated with a 10% rate of deafness in the treated ear.22 Nonetheless, vertigo can be relieved in 90% of cases.22,23 Other protocols may be associated with a lower rate of deafness. ITAG has a place in the treatment of Ménière’s disease, but the optimal treatment protocol and the boundaries of its exact role remain to be defined. Since 1994, when the first edition of this textbook was published, most otologists have greatly decreased the frequency with which they perform ITAG because of the risk of hearing loss. However, a recent longitudinal study of ITAG administration in 31 Ménière’s disease patients reported a markedly reduced rate of profound hearing loss.24 In this study, Wu and Minor reported profound hearing loss in only one patient (3%). In addition, hearing improvement was seen in 5 (16%), unchanged in 21 (65%), and worse in 5 (16%). Vertigo was controlled in 90% of the patients. Their protocol involves a single ITAG administration (26.7 mg/mL gentamicin, 0.4 mL typically injected), 30 minutes of solution contact with the round window, and subsequent removal of the residual gentamicin via aspiration. Minor’s protocol now involves a single ITAG injection, and additional treatments are only administered if episodes of vertigo have persisted at the time of follow-up examination 3 weeks after injection. Aminoglycosides do not seem to be concentrated in cochlear fluids, but the elimination half-life increases with chronic administration, suggesting sequestration of the drug by hair cells.25 Amikacin, dihydrostreptomycin, and kanamycin are primarily cochleotoxic, whereas gentamicin and streptomycin are primarily vestibulotoxic.16 At high doses, streptomycin is also cochleotoxic. For example, streptomycin, 25 mg/kg/day, administered systematically to cats resulted in loss of vestibular hair cells only, but at 100 mg/kg/day, both vestibular and cochlear hair cells were lost.26 The hair cells of the cristae, the maculae, and the cochlea degenerate to different degrees following the administration of aminoglycosides. The primary vestibular neurons, the cochlear nuclei, and the vestibular nuclei are not directly affected, even at high doses.26 The basal turn of the cochlea is the region most susceptible to permanent loss of hair cells, resulting in an initial loss of highfrequency hearing. Although the mechanisms of this differential toxicity are incompletely understood, several contributing factors have been identified, including the route of administration, dose variables, and the specific aminoglycoside used. Damage to vestibular dark cells, which are thought to play a role in the production of endolymph, has been reported following administration of doses of aminoglycoside below the threshold for damage to hair cells. An attractive hypothesis is that the impaired function of dark

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cells would be beneficial in Ménière’s disease since decreased production of endolymph would affect the fluid homeostasis of the inner ear.27,28 Preparation of Gentamicin Solution Gentamicin solution may either be used as a stock solution of 40 mg/mL with a pH of about 5.4, or be buffered to a pH of 6.4 to reduce the discomfort associated with intratympanic injection. One method of preparing the buffered solution is as follows1: 1.5 mL of gentamicin solution (40 mg/mL) is injected into a sterile 5-mL vial. A 0.6 M sodium bicarbonate solution is prepared by combining 2 mL of 8.4% sodium bicarbonate and 1.36 mL of sterile water in a 5-mL sterile vial. Add 0.5 mL of the 0.6 M sodium bicarbonate solution to the sterile vial containing 1.5 mL of gentamicin to form 2 mL of a solution of gentamicin (30 mg/mL, pH 6.4) ready for injection. Injection Technique The patient should be comfortably positioned in the standard otologic position for examination under the operating microscope, supine with the head turned away from the ear to be treated. In this position, the eustachian tube will be uppermost to avoid dependent drainage of the gentamicin solution out of the middle ear. This position is maintained for 30 minutes following the injection, and the patient is instructed not to swallow or clear the middle ear during this period; providing a cup for gentle expectoration during this period helps accomplish this goal. Topical application of phenol to a small injection site on the surface of the tympanic membrane provides anesthesia, and the gentamicin is injected in the middle ear using a tuberculin syringe and a 27- or 25-gauge spinal needle. Typically, about 0.5 mL of solution fills the middle ear. The residual gentamicin is aspirated from the middle ear after 30 minutes of contact with the round window. Administration Protocols Numerous administration protocols have been described. Nedzelski and colleagues22 had patients administer gentamicin intratympanically three times a day via a tympanostomy tube and a small flexible tubing for 4 days. The protocol introduced by Beck and Schmidt29 advocates a once daily regimen until the earliest sign of ototoxicity is observed. With this schedule, 1 to 12 doses are given, with a mean of 4 to 6 doses. A number of other investigators use a dosing regimen that titrates the administration of ITAG using patient response measured by caloric response, audiometric function, and patient symptoms. The rationale is to reduce the risk of hearing loss while maintaining control of vertigo by giving less medication per dose and extending the time of treatment with repeated applications as necessary. A second intratympanic injection of approximately 0.5 mL of gentamicin, 30 mg/mL, pH 6.4, is given 3 weeks after the first if vertigo is not controlled or recurs. However, based on the far lower rate of profound hearing loss seen with the protocol developed by Minor (3% compared with 10%), it is anticipated that scheduled repeated injections will become less common. Selective chemical vestibulectomy had also been used as an alternative to vestibular nerve section for refractory

cases of unilateral Ménière’s disease.22 A tuberculin syringe is used to introduce 2.5 to 25 μg of streptomycin in solution (25 μg/mL) through a fenestration in the horizontal semicircular canal. Shea and Norris30 have reported complete elimination of caloric response and complete relief of vertigo in 166 Ménière’s disease patients undergoing streptomycin perfusion of the inner ear, with preservation or improvement of hearing in 75% of patients. However, a multi-institution trial of this technique reported hearing loss in 68% of 47 patients undergoing labyrinthotomy with streptomycin infusion.31 Parenteral streptomycin has been used successfully to manage cases of refractory bilateral Ménière’s disease. Therapy is titrated to preserve some vestibular function. This method has helped to avoid post-treatment disequilibrium and oscillopsia associated with complete bilateral vestibular ablation. Total streptomycin dose varies from 5 to 70 g in patients undergoing titration therapy, with a mean dose of approximately 25 g administered to achieve the desired endpoint. Langman and associates32 improved or completely relieved episodic vertigo in 16 of 19 patients (84%) undergoing titration therapy for bilateral Ménière’s disease. Persistent severe post-treatment disequilibrium occurred in three patients (16%), and changes in hearing were independent of the effect of streptomycin. Intratympanic Dexamethasone An emerging management technique for recalcitrant Ménière’s disease is the intratympanic injection of dexamethasone. The technical aspects are identical to those described in the ITAG section. The senior author injects dexamethasone (24 mg/mL) and allows the patient to remain supine with the affected ear uppermost for 20 to 30 minutes. The procedure is performed three times, 1 week apart. Other authors have used single-dose applications via an exploratory tympanotomy followed by application, in the round window niche, of dexamethasone 8 mg, in hyaluronic on an absorbable gelatin sponge. A retrospective study of the latter approach in 21 ears of 19 patients was reported by Arriaga and Goldman.33 They found that a single application of dexamethasone/hyaluronan solution did not produce dramatic short-term hearing improvement in patients with endolymphatic hydrops; however, improvements of as much as a 38-dB gain in pure tone acuity (PTA) and 38% gain in the speech discrimination score were reported. This single patient’s gain was tempered by three ears that experienced deterioration after treatment. Conservative performance of intratympanic dexamethasone is appropriate; however, some patients failing medical therapy may benefit from this technique prior to a more aggressive surgical option. Long-term controlled clinical trials remain to be completed that will determine the efficacy of this treatment modality.

Otosyphilis A presumptive diagnosis of otosyphilis is made in the patient with unexplained cochleovestibular dysfunction and positive fluorescent treponemal antibody absorption (FTA-ABS). Penicillin and steroids have been the primary treatment modalities. Although previous studies have

Pharmacotherapy for Vestibular Dysfunction

shown benefit of IM penicillin therapy,34 other studies have demonstrated that the IM route of parenteral therapy fails to achieve treponemicidal levels in cerebrospinal (CSF) fluid. For IM therapy, treatment with 2.4 million units of benzathine penicillin weekly for 3 successive weeks constitutes minimal therapy. Other authors advocate extending therapy for as long as 1 year. New outpatient treatment regimens that include probenicid promise to achieve antitreponemal drug levels in the CSF. Probenecid increases the half-life and facilitates CSF penetration of penicillin derivative antibiotics. These regimens include 1.8 million units of IM procaine penicillin G daily or 1 g oral amoxicillin six times daily, in combination with probenecid 500 mg four times daily. For patients receiving IV therapy, 10 million units of penicillin G per day is administered in divided doses for 10 days, followed by 2.4 million units of IM benzathine penicillin per week for 2 additional weeks. Patients with neurosyphilis, documented by a positive CSF VDRL, 24 million units of penicillin G per day is administered IV for 14 days, followed by a 2-week course of benzathine penicillin and an 8-week course of high-dose oral amoxicillin. Patients with documented penicillin allergy receive 500 mg of tetracycline or erythromycin qid for 30 days. Alternatively, doxycycline (200 mg/day for 15 to 20 days) may improve patient compliance as it is dosed twice a day and may be taken with food. Many studies demonstrate enhanced efficacy when penicillin is combined with steroid therapy. Although dose recommendations vary, prednisone 40 to 60 mg/day for 2 weeks is accepted as minimal therapy. Therapy is continued for 4 weeks in patients who respond and is subsequently tapered according to patient symptomatology. Patients receiving prolonged therapy should be placed on an alternate-day regimen to minimize adrenal suppression. Absolute and relative contraindications to steroid therapy include hypersensitivity to corticosteroids, severe osteoporosis, brittle diabetes mellitus, peptic ulcer disease, diverticulitis, hypothyroidism, cirrhosis, thromboembolic disorders, and psychiatric illness. Since glucocorticoid therapy can reactivate tuberculosis, chemoprophylaxis should be used for patients with a history of active tuberculosis. Seventy-five percent of patients undergoing antibiotic therapy for secondary syphilis will experience an acute, febrile reaction known as the Jarisch-Herxheimer reaction. The reaction typically begins within 4 hours after treatment begins and is manifest by fever and flulike symptoms. This reaction is probably related to release of endotoxin from killed spirochetes or an allergic reaction to treponemal breakdown products. Symptoms typically subside within 24 hours after instituting therapy and seldom require interruption of therapy. However, patients should be informed of this syndrome, as some will experience a transient exacerbation of cochleovestibular symptoms. Administration of prednisone for 24 hours prior to the initiation of antibiotic therapy reduces the febrile component of this reaction.35 Penicillin and steroid therapy has been reported to improve vertigo in 58% to 86% of patients with symptoms secondary to otosyphilis. This compares favorably with patients with hearing loss, of which only 31% improve

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with treatment.36 Patients with disabling tinnitus or vertigo should undergo such therapy regardless of the duration of symptoms because the likelihood of improvement is reasonably high. However, patients with isolated, long-standing hearing loss without fluctuation are less likely to respond to therapy.37

Vestibular Migraine Since the appearance of the first edition, much has been learned about vestibular migraine. Likewise, the frequency of occurrence of this disorder in both adults and children has been recognized to a much greater degree. It is a remarkably common disorder and no doubt represents many of the atypical Ménière’s disease patients described in the past. Migraine has long been considered a vascular disorder, with vasodilation responsible for the headache and vasoconstriction responsible for the neurologic symptoms. Basilar artery migraine produces symptoms related to those areas of the CNS supplied by the posterior circulation.38 However, serotonergic and central vestibular pathways may also be involved in migraine-associated vertigo and vertiginous auras.8 Approximately 30% to 40% of patients with classic migraine experience true vertigo. Other patients can present with vertigo without concomitant headache, referred to as a migraine equivalent.39,40 This disease also occurs in children; unfortunately, the misnomer benign positional vertigo of childhood has been assigned by the neurology community.41 Prophylactic therapy is indicated for those patients whose lives are being negatively affected by the recurrent vertigo associated with vestibular migraine, as all successful regimens have potentially troublesome side effects. The most common indication for prophylaxis is frequent migraine, with symptoms occurring more frequently than two episodes per month for 3 successive months. Interestingly, adults with vestibular migraine more often respond to tricyclic antidepressants or calcium channel blockers than to beta blockers. Conversely, children with vestibular migraine respond to beta blockers extremely well. Empiric therapy with the most commonly used agent may need to be followed with a change in class of medication until symptoms are controlled. Once symptoms are controlled with prophylactic therapy for 6 months, patients are weaned from their medication. If this is tolerated, then retreatment is necessary only if symptoms recur. Sometimes it is necessary to resume treatment with the prophylactic agent for another 3 to 6 months before attempting to wean the medication. Rarely, ongoing therapy is necessary, and this decision is guided by the patients’ clinical features. Very often, children with vestibular migraine stop having this disorder as they approach puberty. Dietary counseling is important, as tyramine- and caffeine-containing foods such as blue cheese, red wine, grape juice, chocolate, and tomatoes may serve as triggers for the migraine attacks. Likewise, excessive caffeinated-beverage consumption, fatigue, stress, and skipping meals may induce vestibular migraine attacks in some patients. Tricyclic antidepressants may be useful adjunct for prophylaxis of migraine associated with panic attacks. For years, the tertiary amine antidepressants such as amitriptyline and imipramine have been used. Though effective, such

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medications have adverse anticholinergic side effects such as constipation, tachycardia, blurred vision, cognitive impairment, and orthostatic hypotension.19 These side effects can be detrimental, especially in the elderly population. As individuals age, physiologic changes influence pharmacotherapeutics. The specific changes involve water volume, cardiac output, circulatory blood flow, bareoreceptor activity, gastric pH, intestinal absorption, hepatic blood flow and function, hepatic enzymatic functions, kidney efficiency, renal blood flow and general function, and visual acuity.42 New forms of tricyclics called secondary amines (e.g., desipramine or nortriptyline) have decreased side effects and are effective in the treatment of migraines. For this reason, the secondary amines are the tricyclics of choice. Beta blockers, calcium antagonists, anticonvulsants, and tricyclic antidepressants are currently the most widely used agents for prophylaxis of migraine.43 Propranolol is normally used in a high-dose range (80 to 240 mg/day) and can produce significant side effects, including fatigue, bronchospasm, congestive heart failure, and male impotence.44 Calcium antagonists such as flunarizine (10-mg dose at night) or verapamil (240 to 320 mg/day) have been beneficial. However, side effects include sedation, weight gain, depression, and extrapyramidal disorders.45,46 When choosing a calcium channel blocker to treat vestibular migraine in adults, the authors usually begin treatment with verapamil (Verelan PM) 100 mg each night. This medication is a sustained release formulation, and the dose is increased after 3 to 4 weeks if the symptoms have not been controlled. Recent studies also identify valproic acid (Depakene) and divalproex sodium (Depakote) as medications for the prophylactic treatment of migraines. The recommended starting dose is 250 mg bid, though some patients may need to titrate to 1000 mg/day. Please note— anticonvulsants are contraindicated in individuals with liver function impairments. Although infrequently used in vestibular migraine, ergotamine tartrate has been the drug of choice for aborting migraine symptoms for many years. It is a vasoconstrictive agent that stimulates α-adrenoceptors and acts as a serotonin antagonist. It also inhibits free uptake of monoamines and sensitizes vascular smooth muscle to sympathetic stimulation. This agent is contraindicated in patients with sepsis or local infection, liver disease, and vascular disease. It should be used with caution in patients with hypertension or peptic ulcer disease. Usual dosage is 2 mg PO or as a rectal suppository, followed by additional 1-mg doses every half hour for two or three additional doses if necessary. Frequent use of ergotamine can lead to rebound headaches.47 Although sumatriptan (Imitrex) should not be used to treat vestibular migraine, it is a common parenterally administered vasoconstrictor that is an effective form of abortive treatment for nonbasilar artery migraine. It is a selective agonist for 5-hydroxytryptamine, a receptor found on the basilar artery and in the vasculature of the dura mater. It is administered as a 6-mg SQ injection and relieves the headache associated with migraine within an hour in 70% of subjects. This agent should be used with caution in patients with hypertension, and it is contraindicated in patients with ischemic heart disease, as

it may induce coronary vasospasm. Currently, sumatriptan is not recommended for patients with basilar migraine.

Vertebrobasilar Insufficiency Approximately one-third of transient ischemic attacks (TIAs) involve the territories of the vertebrobasilar system. These patients often manifest short-lived symptoms such as vertigo, diplopia, dysarthria, bilateral limb weakness, gait ataxia, variable and often bilateral sensory disturbance, and memory loss.48 Antiplatelet therapy has been demonstrated to effectively reduce the incidence of stroke after TIA. This effect has been most clearly established for aspirin, which can reduce by half the risk for stroke after TIA. Although most previous studies have used doses of 1200 mg daily, it is likely that 325 mg/day is equally effective.49,50 Ticlopidine (Ticlid) is another platelet aggregate inhibitor shown to lower the risk for stroke after TIA, particularly for cases of vertebrobasilar insufficiency. This agent may be more effective than aspirin, reducing the risk for stroke by 48% compared with aspirin during the first year after TIA. However, this agent is associated with a risk of neutropenia, which may be life-threatening, and therefore it should be reserved for patients who are intolerant to aspirin therapy. All patients on ticlopidine therapy should have complete blood count (CBC) and white cell differential determination made at least once every 2 weeks through the first 3 months of therapy. Neutropenia reverses within 1 to 3 weeks after discontinuing treatment. The efficacy of other compounds remains unproven. Dipyridamole (Persantine) and sulfinpyrazone (Anturane) confer no added benefit to aspirin therapy and are no longer recommended.50 Pentoxyifylline (Trental) is a xanthine derivative that decreases blood viscosity and enhances microcirculation. This agent has been shown to enhance tissue oxygen levels in patients with peripheral vascular disease, and it may be useful for cases of vertebrobasilar insufficiency. Full anticoagulation is typically reserved for patients with impending or evolving stroke. Occasionally, anticoagulants are used for tight stenosis of intracranial arteries, particularly if TIAs persist despite antiplatelet therapy.50 Therapy is commenced with continuous IV infusion of heparin to maintain a partial thromboplastin time that is 1.5 to 2.5 times normal. Subsequently, warfarin is added, and heparin is discontinued when the prothrombin time is elevated to 1.5 to 2.5 times normal. Over 150 drugs have been reported to speed recovery after a stroke, but none has been proven to be effective by a careful clinical study. Glucocorticoids have been used extensively to limit cerebral edema, which may render viable brain that is sensitive to further ischemic damage. However, clinical studies indicate that steroids are ineffective after ischemic infarction. Other commonly employed interventions, including osmotic and loop diuretics and hyperventilation, have not been subject to adequate clinical trial to confirm efficacy.51 Several compounds are currently being investigated and may prove beneficial for recovery after acute stroke. Such agents include gangliosides, free-radical scavengers, 21aminosteroids, and amphetamine.51 Preliminary studies show that dihydroergocristine, an ergot alkaloid with

Pharmacotherapy for Vestibular Dysfunction

potent dopaminergic activity, may reduce hypoxia-induced cerebral metabolic changes.52 The calcium channel antagonist flunarizine has been shown to protect brain tissue against neuronal damage in several models of cerebral ischemia.53 The ultimate utility of these agents in stroke patients awaits further clinical investigation.

Familial Ataxia Syndrome Familial ataxia syndrome is a rare, autosomal-dominant disorder that manifests by recurrent episodes of vertigo and ataxia in several members of a family. Other prominent symptoms can include diplopia, dysarthria, tinnitus, and paraesthesia, but symptoms can vary considerably between families. Familial ataxia syndrome is one of the most treatable causes of chronic episodic vertigo. Acetazolamide, a carbonic anhydrase inhibitor diuretic, effectively prevents the episodic vertigo and ataxia. The mechanism of this action remains unclear. Systemic acetazolamide produces CNS acidosis by reducing serum lactate and pyruvate, but serum levels of lactate and pyruvate are normal in patients with this syndrome. The antihistamine dimenhydrinate, the benzodiazepine alprazolam, and the calcium antagonist flunarizine have been shown to be effective for treating symptomatic vertigo associated with the familial ataxia syndrome.54,55 Recently, mutations in the calcium channel gene CACNA1A have been demonstrated in patients suffering from episodic ataxia type 2.39 This subtype of familial ataxia syndrome is characterized by episodic vertigo and ataxia. In contrast, mutations in CACNA1A have not been observed in families with migraine headaches and episodic vertigo.56

Psychophysiologic Dizziness Dizziness is associated with a wide range of psychiatric illnesses. Patients with anxiety disorders manifested by panic attacks are particularly susceptible to experience disequilibrium, often described as a feeling of imbalance or even a sensation of spinning inside the head. At present, the term psychiatric dizziness should be restricted to dizziness (1) that is a component of a recognized psychiatric syndrome and (2) that cannot be explained by clinical evidence of vestibular dysfunction.4 Psychiatric disorders associated with frequent complaints of dizziness include psychosis, abasia, depression, hysteria, panic disorder with agoraphobia, acrophobia, phobic postural vertigo, lightheadedness secondary to hyperventilation during panic, and the obsessive personality disorder. Patients with schizophrenia are more susceptible to motion sickness and show an increased incidence of abnormalities on vestibular testing. Certain compounds, including lactate, caffeine, isoproterenol, yohimbine, and benzodiazepine antagonists, have been shown to elicit panic attacks in susceptible individuals. This evidence suggest a possible organic basis for the disequilibrium associated with psychophysiologic dizziness that would be amenable to specific pharmacotherapy.55 Treatment of psychophysiologic dizziness relies on patient reassurance, psychotherapy, and pharmacotherapy. Three classes of compounds have been shown to be effective in reducing the frequency of panic attacks.

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These agents include the benzodiazepines, tricyclic antidepressants, and monoamine oxidase inhibitors. Though clinically all are effective, the side effects must be taken into consideration.3,16 Benzodiazepines can have rebound symptoms following medication cessation. In addition, anxiety disorders are highly comorbid with depressive disorders and in fact can be exacerbated by benzodiazepines. Addictive tendencies also must be taken into consideration. Tricyclic antidepressants have high anticholinergic side effects. Safety becomes an issue in patient populations with coronary artery disease or cardiac dysrhythmias. Monoamine oxidase inhibitors have multiple food and drug interactions. In fact, they are contraindicated in populations with heart failure, pheochromocytoma, hypertension, liver disease, cardiovascular disease, seizure disorders, diabetes, and suicidal tendencies.13,19 Nevertheless, when used appropriately, these drugs can be highly effective. Because of the numerous side effects of the previously stated compounds, a fourth class of drugs is presently under investigation. These include the selective serotonin reuptake inhibitors (SSRIs) such as Prozac, Zoloft, Paxil, Luvox, and Celexa. Side effects such as agitation, headache, gastrointestinal upset, insomnia, and sexual dysfunction may occur. Formal analysis is pending at this time although the preliminary data look promising.13

Future Perspectives The pharmacotherapy of vertigo caused by other common causes of vestibular dysfunction currently relies on nonspecific suppression of symptoms. This is often the case because the underlying pathophysiology of many vestibular syndromes remains poorly understood. Current techniques of molecular biology promise to expand our understanding of both the physiology and pathophysiology of the human vestibular system. This knowledge may lead to the development of future forms of specific pharmacotherapy. For instance, cell and molecular biologic techniques such as immunohistochemistry, in situ hybridization histochemistry, and immunoelectron microscopy have been used to identify neurotransmitters and receptors involved in modulation of primary afferent pathways in the vestibular neuroepithelium.7 These types of studies could lead to the development of pharmacotherapy aimed specifically at the vestibular end-organ. Vestibular neuronitis (neuritis) is an idiopathic form of acute unilateral vestibular paresis that is the third most common cause of vertigo. Current management relies on nonspecific treatment employing vestibular sedatives, physical therapy, and vestibular exercises.55 The epidemic occurrence of this condition, frequently following upper respiratory tract infections, suggests that viral infection of the vestibular nerve may explain the underlying pathophysiology of vestibular neuronitis. Polymerase chain reaction amplification of nucleic acids from archival human celloidin-embedded temporal bone sections57 would provide an extremely sensitive tool to search for specific viral agents in patients with a history of vestibular neuronitis. This technique has recently been employed successfully to localize varicella-zoster genomic DNA in temporal bone sections from patients with Ramsay Hunt syndrome, a

668

PERIPHERAL AUDIOVESTIBULAR DISORDERS

polycranial viral neuropathy with clinical involvement of the vestibular nerve in some of the cases.58,59 Histopathologically, degenerative changes in the vestibular nerve, Scarpa’s ganglion, vestibular neuroepithelium, and decreased synaptic density within the ipsilateral vestibular nuclei are consistent findings.60,61 Epidemiologic and serologic data suggest a viral cause.62,63 The latent virus (e.g., herpes simplex virus) is thought to remain dormant within the vestibular primary afferent neurons (Scarpa’s ganglion). Identification of viral genomic DNA in the temporal bone of patients with vestibular neuronitis may lead to the development of new forms of such specific antiviral therapy. A few small studies appear to demonstrate benefit of high-dose, IV acyclovir (Zovirax), which acts as a substrate for virus-specific thymidine kinase during DNA synthesis, in patients with Ramsay Hunt syndrome.64,65 In addition, the new so-called pro-drugs such as valacyclovir (Valtrex) and famciclovir (Famvir) are available and have the advantage of achieving adequate therapeutic tissue levels via an oral route. Some of the herpes viruses (e.g., varicella-zoster virus) require an IV route for acyclovir to reach tissue levels necessary to treat these infections. Likewise, the use of oral steroids would be appropriate in combination with an antiviral medication. Gene transfer therapy is presently being developed for the treatment of peripheral hearing and balance disorders. One strategy, termed in vivo gene therapy, employs defective viral vectors to introduce a functional gene to replace a damaged gene within the inner ear. Several groups have successfully developed and introduced nonreplicating viral vectors and other vehicles into ganglion cells in vitro or directly into the cochlea in vivo.66 These methods will add an important weapon to our surgical armamentarium after more mechanisms of vestibular and auditory dysfunction are characterized at the molecular level.

SYMPTOMATIC PHARMACOTHERAPY The commonly used antivertiginous medications and their doses are listed in Table 42-5. The effectiveness of each drug has been determined empirically; however, it is difficult to predict which drug or combination of drugs will be most effective, since a patient may respond to one drug but not to others in the same class. Antivertigo drugs are typically classified by their chemical structure (e.g., diazepam is a benzodiazepine), behavioral properties (e.g., diazepam has sedative and anxiolytic properties), or mechanisms of action (e.g., benzodiazepines enhance inhibition via GABAA receptor-gated chloride channels; see Table 42-5). As a group, current antivertigo medications have multiple mechanisms of action, which include potentially efficacious actions that range from antagonism of muscarinic cholinergic, histiminergic, and monoaminergic transmission to calmodulin inhibition and blockade of voltage-gated calcium channels (see Table 42-5). It is also important to note that the direct effects of these drugs may also affect central neurotransmitter levels, which have the potential to affect vestibular pathways. For example, promethazine reduces dopamine turnover and increases noradrenaline turnover, dimenhydrinate reduces dopamine turnover, and meclizine has little effect on monoamine metabolism.67

Furthermore, although flunarizine was characterized initially as nonspecific Ca2+ channel and Na+ channel blocker,68 more recent studies indicate that acute doses increase69,70 and chronic treatment decreases extracellular striatal dopamine and metabolites70 and that flunarizine administration inhibits dopamine uptake.71 Although ample evidence supports the contention that monoaminergic, histaminergic, muscarinic cholinergic, and GABAergic mechanisms are present within the vestibular nuclei (for review see Smith and Darlington72), there is inadequate evidence to associate the efficacy of these medications with any specific central or peripheral sites. Four general classes of drugs are useful for treating vertigo and the associated autonomic symptoms of nausea and vomiting.16 The classes include anticholinergic agents, monoaminergic agents, antihistaminic agents, and antidopaminergic agents. Miscellaneous agents that are also effective include the benzodiazepine diazepam (Valium), the calcium antagonist flunarizine, and the histaminic agent betahistine. Recent evidence has also favored the use of SSRIs and clonazepam,13 which are also particularly useful in minimizing the associated symptoms of anxiety and panic. Carvedilol, a beta blocker that has found clinical applications for treatment of hypertension, is currently being investigated as an agent for the symptomatic relief of vertigo.73

Mechanism of Action Numerous animal studies have documented that drugs with anticholinergic and monoaminergic activity diminish the excitability of neurons in the vestibular nucleus.74,75 Anticholinergic drugs suppress both the spontaneous firing rate and the response to vestibular nerve stimulation.76–78 Iontophoretically applied acetylcholine, methacholine, and carbamylcholine excite neurons in the medial and lateral vestibular nuclei; this excitation is blocked with atropine.79 These observations suggest a cholinergic innervation on secondary vestibular neurons. In addition, cholinergic neurons in the nearby reticular formation project to the vestibular nuclei. However, since muscarinic cholinergic mechanisms are distributed widely in the brain, actions at other levels of central vestibular pathways are also likely. Drugs with significant antihistaminergic activity have long been used in treating vertigo and preventing motion sickness, yet little is known about their mechanism of action. More recent evidence (see Table 42-5) further indicates that standard antihistaminergic antivertigo medications have significant antimuscarinic cholinergic activity in addition to antagonism of histamine H1 receptors. Since histamine excites neurons in the vestibular nuclei,80 it is expected that the combination of antihistaminergic and antimuscarinic actions of these drugs will depress activity in the vestibular nuclei. Since appreciable histaminergic innervation is also present in brainstem autonomic regions and the parabrachial nucleus, the antimotion sickness efficacy of these drugs may reflect actions at multiple levels in vestibuloautonomic pathways. Antagonism of dopamine D2 receptors, serotonin 5-HT2 receptors, and α1-adrenoreceptors are common features of antivertigo drugs with significant antiemetic actions. These drugs include the phenothiazines prochloroperazine

Pharmacotherapy for Vestibular Dysfunction

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TABLE 42-5. Drugs Used for the Symptomatic Treatment of Patients with Vestibular Dysfunction

Sedation

Antiemetic Actions

Dryness of Mucus Membranes

Extrapyramidal Symptoms

Class

Drug

Dosage

Anticholinergic

Scopolamine

+

+

+++

–

Monoaminergic

Atropine Amphetamine Ephedrine

0.6 mg orally q4–6h or 0.5 mg transdermally q3days (commercial production suspended) 0.4 mg orally or intramuscularly q4–6h 5 or 10 mg orally q4–6h 25 mg orally q4–6h 1% nasal spray 25 mg orally q4–6h

– – – – +

+ + + + +

+++ + + ++ +

– + – – –

50 mg orally or intramuscularly q4–6h or 100 mg suppository q8–12h 50 mg orally or intramuscularly q4–6h or 100 mg suppository q8h 25 or 50 mg orally, intramuscularly, or as a suppository q4–6h 5 or 10 mg orally or intramuscularly q6h or 25 mg suppository q12h 25 mg orally or intramuscularly q6h

+

+

++

–

+

+

+

–

++

+

++

–

+

+++

+

++

+++

++

+

+++

+, or +++ at high doses +

+

–

–

+

–

–

Antihistamine

Phenothiazine

Benzodiazepine

Butyrophenone

Ca2+ channel antagonist Beta-blocking agent Histaminic

Meclizine (Antivert) Cyclizine (Marezine) Dimenhydrinate (Dramamine) Promethazine (Phenergan) Prochlorperazine (Compazine) Chlorpromazine (Thorazine) Diazepam (Valium)

2, 5, or 10 mg orally, intramuscularly, or intravenously q4–6h

Clorazepam (Klonopin) Lorazepam (Ativan) Haloperidol (Haldol) Droperidol (Inapsine) Flunarizine (Sibelium) Carvedilol

0.25 or 0.5 mg orally q8h 0.5, 1 or 2 mg orally q8h PRN

++

+

–

–

1 or 2 mg orally or intramuscularly q8–12h 2.5 or 5 mg intramuscularly q12h

+++

++

+

++

+++

++

+

++

10 mg/day orally

–

+

–

++

Titrated (investigational)

–

–

–

–

Betahistine

8 mg orally q 8h

+

+

–

–

(Compazine) and chlorpromazine (Thorazine) and the butyrophenones haloperidol (Haldol) and droperidol (Inapsine). The antiemetic actions are presumed to be due to effects at sites other than the vestibular nuclei. However, several potential direct actions are possible on vestibular pathways. Since these drugs have antihistaminergic (H1) activity, they are expected to share actions with the antihistaminergic antivertigo drugs. Chlorpromazine also has antimuscarinic activity and has been shown to depress the responsiveness of vestibular nucleus neurons. The possible actions of these drugs on noradrenergic and serotonergic transmission in the vestibular nuclei are more complex. For example, norepinephrine has been reported to increase and decrease the background activity of vestibular nucleus neurons, presumably via both α1- and α2-adrenoceptors.81 Since serotonin also has excitatory, inhibitory, and biphasic effects on different vestibular nucleus neurons, the precise mechanisms of action are unknown. However, the emergence of symptoms of a balance disorder after abrupt discontinuation of an SSRI (SSRI discontinuation syndrome)8 indicates that serotoninergic mechanisms are perhaps a critical component of central vestibular neurochemistry. Clinically, it is important to note that extrapyramidal side effects of these medications result from their affinity for dopamine receptors.

Several tranquilizers are effective in suppressing vertigo. Diazepam (Valium) decreases the resting activity of vestibular nuclei neurons, possibly by decreasing another reticular facilitative system. It also affects crossed vestibular and cerebellovestibular inhibitory transmission and it decreases the production of CSF centrally.77,78,82,83

Strategy in the Treatment of Vertigo The choice of drug or drug combination is based on the known effects of each drug (see Table 42-5) and on the severity and time course of symptoms. Prolonged severe vertigo is an extremely distressing symptom. The patient prefers to lie still with eyes closed in a quiet, dark room. In this setting sedation is desirable, and the tranquilizing medications listed in Table 42-4 are most effective. Each of these drugs has significant side effects, however, and therefore must be used with caution. Parenteral diazepam, for example, can cause respiratory depression and hypotension and should be used only in a hospital, where emergency resuscitation equipment is available. If nausea and vomiting are severe, the antiemetic prochlorperazine can be combined with the antivertiginous medication. The patient with chronic recurrent vertigo usually attempts to carry on normal activity, and therefore sedation

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PERIPHERAL AUDIOVESTIBULAR DISORDERS

is undesirable. Antihistaminic, monoaminergic, and anticholinergic medications are useful. Of the antihistamines, promethazine (Phenergan) has the most sedating effect and is therefore useful only when moderate sedation is desired. A combination of promethazine and the sympathomimetic ephedrine (25 mg of each) produces less sedation than promethazine alone and is more effective in relieving associated autonomic symptoms.16,19 Meclizine (Antivert), cyclizine (Marezine), dimenhydrinate (Dramamine), and scopolamine can be effective in treating mild episodes of vertigo. Central compensation for peripheral vestibular dysfunction appears to involve changes in contributions of the intact labyrinth, use of alternative gravitoinertial sensory cues (vision, proprioceptive, somatosensory, and cardiovascular), and adoption of different strategies for performing movements. Since this process is a form of motor learning, it is essential that the patient return to normal activity to recalibrate central vestibular pathways. Viewed from this perspective, the combined sedative and antivertigo properties of medications for symptomatic relief require a therapeutic trade-off of acute relief at the expense of attenuating compensation. On the other hand, sympathomimetics and vestibular rehabilitation therapy can be added to facilitate the compensatory process. Symptomatic management of positional vertigo is difficult because, although the vertigo is severe, it is short-lived. To completely suppress these brief episodes, heavy sedation throughout the day would be required, which is usually unacceptable to the patient. The most common variety, benign paroxysmal positional vertigo, has a short duration (usually 30 seconds or less); however, some patients will complain of vestibular dysfunction lasting for much longer intervals. This initial patient response can be extremely misleading, unless the otolaryngologist aggressively attempts to separate the episode of true vertigo from the autonomic dysfunction that follows. The severity of the autonomic dysfunction varies on any individual and may be severe with disabling imbalance and unsteadiness combined with nausea and diaphoresis. Other patients will experience mild true vertigo with movement in the plane of the involved semicircular canal. Very often the patient will identify the plane of rotation that elicits the vertigo and assiduously avoid this movement. Spontaneous remission occurs in more that 90% of patients within 6 months, although a small percentage do have recurrence.84 A simple explanation of the nature of the disorder and its favorable prognosis helps to relieve the patient’s anxiety. Medications with mild sedative effects (e.g., diazepam, meclizine, or cyclizine) are useful when the episodes recur frequently and to decrease the autonomic dysfunction that commonly impairs the patient’s quality of life. Particle repositioning maneuvers and vestibular rehabilitation therapy are extremely effective in the treatment of benign positional vertigo. In rare cases of intractable benign positional vertigo, transection of the posterior ampullary nerve or plugging of the posterior semicircular canal has resulted in prompt remission of symptoms.1

Prophylaxis of Motion Sickness Generally the antivertiginous medications listed in Table 42-5 are also effective in treating and preventing motion

sickness. The principal symptoms of motion sickness are malaise and nausea rather than vertigo, which may be considered as visceral referred symptoms of somatic origin.2 Tolerance develops after 2 or 3 days of constant stimulation, and prophylactic use of drugs several hours before travel is more effective than treatment of symptoms.16,85 Oral or parenteral scopolamine was one of the first drugs used to treat motion sickness and was the first drug proved effective in its prevention. In the 1940s controlled drug trials were carried out on military recruits during amphibious training, aviation training, and swing tests. A dose of 0.6 to 0.8 mg of scopolamine protected 50% of susceptible subjects for at least 8 hours. However, untoward effects (primarily drowsiness, dryness of the mouth, and blurred vision) limited the use of oral or parenteral scopolamine for motion sickness.19,42 With the introduction and subsequent general use of antihistamines, particularly dimenhydrinate, scopolamine was neglected for many years. Interest in scopolamine was rekindled, in the form of transdermal scopolamine (Transderm-Scop). With this delivery system, scopolamine is gradually released through a microporous polypropylene membrane contained in a patch that is placed on the skin behind the ear. A small dose (0.05 mg) is slowly released and absorbed over a 3-day period. Initial clinical trials indicate that transdermal scopolamine is effective in preventing motion sickness with minimal side effects, the main side effect being dryness of the mouth.86,87 The use of transdermal scopolamine for more than 3 consecutive days can, on discontinuation of therapy, result in withdrawal symptoms that mimic motion sickness, including dizziness, nausea, vomiting, and headache.88,89 To be effective the patch must be in place several hours before exposure to motion; however, production of this product has been suspended. Future studies will determine whether other antivertiginous drugs can be effectively administered in this manner. Clinical trials of antimotion sickness drugs under controlled laboratory conditions have shown that combinations of drugs are often more effective than any single drug.16,19,42 Particularly effective combinations have included scopolamine (0.6 mg), promethazine (25 mg) and dextroamphetamine (10 mg), and promethazine (25 mg) and ephedrine (25 mg). As in the treatment of vertigo, it is difficult to predict which drug or drugs will be most effective in preventing motion sickness in an individual. In controlled laboratory experiments the responses of normal volunteers to the same drug or combination of drugs often vary greatly, even when identical motion stimuli are used.

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30. Shea JJ, Norris CH: Streptomycin perfusion of the labyrinth. Acta Otolaryngol (Stockh) (Suppl) 485:123–130, 1991. 31. Monsell EM, Shelton C, Anthony PF, et al: Labyrinthotomy with streptomycin infusion—Early results of a multicenter study. Am J Otology 13:416–422, 1992. 32. Langman AW, Kemink JL, Graham MD: Titration streptomycin therapy for bilateral Meniere’s disease: Follow-up report. Ann Otol Rhinol Laryngol 99:923–926, 1990. 33. Arriaga MA, Goldman S: Hearing results of intratympanic steroid treatment of endolymphatic hydrops. Laryngoscope 108:1682–1685, 1998. 34. Zoller M, Wilson WR, Nadol JB: Treatment of syphilitic hearing loss. Ann Otol Rhinol Laryngol 88:160–165, 1979. 35. Darmstadt GL, Harris JP: Leutic hearing loss: Clinical presentation, diagnosis, and treatment. Am J Otolaryngol 10:410–421, 1989. 36. Gleich LL, Linstrom CJ, Kimmelman CP: Otosyphilis: A diagnostic and therapeutic dilemma. Laryngoscope 102:1255–1259, 1992. 37. Smith ME, Canalis RF: Otologic manifestations of AIDS: The otosyphilis connection. Laryngoscope 99:365–372, 1989. 38. Olsson JE: Neurotologic findings in basilar migraine. Laryngoscope (Suppl) 52:1–41, 1991. 39. Baloh RW: Episodic vertigo: Central nervous system causes. Curr Opin Neurol 15(1):7–21, 2002. 40. Parker W: Migraine and the vestibular system in adults. Am J Otol 12:25–34, 1991. 41. Weisleder P, Fife TD: Dizziness and headache: a common association in children and adolescents. J Child Neurol 16(10):727–730, 2001. 42. Schwartz J: Clinical pharmacology. In Hazzard W, Bierman E, Blass J, et al (eds.): Principles of Geriatric Medicine and Gerontology, 3rd ed. New York, McGraw-Hill, 1994, pp 259–275. 43. Solomon D: Distinguishing and treating causes of central vertigo. Otolaryngol Clin North Am 33(3):579–601, 2000. 44. Freitag FG: The use of beta blockers in migraine. In Diamond S (ed.): Migraine Headache Prevention and Management. New York, Marcel Dekker, 1990, pp 57–93. 45. Olesen J: Calcium antagonist in migraine and vertigo: Possible mechanisms of action and review of clinical trials. Eur Neurol 30 (Suppl 2):31–34, 1990. 46. Schmidt R, Oestreich W: Flunarizine in migraine prophylaxis: The clinical experience. J Cardiovasc Pharmacol 18(Suppl 8):S21–S26, 1991. 47. Krunkel RS: Abortive treatment of migraine. In Diamond S (ed.): Migraine Headache Prevention and Management. New York, Marcel Dekker, 1990, pp 45–54. 48. Oas JG, Baloh RW: Vertigo and the anterior inferior cerebellar artery syndrome. Neurology 42:2274–2279, 1992. 49. Sivenius J, Riekkinen PJ, Smets P, et al: The European Stroke Prevention Study (ESPS): Results by arterial distribution. Ann Neurol 29:596–600, 1991. 50. Wade J: Transient ischemic attacks. Practitioner 233:1089–1092, 1989. 51. Goldstein LB, Davis JN: Restorative neurology: Drugs and recovery following stroke. Stroke 21:1636–1640, 1990. 52. Drago F, Valerio C, Nardo L, et al: Zerebrale wirkungen von dihydrocristin. Arzneimittelforschung 42(11A):1391–1394, 1992. 53. Pauwels PJ, Leysen JE, Janssen PA: Ca++ and Na+ channels involved in neuronal cell death: Protection by flunarizine. Life Sci 148: 1881–1893, 1991. 54. Baloh RW, Winder A: Acetazolamide-responsive vestibulocerebellar syndrome: Clinical and oculographic features. Neurology 41: 429–433, 1991. 55. Brandt T: Vertigo: Its Multisensory Syndromes. New York, Springer-Verlag, 1991. 56. Kim JS, Yue Q, Jen JC, et al: Familial migraine with vertigo: No mutations found in CACNA1A. Am J Med Genet 79(2):148–151, 1998. 57. Wackym PA, Simpson TA, Gantz BJ, Smith RJH: Polymerase chain reaction amplification of DNA from archival celloidin-embedded human temporal bone sections. Laryngoscope 103:583–588, 1993.

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58. Wackym PA: Molecular temporal bone pathology: II. Ramsay Hunt syndrome (herpes zoster oticus). Laryngoscope 107:1065–1075, 1997. 59. Wackym PA, Popper P, Kerner MM, Grody WW: Varicella-zoster DNA in temporal bones of patients with Ramsay Hunt syndrome. Lancet 342:1555, 1993. 60. Baloh RW, Lopez I, Ishiyama A, et al: Vestibular neuritis: Clinicalpathologic correlation. Otolaryngol Head Neck Surg 114:586–592, 1996. 61. Nadol JB Jr: Vestibular neuritis. Otolaryngol Head Neck Surg 112:162–172, 1995. 62. Sekitani T, Imate U, Noguchi T, Inokuma T: Vestibular neuronitis: Epidemiological survey by questionnaire in Japan. Acta Otolaryngol (Stockh) (Suppl) 503:9–12, 1993. 63. Shimizu T, Sekitani T, Hirata T, Hara H: Serum viral antibody titer in vestibular neuronitis. Acta Otolaryngol (Stockh) (Suppl) 503:74–78, 1993. 64. Inamura H, Aoyagi M, Tojima H, Koike Y: Effects of acyclovir in Ramsay Hunt syndrome. Acta Otolaryngol (Stockh) (Suppl) 446:111–113, 1988. 65. Uri N, Greenberg E, Meyer W, et al: Herpes zoster oticus: Treatment with acyclovir. Ann Otol Rhinol Laryngol 101:161–162, 1992. 66. Lalwani AK, Jero J, Mhatre AN: Current issues in cochlear gene transfer. Audiol Neurootol 7(3):146–151, 2002. 67. Oishi R, Shishido S, Yamori M, Saeki K: Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain. Naunyn-Schmiedebergs Arch Pharmacol 349:140–144, 1994. 68. Holmes B, Brogden RN, Heel RC, et al: Flunarizine: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs 27:6–44, 1984. 69. Fadda F, Gessa GL, Mosca E, Stephani E: Different effects of the calcium antagonists nimodipine and flunarizine on dopamine metabolism in the rat brain. J Neural Transm 75:195–200, 1989. 70. Reiriz J, Ambrosio S, Cobos A, et al: Dopaminergic function in rat brain after oral administration of calcium-channel blockers or haloperidol: A microdialysis study. J Neural Transm 95:195–207, 1994. 71. Devoto P, Pani L, Kuzmin A, DeMontis G: Inhibition of [3H] dopamine uptake by flunarizine. Eur J Pharmacol 203:67–69, 1991. 72. Smith PF, Darlington CL: Pharmacology of the vestibular system. Bailliere’s Clin Neurol 3:467–484, 1994. 73. McTavish D, Campoli-Richards D, Sorkin EM: Carvedilol: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy. Drugs 45:232–258, 1993.

74. Brown RD, Wood CD: Vestibular pharmacology. Trends Pharmacol Sci Feb:150–153, 1980. 75. Matsuoka I, Domino EF, Morimoto M: Adrenergic and cholinergic mechanism of single vestibular neurons in the cat. Adv Otorhinolaryngol 19:163–178, 1973. 76. Jaju BP, Wang SC: Effects of diphenhydramine and dimenhydrinate on vestibular neuronal activity of cat: A search for the locus of their antimotion sickness action. J Pharmacol Exp Ther 176:718–724, 1971. 77. Matsuoka I, Chikamori Y, Takaori S, et al: Effects of Chlorpromazine and diazepam on neuronal activities of the lateral vestibular nucleus in cats. Arch Otorhinolaryngol 209:89–95, 1975. 78. Ryu JH, McCabe BF: Effects of diazepam and dimenhydrinate on the resting activity of the vestibular neuron. Aerosp Med 45: 1177–1179, 1974. 79. Yamamoto C: Pharmacologic studies of norepinephrine, acetylcholine, and related compounds on neurons in Deiter’s nucleus and the cerebellum. J Pharmacol Exp Ther 156:36–47, 1967. 80. Wang JJ, Dutia MB: Effects of histamine and betahistine on rat medial vestibular nucleus neurones: Possible mechanisms of action of anti-histiminergic drugs in vertigo and motion sickness. Exp Brain Res 105:18–24, 1995. 81. Schuerger RJ, Balaban CD: Organization of the coeruleo-vestibular pathway in rats, rabbits and monkeys. Brain Res Reviews 30:189–217, 1999. 82. Bernstein P, McCabe BF, Ryu JH: The effect of diazepam on vestibular compensation. Laryngoscope 84:267–272, 1974. 83. Steiner FA, Felix D: Antagonistic effects of GABA and benzodiazepines on vestibular cerebellar neurons. Nature 260(5549): 346–347, 1976. 84. Baloh RW, Sakala S, Honrubia V: Benign paroxysmal positional nystagmus. Am J Otolaryngol 1:1–6, 1979. 85. Graybiel A, Wood CD, Knepton J, et al: Human assay of antimotion sickness drugs. Aviat Space Environ Med 46:1107–1118, 1975. 86. McCauley ME, Royal JW, Shaw JE, et al: Effect of transdermally administered scopolamine in preventing motion sickness. Aviat Space Environ Med 50:1108–1111, 1979. 87. Price N, Schmitt LG, Shaw JE: Transdermal delivery of scopolamine for prevention of motion induced nausea in rough seas. Clin Ther 2:258–262, 1979. 88. Meyboom RHB: More on Transderm-Scop patches. (Letter) N Engl J Med 311(21):1377–1378, 1984. 89. Saxena K, Saxena S: Scopolamine withdrawal syndrome. Postgrad Med 87:63–66, 1990.

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Outline The Contemporary Concept of Neurotologic Skull Base Surgery Fundamental Considerations Special Operating Room Requirements Patient Positioning Instrumentation Hemostasis Vascular Considerations Approaches to Lesions Primarily in the Cranial Base Temporal Bone Petrous Apex, Petroclival Junction, and Foramen Lacerum Clivus Jugular Foramen Infratemporal Fossa

Chapter

Surgical Neurotology: An Overview

Transbasal Approaches to Intracranial Tumors Internal Auditory Canal and Cerebellopontine Angle Retrosigmoid Approach Transpetrosal Approaches Middle Fossa Craniotomies Middle Fossa Approach to the Internal Auditory Canal Extended Middle Fossa Approach to the Cerebellopontine Angle Middle Fossa-Transpetrous Apex Approach to the Ventral Pons and Anterior Cerebellopontine Angle Intracranial Aspect of Jugular Foramen

The Ventral Surface of the Brainstem Combined Craniotomy of the Middle and Posterior Cranial Fossae Transcochlear Approach Meckel’s Cave The Craniovertebral Junction Surgical Anatomy Indications Technical Considerations Advantages Disadvantages Vertebrobasilar Lesions Reconstruction of the Cranial Base Closure of Defects Prevention of Cerebrospinal Fluid Leakage

THE CONTEMPORARY CONCEPT OF NEUROTOLOGIC SKULL BASE SURGERY The earliest surgical efforts to approach the skull base took place not long after the introduction of anesthesia in the latter portion of the nineteenth century. Pioneering efforts include those of Krause, Frazier, and others to approach the trigeminal ganglion in Meckel’s cave for the relief of tic douloureux.1 It was obvious even to early surgeons that the most direct approach to certain inaccessible intracranial lesions was through the cranial base rather than the convexity. Transtemporal approaches to the cerebellopontine angle were first proposed by Panse in 1904 (although he never performed the procedure) and were tentatively explored by Borchardt in 1905, Quix in 1911, and a few others during the early decades of the twentieth century.2–4 The openings provided in these fledgling efforts proved too deep and narrow for effective action against the giant tumors typical of the era. In addition, the problem of closure against cerebrospinal fluid (CSF) leakage had not yet been surmounted, nor had methods been invented to permit atraumatic removal of bone from the carotid artery, the facial nerve, or other important neurovascular structures that traverse the base of the skull. Thus, for the first twothirds of the twentieth century, surgeons preferred to expose tumors in and around the base of the brain by opening the

Robert K. Jackler, MD

simple platelike calvaria in preference to navigating the dauntingly complex osteology of the cranial base. This simpler solution was seen as expeditious despite the fact that it frequently required injurious degrees of brain retraction. In the early 1960s, House and others, armed with modern operating microscopes possessing potent sources of illumination and controllable high-speed drill systems, resurrected and ultimately made practical a number of skull base approaches that had been tried much earlier and discarded as impractical. (See William F. House’s personal commentary on this early microsurgical era in this text’s foreword.) As a specialized endeavor, skull base surgery is a relatively new field. It defined itself during the 1980s as a direct result of the introduction of three fundamental technological innovations: (1) high-resolution multiplanar imaging (computed tomography [CT], magnetic resonance imaging [MRI]) to provide detailed tumor maps, (2) improvements in microsurgical optical systems and instrumentation, and (3) the invention of neurophysiologic monitoring. Two nontechnological factors were also essential in the development of contemporary skull base surgery. The first was the increasing willingness of patients to travel from their home region to distant centers with specialized expertise and technical resources. This fostered the accumulation of sufficient experience to both hone skills and undertake meaningful outcomes analysis. The second nontechnical 675

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advance has been the willingness of surgeons to collaborate in a multidisciplinary fashion to share expertise and to mitigate the limitations imposed by operator fatigue in prolonged microsurgical procedures. As with most new endeavors, initial enthusiasm for newfound surgical capabilities was at times out of proportion to their ultimate value. Accumulated experience has tempered practice to some degree and fewer adventuresome resections for advanced high-grade malignancies are now undertaken. With benign tumors, the usual goal is radical resection when morbidity can be kept low. The current trend, in selected situations, is toward less than total resection when the risk of debilitating neuropathy (e.g., diplopia, facial palsy) is high. In many cases such remnants will not grow or can be controlled with stereotactic radiosurgery. Although their place in the surgical armamentarium continues to evolve, it has become abundantly clear that skull base surgical approaches have greatly improved the prognosis for patients afflicted by lesions in and around the skull base in terms of both the likelihood of cure and the preservation of brain and cranial nerve function. The term skull base surgery is somewhat of a misnomer in that only a minority of these procedures in neurotology are actually carried out for disease intrinsic to the skull base. Rather, a majority are undertaken to provide exposure for inaccessible intracranial disease located either beneath the cerebral cortex or adjacent to the brainstem. A high percentage of neurotologic skull base procedures are craniotomies designed to expose lesions situated against the anterior or lateral aspects of the midbrain, pons, and/or medulla. In its essence, the fundamental concept of transbasal craniotomy is the removal of skull base bone to minimize (or even prevent) the need for retraction of the brain (cerebrum, cerebellum). In line with this concept, the organization of this chapter has two major sections: (1) approaches to lesions that are largely intrinsic to the cranial base (e.g., glomus jugulare, petrous apex cholesterol granuloma) and (2) procedures undertaken to expose primarily intracranial disease (e.g., meningioma, schwannoma, epidermoid). It has been traditional to present the subject of skull base surgery by rostering each operative approach and explaining its utility. However, rational treatment decisions are based on an analysis of the advantages and disadvantages of the various technical options for a given anatomic location. It hope that the topical organization of this chapter according to the anatomic site of interest will prove more useful during treatment planning. For additional illustrations of the procedures introduced in this chapter, please refer to this volume’s accompanying surgical atlas5 (Fig. 43-1).

FUNDAMENTAL CONSIDERATIONS Special Operating Room Requirements To be suitable for neurotologic surgery an operating room must be fairly large to accommodate the variety of instrumentation required for these procedures. Arrangement of the room requires complex planning to efficiently position the operating microscope, surgical drill, mono- and bipolar cautery, neural monitoring equipment, as well as a large table of surgical instruments and the considerable complement of devices needed to monitor the patient undergoing neuroanesthesia. In addition, many situations call for the

7,8 IAC CO GG

5

ME EAC

P

M

Cb

SCC CPA SS 4V

Figure 43-1. An axial view of the skull through the level of the internal auditory canal and cerebellopontine angle. Cb, cerebellum; Co, cochlea; CPA, cerebellopontine angle; EAC, external auditory canal; GG, geniculate ganglion of the facial nerve; IAC, the internal auditory canal; M, mastoid air cell system; ME, middle ear; P, pons; SCC, semicircular canals; SS, sigmoid sinus; 4V, fourth ventricle; 5, trigeminal nerve; 7, facial nerve; 8, audiovestibular nerve.

use of specialized surgical tools such as the Cavitron ultrasonic aspirator (e.g., CUSA) or laser. An electrically quiet environment is essential during neurotologic surgery because 60-cycle noise readily obscures the faint potentials detected by neural monitoring equipment. The need for a television monitor to display the microsurgical view is obvious in educational settings, but it is also important to provide context to the neurophysiologic monitoring team and to involve the scrub nurse and circulator better in the progress of the procedure.

Patient Positioning The great majority of neurotologic procedures are done with the patient in the supine position with the head rotated away from the surgeon (Figs. 43-2 and 43-3). Exposure of the suboccipital region may be accentuated by use of a bolster under the ipsilateral shoulder. A headholder (e.g., Mayfield design) that permits removal of the rostral portion of the surgical table may enhance posterior exposure. This also helps to maintain a stable head position and provides a convenient attachment point for brain retractors. Overrotation of the head should be avoided because it might impair venous return via the vertebral system, thereby creating a tendency toward cerebellar swelling. The true lateral or park bench (3/4 rotated) positions may also be used, but with greater pressure on the contralateral arm and hip. Insufficient padding during a prolonged procedure may lead to pressure necrosis or neurologic injury, particularly to the brachial plexus or ulnar nerve. The prone position is important for midline cerebellar tumors, but it has little role in the extra-axial tumors typically addressed by the neurotologist. The sitting position, which is still employed for posterior fossa surgery by a few centers, is steadily decreasing

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Figure 43-2. Operating room setup used in neurotology for a lateral transtemporal procedure.

in popularity. The primary advantage of the upright position is that blood drains away from the operative field. However, the dual risks of air embolization and injury to the cervical spinal cord render this position less desirable.6 It also creates an uncomfortable position for the surgeon in which to perform a prolonged microsurgical procedure. Under certain circumstances, the surgeon must be prepared to change the patient’s position during surgery. When reconstruction with a trapezius or latissimus dorsi myocutaneous flap is planned, the patient’s back must be prepped and draped. During mobilization of the flap, the patient is temporarily rotated into the lateral position. During neurotologic surgery the operating table should be reversed so that the patient’s head is located at the foot of the bed. This permits the surgeon to sit during microsurgery without obstruction under the table that might interfere with a comfortable leg position. Since a reversed table might tend to tip over with obese patients, use of an extra heavy table is desirable. Alternatively, additional weight (e.g., sandbags) can be tied to the end of the bed to counterbalance this tendency. The operating table is frequently turned from side to side during neurotologic procedures. An electrically controlled bed-positioning system, which can be operated by either the anesthesiologist or nurse, is a substantial convenience. A typical operating table has a limited range of side-to-side tilt, usually approximately 15 degrees. Certain models permit rotation in the range of 30 degrees, which can be of significant advantage during neurotologic procedures. To help maintain position when using extreme tilts, it is important to support the patient

Figure 43-3. Operating room setup used in neurotology for a middle fossa procedure.

with a well-padded kidney brace or a similar apparatus attached to the bed frame.

Instrumentation In neurotologic surgery, a diverse set of microsurgical instruments are required. Heavy, blunt elevators are needed for elevation of the periosteum and mobilization of dura from the cranial base. More delicate dissection tools are needed for mobilization of brain and cranial nerves as well as dissection of arachnoid planes. To accommodate for the deep field of action typical of neurotologic procedures, instruments must have considerably longer shafts than those used in conventional otologic surgery. An excellent collection of instruments for neurotologic surgery is the Rhoton microsurgical instrument set, which includes a selection of arachnoid knives of various sizes, hooks, needles, fine curettes, as well as blunt dissectors in several sizes and angulations. A variety of suction instruments between 5 and 12 French are needed. Large-bore suction catheters are required when rapidly removing bone or during episodes of brisk hemorrhage. Smaller, fenestrated suctions facilitate maintaining a dry field while minimizing the potential of accidentally injuring a cranial nerve or small vessel. Tip fenestrations reduce the unwanted tendency of the suction to ingest and tear delicate tissues such as cranial nerve fibers and small

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blood vessels. Often to work in a deep field, an extra long suction is desirable (standard is 10 cm, extra long is 12.5 cm). It is often helpful to have two suction lines available during neurotologic procedures, one of which can be attached to the posterior arm of a retractor to facilitate removal of irrigant solution. Although it should be minimized whenever possible, a degree of brain retraction is required in many neurotologic procedures. Brain retractors may be anchored to the surgical table (e.g., Greenberg), to a headholder (e.g., Mayfield), or on a Weitlander style retractor (e.g., Apfelbaum, Wiet, Silverstein). As a general rule, the cerebellum is more tolerant to brain retraction than the temporal lobe. Moderate cerebellar retraction seldom leads to dysmetria; elevation of the temporal lobe to a similar degree occasionally results in a transient dysphasia and memory disturbance, particularly when the dominant side is involved. The removal of most tumors managed by neurotologists can be considered as two stages: (1) debulking of the tumor’s core and (2) microdissection of the brain, cranial nerves, and vessels from the tumor’s capsule. Several special tools have been developed to facilitate the former task. The ideal tumor debulking implement works rapidly, incites minimal hemorrhage, and respects the tumor capsule in order to avoid accidental injury to a vessel or cranial nerve coursing on the tumor surface. The ultrasonic aspirator (e.g., Cavitron ultrasonic surgical aspirator) rapidly debulks lesions while minimizing the risk of inadvertently violating the capsular plane.7 The House-Urban rotatory dissector is also in widespread use but is less respectful of the capsular surface and is therefore more dangerous, especially in inexperienced hands. Finally, the surgical laser performs the debulking task admirably, but high-power densities are needed to provide reasonable speed.8 Unfortunately, none of these special tools is particularly useful in liberating delicate structures from the capsular surface. The heat generated by laser burst toughens arachnoid much as heat coagulates the white of an egg. This has the effect of rendering surgical planes both more obscure and tenacious. Development of the capsular planes requires painstaking microdissection using fine scissors along with a combination of both sharp and blunt dissectors. A surgical drill used in neurotologic surgery must be sufficiently powerful to rapidly excavate bone as well as delicate enough to permit removal of thin osseous edge adjacent to a naked cranial nerve. Suitable designs with variable torque are available powered by either electricity or compressed air. Although most work may be accomplished with a straight handpiece, an angled handpiece affords improved visibility in deep and narrow operative fields. Special handpieces with long, narrow shafts have been developed for particularly constricted exposures. Burrs in a variety of sizes and both cutting and diamond varieties are needed. Large diamond burrs (e.g., 6 mm, 8 mm, and 10 mm) are especially important because they permit atraumatic removal of bone from dural surfaces. Copious irrigation while the surgeon is drilling should both increase burr life as well as avoid untoward heat buildup, which may injure underlying neural structures. The use of topical antibiotics (e.g., bacitracin) in irrigant solutions during neurotologic procedures has been suggested as a means of lessening the bacterial inoculum, thereby reducing infectious complications.9 It should be noted that bacitracin solution induces a froth that may occlude the values in the surgical suction line.

Hemostasis Hemostasis is important in neurotologic surgery both for the obvious reason of reducing blood loss and to maintain a blood-free field to permit an orderly microsurgical dissection. Bipolar cautery is most important intracranially to limit current spread to the adjacent neural structures. Recently developed bipolar cautery units with automated irrigation systems are most convenient and reduce the tendency of the forceps to adhere to the cauterized tissue. At times, use of cautery is unwise either because of the proximity of the bleeder to a cranial nerve or because the hemorrhage is diffuse and not amenable to pinpoint control. In such cases, an application of thrombin-soaked Gelfoam pledgets or a pad of lyophilized collagen (Avitene) may control minor oozing. Control of bone bleeding can usually be accomplished with diamond burrs, especially if irrigation is momentarily halted. Diamond burrs create a fine bone paste, which impacts and occludes small vascular channels in bone. Reversing the direction of a cutting burr may accomplish the same task. More stubborn bone bleeders can be controlled through the application of bone wax. Not infrequently, while the surgeon is working around dural sinuses, hemorrhage develops due to either a mural tear or avulsion of an emissary vein. This may be controlled by placing a wad of oxidized cellulose (Surgicel) over the defect and holding it in position with a retractor. When controlling bleeding from a major sinus or the jugular bulb, it is important to prevent embolization of the packing material. This risk is minimized by extraluminal application of a piece of Surgicel substantially larger than the defect. If further drilling is required near the Surgicel packing, it must be covered by a smooth material such as Telfa because Surgicel fibers readily become entangled in the shaft of the drill.

Vascular Considerations The three major arterial braches of the vertebrobasilar system traverse the cerebellopontine angle: posterior inferior cerebellar artery (PICA), anterior inferior cerebellar artery (AICA), and the superior cerebellar artery (SCA) (Fig. 43-4). The skill required to preserve these arterial structures is essential for a surgeon performing intracranial tumor microdissection. PICA is located inferiorly, passing close to the roots of the lower cranial nerves. It may become enmeshed in the intracranial aspect of jugular foramen tumors and is occasionally involved in meningiomas of the lower clivus and craniovertebral junction. Disruption of PICA gives a lesion of the lateral medullary (Wallenberg’s) infarction characterized by a variable combination of dysphagia, dysarthria, vocal cord paralysis, vertigo, facial paralysis, and ataxia, as well as ipsilateral Horner’s syndrome and contralateral hemisensory disturbance.10 AICA is often mentioned to possess a “loop” in the CPA, which gives off a distal branch into the IAC, which supplies the inner ear (internal auditory artery).11 However, AICA has in reality two loops, the first of which is applied to the brainstem surface and provides nutrient perforators to the brainstem (Fig. 43-5). The second, more distal loop lies laterally in the CPA, where it gives rise to the IAC artery. Interruption of the first loop gives a devastating

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IAA

SCA

PICA

AICA

Figure 43-4. The major arteries of the cerebellopontine angle. AICA, anterior inferior cerebellar artery; IAA, internal auditory artery; PICA, posterior inferior cerebellar artery; SCA, superior cerebellar artery.

neurologic injury with hemiplegia and multiple central cranial nerve dysfunctions, whereas loss of the distal loop causes a more focal cerebellar peduncular infarction with persistent ataxia11,12 (Fig. 43-6). The superior cerebellar artery is sometimes placed at risk in exposing transtentorial tumors. Injury to the SCA causes dysmetria, dysdiadochokinesia, dysarthria, ataxia, vertigo, and sometimes diplopia.13 Preservation of the veins of the posterior fossa is much less critical than preservation of the arteries. The petrosal

Figure 43-5. The anteroinferior cerebellar artery has two loops: a proximal segment providing nutrient branches to the brainstem and a lateral loop lying free in the cerebellopontine angle. The lateral loop gives rise to the internal auditory artery.

Figure 43-6. Occlusion of the proximal trunk of the anteroinferior cerebellar artery results in an extensive pontomedullary infarction (gray region). Blockage of the distal segment give a focal infarction of the middle cerebellar peduncle (dark circle).

vein (also know as Dandy’s vein) parallels the trigeminal nerve just beneath the tentorium. It can often be preserved, but in large tumors is frequently taken without consequence. Rarely does its division lead to cerebellar venous congestion.14 Numerous veins travel roughly rostrocaudally on the brainstem surface. At least some of these need to be taken during removal of a large CPA tumor and, fortunately, their interruption seldom leads to adverse consequences. An important exception to the usual rule that dividing veins is of low risk is the vein of Labbé.15 This large vein drains the temporoparietal region and bridges from the cortical surface to enter the transverse sinus (Figs. 43-7 and 43-8). It is at risk during tentorial division in the combined approach to the posterior and middle fossa (see below). Division or occlusion of a dominant-side vein of Labbé may result in speech disturbance and contralateral hemiparesis or even hemiplegia (Fig. 43-9). In a combined-approach

Figure 43-7. The vein of Labbé, which bridges from the cortex to enter the transverse sinus, drains the temporoparietal region.

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A

Figure 43-9. A temporoparietal venous infarct resulting from occlusion of the vein of Labbé.

B Figure 43-8. A, Two common courses of the vein of Labbé in its route toward the transverse sinus. The vein may lie on the upper surface of the tentorium or even run between its leaves. B, To avoid the vein of Labbé during tentorial division in the combined middle and posterior fossa approach, it is prudent to first identify the course of the view on the upper surface of the tentorium. When necessary, the tentorial division should be placed more medially to prevent injury to this important venous structure.

craniotomy, great care is taken to preserve this functional end vein whenever possible.

APPROACHES TO LESIONS PRIMARILY IN THE CRANIAL BASE Temporal Bone Several tumor types may necessitate extensive resection of the temporal bone.16 The most common such tumor is invasive squamous cell carcinoma arising from the external auditory canal. Relatively early, it extends beyond the confines of the ear canal and grows along the skull base into the infratemporal fossa. The inner ear, dura, and vascular compartment of the temporal bone can be involved in advanced cases. Adenomatous tumors, especially the aggressive papillary adenocarcinoma of endolymphatic sac

origin, may also require a temporal bone resection. Sac tumors have a tendency to traverse the posterior fossa dura and press against the cerebellar hemisphere. Adenocystic carcinoma of the temporal bone usually arises from salivary tissue adjacent to the external auditory canal. Extensive perineural invasion is usually well established even in early lesions. In children, aggressive temporal bone tumors, except sarcomas, are uncommon. Rhabdomyosarcomas, the most frequent variety, are usually anatomically extensive upon presentation. The degree of temporal bone resection is determined by the anatomic extent of the tumor and its biologic tendencies.17 The minimal temporal bone resection for squamous carcinomas entails en bloc removal of the external auditory canal (Figs. 43-10 and 43-11). The so-called sleeve excision of the soft tissue of the ear canal is inadequate for malignant disease. According to the extent of tumor involvement, some or all of the adjacent parotid gland and temporal mandibular joint may be included in the specimen. Medial extension into the inner ear or vascular compartment (carotid canal and jugular bulb) is exenterated piecemeal with the drill rather than en bloc by most surgeons. In endolymphatic sac tumors, the posterior fossa dura must be included in the specimen, and the ear canal can sometimes be preserved. Resection in adenocystic carcinoma should be thorough but not unnecessarily radical. These lesions are seldom cured even when the primary lesion is small and initial surgery extensive. Fortunately, they tend to progress slowly. Surgery in temporal bone sarcomas is only adjunctive to chemotherapy. Since perimeningeal or intracranial spread are risk factors for recurrence, cytoreduction by removing the peridural component is often desirable. One general theme in temporal bone resection is that, unless it is grossly infiltrated by tumor, a functioning facial nerve should be preserved whenever possible. When postoperative radiotherapy is anticipated, it is usually wisest to

Surgical Neurotology: An Overview

Figure 43-10. Axial view of the three types of temporal bone resection for malignancy: sleeve resection of the external auditory canal (solid line), lateral temporal bone resection (dotted line), total temporal bone resection (dashed line). Most of these resections are performed for squamous cell carcinoma arising from the external auditory canal. It is generally acknowledged that sleeve resection is insufficient therapy for malignant disease. In the lateral temporal bone resection, the ear canal is removed en bloc with the tympanic membrane and lateral ossicles. A parotidectomy and/or neck dissection often supplements the temporal bone specimen.

close the external meatus to reduce the risk of osteoradionecrosis. Leaving the ear open in an effort to preserve hearing is usually ineffective because radiotherapy typically induces a severe cochleopathy over time. Extensive bony defects are best filled with well-vascularized tissue. A regional flap of temporalis muscle is usually effective. When large cutaneous defects are present (e.g., following resection of the pinna), then either a myocutaneous flap (e.g., trapezius) or a free flap (e.g., rectus abdominis) is necessary to close the defect. When dural resection is required, it is repaired with fascia, and the eustachian tube is obliterated to prevent CSF otorhinorrhea. The role of carotid resection in temporal bone tumors is controversial. Some advocate resection when the artery is encased by tumor if the patient passes a preliminary test occlusion. However, test occlusion is a fallible predictor and devastating postoperative stroke can still occur. In the author’s opinion, planned carotid resection of high-grade malignancies is seldom justified and should be considered contraindicated in benign tumors.

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Figure 43-11. Lateral temporal bone involves resection of the external auditory canal and may include a resection of the parotid and condylar head in continuity with the ear canal. Condylectomy brings into view the pterygoid muscles that may be resected to the level of the pterygoid plates if necessary.

and are most accurately called petrous apicotomy rather than apicectomy (Figs. 43-12 and 43-13). Actual resection of the apex, petrous apicectomy, may be undertaken for tumor resection, for the rare cholesterol granuloma that is not amenable to either transtemporal or transsphenoidal drainage, or as an adjunctive procedure in the exposure of tumor located ventral to the pons of basilar tip aneurysms (the latter to be discussed later). The most common primary tumor of the petrous apex is chondrosarcoma arising from

Petrous Apex, Petroclival Junction, and Foramen Lacerum The petrous apex is the medial portion of the petrous ridge. It is bounded laterally by the otic capsule and medially by the clivus. Most surgery of the petrous apex involves creation of a small drainage portal between the middle ear or mastoid and the petrous apex skirting the structures of the inner ear.18 Such procedures are conducted for inflammatory conditions (petrous apicitis, cholesterol granuloma)

Figure 43-12. Petrous apicotomy for drainage of a cholesterol granuloma into the middle ear.

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Figure 43-13. Subtemporal approach for petrous apicectomy as performed for chondrosarcoma of the petroclival junction. In this case, the intrapetrous carotid artery has been skeletonized.

Figure 43-15. Exposure of a petroclival junction chondrosarcoma surrounding the intrapetrous carotid artery. Downward displacement of the zygoma and division of the third division of the trigeminal nerve is necessary only with substantial inferior spread.

the cartilage that fills foramen lacerum19 (Fig. 43-14). These originate at the petroclival junction and may erode laterally into the inner ear and medially into the clivus.20 Posteriorly, they may prolapse into the cerebellopontine angle. Secondary involvement of the petrous apex may occur due to lateral spread of clival chordoma or deep penetration of intratemporal tumors such as squamous cell carcinoma. The surgical approach to petrous apex chondrosarcoma is via a subtemporal craniotomy (Fig. 43-15). Extradural

elevation of the temporal lobe brings into view the anterior surface of the petrous ridge. The tumor is approached by resecting the petrous ridge between the internal auditory canal and Meckel’s cave. This necessitates division of the greater superficial petrosal nerve with resultant dry eye. Dissection can be carried medially into Meckel’s cave but caution must be exercised to avoid injury to the sixth nerve in Dorello’s canal. The floor of the apical resection is the horizontal course of the intrapetrous carotid artery.

Figure 43-14. Chondrosarcoma of the petroclival junction arising in the cartilage of foramen lacerum.

Figure 43-16. Clival chordoma.

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This subtemporal transpetrous apex approach also affords limited access to the posterior cranial fossa. Most apical chondrosarcomas can be resected in a single stage, but those with extensive posterior fossa components require a twostage approach: retrosigmoid for the intracranial component and subtemporal for the segment in the cranial base.

Clivus The clivus is not a bone in and of itself. Rather it is a long sloping plane extending from the anterior lip of the foramen magnum to the dorsum sellae and clinoids. It is composed of two bones: the occipital bone anterior to the foramen magnum and the dorsal component of the sphenoid bone. The brainstem and vertebrobasilar system lie adjacent to its dorsal surface. The great majority of clival tumors that are managed surgically are chordomas arising from notochordal remnants oriented along the midline of the cranial base (Fig. 43-16). Chordomas that have remained extradural and are confined to the midline skull base are approached anteriorly, most commonly via either a transsphenoethmoidal or a transoral approach.21–23 The anterior strategy is to create a modest opening into the tumor cavity and then blindly excavate the gelatinous tumor by scraping the cavity walls with curettes. The neurotologist becomes involved in chordoma surgery when the tumors spread intradurally or spread laterally behind the intrapetrous carotid arteries. Chordomas that breech the posterior fossa dura compress the midbrain, pons, and/or medulla and abut the basilar artery. Anterior approaches are not advisable for intradural tumors because they 1. Provide a deep field of action ill suited for microdissection 2. Approach the brainstem-tumor interface from a disadvantageous direction 3. Traverse contaminated spaces 4. Present great difficulty in resealing the dura to avoid CSF fistula Lateral approaches to the intracranial component of clival tumors typically require a combination of middle and posterior fossa craniotomy.24 This is most often achieved with a single opening consisting of a limited petrosectomy (retrolabyrinthine approach) and a middle fossa opening joined by division of the tentorium. As is discussed throughout this chapter, this combined-approach craniotomy has become a workhorse for approaching tumors located anterior and lateral to the brainstem. Tumor resection is carried out through two intervals: between the jugular foramen nerves (IX–XI) and the complex of cranial nerves VII–VIII, and also between cranial nerves VII–VIII and the root entry of the fifth nerve. Although this presigmoid combined approach affords excellent access to the posterior intradural component, it is limited anteriorly in the cranial base. A second stage anterior approach to address a ventrally situated tumor (e.g., in the perisphenoid region) may be required.

Jugular Foramen The jugular foramen is traversed by the jugular vein along with the glossopharyngeal (IX), vagus (X), and accessory nerves (XI)25 (Fig. 43-17). Anteromedially is the internal carotid artery. Superiorly is the hypotympanum and

Figure 43-17. Overview of jugular foramen relationships.

otic capsule. Laterally is the mastoid and, very important, the vertical segment of the facial nerve canal. Posteriorly are the lower reaches of the posterior fossa adjacent to the lateral aspect of the pontomedullary junction and medulla. The most common tumors of the jugular foramen are paraganglioma (glomus jugulare), schwannoma of the lower cranial nerves, and meningioma. Glomus tumors and meningiomas often present with a visible component in the middle ear, whereas schwannomas do not. Each may occur in one of four anatomical varieties: (1) limited to the jugular foramen in the cranial base, (2) pear-shaped with a component in the infratemporal fossa, (3) pear-shaped with a lobe in the posterior cranial fossa, and (4) dumbbell-shaped with sizable components both intra- and extracranially. Common to all jugular foramen operations is a transmastoid opening of the jugular foramen and exposure of the great vessels in the upper neck. Safe surgery in the jugular foramen requires proximal (sigmoid sinus) and distal (jugular vein) vascular control. Since the descending facial nerve

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Figure 43-18. Jugular foramen approach. It is possible to expose the jugular foramen without rerouting the facial nerve or destroying the conductive hearing apparatus. Jugular foramen surgery requires that the sigmoid-jugular complex be controlled both proximally (either by suture ligature or extraluminal packing, as depicted here) and distally in the neck. The hypotympanum can be exposed by an inferiorly based tympanomeatal flap. CA, carotid artery; FN, facial nerve; JB, jugular bulb; JV, jugular vein; P, parotid gland; SCC, semicircular canals; SS, sigmoid sinus; TM, tympanic membrane; 9, glossopharyngeal nerve; 10, vagus nerve; 11, accessory nerve; 12, hypoglossal nerve.

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EAM

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XII

AP EC IC MC

X JV SCM

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XI

DM Figure 43-19. The fallopian bridge approach in which the vertical segment of the facial nerve is skeletonized to afford exposure of the jugular foramen.

overlies the jugular bulb, many advocate an anterior rerouting to provide unhindered access.26 Others, including the author, prefer a fallopian bridge technique, leaving the facial nerve in situ and working around it27 (Figs. 43-18) through 43-22). Unless there is extensive destruction of the middle ear and ear canal (assuming integrity of the inner ear and eighth nerve), auditory function can usually be preserved. Extensive erosion of the ear canal or inner ear many necessitate removal of the canal wall, closure of the meatus, and obliteration with adipose tissue. Of course, this creates a maximum conductive hearing loss. When necessary, tumor can usually be microdissected from the genu of the carotid artery with minimal risk of injury. When the tumor is markedly adherent to the carotid wall, a thin remnant should be left and thoroughly coagulated with bipolar cautery. Planned carotid resection is not indicated in benign tumors of the jugular foramen. Intracranial extension of a jugular foramen tumor necessitates a transjugular posterior fossa craniotomy, which is discussed separately.

Figure 43-20. A medium-sized glomus jugulare tumor, which fills the jugular bulb and extends intraluminally into both the sigmoid sinus and jugular vein. Note the small tongue of tumor that has penetrated into the hypotympanum. This otoscopically visible “tip of the iceberg” is often the clinical feature that leads to the detection of these lesions.

Figure 43-21. When the tumor extensively erodes the carotid wall, adequate exposure requires anterior rerouting of the facial nerve and a canal wall down mastoidectomy. This maneuver provides unrestricted access to the vascular otobase. Note that the ear canal, tympanic membrane, and lateral two ossicles have been removed and that the external meatus has been sewn shut. It is helpful to be familiar with the course of the ascending pharyngeal artery, the primary blood supply to the jugular foramen. In the presence of a vascular tumor, it is often much larger than it is depicted here. AP, ascending pharyngeal artery; C1, transverse process of C1; DM, digastric muscle; EAM, external auditory meatus; EC, external carotid artery; IC, internal carotid artery; JV, jugular vein; MC, mandibular condyle; SCM, sternocleidomastoid muscle; SM, styloid muscles; 7, facial nerve; 9, glossopharyngeal nerve; 10, vagus nerve; 11, accessory nerve; 12, hypoglossal nerve.

Infratemporal Fossa The term infratemporal fossa is generally used to describe the complex of structures located beneath the temporal bone.28 This region includes a number of different anatomic compartments (e.g., parapharyngeal space, pterygomaxillary fossa) and contains within it the deep portion of the parotid gland, pterygoid muscles and their associated vascular plexus, cranial nerves IX–XII, the jugular vein, and the carotid artery. The more common primary lesions in this area include tumors of the deep lobe of the parotid gland, glomus

Figure 43-22. A large glomus tumor, which erodes the genu of the internal carotid artery. It has significant intraluminal components in both the sigmoid sinus and jugular vein. Note the extraluminal packing of the sigmoid sinus.

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TRANSBASAL APPROACHES TO INTRACRANIAL TUMORS Internal Auditory Canal and Cerebellopontine Angle Surgery of tumors of the internal auditory canal and cerebellopontine angle is a central issue to neurotology. Perhaps the greatest advances in neurotologic surgery in recent decades have taken place in the management of benign, extra-axial tumors of the posterior fossa, particularly those of the cerebellopontine angle (CPA). The classical suboccipital approach, formerly the workhorse used in virtually all such tumors, has been largely supplanted by the retrosigmoid and transtemporal approaches (Fig. 43-24). The retrosigmoid approach is a modified suboccipital opening, which reduces the need for cerebellar retraction while providing wide exposure and maintaining the possibility of hearing preservation in selected cases. A family of

Figure 43-23. The infratemporal fossa approach, as described by Fisch, has three primary varieties: type A for the jugular foramen region, mandibular fossa, and posterior infratemporal fossa; type B for the apical petrous bone and clivus including the intrapetrous course of the carotid artery; type C is an anterior extension used for exposure of the infratemporal fossa, pterygopalatine fossa, parasellar regions, and nasopharynx.

vagale, and lower cranial nerve schwannomas. Examples of secondary involvement include downward excursion of a glomus jugulare, lateral penetration of nasopharyngeal carcinoma, and neoplastic spread along the third division of the trigeminal nerve. Meningiomas can also spread extradurally to this area via either the foramen ovale or the jugular foramen. Operative approaches to the infratemporal fossa may be considered in two broad categories: preauricular or postauricular (Fig. 43-23). Postauricular approaches to the infratemporal fossa are usually indicated for (1) tumors of the jugular foramen with a substantial component in the upper neck, (2) deep lobe parotid tumors that erode the temporal bone (e.g., penetrate the fallopian canal or erode the ear canal), and (3) ear canal squamous cell carcinomas that penetrate beneath the temporal bone. Preauricular approaches are used for more anteriorly based tumors that do not involve the petrous bone. Some examples include (1) schwannoma of the third division of the trigeminal nerve, (2) meningioma penetrating foramen ovale, and (3) tumors in the paranasopharyngeal region. Several adjunctive techniques are often needed to enhance exposure during the infratemporal fossa procedure. Resection of the mandibular condyle facilitates wide exposure for malignant disease. A pseudoarthrosis usually forms and the effect on mastication is not usually debilitating. Temporary downward displacement of the zygomatic arch facilitates exposure of temporal and sphenoidal (greater wing) floor lesions while minimizing the need for retraction of the temporal lobe. In such lesions, resection of the glenoid fossa may be necessary. Finally, approach to the more medial aspect of the infratemporal fossa usually requires section of the third division of the trigeminal nerve.

Figure 43-24. An axial schematic view of the common posterior fossa craniotomies used to access the CPA. In the retrosigmoid approach, an opening is created in the suboccipital bone plate behind the sigmoid sinus. The three transtemporal approaches open the posterior fossa dura anterior to the sigmoid sinus, through the posterior aspect of the petrous pyramid. Note that the transtemporal craniotomies require removal of 1 to 2 cm of retrosigmoidal bone to allow for posterior displacement of the sinus. In the retrolabyrinthine approach, bone is removed up to the semicircular canals. This provides a limited view of the posterior aspect of the CPA. In the translabyrinthine approach, the balance canals are also removed, a maneuver that both provides access to the IAC and enhances CPA exposure. In the transcochlear approach, the entire inner ear is removed and the facial nerve is posteriorly rerouted from its intratemporal course. This technique provides access to the anterior aspect of the CPA and the space ventral to the brainstem.

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presigmoid or transtemporal approaches have been developed to further reduce the degree of brain retraction required as well as to reduce the depth of the operative field. Although the transpetrosal approaches are technically more complex than retrosigmoid openings, they do possess a somewhat lower morbidity while providing ample exposure for the vast majority of extra-axial posterior fossa tumors. The amount of the petrous bone removed in the transpetrosal approach depends on the degree of exposure required. In the retrolabyrinthine approach, the only transpetrosal craniotomy that spares the inner ear, only limited exposure of the midportion of the CPA is provided. This opening is generally considered suitable only for problems confined to the root entry zone of the seventh and eighth nerve complexes, such as selective vestibular neurectomy and vascular loop decompression. With the capability of providing access to the entire CPA, the translabyrinthine approach is much more versatile than the retrolabyrinthine. The transcochlear approach, a more radical transpetrosal craniotomy that involves a complete exenteration of the inner ear and requires rerouting of the intratemporal course of the facial nerve, extends the translabyrinthine exposure to include the ventral surface of the pons and the prepontine cistern. Logically, it seems obvious that the angle of view to the CPA and brainstem should differ substantially between retro- and presigmoid approaches. In practice, however, the perspective of these structures is quite similar in the two techniques. The reason is that in the retrosigmoid approach, bone is removed up to the edge of the sigmoid sinus and the surgeon views along the front edge of the craniotomy opening; in the presigmoid approaches, bone is removed behind the sinus, permitting its retraction posteriorly, and the surgeon views along the posterior edge of the opening. Thus, the angle of view toward the vital structures of the CPA is actually quite similar. Some earlier publications, particularly in the neurosurgical literature, have disparaged the presigmoid approaches (especially translabyrinthine) as providing insufficient exposure of the brainstem.29 These objections undoubtedly arise from neurosurgical collaboration with an inexperienced temporal bone surgeon who provided inadequate presigmoid opening for intracranial microdissection.

Figure 43-25. Retrosigmoid approach to a medium-sized acoustic neuroma seen in axial section. Note that the internal auditory canal has been drilled open to expose the intracanalicular component of the tumor. The degree of cerebellar retraction required in this approach varies, but it is often less than depicted here.

SS CC

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Retrosigmoid Approach The retrosigmoid (RS) approach provides a panoramic exposure of the posterior fossa from the tentorium to the foramen magnum (Figs. 43-25 and 43-26).30–32 Access is provided to the cerebellar hemisphere, the lateral aspect of the pons and medulla, and the root entry zones and cisternal courses of cranial nerves V through XI. By unroofing the posterior bony covering of the internal auditory canal (IAC), the seventh and eighth nerves can be readily exposed to the fundus of the canal. The fifth nerve can also be traced for part of its course into Meckel’s cave and the middle fossa floor by exenteration of the apical portion of the petrous pyramid. Exposure with the RS approach is limited superiorly by the tentorium, although it may (as with all other types of

Co

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Figure 43-26. Retrosigmoid craniotomy (left side) illustrating the surgical anatomy of the posterior fossa exposure. The venous sinuses and inner ear structures have been made visible to help clarify their relationships to intracranial structures. BS, brainstem; CC, common crus; Ch, choroid plexus; Co, cochlear; ES, endolymphatic sac; Fl, flocculus; IV, inferior vestibular nerve; JB, jugular bulb; JV, jugular vein; PA, porus acusticus; PSCC, posterior semicircular canal; SS, sigmoid sinus; SSCC, superior semicircular canal; SV, superior vestibular nerve; VA, vestibular aqueduct. Cranial nerves: 5, trigeminal; 7, facial; 8, audiovestibular; 9, glossopharyngeal; 10, vagus; 11C, accessory (cranial portion); 11C, accessory (spinal portion).

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posterior fossa craniotomy) be combined with a middle fossa or transtentorial exposure. Inferiorly, the limit is the foramen magnum, which can be exposed when the need arises through inferior extension of the craniotomy accompanied with upper cervical laminectomy as required. Anteriorly, exposure is limited by the long field of action, the bridging of cranial nerves VII and VIII superiorly and IX–XI inferiorly, and the inadvisability of applying retraction to the brainstem. Indications Because of its wide exposure, the RS approach is versatile. Were it not for the lower morbidity of transpetrosal approaches and their greater versatility with regard to cranial base extension, the RS craniotomy could be used for virtually all extra-axial posterior fossa tumors that did not arise in the anterior midline or deeply penetrate the cranial base. Indeed, a number of centers follow this policy. Even in centers experienced with transpetrosal approaches, the RS approach is often used for selective vestibular neurectomy; vascular decompression of fifth (trigeminal neuralgia), seventh (hemifacial spasm), eighth (disabling positional vertigo, tinnitus), or ninth (glossopharyngeal neuralgia) cranial nerves; hearing conservation approaches to acoustic neuromas with small cisternal components; and in the removal of meningiomas, epidermoids, and other nonacoustic CPA tumors when hearing is intact (Figs. 43-27 through 43-29).33–37 Technical Considerations In the suboccipital (SO) approach a large paramedian opening is created in the suboccipital convexity, usually bounded laterally at the first encounter with the mastoid air cell system. This usually places the anterior edge of the craniotomy well behind the sigmoid sinus. Because of its more posterior orientation, a greater degree of cerebellar

Figure 43-28. Retrosigmoid approach to a large acoustic tumor that deeply invaginates the internal auditory canal. To expose the lateral extent of the tumor, portions of the inner ear must be removed.

retraction is required to access the CPA and the IAC. The classical SO approach has largely supplanted the RS approach in recent years. The bony opening in the RS approach is situated immediately posterior to the sigmoid sinus and immediately inferior to the transverse sinus. The size of the opening varies according to the size and location of the lesion being addressed, but it can usually be limited to approximately 3 × 3 cm. In most cases, two technical problems are created by this close approach to the dural sinuses. Entry into the mastoid air cells was greatly

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Figure 43-27. Retrosigmoid approach to a small acoustic tumor that does not deeply invade the internal auditory canal. In such cases, it may be possible to open the internal auditory canal without violating the inner ear. The endolymphatic sac and aqueduct are often helpful landmarks in preventing injury to the otic structures. C, cochlear division of the eighth nerve; 7, facial nerve; 8, audiovestibular nerve.

5

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Figure 43-29. Retrosigmoid approach to selective vestibular neurectomy. A small craniotomy is performed with minimal cerebellar retraction, just sufficient to expose the entry zone of the seventh and eighth nerve complexes. To denervate the vestibular system, the rostral portion of the eighth nerve is divided. C, cochlear division of the eighth nerve; Ch, choroid plexus; Fl, flocculus; V, vestibular division of the eighth nerve; 5, trigeminal nerve.

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feared in the past due to concern for contamination of the wound. However, it is now understood that the normal mastoid air cell system is sterile and thus wound inoculation seldom occurs. The second consideration is CSF leakage, which remains problematic especially when extensive pneumatization is present. Transected air cells are sealed with either bone wax or hydrophobic bone cement. To be most effective, not only should sealant be impacted into opened air cells, but a continuous thin sheet should be created as well. Due to the thickness of the musculature overlying this region, the bone may be simply removed (craniectomy) without leaving a particularly vulnerable skull defect. Some argue that the persistence of a bone defect permits adherence between the posterior fossa dura and the suboccipital musculature, a condition that may contribute to the development of headaches. In addition, meningoceles may occur, particularly in patients with hydrocephalus. To avoid this, an osteoplastic bone flap may be created, but this is technically difficult to produce without injuring the sigmoid sinus. We favor replacing the morselized bone fragments harvested during opening into the defect at the end of the procedure. In our experience, this is more readily achievable technically than a bone flap and heals satisfactorily as a firm bony plate. The relative position of the sigmoid sinus effects exposure via the RS approach. An anterior lying sigmoid sinus is favorable, affording a more directly lateral point of view. Conversely, a posterior lying sigmoid sinus may be a hindrance, forcing the exposure to a disadvantageously posterior perspective. In such circumstances, some have recommended that a mastoidectomy be performed with decompression of the sinus, thus allowing its retraction anteriorly with dural stay sutures. An inferiorly located transverse sinus may similarly impose limitations as it forces the surgeon to work from a more inferior perspective. When the patient’s neck is short and the shoulder is large, there may be both limited access to the retrosigmoid region and the need to carry out dissection at a relatively awkward angle. This circumstance may also prevail in patients with limited neck mobility due to advanced age or disease of the cervical spine. The surgeon should avoid the tendency to compensate for unfavorable anatomy by overrotating the head because this may crimp the vertebral veins and contribute to a tendency for cerebellar swelling. In extreme cases of a short and fat neck or cervical immobility, the sitting position may be chosen. After dural opening, it is essential to liberate CSF from the cisterna magna before retracting the cerebellum. This is accomplished by gently elevating the cerebellum and fenestrating the cistern’s arachnoid covering. Failure to release CSF at an early stage risks untoward swelling of the cerebellum during premature efforts at retraction. Such cases of cerebellar swelling, which may rarely occur despite meticulous technique, require abandonment of the procedure. In cases of massive swelling, the protuberant cerebellum may need to be resected followed by a loose closure, leaving the dura open. Under such dire circumstances, opening of the foramen magnum ring may discourage postoperative tonsillar herniation. To expose the midportion of the CPA, the cerebellum must be gently retracted medially. In the RS approach,

surprisingly little retraction is often needed. In exposing the mid-CPA, our measurements indicate the need for only 1 to 2 cm of medial displacement in the average case. After draining the cisterna magna and administering intravenous mannitol to shrink the cerebellum, the more lateral portion of the CPA can often be visualized without retraction. A substantially greater degree of retraction is required, however, when the tumor deeply invaginates the pons and cerebellar peduncle. Resection of the lateral one-third of the cerebellum to improve exposure, a maneuver formerly in widespread use, is virtually never required today. To prevent injury to its surface, it is best not to place a retractor directly on the cerebellum. We prefer to use a Telfa strip (approximately 2 × 6 cm) under the retractor. Alternatively, a Silastic-coated malleable retractor blade may be used. Narrow retractors tend to indent or even lacerate the cerebellar surface. Wider retractor blades tend to distribute the retraction force over a wider surface and minimize potential for injury. When tumors penetrate the IAC, the canal’s osseous posterior lip must be removed. Intradural drilling produces copious amounts of bone dust, which is a meningeal irritant that may contribute to postoperative aseptic meningitis and persistent headache. An effort should be made to confine the debris created while drilling so that it can be evacuated with suction. This may be achieved, with incomplete success, by placing Gelfoam into the CPA and covering it with a rubber dam. Despite these precautions, it is not uncommon to find bone dust adhering to relatively inaccessible arachnoid surfaces in the prepontine cistern along the basilar artery as well as in the jugular foramen region. Adequate exposure of the IAC contents requires not only visibility, but sufficient room for the unrestricted use of microsurgical instruments. Generally, this necessitates creation of troughs that are several millimeter wide above and below the IAC, which are deepened beyond the plane of the anterior face of the canal. This deep excavation is necessary to permit insinuation of a hook or other angled instrument into the plane between the tumor and the anteriorly located facial nerve. On occasion, an unusually high jugular bulb may lie against the inferior aspect of the IAC or even overlap it to some degree. Care must be taken to avoid injury to this structure because it is difficult to compress it sufficiently without obscuring the intracanalicular portion of the tumor. A high jugular bulb inhibits formation of a trough beneath the IAC, particularly in the medial portion of the canal adjacent to the porus acusticus. This limitation can generally be overcome by elevating the tentorium and addressing the IAC component primarily from above. When hearing conservation is a goal, it is important to be aware that only approximately the medial two-thirds of the IAC may be opened via the RS approach without violating the vestibule of the inner ear (see Figs. 43-27 and 43-28).38,39 Some have advocated using the endolymphatic sac and aqueduct as a guide to avoid entry into the labyrinthine structures. In most cases, we prefer opening the canal to the level of the tumor’s deepest penetration, regardless of its relationship to the inner ear. This allows tumor dissection to commence with direct visualization of the tumor-nerve interface and greatly reduces the likelihood of

Surgical Neurotology: An Overview

tumor recurrence due to incomplete resection from the fundus. Unlike tumor remnants in the CPA, which are often devoid of vascular supply, tumor residual in the fundus of the IAC is likely to possess a vascular stalk capable of supporting tumor regrowth.40 In a few patients with normal or near normal hearing, undertaking the risk of an indirect dissection may be warranted. In such cases, an attempt should be made to confirm complete excision from the lateral recess of the canal by visualization with an endoscope or mirror. Opening of the IAC may transect mucosally lined air cells that are present in proximity to the canal in 30% to 40% of adults. To avoid CSF leakage, these must be closed with bone wax or hydrophobic bone cement. In addition, many surgeons place a tissue graft into the petrosal defect created by opening the IAC. A free graft of either muscle or fat may be employed, which may be maintained in position by a dural suture, autologous fibrin glue, or a combination of the two. Since muscle may simulate recurrent tumor on subsequent enhanced MRI, fat is preferred in most centers because its signal can be suppressed. When pneumatization is extensive, we use a prophylactic lumbar subarachnoid drain to discourage CSF leakage. Advantages The primary advantage of the RS approach is its versatility. Because it provides a relatively panoramic exposure of the posterior fossa from the tentorium to the jugular foramen, the RS approach is suitable for use in a wide variety of tumors as well as vascular abnormalities affecting this region. In selected lesions, it affords the possibility of hearing preservation.41–43 Disadvantages The RS approach, due to its relatively posterior angle of view, provides only limited visualization of the region ventral to the brainstem. Exposure of the ventral surface of the pons and medulla and the posterior aspect of the clivus is obstructed both by cranial nerves V through XI, which bridge the CPA, as well as by the interposed lateral surface of the brainstem. The presigmoid transtemporal approaches, which offer a more anterior angle of view, are more suitable for the majority of tumors in front of the brainstem. Some argue that the need for cerebellar retraction is a disadvantage of the RS approach. However, when performed gently, retraction seldom leads to postoperative cerebellar dysfunction. A more important disadvantage is the frequent occurrence of persistent postoperative headaches. In a study of CPA tumors at the University of California at San Francisco, headache persisted beyond the sixth postoperative month in 64% of patients following RS craniotomy but in only 34% after the TL approach.44 More important, 12% of RS patients reported long-lasting severe and disabling headache, whereas no TL patients were so afflicted. Of interest, most severe headache sufferers had small tumors and had undergone a hearing conservation attempt. The reason for the higher incidence of headache following the RS approach is uncertain, but it may well be related to the widespread soilage of posterior fossa arachnoid with bone dust generated during intradural drilling of the posterior lip of the IAC. During a transtemporal craniotomy, by contrast, all drilling is

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completed before opening the dura. Presumably, the irritation of bone dust may lead to a form of chronic aseptic meningitis. Arguing in favor of this etiology is the relative responsiveness of such headaches to corticosteroids and nonsteroidal anti-inflammatory drugs. An additional observation that supports this mechanism is the frequent occurrence, during a severe headache, of a bulging operative site suggestive of transient increased posterior fossa pressure. Other possible etiologies of post RS craniotomy headache include occipital neuralgia and a coupling of the posterior fossa dura with the suboccipital musculature. In support of the latter hypothesis is the fact that post RS headache is triggered by cough or straining in some patients. In this regard, such headaches are similar to those associated with the Arnold-Chiari deformity and other malformations of the craniovertebral junction. Recently, it has been reported that reconstruction of the suboccipital skull somewhat reduces the risk of persistent headache.45,46 Some have maintained CSF leak has been more common following RS craniotomy than following transtemporal techniques, as well as more stubborn and difficult to manage.47,48 Via the RS approach, it is technically difficult to hermetically seal all transected cells when the petrous apex is extensively pneumatized. In addition, closure is attempted at only one location—along the cut edge of petrous bone. In the transtemporal approaches, a second line of defense is created either at the entrance of the aditus-ad-antrum or through obliteration of the eustachian tube. As opposed to CSF otorhinorrhea, CSF wound leak may be less common following the RS approach due to the multilayer closure afforded by the thick occipital musculature. In a recent study at the University if California at San Francisco, the incidence of CSF leakage was equal (approximately 10%) following the translabyrinthine (TL), RS, and middle fossa (MF) approaches.49 Transpetrosal Approaches The transpetrosal approaches (also known as transtemporal) are a family of three craniotomy techniques (retrolabyrinthine, translabyrinthine, and transcochlear) (see Fig. 43-24), which progress from a limited petrosectomy that provides only a small view of the CPA to radical resection of the contents of the petrous pyramid with wide posterior fossa exposure. Retrolabyrinthine Surgical Exposure: The retrolabyrinthine (RL) approach consists of a small posterior fossa craniotomy, which is performed between the sigmoid sinus and the otic capsule (Figs. 43-30 and 43-31).50,51 It provides limited exposure of the posterior fossa, confined to the region of the entry zone of the fifth, seventh, and eighth nerves. More lateral structures, such as the porus acusticus and IAC, cannot be visualized because they are blocked by the otic capsule. Indications: The RL approach was first described in the early 1970s as an approach to the root entry zone of the trigeminal nerve in tic douloureux, but was not used widely until the early 1980s when it gained popularity as a means of exposing the brainstem entry of the eighth nerve for vestibular neurectomy.34,52,53 In recent years, the retrosigmoid approach has regained favor for this procedure

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Figure 43-30. Retrolabyrinthine craniotomy in axial view. Note that the bone overlying the sigmoid sinus is removed together with 1 to 2 cm of retrosigmoid occipital plate.

due to its wider exposure. Much less common, the RL has been used to perform vascular decompression of the eighth nerve for tinnitus or chronic vertigo or even as an approach to midbasilar artery aneurysms.54,55 Recently, a combined retrolabyrinthine and subtemporal exposure has

L

ES

P

7

8

Figure 43-31. Retrolabyrinthine craniotomy (left side) illustrating the surgical anatomy of the posterior fossa exposure. The dura has been incised anterior to the sigmoid sinus, allowing the endolymphatic sac (ES) to be retracted forward. A limited posterior fossa exposure in the region of the brainstem entry of cranial nerves 7 and 8 is provided. L, lateral semicircular canal; P, posterior semicircular canal; 7, facial nerve; 8, audiovestibular nerve.

become popular for transtentorial lesions, which are related to both the pons and midbrain (see later section on combined craniotomies).56,57 Technical Considerations: The RL approach is a posterior fossa craniotomy with a limited exposure to the midportion of the CPA. A curved skin incision is performed approximately 4 cm behind the postauricular sulcus. The mastoid periosteum is elevated to the level of the posterior aspect of the external auditory canal. With a cutting burr, the mastoid air cell system is thoroughly exenterated to the level of the semicircular canals. The anterior limit of the dissection is the osseous external auditory canal. Posteriorly, the sigmoid sinus is skeletonized with a cutting burr, as are approximately 2 cm of retrosigmoid dura. A large diamond burr is used to completely remove the bony covering of the sinus and adjacent dura. A thin bone plate (Bill’s island) may be left over the anterior aspect of the sigmoid sinus. This has been advocated by some to protect the sinus from injury by the rotating shaft of the drill when working more deeply within the temporal bone. When the bony island forms a cupula that restricts sigmoid retraction, it may be broken up into small plates (“cornflaked”) to facilitate retrodisplacement. Other surgeons completely remove this bony covering and use a retractor to guard the sinus from inadvertent injury. The sigmoid sinus must be exposed superiorly from the transversesigmoid junction to the jugular bulb region inferiorly in order to obtain the maximum posterior fossa exposure afforded by this technique. Although a 6- to 8-mm diamond burr is satisfactory for this task, we prefer a 10- to 12-mm burr, which is quicker and less traumatic. Frequently, mastoid emissary veins are encountered, which must be controlled with bipolar cautery. Lacerations of the sigmoid sinus or avulsions of emissary veins are readily controlled by extraluminal tamponade with hemostatic gauze (e.g., Surgicel). It is best to avoid intraluminal packing of the sigmoid sinus because this risks embolization of the packing material. The possibility of air embolism should also be kept in mind by the surgeon, although this risk is very low when the patient is in the supine position. After decompression of the sigmoid sinus, it is retracted posteriorly and the posterior aspect of the otic capsule is carefully skeletonized. Care must be taken to avoid entry into the posterior semicircular canal because this is likely to harm hearing. The dura is incised near to the sigmoid sinus and carried medially both along the superior petrosal sinus and toward the jugular bulb. This creates a rectangular dural flap, which contains but does not interrupt the endolymphatic sac. Exposure of the midportion of the CPA requires gentle retraction of the cerebellum posteriorly. The flocculus frequently must be mobilized through release of its arachnoid tethers. Selective vestibular neurectomy is accomplished by dividing the rostral fibers of the eighth nerve near the brainstem entry. Following completion of the procedure, the surgical defect is obliterated with an abdominal fat graft. This is necessary to avoid CSF leakage because watertight dural closure cannot easily be obtained. Advantages: The purported advantage of this approach compared with retrosigmoid craniotomy is a lower incidence of persistent postoperative headaches. However, little data is available that compares the two openings. Although most would agree that persistent headaches are more

Surgical Neurotology: An Overview

frequent with the RS approach when the IAC is drilled open, when the nerve is cut proximally (as in the RL approach), there may be little or no difference in the incidence of this bothersome complication. Meningitis and wound infection are infrequent following the RL approach, partly because of the relatively short duration of this procedure. Disadvantages: The primary disadvantages of the RL approach is its narrow field of action, which provides only limited exposure of the CPA. In general, when used as the sole opening, the RL approach is not particularly well suited for tumor surgery. A second disadvantage is the incidence of CSF otorhinorrhea, which is probably greater than that for a comparable RS approach performed without opening the IAC. This is due to the inability in the RL approach to close dura primarily. Finally, the need for a separate incision on the abdomen to harvest a fat graft may be seen as a disadvantage by some patients. Translabyrinthine Surgical Exposure: The TL approach is an anterosigmoid posterior fossa craniotomy, which provides exposure of the CPA including the lateral aspect of the pons, the ventral surface of the lateral cerebellar hemisphere and its associated peduncles, and the proximal portion of cranial nerves V, VI, VII, and VIII (Figs. 43-32 and 43-33).8,58–63 The root entry zone and CPA course of nerves IX, X, and XI is seen to a variable degree depending on the course of the sigmoid sinus. Indications: The primary indication for the TL approach is acoustic neuroma (Fig. 43-34).64–70 Ample exposure is afforded for even very large eighth nerve tumors. The approach may also be used for meningiomas, epidermoids, and other tumors of the CPA when hearing is poor.71,72

Figure 43-32. Translabyrinthine approach to a 2-cm acoustic neuroma in axial view. Bone is removed from the external auditory canal to behind the sigmoid sinus. The internal auditory canal is exposed by removal of the semicircular canals.

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GG 7

JV

7 Ca JB I S V V 11 10 9

7

8

SPS

6

5

Ch Fl Cb

T

SS D TS

Figure 43-33. Translabyrinthine craniotomy (left side) illustrating the surgical anatomy of the posterior fossa exposure. Ca, cochlear aqueduct orifice; Cb, cerebellum; Ch, choroid plexus; D, dura; Fl, flocculus; GG, geniculate ganglion; IV, inferior vestibular nerve; JB, jugular bulb; JV, jugular vein; SPS, superior petrosal sinus; SS, sigmoid sinus; SV, superior vestibular nerve; TS, transverse sinus. Cranial nerves: 5, trigeminal; 7, facial; 8, audiovestibular; 9, glossopharyngeal; 10, vagus; 11, accessory (cranial portion).

Cochleovestibular neurectomy can also be accomplished through this route.73 The TL approach is not suitable for tumors that extend into the inferior aspect of the posterior fossa because this region is obscured by the jugular bulb and the horizontal course of the sigmoid sinus.

Figure 43-34. Translabyrinthine approach to a medium-sized acoustic neuroma. Sufficient exposure is afforded to remove even very large cerebellopontine angle tumors.

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This anatomic limitation precludes exposure of the neural compartment of the jugular foramen or foramen magnum. The TL approach has also been advocated for aneurysms of the midportion of the basilar artery. For transtentorial lesions, the TL approach may be combined with a subtemporal opening (see later section on combined craniotomies).60,74 A combined TL and RS opening with sacrifice has been advocated for certain large CPA tumors in the past, but it is seldom used today.75 Technical Considerations In the TL craniotomy the bony opening extends from the posterior aspect of the external auditory canal to behind the sigmoid sinus.76 The amount of retrosigmoid bone removal depends on the size of the tumor being removed and the position of the sigmoid sinus. Although the distance between the sigmoid sinus and the ear canal is initially narrow, progressive removal of the petrous bone enlarges it substantially. Thorough removal of the bone overlying the sinus and the posterior fossa dura behind it is essential to permit its mobilization. This is accomplished by use of cutting burrs until the blue tint of the sinus is evident through a thin sheet of bone. The remaining plate is removed using large diamond burrs (see section on RL approach for further discussion). Use of large burrs is important because they are rapid and also present a relatively large working surface and are therefore less likely to tear the sinus or dura. The sigmoid should be decompressed from the transverse-sigmoid junction superiorly to the jugular bulb inferiorly. There is much variability to the anatomic location of the sigmoid sinus. When the sigmoid sinus lies far forward, it may even contact the ear canal. Even with such an adverse configuration, ample CPA exposure can be obtained. Following sigmoid mobilization, the remainder of the mastoid is rapidly removed to the level of the semicircular canals. In the process, bone is removed from the sinodural angle to expose the superior petrosal sinus. Labyrinthectomy is performed using a cutting burr, commencing in the sinodural angle. By creating troughs parallel to the middle and posterior cranial fossa dura, the remaining labyrinth can be removed with the side of the cutting burr. This is preferable because the tip of a rotating burr tends to skate and is therefore more difficult to control. The facial nerve is closely related to the inferior aspect of the lateral semicircular canal and to the inferoanterior end of the posterior semicircular canal. The final remnant of the semicircular canals is removed with a diamond burr to permit atraumatic exposure of the horizontal and second geniculate portions of the facial nerve. Deepening the opening beneath the facial nerve exposes the vestibule of the inner ear with all three semicircular canal ampullae and the otolithic organs. Obtaining this exposure is important in gaining access to the terminal portions of the superior and inferior vestibular nerves. Partial labyrinthectomy with sealing of the transected portion of the inner ear with bone wax has been proposed as a means of possibly sparing hearing.77 However, complete exposure of the fundus requires a wide opening of the vestibule, a maneuver very likely to severely traumatize the membranous labyrinth. Following labyrinthectomy, the bone deep to the labyrinth is then rapidly removed to the level of the IAC. As the exposure progressively deepens, the plate of bone over the posterior fossa dura is gradually

removed to the level of the porus acusticus. Removal of the middle fossa plate from the subtemporal dura is optional. Softening of the temporal floor permits extradural elevation of the temporal lobe and is indicated during exposure of large tumors. It is also helpful in small tumors when the tegmen lies at an unusually low level. Wide exposure of the IAC is an essential part of the procedure. Deep bony troughs are drilled above and below the canal to bring it into high relief. Superiorly, a furrow is created between the IAC and the middle fossa dura. Care must be exercised while removing the last eggshell of bone from the superior aspect of the canal because the facial nerve lies immediately beneath the dura in this location. The inferior furrow is created between the IAC and the jugular bulb. The cochlear aqueduct is often encountered while removing this bone and is a useful landmark in the identification and preservation of the dural envelope of the neural compartment of the jugular foramen.78 When the jugular bulb is atypically high, it may impede the creation of the inferior bony trough. In extreme cases, it may cover part or all of the IAC just proximal to the porus. Some have advocated decompression and inferior displacement of the high jugular bulb in such cases. This remains an option but adequate exposure can usually be obtained, in spite of this anomaly, by elevating the temporal dura and extending the superior trough to the level of the tentorium to provide enhanced exposure of the canal from its superior aspect. It is important to realize that a high jugular bulb, even though it may obstruct visualization of the midportion of the canal and the porus, does not obscure the lateral end of the IAC. Thus, even when the bulb is very high, the proximal facial nerve plane may be readily established. It should be stressed that the removal of bone around the IAC, particularly at the porus acusticus, should be aggressive. Inadequate beveling of the porus may leave an overhang that impedes visualization of the facial nerve at its vulnerable abrupt turn immediately medial to the porus. When the tumor is large, it is important to extend the bony opening well beyond the level of the IAC into the petrous apex to provide enhanced exposure of the anterior aspect of the CPA.79 The dura of the IAC is incised slightly inferior to its meridian to avoid potential injury to the facial nerve (FN), which usually lies superior and deep to the superior vestibular nerve. Separate flaps are then peeled superiorly and inferiorly to fully expose the canal contents. There are several methods of opening the dura of the posterior cranial fossa in the TL approach. In most widespread use is a flap that parallels the superior petrosal sinus above and inferiorly spans the gap between the sigmoid sinus and the apex of the jugular bulb. These are connected across the mouth of the porus acoustic, thereby creating a rectangular dural flap, which is then dissected off of the cerebellar surface. When opening the dural overlying the CPA does not result in the free flow of CSF, the inferior aspect of the cerebellum should be gently elevated to permit incision of the arachnoid of the cisterna magna before commencing tumor dissection. With this decompression accomplished, the cerebellar attachments to the tumor can be liberated, permitting its gentle retraction laterally. After mobilization of the cerebellum’s arachnoidal and vascular tethers, particularly to the petrosal veins superiorly, little retraction is

Surgical Neurotology: An Overview

required in smaller tumors. Significant cerebellar retrodisplacement may still be needed in large tumors that deeply invaginate the cerebellar peduncle. In a properly performed TL craniotomy, excellent exposure of the CPA is provided from the tentorium to the jugular foramen. Much as a high jugular bulb may obscure the IAC, a high lying sigmoid course may inhibit visualization of the inferior aspect of the CPA. While there is some association between high sigmoid course and high jugular bulb, either may occur in the absence of the other. Restricted access to the inferior portion of the CPA is seldom problematic in acoustic neuromas which, once debulked, readily mobilize into the operative field. In addition, acoustic tumors rarely adhere to the lower cranial nerves. Meningiomas, by contrast, adhere to dural surfaces and typically do not easily mobilize. They also are more likely to enmesh the lower cranial nerves. For this reason, we do not use the TL approach in nonacoustic tumors that extend inferiorly toward the jugular foramen and/or foramen magnum unless a concurrent transjugular craniotomy is planned. A partial dural repair is often possible following a TL craniotomy, but a substantial dural defect typically persists. Obliteration of both the osseous and dural defects is customarily accomplished with fat harvested from the abdomen or iliac crest region. Fat is laid in strips into the cavity until it tightly fills the defect from the dura to the skull surface. Frequently, some fat prolapses into the cavity left behind by tumor dissection and comes to abut the brainstem. Fortunately, adipose tissue is pliable and seldom induces a mass effect. Following a TL approach, the primary route for CSF leaks is via the aditus-ad-antrum, a narrow cleft located quite superficial within the craniotomy opening. A strip of fascia (temporalis or rectus) may be lain over this area in an attempt to seal it. Some surgeons prefer to obstruct the eustachian tube orifice through a facial recess approach. However, this opening increases the communication between the craniotomy cavity and the middle ear and provides only limited access to the tube orifice, making closure via this method somewhat insecure. Advantages: When compared with RS craniotomy, TL approaches have a somewhat lesser morbidity.47 This is most notable in the reduced incidence of persistent postcraniotomy headaches, which are quite frequent following the RS approach.44 Several factors may contribute to this including the minimization of brain retraction, the reduced level of trauma to the suboccipital musculature, and the ability to complete all drilling before the dura is opened. In the RL approach to acoustic tumors, the IAC must be drilled open intradurally, a maneuver that inevitably leads to some soilage of the posterior fossa arachnoid with bone dust and may contribute to postoperative aseptic meningitis. Although the literature is quite variable on its relative incidence, in our experience CSF leak is equally common among the various approaches to the CPA.49,80–83 Persistent CSF leak that follows an RS craniotomy is often repaired through a transtemporal approach.84 A second advantage of the TL approach becomes apparent when the facial nerve has become disrupted. To avoid a nerve graft, it is possible to mobilize the nerve out of its redundant course through the temporal bone, thereby gaining between 10 to 15 mm of length. This “mastoid-meatal”

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rerouting permits repair of short FN deficiencies with a single anastomosis, which is preferable to the two anastomoses required with interposition graft. In the RS approach, the only option for repair of an FN dehiscence when the ends are not approximated is nerve grafting. The TL approach also has a relative advantage over the RS approach under certain circumstances in the angle of view toward the brainstem. The more anterior perspective permits a more direct view of the brainstem surface, particularly when the tumor has posteriorly rotated and deeply indented the pons and middle cerebellar peduncle. By comparison, the exposure of the tumor interface via the RS approach is more tangential in such cases. A widely touted advantage of the TL approach is the ability to identify the FN at the lateral end of the IAC prior to its involvement with tumor. Although it is certainly reassuring to the surgeon to locate the FN at the earliest possible time, we have never had particular difficulty in identifying or preserving the FN during removal of the intracanalicular portion of an acoustic tumor. This advantage may be more important when anatomic arrangements are less predictable than in acoustic neuroma, such as in meningioma or in revision cases. Disadvantages: The primary disadvantage of the TL approach is the necessity of sacrificing hearing in the operated ear. This is less of a concern in acoustic tumors, where useful hearing can seldom be preserved, that it is for other lesions of the CPA and IAC such as meningioma and epidermoids. In many cases, the decision algorithm used to choose among the various surgical approaches is quite complicated and depends on numerous factors including tumor size, location, and type. While sacrificing hearing in an ear should never be taken lightly, in many cases it is warranted when the probability of preserving hearing is remote or when the anatomic features of the tumor indicate the need for more anterior exposure. A minor disadvantage of the TL approach is the requirement for a fat graft to obliterate the defect. To some individuals, this may create an undesirable abdominal scar. This can be easily avoided in women, who usually have a fat pad in the hip region, which is accessible through an incision placed just below the iliac crest. This hides the scar under the waistband of most bathing suits. As previously mentioned, the TL approach provides only limited exposure of the lower portion of the CPA, particularly when the lower sigmoid sinus course is relatively high. As a general rule, we prefer not to use this opening for nonacoustic tumors that extend inferiorly medial to the jugular foramen or toward the foramen magnum unless a concurrent transjugular exposure is planned. When the facial nerve takes an acute anterior angulation at the porus acusticus, the course of the displaced nerve is less well seen with the TL approach than with the RS approach due to its more posterior angle of view. It is possible to overcome this obliquity by mobilizing the nerve into the operative field, but we feel that dissection of the nerve-tumor interface is less traumatic when the nerve is left in situ throughout its cisternal course. Fortunately, the geometry involved is seldom troublesome and, in our experience, FN functional outcome in acoustic neuroma surgery is the same following either the TL or RS approach.

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Middle Fossa Craniotomies The MF or subtemporal approach is actually a versatile family of procedures carried out beneath the temporal lobe that may provide access to a number of anatomic regions. Historically, the earliest subtemporal procedures were performed to expose the trigeminal nerve in the treatment of tic douloureux. Over the past 20 years, the MF procedure has gained widespread application for exposure of the IAC and CPA in the management of small vestibular schwannomas, facial nerve lesions, and in the performance of selective vestibular neurectomy. MF procedures are also employed for other lesions in the temporal floor. Lateral to the otic capsule, the middle ear and mastoid may be opened from above to continue facial nerve exposure beyond the IAC, to gain exposure to tumors of this area, or to repair encephaloceles or CSF leaks through the tegmen. Medial to the otic capsule, lesions in the petrous apex and the lateral aspect of the clivus (e.g., tumors, cholesteatomas, cysts) may be addressed. Removal of the petrous apex permits exposure of the intrapetrous portion of the internal carotid artery. Approaches to the far anterior reaches of the middle fossa floor, particularly cavernous sinus procedures, are often accompanied by downfracture of the zygomatic arch to minimize the need for temporal lobe retraction. An MF opening may also serve as a route to the posterior fossa. The extended MF approach widens the IAC exposure and affords a limited view of the CPA. Removal of the portion of the petrous pyramid between the IAC and the Meckel’s cave creates an opening into the anterior, superior CPA and provides a small exposure of the ventral aspect of the upper pons. Finally, for tumors involving both fossae, an MF approach may be combined with any of the posterior fossa craniotomies (retrosigmoid, retrolabyrinthine, translabyrinthine, transcochlear) as circumstances warrant. For details of these procedures, see section “Combined Craniotomy of the Middle and Posterior Cranial Fossae.”

Figure 43-35. Schematic view of the internal auditory canal from above in the middle fossa approach.

the overhang of the transverse crest.86 In addition, the entry of the facial nerve into the labyrinthine segment direct visualization of the anterior portion of the fundus. When used in facial nerve lesions, the bony opening in the temporal floor is often extended to expose the facial nerve distal from the IAC into its labyrinthine segment and, by opening the tegmen tympani, in its horizontal course as well. Indications: A major indication for the MF approach to the IAC is tumors, particularly intracanalicular acoustic neuroma, but also facial nerve schwannomas, meningiomas,

Middle Fossa Approach to the Internal Auditory Canal Surgical Anatomy The MF approach to the IAC involves a small temporal craniotomy followed by extradural retraction of the temporal lobe to expose the temporal floor (Figs. 43-35 and 43-36).85 The superior aspect of the IAC is opened with a rotating burr. The MF approach is capable of exposing the entire IAC from its fundus laterally to the porus acusticus medially without violating any portion of the inner ear. Among approaches to the IAC, it is unique in this capability. To expose any portion of the IAC via the direct lateral (translabyrinthine) approach requires removal of the semicircular canals with resultant deafness in the operated ear. The posterior (retrosigmoid) approach to the canal is capable of exposing only approximately the medial two-thirds of the canal without exenteration of a portion of the otic capsule. Thus, the MF approach is particularly well suited for intracanalicular tumors where hearing conservation may be possible. However, limitations exist in exposing the fundus via the MF approach. The inferior compartment of the distal end of the IAC is obscured by

Figure 43-36. Middle fossa approach to an intracanalicular acoustic neuroma seen in surgical view. Note that the bony troughs around the internal auditory canal are wide medially at the porus but narrow laterally to prevent injury to the cochlea and semicircular canals. When the tumor has originated from the inferior vestibular nerve, the facial nerve may lie draped on the tumor’s superior surface, as depicted here.

Surgical Neurotology: An Overview

and vascular tumors, among others.87,88 It has also been widely used for nonneoplastic facial nerve diseases including repair of nerve injury associated with temporal bone fracture and decompression of the fallopian canal in Bell’s palsy and herpes zoster oticus.89,90 Vestibular neurectomy may also be accomplished via the MF route, although posterior fossa approaches have become more popular in recent years.91 A proposed indication is bony decompression of the IAC, without tumor removal, in patients with bilateral acoustic neuroma in an effort to retard progressive hearing loss.92 IAC decompression may also be undertaken in osseous dysplasias, such as Paget’s disease and osteopetrosis, where bony stenosis results in hearing deterioration or facial nerve dysfunction. Technical Considerations: For exposure of the IAC, the craniotomy should be centered over the canal. A relatively small opening, approximately 3 × 3 cm, is sufficient. Due to the anterior angulation of the petrous pyramid, the opening should be placed roughly two-thirds in front of the ear canal and one-third behind it. To minimize the need for temporal lobe retraction, bone should be removed flush with the temporal floor. The dura over the anterior face of the petrous bone is elevated to the level of the bony trough made by the superior petrosal sinus at the crest of the pyramid. There is usually no need to elevate the MF dura anteriorly toward foramen spinosum because this risks troublesome bleeding from the middle meningeal artery. A specialized MF retractor is very helpful in maintaining stable and atraumatic temporal lobe elevation.93 The temporal floor is often relatively flat and featureless. There are two methods of identifying the plane of the IAC. The technique popularized by William House involves tracing the greater superficial petrosal nerve to the geniculate ganglion and thereby identifying the fundus of the canal. Ugo Fisch advocates identification of the superior semicircular canal lying within the arcuate eminence and locating the canal at a 60-degree angle to it. The author tends to use whatever clues are most apparent to suggest the probable location of the canal and then to drill at the deepest point of the exposure directly toward the porus acusticus where the probability of injury to the otic capsule is least.94 Once the anterior and posterior extents of the IAC dura have been defined medially, the lateral portion of the canal is then unroofed (Figs. 43-37 and 43-38). Following completion of the procedure (tumor removal, neurectomy, nerve decompression, or repair), the cut air cells are waxed and a muscle plug is placed in the IAC. When the middle ear has been opened from above, a small bone graft harvested from the thin lower edge of the craniotomy flap is placed over the opening to prevent the temporal dura from resting on the ossicular heads and causing a conductive hearing loss. Advantages: The primary advantage of the MF approach to IAC lesions is the possibility of hearing conservation.95 The approach also provides access to the geniculate ganglion region—a site of predilection for facial nerve tumors, injuries, and inflammations—that is unequaled by other techniques. Disadvantages: In AN, the facial nerve may lie in a disadvantageous position, between the surgeon’s line of sight and the tumor, particularly when the tumor has originated from the inferior vestibular nerve (see Fig. 43-36).

695

EAC GG

ME

GSPN SSCC MMA

SPS

CO

7 SVN

Figure 43-37. Middle fossa approach to the internal auditory canal seen in surgical view. The external auditory canal (EAC), middle ear (ME), cochlea (Co), and superior semicircular canal (SSCC) normally lie beneath bone but are made visible as an aid to orientation. GG, geniculate ganglion; GSPN, greater superficial petrosal nerve; MMA, middle meningeal artery; SPS, superior petrosal sinus; SV, superior vestibular nerve; 7, facial nerve.

Although this is unlikely to result in severe injury to the nerve, it does require a greater degree of manipulation during tumor removal beneath it. In the author’s experience, this makes transient nerve dysfunction more common with the MF approach than with lateral (translabyrinthine) or

SV IV 7

Figure 43-38. Middle fossa vestibular neurectomy. After opening the internal auditory canal, a segment of both the superior (SV) and inferior (IV) vestibular nerves is removed including both Scarpa’s ganglia; 7, facial nerve.

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posterior (retrosigmoid) exposures of intracanalicular acoustic tumors. As a general rule, the temporal lobe is less forgiving of retraction than the cerebellum. Following the limited extradural retraction necessitated by an IAC approach, transient memory disturbances or auditory hallucinations may occur but are seldom of clinical significance. Dominant side retraction may result in disturbance of speech, although this is rare in IAC surgery and generally recovers promptly. Electroencephalogram (EEG) changes have been reported in the early postoperative period, but epilepsy is rare.96 Postoperative epidural hematoma may occur and have serious consequences if not promptly recognized. Risk of this complication may be minimized by tacking up the dura to the craniotomy flap during closure. Compared with other approaches to the IAC, a final disadvantage of the MF procedure is the significantly less cosmetically appealing head shave required. Extended Middle Fossa Approach to the Cerebellopontine Angle Surgical Anatomy The extended MF approach is a modification of the MF approach to the IAC designed to increase the degree of exposure of the CPA (see Fig. 43-39).97–99 By skeletonization of the superior semicircular canal and cochlea, the bone surrounding the porus acusticus can be widely flared. Exposure of a small extracanalicular tumor component can then be achieved by elevation of the superior petrosal sinus and tentorium. Increased exposure of the CPA may be realized by either of two maneuvers: exenteration of the otic capsule or division of the superior petrosal sinus and tentorial edge. Indications The extended MF approach to the CPA has been used increasingly in recent years. Its proponents recommend its use in small and medium-sized acoustic neuromas that possess both an IAC and CPA component.99–101 The practical upper limit on the use of this technique is with a tumor that has significant brainstem contact (approximately 15 to 18 mm) in the CPA component. Substantial hearing conservation has been achieved in these larger tumors but at the cost of some increased facial nerve morbidity.102 Technical Considerations Following a standard MF opening with unroofing of the IAC, bone anterior and posterior to the porus is exenterated to the level of the dura of the posterior petrous face (Fig. 43-39). The posterior limit of the opening is the superior semicircular canal. The theoretical anterior limit is the lateral wall of Meckel’s cave, although it is not usually necessary to remove bone that far forward. A particularly wide mobilization of the subtemporal dura is required to permit elevation of a broad segment of the superior petrosal sinus and tentorium. If division of the sinus is elected, its cut ends are controlled with hemoclips. Advantages When the otic capsule is preserved, the extended MF approach offers the possibility of removing small and

Figure 43-39. Extended middle fossa approach to an acoustic neuroma with a 2-cm component in the cerebellopontine angle. To achieve greater posterior fossa exposure, the superior petrosal sinus and the tentorium are divided.

medium-sized acoustic neuromas with the preservation of hearing. Disadvantages The main disadvantage of the extended MF approach is that the facial nerve may lie over the superior surface of the tumor in a position that requires it to be manipulated to a greater extent during tumor removal than with lateral (TL) or posterior (RS) techniques. At least in theory, the requirement for more prolonged and relatively vigorous retraction of the temporal lobe may increase the risk of postoperative speech and/or memory disturbance and may contribute to the delayed development of a seizure disorder. Fortunately, these complications are seldom encountered. Another concern is the limited exposure of the inferior aspect of the CPA. This may render it difficult to control vessels, such as the AICA and PICA, which may be situated below the tumor. Middle Fossa-Transpetrous Apex Approach to the Ventral Pons and Anterior Cerebellopontine Angle Surgical Anatomy The middle fossa-transpetrous apex (Kawase) approach employs a middle fossa opening to create a small posterior fossa craniotomy via removal of the medial portion of the petrous pyramid and the lateral aspect of the clivus (Fig. 43-40). 103,104 Conceptually, it is similar to the extended middle fossa approach but instead of exposing the mid-CPA, the target is the anterior CPA and the ventral surface of the pons (Fig. 43-41). The bony window in the petrous pyramid is rhomboidal. It is bounded posteriorly by the otic capsule and IAC, anteriorly by Meckel’s cave, inferiorly by

Surgical Neurotology: An Overview

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carotid from its bony canal; however, this maneuver carries a significant morbidity and is seldom justified. Indications The primary indication for the middle fossa-transpetrous apex approach are dumbbell-shaped tumors which, although predominantly located on the middle fossa floor, possess a small posterior fossa component.105–107 Particularly suitable are meningiomas and trigeminal schwannomas that traverse Meckel’s cave to involve both the middle and posterior cranial fossae. The ideal tumor is limited to the anterosuperior CPA and ipsilateral prepontine cistern. The middle fossa-transpetrous apex approach has also been used to expose aneurysms of the mid and lower basilar artery.108,109 Technical Considerations

Figure 43-40. Middle fossa-transpetrous apex (Kawase) approach to the ventral pons and the anterior cerebellopontine angle as viewed from above. By down fracture of the zygomatic arch and removal of the medial portion of the petrous pyramid, a view of the lateral and anterior portions of the upper pons is provided.

the petrous carotid artery, and superiorly by the tentorium. Posterior fossa exposure includes the pons, basilar artery, and cranial nerves V through VII. The posterior fossa exposure is limited inferiorly by the carotid artery in the base of the petrous pyramid. Enhanced inferior exposure can be obtained by displacement of the intrapetrous

The middle fossa-transpetrous apex approach requires a large, anteriorly placed bone flap. Fracture and downward displacement of the zygomatic arch flattens the angle of view and reduces the need for temporal lobe retraction. The petrous apex may be drilled either intra- or extradurally. When the tumor extends anteromedially toward Meckel’s cave and the cavernous sinus, intradural exposure is typically required. During removal of the dura of the anterior petrous face, the greater superficial petrosal nerve must be sacrificed. Care should be taken to identify and sharply section this nerve lest traction be placed on it during drilling, which might injure the facial nerve at the geniculate ganglion. To maximize the bony opening, the dura of the medial IAC and Meckel’s cave is exposed. Caution must be observed toward the lateral end of the IAC due to the proximity of the cochlea. The depth of petrous apex removal is dictated by the most inferior extent of the tumor in the posterior fossa. At its maximum, the horizontal carotid artery is skeletonized, leaving intact this eggshell of bone. By opening the dura of Meckel’s cave, the entire fifth nerve can be exposed from its brainstem origin to the foramen ovale inferiorly and the cavernous sinus superiorly. The posterior fossa exposure can be augmented, particularly in the posterior direction, by division of the tentorium. Advantages

Figure 43-41. Middle fossa-transpetrous apex approach to the ventral pons and the anterior cerebellopontine angle in surgical view. Following downward retraction of the zygomatic arch and temporalis muscle, the temporal lobe is elevated and the medial aspect of the petrous pyramid is removed between the cochlea and Meckel’s cave. This affords a view (inset) of the fifth (5), sixth (6), and eighth (8) nerves along with the lateral and ventral surface of the pons and upper portion of the basilar artery. Co, cochlea; V3, third division of the trigenical nerve at foramen ovale.

The middle fossa-transpetrous apex approach provides exposure of the ventral surface of the upper pons without sacrificing hearing, requiring facial nerve rerouting, or necessitating brainstem retraction, which may be needed in either the lateral or posterior approaches to this region. In selected tumors that involve both the middle and posterior cranial fossae, this approach permits tumor resection without the need for two separate or combined craniotomies (see the earlier section “Approaches to Lesions Primarily in the Cranial Base”). In addition, the middle fossatranspetrous apex approach, as a result of downward displacement of the zygoma and the removal of the apical petrous bone, requires substantially less temporal lobe retraction than the classically described middle fossa-transtentorial approach. Disadvantages The primary disadvantage of the middle fossa-transpetrous apex approach is its limited exposure of the posterior

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fossa contents. The abducens nerve is particularly vulnerable where it enters Dorello’s canal just deep to the posterior margin of the craniotomy. As a general rule, this approach is suitable for tumors that neither extend inferior to the nerve VII–VIII complex nor spread significantly across the midline. The only nerve inherently sacrificed in the process of the craniotomy, the greater superficial petrosal nerve, may result in a dry eye, although this is seldom troublesome in the absence of facial palsy. In addition, prolonged temporal lobe retraction may be required with its attendant risk of parenchymal hemorrhage or edema. Intracranial Aspect of Jugular Foramen The intracranial aspect of the jugular foramen (JF) can be viewed via the retrosigmoid approach (Figs. 43-42 and 43-43). This exposure is sufficient for tumors that are wholly intracranial or possess only small portions in the neural compartment of the JF. Most tumors (e.g., glomus, meningioma, lower cranial nerve schwannoma) that possess a substantial intracranial component also extensively involve the skull base. However, some meningiomas arising from the lower clivus, sigmoid sinus, or posterior petrous ridge spread along the dural surface and prolapse to a limited degree into the funnel-shaped dural envelope surrounding the lower cranial nerve entry into the skull base. Analogous to opening of the posterior aspect of the IAC, the neural compartment of the JF may be exposed to a degree working from behind via the RS approach. Most JF tumors with an intracranial component require a transjugular craniotomy.110,111 This technique differs from the presigmoid (transpetrosal) and retrosigmoid approaches in that, taking advantage of the fact that these tumors typically occlude venous flow within the jugular foramen, it involves resection of the sigmoid sinus (Figs. 43-44 through 43-46). This affords an augmented view of the lower CPA in the region of the intracranial component of the JF tumors. Transjugular craniotomy permits singlestage resection of virtually all large JF tumors. On rare occasions, a two-stage procedure may be selected when a very large neck component exists. Extensive neck dissection, when combined with a sizable cranial base defect,

A

B Figure 43-43. Limited access to the neural compartment of the jugular foramen can be obtained by drilling open the intracranial aspect of foramen during retrosigmoid craniotomy (A). Tumor, most commonly meningioma, is microdissected from the lower cranial nerves (B).

IAC

HC Figure 43-42. A saggital section through the midline illustrating the jugular foramen and its osseous relations from the medial perspective. Tumors of the jugular foramen are often dumbbell shaped, possessing both an intra- and an extracranial component connected by a segment within the cranial base. HC, hypoglossal canal; IAC, internal auditory canal.

presents a high risk of pseudomeningocele formation. To discourage CSF leakage into the extracranial resection cavity, tissue planes should be opened to the least possible degree (e.g., no skin flaps are elevated) and meticulous hemostasis should be obtained to avoid the need for placement of a drain, which would only encourage flow across the dural defect. When staging of a glomus tumor is elected, it is essential to resect the neck component first because this serves to devascularize the intracranial aspect. Technical features of a transjugular craniotomy include wide pre- and postsigmoid dural exposure. The sigmoid sinus is ligated just below the transverse-sigmoid junction, the jugular view is tied off in the upper neck, and the petrosal

Surgical Neurotology: An Overview

699

VA XI X IX

V

Ch Cb VII, VIII

F

Figure 43-44. Transjugular craniotomy illustrating the degree of intracranial exposure obtained following resection of the sigmoid-jugular system and wide opening of the posterior fossa dura. Note the multiple small rootlets of the lower cranial nerves emanating from the lateral surface of the medulla. In contrast to extracranial procedures, the sigmoid sinus is ligated proximally rather than packed extraluminal. Cb, cerebellum; Ch, choroid; F, flocculus; VA, vertebral artery; 5, trigeminal nerve; 7, facial nerve; 8, audiovestibular nerve; 9, glossopharyngeal nerve; 10, vagus nerve; 11, accessory nerve.

sinuses are controlled with Surgicel in the medial aspect of the jugular bulb. In most cases the ear canal and inner ear can be left in situ. Hearing can often be conserved in JF tumors even with large intracranial components. The ear canal is removed and the meatus sewn shut in only two circumstances: when extensive erosion of the middle ear and canal wall precludes their preservation and when

Figure 43-46. Exposure of a jugular foramen schwannoma after transection and removal of the sigmoid sinus and jugular bulb. Note that the fan of fibers comprising the ninth, tenth, and eleventh nerves takes an oblique course between their horizontally oriented intracranial roots and their vertically aligned peripheral trunks. In this case, the residual nerve fibers are positioned on the medial surface of the tumor.

augmented anterior exposure of the apical petrous bone and carotid artery is needed. In our experience, rerouting of the facial nerve is seldom required even with extensive intracranial disease. The relationship of the lower cranial nerves to the tumor penetrating the jugular foramen is the key determinant in whether the nerves can be preserved.110,112 When the nerves lack function preoperatively, they are resected with the tumor. When at least partial function remains, a diligent effort at their microsurgical preservation should be undertaken with neurophysiologic guidance. Meningiomas that arise laterally and glomus tumors are most favorable for neural preservation. Meningiomas that arise off the lower clivus and penetrate the neural compartment from its medial aspect present themselves medial to the fan of lower nerve roots and neural preservation is technically challenging. Some larger glomus tumors come to lie medial to the lower nerve through deep penetration along the petrosal sinuses.

The Ventral Surface of the Brainstem Combined Craniotomy of the Middle and Posterior Cranial Fossae

Figure 43-45. Transjugular craniotomy without rerouting of the facial nerve. Leaving the facial nerve in situ is not an impediment to exposure to the intracranial region adjacent to the jugular foramen.

Tumors that possess sizable components both above and below the tentorium represent a particularly arduous surgical endeavor.113 The majority are intimately related not only to the pons but to the midbrain as well. The most obvious approach to such lesions is to perform separate craniotomies of both the middle and posterior cranial fossae, either at one sitting or in two stages. A combination of retrosigmoid and middle fossa craniotomies has been employed by some surgeons, but this approach has several distinct disadvantages (Fig. 43-47).114,115 Foremost among

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4 MB

P 5 T

Figure 43-47. The classical method of exposing both the posterior and middle cranial fossae is by creating two separate opening: retrosigmoid and subtemporal. This disconnected approach, with the surgical exposures separated by the transverse sinus superficially and the tentorium in the depth, necessitates a much greater degree of brain retraction than contemporary approaches to tumors that involve both fossae.

these are the need for significant retraction of both cerebellum and temporal lobe and the tendency to place traction on the vein of Labbé. In addition, exposure ventral to the pons is quite limited due to the posterior angulation afforded by the retrosigmoid infratentorial opening. The degree of brain retraction required to gain access to both the supra- and infratentorial regions simultaneously may be substantially reduced by partial or total petrosectomy. The cranial base defect created by removal of the temporal bone provides a cavity through which the surgeon can visualize both above and below the tentorium with relatively little brain retraction. The amount of petrous bone removed depends on a number of factors—the status of hearing, the size and location of the tumor, and the severity of brainstem compression, among others. The most frequently employed of the transtemporal-middle fossa procedures is the retrolabyrinthine-middle fossa approach, which offers the potential of maintaining hearing (Fig. 43-48 through 43-51).56,54,116–126 A minor enhancement of exposure with the retrolabyrinthine approach may be obtained through partial labyrinthectomy.127 Combinations of translabyrinthine or transcochlear openings with the middle fossa approach may also be used under certain circumstances.128,129

Figure 43-48. Division of the tentorium in the combined-approach craniotomy. Care must be exercised when dividing the free margin to avoid injury to the fourth cranial nerve. MB, midbrain; P, pons; T, tentorium; 4, trochlear nerve; 5, trigeminal nerve.

the brainstem. The tentorium cerebelli, a collagenous dural membrane, separates the posterior and middle cranial fossae. Posteriorly, the tentorium attaches to the transverse sinuses and the internal occipital protuberance. Anterolaterally, it attaches to the crest of the petrous ridge where it intermingles with the dura surrounding the superior petrosal sinus. Anteromedially, the tentorium terminates in a free edge dorsal to the midbrain. The space between the free edge of the tentorium and the brainstem is known

VL

VL

Surgical Anatomy The anatomy of the various middle and posterior fossae craniotomies will not be repeated here, but certain anatomic features relevant to interconnecting the middle and posterior fossae will be reviewed. Tumors that traverse the tentorial plane usually pass through the tentorial notch, Meckel’s cave, or the space between the clivus and

Figure 43-49. Combining a retrolabyrinthine posterior fossa craniotomy with a middle fossa craniotomy and splitting the tentorium provides exposure of transtentorial tumors that involve the lateral aspect of the pons and midbrain. Retraction of the posterior portion of the temporal lobe should be gentle to prevent injury to the vein of Labbé (VL).

Surgical Neurotology: An Overview

4

701

Certain tumors, particularly meningiomas and trigeminal schwannomas, involve both the middle and posterior fossae by traversing Meckel’s cave. Meckel’s cave is a dural reflection that houses the trigeminal nerve and its semilunar ganglion. It overlies the medial aspect of the petrous apex and is bounded superiorly by the petroclival ligament. Its superomedial border is related to the abducens nerve in its course through Dorello’s canal. Combined transtemporal-middle fossa procedures usually expose the pons, midbrain, and cranial nerves IV through VIII. Cranial nerves II, III, and IX through XI may be readily exposed when required. The amount of pontine exposure depends on the extent of petrous bone resection. With the retrolabyrinthine approach, only the lateral aspect of pons is visible; with the transcochlear approach, the ventral aspect of the brainstem can be visualized as well. Indications

Figure 43-50. Combined approach craniotomy to a meningioma involving the posterior petrous pyramid, the clivus, Meckel’s cave, and the cavernous sinus. 4, trochlear nerve.

as the tentorial notch, or incisura. The trochlear nerve closely parallels the free edge of the tentorium and is frequently at risk in transtentorial procedures. Immediately beneath this edge is the petrosal vein (Dandy’s vein) and the superior cerebellar artery usually lies just above it.

TL T

T

9 7 8

4

Cb 5 P MB

Figure 43-51. The exposure obtained from a left retrolabyrinthine-middle fossa approach to a clival tumor. This technique is indicated when the lesion has an intimate relationship with the anterior surface of the brainstem and vertebrobasilar system. It is also capable of addressing a tumor component that lies posterior to the internal carotid artery, an area not accessible via the anterior approaches. The tentorium has been incised to provide exposure of both posterior and middle cranial fossae through gentle retraction of the cerebellum and temporal lobe. The tumor can be seen prolapsing posteriorly from the clivus with indentation of the brainstem and splaying of the cranial nerves. Cb, Cerebellum; MB, midbrain; P, pons; T, tumor; TL, temporal lobe; 9, glossopharyngeal nerve; 4, trochlear nerve; 5 trigeminal nerve; 7, facial nerve; 8, audiovestibular nerve.

Tumors that involve both posterior and middle fossae may be divided into two broad classes: those that require a wide exposure of both fossae and those that require a large exposure of one fossa and only a limited opening of the other. Among tumors that require wide exposure of both fossae, meningioma is by far most common. In the spectrum of technical difficulty, meningiomas that arise from the tentorium are usually more readily approached due to their lateral location. At the other end of the difficulty scale are extensive clival meningiomas, which are particularly challenging because of their deep midline location as well as their intimate relationship with the vertebrobasilar system. Tumors that predominantly lie in either the middle or posterior cranial fossa and possess only a small extension into the other fossa may occasionally be managed by modification of conventional middle or posterior fossa craniotomy technique. For example, during transtemporal approaches to the CPA, the tentorium may be elevated or even divided to enhance superior exposure for some distance above the tentorium into the incisura. Similarly, tumors that traverse Meckel’s cave are often asymmetrically bilobed with a predominant component in one fossa. Tumors largely on the temporal side with a small posterior fossa component can be approached via a middle fossa-transpetrous apex approach. Conversely, when the posterior fossa component predominates, a limited opening through Meckel’s cave may be created during posterior fossa craniotomy. In either the retrosigmoid or translabyrinthine approaches, this may be accomplished by drilling away a rhomboidal portion of the petrous apex between the IAC and Meckel’s cave. This maneuver is analogous to that used in the middle fossa-transpetrous apex approach, but it is done in reverse, from posterior to anterior. Technical Considerations The details of the various middle fossa and transtemporal approaches (retrolabyrinthine, translabyrinthine, and transcochlear) will not be repeated here and the reader is directed to the relevant section of this chapter. A special consideration of the combined approaches is the need to divide the tentorium. The superior petrosal sinus can usually be easily controlled by application of hemoclips. Care must be exercised when dividing the free edge of the tentorium to prevent injury to the trochlear nerve.

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The cortical veins on the inferior aspect of the temporal lobe merit special mention because they are a potential cause of significant morbidity during extensive subtemporal procedures.130 The vein of Labbé constitutes the major superficial venous drainage of the posterior temporal and inferior parietal lobes (Fig. 43-7). Interruption of Labbé’s vein on the dominant side frequently induces aphasia. The left side is dominant in approximately 95% of individuals— 100% of right-handed and 80% of left-handed persons. Less common, massive swelling may occur followed by uncal herniation and ultimately death due to brainstem herniation. Labbé’s vein is at greatest risk posteriorly, near its entry to the transverse sinus. Retraction of the posterior portion of the temporal lobe must be performed gently, lest traction be placed on this vein, which tears quite easily. Since prolonged retraction of the temporal lobe may induce thrombosis of Labbé’s vein, it is wise to release retraction periodically for short periods during lengthy procedures and to use the minimal degree of retraction needed to provide adequate surgical exposure. To reduce traction placed on the vein of Labbé during combined procedures, Spetzler and Daspit advocate division of the sigmoid sinus (when the contralateral sinus is patent) distal to the takeoff of the superior petrosal sinus.121,131 This permits the lateral sinus, along with the entry of the vein of Labbé, to be retracted superiorly along with the tentorium.

There are actually three varieties of “transcochlear” approaches: (1) the original TC approach described by House in 1976 to approach the anterior CPA, (2) the extended TC approach to the prepontine region and clivus, and (3) the transotic approach described by Fisch to remove small acoustic neuromas.132–135 The term transcochlear has been adopted to describe an extension of the translabyrinthine approach that entails an exenteration of the entire inner ear, not just the semicircular canals. It should be noted that many TC operations involve a great deal more than mere removal of the cochlea and may be more aptly termed transpetrosal or even petroclival craniotomies. Intracranial structures that can be exposed by the classical TC approach include the entire lateral aspect of the pons and upper medulla, cranial nerves V through XI, as well as the midbasilar artery. Its posterior fossa exposure is extensive except inferiorly where it is limited in the area of the jugular foramen and foramen magnum. The degree to which the neural compartment of the jugular foramen is visible depends on the height of the jugular bulb. Modifications to the TC approach have been described which, in addition to the exposure provided by the standard TC approach, permit visualization of the anterior aspect of the pons, both sixth nerves, and improves visualization of the basilar artery and vertebrobasilar junction.133,136 The transotic approach of Fisch is the most limited of the three, designed to expose only the IAC and mid-CPA.132

Advantages

Indications

Combining a posterior and middle fossa exposure into a single craniotomy around and/or through the temporal bone has a number of advantages. First and foremost, it reduces the amount of brain retraction needed to expose complex lesions adjacent to the brainstem. Second, it typically requires only a single-stage procedure where two stages might otherwise have been needed. Finally, combined transbasal craniotomy often permits a greater degree of tumor resection than could be achieved by separate retrosigmoid and subtemporal procedures.

The primary indication for the TC approach are CPA tumors such as meningiomas, which penetrate the petrous apex medial to the IAC. Lesions that arise in the apex (e.g., chondrosarcoma, chordoma) can also be approached in this manner particularly when they possess substantial intradural components. For tumors limited to the upper aspect of the prepontine space that do not encase the basilar artery, the subtemporal transpetrosal approach is occasionally a viable alternative. An additional indication for the TC approach is a large recurrent or residual acoustic neuroma when the facial nerve has been disrupted during the earlier surgery. When the audiovestibular and facial nerves are intact, every effort should be made to employ an alternative approach that does not sacrifice these functions. In our institution, the TC approach has been seldom used in recent years because of its morbidity (deafness, facial nerve dysfunction), having been supplanted in most cases by the combined-approach craniotomy. The TC approach is still used in cases of preexisting facial palsy and for certain vascular lesions such as midbasilar artery aneurysms. The extended TC approach is indicated for tumors that lie ventral to the brainstem, typically between the clivus and pons. The most common reason for performing an extended transcochlear approach is meningioma of the clivus of petroclival region. The conventional retrosigmoid approach to lesions that lie directly anterior to the pons is limited by (1) the narrow opening between the pons and petrous pyramid when viewed from behind, (2) cranial nerves V, VII, and VIII, which bridge across the exposure and constrain working space to narrow intervals between these nerves, and (3) the need for vigorous retraction of the cerebellum and pons (Figs. 43-52 and 43-53). In contrast to purely prepontine tumors, many petroclival

Disadvantages There are few disadvantages of combined posterior and middle fossa craniotomy when compared with separate procedures. Of course, aggressive removal of the temporal bone sacrifices hearing, but a hearing-sparing retrolabyrinthine-middle fossa technique often provides sufficient exposure. Although unilateral hearing loss may be required for tumors extending ventral to the brainstem, this is not an unreasonable sacrifice in the context of these serious lesions. Posterior facial nerve rerouting (transcochlear-middle fossa approach), which induces at least a temporary facial palsy, should be reserved for particularly complex tumors located largely in front of the pons. Transcochlear Approach Surgical Exposure The transcochlear (TC) approaches are a group of three anterosigmoid posterior fossa craniotomies which, when compared with the translabyrinthine approach, provide an enhanced view of the anterior aspect of the CPA.

Surgical Neurotology: An Overview

ET

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CA

Figure 43-52. Transcochlear approach to a prepontine tumor seen schematically in axial view. The facial nerve has been fully rerouted from the brainstem to the stylomastoid foramen and the external auditory canal, as well as both middle and inner ear have been removed. The eustachian tube (ET) is occluded. The intrapetrous carotid (CA) is the anterior limit of the exposure.

lesions can be removed successfully via the retrosigmoid approach. Such lesions displace the brainstem toward the opposite side, thereby opening the choke point between the pons and petrous bone. This geometric arrangement can be appreciated on preoperative MRI scans. The additional morbidity of the extended TC approach (unilateral hearing loss, transient facial palsy) is justified by the direct and unencumbered view provided of the anterior and lateral pontine surface. In these life-threatening lesions, direct visualization of the tumor-brainstem and tumor-basilar artery interface is critical to achieve adequate tumor resection and limit the risk of pontine infarction. The extended TC approach also provides a more favorable angle for the identification and preservation of the abducens nerve. Technical Considerations The initial stages of the TC approaches are identical to those of the TL approach. In addition, both of the TC and extended TC approaches involve complete exenteration of the inner ear (cochlear and semicircular canals) as well as a posterior rerouting of the facial nerve. The facial nerve is elevated from its canal over its entire course from the stylomastoid foramen to the porus acusticus. It is then rotated posteriorly and inferiorly on the cerebellar hemisphere and posterior fossa dura. This removes the major impediment to anterior exposure in a transtemporal craniotomy. These maneuvers permit opening of the posterior fossa dura to extend substantially more anteriorly and medially than with the TL approach. In the classical TC opening the external auditory canal and middle ear are left intact, but in the extended TC

Figure 43-53. Transcochlear approach to a prepontine tumor seen schematically in axial view (a) and in surgical perspective (b) (left side). By rerouting the facial nerve and exenterating the entire otic capsule, petrous apex, and lateral aspect of the clivus, an unobstructed view is obtained of the ventral aspect of the pons. Cb, cerebellum; Ch, choroid; ET, eustachian tube; Fl, flocculus; JV, jugular vein; SPS, superior petrosal sinus; SS, sigmoid sinus; TS, transverse sinus; 5, trigeminal nerve; 6, abducens nerves; 7, posteriorly rerouted facial nerve; 8, transected audiovestibular nerve.

approach both of these structures are removed and the external auditory meatus is closed in a fashion that is watertight to resist CSF pressure. Extended TC procedures remove the entire apical petrous bone and often the lateral aspect of the clivus as well. The inferior limits of exposure inferiorly are the jugular bulb and intrapetrous portion of the carotid artery. In both the classical and extended TC approaches the operative defect is obliterated with abdominal fat. In the extended TC approach the eustachian tube is obliterated to prevent CSF leakage, typically with bone wax followed by a muscle plug. The transotic approach differs substantially for the TL and other TC approaches in that the sigmoid sinus is not decompressed and only a limited posterior fossa opening is created. As in the extended TC approach, the ear canal and middle ear are completely removed, the meatus sewn shut, and the eustachian tube obliterated. The transotic technique is the only version of the TC approach that leaves the facial nerve in situ. Advantages The TC approaches, especially the extended TC approach, provides access to tumors anterior to the pons that would, in many cases, otherwise be considered inoperable. Often, the ventral surface of the pons can be visualized without the need for brain retraction. The transotic approach has been recommended by its inventor as a means of approaching small acoustic neuromas without brain retraction while minimizing the risk of CSF leakage.

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Disadvantages As the cochlea is removed during the craniotomy, deafness in the operated ear is inevitable. In addition, posterior rerouting of the facial nerve usually results in a transient total facial palsy. Recovery generally occurs over 6 to 12 months but may be incomplete with a degree of asymmetry and synkinesis. Posterior rerouting requires sacrifice of the chorda tympani and greater superficial petrosal nerves, which results in minor diminution in taste and an ipsilateral dry eye. In contrast to posterior rerouting for the TC approach, anterior rerouting of the facial nerve to expose the jugular foramen region often leaves facial function intact, and when transiently impaired, it usually returns to normal.

Meckel’s Cave The operative approach to Meckel’s cave depends on whether the tumor is largely in the middle fossa, posterior fossa, or bilobed with substantial components in both fossae5,137 (Figs. 43-54 through 43-56). Analogous to opening of the IAC during the RS approach, Meckel’s cave may also be exposed to a degree working from behind and below. By removing the bone of the petrous apex between the IAC and tentorium, the posterior and inferior aspect of Meckel’s cave and the trigeminal ganglion within it can be exposed. This maneuver is particularly helpful in the removal of petroclival meningiomas that penetrate Meckel’s cave as well as in trigeminal schwannomas that possess only a small subtemporal component. The rhomboidal bony opening created in opening Meckel’s cave from behind is identical to that exenterated from above during the subtemporal-transpetrosal (Kawase) approach. Meckel’s cave tumor with substantial components in both fossae are approached via a combined retrolabyrinthine-subtemporal craniotomy138–140 (Fig. 43-57).

The Craniovertebral Junction Surgical Anatomy

Figure 43-55. Trigeminal schwannoma with a predominant posterior fossa component is approached via a retrosigmoid posterior fossa craniotomy in which Meckel’s cave is opened from behind.

problems, approaches to anteriorly placed intradural lesions may benefit from the skills of a neurotologist who is familiar with the posterolateral skull base. Conventional FM approaches involve removal of the posterior aspect of the osseous ring combined with suboccipital craniotomy and laminectomy of one or more cervical vertebra. However, this opening affords negligible exposure of the ventral aspect of the medulla and upper cervical spinal cord. A transoral route has long been used successfully for anteriorly placed extradural lesions (e.g., odontoid fractures, intraosseous tumors). The problem with such exposures for intradural lesions is the need to create a large and difficult-to-reconstruct opening between the pharynx and the subarachnoid space with resultant high risk of CSF leakage and infection.42 An additional problem with the midline transoral approaches is its limited ability to deal with lateral tumor extensions.141,142 Anterior transcervical approaches that traverse the clivus have also been proposed.143 These limitations with anterior and posterior

Although most posteriorly placed tumors that involve the foramen magnum (FM) region are purely neurosurgical

Figure 43-54. Trigeminal schwannoma with a predominant middle fossa component is approached via a subtemporal transpetrous apex approach.

Figure 43-56. A bilobed trigeminal schwannoma with significant components in both the posterior and middle fossae is approach via a combined-approach craniotomy (retrolabyrinthine-subtemporal) made confluent by division of the tentorium.

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HC

Figure 43-57. Operative view of a combined-approach craniotomy to a bilobed trigeminal schwannoma.

approaches lead to the development of far lateral approaches to the craniovertebral junction. The lateral approach to the FM provides exposure of the lateral aspect of the pons, medulla, and upper cervical spinal cord.144–150 The space ventral to the brainstem and spine is also brought into view to a variable degree depending on both the aggressiveness of bony removal (particularly the extent of condylectomy) and the degree to which the tumor has posteriorly displaced these structures. Cranial nerves IX through XII and the upper cervical nerve roots are in the surgical field. The approach is readily combined with a wide posterior fossa craniotomy with exposure of cranial nerves V through VIII in the cerebellopontine angle.

Figure 43-58. Far lateral approach to the foramen magnum. Superior perspective of the cranial base illustrating the extent of osseous removal.

remaining suboccipital convexity is removed to the level of the foramen magnum ring. The attachments of the suboccipital musculature can be liberated rapidly with electrocautery. As the FM is approached, caution must be exercised while dividing muscles and ligaments not to stray from the plane of the cranial base to prevent injury to the vertebral artery coursing over the arch of the atlas. Extradural elevation of the cerebellum opens the narrow cleft at the lateral aspect of the craniovertebral junction and permits orderly removal of bone using a rotating burr. As the last portion off the FM ring is removed, a diamond burr is used to prevent injury to the marginal sinus.

Indications The primary indication for the far lateral approach to the FM is anteriorly situated meningiomas that straddle the craniovertebral junction.151,152 It may also be useful in a variety of other benign and low-grade malignant tumors that affect this region. A potential role in the management of aneurysms of the lower vertebral artery has also been proposed.153

C JF FN EC

Technical Considerations The lateral approach to the FM begins with removal of the suboccipital convexity and laminectomy of the upper cervical vertebra as required for cervical extension of the tumor. In preparation for removal of the lateral aspect of the FM, the ring bone is removed up to the sigmoid sinus, the posterior margin of which is exposed throughout its cranial base course all the way to the jugular foramen (Figs. 43-58 through 43-60). To prevent injury to the vertical segment of the facial nerve in the mastoid, which lies just superficial to the jugular bulb, mastoidectomy is performed with identification of the fallopian canal. After removal of bone behind the entire sigmoid course, the

Figure 43-59. Far lateral approach to the foramen magnum. Inferior perspective of the cranial base illustrating the extent of osseous removal. Note the direct lateral angle of view achieved through partial removal of the occipital condyle. C, occipital condyle; JF, jugular foramen; FN, facial nerve at stylomastoid foramen; EC, ear canal.

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transoral approaches, the lateral exposure of FM eliminates the need for traversing bacterially contaminated regions and has a lower potential for CSF leak. Exposure of both the intra- and extracranial portions of the vertebral artery reduces the risk of vascular injury and affords an opportunity to establish vascular control in the event the vessel is injured. Disadvantages

Figure 43-60. Far lateral approach to the foramen magnum. The osseous opening involves retrosigmoid craniotomy, upper cervical laminectomy, and mastoidectomy to permit tracing of the inferior aspect of the sigmoid sinus to the jugular bulb without risking injury to the descending facial nerve. Exposure of the ventral aspect of the pons, medulla, and cervical spine is created through the intervals between the lower cranial nerves (IX–XII) and the upper cervical roots. The view of the brainstem is obscured, in this illustration, by the presence of a lower clival meningioma.

As removal of the ring proceeds anteriorly, it broadens to form the occipital condyle. A variable portion of the occipital condyle is removed depending on the location of the tumor. In the process of removing the condyle, the posterior condylar vein is encountered. This often impressively large branch, which communicates with the jugular bulb, is occluded with bone wax or Surgicel. After dural incision the tumor can be seen ventral to the medulla and spinal cord through the overlying lower cranial nerves IX through XII and the upper cervical roots. Tumor removal is impeded somewhat by the interposition of these nerves so the surgeon must either work through the narrow intervals between nerve fibers or sacrifice some of them. The spinal portion of the accessory nerve is at particular jeopardy. We have found that electrophysiologic monitoring of the lower cranial nerves provides the surgeon useful information while dissecting around these nerves.154 Anterior lesions at the FM are typically intimately related to the vertebral artery and vertebrobasilar junction. Exposure of the vertebral artery from its emergence out of foramen transversarium across the atlas to its dural penetration and ultimately to its junction with the basilar artery is an essential part of this procedure. Particular care must be exercised in liberating the dural cuff that surrounds the vessel during its intracranial penetration. Advantages The primary advantage of the far lateral approach is its ability to expose inaccessible lesions ventral to the brainstem while minimizing brain retraction. When compared with

The tumor must be removed through a veil of closely spaced fibers of the ninth, tenth, eleventh, and twelfth cranial nerves. Often, some of these must be sacrificed; others may be temporally dysfunctional due to the effects of microsurgical manipulation. Postoperative aspiration may require a temporary tracheotomy. Our policy is to perform a tracheotomy at the time of craniotomy when fibers of both the ninth and tenth nerves are taken. Otherwise, the patient is observed in the intensive care unit for several days and feedings begun if a cine barium swallow does not indicate a tendency to aspirate. Even with pronounced postoperative aspiration, the patient’s swallowing ability gradually recovers over several weeks. Augmentation of the paralyzed vocal cord (e.g., Teflon injection) is often beneficial. Excessive removal of occipital condyle may theoretically lead to craniovertebral instability or torticollis, although this has not been our experience to date. Reconstruction of the condyle with a bone graft may reduce this risk.

Vertebrobasilar Lesions Cranial base approaches are sometimes used in vascular lesions of the vertebrobasilar system. The subtemporaltransapical approach was first described by Kawase for the exposure of basilar tip aneurysms.155,156 Rare aneurysms of the horizontal segment of the intrapetrous carotid artery may all be exposed subtemporally. Aneurysms of the midbasilar artery are among the most challenging of intracranial vascular lesions (Figs. 43-61 and 43-62). In contrast to most prepontine tumors, the brainstem has neither been posteriorly displaced nor rotated to facilitate exposure of its ventral aspect. Exposure of midbasilar artery aneurysm is one of the few instances in which we still recommend the classical transcochlear approach with complete rerouting of the facial nerve and sacrifice of hearing.157 A lateral, transcondylar approach to foramen magnum is often helpful in the exposure of aneurysms of the vertebrobasilar junction and intracranial segment of the vertebral artery. Intraparenchymal vascular malformations of the brainstem are sometimes best approached via the lateral perspective afforded by the transtemporal approach. Exophytic brainstem tumors that involve the CPA can also be approached transpetrosally.158

RECONSTRUCTION OF THE CRANIAL BASE Closure of Defects The workhorse for closing skull base defects (see also Chapter 59) is free adipose tissue harvesting from the

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Figure 43-63. Obliteration of a translabyrinthine defect with overlapping strips of abdominal adipose tissue. Figure 43-61. Schematic axial view of a transcochlear approach to a midbasilar artery aneurysm.

abdomen of iliac crest region (Fig. 43-63). For more extensive defects, particularly to repair the temporal floor in encephalocoele, a temporalis muscle rotational flap is versatile (Fig. 43-64). Most often only the posterior half is needed, thus avoiding a cosmetically significant hollowing of the temple. This flap is also commonly used in temporal bone resection for cancer to provide a vascularized closure in preparation for radiation therapy. In extensive defects of the cranial base, particularly those associated with a cutaneous defect, a regional myocutaneous flap is indicated (Fig. 43-65). Options often selected include the trapezius and pectoralis flaps. When these flaps have been compromised, a free flap, such as the rectus abdominis, is selected.

Figure 43-62. Aneurysm of the midbasilar artery viewed through a transcochlear approach. The facial nerve had been posteriorly rerouted. The anterior limit is the carotid genu.

Prevention of Cerebrospinal Fluid Leakage Prevention of CSF leakage is a central theme in neurotologic surgery. Free adipose tissue grafts, which shrink by about 50% of their initial volume over time, obliterate defects and foster formation of a neodura on their medial aspects. Others advocate use of hydroxylapatite or other synthetic obliterative material.159 In transtemporal craniotomies, it is sometimes possible to reconstruct the dural

Figure 43-64. Temporalis muscle rotation flap. Often only the posterior half of the muscle provides sufficient coverage. Using only this portion of the muscle eliminates the need for fenestration of the zygomatic arch and prevents a cosmetic defect in the temporal region.

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Skin incision Muscle incision Pivot point of flap

Figure 43-65. Use of a trapezius myocutaneous flap to close a temporal bone defect.

defect with a fascia graft. Options for harvesting include the adjacent temporalis fascia, splitting the rectus sheath when harvesting fat graft, or fascia lata. Closure can be supplemented by covering the fossa incudis with an onlay of fascia. Some surgeons advocate extraction of the incus with insertion of fat or muscle plug. However, if this maneuver inadvertently distracts the stapes from the oval window, this creates a direct pathway from the craniotomy defect into the middle ear. When the ear canal has been resected, closure of the eustachian tube under direct vision can be achieved with bone wax or other substance. Many methods have been put forward for the operative management of postoperative CSF leak that persists despite conservative measures such as fluid restriction and lumbar subarachnoid drainage. A highly reliable method is to close the meatus, remove the ear canal, hermetically close the eustachian tube under direct visualization, and fill the resulting cavity with a free adipose graft. When CSF otorrhea traverses a hearing ear, less aggressive measures such as rewaxing transected cell tracts may suffice but has a substantial failure rate.

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80. Ekvall L, Bynke O: Prevention of cerebrospinal fluid rhinorrhea in translabyrinthine surgery. Acta Otolaryngol (Suppl) 449:15–16, 1988. 81. House JL, Hitselberger WE, House WF: Wound closure and cerebrospinal fluid leak after translabyrinthine surgery. Am J Otol 4:126–128, 1982. 82. Sataloff RT, Myers DL: Techniques for decreasing the incidence of cerebrospinal fluid leaks following translabyrinthine surgery. Am J Otol 8:73–74, 1987. 83. Tos M, Thomsen J: Cerebrospinal fluid leak after translabyrinthine surgery for acoustic neuroma. Laryngoscope 95:351–354, 1985. 84. Harner SG, Laws ER Jr: Translabyrinthine repair for cerebrospinal fluid otorhinorrhea. J Neurosurg 57:258–256, 1982. 85. Brackmann DE, House JR 3rd, Hitselberger WE: Technical modifications to the middle fossa craniotomy approach in removal of acoustic neuromas. Am J Otol 15:614–619, 1994. 86. Driscoll CD, Jackler RK, Pitts LH, Banthia BS: Is the entire internal auditory canal visible during the middle fossa approach for acoustic neuroma? Am J Otol 21:382–388, 2000. 87. House WF, Shelton C: Middle fossa approach for acoustic tumor removal. Otolaryngol Clin North Am 25:347–360, 1992. 88. Shelton C, Brackmann DE, House WF, Hitselberger WE: Middle fossa acoustic tumor surgery: Results in 106 cases. Laryngoscope 99:405–408, 1989. 89. Fisch U: Surgery for Bell’s palsy. Arch Otolaryngol 107:1–11, 1981. 90. Gantz BJ, Rubinstein JT, Gidley P, Woodworth GG: Surgical management of Bell’s palsy. Laryngoscope 109:1177–1188, 1999. 91. Green JD, Shelton C, Brackmann DE: Middle fossa vestibular neurectomy in retrolabyrinthine neurectomy failures. Arch Otolaryngol Head Neck Surg 118:1058–1060, 1992. 92. Gadre AK, Kwartler JA, Brackmann DE, et al: Middle fossa decompression of the internal auditory canal in acoustic neuroma surgery: A therapeutic alternative. Laryngoscope 100:948–952, 1990. 93. Driscoll CLW, Jackler RK, Pitts LP, Banthia V: Extradural temporal lobe retraction in the middle fossa approach to the internal auditory canal: A biomechanical analysis. Am J Otol 20:373–380, 1999. 94. Jackler RK, Gladstone HB: Locating the internal auditory canal during the middle fossa approach: An alternative technique. Skull Base Surg 5:63–67, 1995. 95. Irving RM, Jackler RK, Pitts LP: Hearing preservation surgery in vestibular schwannoma surgery: Comparison of the middle fossa and retrosigmoid approaches. J Neurosurg 88:840–845, 1998. 96. Thomsen J, Stougaard M, Becker B, et al: Middle fossa approach in vestibular schwannoma surgery. Postoperative hearing preservation and EEG changes. Acta Otolaryngol 120:517–522, 2000. 97. Dautheribes M, Migueis A, Vital JM, Guerin J: Anatomical basis of the extended subtemporal approach to the cerebellopontine angle: Its value and limitations. Surg Radiol Anat 11:187–195, 1989. 98. Wigand ME, Haid T, Berg M: The enlarged middle cranial fossa approach for surgery of the temporal bone and of the cerebellopontine angle. Arch Otorhinolaryngol 246:299–302, 1989. 99. Kanzaki J: Acoustic tumor surgery: Results of the extended middle cranial fossa approach and related investigations. Acta Otolaryngol Suppl 487:1–157, 1992. 100. Haid GT, Wigand ME: Advantages of the enlarged middle fossa approach in acoustic tumor surgery. A review. Acta Otolaryngol 112:387–407, 1992. 101. Wigand ME, Haid T, Berg M, et al: Extended middle cranial fossa approach for acoustic neuroma surgery. Skull Base Surg 1:183–187, 1991. 102. Satar B, Jackler RK, Oghalai J, et al: Risk-benefit analysis of using the middle fossa approach for acoustic neuromas with > 10 mm cerebellopontine angle component. Laryngoscope 112:1500–1506, 2002. 103. House WF, Hitselberger WE, Horn KL: The middle fossa transpetrous approach to the anterior-superior cerebellopontine angle. Am J Otol 7:1–4, 1986.

104. Sen CN, Sekhar LN: The subtemporal and preauricular infratemporal approach to intradural structures ventral to the brain stem. J Neurosurg 73:345–354, 1990. 105. Hakuba A, Nishimura S, Jang BJ: A combined retroauricular and preauricular transpetrosal-transtentorial approach to clivus meningiomas. Surg Neurol 30:108–116, 1988. 106. Kawase T, Shiobara R, Toya S: Anterior transpetrosal-transtentorial approach for sphenopetroclival meningiomas: Surgical method and results in 10 patients. Neurosurgery 28:869–875. 1991. 107. Sekhar LN, Janecka IP, Jones NF: Subtemporal-infratemporal and basal subfrontal approach to extensive cranial base tumours. Acta Neurochir (Wien) 92:83–92, 1988. 108. Kawase T, Toya S, Shiobara R, Mine T: Transpetrosal approach for aneurysms of the lower basilar artery. J Neurosurg 63:857–861, 1985. 109. Pitelli SD, Almeida GG, Nakagawa EJ, et al: Basilar aneurysm surgery: The subtemporal approach with section of the zygomatic arch. Neurosurgery 18:125–128, 1986. 110. Oghalai JS, Leung MK, Jackler RK, McDermott MW: Transjugular craniotomy for the management of jugular foramen tumors with intracranial extension. Otol Neurotol 25:570–579, 2004. 111. George B, Tran PB: Surgical resection of jugular foramen tumors by juxtacondylar approach without facial nerve transposition. Acta Neurochir (Wien) 142:613–620, 2000. 112. Lustig LR, Jackler RK: The variable relationship between the lower cranial nerves and jugular foramen tumors: Implications for neural preservation. Am J Otol 17:658–668, 1996. 113. Jackler RK, Sim D, Gutin P, Pitts LH: A systematic approach to intradural tumors located anterior to the brainstem. Am J Otol 16:39–51, 1995. 114. Malis LI: Surgical resection of tumors of the skull base. In Wilkins RH, Rengachary SS (eds.): Neurosurgery. New York, McGraw-Hill, 1985, pp 1011–1021. 115. Sakaki S, Takeda S, Fujita H, Ohta S: An extended middle fossa approach combined with a suboccipital craniectomy to the base of the skull in the posterior fossa. Surg Neurol 28:245–252, 1987. 116. Al-Mefty O, Smith RR: Clival and petroclival meningiomas. In Al-Mefty O (ed.): Meningiomas. New York, Raven Press, 1991, pp 517–537. 117. Ammirati M, Samii M: Presigmoid sinus approach to petroclival meningiomas. Skull Base Surg 2:124–128, 1992. 118. Herzog JA, Bucholz R, Hoffman W: The trans-sigmoid, retrolabyrinthine, transtentorial approach to the brainstem. Otolaryngol Head Neck Surg 104:130–131, 1991. 119. Nishimura S, Hakuba A, Jang BJ, Inoue Y: Clivus and apicopetroclivus meningiomas. Report of 24 cases. Neurol Med Chir (Tokyo) 29:1004–1011, 1989. 120. Samii M, Ammirati M, Mahran A, et al: Surgery of petroclival meningiomas: Report of 24 cases. Neurosurgery 24:12–17, 1989. 121. Spetzler RF, Daspit CP, Pappas TE: Combined approach for lesions involving the cerebellopontine angle and skull base: Experience with 30 cases. Skull Base Surg 1:226–234, 1991. 122. Abdel Aziz KM, Sanan A, van Loveren HR, et al: Petroclival meningiomas: Predictive parameters for transpetrosal approaches. Neurosurgery 47:139–150, 2000. 123. Cho CW, Al-Mefty O: Combined petrosal approach to petroclival meningiomas. Neurosurgery 51:708–716, 2002. 124. Horgan MA, Anderson GJ, Kellogg JX, et al: Classification and quantification of the petrosal approach to the petroclival region. J Neurosurg 93:108–112, 2000. 125. Oghalai JS, Jackler RK: Anatomy of the combined retrolabyrinthinemiddle fossa craniotomy. Neurosurg Focus 14:1–4, 2003. 126. Kirazli T, Oner K, Ovul L, et al: Petrosal presigmoid approach to the petro-clival and anterior cerebellopontine region (extended retrolabyrinthine, transtentorial approach). Rev Laryngol Otol Rhinol (Bord) 122:187–190, 2001. 127. Magliulo G: Modified retrolabyrinthine approach with partial labyrinthectomy: Anatomic study. Otolaryngol Head Neck Surg 124:287–291, 2001.

Surgical Neurotology: An Overview

128. Portmann D, Guerin J, Darrouzet V, et al: Translabyrinthinetranstentorial approach to the cerebellopontine angle: Advantages and limits. In Tos M, Thomsen J (eds.): Proceedings of the First International Conference on Acoustic Neuroma. Amsterdam, Kugler, 1992, pp 413–416. 129. Thedinger BA, Glasscock ME, Cueva RA: Transcochlear transtentorial approach for removal of large cerebellopontine angle meningiomas. Am J Otol 13:408–415, 1992. 130. Sasaki CT, Allen WE, Spencer D: Cerebral cortical veins in otologic surgery. Arch Otolaryngol 103:730–734, 1977. 131. Daspit CP, Spetzler RF, Pappas CTE: Combined approach for lesions involving the cerebellopontine angle and skull base: Experience with 20 cases: Preliminary report. Otolaryngol Head Neck Surg 105:788–796, 1991. 132. Browne JD, Fisch U: Transotic approach to the cerebellopontine angle. Otolaryngol Clin North Am 25:331–347, 1992. 133. Horn KL, Hankinson HL, Erasmus MD, Beauparalant PA: The modified transcochlear approach to the cerebellopontine angle. Otolaryngol Head Neck Surg 104:37–41, 1991. 134. Angeli SI, De la Cruz A, Hitselberger W: The transcochlear approach revisited. Otol Neurotol 22:690–695, 2001. 135. Mortini P, Mandelli C, Franzin A, et al: Surgical excision of clival tumors via the enlarged transcochlear approach. Indications and results. J Neurosurg Sci 45:127–139, 2001. 136. Pellet W, Cannoni M, Pech A: The widened transcochlear approach to jugular foramen tumors. J Neurosurg 69:887–894, 1988. 137. Samii M, Tatagiba M, Carvalho GA: Retrosigmoid intradural suprameatal approach to Meckel’s cave and the middle fossa: Surgical technique and outcome. J Neurosurg 92:235–241, 2000. 138. Cheung SW, Jackler RK, Pitts LP, Gutin PH: Interconnecting the posterior and middle fossa for tumors which traverse Meckel’s cave. Am J Otol 16:200–208, 1995. 139. Al-Mefty O, Ayoubi S, Gaber E: Trigeminal schwannomas: Removal of dumbbell-shaped tumors through the expanded Meckel cave and outcomes of cranial nerve function. J Neurosurg 96:453–463, 2002. 140. Yoshida K, Kawase T: Trigeminal neurinomas extending into multiple fossae: Surgical methods and review of the literature. J Neurosurg 91:202–211, 1999. 141. Crockard A: Surgery for anteriorly placed meningiomas at the foramen magnum. In Schmidek HH (ed.): Meningiomas and Their Surgical Management. Philadelphia, WB Saunders, 1991, pp 471–479. 142. Miller E, Crockard HA: Transoral transclival removal of anteriorly placed meningiomas at the foramen magnum. Neurosurgery 20:966–968, 1987.

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143. Stevenson GC, Stoney RJ, Perkins RK, Adams JE: A transcervical transclival approach to the ventral surface of the brain stem for removal of a clivus chordoma. J Neurosurg 24:544–551, 1966. 144. Bertalanffy H, Seeger W: The dorsolateral, suboccipital, transcondylar approach to the lower clivus and anterior portion of the craniocervical junction. Neurosurgery 29:815–821, 1991. 145. George B, Dematons C, Cophignon J: Lateral approach to the anterior portion of the foramen magnum. Application to surgical removal of 14 benign tumors. Surg Neurol 29:484–490, 1988. 146. Lang J, Kessler B: About the suboccipital part of the vertebral artery and the neighboring bone-joint and nerve relationships. Skull Base Surg 1:64–71, 1991. 147. Sen CN, Sekhar LN: An extreme lateral approach to intradural lesions of the cervical spine and foramen magnum. Neurosurgery 27:197–204, 1990. 148. Wanebo JE, Chicoine MR: Quantitative analysis of the transcondylar approach to the foramen magnum. Neurosurgery 49:934–941, 2001. 149. Dowd GC, Zeiller S, Awasthi D: Far lateral transcondylar approach: Dimensional anatomy. Neurosurgery 45:95–99, 1999. 150. Nanda A, Vincent DA, Vannemreddy PS, et al: Far-lateral approach to intradural lesions of the foramen magnum without resection of the occipital condyle. J Neurosurg 96:302–309, 2002. 151. Guidetti B, Spallone A: Benign extramedullary tumors of the foramen magnum. Adv Tech Stand Neurosurg 16:83–120, 1988. 152. Scott EW, Rhoton AL: Foramen magnum meningiomas. In Al-Mefty O (ed.): Meningiomas. New York, Raven Press, 1991, pp 543–568. 153. Heros RC: Lateral suboccipital approach for vertebral and vertebrobasilar artery lesions. J Neurosurg 64:559–562, 1986. 154. Lanser MJ, Jackler RK, Yingling C: Regional monitoring of the lower (ninth through twelfth) cranial nerves. In Kartuch JM, Bouchard KR (eds.): Neuromonitoring in Otology and Head and Neck Surgery. New York, Raven Press, 1992, pp 131–150. 155. Ng PY, Yeo TT: Petrosal approach for a large right posterior cerebral artery (P2) aneurysm. J Clin Neurosci 7:445–446, 2000. 156. Seifert V: Direct surgery of basilar trunk and vertebrobasilar junction aneurysms via the combined transpetrosal approach. Neurol Med Chir (Tokyo) 38(suppl):86–92, 1998. 157. MacDonald JD, Antonelli P, Day AL: The anterior subtemporal, medial transpetrosal approach to the upper basilar artery and ponto-mesencephalic junction. Neurosurgery 43:84–89, 1998. 158. Ahn M, Jackler RK: Exophytic brain tumors mimicking primary lesions of the cerebellopontine angle. Laryngoscope 107:466–471, 1997. 159. Kveton JF, Goravalingappa R: Elimination of temporal bone cerebrospinal fluid otorrhea using hydroxyapatite cement. Laryngoscope 110:1655–1659, 2000.

Complications in Neurotologic Surgery Outline G. Robert Kletzker, MD, FACS Robert J. Backer, MD

John P. Leonetti, MD Peter G. Smith, MD, PhD

Introduction Perioperative Considerations Vascular Management in Neurotologic Surgery Control of Venous Bleeding Control of Arterial Bleeding Hemorrhage Blood Transfusions Intracranial Complications

INTRODUCTION Surgeons involved in neurotologic surgery need to be acquainted with the potential complications. Hemorrhage, cerebral edema, arterial or venous infarction, pneumocephalus, cerebrospinal fluid (CSF) leak, infection, and acquired cranial nerve deficits may occur in any surgical procedure in which transcranial approaches are used. Specific compartments of the cranial cavity have varying degrees of tolerance to operative alterations. For example, relatively small changes in the blood flow in the posterior fossa may severely alter the delicate functions of the brainstem. 1 Removal of lesions of the skull base may leave large intracranial or extracranial communications, requiring complex reconstructive techniques for closure. Manipulation of cranial nerves may affect the patient's appearance and daily function. Minimization of complications begins with a comprehensive preoperative neuroradiographic assessment, including high-resolution computed tomography (HRCT), magnetic resonance imaging (MRI), and conventional or magnetic resonance angiography (MRA) (Fig. 44-1). Anticipation of the limits of resection and the neurovascular structures that may be encountered during the dissection are the foundation of the collaborative planning by a cranial base team to achieve a safe, oncologically sound resection.v" Advances in technologies have made intraoperative imaging available with MRI scanners based in the operating theater. Few institutions currently use this expensive equipment. More widespread use of stereotactic navigational systems is improving the safety of neurotologic surgery in a cost-effective manner. Commercially available systems allow for 1 to 3 mm of accuracy in localizing anatomic structures during surgery. Preoperative images (CT and MRI) are computer loaded, and surgical 712

Postoperative Stroke: Evaluation and Managemeilt Cerebral Edema: Evaluation and Management Pneumocephalus Seizures Cerebral Spinal Fluid Leak Infections Cranial Nerve Injuries

instruments are registered to anatomic and fiducial reference points, after the patient is secured on the operative table (Fig. 44-2). The systems provide confirmation of anatomic landmarks with visualization of the correlate position on the scans, in three-plane views. Fixed boney structures of the skull base are ideally suited to stereotactic navigational systems for confirmation of anatomy and the precise localization of instruments. This is advantageous for estimating distances to anticipated vital structures particularly in narrow dissection fields, such as approaches to the petrous apex and middle cranial fossa (Fig. 44-3). Because the images do not show resected structures or shifts in brain, which occur with tumor removal, there is a lack of "real time" quality to the systems which must be considered when utilizing stereotactic imaging. The technology is adjunctive but not a substitute for anatomic knowledge. The time required to register the patient's anatomic reference points to confirm the accuracy of positions on the computerized images and the expense of the systems, have been proven cost effective at institutions which are proficient in the use of stereotactic navigational systems.v" Intraoperative monitoring of the cranial nerve provides information to the operative team on the nerves' physiologic status and thus aids in neural protection. Electrophysiologic information of the functional integrity of cranial nerves has become both sophisticated and standardized in neurotologic surgery. Advances in interventional radiology have added to the safety and efficiency of cranial base surgery. Balloon occlusion testing of the internal carotid artery estimates the patient's tolerance to carotid artery ligation and competency of the circle of Willis. Selective arterial occlusion with embolization techniques has proven beneficial in the management of selected highly vascular lesions.

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large tumors to prevent generalized cerebral hypoperfusion (Fig. 44-4). Communication between all members of the surgical team enhances the well-being of the patient and efficiency of the operation. 10,11

VASCULAR MANAGEMENT IN NEUROTOLOGIC SURGERY The axiom that "bleeding is the enemy of the surgeon" is apropos in neurotologic and cranial base surgery. Control of bleeding is paramount in preventing the obscuring of a critical dissection and to avoiding a potential catastrophic complication. The vascular structures encountered with the various approaches must be anticipated and managed in a systematic fashion. Alterations of vascular structures by lesions can often be predicted or visualized by imaging studies. A familiarity with anatomic variations of vascular structures is a prerequisite for the neurotologic surgeon.I'

Control of Venous Bleeding

Figure 44-1. Coronal MRI demonstrating a petroclival meningioma with extension into the middle and posterior cranial fossa.

PERIOPERATIVE CONSIDERATIONS A preoperative assessment of cranial nerve status is necessary for objective evaluation of outcomes and assists in the intraoperative monitoring of cranial nerve function during surgery. The anesthesiologist, surgeon, nurses, and electrophysiologist coordinate patient positioning, placement of catheters, and cardiac and neural monitoring leads to maximize the patient's safety and operative efficiency. Priority is given to the induction of general anesthesia so as to reduce the risk of increasing intracranial pressure." Once adequate airway control is established, adjuvant arterial, intraventricular, or lumbar catheters are methodically inserted. A nasogastric tube, urinary catheter, and pneumatic stockings are secured prior to placement of the patient in three-point fixation. Avoidance of excess neck flexion that may impair venous return is particularly important if major venous structures are obliterated or resected. Troublesome intracranial hypertension may occur if flow through the contralateral internal jugular vein is compromised. Integrity of all electrophysiologic and hemodynamic monitors is confirmed prior to the isolation of the operative field. Attainment of adequate exposure with minimal brain retraction is of paramount importance in these lengthy operations. Adjustment of intracranial pressure by removal of cerebral spinal fluid, hyperventilation, or osmotic diuresis assists surgical exposure. Hypotensive anesthesia aids in minimizing blood loss in the resection of vascular lesions, such as meningiomas. Caution must be exercised in using hypotensive techniques during prolonged operations for

Approaches to the posterior fossa require management of bleeding from one or more emissary veins that drain the transverse and sigmoid sinuses.P'!" Bone removal of the mastoid and occipital cortex is carried out with a rotary drill in sweeping motions with continuous suction irrigation and bone rongeurs. The blue coloration of the venous sinuses can be visualized under a thin shell of intact bone, which can be removed with blunt dissection after bleeding from emissary veins is controlled with bone wax. Bipolar electrocautery can then be used to ensure coagulation of the venous stump at its point of entry into the sigmoid sinus. IS Troublesome bleeding may ensue if the vein is tom at its juncture with the sinus. Small dural tears can be controlled with bipolar cautery or placement of oxidized cellulose gauze (Surgicel) held in place for a short time under a cotton patty. A simple or figure-of-eight 4-0 silk suture can also approximate the dural margins and hold the Surgicel in place over the rent vessel. Larger sinus openings require extraluminal or intraluminal packing with a large sheet of Surgicel, with care not to further rend the vessel with excessive pressure (Fig. 44-5).

Figure 44-2. Perioperative registration of stereotactic neuronavigational system to a fixed panel on skull post and fiducial markers.

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Figure 44·3. Triplanar CT views of stereotactic navigational system. Instrument trajectory seen in bottom rightfor petrous apex cholesterol granuloma drainage via an intralabyrintine approach.

There is additional risk of air entry into the venous system if the head is elevated above the level of the heart; a problem more often encountered in the sitting than in the supine position. In the event of the inadvertent opening of the sinus heralded by the brisk outflow of deoxygenated blood, the anesthesiologist should be alerted so as to monitor for air

emboli. Intravascular crepitation, hypotension, tachycardia, or a decline in end-expiratory Pco, are the signals of air emboli, which require immediate treatment. Rotation of the table to a left Trendelenburg position should isolate any intravascular air into the right cardiac ventricle where it may be aspirated through a central venous catheter.

Figure 44-4. Sagittal MRI of large recurrent trigeminal schwannoma.

Figure 44·5. Sigmoid sinus obliteration with intraluminal packing of oxidized cellulose gauze. (From Leonetti JP. Smith PG. Grubb RL: Control of bleeding in extended skull base surgery. Am J Otol11 :254-259. 1990.)

Complications In Neurotologlc Surgery

Discontinuance of nitrous oxide, administration of 100% oxygen, positive pressure ventilation, and vasopressors are infused while digital pressure is applied over the venous opening. Aggressive attendance to the earliest warning signs of intravascular air can prevent the major complication of a stroke from air emboli.P-'? The planned resection of dural sinuses may be indicated for such lesions as glomus jugulare tumors. The sigmoid sinus may be ligated with vascular clips or 2-0 silk sutures passed circumferentially around the vessel through small stab incisions in the dura, several millimeters from the margin of the sinus. IS Maintaining the patency of the transverse sinus is of paramount importance whenever the sigmoid or superior petrosal sinuses are ligated. Retrograde thrombosis through the inferior cerebral vein of Labbe is a potential complication of transverse sinus ligation, leading to catastrophic venous cerebral infarction.'? The petrosal vein may lie in close proximity to the superior petrosal sinus; preserving this vein with transpetrosal approaches minimizes the risk of brainstem venous infarction.i? Proximal control of the internal carotid artery and jugular vein with placement of vessel loops in the high cervical region preempts resection of tumors within the jugular bulb via infratemporal fossa approaches. This precautionary measure should be taken as well when any approach requires extensive dissection around the petrous portion of the internal carotid artery.n,n Venous bleeding from the cavernous sinus is often encountered with resection of lesions, such as meningiomas, chondrosarcomas, or chordomas, from the trigeminal ganglion and petroclival regions. Venous tributaries from the ophthalmic, cerebral, and retinal veins of the superior orbital fissure, as well as the sphenoparietal and petrosal (inferior and superior) sinuses, carry highly oxygenated, bright red blood that may appear arterial. Venous bleeding in this area may also have a pulsatile quality, further replicating an arterial hemorrhage. Controlling hemorrhage from the cavernous sinus, requires gentle pressure on Surgicel gauze held in place with a suction tip covered by a cotton sponge. Vital neurovascular structures contained within the sinus cavity preclude injudicious pressure to tamponade the bleeding. Overpacking of the sinus with thrombotic gauze may result in pressure injury to cranial nerves III through VI or compression of the internal carotid." Once bleeding is controlled the Surgicel is trimmed with a few millimeters of excess gauze left over the outer surface of the torn dura, and care is taken not to dislodge the gauze during regional dissection. Patience and gentle technique are required of the surgeon to control venous bleeding from the cavernous sinus.

carried out early in the procedure. Contrary to the occlusion of draining veins, the selected intentional ligation of arteries has a more beneficial effect when there is a time lapse between arterial ligation and tumor removal. The longer the time between venous occlusion and tumor excision, however, the greater the potential for vascular congestion within the tumor and intraoperative bleeding. Tumors arising in the infratemporal fossa and upper aerodigestive tract often have contributing vascularity from the external carotid system. Preoperative angiogramdirected embolization of arterial feeders, 1 to 2 days before resection, is often helpful in hernostasis.i" This technique has been used most successfully with paragangliomas, meningiomas, and angiofibromas (Fig. 44-6). Ligation of the arteries as close to the tumor as possible offers significant vascular control, particularly when embolization has not been feasible. Specific vessels that require control to gain adequate tissue mobilization for tumor exposure vary with the approach. Care in electrocoagulation is warranted, keeping in mind adjacent structures that may be injured, as hemostasis is obtained. The facial nerve, which is skeletonized or mobilized in posterior approaches, is vascularized by the stylomastoid artery in the vertical mastoid segment. Medial to the digastric ridge, this artery causes bleeding that requires coagulation. The facial nerve, because of its close proximity, may suffer irreversible electrothermal injury if it is included in the field of cautery. Bipolar coagulation at a low setting, with concomitant irrigation will minimize this risk. Mobilizing the facial nerve with its fibrous covering and attendant artery at the stylomastoid foramen allows transposition without compromising its vascular supply." Similarly, isolation and ligation of the superior occipital artery from the underlying 11th cranial nerve is preferred over unipolar coagulation to obtain hemostasis with neural preservation. Isolation of the cranial nerves exciting the jugular foramen, prior to ligation of the

Control of Arterial Bleeding In addition to accessing the cervical vessels for proximal control, gaining exposure of tumor vessels via combined approaches has become a standard practice in extended cranial base surgery. Ligation of feeding vessels can immensely reduce operative blood loss during tumor removal and improve visibility during resection and thus the safety of the procedure. Guided by the preoperative angiogram, the ligation of selected arteries is planned and

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Figure 44-6. Angiogram of glomus jugulare tumor showing preoperative vascularity (left), much decreased after embolization (right).

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internal jugular vein, is a standard principal of neck dissections proven successful in protecting adjacent nerves while obtaining vascular control. Control of the internal carotid artery (lCA) is of paramount importance in resection of the temporal bone. The pterional and infratemporal fossa approaches are used when the carotid must be mobilized from its petrous encasement (Fig. 44-7). Ideally, adequate proximal and distal exposure is obtained prior to any carotid mobilization. 26 ,27 Intraluminal balloon occlusion affords distal control in managing pathologic lesions of the petroclival region, where complete exposure is impaired.i'v" Preoperative balloon occlusion testing provides invaluable information concerning the collateral cerebral circulation and the patient's ability to tolerate carotid resection without suffering irreversible neurologic sequelae.'? Failure of the carotid occlusion trial warrants bypass grafting of the internal carotid artery with a vein graft if the malignant histopathology dictates ICA resection.l'<" The petrous portion of the carotid is more often not included in the resection, but may need to be mobilized for adequate exposure (Fig. 44-8).34 The caroticotympanic artery arises from the posterior aspect of the ICA proximal to the genu at the bony-cartilaginous junction of the eustachian tube. This small-caliber vessel can bleed profusely if avulsed during carotid mobilization. Exposure of the petrous carotid is performed by thinning the bone with a diamond burr and then gently separating the "eggshell" fragments with a freer elevator off of the adventitia. Minimal vessel compression is accomplished with bone removal." ICA exposure is often required during transtympanic, infralabyrinthine, and middle cranial fossa approaches to the petrous apex. The cochlea, geniculate ganglion, and greater superficial nerve are valuable landmarks in guiding the dissection and must be identified prior to complete bone excavation of the petrous canal. Greater exposure is required for ICA mobilization, which also necessitates extremely gentle handling of the artery to prevent kinking or the potentially disastrous complication of vasospasm.I'<" Spasm of the carotid can occur with excess mechanical manipulation, temperature changes, drying of the adventitial surface, or prolonged exposure to blood. The preventative measures taken whenever the vessel is exposed include

gentle tissue handling and frequent irrigation of the carotid's surface with isothermal saline. Despite these precautions, vasospasm may develop. The sequelae of carotid artery vasospasm vary with the severity and duration of the constriction. In our experience the most profound consequences occurred in the younger patients whose vascular tonicity and reactivity were relatively hypersensitive.tv'" Hemodilution and hypertensive therapy, as for vasospasm following subarachnoid hemorrhage, may be effective in preventing catastrophic infarction. At the earliest detection of segmental reduction of the vessel caliber, topical application of 10% lidocaine, 1.5% or 3% papaverine, and 25 mg/mL chlorpromazine have been shown to inhibit vascular smooth muscle contraction. These agents are effective spasmolytics, which may be applied to the constricting vessel to counteract the myogenic response. The efficacy of calcium channel blockers (e.g., nimodipine) has not been proven in large-vessel spasm, although it is systemically administered in the management of mediumcaliber cerebral artery spasm. The sequelae of prolonged vasospasm are endothelial, intimal, and vessel media injuries. Spasm unabated for as little as 2 hours can lead to irreversible injury and thrombosis. The darkened coloration of the vessel surface in the region of constriction is an ominous sign of significant vascular injury and impending thrombosis. Decreased vessel

Figure 44-7. Intraoperative exposure of the internal carotid artery (large arrow) and the facial nerve (small arrow) after removal of boney encasement.

Figure 44-8. Three-dimensional CT of a meningioma that encased the ICA and necessitated mobilization of the artery for tumor extirpation.

Complications In Neurotologlc Surgery

pulsations, distal to the site of constriction, noted on visualization, palpation, or Doppler auscultation, may be the first warning signs of impaired perfusion. Slowing of electroencephalographic waves have been seen during intraoperative monitoring when regional blood flow falls below 18 mL/lOO g/min. Altered ventilation to elevate oxygen and carbon dioxide levels and maximizing blood pressure are undertaken in an attempt to maintain cerebral perfusion.t'r" Anticoagulants are contraindicated at the time of surgery, but may be considered in the patient who has developed delayed thrombosis. The risk of delayed carotid spasm and decreased perfusion has been reported in both carotid mobilization and trauma. Declining neurologic status or increasing intracranial pressure in the postoperative period warrant evaluation by CT and angiography. Surgical dressings that may compress the carotid should be removed, and the wound should be explored to evacuate hematoma if carotid spasm is confirmed angiographically. Measures to decrease intracerebral pressure are concurrently undertaken.

HEMORRHAGE Meticulous hemostasis around the dura is accomplished with bipolar coagulation, especially of the bridging veins to the sinuses. Dural tacking sutures prevent blood from enlarging the epidural space. Coagulants, such as oxidized cellulose (Surgicel) or microfibrillary collagen (Avitene) are packed in the epidural space securely under the tacking sutures. These precautions should tamponade any bleeding from a venous source and prevent epidural hemorrhages, which arise from bridging veins between the brain, dura, and diploe." Assurance that the branches of the middle meningeal artery, which supply the dura mater, have been adequately coagulated prior to wound closure, prevents hematoma formation. Postoperative epidural hematomas from an arterial source may produce mass effect with rapid onset of focal neurologic deficits. Postoperative hematomas can occur in the subdural or epidural space or within the excavation site of tumor removal. Cessation of bleeding from the brain surface after tumor removal may be assisted by the application of warm saline, peroxide-soaked cotton, or freshly cut muscle plugs, which will promote vasoconstriction and clot formation. Topical thrombin or liquefied cellulose (gelfoam) can be applied to surfaces that ooze blood to add stability to the clots. Meticulous hemostasis on the brain surface with bipolar cautery is essential to prevent intraparenchymal bleeding. Highly vascular structures such as the choroid plexus around the cerebellar flocculus, in the cerebellopontine angle, present a risk of intraventricular hemorrhage and obstruction of the aqueduct with clot if hemostasis is not obtained.t" The rate at which focal neurologic signs develop varies with location and source of bleeding. The presence of accumulating blood will generate focal neurologic signs, such as hemiparesis or aphasia, by mass effect. Hemiparalysis, obtundation, a fixed dilated pupil, and respiratory distress are the hallmarks of rapidly increasing intracranial pressure with peduncular herniation. In attempting to reverse the neurologic decline, urgent identification and treatment of a focal hemorrhage is rnandatory.v-"

717

Identifying the location and size of the hematoma usually requires CT scanning. Rarely, rapid brainstem deterioration or extensive hemorrhage, such as with a carotid rupture, mandate immediate exploration prior to imaging studies, to control bleeding and evacuate extravasated blood. Emergent wound decompression without imaging studies may be warranted in these grave situations when likely fatality or devastating neurologic sequelae would result from any delay in treatment (Fig. 44-9).

Blood Transfusions In the majority of neurotologic operations with extended dissections, such as for glomus tumor and temporal bone resections, blood loss frequently exceeds 1 L. Planned transfusions with autologous or related donor blood reduces the risk of transmission of blood-borne infections such as AIDS and hepatitis. When necessary, banked blood products are administered for restoration of blood volume and hemostatic fluid balance. Excessive hemorrhage, often encountered in tumor extirpation from the lateral cranial base, poses additional potential complications with blood replacement. The incidence of direct transfusion reactions, acid-base derangements, coagulation defects, and cardiopulmonary complications increase proportionally with the number of required transfusions." Hypotension, bradycardia, and other cardiac arrhythmias may be induced by the binding of citrate within preserved blood to the circulating ionized calcium. The administration of 1 g of calcium chloride for every two units of transfused blood will compensate for this relative hypocalcemia. Cardiac arrest can be induced as well by the administration of multiple units of banked blood, which may have high levels of potassium. Massive transfusions

Figure 44-9. Noncontrast axial CT showing acute hemorrhage (White) in the posterior cranial fossa after acoustic neuroma resection.

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SURGICAL NEUROTOLOGY

should be a mix of fresh and stored whole blood to prevent iatrogenic hyperkalemia. Lowered cardiac output or acid-base alterations may be induced by the rapid infusion of blood that has been refrigerated. Transfusion of three to five units given over a 2-hour period may lower core body temperature 4°C. In light of this, all transfusions must be warmed to body temperature prior to administration. Coagulopathies resulting from dilutional thrombocytopenia or the clotting factor deficiencies in banked blood may increase the risk of hemorrhage and make the task of obtaining hemostasis excessively difficult. Aberrancies in the calcium-dependent clotting cascade compound bleeding tendencies, with hypocalcemia arising from multiple transfusions. Intraoperative monitoring of prothrombin and partial thromboplastin times, serum calcium and potassium levels, and platelet counts is warranted during these lengthy procedures. One unit of fresh frozen plasma and concentrated platelet packs should accompany the administration of each four units of banked blood to prevent coagulopathies.F Cardiopulmonary complications resulting from rapid volume replacement may lead to pulmonary edema and acute respiratory distress syndrome in the early postoperative period. Disseminated intravascular coagulation due to escape of fibrin and microaggregated cells from standard mesh filters may obstruct the pulmonary microvasculature and further impair oxygen diffusion. Pulmonary emboli may prove lethal, particularly in this compromised state, underlining the importance of careful attention to anti thrombosis measures, use of micropore filters, and meticulous fluid balance.

INTRACRANIAL COMPLICATIONS

Postoperative Stroke: Evaluation and Management The incidence of stroke is fortunately low in neurotologic surgery. More extensive operations that include several intracranial compartments and require manipulation of the vasculature have an increased risk of vascular complications. Prolonged operative time and brain retraction, inherent in some approaches, are contributing factors that increase the risk of stroke. Cerebral vascular accidents may be caused by embolic or thrombotic vascular occlusion, arterial spasm, venous infarction, or progressive intraluminal vascular occlusion due to intimal dissection. Venous infarctions may result postoperatively, despite gentle technique in the manipulation of cortical veins. 48,49 Arterial insufficiency is usually manifested by the sudden onset of a new neurologic deficit, whereas venous infarction may have an insidious presentation. New-onset seizures, altered mental status, or mild motor deficits may be the first signs of venous infarction. CT may show an area of hypodensity in the location of impaired venous flow or areas of hemorrhage adjacent to an infarction, which appear hyperdense (Fig. 44-10). MRI reveals changes on the flair and diffusion images and magnetic resonance venography (MRV) assists in diagnosing progression of major venous sinus occlusion. Treatment of

Figure 44-10. Temporal venous infarction resulting from occlusion of the vein of Labbe.

venous infarction is usually supportive. Anticonvulsants are indicated if seizures are present. Major venous sinus occlusion is treated with anticoagulation when the neurologic deficits appear to be progressing or the level of consciousness continues to decline. Lysis of the clot with tissue plasminogen activator (TPA) by the interventional neurosurgeon or radiologist is indicated when anticoagulation fails to halt the neurologic decline. Venous sinus occlusion may also lead to increased intracranial pressure. Ventriculostomy is indicated when the Glasgow coma score falls to 8 or below. Aggressive treatment with osmotic diuretics, sedatives, and mechanical ventilation may be necessary for the comatose patient. Lumbar puncture may be appropriate for the awake patient with complaints of headaches or visual changes. Psuedotumor cerebri is not uncommon after major venous sinus occlusion. Medical therapy with a carbonic anhydrase inhibitor (Diamox) will frequently control the raised pressure in the patient with papilledema. Rarely, either ventriculoperitoneal or lumboperitoneal shunting will be necessary to control symptoms when the visual loss does not respond to medical therapy. CT detection of an area of confined infarction or intracerebral hemorrhage may only warrant aggressive medical therapy if the hemorrhage is not expanding or creating undue mass effect. A focal intracranial accumulation of blood or air will most likely create focal neurologic defects requiring emergent exploration and evacuation to relieve the pressure effect and prevent irreversible sequelae.P'!' The rapidity with which a neurologic alteration occurs may prove helpful in the initial clinical assessment. Generalized cerebral edema is most apt to occur in the first few days, whereas postoperative stroke may occur in the immediate recovery period or remote from the operative

Complications In Neurotologlc Surgery

session. Intense clinical monitoring of the patient's status and expedient imaging studies are mandated to detect and manage any intracranial complications, and thus minimize resultant deficits.

719

Tumors such as meningiomas may incite edema in the adjacent brain tissue (Fig. 44-11).52 Retraction or manipulation of the brain during tumor extirpation leads to varying degrees of cerebral swelling, which most commonly manifests in the first 3 postoperative days. Preoperative CT and MRI provide the initial assessment of tumor volume, cerebral edema, mass effect, and midline shift. Ventricular size and shape allow the volume of CSF and the likelihood of hydrocephalus to be estimated. Cerebral compromise evident prior to surgery increases the likelihood of significantly worsened cerebral edema with tumor removal. Clinically significant edema is most commonly heralded by evidence of increased intracranial pressure as measured by an intraventricular drainage catheter, a decline in the patient's mentation or level of alertness, or progressive focal neurologic deficits such as aphasia or limb weakness. Generalized edema that occurs as a result of brain manipulation or retraction, or venous outflow obstruction becomes most pronounced several days after surgery. 53-55 Depending on the degree of lethargy, rapidity of the neurologic decline, or severity of the process, the first step in management is to obtain a CT scan. Expansile lesions, such as a subdural hematoma or hydrocephalus, must be

eliminated as a cause of the clinical decline prior to institution of pressure-reduction maneuvers. Surgical exploration to evacuate intracerebral blood clots or subdural hematomas is performed on first detection of these causes of compromised cerebral function. Controlling bleeding and removal of pressure-producing lesions often arrests progressive neurologic injury if therapy is instituted quickly. The principles of treatment rely on the ability to alter the volume of brain, CSF, or blood to control intracranial pressure.P-" Reduction of elevated intracranial pressure begins with pharmaceutical, mechanical, and ventilatory measures. Ischemia will result from diffuse cerebral edema and should be addressed in an aggressive manner to prevent neurologic injury. 58,59 Regulation of the intracranial fluid volume during surgery affords greater exposure and reduces the need for brain retraction. Closed-system lumbar or intraventricular catheters placed in a sterile fashion preoperatively provide access for CSF drainage and the regulation of intracranial pressure. Lumbar CSF drainage may be contraindicated in large posterior fossa or transtentorallesions when there is a risk of brain herniation with decompression (Fig. 44-12). Epidural manometry to monitor intracranial pressure is an alternative when drainage of CSF is prohibited. An intraventricular catheter is the preferred device for both removal of CSF and direct measurement of intracranial pressure." In selected cases, preoperative intravenous steroids (dexamethasone in 4- to lO-mg doses) are begun preoperatively and continued every 6 hours for 3 days. The dose is tapered and discontinued over the ensuing 3 to 10 days, as the patient's recovery allows.P'' This regimen is routinely

Figure 44-11. Cerebral edema adjacent to a large petroclival meningioma.

Figure 44-12. Bilateral acoustic neurofibromas responsible for aqueduct obstruction.

Cerebral Edema: Evaluation and Management

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used to rrururruze edema associated with tumor removal when significant dissection or retraction of brain is required. Hyperventilation is a short-acting method of decreasing the intravascular blood volume, secondary to the effect of hypocarbia on the autoregulatory controls of the cerebral vasculature. The arterial Pea, should be maintained between 25 to 30 mm Hg with hyperventilation.f This method of pressure control is most pronounced in the immediate perioperative period and loses efficacy as a pressure control modality after approximately 36 hours of continuous use. Controlled hypotension, hypothermia (30 to 32°C), and barbiturate-induced coma are other perioperative modalities that may be employed adjunctively to minimize cerebral edema. Hyperosmolar agents and diuretics are useful medications for reducing interstitial fluid volume. Their rapidity of action allows for intraoperative use or to arrest acute postoperative edema. Mannitol is a hyperosmolar agent that remains in the intravascular compartment and draws interstitial fluid into blood vessels by its osmotic gradient. Mannitol is given intravenously in doses of 0.25 to 1.0 g infused over 20 minutes every 6 to 12 hours. Furosemide is a frequently used diuretic that promotes the egress of interstitial edematous fluid by the renal excretion of excess water and electrolytes. This creates an osmotic gradient, which, like mannitol, mobilizes excess fluid from the extracellular compartment. Furosemide is administered intravenously in doses of 20 to 60 mg every 4 to 6 hours. Care must be taken to monitor serum potassium levels and replenish diuresed electrolytes.

Pneumocephalus Pneumocephalus is not uncommonly seen on postoperative CT. Small pockets of air trapped after craniotomy normally resorb within 7 to 10 days. Air accumulating under pressure causes focal neurologic deficits. A tension pneumocephalus, if untreated, can be a fatal complication.?' "Ball valving" of soft tissues in the basicranium after removal of bone, with forced inspired air entering the epidural space, can lead to mass effect and subsequent neurologic deterioration. Risk factors for this complication increase with positive pressure ventilation, especially with a tracheostomy tube, after combined intracranial and parapharyngeal resections. Continuous lumbar catheter drainage may create a relative intracranial "vacuum" of negative pressure and draw air into the intracranial space. Particular caution with lumbar drains is warranted in elderly patients, whose brain laxity may increase the risk of pneumocephalus.f Intracranial air is significant when tension develops, as indicated by signs of increased intracranial pressure or CT evidence of midline shift of the ventricles. A tension pneumocephalus mandates expedient decompression (Fig. 44-13). Any source of air access in the incision line or neck wounds must be sealed off with appropriate tissues of fascia or vascularized muscle. Residual accumulations of air, noted on scans, may need to be evacuated if they fail to resorb or if any neurologic compromise may be caused by the pneumocephalus. Because a concurrent CSF leak frequently accompanies a persistent pneumocephalus, a diligent search for potential sites of fluid leaks is warranted.

Figure 44-13. A persistent pneumocephalus following a frontotemporal craniotomy and infratemporal resection of a large meningioma.

Seizures The occurrence of seizures in the postoperative period may signal the development of a hemorrhage, venous or arterial infarction, hematoma, or other complications leading to a mass effect and cerebral irritation. Manipulation, dissection, or resection of brain parenchyma can lead to an irritable focus of the cerebrum that manifests as focal seizures. Prophylactic anticonvulsant therapy with phenytoin (Dilantin) is advocated when considerable manipulation or resection of the brain has been required for tumor removal. The initial loading dose is 18 mglkg intravenously followed by maintenance dosing of 300 mg/day. Clinical observation of persistent seizure activity along with serial serum drug levels guide adjustment of the dosing regimen.tl-?

CEREBRAL SPINAL FLUID LEAK The most common complication reported after neurotologic procedures is the development of a CSF leak. An 8% incidence of spinal fluid leakage with posterior fossa acoustic tumor removal has been reported through the Acoustic Neuroma Association by collaborative investigators nationwide. Resection of large segments of dura with extensive tumor removal has led to leaks of spinal fluid in a significant number of patients undergoing cranial base surgery through combined surgical approaches.v'<"

Complications In Neurotologlc Surgery

The method of reconstruction significantly influences the incidence of CSF leakage. When the continuity of the dura has been disrupted, reestablishing a water-tight seal is more difficult. Fascia grafts may be used to reconstitute the dura. Autologous fat grafts to fill a limited posterior fossa dural defect in the mastoid cavity will provide a water-tight seal. This reconstruction has proven reliable in translabyrinthine approaches for decades. Skull base surgery, which exposes large areas of the basicranium, requires more sophisticated methods of reconstruction.w-? Freetissue transfer, with myogenous and myocutaneous grafts, has markedly decreased the incidence of postoperative CSF leaks and subsequent wound infections (Fig. 44_14).7 3,74 Intraoperative lumbar drainage catheters are used to assist in the control of intracranial pressure and in the relaxation of the brain to minimize retraction. Postoperatively the catheter may be left in place to drain CSF at a maximum rate of 300 mLl24 hours, to help prevent the development of a CSF leak. The spinal fluid drainage may be used for 5 days with the patient on strict bedrest, with the head of bed elevated 15 to 30 degrees. A sterile mastoid or Barton's dressing is maintained over the wound to promote water-tight healing. Antibiotics are continued for the duration of the catheter's placement.Z'v" Excess production of spinal fluid may need to be reduced if a persistent CSF leak or hydrocephalus develops following discontinuation of the lumbar drain. Acetazolamide sodium (Diamox 500-mg) is administered orally or intravenously twice a day. Advances in imaging modalities, stereotactic navigational systems, electrophysiologic monitoring, and standardization of skull base approaches have improved the safety of

Figure 44-14. Sagittal MRI demonstrating a rectus abdominis myogenous, free-tissue graft filling the surgical defect of the infratemporal fossa.

721

neurotologic operations. Anticipation of potential problems associated with the manipulation of delicate neurovascular structures helps to prevent complications. Meticulous patient preparation and refined surgical techniques in resection and reconstruction help to optimize treatment results. Early recognition of complications and expedient intervention can minimize the sequelae of complications associated with neurotologic and cranial base surgeries. CSF leaks contribute to wound infections, fistulae formation, and meningitis. Prevention of these complications is best accomplished by wound closure with well-vascularized tissues. Pedicled myocutaneous or vascularized free flaps is required to reconstruct large defects of the basicranium. In the event of a CSF leak despite taking these precautionary measures, wound exploration and secondary reconstruction may be required. Detection of clear rhinorrhea or otorrhea, with a "halo sign" on a cotton sheet, alerts the clinician to the likelihood of a leak. If a sample of fluid can be collected, chemical analysis showing a glucose concentration greater than 30 mg/mL or identification of transferrin (~-1 or -2) by immunoelectrophoresis is confirmatory for CSF.77,78 Fluid in the nasopharynx, which is suspected to be CSF, can be collected in cotton pledgets and scanned for radioactive isotopes 12 hours following intrathecal nucleotide instillation. This study is beneficial when chemical and protein analysis of fluid is inconclusive. Contrast cisternography with CT imaging is often helpful in confirming and localizing the site of a spinal fluid leak.

INFECTIONS Fortunately, the general incidence of wound infections following neurotologic operations is low. The risk of wound infection rises, however, with the extent of resection, length of surgery, potential dead space, and hematoma formation.i? The development of a wound infection in the early postoperative period is significant, as meningitis, brain abscess, or other potentially life-threatening complications may ensue. The use of prophylactic antibiotics, which attain high CSF levels, are warranted in neurotologic operations. One gram of cefazolin (Ancef) is infused prior to skin incision and continued intravenously every 8 hours for three doses, following noncontaminated cases. Similar effective prophylactic coverage of gram-positive organisms is provided by vancomycin hydrochloride, 1 g every 12 hours for 24 hours. There is minimal risk of ototoxicity or nephrotoxicity with this prophylactic regimen, provided the serum creatinine level is normal. Administration of vancomycin beyond the peri operative period requires serial monitoring of creatinine and serum drug levels. Lengthy surgeries or those with likely bacterial contamination by exposure of the aerodigestive tract with the intracranial cavity, require prophylaxis against mixed flora and anaerobic organisms. Unasyn is a single-regimen administration of ampicillin sodium with sulbactam, given in doses of 3 g every 8 hours. Alternatively, ampicillin (1 g) and metronidazole hydrochloride (Flagyl, 500 mg) can be infused every 6 hours. Protection against gram-negative organisms, particularly Pseudomonas aeruginosa, is afforded by combining clindamycin phosphate (Cleocin 600 to 900 mg) with either ceftazidime (Fortazl to 2 g) or gentamicin

722

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sulfate (80 to 100 mg) every 8 hours. Precautions against nephro-ototoxicity are needed with the aminoglycosides, particularly when used with vancomycin. The classic findings of deep-wound infections may be absent in the early stages of development. Febrile episodes are often the early warning sign of a postoperative infectious process, prior to the development of skin erythema, tissue swelling, or wound drainage. Any deviation from the normal postoperative course prompts evaluation with white blood cell counts with leukocyte differential, chest radiograph, urinalysis, and serial blood cultures. These tests will help confirm an infectious source of fever. The most common cause of postoperative fever is pulmonary atelectasis. Incentive spirometry, positive pressure ventilation, and vigorous pulmonary toilet typically correct alveolar collapse and normalize the temperature. A visible pulmonary infiltrate on chest radiograph is managed similarly, with the addition of broad-spectrum antibiotic therapy pending identification of a specific pathogen by sputum culture. Indwelling urinary or central venous catheters, in place for greater than 5 postoperative days, should be discontinued, cultured, and replaced. When a febrile source cannot be rapidly discovered, meningitis should be considered and lumbar puncture performed." Infectious disease consultation should be sought when an infection is not readily isolated but is suspected on clinical grounds. Rare causes of fever, such as medication reactions, deep venous thrombosis, pulmonary embolus, parotitis, or prostatitis, can be identified more quickly when consultation is obtained. Deep-tissue infections are often quickly visualized by CT or MRI of the head and neck. Lucency adjacent to sites of resection, exhibiting peripheral contrast enhancement, are indicative of an abscess. Computer-directed aspiration will allow collection of materials for sensitivity assays. Adequate drainage and antibiotic therapy are instituted after a focal site of infection is confirmed. Subdural, epidural, and parapharyngeal abscesses mandate emergent open drainage and may require revision of the reconstruction with well-vascularized tissues. Pedicled myocutaneous or freely transferred myogenous grafts are most useful and versatile in this regard (Fig. 44-15).81 Reconstruction revisions are staged until the infection is well controlled to prevent abscess loculation. Specific antibiotic therapy, as directed by culture and sensitivity results, is continued with assistance by infectious disease consultants, until all infection is eradicated. Vigilant monitoring to recognize potential adverse effects of therapy and to ensure complete control of infection is paramount to the patient's eventual

Figure 44-15. Pedicled trapezius myocutaneous flap reconstruction following total temporal bone resection.

cystic carcinomas have a great propensity for intraneural or perineural growth, thus necessitating aggressive excision of nerves adjacent to tumor (Fig. 44-17). Benign lesions that cause compressive neuropathies, such as schwannomas, meningiomas, and paragangliomas, may exhibit extensive involvement of the nerves exiting the cranial base.P' Neural preservation may not be feasible. Microdissection techniques and electrophysiologic monitoring have

recovery.V

CRANIAL NERVE INJURIES Cranial nerves III through XII are at risk for injury in the spectrum of neurotologic surgery (Fig. 44-16). The decision to resect specific nerves involved with tumor is dictated by the histologic process and the degree of function present before surgery.83 Malignant lesions that involve neural structures mandate their removal and a careful search for microscopic neural involvement by frozen section examination at the time of surgery. Squamous cell and adenoid

Figure 44-16. Paralysis of leftabducens and facial nerves secondary to a temporal bone infection involving the petrous apex.

Complications In Neurotologlc Surgery

723

Figure 44-17. Perineural growth around the oculomotor nerve of a squamous cell carcinoma resected from the cavernous sinus.

evolved to enhance the preservation of cranial nerves during tumor resection (Fig. 44_18).11,85 Attempts to control bleeding, particularly at the jugular foramen and cavernous sinus, may produce nerve paresis due to overzealous packing with oxidized cellulose. This complication is best avoided by gentle technique to obtain hemostasis. Locating the several inferior petrosal sinus openings into the medial jugular bulb is particularly helpful in controlling bleeding in the jugular fossa and preventing undue pressure on the nerves in the pars nervosa. The facial nerve is the most frequently impaired cranial nerve in neurotology, and its preservation requires constant management. The common immediate problems associated with facial paralysis involve incompetent eye closure and exposure keratitis. Lacrilube ophthalmic ointment and a moisture chamber or lid taping at night, along with the application of artificial tears every 2 hours, will prevent drying of the eye in the immediate postoperative period.

Figure 44-18. Electrode on the cochlear nerve for direct intraoperative monitoring of cranial nerve VIII during a vestibular neurectomy.

Figure 44-19. Gold weight implant in upper eyelid.

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SURGICAL NEUROTOLOGY

Figure 44-20. Fiberoptic laryngoscopy showing paralysis of the right vocal cord following glomus jugulare tumor resection.

Ophthalmologic evaluation with corneal staining is advisable for a baseline examination to rule out any corneal abrasions. The placement of a gold weight in the upper eyelid will restore competent lid closure either temporarily or permanently (Fig. 44-19). Canthoplasty of the lower eyelid is necessary in those individuals who develop significant ectropion or have extreme lower lid laxity that prevents complete corneal protection. Marked disfigurement of the face with asymmetry and oral incompetence may need to be corrected by muscle sling procedures using the temporalis or masseter muscles. Primary or crossed facial nerve grafting or hypoglossal-to-facial nerve anastamosis is useful in restoring tonus to the facial musculature, as are primary nerve grafts in suitable candidates.P-" Electrical stimulation of the face, massages, and biofeedback exercises are directed by the physical therapists and are often helpful in maximizing the effects of the facial reanimation procedures. The cochlear vestibular system is often sacrificed, a complication that is without remediation. Recent attempts to implant electrodes on the cochlear nucleus in the brainstem offer some hope of restoring audition in patients whose tumor removal sacrifices all remaining hearing. This is a major benefit to patients with neurofibromatosis who have bilateral acoustic neuromas." Problems with deglutition and phonation are not infrequent following glomus tumor surgery due to the paresis or paralysis of the glossopharyngeal and vagus nerves. Perioperative pulmonary toilet through the tracheostomy helps prevent pneumonia. Decannulation of the tracheostomy is accomplished along with assessment of the vocal cord function by direct fiber-optic laryngoscopy and swallowing evaluation by modified barium cineradiography (Fig. 44-20). Persistent aspiration may require medialization of the vocal cord by endoscopic injection of Teflon or collagen or an external thyroplasty procedure. Pooling of secretions in the pyriform sinus, which causes aspiration, may be corrected by cricopharyngeal myotomy.'" This problem may be particularly bothersome and seems to be caused by the lack of pharyngeal sensation following glossopharyngeal

nerve section. Swallowing training by a speech pathologist is often most beneficial to these patients.

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Complications In Neurotologlc Surgery

17. Shuller DE, Hart M, Goodman )H: The surgery of benign and malignant neoplasms adjacent to or involving the skull base. Am ) Otol10:305-313,1989. 18. Fisch U: Infratemporal fossa approach for glomus tumors of the temporal bone. Ann Otol Rhinol LaryngoI91:474-479, 1982. 19. Spector G), Sobol S: Surgery for glomus tumors at the skull base. Otolaryngol Head Neck Surg 88:524-530, 1980. 20. Johanson C: The central veins and deep dural sinuses of the brain. Acta Radiol (Suppl 107), 1954. 21. Gardner G, et al: Skull base surgery for glomus jugulare tumor. Am ) OtoI6:126-134, 1985. 22. Krespi YF: Cancer surgery of the skull base. Clin Plast Surg 12:389-392, 1985. 23. Sekhar LN, et al: Operative exposure and management of the petrous and upper cervical internal carotid artery. Neurosurg 19:967-982,1986. 24. Brugge KG, Lasjaunias P, Chiu MC: Super-selective angiography and embolization of skull base tumors. Can) Neurol Sci 12:341-344, 1985. 25. Brackmann DE: The facial nerve in the infratemporal approach. Otolaryngol Head Neck Surg 97:15-17, 1987. 26. Ariyan S, Sasaki CT, Spencer D: Radical en block resection of the temporal bone. Am) Surg 142:443-227, 1981. 27. Mickey B, Close L, Schaefer S, Samson D: A combined frontotemporal and lateral infratemporal fossa approach to the skull base. J Neurosurg 68:678-683, 1988. 28. Humphreys DH, Schwartz MR, Jenkins HA: Meningioma: A case of transcranial recurrence managed by base-of-skull technique and a review of tumor. Head Neck Surg 93:563-570, 1985. 29. Samii), et al: Surgery of petroclival meningiomas: Report of 24 cases. Neurosurgery 24:12-17,1989. 30. Devries E), et al: Elective resection of the internal carotid artery without reconstruction. Laryngoscope 98:960-966, 1988. 31. Leonetti )P, Smith PG, Grubb RL: The perioperative management of the petrous carotid artery in contemporary surgery of the skull base. Otolaryngol Head Neck Surg 103:446-451, 1990. 32. Sekhar LN, Schramm VL, Jones NF: Subtemporal-preauricular infratemporal fossa approach to large lateral and posterior cranial base neoplasm.) Neurosurg 67:488--499, 1987. 33. Urken ML, Biller HF, Haimov M: Intratemporal carotid artery bypass in resection of a base of skull tumor. Laryngoscope 95:1472-1477,1985. 34. Nager G, Heroy ), Hoeplinger M: Meningiomas invading the temporal bone with extension to the neck. Am) Otol 4:297-324, 1983. 35. Fisch U: Infratemporal fossa approach to tumors of the temporal bone and base of the skull.) Laryngol Otol 92:949-967, 1978. 36. Fisch U, Derald), Senning A: Surgical therapy of internal carotid artery lesions of the skull base and temporal bone. Otolaryngol Head Neck Surg 88:548-554,1980. 37. Leonetti )P, Smith PG, Linthicum F: The petrous carotid artery: Anatomic relationships in skull base surgery. Otolaryngol Head Neck Surg 102:3-12, 1990. 38. SataloffRT, Myers DL, Lowry LD, Spiegel)R: Total temporal bone resection squamous cell carcinoma. Otolaryngol Head Neck Surg 96:4-14,1987. 39. Landolt AM, Millikan CH: Pathogenesis of cerebral infarctions secondary to mechanical carotid artery occlusion. Stroke 1:52-62, 1970. 40. Smith PG, Killeen TE: Carotid artery vasospasm complicating extensive skull base surgery: Cause, prevention and management. Otolaryngol Head Neck Surg 97:1-7, 1987. 41. Malis LI: Surgical resection of tumors of the skull base. In Wilkins RH, Rengachary SS (eds.): Neurosurgery. New York, McGraw-Hili, 1985, pp 1011-1021. 42. Schettini A, Cook A\N, Owre ES: Hyperventilation in craniotomy for brain tumor. Anesthesia 28:363-371,1967. 43. Poppen)L: Prevention of postoperative extradural hematoma. Arch N eurol Psych 34:1068-1 069, 1935.

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44. Symon L: Control of intracranial tension. In Symon L, Thomas D, Clark K (eds.): Rob & Smith's Operative Surgery Neurosurgery, 4th ed. London, Butterworth, 1989, pp 1-11. 45. Krespi YF, Sisson GA: Skull base surgery in the composite resection. Arch OtolaryngoI108:681-684, 1982. 46. Leonetti )P, Smith PG, Grubb RL: Management of neurovascular complications in extended skull base surgery. Laryngoscope 99:492--496, 1989. 47. Baker R), Nyhus LM: Diagnosis and treatment of immediate transfusion reaction. Surg Gynecol Obstet 130:665-670, 1970. 48. Baker L, Lee)C: The effect of acute hypoxia and hypercapnia on the ultrastructure of the central nervous system. Brain 91:697-706, 1968. 49. Kinal ME: Hydrocephalus and the dural venous sinuses.) Neurosurg 19:195-201,1962. 50. Smith PG, Grubb RL, KIetzker GR, Leonetti)P: Combined pterional-anterolateral approaches to cranial base tumor. Otolaryngol Head Neck Surg 103:357-363, 1990. 51. Weiss RM: Massive epidural hematoma complicating ventricular decompression: Report of a case with survival. ) Neurosurg 21: 235-236,1968. 52. Challa VR, et al: The vascular component in meningiomas associated with severe cerebral edema. Neurosurg 7:363-368, 1980. 53. Fitz-Hugh GS, Robins RB, Craddock Wl): Increased intracranial pressure complicating unilateral neck dissection. Laryngoscope 76:893-906, 1966. 54. Rosen HM, Simeone FA: spontaneous subdural hygromas: A complication following craniofacial surgery. Ann Plast Surg 18:245-247, 1987. 55. Symonds CP: Hydrocephalic and focal cerebral symptoms in relation to thrombophlebitis of the dural sinuses and cerebral veins. Brain 60:531-550,1937. 56. Brookes GB, Graham M: Benign intracranial hypertension complicating glomus jugulare tumor surgery. Am) Otol 5:350-354,1984. 57. Horwitz NH, Rizzoli HV: Postoperative complications of intracranial neurological surgery. Baltimore, Williams & Wilkins, 1982, pp 1-34. 58. Ames A, er al: Cerebral ischemia: the no-reflow phenomenon. Am) Pathol 52:437--447, 1987. 59. Chiang), et al: Cerebral ischemia: Vascular changes. Am) Pathol 52:455--465, 1968. 60. Smith Hp, et al: Biologic features of meningiomas that determine the production of cerebral edema. Neurosurgery 8:433--458, 1981. 61. Matsuba HW, Thawley SE, Smith PG: Tension pneumocephalus: A case following surgery. Am) Otol 7:208-209, 1986. 62. Pitta LH, et al: Pneumocephalus following ventriculoperitoneal shunt: Case report.) Neurosurgery 43:631-633, 1976. 63. Acoustic Neuroma Foundation: Acoustic Tumor Registry Annual Report. Carlisle, PA, 1990. 64. Close LG, et al: Resection of upper aerodigestive tract tumors involving the middle cranial fossa. Laryngoscope 95:908-914,1985. 65. Gardner G, Robertson )H, Clark WC: Transtemporal approached to the cranial cavity. Am OtoI6:114-120, 1985. 66. Glass ME, Dickins )RE: Complications of acoustic tumor surgery. Otolaryngol Clin North Am 15:883-895, 1982. 67. Jackson CG, Glasscock ME, Nissen A), Schwaber MK: Glomus tumor surgery: The approach, results and problems. Otolaryngol Clin North Am 15:897-915, 1982. 68. Myers DL, Sataloff RT: Spinal fluid leakage after skull base surgical procedures. Otolaryngol Clin North Am 17:601-611, 1984. 69. Bakamjian VY, Souther S: Use of temporal muscle flap for reconstruction are orbito-maxillary resections for cancer. Plast Reconstr Surg 56:171-177,1975. 70. Jackson IT: Advances in craniofacial tumor surgery. World) Surg 13:440--453, 1989. 71. Jackson IT, Adham MN, Marsh WR: The use of galeal frontalis flap in craniofacial surgery. Plast Reconstr Surg 76:905, 1986. 72. Schuller DE: Latissimus dorsi myocutaneous flaps for massive facial defects. Arch Otolaryngol 108:414-417, 1982.

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73. Jones NF, Schramm VL, Sekhar LN: Reconstruction of the cranial base following tumor. Br J Plast Surg 40:155-162, 1987. 74. Jones NF, Sekhar LN, Schramm VL: Free rectus abdominis muscle flap reconstruction of the middle and posterior cranial base. Plast Reconst Surg 78:471-479,1986. 75. Graf C), Gross CE, Beck DW: Complications of spinal drainage in the management of cerebrospinal fluid fistulae: Report of 3 cases. J Neurosurg 54:392-395,1980. 76. McCallum J, Maroon JC, Janetta PJ: Treatment of postoperative cerebrospinal fluid fistulas by subarachnoid drainage. J Neurosurg 42:434-437, 1975. 77. Irjala K, Suonpaa J, Laurent B: Identification of CSF leakage by immunofixation. Arch Otolaryngol 105:447-448, 1979. 78. Leonetti JP, Anderson D, Marzo S, Moynihan G: Cerebrospinal fluid fistula after transtemporal skull base surgery. Otolaryngol Head Neck Surg 124:511-514, 2001. 79. Ketchum AS, Hoye RC, Van Buren JM, Johnson RH: Complications of intracranial facial resection for tumors of the paranasal sinuses. AmJ Surg 112:591-596, 1966. 80. Garfield J: Intracranial abscess. In Symon L, Thomas D, Clark K (eds.): Rob & Smith's Operative Surgery, Neurosurgery, 4th ed. London, Butterworth, 1989, pp 83-93.

81. Baker SR: Surgical reconstruction after extensive skull base surgery. Otolaryngol Clin North Am 17:591-599, 1984. 82. Strong AJ, Ingham HR: Surgical and microbiologic management of subdural and extradural abscesses. In Symon L, Thomas D, Clark K (eds.): Rob & Smith's Operative Surgery, Neurosurgery, 4th ed. London, Butterworth, 1989, pp 94-101. 83. Sataloff RT, Myers DL, Kremer FB: Management of cranial nerve injury following surgery of the skull base. Otolaryngol Clin North AmI7:577-589,1984. 84. Glasscock ME, Jackson CG, Dickins JRE, Wiet RJ: Panel discussion: Glomus jugulare tumors of the temporal bone, the surgical management of glomus tumors. Laryngoscope 89:1640-1655, 1979. 85. Hitselberger WE, House WF: A combined approach to the cerebellopontine angle. Arch Otolaryngol 84:267-285, 1966. 86. Baker DC, Conley J: Facial nerve grafting: A 30-year retrospective review. Clin Plast Surg 6:343-351,1979. 87. Conley J, Baker DC: Hypoglossal-facial nerve anastomosis for reinnervationof the paralyzedface. Plast Reconstr Surg 63(1):63-72, 1979. 88. Luetje CM, et al: Feasibility of multichannel human cochlear nucleus stimulation. Laryngoscope 102:23-25, 1992. 89. Levine TM: Swallowing disorders following skull base surgery. Otolaryngol Clin North Am 21:751-759,1988.

45

Outline Introduction History Epidemiology Tumor Biology Pathogenesis Molecular Genetics Molecular Mechanisms Endocrine Relationships Radiation Gross and Microscopic Pathology Gross Pathology Histopathology Growth Characteristics Growth Pattern Growth Rate Measurement of Acoustic Neuromas Clinical Manifestations Typical Clinical Presentation Signs and Symptoms Hearing Loss Tinnitus Vertigo, Dysequilibrium, and Dysmetria Facial Anesthesia and Pain Facial Weakness and Spasm Headache Ophthalmologic Manifestations Lower Cranial Nerves Late Symptoms Sudden Neurologic Deterioration Audiologic Diagnosis Pure Tone and Speech Audiometry Auditory Brainstem Responses Otoacoustic emissions Vestibular Testing Electronystagmography Rotatory Testing Dynamic Posturography

Chapter

Acoustic Neuroma (Vestibular Schwannoma)

Utility of the Vestibular Test Batteries Radiology Diagnostic Protocols for Suspected Acoustic Neuroma Delayed Diagnosis Management Conservative Management Microsurgical Management The Role for Incomplete Resection Outcome of Acoustic Neuroma Surgery Decentralized versus Centralized Hospitals Mortality Complications Intracranial Vascular Complications Traumatic Parenchymal Injury Cerebrospinal Fluid Leak Meningitis Impact of Acoustic Neuroma Removal on the Quality of Life Facial Mimetic Function Vulnerability of the Facial Nerve Role of Facial Nerve Monitoring Results in Contemporary Series The Course of Postoperative Facial Palsy Management Options When the Facial Nerve Is Disrupted Care of the Eye in Facial Palsy Hearing Conservation Pathology and Pathophysiology of Cochlear Nerve Involvement

Assessing Candidacy for a Hearing Conservation Attempt Definition of a Successful Result Results in Clinical Series Long-Term Hearing Results Special Considerations in Bilateral Acoustic Neuroma and Only Hearing Ears Hearing Loss in the Ear Contralateral to an Acoustic Neuroma Rehabilitation of Unilateral Hearing Loss Tinnitus Vestibular Rehabilitation Headache Social and Occupational Rehabilitation Radiation Therapy Conventional Radiotherapy Stereotactic Irradiation Fate of the Tumor following Stereotactic Radiation Audiovestibular Function after Stereotactic Radiation Cranial Nerve Function following Stereotactic Radiation Complications following Stereotactic Radiation Secondary Oncogenesis following Stereotactic Radiation Indications for Stereotactic Radiation in Unilateral Acoustic Neuroma Radiation after Surgery and Surgery after Radiation Bilateral Acoustic Neuroma Auditory Brainstem Implant Conclusion

Robert K. Jackler, MD Markus H. F. Pfister, MD

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INTRODUCTION In neurotologic practice, a substantial fraction of the clinician’s time is spent either in performing diagnostic evaluation for or engaged in the treatment of acoustic neuroma (AN). Historically, these tumors figured prominently in the development of both diagnostic and surgical neurotology. Techniques developed for their identification and removal catalyzed the development of diagnostic audiology, imaging technologies, microsurgery, hemostatic methods, cranial nerve monitoring, and many innovative operative approaches that have subsequently been expanded and applied to other diseases. These tumors are characterized by a multiplicity of clinical presentations, a technologically sophisticated diagnostic armamentarium, a diversity of challenging surgical approaches, and patients who respond remarkably well to therapy, especially when compared with results obtained with other intracranial tumors. Given these attributes, it should not be surprising that ANs, which have been termed the queen of intracranial tumors by some, have captured the interest of so many clinicians and researchers. The high level of interest in these lesions has led to numerous recent advances in understanding their biology as well as progressive refinement of diagnostic and therapeutic methods.

HISTORY Acoustic neuroma was first described in the latter part of the 1700s and by the mid-1800s, neurologists understood that patients who manifest unilateral deafness, facial numbness, and progressive blindness caused by “optic neuritis” (papilledema) were afflicted by a tumor of the cerebellopontine angle (CPA)1–4 (Fig. 45-1). At this time the only intracranial tumors that could be reliably localized involved either the motor strip or cranial nerves at the base of the brain. ANs figured prominently in the early development of neurologic surgery because they were readily diagnosable with signs and symptoms alone. The earliest attempt to remove an AN was performed in 1891 by Charles McBurney of New York, who has been immortalized by the appendectomy incision that bears his name.5 They reported that after opening the suboccipital plate with a mallet and gouge, the cerebellum swelled massively, so much so that it became necessary “to shave off the excess.” No tumor was removed and the patient expired 12 days later. The first successful results were achieved in 1894 by Ballance in London and Annandale in Scotland.6–9 In these early attempts a unilateral suboccipital craniotomy was employed, complete removal was performed by finger dissection, hemostasis was obtained by packing the CPA with gauze, and there was great emphasis on operative speed (Fig. 45-2). The outcome was dismal. At the International Congress of Medicine in London in 1913 the results of Victor Horsley (London), von Eiselsberg (Vienna), and Fedor Krause (Berlin) were presented.10 In 63 patients, surgical mortality was 78% and most of the survivors were severely crippled. It should be realized that all of these early cases were moribund at the time surgery was undertaken. Indeed, hydrocephalus was virtually universal in AN surgical candidates well into the 1930s and

Figure 45-1. Early drawing of an acoustic neuroma. (From Cruveilhier J: Anatomie pathologique du corps humain. Paris, ii, Part 26, pp 1–8, 1835–1842.)

was frequent until the computed tomography (CT) and magnetic resonance imaging (MRI) era. In the past 5 years at our institution hydrocephalus was present in only 4% of patients with ANs.11 The next era in AN surgery was ushered in by Harvey Cushing of Johns Hopkins and later Harvard (Fig. 45-3). In 1905, he advocated decompression of the posterior fossa by extensive removal of suboccipital bone.12 He reasoned that few tumors could be safely removed and that bony decompression alone might be beneficial. After this proved fruitless, he developed a technique of subtotal tumor debulking via a bilateral suboccipital craniectomy. Cushing’s greatest contributions were that he was gentle with tissues, meticulous with hemostasis, and operated deliberately without undue emphasis on speed.13,14 For hemostasis he employed Horsley’s bone wax (described in 1892) and two of his own innovations: silver clips (1911) and electrocautery (1928).15–17 By gutting only the core of the tumor, he avoided interrupting the vasculature of the brainstem and often preserved cranial nerve function. The mortality rate of his surgical patients, which was 20% in 1917, decreased following adaptation of further technical refinements, such as partial cerebellar resection, to only 4% by 1931.18 Although Cushing’s operative mortality was low, many patients succumbed to their residual tumor in later years. The next era in AN surgery was pioneered by Walter Dandy of Johns Hopkins, a pupil of Cushing. In 1916, while still a resident in training, Dandy reported a case in which he removed an AN completely.19 Cushing, who had vehemently maintained that attempts at total removal were “foolhardy in the extreme” was infuriated. Subsequent reports by Dandy in 1922, 1925, 1934, and 1941 described a unilateral suboccipital approach during which, following

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Figure 45-3. Four surgical approaches to acoustic neuroma as envisioned by Harvey Cushing in 1917. A, Suboccipital. B, Translabyrinthine. C, Combined retrosigmoid-translabyrinthine. D, Bilateral suboccipital. (Cushing H: Tumors of the Nervus Acusticus and the Syndrome of the Cerebello-Pontine Angle. Philadelphia, Saunders, 1917.) Figure 45-2. Removal of a posterior fossa tumor by finger dissection. (From Krause F: Surgery of the Brain and Spinal Cord. New York, Rebman, 1912.)

gutting of the tumor, he gently drew the capsule away from the brainstem.20–23 His eventual surgical mortality rate of about 10% was higher than Cushing’s, but this reflected his more radical philosophy of total tumor removal. There remained much animosity between Cushing and Dandy throughout their careers and the two rarely spoke with each other.24 The translabyrinthine approach, which was eventually perfected by William House in the early 1960s, has a rich early history. It was proposed by two authors in 1904, one in America and one in Europe. Rudolph Panse, an otopathologist from Dresden, proposed a translabyrinthine approach but did not actually perform one.25 George Woolsey and Charles Elsberg of New York also suggested it, citing the poor results with the suboccipital approach of the day.26 They performed cadaver dissections in which they determined that the shortest route to the CPA commenced 1 cm to 2 cm behind the ear. In 1905, M. Borchardt performed the first combined suboccipitaltranstemporal approach during which he chiseled away the temporal bone to the level of the internal auditory canal to improve exposure of the tumor.27,28 The first purely translabyrinthine craniotomy was performed by F. H. Quix of Utrecht in 1911.29 The initial operation was aborted because of bleeding from the superior petrosal sinus. It was completed at a second stage 4 days later. The operation consisted of radical mastoidectomy followed by chiseling

away the inner ear, including the facial nerve, to the level of the carotid artery. Although the patient survived the operation, he succumbed 6 months later. Postmortem examination revealed that only a tiny amount of tumor had been removed. Several reports followed by H. Marx of Heidelberg (1913),30 Von Schmiegelow of Copenhagen (1915),31 and Zange of Berlin (1915),32 but the technique passed into obscurity because of problems with inadequate exposure, hemorrhage from the surrounding venous sinuses, cerebrospinal fluid leak, and meningitis. The translabyrinthine approach was dismissed by Cushing in his classic monograph Tumors of the Nervus Acusticus (1917) in which he maintained that it was a deep wound with a narrow field of action, which would be suitable only for tiny tumors.13 In 1921, writing in Laryngoscope, Cushing stated: “If the otologist has ambitions to treat these lesions there is no possible route more dangerous or difficult than this one which has been proposed by Panse, Quix, and Schmiegelow.”14 He went on to say that “A proposal of this sort I am sure would never occur to an otologist who has general surgical training before he engaged in the particular surgery of his specialty.” These sentiments were echoed by Dandy who in 1925 called the translabyrinthine approach “a wholly impractical suggestion.”21 Such vehement opinions from the masters of their day relegated the translabyrinthine technique to utter obscurity until William House, armed with a surgical drill and operating microscope, successfully resurrected it in the early 1960s.33–35 The degree to which these early failed attempts passed from the common knowledge is well illustrated by the fact that William House

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was unaware of these pioneering efforts until some years after he had reintroduced the method. Facial nerve preservation, a primary issue in AN management, was not achieved until 1931 by Sir Hugh Cairns of London.36 Remarkably, cranial nerve monitoring had first been used by Fedor Krause of Berlin in 1898 when he identified the facial nerve “by faradic stimulation” during an eighth nerve section for tinnitus.37 Herbert Olivecrona of Stockholm, during the late 1930s and 1940s, was the first to place great emphasis on facial nerve preservation. He also employed electrical stimulation to identify the nerve and had a special nurse to observe the face during the procedure. In 1940, he reported a 65% success rate in anatomic preservation of the nerve, but only 4% early function.38 What makes these results especially remarkable is that they were achieved more than two decades before William House first used the operating microscope in AN surgery.33 The presence of tumor in the internal auditory canal was first recognized in 1910 by Folke Henschen, a Swedish pathologist.39 The radiographic appearance of porus erosion was well described by H. Stenvers of Utrecht (1917) and E. Towne of San Francisco (1926).40,41 Nevertheless, surgeons did not address this component of the tumor routinely until the 1950s. Neither Cushing nor Dandy removed this portion of the tumor. Most surgeons, even at the mid-twentieth century, truncated the tumor at the porus acusticus and coagulated the remnant. In their excellent monograph of 1957, J. Pool and A. Pava of New York state that “removal of tumor from the IAC is an essential part of the procedure.”2 They employed a sharp chisel, curette, and Kerrison rongeur rather than the less traumatic rotating burr that is popular today. It is clear that the excellent results obtained today with AN surgery are derived from efforts of intrepid early surgeons who, despite primitive equipment and dismal results, persevered until the fundamental obstacles to successful results were painstakingly analyzed and ultimately overcome (Table 45-1).

EPIDEMIOLOGY Acoustic neuromas constitute approximately 6% of intracranial tumors, a relative incidence that has been TABLE 45-1. Evolution of Operative Mortality in Acoustic Neuroma Surgery Author

Year

Cases

Krause37 Horsley17 von Eiselsberg10 Cushing13,14,18

1913 1913 1913 1917 1921 1932 1922 1925 1941 1940 1986 1990 2003

31 15 17 33 19 50 3 22 46 130 610 500 2643

Dandy20,21,23 Olivecrona38 Glasscock190 Luxford348 Barker216

Mortality 84% 67% 77% 20% 16% 4% 33% 50% 11% 21% 0.6% 0.4% 0.5%

consistent over many decades.13,42 They occur in all races, although it is not yet known whether in equal frequency. A female sex predilection has been noted by some, although not to a substantial degree. Because few countries have comprehensive tumor registries, establishing the incidence of AN in the population at large is somewhat inexact. In Denmark, a country with a rather comprehensive national database, the reported incidence of newly diagnosed AN is 9.4 per million per year with a slow increase in recent years to 13 per million, almost certainly due to better diagnostic imaging.43,44 A review of experience in a large Health Maintenance Organization in the United States (patient population of 2 million) found a yearly incidence of approximately 10 per million per year.45 Given that the current U.S. population is some 250 million, this translates to roughly 2500 newly diagnosed tumors per year. It has been aptly pointed out that the frequency of diagnosis of AN reflects not necessarily the true incidence of AN in the population at large but rather merely the fraction of tumors that have been discovered. Occult AN has been the subject of controversy for many years. In 1932, Hardy and Crowe performed an autopsy series and purportedly detected a 2.5% incidence of AN (6/250).46 In 1970, Leonard and Talbot reviewed the same pathologic material and reclassified four of the previous cases as nontumors, yielding a corrected incidence of 0.8%.47 Were this correct, some 2 million Americans would have an occult AN! Arguing against this prediction is the observation that with gadolinium-enhanced MRI scans, which are capable of detecting ANs down to the millimeter, very few ANs are being discovered incidentally on scans obtained for reasons other than suspected CPA disease. In a series from the MRI era, only 2 entirely asymptomatic tumors were encountered over a 4-year period out of a population of 126 tumors in the study group.48 Given the large number of gadolinium-enhanced MRI scans being obtained in the United States today, if the actual incidence of asymptomatic ANs approached 0.8% of the population, centers specializing in AN management would be inundated by patients with incidentally discovered tumors. Undoubtedly, a significant prevalence of undetected ANs exist in the population, but the actual incidence is most likely several orders of magnitude lower than the figure suggested by historical autopsy studies. In a recent retrospective review there were a total of 9 out of 46,414 patients with incidentally discovered ANs, a prevalence of approximately 2 in 10,000 adults.49 Acoustic neuromas occurs in two forms: sporadic and those associated with neurofibromatosis type 2 (NF2). Sporadic tumors are unilateral and comprise some 95% of cases while NF2-associated lesions are typically bilateral and account for some 5% of patients with ANs. Age at the time of diagnosis tends to differ between the two tumor types. Sporadic ANs tend to begin in midlife with a recent study showing a mean presentation in of 50 years.48 A new study suggests that familial occurrence of unilateral vestibular schwannoma (VS) may be genetically inherited since it occurs more often than would be estimated by chance alone.50 ANs in NF2 patients present at a younger age with a mean presentation of 31 years according to a recent study.51 Much variability in the age of onset has been noted with a few tumors being detected during

Acoustic Neuroma (Vestibular Schwannoma)

childhood and a rather substantial fraction during advanced age.52–54 Tumors in childhood may attain large size and, presumably due to a rapid growth rate, may possess an unusual degree of vascularity. Neurofibromatosis type 2 is a rare disease, with a prevalence in the population of about 1 in 30,000 to 50,000 people. This means that there are no more than several thousand afflicted individuals in the United States. NF1, by contrast, is much more common than NF2 with a prevalence of some 30 to 40 per 100,000 people. There are approximately 80,000 individuals with NF1 in the United States. Virtually all patients with NF2 eventually manifest bilateral ANs, but they are rare in NF1. The literature on NF1 and NF2 was often ambiguous and overlapping until relatively recently.55 Although the exact incidence is unknown, probably fewer than 2% of NF1 patients develop a unilateral AN and virtually none develop bilateral tumors.56

TUMOR BIOLOGY Pathogenesis Acoustic neuromas are schwannomas that arise from the vestibular division of the eighth cranial nerve57,58

A

731

(Fig. 45-4). Technically, they are neither neuromas nor acoustic, at least in the sense that their origin is not from auditory fibers. Because the term acoustic neuroma is a misnomer, a Consensus Development Conference of the National Institute of Health on the subject recommended that this widely used term be replaced by the more accurate vestibular schwannoma.59 The vestibular nerve, which has an approximately 2-cm course between the brainstem and the inner ear, possesses two divisions. Although formerly some have maintained that superior vestibular schwannomas predominate, current opinion favors an equal origin in the superior and inferior divisions of the nerve.60 A recent study from Japan suggests that about 85% of VSs originate in the inferior vestibular nerve.58 The eighth nerve is unusual among cranial nerves in that it possesses a long segment of central myelin. It has been proposed that ANs may arise in the region of the transition zone between the central and peripheral myelin, also known as the Obersteiner-Redlich zone.61 The evidence in the recent literature indicates that most vestibular nerve schwannomas originate lateral to the glial-schwannian junction of the nerve and not from the transition zone.62 In the proximal segment of the eighth nerve, myelin is laid down by oligodendroglial cells, while distally it is produced by Schwann cells. The neuroglial-neurilemmal junction

B

Figure 45-4. Schwannoma (A) compared with that of neurofibroma (B). Acoustic neuromas, even those associated with neurofibromatosis, are schwannomas originating from the vestibular division of the eighth cranial nerve. (From Armed Forces Institute of Pathology: Tumors of the peripheral nervous system, ATLAS #672-231, 1967.)

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most often occurs in the vicinity of the vestibular (Scarpa’s) ganglion, but its location varies considerably. This variability has been argued to account for the variable site of origin of ANs along the vestibular nerve. Arguing against the transition zone as the site of AN formation is the appearance of schwannomas apparently originating distal to it as well as multicentric origins of AN along the eighth nerve in the same patients, particularly those who have NF2s.61,63 A reasonable alternative explanation based on available evidence is that ANs originate from the Schwann cell population associated with the vestibular ganglion. It has been observed that the greatest density of Schwann cells along the eighth nerve exists at this location.64 Also supportive of this hypothesis is the finding that the junction zone and other segments of the nerve possess a consistently lower density of Schwann cells than the ganglion region does. In larger tumors, it is seldom possible to ascertain the precise site of origin along the nerve. Observations from smaller tumors indicate that most ANs arise in the internal auditory canal (IAC). A small minority of tumors originate from the nerve in its course through the CPA cistern. In our experience, all of these medial ANs began just outside the porus. We have never observed a small tumor that arose in the medial half of the cisternal course or in the brainstem root entry zone. A few schwannomas have even been reported to have arisen in the inner ear, presumably from myelinated dendrites of the vestibular nerve proximal to Scarpa’s ganglion.65,66

Molecular Genetics Great strides have been made in recent years concerning the genetic basis of AN formation. Through a variety of molecular genetic techniques, the gene responsible for AN associated with NF2 has been localized to the long arm of the chromosome 22.67–70 The disease gene was identified in 1993, and codes for a 587 amino acid protein.71,72 The product of this gene resembles certain proteins (moesin, ezrin, and radixin), which are thought to link the cell membrane with cytoskeletal components. The NF2 gene has been shown to be inactivated both in familial as well as sporadic cases. Oncogenes are regions of the genome that, when damaged, lead to tumor formation. In many instances, the defective gene elaborates a product that induces a neoplasm. In AN, by contrast, evidence points to the existence of a “tumor suppressor” gene, which, if inactivated, results in tumor growth.57 It has been speculated that the gene product is a substance that regulates Schwann cell division which, when deficient, results in excessive cellular proliferation. Because the absence of this gene product results in tumor formation, it is necessary for both copies of the involved chromosome to be dysfunctional. Thus, two mutations are required to induce an AN—one that damages each chromosomal copy. This “double hit” hypothesis fits well with theories on the genetic origin of sporadic ANs as well as those associated with NF2. In sporadic AN, two silencing mechanisms must occur in one cell to incite tumor growth. For this to occur, it must be assumed that the gene has a high spontaneous mutation rate; otherwise, such a dual event would be extraordinarily rare. It has been demonstrated that patients with NF2 carry a defective copy of the gene. When a spontaneous event inactivates

the sole remaining functional copy of the AN suppresser gene, a tumor results. Because spontaneous events happen fairly frequently, these individuals eventually develop multiple schwannomas. The nature of the genetic injury of chromosome 22 in AN has been studied in some detail.73 A major rearrangement of the chromosome was detected in 57% (23/39). The most common finding was a large interstitial deletion. Deletion of one entire copy of chromosome 22 (monosomy) was also noted in some cases as was terminal deletion, mitotic recombination, and deletion with reduplication. In the 43% (16/39) of tumors in which no chromosomal rearrangement was detected, more subtle mutations through the AN suppresser gene were suspected that were beyond the resolution of the methods employed in the study. Newer studies reveal that nearly all sporadic VSs show evidence of NF2 gene inactivation.74 Chapter 5 (Molecular Genetics in Neurotology) offers a more detailed discussion of the molecular genetics of this condition.

Molecular Mechanisms Although the biochemical aberrations that lead to AN growth have yet to be elucidated, some investigations have been performed concerning the possible role of substances known to be involved in growth regulation of neural tissue. An increased expression of the mRNA that codes for fibroblast growth factor (FGF), a potent mitogen for many connective tissue types, has been found in AN.75 Of interest, FGF mRNA was not elevated in meningiomas, a type of tumor that often coexists with AN in NF2 patients. One growth-promoting substance that may be implicated circumstantially in AN pathogenesis is platelet-derived growth factor (PDGF). The gene for this polypeptide is located on chromosome 22 near the NF2 gene. Evidence of a role for any of the above-mentioned growth factors in AN formation is decidedly preliminary. In recent studies, the NF2 gene product, Merlin/Schwannomin, has been found to interact with the two PDZ domains (postsynaptic density domains) that contain protein EBP50/NHE-RF, which is itself known to interact with the PDGF receptor (PDGFR) in several cell types. An up-regulation of both PDGFR and EBP50/NHE-RF and an interaction of both proteins were found in primary human schwannoma tissue. Upon PDGF stimulation in culture, Merlin/Schwannomin appeared to inhibit the activation of the MAPK and PI3K signaling pathways, impinging on the phosphorylation of Erk 1/2 and Akt, respectively. The data suggest that PDGFR is more rapidly internalized by the schwannoma cells overexpressing NF2. Therefore, this process is suggested as a model for a mechanism of Merlin/Schwannomin tumor suppressor function, which intermediates acceleration of the cell surface growth factor degradation.76 Another recent study suggests that a major cellular consequence of NF2 deficiency in primary cells is an inability to undergo contact-dependent growth arrest and to form stable cadherin-containing cell-to-cell junctions. These studies indicate that merlin functions as a tumor and metastasis suppressor by controlling cadherinmediated cell-to-cell contact.77

Acoustic Neuroma (Vestibular Schwannoma)

Endocrine Relationships A possible influence of sex hormones over AN growth has been postulated based on several clinical and experimental observations. In terms of genetic expression, a maternal effect has been noted in both NF1 and NF2. This was established through the observation that there is a higher morbidity among NF patients born to an affected mother than among those born to an affected father.78 Clinical series have consistently observed a slightly higher incidence of AN in women than in men, particularly postmenopausal women.44 In addition, the onset of NF2 may be earlier in women than men. It has also been proposed that the AN growth rate may accelerate during pregnancy.79 A number of investigations have been carried out in an attempt to clarify the possible influence of estrogen, progesterone, and testosterone in AN growth.80–82 High-affinity estrogen and progesterone receptors have been identified in a variable percentage of ANs. 82,83 In one investigation, cytosolic estrogen receptors were identified in 30% of ANs, cytosolic progesterone receptors were detected in 40%, and cytosolic androgen receptors in 80%.82 In a recent series, 33% of schwannomas showed expression for progesterone receptor; estrogen receptor mRNA levels were undetectable in all tumors.80 While the possible molecular mechanism of estrogen and progesterone effect on AN has yet to be elucidated, it is possible that they promote growth through inducing proliferation of the vascular endothelium.84 In breast carcinoma, the presence of estrogen receptors is an important factor in predicting responsiveness to antihormonal chemotherapy. An evaluation of antiestrogen chemotherapy may be undertaken in the future in both sporadic AN as well as in NF2. However, the relatively low rate of receptor positivity predicts that only a small subset of tumors, if any, will be influenced by this form of treatment. The level of gastrointestinal hormones has also been evaluated in AN.85 In an evaluation of 19 ANs, some tumors demonstrated elevation of the precursors of gastrin and cholecystokinin, but enhancement of the active peptides was not present. The significance of these observations is unknown.

733

was 0.9 (P = 0.07) and did not vary significantly by the frequency, duration, and lifetime hours of use. The short duration of widespread cellular telephone use, however, precludes definite exclusion as a risk for AN development.

GROSS AND MICROSCOPIC PATHOLOGY Gross Pathology The great majority of ANs are benign, relatively slowly growing neoplasms. Upon gross inspection, they are usually yellowish-white or gray and frequently possess cystic components. Many ANs appear internally heterogeneous and contain interspersed regions of soft and firm consistency. Their surface is typically smooth and regular. The most pronounced vascularity appears on the tumor surface, taking its origin from numerous small vessels of the IAC, CPA, and brainstem surface. Although ANs are frequently described as well encapsulated, little true capsule appears evident. Nevertheless, as a general rule, the tumor surface does tend to be firmer and more vascular than its central regions.

Histopathology Classically, histopathologic examination of AN reveals two morphologic patterns: Antoni A and B89–92 (Fig. 45-5). Antoni type A describes a densely packed cells with small, spindle-shaped, densely staining nuclei. Antoni type B refers to a looser cellular aggregation of vacuolated, pleomorphic cells. The Antoni B morphology seems to occur predominantly in larger tumors. In a particular AN, one type may predominate or they may be thoroughly admixed. The predominance of one variety does not appear to be of clinical significance. A whirled appearance of Antoni A type cells is a Verocay body. Nuclear atypia is occasionally seen and does not necessarily imply greater clinical aggressiveness. In Antoni B configurations, the presence of large, atypical, hyperchromatic nuclei has been

RADIATION Radiation therapy is a valuable adjunct in treatment of head and neck malignancy and selected benign lesions of the head and neck. To date, little attention has been paid to the long-term effects of radiation to the temporal bone. Recent reports highlight the possibility of radiation-induced malignancies in the temporal bone86 at a low incidence but with very poor prognosis. Therapeutic irradiation has also been shown to be capable of inducing benign intracranial schwannomas.87 Recent studies have examined the risk of radiofrequency radiation emitted from cellular telephones on the development of AN. The hypothesis that intracranial energy deposition from handheld cellular phones might cause AN was tested in an epidemiologic study of 90 patients and 86 control subjects.88 In patients who used cellular telephones, the tumor occurred more often on the contralateral than ipsilateral side of the head. The relative risk

Figure 45-5. Photomicrograph of an acoustic neuroma with regions of both Antoni type A (more dense) and B (looser) morphology. Verocay bodies, palisading nuclei around regular central regions, are also typical of schwannomas. (From Armed Forces Institute of Pathology: Tumors of the peripheral nervous system, ATLAS #672-231, 1967.)

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termed ancient schwannoma by pathologists. A positive S-100 immunoperoxidase stain is confirmatory of Schwann cell origin.93 Although not usually needed, electron microscopy may assist in confirming the diagnosis of AN through identification of the typical Schwann cell basement membrane.94 During their growth ANs are “pushers” that progressively displace adjacent structures, often without macroscopic signs of invasion. Upon close examination, however, a substantial tendency toward microinvasiveness has been detected.63,95–98 Degeneration of a benign AN into a malignant schwannoma has been reported, but is exceedingly rare.99,100 Malignant schwannoma has been reported to arise in approximately 5% of patients with NF1, although a thorough search of the literature failed to identify such a tumor of eighth nerve origin.101 A number of peripheral malignant schwannomas have arisen following irradiation therapy to apparently benign lesions.102

GROWTH CHARACTERISTICS Growth Pattern Growth of ANs can be considered in four anatomic stages: intracanalicular, cisternal, brainstem compressive, and hydrocephalic (Table 45-2). ANs typically begin in the IAC and can be discovered at a stage when they are wholly intracanalicular (Figs. 45-6 and 45-7). As they begin to protrude into the CPA cistern, they initially displace CSF, cranial nerves VII and VIII, and the anterior inferior cerebellar artery (AICA) (Figs. 45-8 and 45-9). Upon contacting the lateral pontine surface, the brainstem compressive stage commences (Fig. 45-10). At approximately this time the fifth cranial nerve becomes involved. As brainstem compression becomes severe, the fourth ventricle collapses and the hydrocephalic stage begins (Figs. 45-11 and 45-12). This growth pattern is highly stereotypic, but some variations exist. As mentioned earlier, the degree of IAC involvement varies widely and some tumors even spare the

A

TABLE 45-2. Symptomatic Progression of Acoustic Neuroma with Tumor Growth Stage

Symptoms

Intracanalicular

Hearing loss Tinnitus Vertigo Hearing loss worsens Vertigo diminishes Dysequilibrium increases Midfacial and corneal hypesthesia (V) Occipital headache (occasionally) Ataxia begins Worsening trigeminal symptoms Gait deteriorates Headache becomes generalized Visual loss due to increased intracranial pressure Lower cranial nerve dysfunction (Hoarseness, dysphagia, aspiration, shoulder and tongue weakness) Long tract signs Death due to tonsillar herniation

Cisternal Brainstem Compressive Hydrocephalic

B Figure 45-6. Illustration (A) and MRI scan (B) in the axial plane of an intracanalicular acoustic neuroma.

IAC entirely. The cisternal component, which is typically globular and centered over the IAC, can be ovoid or have its center of mass lie above the plane of the IAC. Tumors that are ovoid in the medial-lateral plane may indent the brainstem to a degree that seems out of proportion to its diameter. Similarly, tumors ovoid in the anterior-posterior plane may become relatively large with minimal brainstem compression. Cystic components or intratumoral hemorrhagic regions can also distort the tumor’s geometry and result in an asymmetric bulge.

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A

Figure 45-7. Schematic illustration of an intracanalicular acoustic neuroma in the coronal plane.

Growth Rate The growth rate of ANs has been studied both in vitro and in vivo. The fraction of dividing cells in an AN has been assessed by immunohistochemical means with the fraction of proliferating cells ranging between 0.36% and 3.15%.103 Similar findings were obtained for schwannomas of various sites of origin evaluated via preoperative infusion of the thymidine analog 5-bromodeoxyuridine. In this study, the fraction of tumor cells in replication (S-phase) was found to vary from 0.1% to 3.1% (mean 0.9%).104 A wider range was detected in a study of archival formalinfixed tissue subjected to flow cytometric analysis.105 The S-phase fraction varied from 1.1% to 20.7% (mean 6.3%). Of interest, evaluation of the clinical records of the 49 patients in this study failed to reveal a correlation between proliferative rate and patient gender, symptom manifestation, or tumor size. A possible correlation with tumor growth rate could not be excluded from this study. It has also been observed that small tumors have a lower mitotic index on average than larger tumors.106 No correlation has been detected between the age of the patient and the proportion of mitotically active cells in AN.106 Several studies have been performed using Ki-nuclear antigen as well as PCNA (proliferative nuclear antigen) as an indicator of tumor growth.107,108 The results suggest that the growth rate of vestibular schwannomas varies and

B Figure 45-8. Illustration (A) and MRI scan (B) in the axial plane of an acoustic neuroma in the cisternal stage.

may explain the difficulties in estimating the growth of neuromas on the basis of clinical aspects only. Although ANs grow at a variable rate, they are, by and large, slowly growing tumors (Table 45-3). Only in recent years, since the advent of CT and MRI scanning, has accurate serial measurement of untreated tumors become possible. There are numerous studies of ANs serially studied by high-resolution imaging studies in the literature. When the available data are analyzed, ANs increase in diameter an average of 0.1 cm to 0.2 cm per year. In one large study, 50 patients were followed an average of 41.7 months with a range of 7 to 152 months.109 The mean diameter growth was 0.11 cm per year with a range from −0.51 cm (reduction in size) to 0.98 cm growth per year. Although only a few patients had a reduction in tumor diameter, 34% showed no discernible growth, and in only 22% did

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SURGICAL NEUROTOLOGY

A

A

B Figure 45-9. Schematic illustration (A) and MRI scan (B) of a cisternal stage acoustic neuroma in the coronal plane.

growth exceed 0.2 cm per year. In a meta-analysis study, 526 patients were followed an average of 36 months.110 The mean growth rate was 0.18 cm with 54% of patients showing radiologic growth. The growth group with 178 patients showed a mean growth rate of 0.4 cm per year (range 0.14 cm to 0.56 cm per year). One must be cautious in interpreting these data to indicate that a large fraction of ANs remain stable over the long term. First, patients in the above studies were deemed suitable for observation, undoubtedly based, in most cases, on a relatively mundane clinical course. Patients with more dramatic or rapid-paced symptomatology would not have been managed conservatively and thus the patient population is somewhat biased. Second, insufficient observations are available for 5-, 10-, or even 20-year intervals and patients often relate a gradual symptomatic progression over such periods. It is probable that most tumors that are

B Figure 45-10. Illustration (A) and MRI scan (B) in the axial plane of an acoustic neuroma in the early brainstem compressive stage.

apparently stable for 1 or 2 years will eventually demonstrate clinically relevant progression if observed for a decade or longer. Third, the criteria to measure the tumor size are still variable and not even consistent in the same institution. For this reason, the clinician is wise to avoid overly reassuring younger patients. Fortunately, the fraction of rapidly dividing tumors (exceeding 1 cm per year) is small, perhaps

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A A

B Figure 45-11. Illustration (A) and MRI scan (B) in the axial plane of an acoustic neuroma in the late brainstem compressive stage.

only 10. It is also helpful for the clinician to be aware that once a growth rate has been established for a particular tumor, this tends to remain consistent over time.111 This observation may be helpful in counseling the older patient regarding likely growth of the tumor over his or her predicted lifespan. Nevertheless, the correlation between the rate of tumor growth and the pace of symptomatic progression is imperfect. Some patients suffer symptomatic

B Figure 45-12. A, Coronal representation of the brainstem deflection associated with a large acoustic neuroma. (From Cushing H: Tumors of the Nervus Acusticus and the Syndrome of the Cerebello-Pontile Angle. Philadelphia, Saunders, 1917). B, Coronal MRI scan illustrating dramatic pontine compression caused by a large acoustic neuroma. Note the obstruction of the fourth ventricle and dilatation of the lateral ventricles.

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TABLE 45-3. Natural History of the Untreated Acoustic Neuroma Report Selesnick110 Charabi349 Walsh182

Year Pre-1998 2000 2000

No. of Patients

Follow-up (mean)

558 126 72

3 yr 3.8 yr 3.2 yr

Stable

Smaller

Larger

— 12% 50%

— 6% 14%

54% 82% 37%

progression, particularly in hearing and balance function, despite imaging studies that demonstrate no growth. As a final caveat, many clinicians have maintained, based on anecdotal observations, that ANs seem to progress more slowly in the aged. However, this contention is supported by neither clinical nor laboratory studies, both of which show a range of growth rates in the elderly similar to that in younger individuals. Vestibular schwannoma growth rates in NF2 are generally higher in younger people but are highly variable, even among multiple NF2 patients of similar ages in the same family112 (Fig. 45-13). Occasional ANs expand at a rate far exceeding the norm due to rapid enlargement of a nonneoplastic component of the tumor (Fig. 45-14). Abrupt hemorrhage into an AN has been reported and may result in the sudden worsening of neurological status.113 Such intratumoral hemorrhage can be triggered by head injury or vigorous physical exertion. In addition, accumulation of fluid in cystic regions of the tumor may lead to a relatively rapid increase in mass effect. Both intratumoral hemorrhage and cystic expansion can result in a rise in tumor volume at a rate well in excess of that possible through growth of the cellular component of the tumor. It has been estimated that one of these events occurs in approximately 2% of ANs.114

A

B Figure 45-13. Bilateral acoustic neuromas associated with neurofibromatosis type 2.

Figure 45-14. Cystic acoustic neuroma before (A) and after (B) sudden expansion as a result of intratumoral hemorrhage.

Acoustic Neuroma (Vestibular Schwannoma)

Measurement of Acoustic Neuromas

CLINICAL MANIFESTATIONS

There is still no universally accepted method of measuring ANs. However, a common language for expressing tumor size is essential for valid comparisons among diagnostic and therapeutic modalities. Two features of ANs complicate measurement: their irregular geometry and the nonlinear relationship between tumor diameter and volume. Were ANs spherical, then a simple assessment of tumor diameter in a single plane would be sufficient. However, inclusion of the narrow tongue of tumor in the IAC in diameter measurements tends to substantially overestimate tumor size. Most authors advocate description of an AN’s size in terms of the diameter of the CPA component of the tumor as measured in three axes: (1) parallel to the petrous ridge, (2) perpendicular to the petrous ridge, and (3) vertically.115 The first two measurements are determined from axially oriented scans, the third from coronal images (MRI or CT). Thus, a tumor may be expressed as being 3.2 × 4.1 × 3.9 cm, for example. For ease of comparison, many would simplify this to the single largest axial dimension (e.g., 4.1 cm). As little data is published in the literature using other than a single diameter measurement, this method is used in the present chapter. Of course, wholly intracanalicular tumors must be considered separately because they possess no CPA component. Definition of AN size ranges into small, medium, large, and giant sizes is useful in permitting comparison among treatment groups. While there is no unanimity in defining these ranges, it is reasonable to divide ANs into the following categories: intracanalicular, smaller than 1.0 cm, 1.0 cm to 2.5 cm, 2.5 cm to 4 cm, and larger than 4 cm. Attempts are under way to establish an internationally accepted measurement standard.115,116 It has been pointed out that relatively small increases in tumor diameter produce a much greater increase in tumor volume.117 If it is assumed that the CPA component of most ANs are roughly spherical, then the interrelationship of tumor diameter and volume can be estimated as 4/3 πr3 where diameter = 2r. As computed imaging programs become more sophisticated, comparison of tumor size based on volumetric calculations is likely to replace diameter-based measurement systems.

Typical Clinical Presentation Although it is possible to describe a typical clinical presentation of AN, it is important for the clinician to be aware of remarkable degree of variability in the manifestations of these tumors (Table 45-4). With this caveat in mind, it is helpful for the diagnostician to develop a mental framework based on the most representative symptom complex for each stage of AN growth. The symptoms associated with intracanalicular ANs are typically limited to the eighth nerve: hearing loss, tinnitus, and vestibular dysfunction. During the cisternal stage, hearing loss may worsen and vertigo gradually becomes replaced by dysequilibrium. At about the time when brainstem compression begins, trigeminal symptoms commence, initially in the midfacial region. As brainstem compression becomes severe, the fourth ventricle collapses and hydrocephalus results. Chronic hydrocephalus frequently results in visual loss and persistent headache. The terminal stages involve contralateral long tract signs (e.g., hemiparesis) and eventual respiratory death due to herniation of the cerebellar tonsils.

Signs and Symptoms Hearing Loss Occurring in well over 95% of patients, hearing loss is the most frequent symptom of AN. The mechanism, in most cases, is from compression and/or infiltration of auditory nerve fibers. Impairment of the blood supply to the nerve or inner ear also plays a role in some cases. In the majority of patients, hearing loss progresses gradually over many years, eventually leading to total deafness in the tumor ear. The loss is typically unilateral or asymmetric which, in its early stages, preferentially involves the high frequencies. Characteristically, speech discrimination is affected out of proportion to pure tone hearing loss. Atypical forms of hearing loss are relatively frequent. In a study of a large group of patients with ANs, only 66% had a high-frequency biased hearing loss and approximately 20% had an upsloping or trough-shaped loss, configurations

TABLE 45-4. Clinical Symptoms of Vestibular Schwannoma Clinical Manifestations Hearing Loss Tinnitus Dysequilibrium Vertigo Trigeminal Nerve Facial Nerve Headache Visual Symptoms Lower Cranial Nerves Dysphagia Papilledema Asymptomatic

Cushing13

Mathew350

Selesnick11

100%

97% 66% 46% 5% 33% 22% 29% 15%

85% 56% 48% 19% 20% 10% 19% 3% 0% 0%

63% 77% 100% 87% 53%

739

Matthies119 95% 63% 61% 61% 16.5% 17% 12% 1.8% 2.7%–3.5%

1.6%

Modified after Driscoll CLW: Acoustic Neuroma. In Jackler RK, Driscoll CLW: Tumors of the Ear and Temporal Bone. Philadelphia, Lippincott Williams & Wilkins, 2000.

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frequently ascribed to other causes.118 A sudden decrease in hearing, often equated by clinicians with viral infection or vascular occlusion, occurs in some 26% of ANs.48,119 Presumably, sudden hearing loss results from a spasm or occlusion of the internal auditory artery as a result of tumor compression. In some patients it may be triggered by head trauma or vigorous physical exercise. The loss may be partial or total, and spontaneous recovery is possible.120 Sudden loss may be the sentinel event that leads to a diagnosis or it may occur months or years before the tumor’s discovery. The diagnostician’s dilemma stems from the fact that only some 1% to 2% of patients who have sudden hearing loss will ultimately prove to have an AN. As a general rule, we advocate a diligent search for ANs in patients with sudden hearing loss. A small fraction of patients with ANs have either normal hearing or symmetric hearing loss.48,121 Before the era of high-resolution imaging, most series showed 1% to 3% of patients with AN had normal hearing. In a recent series from the MRI era, 15% of patients with ANs had subjectively normal hearing, of whom 4% were audiometrically normal (SRT < 25 dB, SDS >85%). In addition, 7% of patients had audiometrically symmetric hearing. It is clear that the clinician must be alert to nonauditory symptoms if such tumors are to be detected early. Tinnitus Tinnitus is very frequent in AN since it is many inner ear diseases. In several studies, up to 70% of the patients suffered preoperative tinnitus.48,119,122 In most cases, the tinnitus is high pitched and localized to the tumor ear.123 However, the symptom may be nonlocalizing and may be of unusual pitches. The tinnitus is seldom very disturbing to the patient. A few patients with AN have unilateral tinnitus in the absence of subjective hearing loss. Thus, unilateral tinnitus without explanation is an indication for an evaluation for AN. Vertigo, Dysequilibrium, and Dysmetria Disturbance of the vestibular and cerebellar functions may generate a variety of symptoms in patients with ANs. Vertigo, the cardinal symptom of peripheral vestibular dysfunction, is an illusion of motion that is usually evoked or worsened by a change of head position. Subjectively, the typical complaint is of a whirling sensation, but other sensations such as that of ground rolling or falling backward may occur. Vertigo is episodic, and dysequilibrium is a continuous sense of instability. The patient with dysequilibrium may complain of a minor incoordination or clumsiness, particularly of gait, as well as a generally unsteady feeling. Although there is some overlap, the symptoms of vertigo and dysequilibrium are usually quite distinct in patients with ANs. True vertigo is not commonly associated with ANs. In a recent series, only 19% of individuals reported this symptom, most of whom had small tumors.48 Vertigo is decidedly infrequent with larger tumors at the time of diagnosis, although some patients relate having been through an episode some years before the discovery of their tumor. Thus, it appears that vertigo is generated early in AN growth,

perhaps by destruction of the vestibular nerve or through interruption of the blood supply to the labyrinth. Dysequilibrium is much more prevalent than vertigo, occurring in nearly half of patients with ANs.48 In contrast to vertigo, which decreases in incidence with increasing tumor size, dysequilibrium becomes more frequent with larger tumors. Larger tumors (>3 cm) have a higher than 70% incidence of this disturbing symptom. The most likely mechanisms involved in causing dysequilibrium are uncompensated unilateral vestibular deafferentation and persistent perverse input from the diseased vestibular nerve. The characteristic symptoms of cerebellar dysfunction are intention tremor and gait ataxia. Large ANs indent the lateral cerebellar lobe and peduncles and may impair the output of a sizable fraction of the ipsilateral cerebellar hemisphere. Somewhat surprisingly, overt cerebellar dysfunction is uncommon in ANs and is limited to large tumors.124 Although little information is available on its exact incidence, truncal ataxia appears to be more common than limb ataxia. Patients tend to fall toward the side of the tumor, although not invariably so. Facial Anesthesia and Pain Facial sensory dysfunction occurs in approximately 50% of tumors larger than 2 cm and is rarely present with smaller lesions.48,125 Hypesthesia of the midfacial region is the most common symptom. This decreased sensation is often associated with tingling. Many patients and physicians alike erroneously attribute these symptoms to sinus or dental disease. Gradually, the upper and lower divisions of the trigeminal nerve become involved with the evolution of more widespread hypesthesia, which eventually progresses to anesthesia. In patients with symptomatic trigeminal nerve dysfunction, the corneal reflex is almost always decreased or absent. Of note, the corneal reflex is also impaired in a considerable number of patients with larger tumors who have not been aware of any facial sensory disturbance. Facial pain may also result from ANs. Trigeminal neuralgia is an uncommon but certainly not rare manifestation in large tumors.126 Tumor-associated pain responds quite well to therapy with carbamazepine in much the same manner as the idiopathic form of the disease (tic douloureux). A possible pathogenic mechanism is displacement of a vessel (e.g., the superior cerebellar artery or the petrosal vein) by the tumor into the root entry zone of the trigeminal nerve. Contralateral trigeminal neuralgia has also been reported but is very rare.127 Dysfunction of the motor division of the trigeminal nerve is a symptom limited to a few advanced ANs. Unilateral temporal wasting and masseter atrophy may be noted on exam, and cross bite is a possible functional sequelae. We have encountered one NF2 patient with bilateral masticatory paralysis, a situation that made gavage feeding of puréed foods necessary. Facial Weakness and Spasm It is indeed surprising, given the location of the facial nerve (FN) in the epicenter of tumor growth, that disturbances of facial mimetic function are uncommon during the natural

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history of AN growth. The FN appears to be robust in that it can sustain substantial compression, stretch, and torsion from an AN and maintain its functional integrity. Although overt weakness is uncommon except in very large tumors, a degree of facial twitching occurs in approximately 10% of patents.48 Facial hyperfunction appears to be independent of tumor size. The most common manifestation is a minor quivering of the orbicularis oculi muscle. Hyperfunction can coexist with weakness. Full hemifacial spasm is uncommon. In one such case encountered in our group, an artery displaced by the tumor appeared to impinge on the root entry zone of the FN. The great majority of patients with ANs possess clinically normal facial function; however, subclinical motor impairment is occasionally detected electromyographically. Abnormalities in evoked electromyography and the blink reflex may be demonstrated in a minority of patients with apparently normal facial function.128 The FN is a mixed nerve that possesses a sensory component. It is distributed over the posterior aspect of the ear canal and conchal bowl of the pinna. Diminished sensation over this region has been described as a sign of AN, although it is of little practical significance. This observation is generally known as Hitzelberger’s sign.129

peripheral vision, the development of tunnel vision, and eventual blindness. It should be noted that not all patients with increased intracranial pressure develop papilledema, and not all patients with papilledema develop visual loss. In one study of eight patients with papilledema due to AN, none demonstrated impaired vision.131 Papilledema is usually bilateral and symmetric, although visual loss is frequently asymmetric. Diplopia is an unusual finding in AN. Either the fourth or sixth nerves can be paralyzed by a large AN, although this is extremely rare. The function of the sixth nerve can also be impaired secondarily, as a result of increased intracranial pressure.

Headache

Late Symptoms

The incidence of headache with ANs depends greatly on size. Very few patients with small tumors have headaches that can reasonably be attributed to the tumor. In medium-sized tumors (1 cm to 3 cm) the incidence is approximately 20%, and in large tumors it exceeds 40%.48 Headache associated with AN is variable.2,124,130 Most commonly it is either focused in the suboccipital region or generalized. It is attributable to hydrocephalus in only a minority of cases. Interestingly, not all patients with obstructive hydrocephalus due to AN suffer from headache.

As a result of much improved diagnostic modalities, the advanced symptoms of AN are seldom seen today. In many ways it is illuminating to read the classical descriptions of the agonal stages of the natural history of AN’s symptomatic evolution.3,13 Long tract signs are seldom reported in contemporary studies. Indeed, patients may have advanced brainstem compression and hydrocephalus with severe loss of balance but still have motor and sensory function to the extremities. The progression from hyperreflexia to paresis to paralysis can be quite rapid as increased intracranial pressure becomes critical. The level of injury may be pontine, from direct tumor pressure, or indirect at the lower medulla due to herniation of the cerebellar tonsils. Ipsilateral findings characterize the first mechanism, and the latter may cause bilateral or even contralateral dysfunction. In the final stages of the AN natural history, depressed consciousness and stupor results. Intractable vomiting may occur. In the terminal event, the patient lapses into coma and expires with respiratory arrest.

Ophthalmologic Manifestations The most common ophthalmic manifestations of AN are nystagmus and decreased corneal reflex.131 A degree of spontaneous nystagmus in the horizontal plane is frequent with even small tumors, presumably as a result of vestibular nerve involvement. There is a tendency for the nystagmus to beat toward the intact side, although much variation exists.132 With large tumors, however, pronounced vertical plane nystagmus may be seen as a consequence of brainstem compression. Another important ophthalmic manifestation is papilledema from hydrocephalus. Historically, increased intracranial pressure was ubiquitous at the time of AN diagnosis. Today, it has become a rare finding. In our series, only 4% of patients with ANs had hydrocephalus.48 While hydrocephalus is usually obstructive, due to collapse of the fourth ventricle, it may also be communicating. Communicating hydrocephalus presumably results from substances secreted by the tumor into cerebrospinal fluid (CSF), which impairs the resorptive function of arachnoid granulations. Chronic increased intracranial pressure may lead to optic atrophy manifested by progressive loss of

Lower Cranial Nerves Dysfunction of the lower cranial nerves (IX–XII) can result in hoarseness, aspiration, dysphagia, and/or weakness of the ipsilateral shoulder. Even very large ANs seldom penetrate the jugular foramen, although the intracranial course of these nerve fibers may lie draped on the lower pole of the tumor. Dysfunction of these nerves is sufficiently rare (up to 3.5 %119) that, when present, suspicion of a coexisting schwannoma of the jugular foramen region is warranted.

Sudden Neurologic Deterioration Intratumoral hemorrhage is a rare occurrence in patients with ANs but may result in sudden neurologic deterioration due to the onset of an acute CPA syndrome (see Fig. 45-14).113,133 The patient may experience hearing loss, acute facial spasm or weakness, facial sensory disturbance, hoarseness, and even somnolence and long tract signs. Episodes of hemorrhage might be triggered by vigorous physical exercise or head trauma. Emergent surgical intervention may be required. Extratumoral hemorrhage also occurs in association with AN but is very rare. The patient suddenly develops signs and symptoms of subarachnoid hemorrhage with severe headache, nuchal pain, nausea and vomiting, and

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mental status changes. One possible cause of subarachnoid hemorrhage is rupture of a contact aneurysm arising from a vessel laying against the tumor capsule. In one reported case, the posterior inferior cerebellar artery was aneurysmal.134 Other possible mechanisms include bleeding from a tumor surface vessel or rupture of a hemorrhagic cyst.135

AUDIOLOGIC DIAGNOSIS Pure Tone and Speech Audiometry Because Chapter 7 (Hearing Loss in Neurotologic Disease) comprehensively covers the audiologic diagnosis of AN, only a brief summary is provided here. The primary role of audiologic tests is to help identify the population at risk of an AN.48,121,125,136,137 Conventional pure tone and speech audiometry remain the most useful and cost-effective screening tools in helping to define who should undergo auditory brainstem responses or an imaging study. Based on these two tests a classification has been proposed by the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery to establish guidelines for reporting results in hearing preservation surgery. Therefore, this classification is used in this chapter (Fig. 45-15). The so-called special testing battery, a mainstay in the detection of ANs during the 1960s and 1970s, has essentially no role today. This includes short increment sensitivity index, alternating bilateral loudness balance, tone decay, and other tests. This protocol has been largely abandoned due to its lack of specificity and sensitivity in AN detection when compared with auditory brainstem response (ABR). Two components of this test regimen remain in

Figure 45-15. The American Academy of Otolaryngology-Head and Neck Surgery classification system for hearing following acoustic neuroma surgery. The vertical axis represents the four tone average (500, 1000, 2000, 3000 dB) and the horizontal axis is word recognition score (%).

widespread use: rollover and acoustic reflex decay. In rollover, the speech discrimination worsens with increasingly loud presentation of the phonetically balanced word list. In reflex decay, the acoustic reflex fades during a prolonged presentation of the signal presumably due to fatigue of the auditory nerve. Neither test is very sensitive nor specific, but when one is abnormal, it might trigger the next step in the diagnostic algorithm even when the pure tone and speech results show little cause for suspicion.

Auditory Brainstem Responses The ABR is the most sensitive and specific of all audiologic tests for AN. In documented ANs, a review of the literature reveals that approximately 20% to 30% have no waves, 10% to 20% have only wave I and nothing thereafter, 40% to 60% have all waves but a wave V latency delay, and 10% to 15% have normal findings.138 Among abnormal ABRs, the ABR pattern most specific for AN is the presence of a wave I and nothing thereafter. As a general rule, the larger the tumor, the more severe the ABR abnormalities. However, notable exceptions exist and we have encountered large tumors with normal ABRs. The diagnostic efficiency of ABR has been extensively studied for both its sensitivity and specificity in AN diagnosis.139 Many reports give the sensitivity of ABR in the diagnosis of AN in the range of 96% to 99%.138 However, these studies typically rely on CT scanning or even polytomography as the gold standard of diagnosis. Recent experience, from the era of enhanced MRI scanning, demonstrates a substantially higher rate of false-negative results. Numerous reports of false-negative ABRs have appeared in the literature.138,140 In 1992, Wilson and coworkers reported an overall false-negative rate of 15% (6/40).141 Importantly, ABR was normal in 33% (5/15) of intracanalicular tumors. ABR appears to be more sensitive for larger lesions, with only a 4% (1/25) false-negative rate. In a study of four patients with ANs who had normal conventional ABRs, measurement of the latency-intensity relationships detected abnormalities in three, a substantial improvement in the diagnostic yield.142 The latencies were abnormally long at low intensities but converged toward normal as intensity increased. Neurotologists have generally thought that an abnormal ABR had a fairly high specificity for AN.143 However, recent studies reveal a surprisingly high incidence of falsepositive studies. In one study, only 15% (4/26) of patients with ABRs indicative of a retrocochlear loss proved to have an AN.144 In another study, only 12% (23/185) of patients with abnormal ABRs actually had tumors.145 In a third study, which used the relatively stringent criteria of IT5 > 0.6 msec, only 18% of tested patients actually had CPA lesions.146 Undoubtedly, the incidence of false-positive results is somewhat affected by the sophistication of both the equipment and test giver, as well as by the definitions of abnormality employed. Nevertheless, in real-world audiologic settings, the false-positive rate for ABR in AN diagnosis appears to exceed 80%, a percentage consistent with our own experience. This observation is important in assessing the economic efficiency of diagnostic protocols used in the evaluation of patients with suspected ANs. Of note, it has been reported that the specificity of a

Acoustic Neuroma (Vestibular Schwannoma)

positive ABR is considerably greater in younger individuals.145 In large tumors that cause much brainstem deformation, the contralateral ABR may be abnormal.147 Currently a new ABR technique called stacked ABR seems to show a higher detection rate of VN with fewer false-positive results. Time and studies, however, must show whether this technique has additional value.148–150

Otoacoustic emissions In theory, otoacoustic emissions (OAEs) should make an excellent screening tool for ANs because they reflect outer hair cell function. With OAEs, significant sensory hearing loss suggests a retrocochlear cause. Unfortunately, ANs cause both sensory and neural hearing loss. The sensory hearing loss is presumably caused by either decreased blood supply to the inner ear or other unknown factors. In recent years, several studies have proposed the use of otoacoustic emissions in ANs as risk stratification for hearing conservation.151–154 These studies focused on the identification of patients with impaired retrocochlear conduction but intact cochlear function. Particularly patients with preoperative class C and D hearing and largely immeasurable ABR could benefit from hearing conservation surgery in case of intact cochlear function. However, the number of patients with these criteria seems to be very low and will probably not lead to a significant increase of hearing conservation approaches in patients with preoperative class C or D hearing.155 Further studies will have to evaluate the role of OAEs in AN surgery.

VESTIBULAR TESTING Electronystagmography Vestibular evaluation with electronystagmography (ENG), rotatory testing, and dynamic posturography is frequently abnormal in patients with ANs. The ENG test battery detects some abnormality in approximately 70% to 90% of patients with ANs.132,136,156–159 The caloric response is the most readily quantifiable test in the battery and the one most able to localize the side of pathology. In the setting of AN, a depressed or absent caloric response indicates injury to the superior vestibular nerve or impaired vascularity to the labyrinth from compression of the internal auditory artery. When tumors of all sizes are considered, approximately 50% of tumor ears have absent caloric responses, and most of the remaining patients have a partial reduced response.157,160 While very few larger tumors have normal caloric responses, as many as 50% of small tumors demonstrate caloric symmetry. Since the caloric response is generated by the superior vestibular nerve (innervation to the lateral semicircular canal), tumors originating from this nerve demonstrate a higher frequency of abnormalities. It has been reported that 98% of ANs originating from the superior vestibular nerve show a reduced caloric response; this is true for only 60% of those arising from the inferior division.159 Of course, once an inferior vestibular nerve tumor has attained considerable size, it can be expected to destroy the adjacent superior division. It has been suggested

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that improved sensitivity for small tumors of inferior vestibular nerve origin may be achieved using an infrared video system that records rotatory nystagmus, which can be missed by conventional systems.161 Pathologic nystagmus takes a variety of forms in patients with ANs and may result from either eighth nerve or brainstem dysfunction.132,157,160 Only a minority of patients with small tumors demonstrate spontaneous nystagmus, but it is quite prevalent in larger tumors (75% to 95%). The character of the nystagmus also differs between small and larger tumors. In small tumors, it tends to be characteristic of peripheral labyrinthine dysfunction; in tumors with brainstem compression, central patterns predominate (vertical plane, ageotrophic, nonfatiguing). The nystagmus can be spontaneous, positional, gaze paretic, or dissociated and may be unilateral or bilateral. As a general rule, nystagmus tends to beat preferentially away from the tumor ear.132 Several ENG abnormalities in patients with ANs are attributable only to brainstem compression, and thus are not encountered in smaller tumors. Fixation suppression of caloric induced nystagmus is impaired in roughly 20% to 50% of large tumors.157,160 Disturbances in vestibulo-ocular control may also occur. Asymmetries in optokinetic nystagmus and poor tracking on smooth pursuit are present in a minority of large tumors. Deficient optokinetic responses tend to occur in the direction opposite from the tumor ear.132

Rotatory Testing The integrity of the vestibulo-ocular reflex can be assessed physiologically through use of a rotatory chair device. In one study of 18 patients with ANs, abnormalities were demonstrated in all patients including disturbances in phase lag (72%), gain (62%), and symmetry (100%).162 In another investigation involving 84 tumors, far fewer abnormalities were noted. Overall 74% of patients were normal, including 100% of patients with small tumors.157 In yet another series of 24 patients, 33% of patients with ANs demonstrated no abnormalities on rotatory testing.163

Dynamic Posturography In a study of 40 patients with ANs, a wide variation of responses on sensory organization tests was noted from normal to falling.156 Average performance was somewhat below normal levels. No correlation between posturography performance and caloric test results was found. The authors recommend the test as a means of quantifying the complaint of unsteadiness as well as to monitor the effects of surgery and to guide postoperative rehabilitative efforts. In a retrospective study of six patients with small tumors, patients with inferior vestibular nerve tumors had greater instability at higher sway-referenced gains than did those with superior vestibular lesions.164 Because each patient with inferior vestibular nerve tumors had normal calorics and abnormal posturography, it was proposed that posturography might help to make the preoperative distinction between superior and inferior nerve origin. An awareness of the probable nerve of origin may be relevant to the decision of whether to pursue a hearing conservation approach (as discussed later).

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Utility of the Vestibular Test Batteries Unfortunately, no vestibular test taken alone or in conjunction with others has demonstrated sufficient sensitivity or specificity to be of much use in the diagnosis of AN. The high false-negative rates (i.e., normal test results in patients who have a tumor) preclude using normal vestibular data to exclude a patient from consideration of AN. The high false-positive rate (i.e., abnormal tests results due to causes other than AN) means that vestibular test data, if taken alone, would tend to excessively recommend referral for a definitive imaging study. For these reasons, we do not routinely perform vestibular investigations in patients suspected of having an AN, preferring to rely instead on ABR and imaging studies to decide the issue. Of course, when features of history or physical examination suggest chronic vestibulopathy and AN has been excluded by other investigations, then a vestibular test battery is obtained to guide therapy and rehabilitation. The vestibular test battery can be helpful in prognosticating the speed and completeness of vestibular compensation following AN resection. With progressive growth of an AN, the involved vestibular nerve is gradually rendered nonfunctional. Because this is a slow process, compensation is often imperceptible to the patient who remains functionally intact. However, during tumor removal all residual functioning vestibular fibers are interrupted. This helps to explain the paradoxic finding that patients with small tumors (and thus a greater fraction of intact vestibular nerve fibers) suffer more immediate postoperative vertigo than those with large lesions. On preoperative ENG, the more depressed the caloric response in the tumor ear, the less acute vestibular withdrawal is noted postoperatively. We do not routinely obtain ENG for prognostic purposes because knowledge of this status does not materially alter management of the patient.

RADIOLOGY Chapter 21 (Imaging the Cerebellopontine Angle) comprehensively covers the radiographic diagnosis of AN, so only a brief summary is provided here. There have been four major eras in the evolution of imaging technology in the diagnosis of AN: plain films of the IAC (1910s), polytomography (1950s), CT (1970s), MRI (early 1980s). Both plain films and polytomography do not image the tumor directly, but rather rely on detection of osseous changes involving the IAC. Because a high percentage of ANs do not expand the IAC or do so only minimally, these were not sensitive methods. The addition of contrast (e.g., Pantopaque) into the CPA cistern improved diagnostic efficiency with polytomography, but it was invasive and often difficult to interpret. Contrast-enhanced CT scanning was a substantial advance over prior studies. Tumors larger than 2 cm could be reliably detected, but small lesions were often overlooked. Diagnostic yield could be improved through instillation of several mL of gas into the CPA cistern and IAC, however, this was frequently followed by spinal headache. In addition, gas-contrast CT had a relatively high false-positive rate due to poor penetration of the gas into the IAC. This had the tendency to create a convex-

bordered filling defect suggestive of an intracanalicular AN, particular when the IAC was narrow. The introduction of MRI in the early 1980s was a major improvement in AN diagnosis. Early MRIs demonstrated an excellent ability to detect ANs but were somewhat unreliable when it came to intracanalicular lesions. This has been greatly improved since the introduction of gadolinium-enhanced MRI (Gd-MRI).165,166 ANs enhance with contrast more brightly on T1-weighted scans than any other intracranial tumor. The sensitivity of a thin-section Gd- MRI scan targeted to the IAC is excellent, with lesions as small as 1 millimeter within its resolution. MRI also provides information relevant to surgical approach, which was not made available by earlier studies. Of particular importance in selecting the optimal surgical approach is the depth to which tumor penetrates the IAC. By examination of the lateral extremity of the tumor in relation to the surrounding inner ear structures, which are evident on T1- and especially T2-weighted scans, it is possible to predict whether the tumor can be removed without violating the inner ear. False-negative Gd-MRI scans seem to be very rare, although the exact incidence is hard to establish because no more sensitive study is currently in existence. One potential pitfall occurs when a only a screening MRI study of the entire brain is obtained. With such a study, which is typically performed in thick sections (e.g., 10 mm), it is possible to overlook a small lesion that falls between slices. False-positive Gd-MRI studies have also been reported.167–169 The most common cause appears to be viral mononeuritis of the seventh or eighth nerve.170 In such cases, the neural complex enhances brightly, but it can usually be differentiated from tumor by its normal diameter. Another possible source of mistaken AN diagnosis stems from a reliance solely on contrast-enhanced scans. Because some structures in or around the IAC are inherently bright on T1-weighted scans, they might be mistaken for an enhancing tumor when precontrast scans are not obtained for comparison. For example, a globular region of bone marrow (which is rich in fat and therefore bright on T1-weighted images) adjacent to the IAC may erroneously suggest the presence of a tumor. Such mistaken impressions can be prevented by obtaining both pre- and postcontrast T1-weighted scans. Noncontrast MRI sequences have been recently suggested as an alternative for screening examinations to decrease the cost of imaging (Fig. 45-16). However, these new protocols have a decreased sensitivity particularly for small intracanalicular ANs. Therefore, the gold standard is still a gadolinium-enhanced sequence in order to optimize the detection of small AN.171,172 In addition, enhanced MRI has proved very useful in the evaluation of the postoperative patient.173 It readily identifies residual and recurrent tumor and can usually differentiate it from any associated scar tissue. Scar tissue may enhance to a degree, but it typically appears less intense than tumor, and its distribution usually suggests its true nature. It is common for the meninges of the IAC and CPA to enhance to a degree following AN surgery, and this should not be confused with recurrence. A free muscle graft placed in the drilled IAC during a retrosigmoid or middle fossa procedure may enhance postoperatively. This enhancement is usually not as intense as tumor, but serial

Acoustic Neuroma (Vestibular Schwannoma)

Figure 45-16. Fast spin-echo T2-weighted high-resolution MRI of a small intracanalicular acoustic neuroma. The seventh and eighth nerves can be seen emanating from the medial aspect of the tumor, which shows up as a filling defect in the IAC through the exclusion of CSF, as they course toward their brainstem entry.

imaging studies may be required to confirm that it does not represent residual or recurrent disease. Following a translabyrinthine procedure, during which an adipose graft is placed in the craniotomy defect, it is important to employ fat-saturation techniques to permit recognition of any subtle enhancing components. Although the radiographic differential diagnosis of AN is large, as a practical matter only meningioma is likely to lead to any confusion.174 In a substantial majority of cases it is possible to distinguish between AN and meningioma of the CPA based on their typical imaging characteristics (Table 45-5).175 The reliable feature that differentiates the two is that meningiomas are sessile, typically possessing a broad base along the petrous pyramid, and ANs are globular. It is important to be aware that one of the most characteristic features of meningioma, an enhancing dural tail extending for several millimeters from the periphery of the lesion, can also occur with AN.176,177

DIAGNOSTIC PROTOCOLS FOR SUSPECTED ACOUSTIC NEUROMA Much discussion has appeared in the literature concerning the optimal evaluation of the patient suspected of having an AN or other mass lesion of the CPA, and it should be

TABLE 45-5. Characteristics of Common CPA Tumors on MRI and CT Scans Acoustic Neuroma Globular Centered on IAC Typically penetrate the IAC Often erode the porus acusticus May be cystic

Meningioma Sessile Usually extrinsic to IAC Eccentrically placed to long axis of IAC Hyperostosis Calcification Enhancement of adjacent dura (meningeal sign)

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acknowledged that there exists no clear consensus among experts in the field. The first controversial issue is who should be considered at risk and thereby enter into a pathway of the diagnostic algorithm. Most decisions are initiated from results of routine diagnostic pure tone and speech audiometry. The most obvious indication for further investigation is progressive unilateral sensorineural hearing loss (SNHL) not explainable by another pathologic mechanism (e.g., noise trauma). However, exact guidelines for just how much asymmetry and at what frequency are difficult to codify into a set of practical rules. Overly stringent criteria tend to provoke too many diagnostic excursions and are therefore not economically efficient. While 10-dB or 15-dB asymmetry isolated to 4000 Hz and 8000 Hz very seldom indicates an AN, this same degree of asymmetry across the auditory spectrum is more suspicious. Of course, greater amounts of asymmetry usually should be evaluated. Also of substantial importance are the results of speech discrimination testing. A decrease in speech discrimination score out of proportion to the pure tone loss is well accepted as a cause for heightened suspicion. The timing and audiologic pattern of the asymmetric SNHL also affect risk assessment. Fluctuant, low-frequency SNHL accompanied by the sensation of aural pressure is only rarely a sign of AN. In this circumstance, the clinician may reasonably choose to follow the patient only if no other suspicious indicators are present. By contrast, many clinicians have been falsely reassured by sudden hearing losses, under the mistaken assumption that they are seldom associated with AN. The coexistence of vestibular symptoms also increases suspicion of AN to some degree unless the clinical pattern is characteristic of a peripheral disorder such as endolymphatic hydrops. For example, very few patients with AN exhibit severe episodes of vertigo typical of Ménière’s syndrome. The same cannot be said for individuals with intermittent positioning vertigo or chronic dysequilibrium. The presence of trigeminal nerve dysfunction (hypesthesia, anesthesia, dysesthesia, or pain) coexisting with an asymmetric SNHL is highly suspicious for a mass lesion of the CPA. Until more comprehensive data becomes available on the relative risk of the various historical and audiologic points suggestive of retrocochlear pathology, the decision as to when to proceed with a retrocochlear evaluation will remain a matter of each clinician’s judgment. Once the decision to embark on a retrocochlear evaluation has been made, the next controversial issue is what constitutes the optimal diagnostic protocol. It is generally agreed that a hierarchic combination of auditory, vestibular, and imaging studies are included in the algorithm, but the number and sequence of tests varies considerably.146,178 Elaborate schema have been proposed based on complex numeric treatments of test results intended to guide efficient use of expensive imaging studies.179 In our opinion, such synthetic constructions have little validity and are cumbersome and impractical in their implementation. In recent years, the our diagnostic protocol has become quite simple. Following a routine diagnostic audiologic evaluation, patients considered at low risk of having an AN undergo ABR, providing that sufficient hearing remains to generate an evaluable response. If the ABR is entirely normal, the patient is requested to return in 1 year for follow-up clinical and audiologic examination, sooner if new

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symptoms arise. Some examples of patients considered at low risk include those with minimal pure tone asymmetry, a decades long history of stable asymmetric loss, and unilateral tinnitus with a symmetric audiogram. If the patient is evaluated as high risk or if the screening ABR has been abnormal, then the patient undergoes a gadoliniumenhanced MRI scan. A technically well-performed enhanced MRI with a negative result effectively excludes AN for diagnostic consideration. For patients who cannot undergo MRI because they have metallic implants or claustrophobia, contrast-enhanced CT scan is obtained. Because CT often misses ANs smaller than 1.5 cm in diameter, a gas-contrast cisternogram should be obtained in high-risk individuals if the enhanced CT is negative. CT is also a reasonable, and less costly, alternative in elderly individuals in whom a small tumor would be considered clinically inconsequential.

the United Kingdom, and Canada) than it is in the United States. We can only hope that the incidence of late diagnosis will not rise as a consequence of these economic realities.

MANAGEMENT Three treatment options are currently available: (1) observation with serial imaging, (2) microsurgery, and (3) stereotactic radiation. The choice of option is based on the preservation of life considering the natural course of these benign tumors, possible neurologic sequelae (e.g., cranial nerve dysfunction, ataxia), tumor removal, preservation of facial nerve function, and preservation of hearing. Individual morbidities associated with surgery and radiation have to be considered in this decision-making process.181–184

Conservative Management DELAYED DIAGNOSIS The development of highly sensitive diagnostic technology in recent years (e.g., ABR, gadolinium-enhanced MRI) has led to an increased fraction of small tumors among patients with ANs. Nevertheless, despite the availability of these sophisticated tools, many tumors remain undiagnosed until they have attained considerable size. Undoubtedly, some of these tumors escape early detection because the patient chooses to ignore the relatively minor symptom of hearing loss until it becomes accompanied by more distressing neurologic symptomatology such as dysequilibrium, facial sensory or motor dysfunction, headache, or even visual loss due to papilledema. However, the patient’s inattention accounts for only a portion of late diagnosis. In a distressing number of cases, the patient has consulted a physician with symptoms attributable to the tumor some years before its discovery.48,121,180 In our (admittedly anecdotal) experience, approximately one-half of patients with large tumors give a history of consultation that did not lead to diagnosis. The majority of these physicians were both expert and conscientious. One pitfall in leading to the erroneous conclusion that a tumor is not present stems from reliance on less sensitive diagnostic tests such as CT scan and “special” audiometric diagnostic tests that give false reassurance to the clinician. Even ABR misses a significant fraction of small tumors. When the index of suspicion is high, it is important to obtain an enhanced MRI or, if unavailable, an air-contrast CT. Understandably, diagnosticians have a low index of suspicion when faced with a clinical scenario not conventionally associated with AN. However, a surprisingly high percentage of ANs present with atypical findings such as sudden hearing loss and unilateral tinnitus. Missed diagnostic opportunities will continue to be common in such patients until an improved awareness of the diversity of AN presentation becomes more widespread. Further complicating this issue is the increasing need for frugality in obtaining expensive imaging studies, particularly MRIs, in an era of contracting resources for health care. The mean size of an AN at diagnosis is already substantially greater in medically advanced countries with limited access to MRI (e.g., Denmark,

Conservative management is recommended for patients with small tumors who have a good possibility of not needing any treatment in their predicted natural lifespan. In these cases, it is a reasonable choice of management instead of radiation or microsurgery.185 Factors in favor of conservative management are advanced age, infirm health, minimal symptoms, and long clinical history suggestive of a slow growth rate. If with conservative management these patients remain clinically stable, they should undergo yearly scanning. Patients with stable tumors and failing balance may be treated with gentamicin locally in the middle ear to decrease the aberrant vestibular input. The obvious advantage of “wait and scan” is that it avoids a potentially morbid intervention. According to several recent studies, a marginal fraction of patients need additional treatment (Table 45-6). One disadvantage is the need for periodic radiologic follow-up. In addition, the probability for functional preservation of hearing might be reduced in cases where the tumor grows significantly. Last but not least, the psychologic TABLE 45-6. Reasons for Wait-and-Scan Strategy and Outcomes Reasons for Observation Tumor size Advanced age Patient preference Minimal symptoms Poor general health Asymptomatic tumor Better or only hearing ear

Deen351 (n = 68) 55% 21% 9% 7% 4% 4%

Glasscock352 (n = 34) 68% 53%

Tschudi181 (n = 71)

24%

4.2% 53.5% 19.7% 4.2%

6%

1.4%

76% 24%

88% 12% 0% 52 yr (19–78) 35 mo

Clinical Outcome No treatment Microsurgery Stereotactic radiation Mean age Mean follow-up

85% 13% 2 67 yr (35–80) 45 mo

75 yr (71–90) 41 mo

Modified after Jackler RK, Driscoll CLW: Tumors of the Ear and Temporal Bone. Philadelphia, Lippincott Williams & Wilkins, 2000.

Acoustic Neuroma (Vestibular Schwannoma)

factor for the patient who knows about the lesion should not be underestimated.

Microsurgical Management The priorities in AN surgery are first the preservation of life, second the maintenance of facial nerve function, and third the preservation of socially useful hearing in the tumor ear. Among these goals, the first is nearly always achieved, the second is obtained with regularity, and the latter is realized only under favorable circumstances. Contemporary AN surgery requires an operating microscope, cranial nerve monitoring, and good neuroanesthesia (see Chapter 57, Intraoperative Monitoring of Cranial Nerves). A substantial institutional commitment is necessary to provide appropriate instruments, skilled operating room personnel, cranial nerve monitoring equipment, postoperative intensive care, and the ready availability of neurodiagnostic imaging. AN surgery can be performed by either a neurotologist or neurosurgeon alone, but many centers have found that collaboration between the specialties is desirable because it takes best advantage of the special skills of each.186 Another factor that favors the use of a surgical team is that removal of an AN often requires prolonged delicate microsurgical dissection. The availability of two surgeons minimizes fatigue, which can lead the operator to become impatient and less facile, neither of which is conducive to optimal functional outcome. Surgical procedures employed in the management of AN take place in two broad stages: (1) craniotomy and exposure of the tumor and (2) microdissection of the tumor away from brain, cranial nerves, and adjacent vascular elements (Fig. 45-17). A variety of surgical approaches are used to expose an AN. The most used procedures are the retrosigmoid (RS), translabyrinthine (TL), and middle fossa (MF) approaches. In a few centers, the transotic (TO) and extended MF techniques are in use as well.187,188 Each of these options has advantages and disadvantages, which must be considered by the surgeon in selecting the optimal operative approach to a particular tumor. For a more detailed description of each procedure, see Chapter 43 (Overview of Surgical Neurotology). Centers with a special interest in ANs tend to fall into three broad categories in terms of surgical preference: retrosigmoid preferred, translabyrinthine preferred, and eclectic. Surgeons who adhere to the first two philosophies usually do so as a result of their greater familiarity and comfort with a particular method based on their training and experience. The eclectic philosophy, in which the choice of opening is made according to the attributes of the tumor being exposed, is being adopted by an increasing number of surgical teams, especially those in which neurotologists and neurosurgeons collaborate in the patient’s care.189–192 While it would be desirable from a technical and experiential standpoint to always perform the same approach, in our opinion the differential morbidity among the various options justifies the complexity of a selective protocol. In any event, the choice of opening technique is not the most important determinant of success in AN surgery; rather, the microsurgical skills the surgeons employ while removing the tumor are. The protocol discussed next is the one our team

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at Stanford University uses (Fig. 45-18); however, no consensus exists among experts on the relative role of the various approaches. Selection from the various approaches depends on a number of factors including the level of serviceable hearing, the depth of tumor extension into the IAC, the size of the tumor, and the experience and familiarity of the surgeon.192 The TL, RS, TO, and extended MF techniques all provide exposure of both the IAC and CPA, and the standard MF approach is suitable only for tumor confined to the IAC. Of all the factors taken into account, the amount of residual hearing is most influential. Conservation of useful hearing is a highly desirable goal which, as will be discussed later, is achieved relatively infrequently. Only two procedures afford the possibility of maintaining residual hearing; the RS and MF approaches. Undoubtedly, surgeons would always attempt to save hearing were there not potential adverse consequences from having undertaken the effort. For tumors that involve the CPA, the choice usually boils down to the TL versus the RS approach. The TL approach inherently sacrifices hearing as it traverses the inner ear in the process of creating the craniotomy. However, compared with the RS approach, which provides some chance of hearing conservation, the TL method has a somewhat lower morbidity. This is particularly notable in the incidence of persistent headache. Tumor size, in and of itself, has little effect on the choice between the TL and RS approaches. Either allows removal of even the largest AN. Criticism of the TL approach for insufficient exposure of larger tumors stems from inexperienced temporal bone surgeons who achieved insufficient CPA exposure. In experienced hands, the TL approach is capable of exposing even the largest AN.193,194 The primary anatomic limitation of transtemporal craniotomy for posterior fossa tumor is exposure of the inferior aspect of the CPA, particularly when both the jugular bulb and sigmoid sinus course are high (see Figs. 43-8 and 43-9 in Chapter 43, Overview of Surgical Neurotology). Since ANs seldom extend into the lower reaches of the CPA, this limitation is seldom relevant. Even when an AN has an atypically inferior extension, its capsule can usually be mobilized, following tumor debulking, away from the nerves of the jugular foramen into the central portion of the operative exposure where resection can take place under direct binocular vision. The depth to which the tumor penetrates the IAC, as visualized on gadolinium-enhanced MRI scans, is also a major determinant in the selection of surgical approach. Although the TL approach is capable of exposing the entire IAC from fundus to porus acusticus, the RS and MF approaches often require, particularly at the lateral end, a blind dissection to permit removal of the intracanalicular component of the tumor without need for exenteration of a portion of the inner ear.195 Our current practice is to inform patients that the MF approach is clearly superior for hearing but it carries a higher incidence of persistent facial paresis and synkinesis in tumors with 10- to 18-mm CPA components. The patient then judges the relative importance of hearing and facial function for himself or herself.196 In the RS approach only approximately the medial twothirds of the canal can be exposed without sacrificing a

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Figure 45-17. Steps in the surgical removal of acoustic neuroma. A, After opening the internal auditory canal, the intracanalicular portion is debulked and the facial and cochlear nerves are identified laterally. B, After debulking the intracranial portion of the tumor, the facial and audiovestibular root entry zones into the pons are identified. Continued

A

B

portion of the otic capsule and thus reducing the chance of maintaining residual hearing.197–199 In one study where postoperative CT scan was used to assess labyrinthine integrity, entry into the inner ear was highly correlated with loss of hearing.200 However, minor labyrinthine entries do not inevitably result in deafness. Our preference is to expose the most lateral extension of the tumor in the IAC to permit direct visualization of the tumor interface with its nerve of origin. Indirect dissection of the fundus is sometimes selected, however, particularly in case of good hearing, even though it carries a small possibility of recurrence. Some individuals have tried using right-angled endoscopes to inspect the end of the canal to identify tumor remnants. In our experience, this has not proved helpful because it has been difficult to distinguish, from indirect inspection, between blood-stained neural tissue and residual tumor. In patients with an inner ear extension

of the vestibular schwannoma, a transcochlear approach has been reported as the most suitable approach.201–203 Hearing status also has a major influence in the choice of surgical approach. When the hearing is poor (<50 dB SRT, <50% speech discrimination), we advocate the TL approach regardless of tumor size and location. When the hearing is serviceable, an RS approach is selected providing that the CPA component of the tumor is smaller than 2.5 cm in maximal diameter and the lateral third of the IAC is free of tumor. The tumor size limitation in hearing conservation approaches is based on the observation that useful hearing is almost never preserved following removal of tumors larger than 2.5 cm in diameter.204 This rule need not be adhered to rigidly. It is reasonable to attempt hearing conservation in tumors with even relatively large CPA components when the hearing is particularly good and the IAC is minimally involved. Although the probability of

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Figure 45-17, cont’d. C, The most difficult (and time-consuming) part of the dissection is usually the removal of the last rind of capsule from the most splayed and adherent segment of the facial nerve, typically located just proximal to the anterior lip of the porus acusticus.

C success in such cases is very limited, the well-informed patient might accept the somewhat higher morbidity of an RS craniotomy in hopes of the remote possibility of maintaining some hearing. The importance of the patient’s participation in the treatment planning cannot be overemphasized. Either the RS or MF can be used during a hearing conservation attempt to an intracanalicular tumor. The MF approach probably has the best chance of saving hearing, but this comes at the expense of a greater need to manipulate the FN. From the perspective of the MF approach, the FN may lie between the surgeon’s point of view and the tumor;

Figure 45-18. Acoustic neuroma microsurgical management algorithm used at Stanford University. This scheme represents a general guideline only. Individualized treatment selection depends on numerous factors. Size is expressed in diameter of the CPA component. MF, middle fossa; RS, retrosigmoid; TL, translabyrinthine.

this is seldom the case with the posterior approaches (RS and TL) (see Fig. 43-32 in Chapter 43, Overview of Surgical Neurotology). The choice of approach to intracanalicular tumors that fill the IAC from fundus to porus involves a number of factors. If the amount of residual hearing is marginal and preoperative indicators (e.g., ABR) are not favorable, then a TL approach is recommended under the assumption that minimizing the risk of facial neuropraxia is more important than undertaking an MF approach, which is unlikely to maintain even imperfect hearing. The liability of FN injury with the MF approach is influenced by whether the tumor took its origin from the superior or inferior vestibular nerve. Typically, the FN lies in a less favorable position on the tumor’s superior surface with inferior vestibular nerve tumors. Our group uses coronal MRI images to determine the location of the tumor in relation to the transverse crest. This approach can give a hint on the probable nerve of origin; in addition, ENG may provide some insight. Because the caloric response is generated by the lateral semicircular canal, which is supplied by the superior vestibular nerve, a robust caloric response is suggestive of inferior vestibular origin. When caloric responses are absent, it is by no means certain that the tumor has a superior vestibular origin. An inferior vestibular tumor can compress its neighbor and render it nonfunctional. Aside from the FN factor, it is also more difficult to save hearing in inferior vestibular nerve tumors. They possess a more intimate relationship with the cochlear nerve and the internal auditory artery than tumors that originate in the superior compartment. Another useful factor in assessing the probability of success in hearing conservation attempts is the extent to which the bony walls of the IAC are eroded.196 Our impression is that extensive erosion of the IAC, particularly of its anterior wall, is an adverse prognostic sign. Similarly, if the tumor prolapses into the cochlear

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modiolus on gadolinium-enhanced MRI scan, the probability of hearing preservation is diminished. Once the craniotomy has been completed, tumor removal proceeds in two stages: (1) debulking the central region followed by (2) microdissection of the tumor capsule away from adjacent brain, cranial nerves, and blood vessels. Debulking, which is not technically difficult, can be facilitated by use of an ultrasonic aspirator, laser, or suction dissector. The biggest challenge in AN surgery is preservation of the cranial nerves, which lie draped on the tumor’s surface. Since it shares the IAC and CPA with the audiovestibular nerve, the FN is invariably affected by acoustic tumors. Within the IAC, the FN becomes compressed between the tumor and the osseous walls of the canal (Fig. 45-19). Fortunately, the nerve is seldom very adherent to the tumor in this location. In the CPA, progressive tumor growth stretches the FN over the tumor surface, most commonly in the anterior direction. Anterosuperior and anteroinferior courses are also frequent, and posterior courses are decidedly rare (Fig. 45-20). Familiarity with the variations of the FN course is essential if optimal functional results are to be obtained. Unlike in the IAC, the FN is often adherent to the tumor in the CPA, particularly in the segment just medial to the porus acusticus. The process of removing the tumor from the FN usually commences with the identification of the nerve in the distal IAC. After removal of the intracanalicular component of the tumor, the CPA component is debulked and

A

the FN brainstem entry is identified visually and electrically. The tumor capsule is then sequentially liberated and excised until only a small portion of capsular peel persists on the most adherent segment of the tumor-nerve interface.

THE ROLE FOR INCOMPLETE RESECTION It is generally held that completely excised ANs do not recur. Under certain circumstances, it is reasonable to consider less than complete removal despite the attendant increased risk of regrowth.205–210 This may be planned preoperatively, elected during surgery as a concession to cranial nerve preservation, or mandatory in the case of adverse patient response to efforts at tumor removal. A planned incomplete resection may be undertaken when a more prolonged operation is judged unwise because of the patient’s advanced age or medical condition. Incomplete removal may be elected intraoperatively when dissection planes are poor and the surgeon judges that total tumor removal carries a high risk of anatomically disrupting the FN. The hearing status of the contralateral ear is also relevant. If it is impaired from a second AN or other otologic disease, incomplete removal increases the odds of hearing conservation.211 Whether the surgeon proceeds with radical resection or performs an incomplete removal depends on several factors. Most advocate a more aggressive approach in younger patients. When deciding on the extent of dissection, it is

B

Figure 45-19. The effect of progressive acoustic tumor growth on the facial nerve. A, In the early stages of tumor growth, the nerve becomes compressed between the tumor and the bony walls the IAC. B, As the extracanalicular component expands, the nerve becomes progressively more stretched and splayed over the tumor surface.

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A

B

C

D

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Figure 45-20. Relationship of the facial nerve to a medium-sized acoustic neuroma. In the vast majority of cases, the nerve courses over the anterior surface of the tumor. Most common is direct anterior (A); less common are anterosuperior (B) and anteroinferior (C). Posterior courses are rare in acoustic tumors, but complex superior-posterior routes (D) are occasionally encountered. Continued

important to consider the patient’s priorities with regard to neural preservation versus the risk of suffering recurrent disease. On rare occasions, incomplete resection becomes mandatory when a patient deteriorates intraoperatively, either medically or neurologically, necessitating premature termination of the procedure. An example of this situation is the development of bradycardia associated with hypertension (Cushing’s reflex) during dissection of the tumor from the brainstem. This same phenomenon can

also occur during tumor dissection from the trigeminal nerve and can be controlled by either deepening the anesthesia or applying local anesthetic topically to the nerve without need for curtailing the procedure. In any discussion of incomplete resection, it is important to distinguish whether removal has been “subtotal” or “near total” because it has substantial impact on the risk of recurrence (Fig. 45-21). In subtotal excision, a substantial portion of tumor remains (>25 mm2, >2 mm thick),

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Figure 45-20, cont’d. Direct posterior courses (E) are exceedingly rare in acoustic neuromas, although they are frequent in meningiomas and other tumors of the cerebellopontine angle.

E whereas in near-total removal the residual consists of only a small, thin capsular peel (<25 mm2, <2 mm thick). Because ANs receive their blood supply from both the IAC and brainstem, residual tumor left in contact with these sites carries a higher risk of generating recurrence. Fragments of tumor left in the fundus of the IAC are well known to be capable of generating a recurrence.209,212 By contrast, the thin capsular remnant that hangs free in the CPA after near-total excision is likely to be devitalized and carries a substantially lower likelihood of regrowth. CT and unenhanced MRI are relatively insensitive to small amounts of residual tumor. Gadolinium-enhanced MRI, however, is quite sensitive to tumor fragments.166 (Fig. 45-22). However, enhanced MRI is not always able to differentiate postoperative scar or dural enhancement from tumor. When the presumed residual or recurrent disease is small, only progressive growth on serial enhanced MRI scans provides convincing evidence of the neoplastic nature of the lesion. Enhanced MRI should be able to detect the residual tumor in all cases of subtotal excision; following near-total excision, MRI is able to visualize the known tumor remnant in only some 50% of cases.206,208

In our group we routinely use fat-saturation MRI in all cases to differentiate tumors from scars and dural enhancement. Little has been published on the long-term follow-up of near-total excision cases. In our experience, the recurrence rate after a near-total resection (1/33 = 3%) is low, but it is 10 times higher after a subtotal resection (6/19).210 In one other series of patients followed an average of 5.3 years postoperatively, 38% (3/8) subtotally resected tumors demonstrated signs of growth but none (0/15) of the nearly totally removed did.206 In another study, 29% (4/14) of tumor residuals less than 5 mm in diameter enlarged over a mean follow-up of 5.8 years.208 This study also suggested that cauterization of the tumor remnant reduced the incidence of regrowth. Recurrent tumors enlarged at a rate similar to that of unoperated tumors, an average of approximately 2 mm per year.213 Very-long-term followup is required in order to assess the impact of recurrent disease on the patient’s longevity. In one study, a group of 139 patients with presumed incomplete removal (the IAC was never drilled open during the operation) was evaluated between 20 and 30 years following surgery. Compared with the population at large, there was no excessive mortality

Figure 45-21. Illustration of a medium-sized acoustic neuroma (A) compared with subtotal (B) and near-total (C) removal. In near-total removal, a thin piece of tumor capsule is left attached to the most adherent portion of the facial nerve.

A

B

C

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Figure 45-22. Axial postgadolinium T1-weighted MRI scan illustrating a less than complete resection of an acoustic neuroma. The thin remnant of the tumor surface can be visualized where it was left in situ along the adherent course of the facial nerve. The temporal bone defect is filled with adipose tissue.

beyond the first postoperative year. Two symptomatic recurrences were encountered 13 and 17 years following treatment. This emphasizes the need for late scans to detect slowly evolving recurrence. Following complete excision of an AN, we recommend enhanced MRI scanning including fat-saturation technique at 3 years to screen for unanticipated recurrence. After incomplete removal, scans are obtained yearly for 5 years and then biannually until a decade of stability has passed and more frequently if growth is noted as clinical circumstances warrant. Cystic tumors are particularly likely to recur when merely debulked. We have encountered two cases, both in elderly individuals, where brainstem compression recurred within 2 years following intracapsular debulking and cyst fenestration.113 In these cases, the cause was reformation of the capsule and progressive expansion of the cyst with little growth in the residual neoplastic component of the tumor. As a general rule, we strive to achieve total removal of AN whenever possible. Near-total excision is most often elected when continued dissection threatens disruption of the FN. In a recent series from the University of Michigan, near-total excision was elected in 17% of AN surgeries, typically as a concession to neurologic preservation.206 This incidence is in line with our experience of less than 10% incomplete resection.210 Our policy is to avoid subtotal removal whenever possible, particularly when the tumor possesses a cystic component.

OUTCOME OF ACOUSTIC NEUROMA SURGERY Decentralized versus Centralized Hospitals Results in AN surgery, perhaps to a greater degree than with other intracranial tumors, depends on the experience and microsurgical skill of the surgical team. The vast majority of the published results are derived from experienced groups who have a special interest in the management of these tumors. Results from surgeons who operate on these

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tumors occasionally are not generally as successful as those obtained by specialized teams. An analysis of 59 patients treated at five centers in Denmark over 11 years (1979 to 1990) was reported.214 In this series, each treating center averaged just 1 AN surgery per year. Mortality was 8.5%, well above the <1% reported in most contemporary series. Furthermore, cranial nerve preservation rates were low, as exemplified by the one-third of patients who required FN reconstruction and 58% with grade 6 palsies, despite incomplete resection in 29% of patients. Despite routine use of a suboccipital approach, in no case was residual hearing conserved. Complications such as CSF leak, which occurred in 36%, were also unusually high. Of note, in 16 tumors smaller than 2.5 cm diameter in the CPA, mortality was 12.5%, CSF leak occurred in 50%, and normal facial function was maintained in only 6%.215 A recent study in the United States revealed significantly better outcomes after surgery at high-volume hospitals or by higher volume surgeons, including a trend to lower mortality. In addition, postoperative complications were less likely in these institutions or in cases from higher volume surgeons, which lead to a significant difference in lengthof-stay as well as costs.216 In the anecdotal experience of the author, as well as that of many others interested in the management of these tumors, the findings of the Danish as well as the U.S. study are not aberrations, but rather represent an accurate picture of results by well-intentioned but less experienced surgeons undertaking AN removal. While such arguments put forward by one with a special interest in AN management may seem self-serving, the differential outcome implies that patients with ANs benefit substantially when managed at a center with experienced personnel and the institutional commitment to achieve optimal results.

Mortality The mortality of AN surgery has fallen steadily over recent years to a level under 2% in most major centers. However, there is a significant difference in outcome of patients who had surgery at lowest-caseload-quartile hospitals (1.1% died), compared with 0.6% at highest-volumequartile hospitals.216 Causes of mortality fall into two broad categories: tumor related and medical. Most common among tumor-related causes are ischemic brain injury due to arterial or venous interruption, acute postoperative CPA hemorrhage, meningitis, and air embolism.217,218 Tumor-related mortality occurs almost exclusively in those with large tumors. By contrast, the occurrence of serious medical complications is more related to the patient’s age and underlying medical condition than it is to tumor status. The possible lethal medical complications of AN surgery are the same as those associated with any major operative procedure: pneumonia (atelectasis or aspiration), pulmonary embolus, peptic ulceration, and myocardial infarction, among others.

Complications Postoperative complications are relatively frequent following AN surgery, occurring in approximately 20% of patients.219 See Chapter 44 (Complications in Neurotologic

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Surgery). However, in recent years a significant reduction in large series has been reported.220 As with mortality, the incidence of morbidity is higher in elderly and infirm individuals, in those with large tumors, and in hospitals with fewer skull base procedures. Fortunately, the vast majority of complications are successfully managed and the patient recovers without sequelae. Nevertheless, these contribute to patient discomfort, can prolong recovery, and add to the cost of care. A small minority of complications lead to lasting functional deficits. Intracranial Vascular Complications One of the most devastating complications of AN surgery stems from interruption of the anterior inferior cerebellar artery (AICA) or one of its branches. This artery is intimately related to the capsular surface of ANs. Since the vessel often loops into the vicinity of the porus acusticus, it is at risk during removal of even relatively small tumors. The full-blown AICA syndrome results in extensive infarction of the pons and is usually fatal. Fortunately, with modern microsurgical techniques, complete AICA syndrome has become very rare. Partial AICA syndrome, caused by disruption of the terminal branches of the AICA, results in ischemic injury to the middle cerebellar peduncle and a variable amount of the lateral aspect of the pons221,222 (Fig. 45-23). Although we have never encountered a complete AICA syndrome, several of our patients have developed the partial variety. The dominant symptoms in such cases have been ataxia and dysmetria resulting from blockage of cerebellar connections with the brainstem. Long tract signs, manifested as hemiparesis or hemisensory disturbance,

Figure 45-23. Axial T2-weighted MRI scan demonstrating hyperintensity in the cerebellar peduncle and lateral pons due to an interruption of the distal branches of the anterior inferior cerebellar artery (arrows). This patient suffered from transient ataxia and dysmetria for several months postoperatively.

occur to a variable degree. The prognosis for the partial AICA syndrome is generally favorable, with gait rehabilitation gradually progressing over a matter of months. Limb ataxia also improves, but writing skills and the ability to perform precise manual tasks may remain impaired on the operated side. Postoperative ischemia may also occur as the result of vasospasm involving the vertebrobasilar system.223 Venous infarction can also occur following AN surgery, but is less common than arterial injury. The sigmoid sinus can be injured during either a TL or RS approach. Although hemorrhage from an emissary vein or minor mural bleeding is common, the sinus seldom requires ligation. Nevertheless, the required surface tamponade with a hemostatic such as Surgicel may lead to formation of a thrombus, which eventually clots off the entire vessel. Sudden loss of a one sigmoid/transverse system seldom results in significant venous ischemia. In rare cases where the surgical side carries most of the cerebral venous outflow, congestion and even hemorrhage can occur. Because it may be particularly intense in the temporoparietal region, speech disturbance may result. Rarely, venous congestion due to sigmoid sinus thrombosis is fatal due to progressive cerebral edema. Another possible sequela of sinus occlusion is papilledema with progressive visual loss. In one of our patients, this required fenestration of the optic nerve sheath to relieve neural compression. We have also encountered one case of isolated cerebellar venous infarction associated with hemorrhage, the cause of which was uncertain. It may be speculated that it resulted from interruption of the petrosal vein (Dandy’s vein), which is routinely divided in larger tumors to permit mobilization of the cerebellar hemisphere. Anomalous cerebellar drainage may render the cerebellum vulnerable to loss of this drainage route. The veins that course along the inferior aspect of the temporal lobe can also be injured during surgery.224,225 They are particularly at risk during middle fossa and extended middle fossa approaches. Fortunately, temporal lobe retraction is extradural, so the risk of injury to these vessels is small. Interruption of the vein of Labbé on the dominant side may result in substantial speech disturbance and memory loss, both of which generally improve with time. Postoperative hemorrhage into the CPA is a dreaded complication of AN surgery. It is axiomatic in AN surgery that the procedure is not terminated until all bleeding vessels are well controlled. Even when excellent hemostasis appears to have been achieved, postoperative hemorrhage may still occur in rare cases. The most probable causes are postoperative hypertension, which dislodges a clot from the cut end of a vessel, release from vasospasm, and coagulopathy. When bleeding in the CPA is suspected, the patient should either be rushed back to surgery or undergo a noncontrast CT scan to assess for hemorrhage, depending on the severity of the clinical situation. Air embolism is another potentially serious vascular complication of AN surgery.226 The risk of this complication can be greatly reduced by adaptation of a supine operating position. When the sitting position is used, precordial Doppler monitoring should be performed and a central venous line placed. At the first sign of air embolization, the field should be flooded with irrigant solution and the patient’s head lowered. Air within the right side of the heart may be aspirated through the central venous catheter.

Acoustic Neuroma (Vestibular Schwannoma)

Traumatic Parenchymal Injury The cerebellum, pons, and temporal lobe are vulnerable to injury during resection of ANs. This can result from either retractor injury or a breach of the pial lining during tumor microdissection. Cerebellar and temporal lobe injury are more likely to result from excessive retraction, and pontine injury is more likely due to traumatic dissection. Among these cerebellar injury is fairly common. Postoperative MRI scans frequently reveal a degree of malacia involving the lateral 1 to 2 cm of the cerebellar parenchyma (Fig. 45-24). This is particularly common following the RS approach where retraction is relatively more vigorous. The functional significance of this radiographic finding is not well delineated, and most of these patients recover uneventfully from their surgery. T2-weighted scans are particularly sensitive to detecting subtle degrees of parenchymal injury and often remain permanently abnormal. Rarely, cerebellar injury extends more deeply toward the midline. In such cases prolonged ataxia, which may take many months to resolve, may result. In the past, resection of the lateral third of the ipsilateral cerebellar hemisphere was a fairly common maneuver intended to improve exposure and provide space to accommodate postoperative swelling. Although this was usually well tolerated, modern surgical and neuroanesthetic methods have made it unnecessary. In rare instances, the cerebellum massively swells during surgery. The most likely factors contributing to this are insufficient use of brain-shrinking measures (e.g., mannitol, hyperventilation) and premature application of the cerebellar retractor before liberating CSF from the cisterna magna. Very recently, electroencephalogram (EEG) changes (lowfrequency activity and IEA) have been reported as part of the middle cranial fossa procedure; in translabyrinthineoperated patients EEG changes are fewer.227 Injury of the brain surface during microdissection of the tumor capsule from it can nearly always be prevented. In the vast majority of ANs, an arachnoid plane can be maintained throughout tumor dissection. Occasionally, particularly with very large tumors, the cerebellar and/or pontine

Figure 45-24. Encephalomalacia of the lateral lobe of the cerebellum resulting from retraction during acoustic neuroma surgery. This finding is most likely to occur following a retrosigmoid approach to a large tumor.

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planes are sufficiently obscure that the dissection becomes subpial in places. The underlying brain tissue may be markedly softened or even gelatinous when compression has been extreme and long standing. Although this phenomenon is of little concern on the cerebellar surface, it could be very dangerous on the pons. By employing sharp dissection and using the pontine surface veins as a guide, it is usually possible to prevent direct injury to the brainstem. However, in the rare instances where the capsule is inextricable without risking pontine injury, we favor leaving a thin capsular peel on the most adherent regions. It is important to realize that most pontine injuries associated with AN removal arise indirectly, through vascular compromise, rather than as a result of direct injury. Cerebrospinal Fluid Leak CSF leakage is the most common complication of AN surgery, occurring in some 5% to 15% of patients in most series with a trend toward a higher rate in older patients.219,220,228,229 CSF can escape through either the skin at the wound site or mucosa via the nose (Fig. 45-25). CSF otorhinorrhea is much more common than seepage through the wound. In our experience, CSF otorhinorrhea complicates approximately 13% of translabyrinthine, 10% of middle fossa, and 10% of retrosigmoid procedures. Neither surgical approach nor tumor size affects the rate of postoperative cerebrospinal fluid leakage.230 Wound leaks are substantially less common and occur with approximately equal incidence from the two procedures. Leakage via the wound most often results from too loose a closure of the muscle layers and subcutaneous tissue. However, even the most stoutly closed wound can fail under the onslaught of increased intracranial pressure or when healing is retarded through high-dose corticosteroid therapy. Precautionary measures to decrease the incidence of postoperative complications related to CSF leak in patients with preoperative hereditary coproporphyria (HCP) are the obliteration of exposed air cells, including those around the internal auditory canal, accurate restoration of the dural barrier, and temporary lowering of intracranial

Figure 45-25. Cerebrospinal fluid rhinorrhea.

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pressure with a ventricular or lumbar drain. Patients with persistent symptomatic HCP after tumor excision should be treated with a ventriculoperitoneal shunt. Delaying this decision until the postoperative period is safe and avoids unnecessary shunting in the majority of patients, according to a recent study.231 In mucosal leaks associated with the RS or MF approaches, the most common route of egress is via the transected pneumatic cells of the apical petrous bone, which surround the IAC. Extensive peri-IAC pneumatization is present in approximately 30% of adults. A second possible pathway into the temporal bone exists more superficially at the anterior edge of the RS craniotomy. The retrosigmoid air cells are extradural in this location, but dural closure is often not watertight and CSF may thus gain access to transected cells at this location. Both peri-IAC and retrosigmoid leaks may occur despite diligent efforts by the surgeon to seal opened pneumatic tracts with bone wax, autogenous tissue, fibrin glue, and/or bone cement. Most surgeons occlude transected air cells with bone wax overlain with an autologous tissue graft. Some advocate the use of fibrin glue to augment this closure, although we did not find it helpful in a several-year trial.232 Ionomeric bone cement shows promise as a superior material for filling bony defects and may replace bone wax in the future.233 Transmucosal CSF leaks following a TL craniotomy occur via the fossa incudis directly into the middle ear. These may be discouraged by sealing the communication to the middle ear with a fascial graft or by obliteration of the eustachian tube. Once CSF has entered the temporal bone’s air cell system, the fluid traverses the middle ear and eustachian tube en route to the nasopharynx. Cutaneous CSF leaks are obvious, but the more common transmucosal leaks can be subtle and hard to diagnose. The characteristic finding of episodic gushing of clear fluid from the nose triggered by positional change or exertion is not always present. Some patients report only a sensation of postnasal dripping or a salty taste in the mouth, both symptoms that are hard to confirm objectively. While prevention of CSF leakage begins with meticulous closure of the wound and sealing of any transected air cells, postoperative measures are also important. A tight bandage helps to redirect the CSF gradient medially and discourages wound leaks, as well as those through the exposed retrosigmoid air cells. Compressive bandages probably have little effect on peri-IAC leaks because surface compression is unlikely to transmit significantly to this depth. Additional measures to discourage CSF leakage include elevation of the head of the bed by 30 degrees and fluid restriction for several days following surgery. Prophylactic placement of a lumbar subarachnoid lumbar drain to divert CSF flow is undertaken when extensive entry into well-developed air cells around the IAC has occurred during a RS approach. We do not routinely employ postoperative corticosteroids, except in very large tumors or when surrounding parenchymal edema is evident on preoperative T2-weighted MRI scans. However, when a patient shows signs of postoperative aseptic meningitis (headache, fever, bulging wound), they are instituted. The detrimental tendency for steroids to inhibit wound healing must be weighed against their beneficial ability to reduce the acute hydrocephalus, which may accompany aseptic meningitis.

The initial management of postoperative CSF leak involves simple medical measures such as limited activity, fluid restriction, and administration of the carbonic anhydrase inhibitor acetazolamide (Diamox) to reduce CSF production and stool softeners to obviate the need for straining. Only wound leaks are handled surgically from the outset. These are oversewn at the bedside with one or more vertical mattress sutures. If the leak continues despite these measures, then a lumbar subarachnoid drain is placed and left in for 3 days. The same algorithm is used for CSF otorhinorrhea except that reoperation is undertaken only if the leak persists despite lumbar drainage or recurs once the drain is removed.234–236 In transnasal leaks that traverse a deaf ear, we favor subtotal petrosectomy with closure of the external auditory meatus and blockade of the eustachian tube under direct vision with bone wax followed by a muscle plug.237 When useful residual hearing persists, an intact canal wall mastoidectomy is performed and the fossa incudis is obstructed with an autogenous tissue graft. Transnasal obliteration of the eustachian tube is another method that has been advocated in cases of CSF otorhinorrhea.228 Following surgery for CSF leak, a fresh lumbar drain is placed and left in place for 3 days. A few leaks persist despite all medical and surgical efforts to stem the flow. In such cases, hydrocephalus is often the underlying cause. These persistent leaks are often best managed by permanent CSF shunting. In communicating hydrocephalus, which predominates in this situation, a lumboperitoneal shunt is used. A rare complication of CSF fistula through the ear is tension pneumocephalus.238,239 Some amount of intracranial air is inevitable following posterior fossa craniotomy, but the accumulation of large amounts under pressure is unusual. Contributing to the development of this complication are large-diameter CSF fistulae, the presence of a unidirectional flap valve over the leakage tract, and frequent nose blowing or performance of Valsalva maneuver. Another factor that can trigger tension pneumocephalus is excessive drainage of CSF via a shunt or lumbar drain. Meningitis Meningitis is among the more common complications of AN surgery. In reported series, the incidence varies between 2% and 10%.219,228,240 The majority of infectious cases occur in association with CSF leak, which permits bacterial contamination from the nose or across the skin. Meningitis also arises as a complication of lumbar subarachnoid drainage or as a result of aseptic necrosis of free fat graft placed during neurotologic surgery (Lipoid meningitis).241 The peak incidence of meningitis is the third through the fifth postoperative day. Rarely does it present earlier than this, especially following intraoperative contamination with a particularly virulent microorganism. Delayed meningitis, occurring weeks or months following surgery, is usually due to cryptic CSF otorhinorrhea. The use of perioperative antibiotics to discourage the development of meningitis is controversial. At Stanford University, we administer 2 grams of ceftizoxime just prior to incision and irrigate the wound with a bacitracin solution at the end of the procedure. Favorable outcome in postoperative meningitis hinges on early recognition of this complication. A high or persistent fever, unusually severe headache, and/or any

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sign of altered mental status can indicate the need for cytologic and chemical evaluation of the CSF. Since postoperative fever is common and headache is ubiquitous immediately following surgery, much clinical judgment is required. Nuchal rigidity, a hallmark of meningitis diagnosis in most settings, can be difficult to evaluate following AN surgery as a result of surgical trauma to the cervical musculature. As a general rule, the clinician is wise to have a low threshold for performing a lumbar puncture when a suspicion of meningitis arises. Interpretation of CSF findings following AN surgery is complicated by the pleocytosis that normally follows posterior fossa craniotomy. Aseptic meningitis is even more common than bacterial in the postoperative AN patient. While a high white blood cell (WBC) count (>1000) with a left shift is suggestive of bacterial meningitis, these benchmarks are often breached in aseptic cases as well.242 Conversely, when the clinical index of suspicion is high, intravenous antibiotics should be commenced despite relatively benign CSF findings and continued until the culture results become known. Adequate treatment of postsurgical bacterial meningitis requires a minimum of 7 days of intravenous antibiotics. Aseptic meningitis usually commences somewhat later than infectious cases. The cause appears to be meningeal inflammation induced by blood products, aseptic necrosis of free-fat graft and other irritants (e.g., bone dust) liberated into the posterior fossa during surgery. 240–242 The clinical picture consists of headache, malaise, and occasionally low-grade fever. Symptoms may be rapidly ameliorated by administration of a course corticosteroids. In some cases, symptoms recur with withdrawal of corticosteroids. When this occurs, a prolonged taper or every other day dosing may be given. May patients can be weaned from corticosteroid by gradual substitution of a nonsteroidal antiinflammatory drug such as ibuprofen.

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NF2 than it is in sporadic AN.63 However, little comparative data has been published to support this contention, and the author has observed a number of NF2 tumors that have dissected readily. There are a variety of potential mechanisms for FN injury during AN surgery.246 Stretch or torsion on the nerve can cause significant damage. In this regard, it is important to avoid pushing the tumor anteriorly because it further deforms the nerve in its typical direction of greatest stretch. Similarly, it is important to avoid traction along the course of the nerve because it risks disrupting the nerve’s most fragile segment. It is important in preserving both anatomic and functional integrity to maintain the nerve in its deflected position, contained within its surrounding arachnoid, rather than pull it up into the cavity created by tumor debulking. This helps both to preserve its blood supply and to provide mechanical support for otherwise fragile fiber bundles. Thermal injury may also occur, particularly during bipolar coagulation or through heat generated while drilling. Dissipating heat buildup through copious irrigation is important in preventing this type of neural damage. Probably the most frequent cause of FN injury is mechanical disruption of attenuated nerve fibers during microdissection of the nerve from the tumor capsule. When it appears that radical removal will result in anatomic discontinuity of the nerve, some surgeons elect to leave a thin veil of tumor capsule attached to the most adherent portion of the nerve.205 The willingness to consider a near-total removal is predicated on the assumption that a tiny devascularized capsular peel is unlikely to generate a recurrence. The decision whether to undertake a near-total removal is complex and depends on a number of factors. Prominent among them are the age and the patient’s own priority regarding maintenance of facial function versus assurance of tumor control. Role of Facial Nerve Monitoring

IMPACT OF AN REMOVAL ON THE QUALITY OF LIFE Facial Mimetic Function Vulnerability of the Facial Nerve Most well-informed patients with ANs expect that they will survive AN surgery and avoid major brain injury. Of greatest concern to most individuals is preservation of facial function.243 The FN is dysfunctional preoperatively in only a small minority of patients; however, paresis and paralysis are frequent consequences of surgery. Numerous factors contribute to the probability of maintaining FN integrity.244 Tumor size has a major influence because as the tumor’s diameter increases, the nerve becomes progressively more thin and splayed over its capsule.245 Of even greater importance is the nature of the interface between the tumor and the nerve. The degree of adherence is typically greatest just outside the porus acusticus. Dissection is generally more difficult in larger tumors, but there are exceptions. Occasional intracanalicular tumors are markedly adherent while some very large tumors dissect with remarkable ease. It has also been suggested that the FN is more intimately applied to the tumor capsule in

A substantial improvement in FN outcome has been realized in recent years. Intraoperative FN monitoring has contributed, in no small measure, to this favorable trend. (See Chapter 57, Intraoperative Monitoring of Cranial Nerves.) Several studies have verified the impact of FN monitoring on functional outcome following AN surgery. In a study that compared 91 monitored patients with 91 unmonitored controls, only slightly improved outcomes were noted in small and medium-sized tumors. In large tumors, however, anatomic continuity improved from 41% to 71% when monitoring was used.247 In another study, 111 monitored patients were compared with 207 unmonitored historical controls.248 A reduction in the rate of total paralysis from 15% to 4% was noted when FN monitoring was used. Good predictors of initial facial nerve function are due to a combination of electrophysiologic intensities and tumor size.249 It is now widely accepted among experts in the field that FN monitoring, when skillfully employed, improves FN outcome in AN surgery. Other factors contribute as well to this trend toward better FN prognosis. Of considerable importance is the fact that, in many countries, AN surgery has become concentrated in regional centers. This permits the surgical team to accumulate the experience necessary to obtain

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TABLE 45-7. Anatomic Preservation of the Facial Nerve in Acoustic Neuroma Surgery Author

Year

House353 Glasscock190 Sterkers354 Tos355

1979 1986 1988 1988

No. of Patients 500 616 800 400

Anatomic Preservation 97% 82% 94% 95%

optimal results. The existence of a distinct “learning curve” in AN surgery, where functional results gradually improve over time, is widely acknowledged.250 Another important factor in improved FN outcome is the progressive refinement of microsurgical instrumentation and tumor debulking implements such as the ultrasonic aspirator and laser. Finally, increasingly sophisticated diagnostic technology has permitted detection of an increasing fraction of small tumors, thus favoring FN preservation. Results in Contemporary Series In this chapter no attempt has been made to review exhaustively all the published series on FN outcome following AN surgery. Rather, results from selected series are presented as representative of the state of the art in FN preservation. For a more detailed analysis, consult a recent comprehensive review article on the subject.251 The majority of the published series dwell on anatomic preservation of the nerve as the primary measure for success or failure. Results from large series are impressive, with continuity maintained in between 82% and 97% of cases (Tables 45-7 and 45-8). Of course, the patient cares less about anatomy than physiology and is little consoled when the surgeon says the nerve was intact if it never recovers functionally. In addition, operative estimations of neural integrity are affected by subjective factors and may not always accurately represent the actual status of the nerve. For these reasons, the most apt measure of success in FN preservation is the level of function after the recovery period.

To facilitate interstudy comparison of results, assessment of FN function following AN surgery should be performed using standardized measures, preferably the widely accepted grading scale proposed by House and Brackmann.252 Reported functional results vary widely, at least in part as a result of differences in patient population and grading criteria (see Table 45-8). It is clear that, in many centers, the occurrence of permanent severe or total paralyses has been reduced to well under 10%. Furthermore, most of the patients with unfavorable outcome had tumors from the largest size categories. In our own series, facial nerve outcomes is similar for the RS and TL approaches. One cost of the hearing preservation attempt in our 10- to 18-mm MF group was a significantly worse long-term (>1 year) facial nerve outcome when compared with a size-matched TL cohort (81% grade 1 or 2 compared with 100%). The Course of Postoperative Facial Palsy The great majority of postoperative facial palsies occur in cases where the FN has been left anatomically intact after completion of tumor resection. The time course of neural recovery depends on the extent of neural injury, as well as its location. The pace of recovery falls roughly into two time courses. In less severe injuries, recovery often occurs within 2 months. More severe injuries, presumably those that require remyelination, typically take 8 to 15 months to recover. The more delayed the onset of recovery, the less likely that the patient will regain near normal levels of function and the more likely that some degree of synkinesis will develop. The time course of recovery is typically gradual and is initially evident as improvement in symmetry and tone at rest. Return of voluntary movements usually proceeds from the lower face to the midface and finally the forehead. The process of recovery is often accompanied by an element of hyperfunction, manifested as subtle twitching, less commonly as frank spasm. Following severe injuries with long recovery times, misdirected reinnervation is common. This is manifested as mass motion where the eye tends to close during smiling and the corner of the mouth elevates upon eye closure.

TABLE 45-8. Facial Nerve Function 1 Year Postoperative Follow-up Author

Year

No. of Patients

Normal (Grade 1)

Nadol356 Kanzaki250 Ebersold357

1992 1991 1992

60* 106 161

90% 17% 52%

Lalwani114

1993

129

71%

Arriaga358

1994

164

77%

359

Samii

1997

929

51%

Satar196

2002

153†

82%

Paresis (Grades 2–5) 8% 36% 44% (grades 2 & 3 = 27%) (grades 4 & 5 = 17%) 27% (grades 2 & 3 = 25%) (grades 4 & 5 = 2%) 22% (grades 2 & 3 = 20%) (grades 4 & 5 = 2%) 28% (grades 2 & 3 = 28%) (grades 4 & 5 = 17%) 17.6% (grades 2 & 3 = 17%) (grades 4 & 5 = 0.6%)

Paralysis (Grade 6) 2% 47% 4% 3% 1% 4% 0.4%

*Report limited to small and medium-sized tumors suitable for a hearing conservation approach. † Report limited to small and medium-sized tumors operated with MF approach. A comparable cohort with translabyrinthine approach showed 87.5% grade 1 and 12.5% grade 2 facial nerve function.

Acoustic Neuroma (Vestibular Schwannoma)

It is possible, to some extent, to predict the degree and time course of recovery of facial function from the appearance of the nerve at the end of the procedure and its electrical stimulability. When surgical planes have been favorable, the nerve does not appear unduly splayed, and a low threshold for electrical stimulation persists at the nerve exit from the brainstem, then complete recovery is likely. Conversely, a wide and attenuated nerve that is discolored where it adhered to the tumor and does not stimulate proximally is at substantial risk of poor recovery. Recently, we examined the reliability of FN stimulability proximal to the lesion at the end of surgery as a prognostic indicator of eventual FN functional recovery. None of the 102 patients with a threshold less than 0.4 volts had a recovery at 1 year worse than a grade 3/6. When stimulation was present under 0.1 volts, all achieved grade 1 (89%) or grade 2 (11%) results. A word of caution is in order regarding the prognostic value of electrical stimulability. When the nerve is very splayed, excellent stimulability may remain for a small subpopulation of the FN fibers even when the majority have been disrupted. Thus, when the nerve is very ribboned, it is important to establish whether the lowest threshold is representative of the entire wide band or only one limited region. Postoperative electrodiagnostic testing may also be of value in assessing the patient with postoperative facial paralysis. Electrical stimulability of the nerve may be assessed using either the maximal stimulation test or electroneuronography.253 If the nerve conducts any electrical response to the facial muscles, a more favorable prognosis is established. When no stimulability is found, electromyography may provide some prognostic information. In the late postoperative period, polyphasic reinnervation potentials are an early sign of pending recovery, whereas electrical silence is ominous in that it suggests muscular atrophy. Fibrillation potentials identify surviving muscle elements but imply that reinnervation has yet to commence. Transcutaneous electrical stimulation of the facial muscles has been proposed as a means of maintaining facial muscular tone while awaiting reinnervation. This modality has theoretical appeal; however, there is little scientific data to support its use. Indeed, it has been suggested that it may adversely affect recovery through encouraging the development of synkinesis (K. Doyle, MD: personal communication, 1993). It is not uncommon for a patient to awake from surgery with facial function only to have it gradually deteriorate in the early postoperative period. Although this usually occurs within 72 hours of surgery, we have observed it as much as several weeks later. The probable etiology of delayed weakness is neural edema, perhaps vasogenic, which may be associated with the sterile arachnoiditis that frequently follows AN surgery. As a general rule, the prognosis of delayed onset facial palsy is favorable. Many recover within a matter of weeks as edema subsides. Others require many months to recover, a course suggestive of demyelination. Occasionally patients with delayed facial palsy have incomplete functional return, but only rarely is recovery completely absent. Perioperative administration of corticosteroids has been suggested as a means of reducing the incidence of delayed facial palsy through reduction in neural edema. This treatment has theoretical appeal, but no

759

data is available to support its efficacy and our anecdotal experience is that corticosteroids are ineffective in this regard. Because neural edema may be expected to be especially problematic within the bony confines of the Fallopian canal, performing a bony decompression of the labyrinthine segment at the time of tumor removal has been suggested as a means of preventing the evolution of delayed palsy.254 The nonmotor components of the FN may also be disturbed following AN surgery. Transient taste disturbance is not uncommon following AN surgery due to dysfunction of the taste fibers that supply the anterior two-thirds of the tongue. Typically, this resolves within several months. Dry eye due to decreased lacrimation (parasympathetics travel with the greater superficial petrosal nerve) is also a common sequelae of AN surgery, even when facial motor function has been preserved. In the absence of facial paralysis, this problem is a mild nuisance to most, although it may make wearing of contact lenses difficult. Aberrant reinnervation of the lacrimal fibers may result in gustatory tearing. Socalled crocodile tears usually constitute only a nuisance. When they are particularly severe, relief may be obtained through partial excision of the lacrimal gland. Management Options when the Facial Nerve is Disrupted Clinicians must be aware of the distress felt by some patients experiencing facial palsy after AN surgery and that the level of distress may not be related to the clinical grade of the facial nerve paralysis. According to a recent study, people with low self-esteem, young people, and women suffer from more distress from the facial palsy. Clinicians should thoroughly counsel patients before and after surgery and should implement measures that increase patients’ self-esteem and decrease their distress, especially in these high-risk groups.255 Primary Reconstruction of the Facial Nerve Conceptually, immediate repair of a disrupted FN following tumor removal is appealing. It avoids the need for a second surgery and, unlike nerve crossover procedures, it creates no new neurologic deficits. There are three methods of immediate FN repair: direct suture, mastoid-meatal rerouting and suture, and interposition grafting. The simplest way to repair cranial nerves VII–VII is by mobilization of the transected ends followed by direct suture (Fig. 45-26). In our experience, this is seldom possible because the length of the deficient segment prohibits tension-free anastomosis. In the TL approach, the redundant FN in the mastoid can be mobilized, yielding 5 mm to 10 mm of additional length and permitting repair by direct anastomosis256 (Fig. 45-27). Defects that cannot be bridged in this manner require an interposition graft. During most neurotologic procedures, the greater auricular nerve is used because it is readily available and a good size match. Repair with an interposition graft differs from that with a mastoid-meatal rerouting in that it require two anastomoses. When performing an intracranial anastomosis, it is important to realize that the intracranial segment of CN VII possess no epineurium. For a suture to hold, it must be placed through the substance of the nerve. For this reason, typically

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published series are 84% (16/19), 57% (12/21), 100% (8/8), and 44% (4/9).256–259 Hypoglossal-Facial and Spinal Accessory-Facial Anastomoses

Figure 45-26. Direct facial nerve repair during the translabyrinthine approach through mastoid-meatal rerouting. Mobilization of the redundant intratemporal course provides an additional 10 mm to 15 mm of length to bridge a gap.

only one suture is used passing through the center of the nerve. A reasonable alternative is the use of a nonsuture anastomosis such as a collagen tube or fibrin glue.257,258 The theoretical benefits of sutureless grafting include technical simplicity, reduced foreign body reaction, and prevention of neural trauma caused by the suture needle. Results with direct nerve repair, with or without use of a graft, are modest. The usual result achieves at best a grade 3 or 4 function. Success rates (grade 4 or better) in representative

Figure 45-27. Facial nerve repair in the cerebellopontine angle with a greater auricular nerve interposition graft.

In many cases of FN disruption resulting from AN surgery, the proximal end of the FN exiting from the brainstem is not usable for reconstructive purposes. Although there is seldom complete absence of a stump proximally, the residual fibers may be so ribboned that they technically cannot be joined to a nerve graft which is round in cross-section. Under such circumstances, the proximal portion of a motor cranial nerve may be transposed onto the distal segment of the FN. This technique might also be indicated when an anatomically intact or primarily repaired nerve has not shown signs of recovery by 1 year following surgery. At this point, an electromyogram (EMG) is obtained to detect subclinical signs of reinnervation. When polyphasic potentials are detected, several more months are allowed to pass. If no functional return is evident at this time, or if signs of reinnervation were absent at the 1-year evaluation, then nerve crossover is recommended. The nerve crossover procedure in most widespread use is the hypoglossal to facial anastomosis (Fig. 45-28). One advantage of using the innervation of the tongue is that it, like the facial nerve, is tonically active and therefore provides tone at rest. Hypoglossal-facial anastomosis is performed as a secondary procedure, usually 4 to 6 weeks following tumor removal. It is usually unwise to undertake this procedure at the time of tumor resection because the neck and parotid flaps may fill with CSF flowing from the craniotomy defect. In most individuals, sacrifice of the hypoglossal nerve leads to little difficulty with speech or swallowing, in part due to the partially bilateral innervation of the tongue. However, when vagal and

Figure 45-28. Schematic of the relationship between the hypoglossal and facial nerves in preparation of XII–VII anastomosis for reanimation of the paralyzed face.

Acoustic Neuroma (Vestibular Schwannoma)

glossopharyngeal deficits exist, sacrifice of the hypoglossal nerve is contraindicated because this may decompensate the deglutition mechanism. Satisfactory results, defined as rest tone with some motion, are obtained in more than 80% of cases.260–263 It has been noted that somewhat better results are realized when the procedure is performed within a few months of the nerve disruption.260 However, the procedure may be delayed 1 year or even longer and still have an excellent chance of success. The facial reanimation afforded by a hypoglossal to facial anastomosis is imperfect. At best, patients have excellent symmetry at rest and can train themselves to make a fairly natural smile. Despite excellent reinnervation, many patients obtain an imperfect result due to excessive tone (occasionally with spasm) and marked synkinesis. An anastomosis between the spinal accessory and facial nerves is another reconstructive option. Success rates are similar to the hypoglossal to facial anastomosis if done early after resection of the lesion. However, results are less favorable when the reconstruction has been delayed. To avoid the donor deficit of a weak and possibly painful shoulder, using only a portion of the nerve has been suggested to minimize loss of function. Patient satisfaction with the various facial reanimation techniques has been assessed through a survey of the membership of the AN Association.264 This report included opinions from 61 patients who underwent CN XII–VII anastomosis and 6 who had CN XI–VII crossover. Slightly less than half of the XII–VII group reported a functional return of greater than 50% when compared to the opposite normal face. In the majority of patients, poor eye closure and unsatisfactory facial appearance while smiling persisted. The few patients who had undergone XI–VII procedures were even less satisfied than the XII–VII group. A number of additional options for reanimation of the paralyzed face following excision of AN are available including masseter and temporalis muscle transfers, cross face anastomosis, and innervated microvascular muscle transplants.265 Little data is available on the results of these procedures in patients with ANS. Care of the Eye in Facial Palsy Poor eye closure caused by facial weakness creates a risk of corneal desiccation. A dry cornea may become ulcerated which, if not meticulously managed by physician and patient alike, may lead to the formation of permanent opacities. The facial paralysis that follows AN surgery is usually accompanied by decreased lacrimation resulting from disruption of the parasympathetic innervation to the lacrimal gland. In addition, dysfunction of the fifth nerve, which is frequent with larger tumors, leads to impaired corneal sensation. A dry, anesthetic eye that lacks a blink reflex is virtually certain to develop corneal decompensation without aggressive intervention. Medical management includes the liberal application of artificial tears and lubricating ointments. At night, the eye may be taped shut or protected with an occlusive plastic shield. The classical surgical treatment for the paralyzed eye is tarsorrhaphy, the suturing together of the eyelids to narrow the palpebral fissure and thus improve eye closure. However, tarsorrhaphy is both esthetically and functionally

761

suboptimal for most patients. In recent years, restoration of eye closure through use of upper eyelid gold weights or springs has largely supplanted tarsorrhaphy in most major centers.266,267

Hearing Conservation Pathology and Pathophysiology of Cochlear Nerve Involvement Preservation of hearing in the tumor ear is one of the more challenging goals in AN management. There are approximately 30,000 fibers in the human cochlear nerve. Quantitative histologic studies in experimental animals have shown that up to 75% of the nerve population to a given region of the cochlea can be destroyed without raising the hearing threshold.268 Because greater numbers of functioning fibers are needed to convey complex information, speech discrimination may be affected out of proportion to pure tone loss. Cochlear nerve fiber dysfunction can result either directly from tumor infiltration or indirectly from pressure-induced demyelination or ischemia. Several studies have assessed the frequency of cochlear nerve infiltration by ANs. Although these tumors originate from the vestibular division of the eighth nerve, microscopic involvement of the cochlear division is frequent even when the surgeon sees no gross involvement.96–98,269,270 When the cochlear nerve adheres to the tumor surface, it is probably infiltrated to some degree. The converse, that infiltration is absent when the tumor separates from the nerve easily, is not always true. In a study by Neely, in 3 of 15 cases where the cochlear nerve appeared normal during microdissection from the tumor capsule, residual tumor was noted infiltrating between fibers.97 More important, the proximal eighth nerve trunk medial to the tumor was infiltrated despite a normal appearance in all 6 of 6 cases investigated. Of note, the cochlear nerve lateral to the tumor in the fundus of the IAC was often free of tumor. Although the surgeon may initiate a clean dissection plane in this location, sharp dissection in the medial direction is likely to cleave off fronds of tumor cells that interdigitate with nerve fibers. A clinical-pathologic correlative study of 22 tumors showed significant fiber destruction and tumor infiltration even when the hearing was relatively good and the tumor small.98 In none of these cases was a well-defined connective tissue plane between the tumor and cochlear nerve identified. In another study, immunochemical investigation of the tumor-cochlear nerve interface in 10 mediumsized tumors demonstrated neural invasion in 6.95 Results somewhat at variance with the above-cited studies come from a study of 10 tumors scrutinized by both light and electron microscopy, which detected a relatively low incidence of cochlear nerve invasion.270 Actual cochlear nerve invasion was confirmed ultrastructurally in only three patients, each of whom had NF2. This greater tendency for cochlear nerve invasion in NF2 has been reported by others as well.271 An attempt to distinguish subtle cochlear nerve involvement through the use of staining for the neural tissue–specific protein S-100 was unrevealing as both AN and cochlear nerve stained for this marker.93

762

SURGICAL NEUROTOLOGY

Another factor that influences the probability of cochlear nerve invasion by AN is whether the tumor arose from the superior or inferior vestibular nerve. Because the cochlear nerve lies in the inferior compartment of the IAC, inferior vestibular schwannomas are typically more intimately related to it. Tumors that involve the fundus of the IAC may also be more prone to invade the cochlear nerve due in part to the confined space of this lateral recess. Such tumors also have the potential of invading the cochlea via the modiolus.65 The most important implication of microscopic invasion of the cochlear nerve by AN is not the fear of leaving residual disease, but rather the jeopardy it places the nerve in during tumor microdissection. Undoubtedly, this tendency for the tumor to interdigitate with cochlear nerve fibers contributes to the difficulty of preserving hearing in these tumors. The risk of leaving microscopic tumor residuals, in terms of generating recurrent disease, is unknown, but it is probably small (see the section on “Incomplete Tumor Removal”). There are three requirements for success in a hearing preservation effort: (1) The tumor capsule must be separated from the cochlear nerve without disrupting or unduly traumatizing it, (2) the blood supply of the cochlea and nerve must be maintained, and (3) the inner ear must not be destroyed in the process of exposing the tumor. In only a small minority of ANs is it possible to fulfill all of these requirements and totally excise the tumor. The most frequent reasons for failure of hearing conservation efforts are gross infiltration of the cochlear nerve, which requires its resection, and the necessity of drilling away a portion of the inner ear to expose the lateral terminus of the tumor in the IAC (see the section “Microsurgical Management”). However, it is disconcerting how often the cochlear nerve can be anatomically preserved, at times seemingly having sustained little or no apparent trauma, but nevertheless hearing is lost or seriously degraded postoperatively. There are probably multiple causes for this phenomenon. Dissection along the compressed segment of the nerve may interrupt microvasculature and result in fiber damage or intraneural hemorrhage. Animal studies point to retraction of the cerebellum as a frequent precipitator of auditory dysfunction.272 Clinical observations from intraoperative electrophysiologic changes confirm the occurrence of this phenomenon in humans. Not uncommonly we have observed a sudden loss or substantial latency prolongation of wave V accompanied by preservation of wave I occurring at the time of cerebellar retraction. It is possible that this maneuver places the eighth nerve and its arachnoid tethers under tension, thereby stretching the nerve and/or vasa nervorum. Traction on the nerve can also lead to nerve fiber disruption at one of two particularly weak points. One site of mechanical weakness occurs at the junction of central and peripheral myelin (the Obersteiner-Redlich zone).272 At this transition the central myelin is surrounded by delicate astrocytic processes, and the peripheral fibers are reinforced by a collagenous endoneurial tube. Neural separation at this point may occur preferentially in the central portion of the nerve and thus not be visible externally. A second potential point of weakness exists laterally where the cochlear nerve splays into many small fibers as it penetrates the modiolus. Medially directed traction originating anywhere along the course of the nerve from IAC to

brainstem entry may avulse these fragile fiber bundles from the base of the cochlea. Interruption of vascular supply to the cochlea undoubtedly accounts for some hearing losses associated with AN removal. Either physical interruption or thrombotic occlusion of the internal auditory artery results in cochlear infarction. In contrast to cochlear nerve injury, cochlear dysfunction affects all waves of the ABR. Vasospasm may play a role in intraoperative hearing loss. Topical application of a vasodilator (e.g., papaverine hydrochloride 30 mg/mL) occasionally reverses a sudden deterioration in electrophysiologic measures.273 Based on experiences in an animal model, intraoperative monitoring of cochlear blood flow using a laserDoppler technique has been proposed as a means of providing the surgeon an early warning of cochlear ischemia.274 Some insights into the pathophysiology of intraoperative hearing loss may be gleaned from observations of postoperative patients. Delayed hearing loss occurring in the first postoperative week is fairly frequent following AN surgery. This has been associated with intraoperative deterioration of wave V with preservation of wave I.275 Presumably, late hearing loss results from progressive neural edema or ischemia. Occasionally an ear with poor hearing in the early postoperative period spontaneously improves weeks or months later. This type of delayed recovery is consistent with resolution of a transient neural conduction defect.276 Electrophysiological observations have been made in patients with an anatomically preserved cochlear nerve but no postoperative hearing.277 In two of three patients studied, promontory stimulation revealed preserved electrical stimulability of the cochlear nerve despite deafness. This implies that cochlear infarction with death of hair cells was causative of the hearing loss in these cases. A recent study278 showed that the presence of either the ABRs or near-field cochlear nerve action potentials (CNAPs) was not related to AAO-HNS class outcome. Both techniques had a useful rate of prediction of hearing preservation surgery outcome but in nearly one-quarter of the cases, there was no association between ABR or CNAP responses and hearing preservation. These results have to be considered when determining the clinical usefulness of these techniques. Assessing Candidacy for a Hearing Conservation Attempt A cardinal issue in hearing conservation is who should be considered a candidate. Because the probability of success greatly influences the decision process, preoperative prognostic factors are important.279–281 As a general rule, the better the hearing, the more likely is success in a hearing conservation effort. No rigid auditory criteria can be developed because the decision must always take into consideration the level of hearing in the opposite ear. When the contralateral hearing is normal or nearly so, most surgeons would not recommend a hearing conservation approach when the SRT is greater than 50 dB and/or the SDS is less than 50%. If the concept of useful hearing is taken into account, these exclusionary criteria could reasonably be placed at greater than 30 dB SRT and/or less than 70% SDS. A normal or near-normal ABR is also a

Acoustic Neuroma (Vestibular Schwannoma)

favorable indicator. Conversely, an absent or severely distorted ABR, even when the hearing level is quite good, is an unfavorable prognostic factor. An intact stapedial reflex may also be an auspicious sign. In terms of vestibular testing, a reduced caloric response has been said to be favorable because it suggests superior vestibular origin to the tumor.280 Tumor location and size also play a key role in determining candidacy. The depth to which the tumor extends into the IAC is often the determining feature in the ability to conserve hearing.192 The degree of IAC erosion can also affect results. It seems probable that substantial canal erosion predicts a greater compression of the eighth nerve, although this feature has yet to be studied as an independent variable. Success is only rarely achieved in tumors exceeding 2 cm in cisternal diameter. Nevertheless, this size limit should not be rigidly enforced. A few patients with larger tumors have excellent hearing, nearly normal ABR responses, and a minimal IAC component. While the success rate in such patients is not high, it is also not negligible. It should be emphasized that these criteria apply to AN alone and are not necessarily applicable to other tumors of the CPA. In angle tumors not originating from the eighth nerve (e.g., meningioma, epidermoid), hearing conservation is much more probable than with an AN of similar size and location. Definition of a Successful Result When one considers hearing conservation in AN, the criteria for success must be appropriately defined. Many studies report favorable outcome as mere persistence of any residual hearing in the operated ear. As has been aptly pointed out, when the contralateral ear is normal, most patients derive little benefit from a postoperative tumor ear that hears substantially below normal levels.282,283 The Stenger effect predicts that the patient will little appreciate hearing in the worse ear when it has a threshold in the speech frequencies more than 30 dB higher than the better side. Such rules of thumb have long been employed by otologic surgeons when considering surgery for patients with conductive hearing loss, but this type of analysis has seldom been applied in AN surgery. Speech discrimination is another very important measure of “useful” hearing in a postoperative ear. A speech discrimination score 30% below the better side is unlikely to enhance the patient’s overall communicative ability. Using this 30/30 parameter in assessing potential benefit allows the clinician to counsel the patient more realistically about treatment options. Overly optimistic counseling about hearing conservation may lead to disappointment on the part of the patient whose surgeon proudly points to a postoperative audiogram demonstrating “successful” hearing preservation when he or she can discern little actual benefit. Rather than use a single criterion to assess hearing outcome, a classification system analogous to the House-Brackmann scale used in reporting postoperative facial function has been proposed for reporting hearing results.284

763

retrosigmoid approaches (Table 45-9A and B). Others advocate using either approach depending on the characteristics of the tumor undergoing treatment.190–192,285 Reports on the rate of success in maintaining hearing following AN excision vary widely. Much of the published data is impossible to analyze because the amount of residual hearing is not specified. Still other studies reporting a degree of success include no audiologic data at all. It is important to realize that hearing results discussed next refer only to that subset of patients with ANs who are deemed to be candidates for hearing conservation surgery. While this fraction of the entire AN population varies according to the availability of sensitive diagnostic tools such as ABR and MRI, to the surgical team’s referral pattern, and other factors, it probably constitutes between 10% and 30% of all patients with ANs. With the MF approach to intracanalicular tumors, “measurable” hearing is maintained in approximately 50% of cases.196,281,286 However, “useful” hearing is probably achieved in no more than 25% of these most favorable cases. In our own series of 150 patients with the MF approach and tumors smaller than 18 mm in the CPA, the following results were recorded. In the MF group, class A or B hearing was preserved in 62% of patients with tumors smaller than 10 mm in CPA component and 34% of tumors with 10 mm to 18 mm in the CPA.196 According to a recent study, valuable prognostic indicators for hearing preservation in the MF approach seemed to be the preoperative hearing status, ABR, and intraoperative tumor origin data.153 A major drawback of the MFA technique is the fact that complete resection of IAC tumors involving the fundus requires some degree of blind dissection. Therefore, specialized tools and techniques are required to minimize the risk of neural injury during this indirect dissection. In addition, inspection of the fundus with either mirror or endoscope is often necessary to exclude the possibility of retained tumor fragments.195 In the RS approach to tumors with a cisternal component larger than 2 cm, preservation of useful hearing is diminished.286–289 In our own series, up to 25% of patients retained good hearing.290 The results are, however, dependent on the age of the patients.291 Overall estimates of hearing success rates are less important in deciding the optimal course for a given patient than the interpretation of that individual’s prognostic factors. In the very best group with a small tumor, little IAC involvement, excellent hearing, and a normal ABR, the chance of preserving useful hearing may well reach 50%, whether operated via the RS or MF approach. Indeed, a few fortunate patients will actually achieve an improvement in hearing following tumor removal.292 By contrast, patients whose hearing and tumor characteristics place them at the fringes of candidacy for hearing conservation may have very little chance of success. Taking into account the relatively small fraction of patients with ANs who are candidates and the limited probability for success, it can be estimated that only about 5% of patients with ANs maintain useful hearing in the tumor ear following surgical excision.

Results in Clinical Series In recent years, a number of major centers have reported their results with attempts at hearing conservation. Most reports emphasize use of either the middle fossa or

Long-Term Hearing Results Only recently has long-term follow-up become available for a limited number of patients who have undergone successful

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SURGICAL NEUROTOLOGY

TABLE 45-9A. Hearing Preservation Rates from Several Contemporary Studies AAO-HNS Class‡ Study Glasscock360 Brookes361 Arriaga358 Slattery362 Irving290

Satar196

Number (n) 136 13 26 34 143 25 20 5 17 12 21 104 47

Approach*

Tumor Size (cm)†

38 MF, 98 RS RS RS MF MF MF MF MF RS RS RS MF MF

< 1.5 < 1.0 Mean = 1.66 Mean = 0.72 Mean = 1.2 Intracanalicular 0.1–1.0 1.1-2.0 Intracanalicular 0.1–1.0 1.1–2.0 IC – 0.9 1–1.8

(A+B)

(C)

37 (27%) 6 (46%) 14 (54%) 24 (71%) 74 (52%) 11 (44%) 12 (60%) 1 (20%) 2 (12%) 3 (25%) 3 (14%) 57 (62%) 15 (33%)

7 (5%) 2 (15%) 1 (4%) 1 (3%) 5 (3.5%) 3 (12%) 2 (10%) 0 (0) 0 (0) 1 (8%) 0 (0) 15 (15%) 3 (7%)

Hannover Class§ H1 + H2 Samii289

29 96 249

T1储 T2储 T3储

RS RS RS

H3

6 (21%) 25 (26%) 39 (16%)

7 (24%) 23 (24%) 44 (18%)

*Middle fossa (MF), retrosigmoid (RS), or suboccipital. † Tumor size includes the posterior fossa component except when indicated. ‡ AAO-HNS classification system. § New Hannover classification system. 储 T1, intrameatal; T2, intrameatal and extrameatal; T3, filling the cerebellopontine angle. Modified after Jackler RK, Driscoll CLW: Tumors of the Ear and Temporal Bone. Philadelphia, Lippincott Williams & Wilkins, 2000.

hearing conservation approaches. Unfortunately, there is a notable tendency for gradual deterioration in both pure tone threshold and speech discrimination. In 14 of 25 patients operated via the MF route (mean follow-up = 8.1 years), SRT diminished an average of 12 dB while SDS fell by 25%.293 A similar hearing deterioration was noted in only one of the nonoperated ears. In a study of 11 patients operated via the RS approach, 4 showed significant hearing deterioration over the 3- to 5-year follow-up period.279 The authors suggested fibrosis and impaired vascularity as causes of the progressive loss. In yet another study, 4 of 18 patients demonstrated significant hearing deterioration in the tumor ear over a mean of 5.4 years follow-up.294 Over the long term, an unknown fraction of patients who have had a hearing conservation approach will develop recurrent tumor. We have managed several patients who

suffered symptomatic recurrence some years following RS approach with incomplete exposure of the fundus. This has been noted by others, particularly following a failed hearing conservation attempt.209,279 In these cases it is suspected that a macroscopic portion of tumor was left in the lateral terminus of the IAC, where it retained a blood supply. It is unclear at this time whether microscopic amounts of tumor left in the cochlear nerve are capable of generating a recurrence. Special Considerations in Bilateral AN and Only Hearing Ears Management of bilateral AN (NF2) differs in a number of ways from sporadic, unilateral AN (see Chapter 46)51,295 Because these patients nearly always develop profound,

TABLE 45-9B. Results of Hearing Preservation Surgery Study Cohen287

Dornhoffer363 Rowed288

Number (n)

Approach

Tumor Size (cm)

128

RS

65 11 17 26 68

MF MF MF RS RS

<0.5 0.6–1.0 1.1–1.5 >1.5 <0.5 0.5–1.0 1.0–1.5 Intracanalicular 0.4–1.5

*Pure-tone average < 50 dB and speech discrimination better than 50%. † Pure-tone average < 50 dB and speech discrimination better than 60%.

Serviceable Hearing 32 (37%)* 32 (34%) 38 (24%) 26 (11%) 39 (60%)* 7 (64%) 8 (47%) 13 (50%)† 20 (29%)

Acoustic Neuroma (Vestibular Schwannoma)

bilateral deafness over time, they should be advised to learn lip reading soon after the initial diagnosis. Because these patients are never “cured” of their disease in that the tendency to form intracranial tumors is lifelong, the therapeutic priority should be to maintain function, even at the expense of incomplete tumor removal, should this be required.296 One general rule we follow is that once the ear has become deaf, the tumor should be removed. When both ears hear well, we often recommend a hearing conservation attempt be performed on the side with the larger tumor. Incomplete removal is elected if the eighth nerve appears invaded or if the IAC is penetrated deeply. When removal is successful, the tumor in the second ear may be similarly approached. Unfortunately, even incomplete removal can impair or eliminate residual hearing. We prefer to avoid surgery on the better hearing ear, unless the tumor substantially compresses the brainstem or is enlarging rapidly. Even when both tumors have been successfully removed, this does not preclude the development of new eighth nerve tumors. It is important to realize that in NF2, ANs are not just bilateral, they are also frequently multiple on each side. As long as residual eighth nerve fiber is left in, it may continue to generate new tumors. Some have advocated preserving those eighth nerve fibers that are not obviously involved by tumor, even in a deaf ear, to maintain the possibility of later electrical stimulation via a cochlear implant. In our opinion, once an eighth nerve has become nonfunctional in a patient with NF2, it should be completely excised. If both eighth nerves become nonfunctional, consideration should be given to hearing rehabilitation through electrical stimulation of the brainstem (see Chapter 82, Auditory Brainstem Implant). Osseous decompression of the IAC has been suggested as a means of slowing the hearing loss associated with AN in NF2.297 The theory is that reducing the pressure cone in the IAC permits continued tumor growth for a time with less constriction of the cochlear nerve and IAC artery. Unfortunately, results reported to date have not been impressive. Even chemotherapy has been tried in patients with NF2, although experience is too meager to draw any conclusions.298 Rarely, a patient has deafness in an ear contralateral to an AN due to causes other than a second tumor (e.g., labyrinthitis, trauma, Ménière’s disease). A conservative approach to such tumors is also warranted, unless the history of the disease is a rapid hearing loss of the remaining hearing, brainstem compression has become substantial, rapid tumor growth is evident, or operative intervention carries relatively low risk of hearing loss.299,300 Hearing Loss in the Ear Contralateral to an Acoustic Neuroma It is not widely appreciated that AN surgery may have an effect on the contralateral ear. Sporadic cases in which an apparently normal contralateral ear has become deaf following surgery have been reported.301 The possible roles of meningitis or CSF pressure changes have not been well established. We have observed several patients who suffered a transient (days to weeks) contralateral sensorineural hearing loss in the postoperative period that resembles endolymphatic hydrops in some cases.302

765

Although permanent deafness can result, in most of our cases the contralateral hearing loss was temporary and returned to preoperative levels within 1 to 3 months. It could be hypothesized that low cisternal CSF pressure, transmitted to the inner ear via the cochlear aqueduct, could result in compensatory endolymphatic hydrops.303 Contralateral hearing loss has also been reported in cases of bilateral ANs.304 Noise-induced hearing loss caused by cranial drilling is unlikely to explain severe losses.193 Delayed contralateral sensorineural loss over the long term may also occur, although this phenomenon has not been well studied. It has been proposed that patients with ANs may suffer longterm contralateral hearing loss due to activation of autoimmune mechanisms at the time of surgery.305 In rare cases, decompression of the brainstem may improve auditory function on the opposite side.306 Rehabilitation of Unilateral Hearing Loss Profound hearing loss in one ear constitutes only a minor inconvenience for most individuals, and most choose not to use amplification devices. Because sound directed toward the deaf ear readily passes around the head, ordinary conversations are usually unimpaired. However, difficulty may occur when the good ear is masked by competing sounds in a noisy environment. Two rehabilitative strategies to partially overcome this limitation reroute sounds from the deaf side toward the better hearing ear. When the contralateral ear hears normally, a transcranial strategy can be employed in which a powerful hearing aid is placed on the deaf side to transmit sounds through the cranial base to stimulate the intact cochlea.307 Alternatively, two devices can be placed—one on the deaf ear with a receiving microphone and a second on the good ear with a speaker (CROS). These may be connected by a wire across the back of the neck or wirelessly through an RF transmitter. When the contralateral ear hears imperfectly, the signal in the better hearing ear can also be amplified (BICROS). While the effects of the head shadow can be partially corrected through the above strategies, deficiencies in stereo hearing and the inability to localize sounds associated with monaural hearing are not correctable. Bone-anchored hearing aids (BAHAs) in transcranial routing of signal by implanting the deaf ear are currently under investigation. According to two current studies, patients seem to have a significant improvement in speech intelligibility in noise and greater benefit from BAHA compared with CROS hearing aids as well as a reduced aversion to loud sounds.308,309 In comparison to the above-mentioned options of rehabilitation, this technique needs a surgical procedure and bears small risks of intracranial as well as intracerebral complications.310 Although unilateral hearing loss is seldom a severe functional deficit, loss of hearing in the tumor ear may result in substantial psychological distress to the patient. Once an AN has been discovered, both patient and physician want to cure the tumor without creating new neurologic deficits or worsening existing ones. Intellectually, the physician is aware that unilateral deafness is a relatively small price to pay for ridding oneself of a life-threatening intracranial tumor, and most well-informed patients adjust to this reality quite well. Emotionally, however, it is discouraging to both patient and surgeon that it is seldom possible to maintain

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or restore useful hearing. Despite thorough and realistic preoperative counseling, an occasional patient becomes clinically depressed postoperatively over the loss of hearing and may benefit from short-term psychiatric care. We have seen this phenomenon even in patients who had large tumors who have made an otherwise excellent recovery. It can only be hoped that the high level of interest in hearing preservation on the part of clinical investigators in recent years will ultimately lead to improved techniques that yield a greater degree of success in this endeavor.

Tinnitus Tinnitus is a common complaint in patients with ANs. The effect of tumor removal on tinnitus has been assessed in several studies.122,311–313 One study of 134 patients found that those with preoperative tinnitus showed a small but statistically significant improvement postoperatively although it seldom resolved entirely.311 Of note, those patients with no tinnitus preoperatively had a 50% chance of developing it following resection of their lesion. In another large study (273 patients), 62% complained of tinnitus before surgery, half of whom improved postoperatively.313 Most studies report that very few patients with ANs find the tinnitus very bothersome or intolerable. It remains unpredictable which patients will improve, which will show no change, and which will deteriorate; age and tumor size do not seem to be associated with the impact of surgery on tinnitus.122 The data also suggest that tinnitus may be of relatively minor importance in the overall quality of life of patients following AN surgery. However, candidates for surgery should be thoroughly informed about the possible effect of the operation on their tinnitus. There is reason to suspect that hearing conservation approaches, which leave the cochlear nerve anatomically intact, might have a higher incidence of postoperative tinnitus. However, almost all of the published data on postoperative tinnitus comes from patients who underwent a TL procedure, so it is not possible to ascertain the relative incidence following the various surgical approaches. In a report of an exceptional patient with very distressing postoperative tinnitus following a hearing conservation approach, reexploration and section of the cochlear nerve was performed.312 The neurectomy did not alter the tinnitus, which suggests an autonomous source in the central auditory system may be causative, at least in some patients.

Vestibular Rehabilitation Preoperatively, many patients with AN have a degree of vertigo and/or dysequilibrium, often accompanied by a unilaterally reduced or absent vestibular response on caloric testing. After tumor removal, the unilateral deficit becomes complete if it was not so already. The vast majority of patients compensate well using the contralateral intact labyrinth together with their proprioceptive and visual systems. Compensation is a gradual process, however, and typically takes several weeks or months to achieve the ultimate level of recovery.314 The decompensated state that follows tumor removal is often quite severe, especially for patients with smaller tumors and relatively intact vestibular nerves. Severe vertigo accompanied by nausea, vomiting,

and vigorous nystagmus typically abates over 1 to 3 days. In the short term, administration of vestibular suppressants and antiemetics may comfort the patient. However, when used beyond the early postoperative period, such medications may retard vestibular compensation and are best avoided. The most important factor influencing the compensation process is physical activity. Patients are encouraged to ambulate as soon as possible and given vestibular adaptation exercises to practice. Over the long term, even fully compensated patients are not always entirely normal. Having only one functioning labyrinth makes an individual somewhat more dependent on visual and proprioceptive cues for maintaining balance and coordinating movements. Because of this subtle deficit, patients with ANs, whether before or after tumor removal, often notice a mild imbalance in dark or visually confusing environments. From an occupational standpoint, this mild disability is seldom important, unless the individual is required to perform tasks that take place at heights or otherwise require fine balance skills. An objective measure of the pace and completeness of vestibular compensation following AN removal has been obtained through a comparison of preoperative and sequential postoperative rotatory chair testing results in 26 patients.315 As expected, tumor removal was associated with a acute drop in vestibulo-ocular reflex (VOR) gain, which gradually returned toward normal over time. Abnormalities were most marked at 1 week following surgery and were largely resolved by 3 months. Changes were most notable at lower frequencies (e.g., 0.0125 Hz) with few abnormalities noted above 0.05 Hz. The rate of compensation was not significantly affected by clinical variables such as tumor size, patient age, and gender. The lack of effect of advanced age on the rate of compensation was an important observation, which contradicts conventional wisdom. Many clinicians assume, perhaps incorrectly, that older individuals adapt poorly following an acute loss of vestibular input. Of course, the elderly are more apt to have coexistent sensory deficiencies such as poor vision or a loss of proprioception which can adversely affect recovery. While the size of the tumor had little effect on the pace of the compensation process, it did influence the ultimate level of compensation achieved. It has been hypothesized that larger tumors, through compression of the brainstem, may adversely affect the ability of the vestibular nuclei to reach full compensation. Only a few clinical studies that address recovery of equilibrium following AN removal appear in the literature. In a survey of 57 patients queried between 1 month and 13 years following surgery, balance was generally impaired temporarily following surgery but returned to the preoperative level over time.316 In the early postoperative period, 60% complained of difficulties with walking, running, and stair climbing and 82% had difficulty when rapidly turning the head. In another study of 156 patients, following surgery dysequilibrium was better in 47%, worse in 17%, and unchanged in 29%.313 In a study of postural control ability in 57 patients with ANs both before and 6 months following surgery, a significant improvement was demonstrated following removal of the lesion.317 Based on observations of body sway with eyes both closed and open, it was postulated that decompression of the pons improved the use of visual clues in the feedback control of posture.

Acoustic Neuroma (Vestibular Schwannoma)

Headache As with all craniotomies, some degree of headache is inevitable during the early postoperative period following AN surgery. Significant headache persisting beyond the first month, however, occurs only in a minority of individuals. Persistent headache after AN removal is occasionally focused toward the operative site but is more commonly generalized. The headaches are typically episodic and may be quite severe, even debilitating in rare cases. Many patients report that headache is triggered by coughing or straining. In a few cases, exacerbation may follow ingestion of alcoholic beverages. The time course is variable, but most often headaches wax and wane over several months and eventually disappear. Headache seldom persists beyond 1 year; in rare cases the headache diathesis appears to be long lasting.318 The incidence of persistent headache following AN surgery varies according to the surgical approach and the tumor size. In one study, 100 patients (50 TL, 50 RS) were evaluated for headache during the first postoperative year. At some time during the interval between 1 and 6 months following surgery, 32% of RS patients and 16% of TL patients reported severe headache. By 6 months following surgery, 12% of RS patients continued to suffer severe headache (based on both intensity and frequency) while the incidence in TL patients was zero. Of interest, an inverse relationship between tumor size and the incidence of headaches was noted. The patients at highest risk of suffering persistent postoperative headaches were those with small tumors (<1 cm diameter) whose surgeries took an RS approach for hearing conservation purposes. In addition, craniectomies tend to do worse in respect to postoperative pain.319,320 In a survey of 541 patients enrolled in the AN Association, 34% identified headache as a significant residual problem following their operation.321 In a series of 273 patients from Denmark, headache was identified as a persistent problem in 29%.313 According to a recent study from Finland, the major risk factors for postoperative problems with headache are a retrosigmoidal approach, postoperative gait problems, preoperative headache, and small tumors.322 These series also suggests that if headache is present before surgery, it tends to continue after surgery, and if headache continues for 1 year, it usually persists without being reduced. Management of persistent post-AN headache is largely empirical. In the early postoperative period, narcotics can usually be replaced by nonsteroidal anti-inflammatory drugs such as indomethacin and ibuprofen. These are generally best taken regularly as a preventive measure. This strategy is usually more effective than medicating in response to each episode. As the headaches become mild or infrequent, the medication should be tapered rather than abruptly discontinued. Headaches refractory to this regimen require additional therapy. During the first few postoperative months, a short course of oral corticosteroids many bring dramatic relief. This improvement may be long lasting, but most often is transient with headache recurring following withdrawal of the drug. Occasionally, steroid-responsive headaches can be gradually resolved with low-dose corticosteroids. When possible, they should be administered every other day and gradually tapered

767

over weeks or months. As a general rule, it is best to avoid long-term use of oral narcotics, although occasional use for particularly severe episodes may be warranted. Simple measures such as neck muscle massage, application of heat or cold, and biofeedback therapy bring relief to some patients. Surgical measures to abort persistent postoperative headaches have generally not proved successful. This includes avulsion of the occipital nerve as well reoperation for the purpose of disrupting possible adhesions between the nuchal muscle and the dura. It is important to analyze the mechanism of postoperative headache following AN removal because insight into the underlying cause may suggest preventive strategies. Numerous pathogenic mechanisms have been proposed, including extracranial factors such as nuchal muscle spasm and entrapment of the occipital nerve in the surgical scar with resultant neuropathy. Although these mechanisms may be responsible in a fraction of cases, most clinicians believe that either low-grade aseptic meningitis or an abnormal coupling of the posterior fossa dura with the nuchal musculature are causative in the majority of cases. In the classically performed RS craniectomy, the suboccipital bone is discarded. Dense adhesion between the neck muscles and the dura has been frequently observed clinically and demonstrated histologically in at least one reported case.318 This phenomenon may be avoided by creation of a bone flap, which is replaced at the end of the procedure.320 However, the suboccipital bone plate is relatively thick and turning a flap may be technically difficult, particularly on the edge adjacent to the sigmoid sinus. In recent years, we have removed the suboccipital plate piecemeal and replaced the bone chips at the end of the procedure. In our experience, this reliably heals into a rigid plate, which effectively partitions dura from nuchal musculature. Arguing against dura to muscle adhesion as a common cause of persistent postoperative headache is the observation that headache less frequently follows RS craniotomies performed for other purposes (e.g., hemifacial spasm, tic douloureux, cerebellar tumors) than it does for AN. An alternative explanation for long-lasting postoperative headaches is chronic, aseptic meningitis. RS craniotomy for AN differs from other posterior fossa procedures in that bone is drilled intracranially in the process of exposing the intracanalicular portion of the tumor. Despite efforts to contain it, this tends to disperse bone dust widely throughout the arachnoidal surfaces of the infratentorial compartment. With the TL procedure, by contrast, all drilling is completed before the dural is opened. Evidence in favor of the aseptic meningitis theory includes the greater incidence of headache following the RS as opposed to the TL approach, the frequency of corticosteroid responsiveness, and the occasional wound swelling noted in association with headache episodes. The anecdotal observation that headache is more frequent following RS vestibular neurectomy when the IAC is drilled open than when it is left intact also tends to confirm the culpability of bone dust. Although one or more pathogenic mechanisms may predominate in postoperative headache, undoubtedly a multiplicity of causes exist. Vascular headaches, including migraine variants, are seen occasionally following AN surgery. In one of our RS patients, classical cluster headaches onset following tumor resection. The clinician must be

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SURGICAL NEUROTOLOGY

alert to the possibility of infectious meningitis, particularly in the early postoperative period. Clues to this complication include the severity and duration of the headache as well as its association with fever, malaise, nuchal rigidity, and other neurologic symptoms. Cryptic CSF leak can also cause chronic headache due to low CSF pressure. Historical clues to this entity include positional and exertional triggers, watery rhinorrhea or postnasal drip, and a history of meningitis.

Social and Occupational Rehabilitation In recent years, several aspects on the social and occupational recovery of patients from AN surgery has been published. In a survey of 541 members of the AN Association (a patient information and support organization), only 5% were unable to return to work following tumor removal.321 Eight percent reported an inability to resume normal social life, and 15% noted easy fatiguability. Even these relatively low percentages of global lifestyle changes are probably overestimates because many members join this group for help coping with long-term disability. This selfselection skews the patient population toward those with less favorable outcomes. In a Danish study of 273 patients, adverse vocational impact was noted in 14%, 9% of whom ceased to work and 5% required a change of employment. In a study of 57 patients from Japan, only 63% returned to their same occupation following surgery and 70% resumed driving a car.316 It is intriguing to note that 80% of patients continued to play golf after their surgery. Several factors may contribute to the wide discrepancies in success of occupational rehabilitation among the different countries, including the amount of social support provided to disabled workers. In addition, the availability of sophisticated diagnostic tools such as MRI varies around the world, a factor that may affect the size mixture of tumors at the time of diagnosis and thus create a variable incidence of less favorable longterm outcome. Depression at some time in the postoperative course was noted in 38% of patients in a study from the United States, and it was noted in 17% in the Danish study.313,321 These data are derived from patient response questionnaires and do not reflect actual psychiatric diagnoses. In addition, neither the severity nor the duration of depression was indicated in either study. In our experience, global recovery of a patient following AN surgery depends most on the tumor’s size323 and the patient’s age. It would be highly unusual for an individual younger than 60 years with a tumor smaller than 2 cm not to make an excellent functional recovery. If fact, most younger patients with even very large tumors resume active and productive lives within several months of surgery. By contrast, some elderly individuals remain disabled despite having only small tumors whether they were operated, radiated, or simply observed. The most common cause of disability in the aged is chronic imbalance. In summary, the economic, social, and psychological impact of AN and its surgical management appears to be relatively minor, with few individuals having life-altering consequences.324

RADIATION THERAPY Conventional Radiotherapy There are two forms of radiation therapy in use in the treatment of AN: conventional and stereotactic. Conventional radiotherapy is seldom used in the developed world today although it is still occasionally employed in the developing world where stereotactic equipment is not available. In conventional radiotherapy, a photon beam is delivered at 1.5 to 2 Gy for 5 days per week over the course of 4 to 6 weeks to reach a total dose of approximately 50 Gy.325,326 Since radiation injury preferentially affects dividing cells, one benefit of fractionation is the opportunity for a greater number of cells to enter mitosis during the treatment course. However, because ANs have a very low index of mitoses, only a relatively small number of tumor cells would enter this vulnerable stage during the treatment course. Few reports are available on the effectiveness of conventional irradiation. In one study of 20 patients followed 7 to 46 months (mean 30 months) after radiation, 2 died of their tumors, 2 died of unknown causes, 2 patients developed hydrocephalus, and 2 required salvage surgery.326 Such results are clearly poorer than those of surgical excision and modern stereotactic radiation. The effects of conventional radiotherapy on partially excised AN has also been studied. In a study of 31 patients with ANs, it was concluded that fractionated radiotherapy was of no benefit to those who had undergone total or near-total tumor removal.325 Following subtotal excision, however, 46% (6/13) of unradiated tumors recurred and only 6% (1/17) of irradiated tumors showed signs of symptomatic progression. This seemingly convincing data is open to several criticisms. The two groups may not have been equivalent because patients accrued over nearly 40 years and the term subtotal may have had different meanings to various surgeons over the decades of the study. In addition, recurrence was defined as symptomatic progression, and many seemingly controlled patients could well have had tumor growth if they had been evaluated radiographically. Finally, this study showed a poor prognosis for patients irradiated at the time a postsurgical recurrence was detected. Based on the published data, there is little to commend conventional radiotherapy in the management of ANs.

Stereotactic Irradiation The fundamental concept of stereotactic radiation (SR) is to deliver a precise, conformal dose of radiation with isodose lines tailored to the margins of the tumors. In contrast to conventional radiotherapy, in which a large number of fractions are delivered over many weeks, stereotactic radiation is designed to induce necrosis in the irradiated tissue through a single large dose delivered during a single session or a few fractions delivered within a short period of time. The dose delivered to the center of the tumor is more intense than that at the margin. Stereotactic radiation with photons is most commonly delivered either by a multisource Cobalt-60 gamma unit (the Gamma Knife) (Fig. 45-29). Single-source linear accelerator-based radiotherapy has

Acoustic Neuroma (Vestibular Schwannoma)

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also been developed, most notably with the Cyberknife, which uses a contoured face mask and adaptive technology to accommodate patient movement without the need for rigid immobilization329 (Fig. 45-30). The Cyberknife is essentially a linear accelerator attached to the arm of a computer-controlled high-precision industrial robot. Most centers believe that there are physical limits on the volume of tumor that can be safely radiated, making this a technique primarily suitable for small and mediumsized tumors. Prior to the mid-1990s, the usual dose was approximately 35 Gy to the tumor center and 16 to 18 Gy to the margin. In an effort to reduce cranial nerve morbidity, customary doses have been reduced recently to approximately 25 Gy to the center and 12 to 14 Gy to the margin.330 The effects of a single large dose of radiation on AN cells growing in tissue culture have been evaluated.331 While doses between 30 and 150 Gy clearly induced some damage in the schwannoma cells, a fraction of viable tumor cells persisted even after the largest dose tested, which was six times more than the maximal amount used clinically. Little histopathologic material is available from patients with ANs treated with stereotactic radiation. Histopathologic evaluation of tumors that recurred following stereotactic radiation shows some regions of residual tumor cells but also evidence of necrosis, fibrosis, and vascular hyperplasia.332 The interface between the facial nerve and the tumor has also been noted to be more fibrous following SR.333

Figure 45-29. The Gamma Knife® is a multisource cobalt radiotherapy unit.

been used less than multisource strategies, but the effect is analogous.327 With the linear accelerator, a single beam travels around the patient delivering doses either in a series of arcs or individual “shots” to achieve a highly conformal dose pattern. As a general rule, current generations of linear accelerators require longer treatment times but are more flexible in that they are not limited to the skull cap inherent in the gamma knife and thus can be used anywhere in the body. Either linear accelerator or gamma knife technique is capable of delivering a precise dose to the tumor volume while minimizing the amount of radiation to adjacent normal brain and nerve tissue. Recently, stereotactically delivered proton beams have also been evaluated.328 Protons have a theoretical advantage over photons in that the Bragg peak phenomenon ensures essentially no exit dose beyond the intended limit of treatment. Common to all high-precision radiotherapy techniques is the need to maintain very precise registration of head position during surgery. This begins with obtaining high-resolution CT or MR images to localize the tumor precisely. In most systems, a stereotactic head frame is placed for use during treatment. Implanting metal balls (fiducials) located on the skull surface is an alternative method to maintain orientation. Frameless methods have

Figure 45-30. The Cyberknife® is a linear acceleration mounted onto an industrial robot for delivery of highly precise stereotactic radiotherapy.

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TABLE 45-10. Fate of the Tumor following Single Treatment Stereotactic Radiation in Major Series with Longer-Term Follow-up No. of Patients

Report

Year

Follow-up

Prasad364

2000

95

5–10 yr

Unger365

1999

56

4–6.7 yr

Petit366

2001

23

3.5–7 yr

Kondziolka367

1998

97

5–10 yr

Flickinger330

2001

147

> 1 yr (2.5 median)†

Marginal Dose Mean (range) 13 Gy (9–20)* 12–14 Gy (—) 12 Gy (10–15) 16.6 Gy (12–20) 13 Gy (11–18)

Stable

Smaller

Larger

17% —

74% 34%

6% —

44%

52%

4%

29%

72%

0%

—

35%

—

*Marginal dose data for a larger group. Dose for long-term subset is not defined but is likely on the high end of the range for these earlier cases. † This more recent Pittsburgh series using current dose regimens is included for comparison even though follow-up is short term.

Fate of the Tumor following Stereotactic Radiation Although stereotactic radiotherapy has been used in AN for more than 40 years after being introduced by Lars Leskell and his team in Stockholm, only recently has a substantial body of outcome data been accumulated. Following stereotactic radiotherapy, the tumor remains in situ; the goal is stabilization against future growth rather than the lesion’s disappearance. A modest degree of shrinkage has been reported in roughly one-third to twothirds of patients (Tables 45-10, 45-11, and 45-12). Not uncommonly, the tumor swells somewhat during the first 6 to 18 months after treatment. This phenomenon, which likely stems from radiation-induced edema, should not be mistaken for neoplastic growth. Often a diminution of gadolinium enhancement in the center of the tumor is observed (Fig. 45-31). Numerous earlier studies have examined short-term outcome within the first few years, an inadequate period to assess long-term therapeutic efficacy. Only a few studies, totaling no more than a few hundred patients, report follow-up longer than 5 years (see Tables 45-10, 45-11, and 45-12). In these studies, regrowth was observed in approximately 5% of cases over time. This contrasts with an approximately 50% chance an AN will demonstrate significant growth over a 3-year period based on the natural history of the disease. Caution must be observed in combining earlier studies in which an @ 16 Gy marginal dose was used rather than the @ 12 Gy of protocols popular at present. Nevertheless, a substantial body of data has been accumulated indicating that stereotactic radiation controls ANs in a substantial majority of cases. One special circumstance is

cystic tumors, which have a higher rate of recurrence due to expansion of the cystic component following radiation.334 A recent trend has been toward experimentation with fractionated stereotactic radiation.335,336 Doses are divided, often into a few fractions delivered over 1 to 2 weeks. The concept of fractionation is to reduce complications, especially neuropathy, by allowing biologic recovery time from radiation injury. Unfortunately, fractionation without increasing total dose also reduces the biologic effort on the tumor itself. No significant long-term data has been published to elucidate whether or not fractionation increases risk of recurrence.

Audiovestibular Function after Stereotactic Radiation Little data exists concerning the fate of hearing over the long term. In three recent studies that followed fewer than 100 patients for 4 years, good hearing (Gardner-Robinson grade 1 or 2) was preserved in 47% to 62% (Table 45-13). Higher dose has been correlated with poorer hearing outcome.337 It is not yet clear whether fractionation improves hearing outcome, although preliminary data suggest that it does.338 Hearing preservation in bilateral ANs associated with NF2 appears to be somewhat less favorable than with sporadic unilateral AN.338–340 Hearing results do not appear to be as favorable with proton beam therapy as with photon-based modalities 328,335 Little data exists concerning the outcome of vestibular function after stereotactic radiation. Because the diseased vestibular nerve remains, persistent aberrant vestibular input is likely to remain in a sizable fraction of patients. Anecdotal observations of experienced practitioners is that

TABLE 45-11. Fate of Tumors after Fractionated Treatment Stereotactic Radiation Report

Year

No. of Patients

Follow-up

Marginal Dose

Stable

Smaller

Larger

Williams336

2002

125

Not given

88%

12%

0%

Fuss368

2000

42

1–5.7 yr (1.8 mean) 1.4–10.9 yr (3.5 mean)

Not given

52%

46%

2%

Acoustic Neuroma (Vestibular Schwannoma)

771

TABLE 45-12. Fate of Tumors after Proton Beam Radiation Report

Year

Harsh328

2002

No. of Patients 64

Follow-up 0.5–8 yr (2.8 mean)

radiation does not help older individuals with small tumors and deteriorating balance.

Cranial Nerve Function following Stereotactic Radiation Facial neuropathy has been observed following stereotactic radiation, typically commencing 6 to 12 months following therapy. In the great majority of cases, it is transient and the patient recovers facial function. The incidence of facial neuropathy has been reduced by lowering the marginal tumor dose. In the 1970s, rates of facial neuropathy were nearly 40%.341 The rate at 16 Gy marginal dose, common through the early 1990s was on the order of 10% to 20%. At current dose regimens of 12 Gy, the incidence appears to be on the order of 5% with some series reporting even less. Trigeminal neuropathy, which was formerly quite prevalent at higher doses, occurs infrequently with current dose regimens. Hypesthesia is the most common symptom. The occurrence of trigeminal neuropathy is correlated with larger tumors. Preliminary data suggests that fractionation does reduce the risk of trigeminal or facial neuropathy.338 Proton beam appears to have a higher risk of new neuropathy than photon therapy.328

Complications following Stereotactic Radiation Hydrocephalus may occur following stereotactic radiation, presumably caused by leakage of proteins from the tumor surface leading to impaired CSF resorption. This complication appears to occur in a small percentage of patients. Most neurologic injuries following radiation have onset latencies measured in months; however, a few reports of early deterioration have appeared. In one case, facial palsy

Marginal Dose 12 Gy (11–18)

Stable

Smaller

Larger

55%

39%

6%

and permanent deafness evolved 2 days following radiation of a small NF2 tumor.342 Vertigo, seizures, and persistent new headaches have been reported in the immediate posttreatment period.343 The author has seen several cases of devastating brainstem injury following stereotactic radiation (Fig. 45-32). Precipitous enlargement of the tumor necessitating urgent microsurgical decompression has been reported in a few cases.344 This appears to be a phenomenon primarily for tumors larger than those typically radiated at most centers.

Secondary Oncogenesis following Stereotactic Radiation When contemplating radiation therapy for a benign neoplasm, the risk of inducing a secondary malignant tumor must be carefully weighed. Five cases of malignancy that evolved following stereotactic radiation for AN have been reported in the literature to date (Table 45-14). Unfortunately, each case was lethal. Three were malignant schwannomas and one each glioblastoma and meningeal sarcoma. In three of the five cases, biopsy confirmed an initially benign AN. The other two, who were treated without biopsy, had clinical scenarios highly suggestive of benign AN from the outset. Interestingly, the latency period was 5 to 7.5 years in reported cases, much shorter than the more usual decades-long interval following conventional radiotherapy. The key issue, yet to be determined, is the rate of occurrence of radiation-induced neoplasia following stereotactic radiation for AN. In the best studied intracranial model of conventional radiation, pituitary adenoma, the risk is about 1% at 10 years, 2% at 20 years, and 3% at 30 years.345 Because the radiobiology of stereotactic radiation is different

Figure 45-31. MRI of a small acoustic neuroma before (A) and after (B) stereotactic radiotherapy. Note the loss of central gadolinium enhancement of the tumor on follow-up imaging.

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TABLE 45-13. Long-Term Preservation of Useful Hearing Following Stereotactic Radiation Report

Year

Kondziolka367 Prasad364 Unger365

1998 2000 1999

No. of Patients 32 36 26

Follow-up 5–10 yr 4.3 yr 4 yr

Marginal Dose 16 Gy 13 Gy 12–14 Gy

Preserved Hearing 47% 58% 62%

(Single treatment gamma knife) among patients with serviceable hearing (Gardiner-Robinson grade 1 or 2, better than 50 dB speech reception threshold, and 50% word recognition score) prior to therapy.

from that of conventional fractionated radiotherapy, the analogy is approximate at best.

Indications for Stereotactic Radiation in Unilateral Acoustic Neuroma Because roughly 50% of ANs show little growth over a 3-year period, it is reasonable to withhold treatment for smaller tumors that are minimally symptomatic, especially in older individuals, until the tumor has proved that it needs intervention by demonstrating growth on serial imaging studies. Much controversy exists concerning the relative roles of microsurgery and stereotactic radiation. At the extremes of the range, some centers favor

microsurgery almost exclusively and others advocate a similar policy for radiation. The majority of centers use the different modalities in a variable mixture based on criteria that are not always consistent among groups. In general, centers are more likely to recommend radiation for smaller tumors in older individuals and microsurgery for younger patients with a tumor of any size. Most large tumors are still managed with microsurgery. The rationale is that younger patients are more vulnerable to the potential long-term adverse consequences of radiation (e.g., secondary neoplasia, vaso-occlusive disease). Also, microsurgery is usually definitive, whereas MRI monitoring is needed indefinitely following radiation. Because after radiation therapy a tumor is still present on MRI and has potential for resumption of growth, some patients encounter eligibility difficulties when seeking to change health insurance plans.

Radiation after Surgery and Surgery after Radiation

A

A surprising fraction of stereotactic radiation cases have been AN recurrences following microsurgery. In the author’s experience, the vast majority of these recurrences stemmed from decentralized care at nonspecialized centers where large amounts of tumor were injudiciously left, particularly in the well-vascularized IAC portion of the tumor. Outcome for stereotactic radiation of tumor recurrence is similar to that of unoperated cases. It is not surprising that salvage surgery after radiation failure has a higher rate of complications than primary surgery.333,346,347 Radical resection has a high rate of permanent facial nerve neuropathy. Thus, incomplete removal (near total or subtotal) is a reasonable option in many cases.

BILATERAL ACOUSTIC NEUROMA For discussion of this condition, please see Chapter 46.

AUDITORY BRAINSTEM IMPLANT For a discussion of this innovative rehabilitation method for NF2 patients, please see Chapter 82 (Auditory Brainstem Implant).

B Figure 45-32. Precontrast (A) and postcontrast (B) MRI scans of severe brain edema following gamma knife therapy of a large acoustic neuroma.

CONCLUSION In recent years, dramatic progress has been made in both the clinical and basic science aspects of acoustic neuromas.

Acoustic Neuroma (Vestibular Schwannoma)

773

TABLE 45-14. Malignancies Reported after Stereotactic Radiation for Acoustic Neuroma Report

Year

Dose

AN Size

Thomsen369

2000

Shamisa370

2001

Hanabusa371

2001

Shin372

2002

12 Gy peripheral 20 Gy maximal 11 Gy peripheral 27.2 Gy maximal 15 Gy peripheral 30 Gy maximal 17 Gy peripheral

Comey373

1998

14.4 Gy peripheral 34 Gy maximal

Age at AN Dx

1.5 cm

19

“8.6 mL”

49

2–3 cm

57

3 cm

26

2.7 cm

44

Tumor Type

Latency

Outcome

Meningeal sarcoma Glioblastoma

6 yr

Death

7.5 yr

Death

6 mo

Death

6 yr

Death

5 yr

Death

Malignant schwannoma Malignant schwannoma Malignant schwannoma

Biopsy Confirmation of Initial Benign Schwannoma Shamisa Hanabusa Shin Thomsen Comey

Yes Yes Yes No No

These tumors can now be detected in their earliest stages at a time when treatment offers excellent prospects for functional preservation. Microsurgical techniques have been refined to the point where mortality has been reduced to less than 1% of patients, even for those with large tumors. Increasingly favorable facial and auditory nerve preservation rates are also being realized. Stereotactic radiosurgery (Cyberknife and Gamma Knife) shows increasing promise as a therapeutic option for selected patients. Recent genetic investigations have provided fascinating insights into the molecular genetic aberrations that trigger these tumors. Ultimately, the ideal solution lies in either reversing the pathophysiologic changes of the tumor cells or in preventing their occurrence through genetic engineering. Such modalities, which may seem quite far-fetched today, will undoubtedly be realized once the complex mysteries underlying the tumor’s biology have been unraveled.

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287. Cohen NL, Lewis WS, Ransohoff J: Hearing preservation in cerebellopontine angle tumor surgery: The NYU experience 1974–1991. Am J Otol 14:423–433, 1993. 288. Rowed DW, Nedzelski JM: Hearing preservation in the removal of intracanalicular acoustic neuromas via the retrosigmoid approach. J Neurosurg 86:456–461, 1997. 289. Samii M, Matthies C: Management of 1000 vestibular schwannomas (acoustic neuromas): Hearing function in 1000 tumor resections. Neurosurgery 40:248–260; discussion 260–262, 1997. 290. Irving RM, Jackler RK, Pitts LH: Hearing preservation in patients undergoing vestibular schwannoma surgery: Comparison of middle fossa and retrosigmoid approaches. J Neurosurg 88:840–845, 1998. 291. Oghalai JS, Buxbaum JL, Pitts LH, Jackler RK: The effect of age on acoustic neuroma surgery outcomes. Otol Neurotol 24:473–477, 2003. 292. Shelton C, House WF: Hearing improvement after acoustic tumor removal. Otolaryngol Head Neck Surg 103:963–965, 1990. 293. Shelton C, Hitselberger WE, House WF, Brackmann DE: Hearing preservation after acoustic tumor removal: Long-term results. Laryngoscope 100:115–119, 1990. 294. McKenna MJ, Halpin C, Ojemann RG, et al: Long-term hearing results in patients after surgical removal of acoustic tumors with hearing preservation. AJO 13:134–136, 1992. 295. Miyamoto RT, Campbell RL, Fritsch M, Lochmueller G: Preservation of hearing in neurofibromatosis 2. Otolaryngol Head Neck Surg 103:619–624, 1990. 296. Wigand ME, Haid T, Goertzen W, Wolf S: Preservation of hearing in bilateral acoustic neurinomas by deliberate partial resection. Acta Otolaryngol 112:237–241, 1992. 297. Gadre AK, Kwartler JA, Brackmann DE, et al: Middle fossa decompression of the internal auditory canal in acoustic neuroma surgery: A therapeutic alternative. Laryngoscope 100:948–952, 1990. 298. Jahrsdoerfer RA, Benjamin RS: Chemotherapy of bilateral acoustic neuromas. Otolaryngol Head Neck Surg 98:273–282, 1988. 299. Pensak ML, Tew JM Jr, Keith RW, Van Loveren HR: Management of the acoustic neuroma in an only hearing ear. Skull Base Surgery 1:93–96, 1991. 300. Driscoll CL, Jackler RK, Pitts LH, Brackmann DE: Lesions of the internal auditory canal and cerebellopontine angle in an only hearing ear: Is surgery ever advisable? Am J Otol 21:573–581, 2000. 301. Chovanes GI, Buchheit WA: Bilateral hearing loss after unilateral removal of an acoustic neuroma by the suboccipital approach: Case report. Neurosurgery 19:452–453, 1986. 302. Lustig LR, Jackler RK, Chen DA: Contralateral hearing loss after neurotologic surgery. Otolaryngol Head Neck Surg 113:276–282, 1995. 303. Walsted A, Salomon G, Thomsen J, Tos M: Hearing decrease after loss of cerebrospinal fluid: A new hydrops model? Acta Otolaryngol 111:468–476, 1991. 304. Farrell ML, Harries ML, Baguley DM, Moffat DA: Bilateral acoustic schwannoma: Post-operative hearing in the contralateral ear. J Laryngol Otol 105:769–771, 1991. 305. Harris JP, Low NC, House WF: Contralateral hearing loss following inner ear injury: Sympathetic cochleolabyrinthitis? AJO 6:371–377, 1985. 306. Deans JA, Birchall JP, Mendelow AD: Acoustic neuroma and the contralateral ear: Recovery of auditory brainstem response abnormalities after surgery. J Laryngol Otol 104:565–569, 1990. 307. Chartrand MS: Transcranial or internal CROS fittings: Evaluation and validation protocol. Hear J 44:25–28, 1991. 308. Bosman AJ, Hol MK, Snik AF, et al: Bone-anchored hearing aids in unilateral inner ear deafness. Acta Otolaryngol 123:258–260, 2003.

309. Wazen JJ, Spitzer JB, Ghossaini SN, et al: Transcranial contralateral cochlear stimulation in unilateral deafness. Otolaryngol Head Neck Surg 129:248–254, 2003. 310. Scholz M, Eufinger H, Anders A, et al: Intracerebral abscess after abutment change of a bone anchored hearing aid (BAHA). Otol Neurotol 24:896, 2003. 311. Berliner KI, Shelton C, Hitselberger WE, Luxford WM: Acoustic tumors: Effect of surgical removal on tinnitus. AJO 13:13–17, 1992. 312. Goel A, Sekhar LN, Langheinrich W, et al: Late course of preserved hearing and tinnitus after acoustic neurilemoma surgery. J Neurosurg 77:685–689, 1992. 313. Parving A, Tos M, Thomsen J, et al: Some aspects of life quality after surgery for acoustic neuroma. Arch Otolaryngol Head Neck Surg 118:1061–1064, 1992. 314. LaRouere MJ, Graham MD, Kartush JM, et al: Vestibular compensation in acoustic neuroma patients. In Tos M, Thomsen J (eds.): Proceeding of the First International Conference on Acoustic Neuroma. Amsterdam, Kugler, 1992, pp 913–919. 315. Jenkins HA: Long-term adaptive changes of the vestibulo-ocular reflex in patients following acoustic neuroma surgery. Laryngoscope 95:1224–1234, 1985. 316. Uyama K, Takahashi M, Saito A, et al: Questionnaire evaluation of balance in the performance of everyday activities after acoustic neuroma surgery. Acta Otolaryngol (Suppl) 487:91–98, 1991. 317. Magnusson M, Johansson R, Mercke U, et al: Postural control in subjects with acoustic neuroma and effects of surgery. In Tos M, Thomsen J (eds.): Proceeding of the First International Conference on Acoustic Neuroma. Amsterdam, Kugler, 1992, pp 921–923. 318. Schessel DA, Nedzelski JM, Rowed DW, Feghali JG: Headache and local discomfort following surgery of the cerebellopontine angle. In Tos M, Thomsen J (eds.): Proceeding of the First International Conference on Acoustic Neuroma. Amsterdam, Kugler, 1992, pp 899–904. 319. Santarius T, D’Sousa AR, Zeitoun HM, et al: Audit of headache following resection of acoustic neuroma using three different techniques of suboccipital approach. Rev Laryngol Otol Rhinol (Bord), 121(2):75–78, 2000. 320. Koperer H, Deinsberger W, Jodicke A, Boker DK: Postoperative headache after the lateral suboccipital approach: Craniotomy versus craniectomy. Minim Invasive Neurosurg 42:175–178, 1999. 321. Wiegand DA, Fickel V: Acoustic neuroma—the patient’s perspective: Subjective assessment of symptoms, diagnosis, therapy, and outcome in 541 patients. Laryngoscope 99:179–187, 1989. 322. Levo H, Pyykko I, Blomstedt G: Postoperative headache after surgery for vestibular schwannoma. Ann Otol Rhinol Laryngol 109:853–858, 2000. 323. Rigby PL, Shah SB, Jackler RK, et al: Acoustic neuroma surgery: Outcome analysis of patient-perceived disability. Am J Otol 18:427–435, 1997. 324. Chung JH, Rigby PL, Jackler RK, et al: Socioeconomic impact of acoustic neuroma surgery. Am J Otol 18:436–443, 1997. 325. Wallner KE, Sheline GE, Pitts LH, et al: Efficacy of irradiation for incompletely excised acoustic neurilemomas. J Neurosurg 67:858–863, 1987. 326. Darrouzet V, Maire JP, Guerin J, Bebear JP: Fractionated radiation therapy in the treatment of stage III and IV cerebellopontine angle tumors: Preliminary results in 20 cases. In Tos M, Thomsen J (eds.): Proceeding of the First International Conference on Acoustic Neuroma. Amsterdam, Kugler, 1992, pp 305–307. 327. Spiegelman R, Lidar Z, Gofman J, et al: Linear accelerator radiosurgery for vestibular schwannoma. J Neurosurg 94:7–13, 2001.

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328. Harsh GR, Thornton AF, Chapman PH, et al: Proton beam stereotactic radiosurgery of vestibular schwannomas. Int J Radiat Oncol Biol Phys 54:35–344, 2002. 329. Kuo JS, Yu C, Petrovich Z, Apuzzo ML: The CyberKnife stereotactic radiosurgery system: Description, installation, and an initial evaluation of use and functionality. Neurosurgery 53:1235–1239, 2003. 330. Flickinger JC, Kondziolka D, Niranjan A, Lunsford LD: Results of acoustic neuroma radiosurgery: An analysis of 5 years’ experience using current methods. J Neurosurg 94:1–6, 2001. 331. Anniko M, Arndt J, Moren G: The human acoustic neuroma in organ culture: II. Tissue changes after gamma irradiation. Acta Otolaryngol 91:223–235, 1981. 332. Lunsford LD, Linskey ME, Flickinger JC: Stereotactic radiosurgery for acoustic nerve sheath tumors. In Tos M, Thomsen J (eds.): Proceeding of the First International Conference on Acoustic Neuroma. Amsterdam, Kugler, 1992, pp 279–287. 333. Schulder M, Sreepada GS, Kwartler JA, Cho ES: Microsurgical removal of a vestibular schwannoma after stereotactic radiosurgery: Surgical and pathologic findings. Am J Otol 20:364–367, 1999. 334. Shirato H, Sakamoto T, Takeichi N, et al: Fractionated stereotactic radiotherapy for vestibular schwannoma (VS): Comparison between cystic-type and solid-type VS. Int J Radiat Oncol Biol Phys 48:1395–1401, 2000. 335. Bush DA, McAllister CJ, Loredo LN, et al: Fractionated proton beam radiotherapy for acoustic neuroma. Neurosurgery 50(2):270–273, 2002. 336. Williams JA: Fractionated stereotactic radiotherapy for acoustic neuromas. Int J Radiat Oncol Biol Phys 54:500–504, 2002. 337. Niranjan A, Lunsford LD, Flickinger JC, et al: Dose reduction improves hearing preservation rates after intracanalicular acoustic tumor radiosurgery. Neurosurgery 45:753–762, 1999. 338. Andrews DW, Suarez O, Goldman HW, et al: Stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of acoustic schwannomas: Comparative observations of 125 patients treated at one institution. Int J Radiat Oncol Biol Phys 50:1265–1278, 2001. 339. Kida Y, Kobayashi T, Tanaka T, Mori Y: Radiosurgery for bilateral neurinomas associated with neurofibromatosis type 2. Surg Neurol 53:383–389, 2000. 340. Ito K, Shin M, Matsuzaki M, et al: Risk factors for neurological complications after acoustic neurinoma radiosurgery: Refinement from further experiences. Int J Radiat Oncol Biol Phys 48:75–80, 2000. 341. Noren G: Long-term complications following gamma knife radiosurgery of vestibular schwannomas. Stereotact Funct Neurosurg 70(Suppl 1):65–73, 1998. 342. Tago M, Terahara A, Nakagawa K, et al: Immediate neurological deterioration after gamma knife radiosurgery for acoustic neuroma. J Neurosurg 93(Suppl 3):78–81, 2000. 343. Werner-Wasik M, Rudoler S, Preston PE, et al: Immediate side effects of stereotactic radiotherapy and radiosurgery. Int J Radiat Oncol Biol Phys 43:299–304, 1999. 344. Couldwell WT, Mohan AL: Enlargement of a vestibular schwannoma after stereotactic radiotherapy. Acta Neurochir (Wien) 144:1319–1322, 2002. 345. Erfurth EM, Bulow B, Mikoczy Z, et al: Is there an increase in second brain tumors after surgery and irradiation for a pituitary tumor? Clin Endocrinol (Oxf) 55:613–616. 2001. 346. Pollock BE, Lunsford LD, Kondziolka D, et al: Vestibular schwannoma management. Part II. Failed radiosurgery and the role of delayed microsurgery. J Neurosurg 89:949–955, 1998. 347. Battista RA, Wiet RJ: Stereotactic radiosurgery for acoustic neuromas: A survey of the American Neurotology Society. Am J Otol 21:371–381, 2000. 348. Luxford WM, House WF: Acoustic tumor. In Pillsbury HC, Goldsmith MM (eds.): Operative Challenges in OtolaryngologyHead and Neck Surgery. 1990, pp 77–83.

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349. Charabi S, Tos M, Thomsen J, et al: Vestibular schwannoma growth—long-term results. Acta Otolaryngol Suppl 543:7–10, 2000. 350. Mathew GD, Facer GW, Suh KW, et al: Symptoms, findings, and methods of diagnosis in patients with acoustic neuroma. Laryngoscope 88:1893–1903, 1978. 351. Deen HG, Ebersold MJ, Harner SG, et al: Conservative management of acoustic neuroma: An outcome study. Neurosurgery 39:260–264, 1996. 352. Glasscock ME 3rd, Pappas DG Jr, Manolidis S, et al: Management of acoustic neuroma in the elderly population. Am J Otol 18:236–241,1997. 353. House WF, Hitselberger WE: Translabyrinthine Approach. In House WF, Leutje CM (eds.): Acoustic Tumors. Baltimore, University Park Press, 1979, pp 43-87. 354. Sterkers JM, Bowdler DA: Facial nerve and hearing preservation in acoustic neuroma surgery. In Fisch U, Valavanis A, Yasargil M (eds.): Proceedings of the Sixth International Symposium of Neurological Surgery of the Ear and Skull Base, 1988, pp 203–205. 355. Tos M, Tomsen J: Sequelae after translabyrinthine removal of 400 acoustic neuromas. In Fisch U, Valavanis A, Yasargil M (eds.): Proceedings of the Sixth International Symposium of Neurological Surgery of the Ear and Skull Base, 1988, pp 175–184. 356. Nadol JB Jr, Chiong CM, Ojemann RG, et al: Preservation of hearing and facial nerve function in resection of acoustic neuroma. Laryngoscope 102:1153–1158, 1992. 357. Ebersold MJ, Harner SG, Beatty CW, et al: Current results of the retrosigmoid approach to acoustic neurinoma. J Neurosurg 76:901–909, 1992. 358. Arriaga MA, Luxford WM, Berliner KI: Facial nerve function following middle fossa and translabyrinthine acoustic tumor surgery: A comparison. Am J Otol 15:620–624, 1994. 359. Samii M, Matthies C: Management of 1000 vestibular schwannomas (acoustic neuromas): The facial nerve—preservation and restitution of function. Neurosurgery 40:684–694, 1997. 360. Glasscock ME 3rd, Hays JW, Minor LB, et al: Preservation of hearing in surgery for acoustic neuromas. J Neurosurg 78:864–870, 1993. 361. Brookes GB, Woo J: Hearing preservation in acoustic neuroma surgery. Clin Otolaryngol 19:204–214, 1994. 362. Slattery WH 3rd, Brackmann DE, Hitselberger W: Middle fossa approach for hearing preservation with acoustic neuromas [published erratum appears in Am J Otol 18:796, 1997]. Am J Otol 18:596–601, 1997. 363. Dornhoffer JL, Helms J, Hoehmann DH: Hearing preservation in acoustic tumor surgery: Results and prognostic factors. Laryngoscope 105:184–187, 1995. 364. Prasad D, Steiner M, Steiner L: Gamma surgery for vestibular schwannoma. J Neurosurg 92:745–759, 2000. 365. Unger F, Walch C, Haselsberger K, et al: Radiosurgery of vestibular schwannomas: A minimally invasive alternative to microsurgery. Acta Neurochir (Wien) 141(12):1281–1285, 1999. 366. Petit JH, Hudes RS, Chen TT, et al: Reduced-dose radiosurgery for vestibular schwannomas. Neurosurgery 49:1299–1306, 2001. 367. Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC: Long-term outcomes after radiosurgery for acoustic neuromas. N Engl J Med 339(20):1426–1433, 1998. 368. Fuss M, Debus J, Lohr F, et al: Conventionally fractionated stereotactic radiotherapy (FSRT) for acoustic neuromas. Int J Radiat Oncol Biol Phys 48:1381–1387, 2000. 369. Thomsen J, Mirz F, Wetke R, et al: Intracranial sarcoma in a patient with neurofibromatosis type 2 treated with gamma knife radiosurgery for vestibular schwannoma. Am J Otol 21:364–370, 2000.

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370. Shamisa A, Bance M, Nag S, et al: Glioblastoma multiforme occurring in a patient treated with gamma knife surgery. Case report and review of the literature. J Neurosurg 94:816–821, 2001. 371. Hanabusa K, Morikawa A, Murata T, Taki W: Acoustic neuroma with malignant transformation. J Neurosurg 95:518–521, 2001. 372. Shin M, Ueki K, Kurita H, Kirino T: Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. Lancet 27;360(9329):309–310, 2002.

373. Comey CH, McLaughlin MR, Jho HD, et al: Death from a malignant cerebellopontine angle triton tumor despite stereotactic radiosurgery. Case report. J Neurosurg 89:653–658, 1998. 374. Arriaga MA, Chen DA: Facial function in hearing preservation acoustic neuroma surgery. Arch Otolaryngol Head Neck Surg 127:543–546, 2001.

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Outline Introduction Neurofibromatosis 2 Differentiated from Neurofibromatosis 1 Clinical Characteristics of Neurofibromatosis 2 Definition of Neurofibromatosis 2 Prevalence and Incidence Molecular Genetics Family History Tumor Types Auditory Changes in Patients with Vestibular Schwannomas Other Tumor Types in Neurofibromatosis 2 Treatment Options for Vestibular Schwannomas in Neurofibromatosis 2

Hearing Preservation Observation without Surgical Intervention Middle Fossa Craniotomy and Internal Auditory Canal Decompression without Tumor Removal Retrosigmoid Craniotomy with Partial Removal Nonhearing Preservation, Translabyrinthine/ Suboccipital Approach, Total Tumor Removal Auditory Brainstem Implant Stereotactic Irradiation Management of Neurofibromatosis 2 Genetic Testing Summary

INTRODUCTION Neurofibromatosis 2 (NF2) presents unique challenges to the neurotologist. The disease is quite invasive, requiring a multispecialist team approach. At the same time, the primary impairment is hearing loss due to bilateral vestibular schwannomas. Usually, the presenting complaint will be hearing loss or balance problems, and the neurotologist will be the first specialist to diagnose the disorder. Here we review the differential diagnosis of NF2 from neurofibromatosis 1 (NF1), characteristics of the disease, current treatment, and management options.

NEUROFIBROMATOSIS 2 DIFFERENTIATED FROM NEUROFIBROMATOSIS 1 NF1 has a distinctly different clinical presentation from that of NF2. Positive differentiation of NF2 from NF1 has occurred with genetic analysis. NF1 has been localized to chromosome 17, NF2 to chromosome 22. NF1 is defined as having two or more of the following: • Six or more café au lait macules • Two or more neurofibromas

Chapter

Neurofibromatosis 2

William H. Slattery III, MD Laurel M. Fisher, PhD

• • • •

Freckling Optic glioma Lisch nodules (iris hamartomas) Osseous lesion (sphenoid dysplasia, thinning of the long bone cortex) • A first-degree relative with NF1 Some patients manifest learning disabilities or language disorders as well. A careful examination and a detailed history of the patient’s symptoms will help to distinguish the two diseases.

Clinical Characteristics of Neurofibromatosis 2 Definition of Neurofibromatosis 2 In 1987, the National Institutes of Health Consensus Development Conference on NF developed the guidelines for diagnosis of NF2 as distinct from NF1. NF2 is distinguished by bilateral acoustic neuromas (or vestibular schwannomas [VS]) with multiple meningiomas, cranial tumors, optic gliomas, and spinal tumors.1 A definitive diagnosis is made on the basis of the presence of bilateral vestibular schwannomas, or developing a unilateral vestibular 783

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schwannoma by the age of 30 and a first-degree blood relative with NF2, or developing at least two of the following conditions known to be associated with NF2: meningioma, glioma, schwannoma, or juvenile poster subcapsular lenticular opacity/juvenile cortical cataract1 (Table 46-1). As the definition implies, the presentation of the disease and the genetic mutation linked to the manifestations of the disease exhibit considerable heterogeneity. Yet, within a family, the expression of NF2 tends to be very much the same.2 These two facts, taken together, indicate a large genetic component to the disease, yet with much variability within those parameters in the observed phenotype. Studies have indicated that a truncating mutation (nonsense and frameshift) may be linked with the more severe form of NF2.3–5 The more severe form, termed the Wishart form, is particularly virulent, with unrelenting growth of schwannomas and meningiomas from childhood, resulting in blindness, deafness, paralysis, and death by the age of 40. Despite the strong genotype-phenotype correlation, individual differences in tumor growth occur within subjects, making it difficult to predict how an individual tumor will change over time even when the genotype is known. The mild, or Gardner form, of NF2 is less debilitating. The schwannomas may remain the same size for years, few meningiomas will develop, the patient may not develop symptoms until late in life, and will have fewer disabilities.2–4,6–12 However, the genetic basis of the mild form has not been well described. Prevalence and Incidence Patients tend to be diagnosed with NF2 around age 25 after experiencing symptoms of the disease for an average of 7 years (Fig. 46-1). There are no differences in the proportion of men versus women who develop NF2 and no

TABLE 46-1. Neurofibromatosis 2 Diagnostic Criteria Individuals with the following clinical features have confirmed (definite) NF2: Bilateral vestibular schwannomas (VS) or family history of NF2 (firstdegree family relative) plus 1. Unilateral VS < 30 years or 2. Any two of the following: meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacities/juvenile cortical cataract. Individuals with the following clinical features should be evaluated for NF2 (presumptive or probable NF2): Unilateral VS < 30 years plus at least one of the following: meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacities/ juvenile cortical cataract. Multiple meningiomas (two or more) plus unilateral VS < 30 years or one of the following: glioma, schwannoma, juvenile posterior subcapsular lenticular opacities/juvenile cortical cataract. NF2, neurofibromatosis 2.

prevalence differences by ethnicity. Epidemiologic studies place the incidence of NF2 between 1 in 40,000 live births13 and 1 in 87,410 live births.14 Molecular Genetics In 1987, the NF2 gene was mapped to chromosome 2215 and was localized to 22q12.2 in 1993.16,17 Various types of mutations have been identified, among them single-base substitutions, insertions, and deletions.4,18–20 The mild, or Gardner, type NF2 may be associated with missense mutations, whereas associations between the other mutations and phenotypes are not as clear.21 The occurrence of NF2 is not restricted to families known to carry the mutation. Frequently, genetic mosaicism occurs,22 which may not be picked up by common mutation analytic techniques. It appears that unilateral vestibular schwannoma may exhibit the same type of genetic markers as NF2.23 However, the mutation is confined to the affected tissue.

Figure 46-1. Time from first symptom to first surgery.

Kaplan-Meier Cumulative Proportion

1.0

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30

Neurofibromatosis 2

In persons with NF2, the mutation is present in other types of cells as well.22 Family History Individuals at risk for developing NF2 must be screened to provide an early diagnosis. Individuals at risk include children of NF2-affected patients and their siblings. Because NF2 has a 50% penetrance, all children of NF2 patients have a 50% risk of developing the disease. Siblings of a diagnosed NF2 patient are at risk, especially if the parent has also been identified with NF2. The clinical presentation of NF2 is usually similar within families. The likelihood of NF2 occurring in related individuals who do not exhibit similar clinical symptoms to an affected family member is small. Consideration may still be given for screening. The type of screening and the timing of screening depends on each NF2 center’s preferences. However, we advocate early screening, so that tumors may be diagnosed presymptomatically. We screen potentially affected individuals with a postcontrast T1-weighted MRI of the full head, with fine cuts (at most 3 mm slices, no skip) through the internal auditory canals (IACs). This test will identify most affected NF2 patients by showing any vestibular schwannomas. Screening of the spine or ophthalmology exams should be

A

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considered if the cranial MRI scan is positive. An audiogram (pure-tone thresholds) and the current clinical standard auditory brainstem response (ABR) testing are likely to miss small vestibular schwannomas that a MRI scan can diagnose presymptomatically. MRI scanning is recommended for an at-risk minor when this test can be performed without sedation. This usually occurs when the child is 7 through 9 years of age. A recommended first step for children younger than age 7 is an audiogram. Any child with an NF2-associated symptom (e.g., hearing loss or facial weakness) should be screened without regard to the need of sedation or age and should be performed as soon as possible after the symptoms are apparent.

TUMOR TYPES Bilateral vestibular schwannomas (also acoustic neuroma) are benign neoplasms of the acoustic or eighth cranial nerve24 (Fig. 46-2). The tumors typically are located on the superior vestibular nerve at the glial-Schwann cell junction within the internal acoustic meatus. The consequences of a vestibular schwannoma are numerous, including dizziness, imbalance, tinnitus, hearing loss progressing to deafness, facial nerve paralysis, brainstem compression, and, if left untreated, death.

B

Figure 46-2. Bilateral vestibular schwannomas are characteristic of NF2. A, Small bilateral vestibular schwannomas. B, Medium-size vestibular schwannoma that are compressing the brainstem. C, Giant bilateral vestibular schwannomas that are compressing the brainstem and causing hydrocephalus.

C

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Despite the strong genotypic effect in NF2, there is enormous variability in the number of tumor types (Table 46-2), the rate of progression, and the disabilities experienced. This enormous variability is also found in patient presentation; surprisingly, some patients may be asymptomatic. Patients who have no symptoms when diagnosed have generally been identified on the basis of genetic analysis, conducted because a blood relative has NF2. Although the National Institutes of Health (NIH) criteria for NF2 require the presence of bilateral vestibular schwannoma for diagnosis, patients may first develop a unilateral vestibular schwannoma as a young child with no other tumors, or adult patients may present with multiple meningiomas (cranial and spinal) and no vestibular schwannoma.9,25 Although the NIH criteria for NF2 imply that all NF2 patients will develop bilateral vestibular schwannoma, some researchers are not convinced of this.26 Evans26 based his conclusion on the observation of a possible variant form of NF2 presenting with skin and spinal tumors in the absence of vestibular schwannomas. Nevertheless, in general, the phenotype is reflective of the underlying genotype. Preliminary data from the Natural History of Vestibular Schwannomas in NF2 study conducted at House Ear Institute shows that 10 of 80 (12.5%) enrolled subjects had no symptoms at diagnosis, and 23 (28.8%) had cranial meningiomas and spinal meningiomas in addition to bilateral vestibular schwannoma. Nearly half (47.5%) had one vestibular schwannoma removed prior to enrollment. Generally, the tumor resected prior to enrollment was removed 1.5 years after discovery and was an average of 2.1 cm at removal. Few Natural History patients had spinal tumors or meningiomas removed prior to enrollment. The preliminary data would indicate that, for this sample of NF2 subjects, the most salient medical issue is the growth of their vestibular schwannoma. NF2 subjects tend also to develop cortical and posterior subcapsular cataracts, which can lead to blindness27 (Table 46-3). Retinal hamartomas have been observed in a few cases,2,28–30 but are not as frequent. Some subjects (2% to 3% of subjects)31,32 present with numbness or tingling in their arms or legs. Upwards of 30% of NF2 subjects may have surgery to remove spinal tumors, but the progression of spinal tumors associated with NF2 is not well described. At this time, the presence of vestibular schwannoma in NF2 and the consequences of not treating them are relatively well known, and these tumors may be the most debilitating. Rarely does a vestibular schwannoma turn malignant, and sometimes the unilateral vestibular schwannoma may regress in size altogether. Growth of the tumors does not seem to be related either to loss of heterozygosity (genetic

TABLE 46-3. First Symptoms of Neurofibromatosis 2 Symptoms

Percentage of Patients

Neurologic Skin tumor Vision loss Asymptomatic Tinnitus Weakness Vertigo Other/Unspecified

17.5 11.7 10.7 10.7 7.8 2.9 1.0 4.9

level of analysis) or to auditory functioning (phenotype level of analysis). For this reason physicians recommend at least yearly MRI scans to track changes in size.33–40 Others have suggested that, after a baseline scan, the next scan be at 6 months in order to determine if the tumor is fast- or slow-growing.41

Auditory Changes in Patients with Vestibular Schwannomas Hearing loss is well documented as the most common presenting symptom in patients who have vestibular schwannoma.42–51 Auditory changes over time in vestibular schwannoma patients are less well known. Rosenberg52 studied the natural history of 80 patients with non-NF2 unilateral vestibular schwannoma for an average of 4.4 years. Rosenberg found a positive correlation between tumor growth and worsening pure tone average. However, there was no statistically significant correlation between positive tumor growth and speech discrimination, change in brainstem auditory evoked response, and bithermal caloric electronystagmography test responses over time. Lalwani and colleagues53 reported that pure tone patterns, speech reception threshold, and word recognition scores were significantly worse in NF2 patients who had a mild form of NF2 and large tumors compared with patients with mild NF2 with small tumors. Loss of acoustic reflexes and prolonged wave III and V were also associated with larger tumors. In contrast, patients with severe NF2 showed no relationship among tumor size and pure tone levels, speech reception threshold, or word recognition scores. The lack of association may have been due to the complete loss of hearing in the severe NF2 patients at the time of the assessment. The larger tumors were associated with prolonged ABR wave III and V latencies. No data across time were reported. In general, hearing is progressively impaired with increasing growth of vestibular schwannomas, necessitating the need for surgical intervention or medical treatment in NF2 patients.

Other Tumor Types in Neurofibromatosis 2 TABLE 46-2. Tumor Type Tumor Type Bilateral vestibular schwannoma Skin Meningioma Spinal

Percentage of Patients 99 50 46 60

NF2 has been associated with multiple central nervous system tumors, the most common of which are intracranial meningiomas (Fig. 46-3), spinal tumors, and optic gliomas (in addition to cataracts).54 Nearly all NF2 patients will develop these tumors in time: 50% of NF2 patients present with schwannomas and meningiomas, 90% present with spinal tumors in addition to schwannomas.25

Neurofibromatosis 2

Figure 46-3. Multiple meningiomas can be seen in severe forms of NF2. Meningiomas may occur throughout the cranium and skull base area.

The presence of more than one type of tumor within an individual usually indicates a more aggressive disease course. The co-occurrence of vestibular schwannomas and meningiomas have been linked to a synergistic effect on growth rate, increasing the growth rate of both the schwannoma and meningioma beyond that expected of a sporadic schwannoma or meningioma.55,56 Despite the high numbers of patients with multiple tumors, initially, most meningiomas and spinal tumors are asymptomatic and are first seen on an MRI. In addition, multiple skin tumors are found in persons with NF2. A variety of spinal tumors (Fig. 46-4) occur in NF2 patients and can be found in the cervical, thoracic, and lumbar regions. These tumors are further categorized as either extramedullary or intramedullary tumors, depending

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on their positioning relative to the spinal cord. Extramedullary tumors are commonly schwannomas or meningiomas, whereas intramedullary tumors are often ependymomas, but can also be astrocytomas or schwannomas.57 Although studies have been conducted to determine the number of spinal tumors, they are often too numerous to count, therefore making most observed numbers an underestimation of the exact tumor burden.2,25 Spinal tumors may cause cord compression and bone erosion and can have solid and cystic components.58 As each NF2-related tumor grows and exerts pressure on surrounding structures, treatment encompasses surgical resection or radiotherapy (or both). Another treatment choice, early on in the disease course, is surgical decompression, in which space is created for the growing tumor, relieving the pressure inside the skull or at the spinal cord. Growing meningiomas result in increased intracranial pressure, intractable headache, hydrocephalus, and seizure disorders.59–61 Continued growth of spinal tumors causes loss of motion, numbness, tingling, and, eventually, paralysis. Treatment of optic gliomas frequently results in removal of the eye (thus, blindness).27

Treatment Options for Vestibular Schwannomas in Neurofibromatosis 2 The treatment options for a patient with bilateral vestibular schwannomas vary considerably as a result of the wide variety of tumor sizes and clinical presentations. Associated symptoms (brainstem compression or hydrocephalus), loss of useful hearing, and the status of other intracranial tumors all must be considered when discussing treatment intervention. Hearing Preservation Individuals that present with bilateral small tumors (less than 2 cm in greatest diameter) and good hearing may be candidates for hearing preservation procedures. In these patients, total tumor removal is attempted on the side of the larger tumor or on the side with worse hearing. If hearing is successfully preserved on the first side, then contralateral tumor removal may be attempted 6 months later. Hearing preservation rates for small unilateral tumors have approached 70%.51 However, the results in NF2 patients appear to be worse than those reported in patients with unilateral vestibular schwannomas.62 Doyle and Shelton63 found that 67% of NF2 patients underwent hearing presentation surgery using the middle fossa approach, and 38% of those had serviceable hearing postoperatively. Observation without Surgical Intervention

Figure 46-4. Spinal tumors may be seen in up to 20% to 50% of NF2 patients. Many of these are symptomatic; however, some can become quite large, causing compression of the spinal cord and nerve roots. Excision is necessary when neural function is compromised.

Observation without surgical intervention is the most common treatment option used in patients with NF2 and is used when a small tumor is present in a patient with only one hearing ear or when bilateral tumors are too large for hearing preservation procedures. The individual is assessed routinely to ensure that brainstem compression or hydrocephalus does not result. Initially, an MRI is performed 6 months following diagnosis, and then annual MRI scans are performed to document tumor size and determine if

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intervention is required. Surgical intervention is considered if life-threatening complications occur, the tumors become excessively large (increasing the perioperative morbidity), or the hearing becomes unserviceable. Middle Fossa Craniotomy and Internal Auditory Canal Decompression without Tumor Removal This alternative allows the tumor to grow without causing compression of the seventh and eighth cranial nerves. This procedure is recommended when progression of hearing loss occurs in a patient who is being observed. The bone surrounding the IAC is removed extensively, allowing the entire tumor and seventh and eighth nerve complex to be decompressed. The tumor itself is not removed because this may increase the risk of hearing loss. Stabilization and even improvement of hearing may occur following this procedure.

A

Retrosigmoid Craniotomy with Partial Removal This procedure in NF2 patients carries a significant risk because the cochlear fibers are dispersed throughout the tumor, in contrast to unilateral vestibular schwannomas (Fig. 46-5). The risk of hearing loss with partial removal is much higher, and this procedure is typically not recommended. Nonhearing Preservation, Translabyrinthine/ Suboccipital Approach, Total Tumor Removal This is the most common surgical procedure performed in patients with NF2. Most patients present when the tumor is either too large for hearing preservation or the hearing loss is already at a significant level and hearing preservation is not considered. This approach is used for individuals with large tumors who have brainstem compression even if serviceable hearing exists. The translabyrinthine or suboccipital craniotomy approaches may be used for this procedure. However, the risk of a recurrent tumor is slightly higher with the suboccipital approach and with inexperienced surgeons because residual tumor is often left in the lateral aspect of the IAC. Auditory Brainstem Implant The auditory brainstem implant was developed at the House Ear Institute to allow electrical stimulation of the cochlear nucleus following bilateral vestibular schwannoma removal. The device is placed on the brainstem (Fig. 46-6) during translabyrinthine vestibular schwannoma removal. This device is indicated in individuals who have no serviceable hearing and are undergoing vestibular schwannoma removal. The majority of patients obtain enhanced communication skills with the device. Stereotactic Irradiation Stereotactic irradiation has been recommended for some NF2 patients, but its use must be carefully considered since radiation exposure may induce or accelerate tumors in a patient with an inactivated tumor suppressor gene. It was recently reported that two of four patients who had

B Figure 46-5. Histology of a vestibular schwannoma. A, Unilateral non-NF2 vestibular schwannoma. Typical schwannoma stain with Bodian silver stain. It stains only the nerve fiber, so the schwannoma cells are not evident. However, the fibers on the surface of the tumor are visible. Nerve fibers of non-NF2 vestibular schwannomas are displaced by the schwannomas cells. B, This slide shows another Bodian silver stain with black strands embedded within the tumor, representing the nerve fibers invaded by the tumor. This invasion is different than seen with non-NF2 solitary vestibular schwannomas. Non-NF2 solitary tumors invade the aggregates of cells and push the fibers aside rather than invading between the fibers. Thus, NF2 vestibular schwannomas are histologically different from non-NF2 sporadic, unilateral tumors.

previously received radiation therapy developed a malignancy in the irradiated ear.64 Many algorithms have been proposed as treatment plans, but none are widely accepted among NF2 specialists. The range of treatment options is large, larger than for any other nervous system tumor. The potential benefits of treatment are great (hearing preservation), but the potential risks are also significant, and the riskiest procedures have the greatest potential benefit. Often patients have a window of opportunity when they can choose a risky but potentially beneficial procedure; once the window closes, they cannot go back. Therefore, patients, families, and care providers need to know the natural history of these tumors to better make rational recommendations and decisions regarding these treatment options. In addition, noninvasive and tumor-related markers of behavior need to be identified that can further tailor our anticipatory guidance for any one patient.

Neurofibromatosis 2

Figure 46-6. CT scan demonstrating placement of auditory brainstem implant within the lateral recess of the fourth ventricle.

Management of Neurofibromatosis 2 Initial evaluation of an NF2 patient can be very complex because this is a multisystem disease. However, an inadequate diagnosis may render a patient impaired because early diagnosis and treatment may have prevented further impairments. NF2 patients may typically see many different physicians, each with experience in a different field of expertise. NF2 patients require one physician to lead the treatment team, a case manager as it were, to ensure comprehensive care. Neurologist, geneticist, neurosurgeon, or neurotologist may all function as the lead physician, depending on the NF2 center. A comprehensive battery of tests is necessary for tumor detection and adequate staging. The initial MRI scan demonstrating the presence of bilateral vestibular schwannomas may be inadequate for tumor follow-up. As an example, a cranial scan may not have included the IACs, or a spine series may have focused on only one segment of the spine. An MRI with gadolinium and thin cuts through the IAC is necessary for the head. Particular attention is focused in the IACs, caverness sinus, and jugular foramen areas. Any cranial nerve may have tumor formation and thus should have complete imaging. Auditory assessment is necessary to determine the extent of hearing impairment. At a minimum, this consists of a standard audiogram, with air and bone pure tone thresholds, and speech testing. Some centers prefer additional testing with ABR to assess cochlear nerve function. This is particularly helpful when considering a hearing preservation procedure. Electronystagometry testing has benefit in determining tumor location; however, its utility for clinical assessment is still under investigation. A complete neurologic exam is required for individuals with suspected NF2. The standard neurologic assessment of dermatomes and muscle strength is required for assessment of potential spinal cord impairment. Cranial nerve testing may find subtle abnormalities for which the patient has slowly compensated. In addition, the patient may not even be aware of his or her own impairment. This is particularly true of the lower cranial nerves. A complete MRI spinal cord survey is required to identify tumors within the spine. The use of spine screening is

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still under investigation for all NF2 patients. Patients with a significant tumor burden, a family history of spine tumors, or spinal tumor symptoms should definitely have a spine series. A spine series is required in all symptomatic patients. A neuro-ophthalmology exam is required for all patients with NF2. The potential for deafness in these individuals requires that everything be done to preserve vision. A slit lamp exam is required. It is preferable that a patient be evaluated by an ophthalmologist familiar with NF2. The initial comprehensive evaluation consists, at a minimum, of MRI of the IAC with gadolinium, auditory assessment, and physical examination. A comprehensive examination will include the previously mentioned MRI with the addition of a full spine series, an ABR test, and an ophthalmology examination. The timing of follow-up studies is currently inconsistent among NF2 specialty centers. We recommend repeat testing at 6 months and then yearly testing consisting of an MRI of the head and spine, neurology examination, and audiometric testing. Once the growth rate from the tumors has been determined, some of these tests may be spread out over time. Spinal tumors tend to be very slowgrowing and, once diagnosed, may be imaged every 1 to 5 years. The potential for new tumor formation exists especially in patients with severe disease, and it is important that this information be conveyed to the NF2 patient so that comprehensive follow-up may occur.

Genetic Testing Identification of the NF2 gene on chromosome 22 has made genetic testing possible. It is recommended that patients with NF2 see a genetic counselor to discuss the hereditary consequences of this disease. Genetic blood screening is able to identify the defect on the NF2 gene in approximately 70% to 75% of patients with a known diagnosis of NF2. If the defect is identified, then potential family members may be screened. If the gene is not identified, then blood screening of family members can be performed. The use of blood screening for patients without a diagnosis or with a suspected diagnosis of NF2 is not recommended. New mutations in patients with mild presentation are most likely missense mutations, which are difficult to identify by genetic testing.

SUMMARY Care of the NF2 patient requires knowledge of all tumors and symptoms involved with the disorder. The role of the neurotologist in this care is determined by the specialty center. It is recommended that patients receive care in a center with expertise in NF2.

REFERENCES 1. Gutmann DH, Aylsworth A, Carey JC, et al: The diagnostic evaluation and multidisciplinary management of NF1 and NF2. JAMA 278:51–57, 1997. 2. Parry DM, Eldridge R, Kaiser-Kupfer MI, et al: Neurofibromatosis 2 (NF2): Clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity. Am J Med Genet 52:450–461, 1994.

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3. Evans DG, Trueman L, Wallace A, et al: Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): Evidence for more severe disease associated with truncating mutations [published erratum appears in J Med Genet 36(1):87, 1999] J Med Genet 35:450–455, 1998. 4. Kluwe L, Mautner VF: A missense mutation in the NF2 gene results in moderate and mild clinical phenotypes of neurofibromatosis type 2. Hum Genet 97:224–227, 1996. 5. Ruttledge MH AA, Phelan CM, et al: Type of mutation in the NF2 gene frequently determines severity of disease. Am J Hum Genet 59:331–342, 1996. 6. Baser ME, Mautner VF, Ragge NK, et al: Presymptomatic diagnosis of neurofibromatosis 2 using linked genetic markers, neuroimaging, and ocular examinations. Neurology 47:1269–1277, 1996. 7. Bijlsma EK, Merel P, Fleury P, et al: Family with neurofibromatosis type 2 and autosomal dominant hearing loss: Identification of carriers of the mutated NF2 gene. Hum Genet 96:1–5, 1995. 8. Gardner WJ, Frazier CH: Bilateral acoustic neurofibromas: A clinical study and field survey of a family of five generations with bilateral deafness in thirty-eight members. Arch Neurol Psychiatr 23:266–302, 1930. 9. Mautner VF, Baser ME, Kluwe L: Phenotypic variability in two families with novel splice-site and frameshift NF2 mutations. Hum Genet 98:203–206, 1996. 10. Sainio M, Strachan T, Blomstedt G, et al: Presymptomatic DNA and MRI diagnosis of neurofibromatosis 2 with mild clinical course in an extended pedigree. Neurology 45:1314–1322, 1995. 11. Welling DB: Clinical manifestations of mutations in the neurofibromatosis type 2 gene in vestibular schwannomas (acoustic neuromas). Laryngoscope 108:178–189, 1998. 12. Wishart JH: Case of tumors of the skull, dura mater and brain. Edinburgh Med Surg J 18:393–397, 1822. 13. Evans DG, Huson SM, Donnai D, et al: A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet 29:841–846, 1992. 14. Antinheimo J, Sankila R, Carpen O, et al: Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas [see comments]. Neurology 54:71–76, 2000. 15. Rouleau GA, Wertelecki W, Haines JL, et al: Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature 329:246–248, 1987. 16. Rouleau GA, Merel P, Lutchman M, et al: Alteration in a new gene encoding a putative membrane-organizing protein causes neurofibromatosis type 2. Nature 363:515–521, 1993. 17. Trofatter JA, MacCollin MM, Rutter JL, et al: A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72:791–800, 1993. 18. Merel P, Haong-Xuan K, Sanson M, et al: Predominant occurrence of somatic mutations of the NF2 gene in meningiomas and schwannomas. Genes Chromosomes Cancer 13:211–216, 1995. 19. Merel P, Hoang-Xuan K, Sanson M, et al: Screening for germ-line mutations in the NF2 gene. Genes Chromosomes Cancer 12:117–127, 1995. 20. Welling DB, Guida M, Goll F, et al: Mutational spectrum in the neurofibromatosis type 2 gene in sporadic and familial schwannomas. Hum Genet 98:189–193, 1996. 21. Welling DB: Clinical manifestations of mutations in the neurofibromatosis type 2 gene in vestibular schwannomas (acoustic neuromas). Laryngoscope 108:178–189, 1998. 22. Wu CL, Thakker N, Neary W, et al: Differential diagnosis of type 2 neurofibromatosis: Molecular discrimination of NF2 and sporadic vestibular schwannomas. J Med Genet 35:973–977, 1998. 23. Irving RM, Harada T, Moffat DA, et al: Somatic neurofibromatosis type 2 gene mutations and growth characteristics in vestibular schwannoma. Am J Otol 18:754–760, 1997. 24. Cushing H: Bilateral Acoustic Tumors, Generalized Neurofibromatosis and the Meningeal Endotheliomata. Tumors of the Nervous

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Acoustics and the Syndrome of the Cerebellopontine Angle. Philadelphia, WB Saunders, 1963 (1917 original edition). Mautner VF, Lindenau M, Koppen J, et al: [Type 2 neurofibromatosis without acoustic neuroma]. Zentralbl Neurochir 56:83–87, 1995. Evans DG, Lye R, Neary W, et al: Probability of bilateral disease in people presenting with a unilateral vestibular schwannoma. J Neurol Neurosurg Psychiatry 66:764–767, 1999. Bouzas EA, Freidlin V, Parry DM, et al: Lens opacities in neurofibromatosis 2: Further significant correlations. Br J Ophthalmol 77:354–357, 1993. Good WV, Erodsky MC, Edwards MS, Hoyt WF: Bilateral retinal hamartomas in neurofibromatosis type 2. Br J Ophthalmol 75:190, 1991. Landau K, Yasargil GM: Ocular fundus in neurofibromatosis type 2. Br J Ophthalmol 77:646–649, 1993. Ragge NK, Baser ME, Klein J, et al: Ocular abnormalities in neurofibromatosis 2. Am J Ophthalmol 120:634–641, 1995. Evans DG, Huson SM, Donnai D, et al: A clinical study of type 2 neurofibromatosis. Q J Med 84:603–618, 1992. Lim DJ, Rubenstein AE, Evans DG, et al: Advances in neurofibromatosis 2 (NF2): A workshop report. J Neurogenet 14:63–106, 2000. Matthies C, Samii M, Krebs S: Management of vestibular schwannomas (acoustic neuromas): Radiological features in 202 cases— Their value for diagnosis and their predictive importance. Neurosurgery 40:469–481; discussion 481–482, 1997. Burkey JM, Rizer FM, Schuring AG, et al: Acoustic reflexes, auditory brainstem response, and MRI in the evaluation of acoustic neuromas. Laryngoscope 106:839–841, 1996. Curati WL, Graif M, Kingsley DP, et al: MRI in acoustic neuroma: A review of 35 patients. Neuroradiology 28:208–214, 1986. Duffner PK, Cohen ME, Seidel FG, Shucard DW: The significance of MRI abnormalities in children with neurofibromatosis. Neurology 39:373–378, 1989. Levine SC, Antonelli PJ, Le CT, Haines SJ: Relative value of diagnostic tests for small acoustic neuromas. Am J Otol 12:341–346, 1991. Lhuillier FM, Doyon DL, Halimi PM, et al: Magnetic resonance imaging of acoustic neuromas: Pitfalls and differential diagnosis. Neuroradiology 34:144–149, 1992. Long SA, Arriaga M, Nelson RA: Acoustic neuroma volume: MRIbased calculations and clinical implications. Laryngoscope 103:1093–1096, 1993. Modugno GC, Pirodda A, Ferri GG, et al: Small acoustic neuromas: monitoring the growth rate by MRI. Acta Neurochir 141: 1063–1067, 1999. Irving RM, Moffat DA, Hardy DG, et al: A molecular, clinical, and immunohistochemical study of vestibular schwannoma. Otolaryngol Head Neck Surg 116:426–430, 1997. Strasnick B, Glasscock ME 3rd, Haynes D, et al: The natural history of untreated acoustic neuromas. Laryngoscope 104:1115–1119, 1994. Fucci MJ, Buchman CA, Brackmann DE, Berliner KI: Acoustic tumor growth: Implications for treatment choices. Am J Otol 20:495–499, 1999. Brackmann DE, Owens RM, Friedman RA, et al: Prognostic factors for hearing preservation in vestibular schwannoma surgery. Am J Otol 21:417–424, 2000. Briggs RJ, Brackmann DE, Baser ME, Hitselberger WE: Comprehensive management of bilateral acoustic neuromas. Current perspectives. Arch Otolaryngol Head Neck Surg 120:1307–1314, 1994. Doyle KJ, Nelson RA: Bilateral acoustic neuromas (NF2). In House WF, Luetje CM, Doyle KJ (eds.): Acoustic Tumors: Diagnosis and Management. San Diego, Singular Publishing Group, 1997, Chapter 20. Evans DG, Huson SM, Donnai D, et al: A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet 29:841–846, 1992.

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48. Gadre AK, Kwartler JA, Brackmann DE, et al: Middle fossa decompression of the internal auditory canal in acoustic neuroma surgery: A therapeutic alternative. Laryngoscope 100:948–952, 1990. 49. Kesterson L, Shelton C, Dressler L, Berliner KI: Clinical behavior of acoustic tumors. A flow cytometric analysis. Arch Otolaryngol Head Neck Surg 119:269–271, 1993. 50. Saunders JE, Luxford WM, Devgan KK, Fetterman BL: Sudden hearing loss in acoustic neuroma patients. Otolaryngol Head Neck Surg 113:23–31, 1995. 51. Slattery WH 3rd, Brackmann DE, Hitselberger W: Middle fossa approach for hearing preservation with acoustic neuromas. Am J Otol 18(6):796; 596–601, 1997. 52. Rosenberg SI. Natural history of acoustic neuromas. Laryngoscope 110:497–508, 2000. 53. Lalwani AK, Abaza MM, Makariou EV, Armstrong M: Audiologic presentation of vestibular schwannomas in neurofibromatosis type 2. Am J Otol 19:352–357, 1998. 54. Bouzas EA, Parry DM, Eldridge R, Kaiser-Kupfer MI: Visual impairment in patients with neurofibromatosis 2. Neurology 43:622–623, 1993. 55. Pallini R, Tancredi A, Casalbore P, et al: Neurofibromatosis type 2: Growth stimulation of mixed acoustic schwannoma by concurrent adjacent meningioma: Possible role of growth factors. Case report. J Neurosurg 89:149–154, 1998. 56. Antinheimo J, Haapasalo H, Haltia M, et al: Proliferation potential and histological features in neurofibromatosis 2-associated and sporadic meningiomas. J Neurosurg 87:610–614, 1997.

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57. Patronas NJ, Courcoutsakis N, Bromley CM, et al: Intramedullary and spinal canal tumors in patients with neurofibromatosis 2: MR imaging findings and correlation with genotype. Radiology 218:434–442, 2001. 58. Gillespie JE: Imaging in neurofibromatosis type 2: Screening using magnetic resonance imaging. Ear Nose Throat J 78:102–103, 106, 108–109, 1999. 59. Delleman JW, De Jong JG, Bleeker GM: Meningiomas in five members of a family over two generations, in one member simultaneously with acoustic neurinomas. Neurology 28:567–570, 1978. 60. King A, Gutmann DH: The question of familial meningiomas and schwannomas: NF2B or not to be? [editorial; comment]. Neurology 54:4–5, 2000. 61. Wiebe S, Munoz DG, Smith S, Lee DH: Meningioangiomatosis. A comprehensive analysis of clinical and laboratory features. Brain 122:709–726, 1999. 62. Slattery WH, Brackmann DE: Hearing Preservation and restoration in CPA tumor surgery. Neuosurg Q 7:169–182, 1997. 63. Doyle KJ, Shelton C: Hearing preservation in bilateral acoustic neuroma surgery. Am J Otol 14:562–565, 1993. 64. Baser ME, Ragge NK, Riccardi VM, et al: Phenotypic variability in monozygotic twins with neurofibromatosis 2. Am J Med Genet 64:563–567, 1996.

Chapter

47 Ameet Singh, MD Samuel H. Selesnick, MD

Meningiomas of the Posterior Fossa and Skull Base Outline History Epidemiology Etiology Radiation Trauma Gender Viruses Molecular Pathogenesis Pathology Gross Pathology Microscopic Pathology Grade I Meningioma Histopathology Grade II Meningioma Histopathology Grade III Meningioma Histopathology Immunohistochemistry Diagnosis Audiovestibular Testing Radiology Plain Radiography Angiography Computed Tomography and Magnetic Resonance Imaging General Surgical Principles Preoperative Considerations

HISTORY The term meningioma was proposed by Harvey Cushing in 1922 to describe a benign intracranial tumor of the meninges.1 Prior to this historic naming, the nomenclature surrounding this tumor had been shrouded in controversy. The uncertainty involving the meningioma’s cell of origin had produced a plethora of descriptive names— meningoexothelioma, endothelioma, mesothelioma, and arachnoidal fibroblastoma to name just a few.2 To eliminate confusion, avoid a commitment to a histologic origin, and coalesce several pathologic tumor types arising from different locations, Cushing coined the term meningioma. This was followed by a defining manuscript on meningiomas by Cushing and Eisenhardt in 1938, setting the tone for future investigations of this tumor.3 Acknowledgment: The authors wish to thank Marc Edgar, MD, for supplying the histopathologic material and for his comments on that section. 792

Posterior Fossa Meningiomas Cerebellopontine Angle Meningiomas Introduction History Epidemiology Origin Classification Clinical Presentation Diagnosis Surgical Management Complications Internal Auditory Canal Meningiomas Clival and Petroclival Meningiomas Introduction Origin and Classification Extension Clinical Presentation Diagnosis Preoperative Considerations Approach Selection Surgical History Resection Mortality and Quality of Life Meckel’s Cave Meningiomas Epidemiology

Origin and Classification Clinical Presentation Imaging Surgical Approach Surgical Management Jugular Foramen Meningiomas Introduction Classification Clinical Presentation Diagnosis Surgical Approach Surgical Management Foramen Magnum Meningiomas Introduction Epidemiology History and Classification Clinical Presentation Diagnosis Surgical Approach Surgical Results Hearing Preservation Facial Nerve Preservation Recurrence Radiation Therapy

Meningiomas are thought to have been present as far back as the prehistoric era, as demonstrated by hyperostosis found in the skulls of the pre-Colombian Incas from the Peruvian Andes.4 The first description of a meningioma, however, was noted by a Swiss physician, Felix Plater, in 1614. He described a tumor as “a round fleshy tumor, like an acorn … hard and full of holes and … as large as a medium sized apple … covered with its own membrane … free of all connections with the matter of the brain.”5 Although the first illustrations of a meningioma were published in 1730, the earliest work that dealt exclusively with these tumors was written in 1774 by Antoine Louis in Mémoires de l’ Academie Royale de Chirugie. In his manuscript, Louis named them tumeurs fongueuses de la dure-mere, or fungoid tumors of the dura mater.6 Virchow, who noted the presence of granules in meningiomas named them psammomas (sandlike tumors) in 1859, and considered them akin to sarcomas.7 Golgi, on the other hand, named them endotheliomas in 1869, indicating a more benign histology.8 Several names

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were used to describe these tumors even after Cushing’s Cavendish lecture in 1922. The first known radiologic account of a meningioma was written by Mills and Pfahler in 1902.9 This was followed by several similar reports, including one by Heuer and Dandy in 1916. They described the radiographic findings in 100 brain tumors, 9 of which were meningiomas.10 Ventriculography, a technique described by Dandy in 1918, although slowly adopted, marked a significant improvement in intracranial tumor localization and diagnosis. Skull radiographs and cerebral angiography also aided in the diagnosis of brain tumors in the first half of the century. In addition, the development of sensitive film improved radiographic imaging by replacing glass plates and decreasing the time of exposure. The advent of computed tomographic (CT) scanning in the mid-1970s followed by magnetic resonance imaging (MRI) with contrast agents, diffusion weighted imaging, and fluid attenuated inversion recovery sequences have greatly improved the preoperative diagnosis, therapeutic planning, and surgical outcomes of meningiomas. The surgical removal of a meningioma was first attempted in 1743 by Heister, a German surgeon from Helmstead, Germany. He applied a caustic of lime juice to a meningioma in a 34-year-old Prussian soldier who subsequently developed an infection and died. One of the first successful meningioma operations was performed by Zanobi Pecchioli, an Italian surgeon who extracted a right sinciput meningioma in 1835. The patient was well at 30 months following the operation. In 1887, William Keen, a pioneer of American neurosurgery, was the first to successfully remove a meningioma in the United States. Using meticulous aseptic technique in a 2-hour operation, he extracted an 88-g, left frontotemporal tumor from a 26-year-old carriage maker. The patient, who had a history of head trauma at the age of 3 and presented with headaches, seizures, and partial blindness, recovered and lived over 30 years after the operation. The turn of the century marked an improvement in the outcome of neurosurgical procedures primarily due to aseptic principles, localization of cerebral function, and better surgical techniques.4

EPIDEMIOLOGY A review of six large neurosurgical series accounting for 18,171 tumors found meningiomas to constitute approximately 20% of all intracranial neoplasms.11 In 1938, Cushing and Eisenhardt reported that 13.4% of 2203 brain tumors were meningiomas.3 Multiple series since then have estimated meningiomas to comprise 13% to 26% of all primary brain tumors, with a total annual incidence of approximately 6 per 100,000 people.12 These figures include incidence data from hospital-based as well as population-based studies, which include meningiomas found incidentally at autopsy. Since the majority of meningiomas are benign lesions that remain asymptomatic during life, they represent over 30% of incidental tumors found at autopsy. In symptomatic patients, however, the incidence for benign meningiomas is 2.3 per 100,000 and 0.17 per 100,000 for malignant meningiomas.13 In study of the incidence of primary intracranial neoplasms in Rochester, Minnesota, from 1935 through 1977, autopsies

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on subjects 55 years and older found meningiomas in slightly more than 1%.14 Meningiomas are most commonly found in middle-aged and elderly individuals, with a peak incidence in the sixth and seventh decades of life. These tumors rarely occur in children and show a marked female predominance, with a female to male ratio of 3:2 or 2:1 in a majority of studies.12 This gender bias is reflected in the overall incidence for meningiomas, which ranges from 2 to 7 per 100,000 in women and from 1 to 5 per 100,000 in men.15 In males, the overall age-adjusted incidence rate of cases diagnosed before death was 8.3 per 100,000 population per year, which included a rate of 1.2 for meningiomas. Among females, the overall rate was 10.1, which included a rate of 2.6 for meningiomas.14 The female preponderance seen only in middle-aged patients has been attributed to the effects of estrogen on meningioma growth and development.12 The incidence of meningiomas increases with age. In one series of patients treated from 1950 to 1977 in Rochester, Minnesota, where the postmortem examination rate approaches 70%, approximately 69% of meningiomas were diagnosed at autopsy. Long-term reports also suggest that the incidence of meningiomas is increasing over time.15 In addition, both an improved life expectancy and better neuroimaging to detect asymptomatic meningiomas may result in an increasing prevalence of meningiomas in future epidemiologic studies. Although the incidence of meningiomas is similar in most countries, several series from Africa found that meningiomas accounted for anywhere from 24% to 38% of all intracranial lesions.16 These studies also reported a male rather than female predominance and found that 20% of meningiomas occurred in the second decade of life.2 This high incidence of meningiomas in Africa may be relative and can be explained by a lower incidence of gliomas rather than an absolute increase in meningiomas. However, a population-based survey in Los Angeles, California, also reported a higher incidence of meningiomas (3.1 per 100,000) in African Americans than whites (2.3 per 100,000), thereby suggesting a higher incidence in some populations.17 Meningiomas in children account for 1% to 2% of all intracranial neoplasms. These tumors have a male predominance (71%) and present at a mean age of 10.9 years— higher than that observed for other childhood brain tumors. The incidence of intraventricular (17%), posterior fossa (19%) locations is higher for childhood meningiomas than their adult counterparts.18 Childhood meningiomas are more likely to be malignant. In one study of 51 meningiomas in patients younger than 21 years of age, a higher incidence of the papillary variant, a histologically aggressive subtype, was observed. Approximately 24% of these tumors were associated with neurofibromatosis type 2 (NF2).2

ETIOLOGY Radiation Although head trauma, viruses, and gender are all hypothesized as causal factors in meningioma development, radiation exposure is the only unequivocal risk factor identified in the genesis of these tumors. In fact,

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meningiomas are the most common radiation-induced neoplasms of the central nervous system (CNS). Radiation is thought to introduce single- and double-stranded breaks in deoxyribonucleic acid (DNA) strands. These errors, when permanently incorporated into genes regulating the cell cycle, may lead to tumor formation.19 Although, most animal models have shown the induction of sarcomas and gliomas with radiation, few have shown the development of spinal meningiomas. An example can be found in the rabbit model. When rodents are exposed to cobalt-60 implanted under the dura, meningiomas develop.20 Radiogenic meningiomas can be divided into two major categories based on the dose of radiation administered: lowdose are defined as less than 10 Gy radiation-induced meningiomas. They are discovered years after treatment of nonneoplastic diseases of the head and neck such as tinea capitis. High-dose is defined as less than 20 Gy radiationinduced meningiomas that appear after treatment for head and neck tumors, most frequently medulloblastoma in childhood. A third category, recently proposed, includes a small group of meningiomas that were induced in patients subjected to intermediate doses of radiation between 10 and 20 Gy to the head and neck, application of radium to the skin for vascular nevi, or Thorotrast myelography (visualization of the CNS using thorium dioxide, a radiopaque substance).20 The first case of a high-dose radiation-induced meningioma was reported by Mann and colleagues in 1953. It involved a 4-year-old boy who received 65 Gy to the orbit for an optic nerve glioma. Four years after treatment, he developed a histologically malignant, supraorbital meningioma.21 Meningiomas developing in high-dose irradiated fields have been described in the subsequent literature, but only represent approximately 10% of radiation-induced meningiomas.22 The overwhelming majority of these meningiomas arise in patients treated with low-dose radiation for tinea capitis (ringworm of the scalp). In a study of 10,834 children in Israel treated with radiation doses of 1 to 2 Gy for tinea capitis between 1948 and 1960, 19 patients developed meningiomas. The average latency period from radiation exposure to diagnosis was 20.7 years.15 Results also showed that 89% of the meningiomas could be attributed to radiation exposure that these patients received during childhood. A retrospective review of these children revealed that the incidence of meningiomas in the irradiated children was 4 per 10,000 compared with the incidence of 1 per 10,000 observed in nonexposed subjects.18 Radiation-induced meningiomas are often multiple and more likely to occur over the convexities. Eighty percent of radiogenic meningiomas were found over the convexities compared with 46% of spontaneously occurring meningiomas. The average patient age at presentation for low-, moderate-, and high-dose radiation-induced meningiomas was 45, 32.3, and 34.2 years, respectively. The average time interval from radiation exposure to tumor discovery was 35.2, 26.1, and 19.5 years, respectively. In general, increasing doses of radiation are associated with shorter latency periods and a younger patient age at tumor presentation.23 A female predominance, with a male to female ratio of 1:1.2 and 1:1.6, was also found in moderate- and high-dose radiation-induced meningiomas. Lowdose radiation-induced tumors, however, were found to have a male to female ratio of 1.2:1. This was attributed to

an overwhelmingly male predominance in individuals treated with low-dose radiation for tinea capitis.20 Radiation-induced meningiomas present with an aggressive histologic growth pattern: high cellularity, cellular pleomorphism, and an increased number of giant cells.18 In a study of seven radiogenic meningiomas identified at the Mount Sinai Hospital, three were characterized as atypical.20 In another series of 10 high-dose radiation-induced meningiomas, 4 of 8 tumors examined histologically were considered atypical and had a high bromodeoxyuridine (BrdU) labeling index. In general, radiogenic meningiomas following low-dose radiation to the head have a high recurrence rate of 18.7%, even after complete surgical removal.23

Trauma Berlinghieri, an Italian surgeon from Pisa, Italy, was the first to consider trauma as a cause of meningiomas in 1813.4 Although head trauma has been suggested as another cause of meningiomas, the evidence for such an association remains unconvincing. In a review of 295 patients by Cushing and Eisenhardt, 94, or 30%, had a history of head trauma that appeared to be related to the development of meningiomas. A scar, previous swelling, or depressed fracture was noted in 24 of these patients, thus supporting trauma as for a cause of meningiomas.3 Reports of tumors associated with skull fracture lines, a retained intracranial foreign body, and dural scarring have been found in the literature.24 A recent case-controlled study of 189 women with meningiomas also found a higher incidence of patient-reported trauma than either of the control groups.18 In a 2002 population-based case-control study of 200 case and 400 control subjects, Phillips and coworkers found an increased risk of meningioma formation with head trauma. This statistically significant correlation was found to be especially significant for head trauma occurring 10 to 19 years prior to the diagnosis of a meningioma.25 One theory suggests that release of bradykinin, histamine, and arachidonic acid during trauma may increase the permeability of the blood-brain barrier (BBB), thereby allowing the passage of harmful substances that may lead to the development of meningiomas.18 In 1971, Boldrey commented that, “It is certainly no compliment to our civilization that a tumor more commonly encountered in women than in men should be regarded to have trauma as a major etiologic factor.”16 Several studies have not supported an association between head trauma and meningioma formation. In one such study of 2953 patients at the Mayo clinic with a 29,859 personyear follow-up, an increased risk of meningioma formation was not found in individuals who sustained head trauma, a skull fracture, or post-traumatic amnesia.26

Gender The female predominance in patients with meningiomas suggests a role for sex hormones in the growth and development of these tumors. An association between breast cancer and meningiomas, the presence of estrogen and progesterone receptors on meningiomas, and evidence that meningiomas increase in size during pregnancy further support this hypothesis. A population-based case-control

Meningiomas of the Posterior Fossa and Skull Base

study of adult brain tumors demonstrated a reduced relative risk (RR) for meningiomas in postmenopausal women (RR = 0.59; 95% confidence limits = 0.18 − 1.94). Oophorectomy-induced menopausal patients also exhibited a reduced relative risk for meningioma development (RR = 0.12; 95% confidence limits = 0.01 − 1.30).18 Other case-control studies have shown an increase in meningioma size during pregnancy. The presence of estrogen receptors in 30% of patients and progesterone receptors in 70% of patients in a study of 330 meningiomas support the theory that varying levels of estrogen may contribute to meningioma growth.15

Viruses Several types of adenoviruses, a few polyoma viruses, and a subgroup of papovaviruses have produced CNS tumors in laboratory animals. A papovavirus antigen, as well as BK viral DNA, SV-40, and adenovirus DNA have been found in human meningiomas. Although these findings suggest a role of viruses in meningioma induction and growth, further investigation will be necessary to establish a causal relationship.18

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Although a majority of benign meningiomas exhibit a diploid karyotype or monosomy 22, a significant number have been found to harbor additional mutations. The loss of additional chromosomes or hypodiploidity is associated with progression of benign (grade I) meningiomas to atypical (grade II) or even to anaplastic (grade III) meningiomas. This is in contrast to the hyperdiploidity encountered in the progression toward increasing malignancy of most other solid tumors.27 Atypical meningiomas often contain allelic losses of chromosomes 1p, 6q, 10q, 14q, 17p, and 18q. The above-mentioned aberrations as well as frequent losses of chromosomes 6q, 9p, 10, and 14q are typically found in anaplastic meningiomas. High-grade meningiomas are also found to have chromosomal gains specifically for chromosomes 20q, 12q, 15q, 1q, 9q, and 17q.12 Demonstration of these genetic and chromosomal alterations, specifically the frequently observed deletion of chromosomes 1p and 14, may lead to the establishment of a molecular diagnostic tool for meningioma grading and prognostication.31

PATHOLOGY Gross Pathology

MOLECULAR PATHOGENESIS The overwhelming majority of meningiomas are sporadic tumors, but approximately 2% are hereditary and associated with a number of familial cancer syndromes.27 Most of these hereditary tumors occur in association with NF2, an autosomal-dominant disorder in which patients have a propensity to develop multiple meningiomas, vestibular schwannomas, and, infrequently, ependymomas. Approximately 35% of NF2 patients have meningiomas.28 Hereditary tumors are also found with an increased frequency in Werner’s syndrome, Gorlin’s syndrome, and Cowden’s syndrome. However, the association of meningiomas with these syndromes is less well defined.12 Meningiomas were among the first solid tumors in which a distinctive cytogenetic alteration was identified. Abnormalities of chromosome 22 in human meningiomas were discovered in 1972 and later verified in 61% to 80% of all meningiomas.29 Early molecular studies reported the loss of heterozygosity (LOH) for all sequences on chromosome 22 in meningiomas. Soon thereafter, the NF2 gene was located by linkage analysis on chromosome 22 and subsequently cloned. Recent studies have identified mutations in the NF2 gene on the long arm of chromosome 22 as an important aberration in the development of meningiomas. NF2 mutations are detected in approximately 30% to 35% of all meningiomas and 40% to 60% of sporadic meningiomas.30,31 The majority of these mutations are small insertions and deletions or nonsense mutations, which alter splice sites and cause frameshifts or create stop codons. These modifications alter the production of a protein called merlin, which serves as a structural link between the cytoskeleton and several proteins in the cytoplasmic membrane.12 Merlin is thought to be a tumor suppressor, so that when inactivated in the mouse by targeted mutagenesis, a variety of malignant tumors with a high rate of metastasis arise.32

Meningiomas are derived from arachnoidal cap cells, the external layer of the arachnoid membrane. These tumors are firm, rubbery, and well-circumscribed, with an uneven nodular or smooth surface. Meningiomas can be differentiated into three overall macroscopic appearances: the exophytic tumor, the “en plaque” tumor causing expansion of the meninges over a wide area, and a third variant associated with bony hyperplasia.22 Classically, meningiomas have a broad and firm attachment to the dura. En plaque meningiomas are sheetlike tumors that expand within the meninges. These tumors are commonly associated with hyperostosis and frequently seen at the sphenoid ridges. Irregular, dumbbell-shaped meningiomas are observed to originate from the meninges separating compartments of the cranial cavity. Examples include falcine meningiomas that penetrate the falx and occupy the frontal lobes and tentorial meningiomas that may expand into both the posterior and middle fossae.2,22 The consistency of meningiomas is associated with their intratumoral contents. Calcific psammoma bodies (often found in smaller growths and spinal meningiomas) give these tumors a characteristic “gritty” texture (Fig. 47-1). Advanced mucoid or fatty degeneration, edema, and necrosis can soften the consistency of a tumor. Occasionally, tumors are fluctuant to palpation secondary to the presence of cysts lying near the periphery. In addition, osseous changes in meningiomas can also result from metaplasia within the tumor.2,16,33 Meningiomas have a pinkish gray color, which changes to grayish white after fixation in formalin. Recent or old hemorrhages, which occur in highly vascularized tumors, can cause a reddish brown discoloration. Also, lipid accumulation in the cells may change the appearance of the tumor to yellow.2,22 Significant changes to the surrounding parenchyma, bone, and neurovascular structures can accompany meningioma growth. Pressure atrophy of adjacent parenchyma,

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Figure 47-1. Large psamomma bodies are prevalent in this transitional meningioma (H&E, ×200).

Figure 47-3. Microcystic meningioma with prominent pale vacuoles (H&E, ×200).

invasion of the venous sinuses, and encasement of intracranial vasculature are not common findings. In contrast, frank invasion of neural tissue; infiltration of arterial walls; and extension into extracranial compartments such as the pericranium, petrous bone, and orbit are rarely observed (Fig. 47-2). Hyperostosis, an osteoblastic process at the base of the tumor, is observed in approximately 25% of meningiomas.34 Direct bony involvement and increased subperiosteal bone formation secondary to reduced blood supply are both thought to contribute to this phenomenon. A recent study showed that meningiomas associated with hyperostosis were found to have a threefold increase in alkaline phosphatase.2

The enormous diversity of meningioma histology has defied simple, well-integrated classification. In 1938, Cushing and Eisenhardt were the first to propose an

extensive histologic classification, which included nine types and 22 variants.3 Since then, several additional classification systems have been proposed. Controversy persists because the histology of these tumors has generally shown poor correlation with tumor topography and clinical behavior. However, overall histologic categorization of these tumors has aided in determining their prognosis. In addition, altered histologic changes in a recurrent meningioma have been useful in identifying anaplastic transformation. In 1992, a landmark study of 1799 meningiomas from 1582 patients defined three histologic subtypes: classic, atypical, and anaplastic, which established a clear clinical correlation to a histologic type.35 The current classification scheme of the World Health Organization (WHO) defines groups of meningiomas on the likelihood of recurrence and grade. Grade I tumors are benign and include meningothelial, fibrous (fibroblastic), transitional (mixed) (see Fig. 47-1), psammomatous, angiomatous, microcystic (Fig. 47-3), secretory (Fig. 47-4), lymphoplasmacyte-rich,

Figure 47-2. Atypical meningioma with brain invasion. Note the many well-defined nests of meningioma invading the bland neural tissue (H&E, ×100).

Figure 47-4. Secretory meningioma features pseudopsamomma bodies that exhibit epithelial differentiation (H&E, ×100).

Microscopic Pathology

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Figure 47-5. Clear-cell meningioma is found most often in the posterior fossa. The clear cells are filled with glycogen. Also note the long collagen bundles in this section (H&E, ×100).

Figure 47-6. Chordoid meningioma may be confused with a chordoma (H&E, ×400).

and metaplastic subtypes. These tumors constitute 90% of meningiomas and have a low risk of recurrence and aggressive growth. Grade II tumors are atypical and include the atypical (see Fig. 47-2), clear cell (intracranial) (Fig. 47-5), and chordoid (Fig. 47-6) variants. These tumors comprise 7% of meningiomas and are associated with a higher likelihood of recurrence and aggressive behavior. Grade III tumors are anaplastic and include the rhabdoid, papillary, and anaplastic (malignant) subtypes, as well as tumors of any grade with a high proliferation index with or without brain invasion. These aggressive tumors comprise 3% of meningiomas and have the greatest likelihood of recurrence (Table 47-1).33

psammoma bodies are uncommon in these tumors but are poorly formed when present. These tumors also have a propensity to bleed. Fibrous (fibroblastic) tumors are formed by predominantly spindle-shaped, fibroblast-like cells that form parallel and interlacing bundles, rich in collagen and reticulin. Whorls and psammoma bodies are infrequent, and meningothelial features are often present. Transitional (mixed) tumors contain features of both the meningothelial and fibrous variants (see Fig. 47-1). Lobules and fascicles are found in close arrangements. Tight concentric whorls and psammoma bodies are frequently seen in this subtype. Psammomatous tumors possess a plethora of psammoma bodies, which may become confluent and form irregular calcified and sometimes ossified masses. Occasionally, these tumors are completely replaced with psammoma bodies. They typically occur in the thoracic spine and are typically seen in middle-aged women. Angiomatous tumors contain blood vessels that are dominant in the background of a typical meningioma. The majority of blood vessels are small, thin-walled structures and may obscure the histopathology of the tumor. Unlike hemangiopericytomas, these meningiomas are not aggressive tumors. The size of the meningiomatous vessels may

Grade I Meningioma Histopathology Common Benign Subtypes Meningothelial, fibrous, and transitional tumors are the most common histologic subtypes of meningiomas. Meningothelial tumors are characterized by uniform, polygonal (arachnoid-like) tumor cells forming lobules defined by thin collagenous septae. These cells have oval nuclei with an even chromatin pattern that often show central clearing secondary to glycogenation. Whorls and

TABLE 47-1. WHO Histopathologic Classification for Meningiomas WHO Grade

Incidence

Histologic Subtype

Grade I—Typical

Common

Meningothelial, fibrous, transitional, psammomatous, angiomatous Secretory, microcystic, lymphoplasmacyterich, metaplastic Atypical, clear-cell, chordoid Anaplastic, papillary, rhabdoid Tumors with high proliferation index or brain invasion

Rare Grade II—Atypical Grade III—Anaplastic

Recurrence/ Aggressiveness Low Low Low High

From Louis DN, Scheithauer BW, Budka H, et al: meningiomas. In Kleihues P, Cavenee WK (eds.): Pathology and Genetics of Tumors of the Nervous System. Lyon, IARC Press, 2000, p 314.

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be helpful in distinguishing these tumors from vascular malformations and capillary hemangioblastomas. Rare Benign Subtypes Secretory tumors are characterized by focal epithelial differentiation with glandular lumina containing keratin and staining potential for periodic acid-Schiff (PAS) and carcinoembryonic antigen (CEA) (see Fig. 47-4). The surrounding meningothelial cells are positive for cytokeratin. These tumors may be associated with marked peritumoral edema. Microcystic tumors consist of cells with elongated processes on a loose mucinous background (see Fig. 47-3). This histology gives the tumor an appearance of small cysts. Pleomorphic cells are abundant in this subtype. Lymphoplasmacyte-rich tumors are a rare subtype composed of extensive chronic inflammatory cells on a background of meningothelial cells. This variant is associated with polyclonal gammopathies or anemias. Diagnosis of these meningeal-based hematologic conditions must be considered with this tumor. Metaplastic tumors exhibit prominent focal mesenchymal differentiation. Meningothelial, fibrous, and transitional tumors may show osseous, cartilaginous, lipomatous, myxoid, and xanthomatous changes. Grade II Meningioma Histopathology Atypical meningiomas have greater than or equal to 4 mitoses per high-power field (hpf) and satisfy three or more of the following: increased cellularity, small cell population with an increased nuclear-to-cytoplasmic ratio, prominent nucleoli, uninterrupted patternless or sheetlike growth, foci of spontaneous or geographic necrosis, and brain invasion (Fig. 47-7). These tumors have moderately high proliferation-associated antigen-labeling (MIB-1) indices and correlate with a higher rate of recurrence. Clear-cell tumors are characterized by patternless polygonal cells with few classic meningioma features (see Fig. 47-5). The tumor cells are PAS-positive and have a clear and vacuolated cytoplasm, rich in glycogen. The cerebellopontine angle (CPA) and cauda equina are

preferred locations for these tumors which are associated with aggressive behavior, particularly when discovered at these sites. Chordoid tumors consist of lobules of eosinophilic, vacuolated chordoid cells in a myxoid matrix (see Fig. 47-6). These lesions can mimic the histologic appearance of chordomas, with the exception of the following features: absence of typical physaliphorous cells, whorl formation, positive staining for vimentin and epithelial membrane antigen (EMA), and absence of cytokeratin staining. Chronic inflammatory cells are often present, and peritumoral and intratumoral lymphoplasmacellular infiltrates are prominent in younger patients. Few of the patients with these tumors have hematologic conditions, such as Castleman’s disease. These tumors are also associated with a high rate of recurrence after a subtotal resection. Grade III Meningioma Histopathology Anaplastic meningiomas have more than 20 mitoses per hpf and features of frank malignancy which include whorls, banding, onion skin features, an increased nuclearto-cytoplasmic ratio, increased cellularity, increased rate of mitoses, micronecroses, increasing proliferation fraction of cells, and spider cell tumors. Patients with these tumors have a median age of survival of less than 2 years. Invasion of the brain is insufficient to make the diagnosis, and the cytology can be similar to that of sarcomas, carcinomas, or malignant melanoma. Papillary tumors are a rare meningioma variant that tends to occur in children. They are aggressive lesions defined by perivascular psuedopapillary pattern formation in at least part of the tumor. Local and parenchymal invasion, tendency to recurrence, and metastases occur in 75%, 55%, and 20% of these lesions, respectively.36 Rhabdoid tumors are a recently described entity composed of rhabdoid cells with the following features: rounded cells, eccentric nuclei, prominent nucleoli, and inclusion-like eosinophilic cytoplasm composed of whorled intermediate filaments. These cells may be present only at the time of recurrence. These tumors display anaplastic signs, including a high mitotic rate and elevated MIB-1 labeling indices. This meningioma variant has an aggressive clinical course and carries an unfavorable prognosis.

Immunohistochemistry

Figure 47-7. Darkly staining atypical mitotic nucleii (H&E, ×400).

The immunohistochemistry of meningiomas is reflective of their dual mesenchymal and epithelial nature. Positive staining for vimentin, a cytoskeletal protein in intermediate filaments, is found in 98% of them.22 An equally significant percentage of meningiomas, approximately 95%, display a membranous pattern of immunoreactivity for EMA. Positive staining for EMA is more prominent in the meningothelial and transitional subtypes, meningioma variants with greater epithelial differentiation. EMA staining is less consistent for atypical and anaplastic meningiomas. In addition, gliomas (except for low-grade ependymomas) and hemangiopericytomas do not stain for EMA, making this stain a useful tool in differentiating between these tumors.37

Meningiomas of the Posterior Fossa and Skull Base

Staining for S-100, a nuclear antigen, can be used to distinguish between schwannomas and meningiomas. Strong positive staining for S-100 is seen in 100% of schwannomas, whereas a patchy and weak reaction is found in only 41% of meningiomas.22 Secretory meningiomas strongly stain for CEA, an immunostain primarily seen in the pseudopsammoma bodies of these lesions. These tumors are also known to be associated with an elevated circulating level of CEA. Cytokeratin positivity is also often seen in secretory meningiomas, with far less staining seen in the meningothelial and transitional subtypes. Overall, approximately 20% of meningiomas stain for cytokeratins, and 4% stain for CEA.12,22

DIAGNOSIS Audiovestibular Testing Audiovestibular findings have been studied in only a few series of CPA meningiomas. Basic audiometric data, primarily in the form of pure tone average (PTA) and speech discrimination scores (SDS), have not been reported in a majority of patients. Audiometric brainstem response (ABR) and electronystagmography (ENG) have been studied in even fewer patients. Although abnormal audiologic findings were found in patients harboring CPA meningiomas, none of these series made any definitive conclusions on the topic. Furthermore, only a small percentage of patients in each series underwent comprehensive audiovestibular testing and therefore were perhaps not representative of the entire series. Since CPA and IAC meningiomas have no clear and distinctive audiometric features, most authors agree that audiovestibular testing is a useful but not necessary adjunct to the radiologic investigation of these tumors.38,39 In a 1997 series of 25 patients, Baguley and colleagues reported normal hearing in 5 of 25 (20%) patients, a lowfrequency hearing loss in 3 of 25 (12%), a flat loss in 9 of 25 (36%), a midfrequency hearing loss in 3 of 25 (12%), and a profound hearing loss in 5 of 25 (20%). In contrast, the authors found normal audiometry in only 1.9% of 361 patients with vestibular schwannomas.38 Furthermore, none of the patients with CPA meningiomas exhibited the characteristic high-frequency hearing loss seen in vestibular schwannomas.34,38 Granick and coworkers in a study of 32 patients, of which audiometric data was available for only 23, reported normal hearing in 6 of 32 (26%), a mild hearing loss (20 to 45 dB) in 2 of 32 (9%), a moderate hearing loss (50 to 80 dB) in 7 of 32 (30%), and a profound hearing loss (>85 dB) in 8 of 32 (35%) patients.40 An abnormal SDS was noted in approximately 50% of patients.38,39 In 1985, Laird and colleagues noted an abnormal SDS in 57% of patients, a slightly higher percentage than in other series. The authors of this series reported a median SDS of 76%, compared with 8% for vestibular schwannomas.41 ENG abnormalities have been found in over 90% of patients with CPA meningiomas. Laird and colleagues reported decreased vestibular responses in 9 out of 10 patients, and Granick and coworkers noted the same in 19 of 20 (95%) patients.40,41 Baguley and colleagues found a

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reduction in the caloric response in 12 of 18 (67%) patients, and Aiba and coworkers noted the same in 9 of 12 (75%) cases.38,42 Baguley and colleagues also found no significant relationship between tumor size and abnormal results for audiometry, speech audiometry, and caloric testing.38 The ABR is a useful noninvasive screening technique for diagnosing lesions of the CPA and IAC. Not surprisingly, ABR better reveals evidence of retrocochlear pathology in CPA meningiomas than does basic audiometry.43 Baguley and colleagues noted an abnormal ABR in all 18 patients tested. This abnormal result was also found in patients who had exhibited a normal PTA and SDS. This led the authors to conclude that ABR is more sensitive to distention or compression of the eighth cranial nerve (CN) than basic audiometry. Noting a predominance of larger meningiomas in their series, Baguley and colleagues also suggested that ABR testing may not be sensitive to small CPA lesions and could also miss meningiomas not impinging on the auditory pathway.38 In a study comparing the clinical characteristics of rare CPA lesions, Aiba and coworkers noted an abnormal ABR in 8 of 10 (80%) CPA meningiomas. The authors found a relatively low frequency of ABR and ENG abnormalities in CPA meningiomas compared with vestibular schwannomas.42 In 1995, Hart and Lillehei reported an abnormal ABR in five of seven (71%) cases.39 Granick and colleagues and Laird and coworkers found the same in 100% of their patients.40,41 Although ENG and ABR testing is useful, they are neither specific nor sensitive in discriminating meningiomas from vestibular schwannomas or any other CPA tumors.

Radiology The first radiologic diagnosis of a meningioma was made with plain radiography by Mills and Pfahler in 1902. The tumor was localized with a radiograph that showed a shadow between the frontoparietal suture and posterior meningeal artery.9,44 A more consistent and methodical approach to the radiologic diagnosis of meningiomas, using plain radiography, was introduced by Sosman and Putnam in 1925. Their analysis of 95 intracranial meningiomas showed that 49% of these tumors had characteristic changes on radiographs. These alterations included sclerosis, bone destruction, spicule formation, enlarged vascular channels, calcification, and pneumosinus dilatans, a dilation of the paranasal sinus.45 Ventriculography and pneumoencephalography, two diagnostic techniques introduced by Dandy in 1918 and 1919, respectively, enhanced the localization of meningiomas. However, tumor diagnosis of meningiomas with these techniques remained elusive. For example, differentiating extra-axial from intra-axial lesions was difficult in the absence of additional findings, such as hyperostosis or increased vascularity.44,46 Cerebral angiography was initially described by Moniz in 1927. Two years later, he reported the first angiographic features of meningiomas with Pinto and Lima. An extensive characterization of the angiographic features of 125 tumors, 20 of which were meningiomas, was conducted by List and Hodges in patients undergoing cerebral angiography. The development of computed tomography (CT) by Hounsfield in 1973 and subsequent introduction of intravenous (IV) contrast agents improved the extra-axial

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localization, detection, and characterization of meningiomas. Soon thereafter, MRI was pioneered by Lauterbur and offered extraordinary anatomic detail using magnetic field gradients and multiplanar imaging. The development of IV contrast agents further enhanced the diagnosis of brain tumors, making MRI a superior technique for meningiomas.45,46 Plain Radiography The advent of newer imaging modalities such as CT and MRI have made plain radiography obsolete for the diagnosis of meningiomas. However, characteristic findings of meningiomas found incidentally on a radiograph taken for different reasons can lead to a tumor diagnosis.47 X-ray films are also helpful in defining the extent of a previous surgical procedure or in planning a surgical approach in a patient who previously underwent a craniotomy or metallic cranioplasty.11 Hyperostosis, the most common finding of meningiomas on plain radiograph, has an incidence of 38% to 61%. It is most easily visualized when it involves the cranium or sphenoid bone. Blistering, a pathognomonic finding in meningiomas of the paranasal sinuses, is defined by hyperostosis of the planum sphenoidale, as seen on plain radiography.47 Increased vascularity is the second most common finding for meningiomas on radiographic imaging. A widening of grooves created by meningeal vessels on the inner table of the skull is commonly associated with convexity meningiomas. Broadening of the foramen spinosum is also associated with meningiomas. However, this feature may also be seen with arteriovenous malformations and prolonged carotid occlusive disease.48 Prior to the introduction of CT, calcification was seen in 3% to 18% of meningiomas on plain radiography at initial presentation. It is a rare finding and usually presents in a diffuse, fine, or nodular pattern.47 Angiography Cerebral angiography is often used for the surgical planning and preoperative embolization of a meningioma. Although imaging techniques such as CT and MRI have better sensitivity and specificity, angiography is still used in circumstances of diagnostic uncertainty. Meningiomas classically have a “sunburst” or “spokeswheel” appearance on angiography. This pattern represents a radial arrangement of meningeal vessels that enter at the hilum or dural attachment of the tumor. Dural branches supplying blood to the tumor are large, tortuous vessels that usually arise from meningeal branches of the external carotid system. Typically, the blood supply arises from the vasculature that perfuses the anatomic location where the tumor develops. Large meningiomas may also parasitize pial vessels to supply the periphery of the tumor. A delayed capillary blush is also a classic angiographic feature of a meningioma that is caused by the contrast that persists into the late venous phase. Meningiomas of the CPA and skull base often stain poorly on angiography.48,49 Preoperative planning for the resection of a meningioma may be enhanced by information gleaned from angiographic features of the tumor. Angiography can provide information about the size and location of arterial feeders,

nature of the arterial blood supply (dural, pial, or mixed), overall tumor vascularity, patency of vessels, venous drainage pattern, and the degree of displacement or encasement of arteries and veins. Definitive knowledge of the vasculature involved with the meningioma can greatly aid its resection. Furthermore, preoperative embolization can decrease the overall vascularity of the tumor to diminish operative blood loss and facilitate resection of the tumor.49 Cerebral angiography was extensively employed in the past to make the diagnosis of a meningioma. In a study addressing the utility of angiography, this technique made a specific diagnosis of a meningioma in 83% of cases; it was uncertain or negative in a mere 8% of patients.48 Yet, some of the literature argues that the pattern of tumor vascularity is nonspecific for meningiomas and does not help to differentiate between other hypervascular tumors.50 Imaging techniques such as MRI, and more recently magnetic resonance angiography (MRA), offer a safe, noninvasive, and highly sensitive and specific modality for the diagnosis of a meningioma. Although, a recent meta-analysis of cerebral angiography found a 0.07% risk of a permanent neurologic deficit and a 0.6% risk of an adverse non-neurologic outcome, the complication rate remains higher than for the noninvasive imaging technologies available today.49 Angiography is also seldom requested by surgeons for the preoperative planning of small- or moderate-sized tumors, which can be removed without significant blood loss. Computed Tomography and Magnetic Resonance Imaging Detection CT and MRI have not only improved the detection and diagnosis of meningiomas, but also enhanced the surgical planning and follow-up treatment of these tumors. Although MRI is the modality of choice for the diagnosis and evaluation of meningiomas, CT remains an important imaging technique for several reasons, including its capacity to identify intracranial processes (hemorrhage, hydrocephalus, and mass effect) requiring urgent therapeutic intervention and its ability to exclude nonneoplastic pathology. CT also remains an excellent initial screening tool, given its wide availability in hospitals, good tolerance to patient motion, easier access to acutely ill patients during imaging, and lower cost.48,50 Initial studies comparing CT with MRI showed that small tumors with minimal mass effect or edema were more easily detected with CT. Approximately 10% of lesions were found to be undetectable by MRI and were easily visualized by CT. However, the introduction of IV contrast agents such as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced the ability of MRI to detect even the smallest tumors.47 Recent improvements in the magnetic field strength, acquisition time, slice thickness, and software associated with MRI systems have reduced the diameter of detectable intracranial lesions to less than 3 mm with or without contrast enhancement.49 Excellent delineation between anatomic structures, multiplanar imaging, and three-dimensional computer-generated reconstructions have made MRI the premier diagnostic imaging tool.

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Morphology The morphology of intracranial lesions, particularly meningiomas, plays an important role in their radiologic diagnosis. Meningiomas usually present as well-circumscribed, extraaxial, sessile lesions with a broad dural attachment. These tumors are usually smooth, but are often lobulated when situated adjacent to a rigid anatomic structure. Pedunculated lesions commonly originate from the edge of the falx and have a narrow dural base. En plaque meningiomas are uncommon lesions that usually present at the base of the brain as a narrow band of tissue. Even rarer are intraventricular meningiomas, which present in the lateral ventricles, and fissural meningiomas, which are completely surrounded by brain parenchyma and often mistaken for intra-axial tumors.47 Since most meningiomas are primarily extra-axial, differentiating between intra-axial and extra-axial lesions is an important clue in their diagnosis. Multiplanar imaging and the elimination of beam-hardening artifact on MRI have improved the visualization of the dural base of any lesion, regardless of its location. Coronal and parasagittal imaging can differentiate superficial intra-axial lesions from meningiomas of the high convexity, tentorium, and parasellar region. Metastatic lesions, low-grade astrocytomas, and exophytic masses may also grow intra-axially, and spread along the dural surface, thereby mimicking extraaxial lesions.47 An interface seen between the lesion and cortex is another morphologic feature helpful in establishing an extra-axial location. Displaced arteries and veins, including pial vessels found on the periphery of meningiomas, are hypointense on all pulse sequences. T1-weighted images (T1WI) best identify the interface between a hypointense tumor and hyperintense edema surrounding the lesion. Arachnoid cysts, which often overshadow meningiomas, have a low density on CT, a low intensity on T1WI, and a high intensity on T2-weighted images (T2WI). White matter buckling and “arcuate bowing of adjacent cortical gyri in an accordian-like manner” also suggest an extraaxial tumor.48 Although an extra-axial location may be appreciated on CT, MRI is better at perceiving subtle morphologic characteristics indicative of a meningioma.

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demonstrate mild to moderate hypodensity on CT, hypointensity on T1WI, and hyperintensity on T2WI.47 Flocculent and peripheral curvilinear hyperdensities can be seen in 20% to 30% of meningiomas on CT.47 Approximately 84% of meningiomas exhibit a mottled or speckled heterogeneity on T2WI. This heterogeneity is suspected to be secondary to tumor vascularity, cysts, and calcification. In addition, hypointense punctate or curvilinear shapes representing tumor vessels can be visualized on T1WI and T2WI.48 A majority of meningiomas enhance brightly with Gd-DTPA. Dense calcification and cystic lesions present in some meningiomas prevent their homogeneous enhancement.47 The enhancement with Gd-DTPA is more sensitive than that seen with iodinated contrast on CT. Thus, MRI is the preferred imaging technique for visualizing small or multiple meningiomas, the latter most often seen in patients with NF2.46,50 Contrast enhancement of meningiomas with Gd-DTPA on MRI often reveals a “dural tail,” a flat layer of enhancing dura that extends a few millimeters away the base of the lesion (Fig. 47-8). Although, once thought to be pathognomonic for meningiomas, recent studies have shown its presence in a number of lesions, including superficial intra-axial masses, dural metastases, and vestibular schwannomas. Dural tails have also been found in inflammatory processes, as well as aneurysms. Pathologic examination and electron microscopy have concluded that although a dural tail may indicate tumor infiltration, it could also represent a nonneoplastic reactive change. These could include hyperemia, tissue proliferation, hypervascularity, increased permeability to contrast, or dilation of dural vessels.46,48,49 In one histopathologic study of 54 patients with meningiomas, 31 (57%) were observed to have a meningeal tail on MRI. Tumor invasion was detected in 20 (65%) patients, thereby arguing for wide resection of the tumor to reduce the risk of recurrence.52 Bone Changes Changes in adjacent bone are seen in 15% to 25% of meningiomas. These changes can present as a mild “reactive process” or direct tumor infiltration of the bone. Minor

Density, Intensity, and Enhancement Meningiomas appear isodense (25%) or slightly hyperdense (75%) to brain parenchyma on nonenhanced CT scans.48 These tumors usually undergo intense, homogenous enhancement following administration of IV iodinated contrast agents. These compounds enhance meningiomas by accumulating in the interstitial spaces of the tumor after passing through an abnormal blood-brain barrier found in most extra-axial lesions.51 On MRI T1-weighted (short repetition time/echo time [TR/TE]) images, meningiomas are isointense (60%) or mildly hypointense (30%) to gray matter. On T2-weighted (long TR/TE) and proton density (long TR/short TE) images, these neoplasms are isointense (50%), mildly to moderately hyperintense (40%), or hypointense (10%) relative to the cortex.48 About 10% to 15% of meningiomas display atypical densities and intensities. Most of these meningiomas are hyperdense on CT and hypointense on MRI. Less than 5% of meningiomas

Figure 47-8. Axial T1WI postgadolinium MRI scan revealing a small meningioma on the posterior surface of the porus acousticus, demonstrating a dural tail found at the transition of the tumor mass with the normal meninges posterior to it.

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bony changes on CT include minimal hyperostosis, blistering, and mild erosion secondary to direct pressure of the tumor or dilated vasculature. Gross invasion of bone is marked with striking hyperostosis or bone destruction.48 Extensive hyperostosis is associated with larger meningiomas, especially those located near the sphenoid bone. Hyperostosis may also be the principal manifestation of a en plaque meningioma.49 Osseous changes associated with meningiomas are better appreciated on CT with the use of bone windows, specific settings used to enhance the visualization of these findings.48 Subtle bony changes are better delineated by CT than MRI. CT is therefore the favored imaging modality for this purpose. However, severe hyperostosis, bone destruction, tumor invasion, and obliteration of the diploic spaces can be distinguished on MRI. Tumor infiltration is best appreciated on T1WI as hypointense signals taking the place of the normally hyperintense fat in the bone marrow. Hyperostosis is also seen as a hypointense signal on T1WI.46 Calcification Calcification is present in 15% to 20% of meningiomas (Fig. 47-9). It is easily visualized on noncontrast CT and is found in a variety of forms: punctate (psammomatous), diffuse, rimlike, chunky, or nodular.48 Punctate calcifications are most common and give the meningioma a fine speckled appearance on CT. Central areas of hyperdensity often represent dense calcifications, which can prevent contrast enhancement of a meningioma.51 Calcification, often confused with hemorrhage, can be differentiated with density measurements or by studying bone windows.48 Although small punctate or rimlike calcifications are undetectable on MRI, large nodular calcifications can be easily visualized. Calcium is usually hypointense on T1WI and T2WI, with the latter being more sensitive in the detection of calcium.46

Edema Peritumoral edema is found in 46% to 92% of meningiomas.48 Approximately 66% of patients with symptomatic meningiomas are estimated to have a varying degree of surrounding edema.49 The amount of peritumoral edema is variable and can range from unremarkable to massive. On CT, edema appears as a low-density area surrounding the lesion. On MRI, edema is hypointense on T1WI and hyperintense on T2WI. T2WI is the preferred diagnostic modality for detecting and measuring the amount of peritumoral edema.48 The cause of edema formation remains uncertain, although, blood vessels within meningiomas are known to have endothelial fenestrations. Gap junctions are also known to exist between vessels.11 Venous obstruction, although never proven, has also been suggested as a possible cause of edema formation.51 Tumor size, location, histology, blood supply from pial arteries, degree of parenchymal infiltration, and duration of symptoms have been shown to correlate with the presence of peritumoral edema.11,49 Convexity, falx, parasaggital, sphenoid wing, and frontobasal meningiomas are often associated with edema. In contrast, suprasellar, posterior fossa, and intraventricular meningiomas have little to no edema. Meningothelial and transitional meningiomas are also known to be associated with peritumoral edema.48 Secretory meningiomas have also recently been shown to have a significant amount of surrounding edema. Although numerous studies have established factors correlating with the presence and amount of edema, other studies have found few, if any, associations.12 Vascular Displacement, encasement, narrowing, or occlusion of vascular structures can be caused by meningiomas. Vascular compromise by meningiomas is typically caused by encasement of arteries and direct compression of dural venous sinuses. CT is rarely able to visualize the vascular supply to meningiomas, given similar densities of the vessels and brain parenchyma before or after contrast administration. Dynamic CT, a technique in which a bolus of contrast enhances the arteries before accumulating in the lesion, can be useful in defining the vascular supply to the tumor.51 MRI, however, is far better at evaluating vascular compromise than CT for several reasons. A difference in signal intensity between blood flow in the vessels and soft tissue in the tumor provides superior anatomic detail. Also, multiplanar imaging and the absence of bone artifact help to clearly define the relationship between the tumor and adjacent vasculature.47 In addition, flowsensitive techniques can also be introduced to resolve difficult cases.48 Atypical Characteristics

Figure 47-9. Axial CT scan of the head revealing a calcified left petroclival meningioma.

About 15% of meningiomas present with unusual imaging features, including necrosis, hemorrhage, cystic change, and lipomatous degeneration. Rapid tumor growth may lead to foci of necrotic tissue within the meningioma, which appears hypodense to surrounding tissue on CT. On MRI, these areas have a low attenuation on T1WI and a high attenuation on T2WI.48 Necrotic areas do not enhance on contrast administration. Occasionally, meningiomas

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undergo complete necrosis and present as ring-enhancing lesions, thereby widening the differential to include abscesses, thrombosed aneurysms, and intra-axial tumors, in particular glioblastomas. Morphologic features can help to distinguish meningiomas from many intra-axial lesions. Hemosiderin deposited in the walls of aneurysms seen with MRI can also help to differentiate between these vascular malformations and meningiomas.51 Hemorrhage is seen in 5% of meningiomas. The imaging characteristics vary depending on the age of the blood.48 On CT, an acute hemorrhage is isodense or hyperdense to surrounding tissue and may be confused with calcification. Two to 3 weeks later, after liquefaction of the clotted blood, hemorrhage appears isodense to brain parenchyma and after 4 weeks is hypodense to surrounding tissue.51 On MRI, hemorrhage appears hyperintense on T1WI and hypointense or hyperintense on T2WI. Multiple bleeds over days may produce variable densities and intensities. In addition, massive hemorrhage into the subdural or subarachnoid spaces can complicate or obscure the diagnosis.47 Cystic meningiomas represent only 2% to 4% of all meningiomas. Cysts present as nonenhancing, hypodense areas on CT. On MRI, they are hypointense on T1WI and hyperintense on T2WI. Cysts on the periphery of the tumor may represent secondary arachnoid cysts. The differential diagnosis of cystic meningiomas also includes hemangioblastomas, gangliogangliomas, and cystic gliomas.48 Diffusion weighted imaging (DWI) is a technique that may help to differentiate between solid and cystic tissue. Cystic areas have a low signal intensity as opposed to tissue, which has a high signal intensity on DWI. Lipomatous degeneration, which involves replacement of tissue with fat, is a rarely found in meningiomas. These areas are hypodense on CT, hyperintense on T1WI, and hypointense on T2WI.50

GENERAL SURGICAL PRINCIPLES Skull base meningiomas pose significant surgical challenges due to their ability to invade dura and bone, compress, and encase critical neurovascular structures. The decision to operate is at least partially based on the balance between the morbidity of tumor removal versus the natural history of the untreated tumor. The anticipated risk of short-term impairment must be weighed against the probability of a similar or worse ultimate outcome if the surgery is not performed. The patient’s lifestyle and occupation should also be taken into account.53 The surgeon should discuss the surgical goal, expected results, and anticipated morbidity with the patient. If the patient is asymptomatic with a small tumor and a surgical intervention is deferred, the patient should be available for regular clinical and radiologic follow-up and understand the risks of deferring treatment.54 Patient factors as well as tumor characteristics play a significant role in predicting the morbidity of a surgical procedure. A patient’s age, estimated life expectancy, preoperative Karnofsky performance score, neurologic status, and associated medical conditions such as uncontrolled hypertension, diabetes, bleeding disorder, or infection

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influence the decision for surgery.11,34 Minimal morbidity from a surgical procedure is expected in a young patient with a good functional status and minimal or no comorbidities. The size, location, vascularity, sinus involvement, and extent of a tumor are important factors in determining its resectability. Large vascular meningiomas infiltrating into the dura, bone, and sinuses, as well as those compressing the neurovasculature, are difficult lesions to resect and are expected to cause considerable impairment. In general, young symptomatic patients with a good functional status afflicted with a growing tumor causing progressive neurologic symptoms are the most suitable candidates for surgery. Patients with a strong preference for removal of a tumor that is likely to become symptomatic in the future are also good surgical candidates.55 The basic goals of any surgery are to prolong life and preserve function. To meet these objectives, a surgical procedure must maximize tumor resection without causing damage to the neurovasculature or intra-axial structures.56 The decision to perform a total or subtotal resection rests once again on the functional status of the patient and tumor characteristics. A complete resection of the tumor including a dural margin and removal of any infiltrated bone remains the objective. Petroclival meningiomas, especially those with cavernous sinus involvement, are the most difficult to completely resect. In the event that only a subtotal resection is feasible, the goals must be modified to entail the procurement of an accurate tissue diagnosis and reduction of the mass effect caused by the lesion.53 Prior to surgery, the surgeon must select the approach, review the relevant intracranial anatomy, and study the images displaying the relationship of the neurovascular structures with the tumor. The approach must be selected not only based on the anatomic location of the tumor but also the individual patient. Elderly patients with multiple comorbidities may not tolerate the discomfort and hospitalization mandated by the certain approaches, even though they may be ideal candidates for complete resection.56 Unexpected and unforeseen intraoperative emergencies such as brain swelling, damage to venous sinuses, and significant arterial bleeding must be anticipated for every surgical procedure.11 The relationship of a meningioma to the adjacent cranial nerves is much less predictable than for a vestibular schwannoma. To optimize the functional outcome, it is important for the surgeon to understand the anatomic relationship between the cranial nerves and the tumor. A premeatal (anterior to the IAC) meningioma displaces the facial nerve over its posterior aspect. In contrast, the most common course for the facial nerve in the case of a vestibular schwannoma is anterior. In the case of CPA meningiomas, CN VII often lies between the surgeon and the meningioma, making it more vulnerable to surgical trauma. Retromeatal (posterior to the IAC) meningiomas displace the facial nerve anteriorly, thereby placing the tumor directly between a surgeon’s instruments and the cranial nerve.57,58 Hearing preservation should be attempted with the suboccipital/retrosigmoid or petrosal approach for all patients with retromeatal meningiomas with good preoperative hearing. The suboccipital/retrosigmoid approach, in particular, provides good access for tumors located posterior

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to the porus acousticus with a minimal risk of significant morbidity. Multiple authors have suggested using this approach to maximize hearing preservation even for patients with large tumors and poor preoperative hearing.59,60 Cases in which hearing is to be safeguarded, tumors involving the IAC may be approached with a middle fossa or extended middle fossa approach. Patients with large meningiomas of the IAC with evidence of bony invasion and poor hearing may be treated with a translabyrinthine approach.34 Tumors of the lateral IAC with invasion of the inner ear have been reported. Resection of the inner ear has been proposed in these cases to prevent recurrence.61 Meningiomas may also involve other basal foramina, such as Meckel’s cave, the jugular foramen, and the foramen magnum, which may necessitate the use of alternative approaches.

PREOPERATIVE CONSIDERATIONS Given the differential diagnosis of the CPA and IAC, a preoperative evaluation should include an effort to determine the specific type of tumor present. As stated previously, CT and MRI remain the premier noninvasive tools for detecting and diagnosing specific lesions in the CPA and IAC. These imaging techniques provide specific anatomic information such as length and width of the IAC, precise location of the semicircular canals and jugular bulb, and the extent of pneumatization of the petrous and mastoid bones. This information is especially helpful for the surgeon planning the details of the procedure. The amount and direction of tumor extension may also be gleaned from these data. In cases of hearing loss, hearing tests may also be performed; the loss of discrimination is a more sensitive index than hearing threshold for detecting a neural origin of a hearing disorder. High-resolution cochleomeatal scanning (CMS) of the IAC may be performed to detect the presence of tumor in the canal as well as ascertain the position of basilar vessels rostrally and the jugular vein caudally.62 Angiography was extensively used in the past for diagnosing meningiomas. Today, however, it is rarely used, given the availability of noninvasive imaging techniques such as CT and MRI. It may be indicated in meningiomas of the cavernous sinus and in evaluation of the intrapetrous carotid to determine the patency and feasibility for resection by balloon occlusion testing. Angiography can also be used to determine the patency of any dural sinuses involved with tumor. These tests may rarely cause complications, so they must be selected after weighing their benefits and risks. Preoperative embolization of the external carotid contributions to the tumor’s blood supply may be selected by the operating surgeon. Embolization reduces blood loss intraoperatively and may soften the tumor due to tissue necrosis so that the tumor may be removed by the cavitron ultrasonic suction aspirator (CUSA).34 Blood should be available and cross-matched before surgery. This is especially important for large, hypervascular meningiomas located in close proximity to significant vascular structures. Meningiomas causing significant cerebral edema should be treated with perioperative steroids (4 mg

of dexamethasone every 6 hours).34 These agents improve intracranial compliance and protect the brain from the trauma of surgery. Treatment with anticonvulsants for the prevention of seizures is controversial. Most surgeons administer anticonvulsant therapy prior to the surgery so that therapeutic concentrations may be achieved before the patient is taken to the operating room. Although these medications protect against seizures, they are sometimes associated with lethargy, confusion, and, rarely, an allergic response. In addition, surgeons often question the need for anticonvulsant therapy in the absence of preoperative seizures.11,53 Antibiotic coverage is also recommended for a period of 24 hours to protect against infections. Several medications and techniques may be used to reduce brain edema and shrink the intra-axial structures. These include hyperventilation (CO2 level of 25 mEq/L), administration of an osmotic diuretic such as mannitol (1 to 1.5 g/kg as a 20% solution), and placement of a lumbar drain in anticipation of a prolonged brain retraction for skull base lesions.11,56 Neuromonitoring plays an important role in preserving function in meningioma surgery. Cranial nerve monitoring, especially facial nerve monitoring, is routinely conducted for meningiomas in the CPA and IAC. The trigeminal nerve and recordings from the extraocular muscles are also monitored during surgery for meningiomas involving Meckel’s cave and the cavernous sinus. The cochlear nerve is often monitored in cases selected for hearing preservation. Electrodes may also be placed in the tongue, neck, pharynx, trapezius, or sternocleidomastoid muscles for monitoring the lower cranial nerves (IX through XII) when the meningioma extends to the jugular foramen.34,63 Repetitive, irregular, high-frequency discharges on spontaneous electromyography (EMG) recordings alert a surgeon that a cranial nerve is being acutely stretched or compressed. Specific stimulation of a cranial nerve using electrical stimuli can not only confirm the identity of a particular nerve but also reassure the surgeon that the pathway is intact from the point of stimulation to the muscles generating the recordings.63

POSTERIOR FOSSA MENINGIOMAS Posterior fossa meningiomas account for 9% to 10% of all intracranial meningiomas and represent 7% of all posterior cranial fossa tumors.64–68 In Olivecrona’s series of 4185 brain tumors, posterior fossa meningiomas made up 8.45% of all intracranial meningiomas and 1.7% of all brain tumors.69 Meningiomas are the second most common tumor of the posterior cranial fossa after vestibular schwannomas.39 Prior to the advent of modern neuroradiologic (CT, MRI, angiography) techniques, diagnosis of these tumors was difficult due to conflicting signs and symptoms.64 Early management of these rare lesions was also challenging due to the inability of surgeons to identify their precise location preoperatively.64,65,70 Early series reported high morbidity and mortality rates for the surgical resection of these lesions. The operative mortality rates ranged between approximately 20% and 30%, and the perioperative mortality rate ranged from 0 to 15.7%.64,65 The slow growth rates of these lesions posed a dilemma for the surgeons

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who had to weigh the significant morbidity of surgical removal against progressive functional deterioration of the patient due to an increasing tumor size.65 The introduction of modern neuroradiologic techniques, skull base approaches, and microsurgical techniques have lessened the morbidity and mortality associated with the surgical resection of these tumors.64–66,71 Cushing and Eisenhardt proposed one of the first classification systems for posterior fossa meningiomas in 1938.3 They divided posterior fossa meningiomas into tumors of the basilar groove, posterior cerebellar convexity, the acoustic foramen, and the lateral recess. Since then, several different classification schemes have been proposed to organize posterior fossa meningiomas. In 1953, based on their radiologic and postmortem examinations of 71 posterior cranial fossa meningiomas, Castellano and Ruggerio divided these tumors into five groups. These groups consisted of tumors arising from the cerebellar convexity, tentorium, posterior petrous region, clivus, and foramen magnum and were classified on the basis of the tumor’s site of dural attachment (Fig. 47-10). The posterior petrous ridge was the most common site of dural attachment (42%) followed by the tentorium (30%), clivus (11%), cerebellar convexity (10%), and foramen magnum (4%).72 Russell and Bucy, on the other hand, classified posterior fossa meningiomas according to their location within the posterior cranial fossa, not their site of origin. The CPA was the most common location for these tumors according to these authors.73 Yasargil and Mortara proposed yet another classification system, which divided meningiomas of the posterior cranial fossa into CPA, foramen magnum, clival, petroclival, and sphenopetroclival regions based on his intraoperative findings.74 In a 1983 study of 38 posterior fossa meningiomas, Martinez and coworkers divided these tumors based on their site of dural attachment and also detailed the vascular

Figure 47-10. A view of potential sites of origin of posterior fossa meningiomas including the cerebellopontine angle, petroclival region, cerebellar convexity, and the jugular foramen. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

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supply to these tumors. The lesions were divided into five groups: CPA meningiomas, meningiomas of the cerebellar convexity, tentorium cerebelli meningiomas, peritorcular meningiomas, and clival meningiomas. CPA meningiomas included lesions attached to the posterior ridge of the petrous bone that derived their blood supply from the meningeal branches of the vertebral artery. Meningiomas of the cerebellar convexity originated from the dura covering the cerebellum and obtained their vascular supply from the vertebral and occipital arteries. Tentorium cerebelli meningiomas extended both supratentorially and infratentorially and were supplied by the IAC, the middle meningeal artery, the occipital artery, and terminal branches of the basilar artery. The meningeal branches of the vertebral artery, the middle meningeal artery, and occipital arteries provided blood supply to peritorcular meningiomas. Clival meningiomas obtained their blood supply primarily from the meningeal branches of the IAC and vertebral artery.66 The aforementioned classification schemes illustrate the two primary methods, namely, site of dural attachment and location, that have been used to subdivide posterior fossa meningiomas. Creation of these groupings is necessary to compare surgical morbidity and mortality. Both methods, however, have limitations that complicate the objective comparison of surgical data. Despite the availability of sophisticated, multiplanar imaging techniques, the primary site of dural attachment is difficult to determine preoperatively. In addition, the size and location of the tumor make this determination challenging even intraoperatively.69 Yasargil and Mortara cautioned, “at time … even with close observation through the operating microscope, a precise origin cannot be ascertained.”74 Classifying meningiomas based on their location is also problematic, given the frequent extension of tumors into different areas of the posterior cranial fossa. This lack of a consistent and unified classification scheme has made accumulation, integration, and comparison of surgical data for posterior fossa meningiomas difficult. A more recent classification scheme introduced by Sekhar and colleagues divides posterior fossa meningiomas into six groups based on their site of dural attachment: (1) cerebellar convexity and lateral tentorial (type I), (2) lateral petrous ridge and CPA (type II), (3) jugular foramen (type III), (4) petroclival (type IV), (5) foramen magnum (type V), and (6) unclassified (type VI). Type I meningiomas include lesions originating from the cerebellar dura, tentorium, or transverse, sigmoid or straight sinuses. Type II meningiomas are tumors that arise from the lateral petrous ridge dura, lateral and posterior to the IAC meatus, with or without extension into the canal. Tumors cropping up from the dura in the jugular foramen region or cerebellomedullary angle, with or without extracranial extension, are classified as type III meningiomas. Type IV meningiomas are petroclival meningiomas that arise from the petrous apex, medial petrosal ridge, or upper two-thirds of the clivus, with or without extension into the cavernous sinus or Meckel’s cave. Type V meningiomas are lesions that originate from the dura of the foramen magnum, lower one-third of the clivus, or C1–2 area. And finally, type VI meningiomas are unclassified tumors.65 Although plagued with the same imperfections mentioned for other classification schemes, this is a comprehensive and detailed scheme that may further the accurate collection,

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interpretation, and comparison of surgical morbidity and mortality.

CEREBELLOPONTINE ANGLE MENINGIOMAS Introduction The term cerebellopontine angle (CPA) was introduced in 1902 by Henneberg and Koch when they found two patients with bilateral vestibular schwannomas (acoustic neuromas) in a location they called kleinhirnbruchenwinkel (kleinhirn = cerebellum, bruchen = pons or bridge, winkel = angle).75 The CPA is most simply defined as the space bound by the cerebellum, pons, and petrous temporal bone. It is traversed by multiple neurovascular structures entering or exiting the cranial vault.76,77 It is a large intracranial basal cistern filled with cerebrospinal fluid (CSF) that has a meningeal lining. The CPA is bounded posteriorly by the flocculus and petrosal surface of the cerebellum. Anteriorly, it is enclosed by the posterior surface of the petrous pyramid and lateral aspect of the clivus. The lateral aspect of the tentorium marks the superior limit of the CPA. Inferiorly, this cistern extends along the lateral surface of the medulla. The lateral limit of the CPA is approximated by the posterior aspect of the petrous pyramid and internal acoustic meatus (IAM). The medial limit of this space is defined by the pons.77 Important neurovascular structures that reside in the CPA cistern are the CN VII through VIII nerve complex; the anterior inferior cerebellar artery (AICA) and its branches; the posterior inferior cerebellar artery (PICA); and numerous veins draining the petrosal surface of the cerebellum, the pons, and medulla, which empty into the superior petrosal vein.76,77

History The first CPA meningioma was reported by Rokitansky in 1855.77 Soon thereafter in 1863, Virchow described a “psammoma” originating from the posterior lip of the IAC.7 Although multiple surgical excisions were attempted, the first successful removal of a meningioma was described in 1894 by Charles Ballance. Although the author reported the tumor to be a vestibular schwannoma (acoustic neuroma), evidence reviewed by Cushing suggested that he was one of the first of many who have confused the identity of the two tumors.34 Cushing considered the broad dural attachment of the tumor and the absence of auditory symptoms to strongly suggest that the tumor removed by Ballance was more likely a meningioma.3 Henshen went on to give an account of three CPA meningiomas in 1910 and also reviewed the literature on these specific tumors.77 The history of CPA meningioma surgery continued when Olivecrona detailed the removal of two posterior petrous pyramid meningiomas in 1927 and 1929, with only the latter being associated with a good outcome.77 In a 1938 report on 23 meningiomas, which accounted for 2.4% of his surgical series, Cushing detailed the management of 7 CPA meningiomas. Only one of those patients, however, was reported to have a favorable outcome and was reported to be alive and well 9 years after the operation.

This particular patient had a meningioma that arose from the anterior lip of the IAC. The other six patients did not fare as well and had an average postoperative survival of only 20 months.3 In 1934 and 1936, De Martel and Guillaume described the removal of a CPA tumor. Postoperatively, the patient experienced an improvement in hearing, a significant accomplishment given the absence of modern magnification and surgical techniques.77 In 1953, Castellano and Ruggerio reviewed Olivecrona’s series of 71 meningiomas, 29 of which were classified as CPA tumors. Approximately 79% of the lesions underwent complete excision but this was accompanied by an appalling mortality rate of 43%. The mortality rate for the total resection of CPA meningiomas remained dismal until 1980 when Yasargil and Mortara reported complete removal for 30 of these tumors with a nearly 0% mortality.74 Since then, multiple series have reported excellent surgical excision for CPA meningiomas with minimal or no mortality.

Epidemiology Although, the CPA is the eighth most common site of involvement for all intracranial meningiomas, it is the most common location for meningiomas in the posterior fossa.78,79 Approximately 8% to 18% of all intracranial meningiomas and 30% to 58% of all posterior fossa meningiomas are found in the CPA. Meningiomas account for only 3% to 12% of CPA tumors, making them the second most common tumor in the angle.34,40,41,76,80–83 These tumors tend to occur most frequently in middleaged females. In one of the larger series of CPA meningiomas, Matthies and coworkers reported that meningiomas comprised 18% of tumors in the CPA, a much higher figure than other series.84 Although meningiomas represent a noteworthy pathology in the CPA, the most common lesion remains the vestibular schwannoma, which makes up almost 90% of all lesions in the angle.41,75,78,83

Origin Meningiomas originate from the arachnoid lining cells found in clusters at the tips of arachnoid villi, which serve as the sites of CSF absorption. Arachnoid villi are fingerlike projections of the arachnoid mesothelium that protrude into the sinus wall.85 Intracranially, meningiomas are found along the dural sinuses, their large tributary veins, as well as the exit foramina for vessels and cranial nerves.78,85 In the CPA, meningiomas are thought to arise from arachnoid villi that are associated with large and small venous channels surrounding the petrous portion of the temporal bone.83 These tumors are typically situated near the sigmoid sinus, jugular foramen, torcula, and superior and inferior petrosal sinuses. Concentrations of arachnoid cells found within the IAC, the jugular fossa, the geniculate ganglion, and along the greater and lesser superficial petrosal nerves may also give rise to meningiomas.34,78,85

Classification Akin to the classification schemes for posterior fossa meningiomas, the site of dural attachment as well as location of

Meningiomas of the Posterior Fossa and Skull Base

the tumor are the basis for many of the methods devised for defining and cataloging CPA meningiomas. Castellano and Ruggerio defined CPA meningiomas on the basis of their dural attachment to the posterior petrous ridge in 1953. In a report of 30 posterior fossa meningiomas in 1975, Grand and Bakay defined CPA meningiomas as all lesions that arise from the face of the petrous bone.64 Since then, several authors, including Yasargil and Mortara74 widely accepted this definition and classified CPA meningiomas on the basis of the tumor’s primary site of dural attachment. This definition of CPA meningiomas, however, excluded meningiomas growing in close proximity to the posterior petrous pyramid, but not actually originating from it, including, for example, meningiomas with a dural origin in the lateral clivus or undersurface of the tentorium cerebelli.77 In addition, the precise point of dural attachment is often difficult to determine despite the most favorable imaging techniques and surgical exposure. A classification scheme for CPA meningiomas should not only consider the dural surfaces involved but also take into account the location and anatomic extensions of the tumor. A CPA meningioma should be considered as such when its bulk lies in the CPA or IAC.34 One of the simplest classification schemes for CPA meningiomas divides these tumors into lesions anterior (medial) and posterior (lateral) to the IAC. Samii and Ammirati demonstrated a difference in the clinical presentation, tumor extension, and surgical morbidity and mortality based on a meningioma’s location medial or lateral to the porus acousticus.77 In a series of 22 CPA meningiomas in 1984, Sekhar and Jannetta used a similar scheme to describe tumor extension.80 Given the importance of location as a determinant of approach and outcome, Thomas and King introduced a more comprehensive classification scheme that subdivides CPA meningiomas into six anatomic groups namely lateral, midpetrosal, petroclival, Meckel’s cave, inferior, and IAC. The lateral group includes meningiomas arising in a region defined by the sigmoid sinus laterally, the superior petrosal sinus superiorly, the IAC medially, and the jugular foramen inferiorly. Midpetrosal meningiomas arise from the bone immediately above the IAC stretching to the superior petrosal sinus. The petroclival region lies medial to the IAC between the superior and inferior petrosal sinuses. This area is the most common site for CPA meningiomas. Meningiomas of Meckel’s cave comprise lesions arising from the dura of Meckel’s cave extending into the CPA. Inferior meningiomas come from the narrow stretch of bone between the jugular foramen and IAC. Finally, IAC meningiomas are defined as tumors that arise from and are centered on the IAC.69 Although a number of classification methods have been proposed for CPA meningiomas, the lack of a unified and consistent classification scheme has made the comparison of surgical outcome data problematic. Given the paucity of large series of CPA meningiomas, even subtle variations in cataloging CPA meningiomas by various authors alters the data on surgical resection, morbidity, and mortality. For example, Sekhar and Jannetta suggested that the primary reason for a difference in the resection rate between their series of 22 CPA meningiomas (64%) and Yasargil and Mortara’s series of 30 (100%) was more than likely due to a minor variation in classification. Some of the large

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posterior fossa meningiomas classified as clival tumors by Yasargil and Mortara would have been characterized by Sekhar and Jannetta as CPA meningiomas. Since clival tumors have an increasing likelihood of morbidity and mortality depending on the degree of resection, they are often only partially excised. Meningiomas in the CPA with a significant clival or tentorial extension, which were more likely to be incompletely resected, were cataloged as CPA meningiomas by Sekhar and Jannetta. This dissimilarity in classification may explain a significant discrepancy in the resection rates between the two series.80 Another example of the difficulty associated with the lack of an all encompassing classification scheme was illustrated in a recent series of 41 CPA meningiomas by Thomas and King. These authors defined petroclival meningiomas as those lesions arising from the apex of the petrous bone between the superior and inferior petrosal sinuses.69 Bricolo and coworkers, however, considered this anatomic region to only include tumors with an origin medial to the trigeminal nerve.86 Given the high morbidity and mortality rates associated with petroclival meningiomas, Thomas and King reported a higher resection rate with a lower likelihood of morbidity and mortality for these tumors compared with their Italian counterparts. The variability of inclusion criteria in virtually all series on CPA meningiomas makes a comparison of surgical outcome data between them particularly tricky.69

Clinical Presentation Hearing loss, dysequilibrium, and tinnitus are the most common symptoms reported in patients with CPA meningiomas (Table 47-2).40,41,66,78,87,88 In 1985, Granick and colleagues studied the clinical manifestations and diagnosis of CPA meningiomas in a series of 32 patients. The authors found hearing loss (75%), vertigo or imbalance (59%), and tinnitus (34%) to be the most common symptoms reported by patients at the time of their initial evaluation. Trigeminal nerve dysfunction was also reported to be TABLE 47-2. Clinical Presentation of CPA Meningiomas Sign or Symptom

Frequency

References

Hearing loss Imbalance, dysequilibrium Tinnitus Ataxia Decreased corneal reflex Headache

60% to 75% 50% to 66% 43% to 66% 6% to 81% 50% to 60% 22% to 58%

Facial numbness Trigeminal neuralgia Facial spasm Facial weakness

19% to 64% 7% to 31% 6.7% to 36% 3% to 53%

Dysarthria Dysphagia Papilledema Dementia Diplopia Hemiparesis Otalgia Abducens paresis Visual disturbances

10% to 25% 5% to 19% 5% to 26% 13% to 14% 8% to 25% 5% to 16% 5% to 16% 3% to 18% 2.7% to 19%

40, 41, 64, 69, 74, 79, 84 40, 41, 69, 79, 84 41, 64, 79, 80, 84, 88 40, 64, 69, 72, 74, 79, 88 41, 72, 74 40, 41, 74, 87, 90, 95, 100, 104 40, 41, 72, 74, 79, 88 40, 41, 64, 72, 74, 79, 84 72, 79, 80 40, 41, 64, 72, 74, 79, 80, 82, 84 41, 64 40, 41, 64, 72, 79, 84 41, 64, 66, 69, 79, 80, 82 64, 80 41, 64, 72, 79 40, 64, 66, 72, 80, 84 40, 41 40, 66, 80, 84 40, 64, 66, 79, 84

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frequent in these patients; an alteration in facial sensation was described in 25%, and trigeminal neuralgia was reported in 16%.40,87 Lower cranial nerve abnormalities were noted in 13% of patients. Less common symptoms were headache (22%), visual changes (19%), limb weakness (9%), otalgia (6%), and facial weakness (3%). On physical examination, common otologic and neurologic findings were nystagmus (50%), decreased facial sensation (44%), ataxia (41%), reduced hearing (28%), and facial weakness (28%).40,87 Overall, cranial nerve dysfunction and cerebellar deficits were the most prominent signs and symptoms among patients with CPA meningiomas. Impairments of multiple cranial nerves are some of the earliest clinical signs and symptoms seen in CPA meningiomas. Vestibulocochlear nerve dysfunction is the most frequently reported symptom in multiple series of CPA meningiomas. In one of the earliest series, Grand and Bakay reported on 30 posterior fossa meningiomas, noting eighth nerve dysfunction in 94% of patients with CPA meningiomas.64 The frequency of hearing loss ranged from approximately 60% to 75% in a majority of studies.40,41,64,69,74,79,84 In a retrospective review of Olivecrona’s 71 CPA meningioma cases, Castellano and Ruggerio reported hearing loss as an initial symptom in 57% of their patients.72 In a series of 30 CPA meningiomas, Yasargil and Mortara described hearing loss as a clinical sign on admission in 67% of their patients.74 Sekhar and Jannetta, however, found a significantly lower incidence of hearing loss (14%) in their series of 22 CPA meningiomas. In contrast, these authors reported a far higher incidence of trigeminal nerve dysfunction (73%).80 Martuza suggested that a difference in referral patterns, specifically Jannetta’s interest in trigeminal neuralgia, was more than likely the reason for this discrepancy.80,87 Dysequilibrium, which included imbalance and vertigo, had a more variable presentation, with a large number of series reporting frequencies ranging from 50% to 66%.40,41,69,79,84 Yasargil and Mortara and Minor and colleagues noted low incidences of dysequilibrium at 36% and 37%, respectively.74,88 Castellano and Ruggerio as well as Sekhar and Jannetta reported even lower incidences of dysequilibrium at 27% and 32%, respectively.72,80 Tinnitus was also reported in an unpredictable pattern in a majority of series, with frequencies ranging from 43% to 66%.41,64,79,80,84,88 Trigeminal nerve dysfunction is another commonly reported symptom for patients with CPA meningiomas. Sekhar and Jannetta described trigeminal neuralgia in 64% and facial numbness in 9% of patients in their series.80 This reported incidence of facial pain is significantly higher than that in other series, which found frequencies ranging from 7% to 31%.40,41,64,72,74,79,84 Facial hypesthesia was reported to be present in 25% of patients by Laird and colleagues.41 Facial numbness was found in 19% to 64% of patients in a majority of series.40,41,72,74,79,88 This range excluded the low incidence of 9% reported by Sekhar and Jannetta. On physical exam, a decreased corneal reflex was noted in 50% to 60% of patients.41,72,74 Facial nerve abnormalities, which included weakness, and facial spasm were noted by Grand and Bakay in 44% of their patients.64 Martinez and coworkers, in a study of 19 CPA meningiomas, found a similar incidence of seventh

nerve irregularities in 47% of their patients.66 Facial weakness was reported as a symptom in multiple series ranging from 3% to 53%. On further examination, this large range of frequencies can be separated into three distinct groupings: 3% to 7.5%,40,41,79,84 18% to 25%,64,80,82 and 50% to 53%.72,74 The difference in the involvement of the facial nerve based on the location of the majority of tumors in each series was most likely the cause of the variance. The authors of three separate studies found a difference in the frequency of facial weakness reported by the patient versus that noted on neurologic examination. Granick and colleagues found only 3% of patients complaining of facial weakness. On exam, however, he noted that 28% of patients had mild to moderate facial weakness.40 Laird and colleagues noted a similar difference, in which only 5% of patients mentioned facial weakness, but 15% were found to have the sign on physical exam.41 Matthies and coworkers found the two frequencies to be 3% and 11%.84 Facial spasm was noted in three different studies to be 6.7%, 12.5%, and 36%.72,79,80 Lower cranial nerve (IX, X, XI, XII) abnormalities were reported in 13% to 25% of patients in multiple series.40,41,64,66,72,74,79,80,84 Dysarthria was reported in 10% of patients by Laird and colleagues. Grand and Bakay noted 25% of patients complaining of dysarthria, but 19% mentioned it on physical examination. The frequency of dysphagia was found to be between 5% and 19% in multiple studies on CPA meningiomas.40,41,64,72,79,84 Cerebellar signs were also frequently noted on physical exam for patients with CPA meningiomas. Ataxia was noted on neurologic exam with a frequency of 6% to 81%.40,64,69,72,74,79,88 Nonspecific symptoms such as headache, nausea, emesis, and dizziness were also reported with varying frequencies in multiple series. Akin to many brain tumors, headache is one of the earliest clinical symptoms reported by patients with CPA meningiomas.66 Papilledema was noted in 5% to 26% of patients, signifying an increase in intracerebral pressure.41,64,66,69,79,80,82 Sekhar and Jannetta noted postpapilledemic optic atrophy in 5% of their patients.80 Several uncommon signs and symptoms noted for patients with CPA meningiomas in a small subset of series were visual disturbances (2.7% to 19%), diplopia (8% to 25%), sixth nerve irregularities (3% to 18%), dementia (13% to 14%), hemiparesis (5% to 16%), and otalgia (5% to 6%). Yasargil and Mortara reported subarachnoid hemorrhage as an interesting and unusual presenting symptom in 6.6% of their patients with CPA meningiomas.74 The mean time from the onset of symptoms to diagnosis of a CPA meningioma has been reported in multiple series to range from 4 to 6 years. Martinez and coworkers found a lower mean time of 3.5 years in their series. Granick noted the mean time between the onset of symptoms to the first time the patient consulted a physician to be 6 years, with a range of 1 month to 34 years. The largest time lapse between the first consultation with a physician to the actual diagnosis of a CPA meningioma was 18 years, with a mean time of approximately 4 years. The authors of this study found this delay to be the direct result of a misdiagnosis in 55% of cases.40,87 Yasargil and Mortara also noted a mean interval of 4 years from the first medical evaluation to the diagnosis of a CPA meningioma. The time between the first onset of symptoms to the diagnosis

Meningiomas of the Posterior Fossa and Skull Base

ranged from 1 year to 18 years. This author also noted a gender-specific delay that ranged from 3 years for women and 7 years for men.74 Samii and Ammirati found the time between the onset of symptoms to diagnosis to depend on the location of the tumor. The mean interval for meningiomas posterior to the IAM was 10 months (2 weeks to 2 years) with a median of 1 year. For meningiomas anterior to the porus acousticus, the mean interval was 4.3 years (5 weeks to 5 years) with a median of 3 years.77 The mean age at the time of presentation for CPA meningiomas has been reported by many authors to lie between 50 to 57 years.40,64,79,84 Granick and colleagues found the mean age of presentation to be 55.3 years with a wide age range of 19 to 84 years. However, approximately 20 of the 32 (63%) of the patients were between the ages of 45 to 65 years.40 The median has been noted to range between 52 to 53.5 years in a smaller number of studies.69 Given that meningiomas and vestibular schwannomas have very similar clinical presentations, distinguishing between them based solely on clinical presentation is difficult if not impossible.87 However, subtle differences may help to differentiate between these two tumors in the CPA. In a study conducted by Laird and colleagues in 1985, the clinical presentation as well as audiovestibular results and imaging studies of 20 patients with CPA meningiomas was compared with 131 patients with vestibular schwannomas. At initial presentation, a significantly larger percentage of meningiomas (35%) than vestibular schwannomas (18%) were greater than or equal to 4.1 cm.41 Noteworthy differences in the clinical presentation of meningiomas and vestibular schwannomas were found with respect to hearing loss 60% versus 98%, tinnitus 50% versus 70%, trigeminal neuralgia 15% versus 0%, and lower cranial nerve (IX, X, XI, XII) dysfunction 15% versus 0%.41 Hearing loss for similar-sized lesions was greater for vestibular schwannomas than meningiomas.80 Vestibular schwannomas had a higher incidence of vestibulocochlear nerve dysfunction than meningiomas, but displayed no signs of trigeminal neuralgia or lower cranial nerve dysfunction such as dysphagia or dysarthria in this study.41 Dysequilibrium was found in two-thirds of patients with both tumors. Patients with CPA meningiomas displayed a range of symptoms from positional vertigo to gait instability but not episodic vertigo. Neurologic deficits such as facial numbness, facial palsy, otalgia, and loss of taste occurred in both groups of patients with nearly equal frequencies.41 Nonspecific symptoms such as headache, nausea, emesis, and diplopia also were found in a similar percentage of patients with both tumors. No significant differences in physical examination were noted except for a decreased corneal reflex in meningiomas (50%) versus vestibular schwannomas (33%). This was most likely secondary to the compression of the trigeminal nerve in both groups.41 The clinical comparison between meningiomas and vestibular schwannomas presented by Laird and colleagues is in agreement with the data presented in another study comparing the clinical presentation of both tumors.41 Aiba and coworkers compared the clinical and audiovestibular findings between 141 patients with vestibular schwannomas and 43 patients with nonacoustic lesions in the CPA,

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18 of which were meningiomas.42 Significant clinical differences found between meningiomas and vestibular schwannomas were hearing loss 44% versus 57%, tinnitus 39% versus 51%, and trigeminal neuralgia 6% versus 1%, but also vertigo 28% versus 9%, facial dysthesia 33% versus 1%, and headache 28% versus 2%. In contrast, dysequilibrium, facial numbness, and headache were found in equal frequencies by Laird and colleagues.41,42 Nevertheless, there was significant agreement between the two studies, suggesting an important role for a thorough clinical history and physical examination in making the preoperative diagnosis of a CPA lesion. Although minor variations in the clinical presentation of a CPA lesion may help with the preoperative diagnosis, newer, readily available imaging modalities are more likely to provide a definitive verdict.

Diagnosis Multiple diagnostic tests are available for the diagnosis of CPA lesions. These include physiologic tests such as audiometry, electronystagmography, brainstem evoked response, and blink reflex testing, as well as imaging studies such as polytomography, myelography, angiography, CT, and MRI. Although the physiologic diagnostic tests are useful for detecting CPA masses, they are not helpful in the specific diagnosis of a CPA meningioma. Myelography and angiography were used extensively before the advent of noninvasive imaging technology.40 Angiography is rarely used today except in cases of diagnostic uncertainty or for preoperative embolization of the tumor to decrease blood loss during surgery. CT and MRI are the primary means for diagnosing lesions of the CPA (Fig. 47-11). Bone erosion or invasion, and tumor calcification are more easily detected on CT.

Figure 47-11. Axial T1-weighted gadolinium-enhanced MRI scan revealing a right cerebellopontine angle meningioma. Note its broad sessile base and the absence of widening of the internal auditory canal.

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On the other hand, MRI is better at detecting tumor vascular or neural involvement and extension into the IAC, petrous apex, Meckel’s cave, IAC, petroclival region, and jugular foramen. MRI is also more reliable in differentiating meningiomas from vestibular schwannomas. Although both lesions appear isointense to hypointense on T1WI, with a variable presentation on T2WI, vestibular schwannomas enhance significantly with gadolinium administration compared with meningiomas.89,90

Surgical Management CPA meningiomas have posed a challenge for surgeons, given their close proximity to neurovascular structures and their predisposition to attain massive sizes prior to clinical diagnosis. The likelihood operative morbidity and mortality has been high ever since Cushing reported the first successful removal of a CPA meningioma (Table 47-3).80 These tumors are particularly difficult to excise because of their hypervascularity and attachment to large sinuses in the subtentorial space.91 The difficulties with resecting these tumors also include their variable origin and unpredictable growth extension.84 The introduction of the new skull base approaches, the operating microscope, and microsurgical techniques have dramatically improved the rate of resection, minimized postoperative complications, and preserved functionality. The outcome for patients with CPA meningiomas depends on the patient’s preoperative condition, the location of the tumors, degree of tumor resection, tumor histology, and the use of adjunctive modalities.92 In addition, postoperative imaging has also improved the detection of small asymptomatic recurrences.80

In a study of 56 patients with temporal bone meningiomas in 1992, Arriaga and colleagues reported the use of six surgical approaches: the (1) retrosigmoid, (2) translabyrinthine, (3) transcochlear, (4) retrolabyrinthine, (5) infratemporal, and (6) middle fossa approaches. The authors studied the use of these surgical approaches with respect to the tumor location, morbidity associated with the procedure, and long-term functional outcome. The translabyrinthine approach was employed in 43% of patients, the transcochlear approach in 27%, and the middle fossa approach in 16%. Less often used were the retrosigmoid approach in 9% of cases, the infratemporal fossa approach in 4%, and the retrolabyrinthine approach in 2%. Total excision of the tumor was accomplished in 86% of cases.93 In a series of 22 CPA meningiomas in 1984, Sekhar and Jannetta used the retrosigmoid craniectomy in 19 cases, achieving a complete removal of tumor in 12 patients. The authors employed a subtemporal approach in the remaining three patients and were successful in total excision of the lesion in two patients.80 In a series of 41 CPA meningiomas in 1996, Thomas and King divided these tumors based on their anatomic location. They used the retrosigmoid approach in 10 patients with tumors in close proximity to the IAC and the translabyrinthine approach for midpetrosal and IAC lesions. Complete resection was realized in all groups except for petroclival meningiomas, which are discussed in the next section.69 In a more recent study of 40 CPA meningiomas in 2000, Voss and coworkers used a petrosal approach in 18 of 40 (45%) patients, a suboccipital/ retrosigmoid approach in 11 of 40 (27%), and a translabyrinthine approach in 7 of 40 (17%). The transcochlear and middle fossa approaches were employed in the remaining

TABLE 47-3. Cerebellopontine Angle Meningiomas—Series (1938–2002) Author

Year

Total Cases

Mortality

CPA

TR

Mortality

PR/SR

Mortality

Cushing and Eisenhardt3 Cambell and Whitfield Petit-Dutaillis and Daum D’Errico91 Castellano and Ruggerio72 Russell and Bucy73 Markham et al.110 Hoffman et al. Lang et al. Lecuire et al. Obrador Scott82 Grand and Bakay84 Yasargil and Mortara74 Laird et al.41 Martinez et al.66 Sekhar and Jannetta80 Granick et al.40 Samii and Ammirati77 Schaller et al.92 Matthies et al.84 Thomas and King69 Cudlip et al.68 Paterniti et al.71 Voss et al.79 Roberti et al.65 Batra et al.159

1938 1947 1949 1950 1953 1953 1955 1957 1967 1970 1971 1972 1975 1980 1982 1983 1984 1985 1991 1995 1996 1996 1998 1999 2000 2001 2002

23 5 41 10 71 15 29 12 7 114 42 20 30 50 20 38 22 32 56 13 230 41 52 139 41 161 21

22% 30% 29% 20% 30% 33% 28%

7 5 21 7 29 10 15 12 5 98 10 8 16 30 20 19 22 32 56 13 134 41 18 21 41 9 21

14%

0%

86%

14%

10%

0%

90%

35%

79% 20% 67% 58%

43% 0% 30% 29%

17% 50% 33% 42%

60% 40% 40% 0%

50%

0%

50%

0%

100% 80% 84% 64%

0%

0% 20% 16% 36%

0%

5% 8% 5% 20% 22% 19% 18% 0% 10%

0%

TR, total resection; PR, partial resection; SR, subtotal resection.

57% 27% 10% 4% 16% 0% 0% 8% 0% 0% 12% 5% 0% 0%

95% 92% 95% 73% 78% 81% 82% 100% 90%

26% 0% 0%

0% 0% 0%

0% 0%

0%

0%

Meningiomas of the Posterior Fossa and Skull Base

few cases. Total resection of the meningioma was achieved in 82% of cases, with a subtotal excision in 18% of patients.79 The primary reasons for an incomplete resection were brainstem invasion, cavernous sinus extension, and stubborn adherence of the tumor to the neurovasculature.79,80

Complications Cranial nerve palsies and CSF leaks are the two most common complications following surgery for CPA meningiomas. Bacterial meningitis, aseptic meningitis, wound infection, hydrocephalus, and hemorrhage are less commonly seen complications. Dysfunction of CN V, VII, and VIII, and, less commonly, CN IX, X, and XI are often noted after surgery for CPA tumors.94 CSF leaks usually result from the incomplete obliteration and sealing of the mastoid or petrous apex air cells after a craniectomy for the surgical approach to a CPA meningioma. Increased intracranial pressure, hydrocephalus, or infection can often initiate or exacerbate a CSF leak. Drainage of clear fluid into the middle ear, through the eustachian tube, into the pharynx or nose that worsens with a Valsalva’s maneuver is suggestive of a true CSF leak. Management initially includes placement of a lumbar drain. CSF leaks may also be observed at the wound site secondary to poor wound healing, hydrocephalus, and infection.94 In 2000, Voss and coworkers reported multiple postoperative cranial nerve deficits in their series of CPA meningiomas. These included facial nerve dysfunction in 12 of 40 (30%) of patients, trigeminal neuropathy in 6 of 40 (15%), and vestibulocochlear nerve dysfunction in 5 of 40 (13%). Neuropathies of CN IV, VI, as well as IX and X were noted in 8%, 5%, and 8% of patients, respectively. Not surprisingly, the authors noted a significant difference in the frequency of postoperative cranial nerve dysfunction based on the location of the CPA meningioma with respect to the porus acousticus. Seven of 10 (70%) patients with meningiomas with an origin anterior to the IAC and 6 of 8 (75%) patients with an origin inferior to the IAC displayed new cranial nerve deficits after surgery. Postoperative facial nerve paresis in these patients was 60% and 50%, respectively. In contrast, only two of eight (25%) patients with meningiomas arising posterior to the IAC and two of seven (28%) patients with meningiomas originating superior to the IAC developed new cranial nerve

811

problems. Only 15% of these patients developed postoperative facial nerve paresis. CSF leaks were reported in 9 of 40 (23%) patients, necessitating four wound revisions and two lumbar-peritoneal shunt placements.79 In the study of 56 temporal bone meningiomas, Arriaga and colleagues reported facial nerve preservation in 92% of patients postoperatively. Patients with meningiomas originating from the petrous ridge, petroclival region, or tentorium had a worse long-term facial nerve function than those with tumors located in the region of the sigmoid sinus, IAC, or jugular foramen. Similarly, patients approached with a transcochlear or infratemporal approach that involved direct manipulation of the facial nerve had the worst long-term facial nerve function. The retrolabyrinthine and retrosigmoid approaches, although used in only a handful of patients, were successful at preserving a HB (House-Brackmann) grade of I or II in 100% of patients after more than a year of follow-up. The translabyrinthine approach used in 11 patients was successful in doing the same in 64% of patients. Other complications reported included postoperative ataxia in 35%, long-term ataxia in 27%, CSF leaks in 12%, and meningitis in 7%. More than 90% of patients returned to their preoperative functional status after surgery.93

INTERNAL AUDITORY CANAL MENINGIOMAS The majority of meningiomas found in the IAC originate from outside the canal, typically arising from the posterior face of the petrous bone and prolapsing slightly into the canal. Completely intracanalicular meningiomas are extremely rare. Less than 15 well-documented cases have been reported in the literature (Table 47-4).38,61,81,83,95–103 These tumors arise from the meningeal lining of the IAC and are completely centered on the canal wall. Meningiomas with a significant component in the IAC usually have a broad base along the posterior petrous bone, thus making the determination of the origin particularly difficult.61 The first meningioma of the IAC was reported by Virchow, who noted a histologically proven meningioma arising from the porus internus.3 The next intracanalicular meningioma was reported more than a hundred years later in 1975 when Singh and colleagues described a patient

TABLE 47-4. Clinical Presentation, Approach, and Outcome in IAC Meningiomas Author

Year

Singh et al.99 Brookler et al.100 Langman et al.61

1975 1980 1990

Bohrer and Chole

96

1996

Zeitouni et al.98 Caylan et al.101

1997 2000

Martinez et al.103 Magliulo et al.102

2001 2002

Case

Case 1 Case 2 Case 1 Case 2 Case 1 Case 2 Case 1 Case 2

Age

Gender

14 70 52 54 52 66 60 42 46 48 50 56

Male Female Male Male Male Female Female Male Male Female Male Female

Size (cm) 0.2 2.0 × 2.5

1 1.1 × 0.5 1.2 × 0.5

Presentation HL, CN VII palsy HL, TI, dizziness HL, transient TI Bilateral HL Unilateral TI HL, vertigo AF, dysequilibrium AF, HL, vertigo HL HL, TI unsteadiness Bilateral HL TI

MF, middle fossa; T, translabyrinthine; R, retrosigmoid; HL, hearing loss; TI, tinnitus; AF, aural fullness.

Approach MF T T T MF T T T T T T R

Resection 100% 100% 100%

100% 100%

Outcome CN VII paresis CN VII intact CN VII intact CN VII intact CN VII & VIII intact CN VII intact CN VII intact CN VII intact CN VII intact CN VII HB Grade V CN VII HB Grade I CN VII & VIII normal

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SURGICAL NEUROTOLOGY

tinnitus, fullness, vertigo, and facial palsy. PTA demonstrated a unilateral hearing loss in 9 of 12 (75%) patients and was normal in 3 of 12 (25%).61,96,99,101–103

with complete facial palsy and deafness with a tumor in the lateral end of the IAC that also involved the ampullated end of the lateral semicircular canal.99 Another case involving the posterior semicircular canal, vestibule, and IAC was reported by Brookler and coworkers in 1980.100 Since then multiple authors have reported meningiomas of the IAC in the literature.61,96,98,101–103 Nager and Masica noted the tendency of intracanalicular meningiomas to invade deeper portions of the temporal bone via the lateral end of the IAC.85 These tumors were seen to grow along the nerve fibers into the cochlea, vestibule, and semicircular canals. Infiltration of the perilabyrinthine tracts has also led to the involvement of the middle ear and mastoid portions of the temporal bone.61 Given the deeper involvement of intracanalicular meningiomas, if the lateral end of the IAC is involved, exenteration of the cochlea and the semicircular canal should be considered.34,61 IAC meningiomas are most common during the fourth to sixth decades of life. They occur more frequently in women than men, with a ratio of 5:2.3.102 Their clinical presentations are related to compression of the vestibulocochlear nerve complex rather than parenchymal involvement. Akin to CPA tumors, these lesions become symptomatic as they increase in size within the bony IAC.61,98,101 The advent of high-resolution CT and MRI has permitted the diagnosis of small intracanalicular lesions before irreversible cranial nerve damage has occurred.96 In 12 well-documented cases of IAC meningiomas, 9 (75%) had unilateral hearing loss,

CLIVAL AND PETROCLIVAL MENINGIOMAS Introduction Clival and petroclival meningiomas are some of the most difficult skull base lesions to manage, given their close proximity to critical neurovascular structures.104,105 Due to their location and insidious growth pattern, these tumors may present with significant brainstem compression, involvement of multiple cranial nerves, and encasement of arteries arising from the vertebrobasilar system. Clival and petroclival meningiomas are usually detected after they have attained an enormous size, as their insidious early growth often occurs in the absence of significant signs and symptoms.105 The surgical resection of these lesions is made even more difficult with their propensity to extend to the petrosal and cavernous sinuses, middle cranial fossa, parasellar area, Meckel’s cave, IAC, and foramen magnum.86,104,106–110 Given their depth of location within the skull and anterior relationship to the posterior cranial fossa nerves, the skull base surgeon is relegated to dissecting these tumors between the often attenuated and displaced cranial nerves (Fig. 47-12).57

TUMOR Figure 47-12. A surgeon’s view of a left prepontine petroclival tumor. Draped on the lateral aspect of tumor are CN VII, VIII, and V, limiting direct exposure to the tumor. Access is via a “picket fence” approach working between cranial nerves, which is somewhat limiting. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

JB 5 7 Ch

F1

8

Meningiomas of the Posterior Fossa and Skull Base

Prior to the availability of the operating microscope, microsurgical techniques, skull base approaches, advanced imaging, and intraoperative monitoring, the surgical resection of these tumors was associated with significant morbidity and mortality.106 Although recent series report a dramatic increase in complete resection of these meningiomas accompanied by a decline in postoperative neurologic impairment, considerable morbidity is still associated with the surgical management of these tumors. In a study of 33 petroclival meningiomas, Bricolo and colleagues in 1992 stated that “In nearly all cases, the patient is in a worse clinical and neurological condition after surgery than before, and therefore requires constant and meticulous assistance.”86 In a review of petroclival meningiomas, Sekhar and coworkers believe that although improvements have been made in the management of these tumors, the temporary and permanent postoperative morbidity after surgical resection remains underreported.104

Origin and Classification Akin to other posterior fossa meningiomas, clival and petroclival meningiomas have undergone changes in definition over time. Comparisons between series of patients with clival and petroclival meningiomas have been limited due to the inconsistencies in the classification of these tumors.111 In 1953, using postmortem examinations to localize the site of the tumor, Castellano and Ruggerio defined clival meningiomas as tumors arising from the superior part of the clivus displacing the pons posteriorly.72 Hakuba and colleagues, in 1977, also adopted this definition in a report of six meningiomas of the clivus.112 In 1963, Dany and Mortara described clival meningiomas as tumors originating from any part of the anatomic clivus growing anterior to the basilar artery.106 This definition, however, excluded rare cases in which the meningioma rests between the basilar artery and the pons. Based on their intraoperative observations in 1980, Yasargil and Mortara defined clival meningiomas as tumors “attached at any of the lateral sites along the petroclival borderline, where the sphenoid, petrous, and occipital bones meet.”74 Despite the attempts of these authors to describe and classify these tumors, a precise definition for clival and petroclival meningiomas remains undecided. However, most authors agree that clival tumors arise from the upper twothirds of the clivus, whereas petroclival tumors originate from the petrous ridge anterior to the IAC or the upper two-thirds of the clivus. As previously mentioned, other authors, particularly Bricolo and coworkers, consider petroclival tumors to have an origin strictly medial to the trigeminal nerve.86 Sekhar and colleagues argue that although these definitions aid the surgeon, they fall short of helping to plan the operative approach or gauge the technical difficulties associated with a particular tumor. For example, a soft petrous middle clival tumor poses a very different intraoperative challenge from a hard, vascular, middle clival tumor encasing the basilar artery and multiple cranial nerves.104

Extension Clival and petroclival meningiomas often extend and grow into various regions of the posterior fossa. In a study of

813

41 clival meningiomas, Sekhar and colleagues, in 1990, divided the clivus into three parts: the upper clivus (region above the trigeminal nerves), the middle clivus (region between the trigeminal nerves and the glossopharyngeal nerves), and the lower clivus (region between the glossopharyngeal nerves and foramen magnum). Only 7 of 41 (17%) patients had single involvement of the upper, middle, or lower clivus, whereas the majority of cases, specifically 24 of 41 (59%) patients, had involvement of two regions of the clivus. Only 10 of 41 (24%) patients were found to have tumors in all three regions of the clivus. In the same study these clival meningiomas had various intracranial extensions: the tentorial notch in 32 of 41 (78%) patients, the cavernous sinus in 21 of 41 (51%), the petrous ridge in 19 of 41 (46%), Meckel’s cave in 18 of 41 (44%), the sella turcica in 12 of 41 (29%), the IAC in 9 of 41 (22%), and the middle cranial fossa in 7 of 41 (17%). Cranial and extracranial extensions to the petroclival bone were found in 16 of 41 (39%) patients, to the sphenoid sinus in 5 of 41 (12%), to the infratemporal fossa in 4 of 41 (10%), and the C1–2 area in 3 of 41 (9%).113

Clinical Presentation The average age at presentation for a patient with a clival or petroclival meningioma is in the middle of the fifth decade of life, with an age range of 5 months to 69 years.105,106 Females are affected twice as often as males in a majority of studies. Mayberg and Symon reported that females constituted 64% of their series versus males who made up 36%. The authors also found females to be afflicted at an earlier age of 47 years, versus 54 years for the males.111 In contrast, Castellano and Ruggerio in 1953 and Hakuba and coworkers in 1977 reported an equal incidence of males and females. The duration between the onset of symptoms to diagnosis was reported to average from 3 to 5 years, with a range from 1 month to 17 years in a majority of series.72,112 The incidence as well as the order of symptoms and signs are variable and inconsistent among series. In a review of 44 cases in 1977, Hakuba and coworkers reported a constellation of clinical signs and symptoms, which included increased intracranial pressure (70%), cerebellar involvement (70%), CN V palsy (68%), hearing loss (64%), facial nerve palsy (57%), involvement of the corticospinal tract (57%), CN VI palsy (40%), involvement of CN IX and X (34%), CN III palsy (27%), nuchal rigidity (25%), nystagmus (25%), sensory impairment in the limbs (16%), and psychological disturbance (1%).112 In a later study of 35 meningiomas of the clivus and petrous bone in 1986, Mayberg and Symon reported disturbance of gait and imbalance to be the most common complaints on admission. These were followed by headache, diminished auditory acuity, and facial pain. Vomiting, dysarthria, dysphagia, and somatic motor and sensory disturbances occurred later in the course of the disease. Cranial nerve deficits were noted in more than 90% of patients. CN V, VII, and VIII were most frequently involved. The authors also noted a surprising lack of palsies of CN III, IV, and VI, despite their frequent and intimate involvement with the tumor. The authors did not find any significant correlation between the clinical signs and symptoms, duration of disease, or abnormal physical findings and

Meningiomas of the Posterior Fossa and Skull Base

815

intervention is deferred may be conducted with regular clinical examinations and imaging.108

Approach Selection A plethora of approaches have been developed for the resection of clival and petroclival meningiomas. This is in no small measure due to the extreme difficulty associated with their complete removal. These approaches include the frontotemporal (pterional), occipitotranstentorial, subtemporotranstentorial, suboccipital, combined subtemporal and suboccipital, combined subtemporal and translabyrinthine, transpetrososubtemporal, transcochlear, combined suboccipital-translabyrinthine, transclival, transphenoidal, and extradural transbasal approaches.107,108,118,119 In 1990, Sekhar and colleagues used the retrosigmoid (suboccipital) approach in 20 of 41 (49%) of patients and the frontotemporal/orbitozygomatic/transcavernous approach in 18 of 41 (44%).113 Bricolo and coworkers also preferred the retrosigmoid approach in 23 of 33 (20%) patients. The remaining patients were approached equally with the frontotemporal (15%) or petrosal (15%) approaches.86 The retrosigmoid approach was used more often in patient’s with medium-sized tumors.86,113 This approach is used for petroclival meningiomas that are located centrolaterally and have minimal involvement of the upper clivus and tentorial notch. Advantages of this approach include expeditious access to the tumor. Disadvantages include the position of cranial nerves between surgeon and tumor, cerebellar retraction, and difficulty in accessing the brainstem when it is compressed by the tumor (Fig. 47-13). The frontotemporal/transcavernous approach is used for tumors involving the cavernous sinus and the upper and middle clival area. This approach allows the surgeon to access the upper clival area through the middle cranial fossa with less retraction of the temporal lobe. The disadvantage is the increased morbidity associated with working in the cavernous sinus.104,113 In a study of 46 patients with large clival and petroclival tumors extending below the tentorial incisura, Spetzler and coworkers in 1992 used three variations of combined approaches—the retrolabyrinthine, translabyrinthine, and transcochlear—to approach these lesions (Figs. 47-14 & 47-15). These approaches offer better visualization of the arachnoid plane between the brainstem and tumor, and minimal cerebellar retraction, with excellent superior exposure to the anterior brainstem, middle fossa, and foramen magnum.115,120 Several factors determine the selection of an approach for clival and petroclival meningiomas: tumor size, clival and petroclival region involved, extent and shape of brainstem compression, degree of vertebrobasilar arterial encasement, tumor vascularity, source of the tumor blood supply, venous anatomy, patient’s preoperative neurologic status, goal of the operation (total versus subtotal), and finally the surgeon’s personal experience and preference. Large and extensive tumors require complex approaches, which often require staged operations.104

Surgical History The natural history of clival and petroclival meningiomas is one of relentless progression and eventual patient

Figure 47-13. Axial view of a prepontine petroclival tumor approached via a suboccipital retrosigmoid craniectomy. Note the lengthy distance from the craniectomy opening to the tumor and the cerebellar retraction necessary for exposure. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

death.3,72,106,111 Early series reported an operative mortality rate of over 50% for these lesions. Prior to 1970, only 10 of 26 (38%) patients survived surgery for clival meningiomas, and only one case of successful total removal was reported.106,111 It was these dismal results that led Castellano and Ruggerio in 1953 to conclude that clival and petroclival meningiomas were “inoperable.”72 In a review of 29 clival meningiomas, reported in the literature until 1966, Cherrington and Schneck noted that clival meningiomas had a 1-year survival rate after diagnosis of 25%.121 In a 1977 review of 44 cases of clival and petroclival meningiomas, Hakuba and coworkers noted that out of 31 patients who received surgery, 17 (55%) died within 26 days, 3 (10%) died within 3 months after biopsy or partial removal of tumor, and 1 died 50 days after complete resection of the tumor. At the time of the report, seven patients were still living after partial or subtotal removal. Only three patients survived after complete removal of the meningioma. However, two of them had significant postoperative neurologic deficits.106,112,122 In a series of six patients with completely resected clival tumors in 1977, Hakuba and coworkers reported the death of only one, a significant achievement, given past results in the literature.112 Since then, multiple series have reported much improved results.

816

SURGICAL NEUROTOLOGY

GG JV

7 7

Figure 47-14. A left translabyrinthine approach to the cerebellopontine angle. Note that this is a anterosigmoid exposure allowing excellent visualization of the jugular foramen, CN IX, X, XI, the internal auditory canal, CN VII and VIII, and CN V. Ca, cochlear aqueduct; Cb, cerebellum; Ch, choroid plexus; D, dura; Fl, flocculus; GG, geniculate ganglion; IV, inferior vestibular nerve; JB, jugular bulb; JV, jugular vein; SPS, superior petrosal sinus; SS, sigmoid sinus; SV, superior vestibular nerve; TS, transverse sinus; T, tentorium. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

Ca JB

I S V V

11 10 9

SPS 7

8

6 5

Ch F1 Cb

T

SS D TS

Resection Gross resection of clival and petroclival tumors has markedly improved within the span of little more than a decade. The rate of complete resection of clival and petroclival tumors has ranged from 26% to 85% in a majority of series (Table 47-6).74,86,105–108,111,113,115,117,119,123 With the exclusion of two of the early series by Yasargil and colleagues and Mayberg and Symon as well as a recent one by Jung and coworkers, the percentage of total resection varied between 68% to 88%. In a recent meta-analysis of six separate studies on clival and petroclival meningiomas totaling 298 patients, complete resection was possible in 68% of cases.57 Yasargil and Mortara pointed to the extradural invasion of bone as the primary factor in preventing complete removal of tumor, a feat accomplished in only 35% of patients.74 Fierce adherence of the meningioma to the neurovasculature, invasion of the cavernous sinus, and extradural spread to bone were some of the reasons reported by Mayberg and Symon for subtotal resection of tumors in 1986.111 In a more recent study of 38 petroclival meningiomas in 2000, Jung and coworkers noted several reasons for incomplete resection of tumor: a difficulty in dissecting the tumor from the brainstem in 13 of 38 (34%) patients, adhesion of the tumor to cranial nerves in 9 of 38 (24%), cavernous sinus invasion in 6 of 38 (6%), hypervascularity of the tumor in 4 of 38 (11%), encasement of major vessels in 3 of 38 (8%), and inadequate exposure in 3 of 38 (8%).105

Although gross total resection is preferred, subtotal resection has been associated with a good functional outcome followed by long periods of survival. In 1986, Mayberg and Symon reported that only 4 of 26 (15%) patients demonstrated tumor progression and subsequently died.111 In a series of 22 petroclival meningiomas in 1986, Sekhar and Samii104 found only 1 of 5 (20%) patients had clinical symptomatology suggestive of tumor growth after a subtotal resection. Samii and coworkers113 also reported no reoperations on patients known to have residual tumor. Residual tumor was most likely to be found in the cavernous sinus or in the clivus.104,113 In 2000, Jung and coworkers noted that during a mean follow-up of 47.5 months, tumor progression occurred in 16 of 38 (42%) patients who had a subtotal resection of tumor. The authors also reported that during a follow-up period ranging from 6 months to 141 months (mean 47.5 months), 33 of 38 (87%) patients with subtotal resections had a Karnofsky performance score of more than 80. Although postoperative cranial nerve deficits were observed in 12 of 38 (32%) patients, the degree of impairment was mild.105

Mortality and Quality of Life Prior to 1970, the cumulative mortality rate in a majority of series was greater than 50%.57,111 With the introduction of microsurgical techniques, Yasargil amd Mortara in 1980

Meningiomas of the Posterior Fossa and Skull Base

Figure 47-15. A transcochlear approach to a prepontine petroclival tumor. There is a short distance from the surface of the craniectomy to the tumor. Minimal cerebellar retraction is needed and direct access to the tumor is afforded without intervening cranial nerves after the facial nerve has been rerouted. CA, carotid artery; ET, eustachian tube. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

CA ET

TABLE 47-6. Clival and Petroclival Meningiomas—Review of Series (1977–2000) Author

Year

Total Cases

Mortality

Hakuba et al.112 Yasargil and Mortara74 Mayberg and Symon111 Al-Mefty et al.78 Samii et al.108 Nishimura et al.124 Sekhar et al.113 Spetzler et al.115 Bricolo et al.86 Samii et al.107 Sekhar et al.117 Couldwell et al.123 Zentner et al.109 Jung et al.105

1977 1980 1986 1988 1989 1989 1990 1992 1992 1992 1994 1996 1997 2000

6 20 35 13 24 24 41 18 33 36 75 109 19 64

17% 10% 9% 0% 0% 8% 2% 0% 9% 0% 0% 4% 5% 1.5%

CN, cranial nerve.

817

Postop CN Deficit 50% 54% 31% 46% 91% 22% 39% 76% 60% 33% 34% 34%

Gross Resection 100% 35% 26% 85% 71% 78% 78% 79% 75% 60% 69% 68% 41%

818

SURGICAL NEUROTOLOGY

and Habuka and colleagues in 1977, reported operative mortality rates of 17% and 15%, respectively.74,112 Mayberg and Symon in 1986 reported a postoperative mortality rate in 3 of 35 (9%) patients within 6 months of surgery and in 4 of 35 (11%) patients after 6 months of surgery.130 The vast majority of recent series on clival and petroclival meningiomas have reported a mortality rate of less than 10%.68,86,105,107,113,123,124 In addition, many studies demonstrate a significant number of patients sustaining new neurologic deficits after surgical resection of petroclival meningiomas. The majority of these deficits involved injury to cranial nerves and affected approximately 35% of patients.57 In 1977, Hakuba and coworkers reported six cases of total removal of petroclival meningiomas. Two patients were in excellent condition postoperatively, three patients had mild to minimal impairment, and one died.112 In 1980, Yasargil and colleagues reported 20 cases of clival and petroclival meningiomas. Eleven (55%) patients experienced a good recovery, five had a fair recovery, and two had a poor functional status postoperatively.74 Mayberg and Symon assigned patients preoperatively and postoperatively to one of five clinical grades based on physical examination and functional status. These grades were defined as follows: grade I (no deficit), grade II (neurologic deficit but able to work or manage household), grade III (unable to work but able to care for self ), grade IV (requires nursing care), grade V died of disease. Approximately 57% of patients were assigned a worse clinical grade in the immediate postoperative period. The majority of these patients, however, showed improvement within a month.111 In their series of 24 patients with petroclival meningiomas, Samii and colleagues reported that 12 (50%) patients were able to return to their preoperative level of activity, 8 (33%) were independent but were unable to function as they previously had, and 4 (17%) required nursing assistance.108

MECKEL’S CAVE MENINGIOMAS Epidemiology Lesions of Meckel’s cave comprise less than 0.5% of all brain tumors.125–128 A wide range of lesions are found in this region, including meningiomas, chordomas, lipomas, arachnoid cysts, schwannomas, cholesteatomas, malignant melanotic schwannomas, metastatic carcinomas, sarcomas, melanocytomas, amyloidomas, cylindromas, neuroepitheliomas, fibrous xanthomas, and cysticercosis.125,129 Although several pathologic entities may occupy Meckel’s cave, schwannomas and meningiomas are the most common tumors in this region.126,129 Primary meningiomas of Meckel’s cave are rare tumors that comprise approximately 1% of all intracranial meningiomas.127 In their series of 295 intracranial meningiomas in 1938, Cushing and Eisenhardt noted only 5 meningiomas arising from Meckel’s cave.3 Among 1454 intracranial meningiomas studied at the Mayo Clinic from 1914 to 1960, only 14 were found to be in Meckel’s cave, yielding an incidence of 1%.128 Of the 1511 intracranial meningiomas undergoing surgery at the Neurosurgical Department of Rome

University, 16 were noted to be Meckel’s cave meningiomas, also giving an incidence of 1%.129 In 1992, only 70 cases of Meckel’s cave meningiomas had been reported in the literature, with few other reports noted in the English literature since then.129

Origin and Classification Meckel’s cave meningiomas originate from the dura mater of Meckel’s cave and compress the trigeminal ganglion, which lies in the posteromedial portion of the middle cranial fossa.126 These tumors may invade the middle or posterior cranial fossa, and may infiltrate into the cavernous sinus, or surround the internal carotid artery and the cranial nerves.127 In a retrospective review of 12 meningiomas of Meckel’s cave in 1975, Nijensohn and coworkers divided these tumors into three groups on the basis of their clinical presentation and prognosis. The first and largest group of patients (group I) experienced typical trigeminal neuralgia only; the second group of patients (group II) had a history of atypical trigeminal neuralgia without any neurologic deficits, and the third group (group III) experienced trigeminal symptoms as well as other cranial nerve deficits. The authors noted an excellent prognosis (no tumor recurrence, and resolution of pain) after complete removal of tumor for patients in group I. In contrast, the authors observed a high incidence of tumor recurrence due to subtotal removal, and a return of intractable pain for patients in the group III. Patients in the group II had an intermediate rate of tumor recurrence and trigeminal pain.128 In their series in 1992, Delfini and colleagues did not note a significant difference between patients with typical and atypical neuralgia, with or without other trigeminal nerve impairment. These authors divided Meckel’s cave meningiomas into two instead of three groups. Patients in group I had a history of typical or atypical trigeminal neuralgia with all physical abnormalities limited to facial hypoesthesia. These tumors were small meningiomas confined to Meckel’s cave. Group II patients experienced symptoms of trigeminal dysfunction combined with impairment of other cranial nerves.129 These were larger tumors originating from Meckel’s cave and extending beyond. Delfini and colleagues defined group I patients not only on their distinct clinical characteristics but also noted that these individuals had small globular meningiomas measuring less than 3 cm that only involved Meckel’s cave. Patients in group II were afflicted with larger tumors no longer confined to Meckel’s cave.129 In two separate comments following the report by Delfini and colleagues, Sekhar and Sen considered the larger meningiomas in group II to be cavernous sinus meningiomas. Sekhar suggested that these tumors may have originated in the cavernous sinus or petroclival region and subsequently extended to Meckel’s cave. Both authors agreed that determining the origin is difficult despite information garnered from MRI. No clinical or radiologic evidence of recurrence was found in any patients in group I, with an average follow-up of 6.1 years. Four of 8 (50%) patients in group II showed evidence of recurrence with an average follow-up of 4.5 years. Three of 8 (38%) patients in group II were reported to have tumor progression.129

Meningiomas of the Posterior Fossa and Skull Base

819

Figure 47-16. Meckel’s cave meningiomas may (A) reside primarily in the middle fossa, (B) reside primarily in the posterior fossa and extend into Meckel’s cave, or (C) have a significant posterior and middle fossa component bridged by Meckel’s cave. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

A

B

Samii and coworkers reclassified his series of 21 Meckel’s cave meningiomas into four groups based on tumor location and extension. Type I meningiomas were confined to Meckel’s cave. Types II and III meningiomas originated in Meckel’s cave and extended into the middle fossa and posterior fossa, respectively, without any infiltration into the cavernous sinus. Type IV meningiomas were dumbbellshaped tumors that arose in Meckel’s cave and extended into the middle and posterior fossae with or without infiltration into the cavernous sinus. The authors excluded meningiomas that had a dural attachment close to Meckel’s cave or those that involved it secondarily (Fig. 47-16).127

Clinical Presentation Meningiomas are more common in women than in men. Multiple authors have found this is also true for patients with Meckel’s cave meningiomas. Of the 12 patients in their series reported in 1975, Nijensohn and coworkers noted that 9 were women and 3 were men, with a mean age of 56 years and an age range of 35 to 71 years.128 In an analysis of 30 cases in 1983, Butti and coworkers also found that meningiomas were more common in women (22 cases) than men (8 cases). The author noted an average age of 52 years, with a range of 22 to 71 years.126 In a series of 16 Meckel’s cave meningiomas, Delfini and colleagues noted a female-to-male ratio of 1.6 to 1. The mean age at diagnosis was 41.6 years, with the age range between 22 to 60 years. The mean duration of symptoms was 2.7 years, with a range of 1 month to 20 years. The authors also noted a difference in the mean age between group I and II to be 34.5 years and 57.7 years, respectively. The mean duration of clinical symptoms for group I was 11 months and 4.1 years for group II.129 In the series of 21 Meckel’s cave meningiomas, Samii and coworkers noted a mean patient age of 46.5 years, with an age range of 17 to 72 years. The average time of onset of symptoms to diagnosis was 3.3 years.127 Tumors of Meckel’s cave are most often associated with dysfunction of the fifth cranial nerve.125 In a study of 12 patients with lesions of Meckel’s cave, of which 4 were meningiomas, Beck and Menezes noted that 9 of 12 (75%) patients presented with CN V deficits. Trigeminal neuralgia was noted in only three patients. Two of these patients were found to have histologically proven meningiomas. Seven of 12 (58%) patients experienced other cranial nerve involvement.125 Not surprisingly, the most

C common symptom of meningiomas located in Meckel’s cave is a deficit of the fifth cranial nerve.129 Typical and atypical trigeminal neuralgia has been noted in approximately 65% of all published cases.126,129 In one large study on meningiomas of Meckel’s cave in 1992, typical or atypical trigeminal neuralgia was noted in 10 of 16 (63%) patients. Cranial nerve impairment was found in 7 of 16 (44%) patients in this series.129 In 1997, Samii and colleagues noted trigeminal nerve impairment as the earliest sign in 15 of 21 (75%) patients, with hearing loss mentioned as the next most common symptom. The authors also reported trigeminal pain and hypesthesia as the main symptoms of types I and III meningiomas.127 In their series in 1975, Nijensohn and coworkers noted that patients in group I described their facial pain as superficial, intense, brief, and paroxysmal—typical symptoms of trigeminal neuralgia. This pain was observed to be limited to some part of the trigeminal nerve distribution. In addition, most of these patients reported trigger points at some time during the course of their disease. Patients in group II reported atypical facial pain that was described as constant, burning, and deeper than that experienced by patients in group I. Patients in group III experienced atypical facial numbness and pain. These patients also had other cranial nerve involvement. One patient had ipsilateral optic atrophy and a decreased sense of smell as well as partial CN III and IV palsies. Another patient experienced hearing loss with intact labyrinthine function.128 In 1967, Kerr proposed that the progressive breakdown of the myelin sheaths due to degenerative changes secondary to tumor growth was the probable cause of trigeminal neuralgia.128 In their series, Beck and coworkers noted that the three patients with facial pain had lesions that extended into the posterior fossa, compressing the root entry zone of the fifth nerve.125 In contrast, patients with tumors that remained confined to the Meckel’s cave had no CN V dysfunction. These findings are in agreement with current theories on the causes of trigeminal neuralgia.

Imaging CT and MRI are the diagnostic modalities of choice for lesions involving Meckel’s cave. Precise information on the size, location, and nature of the lesion may be obtained with the use of CT multiplanar high-resolution imaging. CT is particularly useful for detecting bony changes and

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approach combined with the Kawase approach. In addition to providing good exposure of the tumor and its extensions, this technique reduces retraction of the temporal lobe, vein of Labbé, and cerebellum. Recently introduced preoperative techniques, such as balloon occlusion testing, can help the surgeon assess the collateral circulation in the event that the ipsilateral carotid artery needs to be occluded temporarily for resection of the tumor. In a series of 21 Meckel’s cave meningiomas in 1997, Samii and coworkers varied their surgical approach based on the tumor location and extension. For type I (restricted to Meckel’s cave) and type II (middle fossa extension) meningiomas, the authors used the pterional transsylvian approach. Type III (posterior fossa extension) meningiomas were removed with a suboccipital retrosigmoid approach, and type IV (middle and posterior fossae extension) meningiomas were excised with a combined subtemporalsuboccipital approach.127

Surgical Management

Figure 47-17. T1-weighted gadolinium-enhanced axial MRI scan revealing a meningioma of Meckel’s cave extending toward the posterior aspect of the cavernous sinus.

intratumoral calcification. MRI is useful for identifying tumor invasion into cavernous sinus and for accurately identifying trigeminal nerve compression (Fig. 47-17). Postoperative gadolinium-enhanced MRI images are able to delineate the extent of tumor resection. Delfini and colleagues also believe that cerebral angiography is necessary for detailing the precise anatomic relationship between the tumor and surrounding vascular structures, especially the carotid artery.129

Surgical Approach Small tumors localized to Meckel’s cave may be approached with the subtemporal intradural approach. Delfini and colleagues used this approach in 12 of 16 (75%) patients, the majority of whom had small, globular meningiomas measuring less than 3 cm confined to the posteromedial portion of the middle cranial fossa.129 Compared with the intradural approach, the extradural approach provides the surgeon with a better exposure and reduces the risk of damage to the superficial petrosal nerve damage. However this approach is inadequate for patients with tumor extension into the cavernous sinus (see Fig. 47-17). Delfini and colleagues used a frontotemporal craniotomy followed by a superior or lateral approach to cavernous sinus for tumors involving the cavernous sinus. Tumors with extension into the posterior cranial fossa can be approached with a combined subtemporal-suboccipital approach. Two skull base approaches with excellent exposure include the petrosal approach and the subtemporal

Several factors must be considered prior to the surgical removal of Meckel’s cave meningiomas. These include extension of the tumor into the surrounding structures (especially the CPA and middle fossa), cavernous sinus infiltration, carotid artery encasement, petrous apex erosion, and cranial nerve impairment.127 In a series of 12 Meckel’s cave lesions in 1987, Beck and Menezes noted that although the CN V palsies persisted after surgery, ocular motor muscle palsies were alleviated. Impairment of CN V remained in 9 of 12 (75%) patients, despite complete tumor removal in 11 of 12 (92%) patients.125 In 1975, Nijensohn and coworkers reported that patients in group I had small, friable tumors, which were easily removed and did not recur. These patients also reported complete alleviation of their trigeminal neuralgia after surgical resection of the tumor and a trigeminal sensory rhizotomy.128 In one of the largest series of Meckel’s cave meningiomas, Delfini and colleagues reported a Simpson grade I (macroscopically complete resection of tumor and its dural and bony attachments) removal in 7 of 8 (88%) patients in group I and a grade II removal in the eighth patient. No recurrences were reported, and facial pain was alleviated in all eight patients. In addition, no new neurologic deficits were present postoperatively. In contrast, grade I removal was accomplished in only 1 of 8 (13%) patients in group II. A Simpson grade II (macroscopically complete resection of tumor with endothermy coagulation of its dural attachment) removal was reported in five patients (63%), and a Simpson grade III (macroscopically complete resection of tumor without coagulation of its extensions) removal was noted in two patients (25%). One patient died intraoperatively and another succumbed after recurrence of the meningioma. This difference in outcome was reflective of the large and extensive tumors present in group II patients.129 In the most recent series in 1997, Samii and coworkers reported radical surgical removal in 76% of their patients with complete excision of all type I and III meningiomas. Subtotal resection (Simpson type III or IV ) was noted in the single type II meningioma and 4 of 5 (80%) type IV meningiomas due to cavernous sinus invasion. Facial pain was alleviated in all patients after surgical removal,

Meningiomas of the Posterior Fossa and Skull Base

but trigeminal hypesthesia was resolved in only 35% of patients. Immediate postoperative complications included cranial nerve impairment, hemiparesis, and diplopia.127 Radiotherapy has been used as adjuvant treatment of subtotally resected or unresectable meningiomas of Meckel’s cave. It may also be used in elderly patients with a poor preoperative functional status and short life expectancy who have large tumors with a high risk of operative and postoperative mortality.

JUGULAR FORAMEN MENINGIOMAS Introduction The jugular foramen is a depression on the medial and inferior surface of the petrous bone formed at the interface of the temporal and occipital bones. It measures approximately 15 mm × 10 mm. In two-thirds of cases, the right jugular foramen is larger than the left.130–132 The anteromedial aspect of the foramen is occupied by the inferior petrosal sinus and CN IX, X, and XI. The jugular bulb and internal jugular vein are found in the posterior aspect of the foramen.130,133 Three major tributaries, the inferior petrosal sinus, the condylar vein, and the sigmoid sinus, empty into the jugular bulb.130,133 The sigmoid sinus has a constant drainage pattern into the jugular bulb, whereas the inferior petrosal vein and condylar vein are more variable. The jugular bulb is separated from the carotid artery by a dense fibrous band and a thin plate of bone called the carotid crest. The three most common tumors in the jugular foramen include glomus jugulare tumors (paragangliomas), schwannomas, and meningiomas. Paragangliomas are the most common lesions of the jugular foramen followed by schwannomas of CN IX, X, and XI. Chondrosarcoma, invasive squamous cell carcinoma, chordoma, and metastatic disease from renal or thyroid carcinoma are rarer lesions of the jugular foramen.130,132–134

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Classification Tumors of the jugular foramen may be divided into primary and secondary lesions.133 In a review of 55 lesions of the jugular foramen, Samii and Bini noted that 25 tumors were located in the jugular foramen and were defined as primary tumors, whereas 30 tumors involved the foramen but did not arise from it and were defined as secondary tumors. Two-thirds of secondary tumors were meningiomas.130 Primary intrinsic jugular foramen meningiomas are exceedingly rare lesions that arise from the arachnoid cells located within the jugular foramen associated with the jugular bulb and in close association with the lower cranial nerves (Fig. 47-18).85 These tumors are centered on the jugular foramen and may erode into the hypotympanum, infralabyrinthine temporal bone, and middle ear. Larger primary jugular foramen meningiomas often have simultaneous intracranial or extracranial extensions.133,134 Secondary extrinsic jugular foramen meningiomas are intracranial lesions that can extend to the jugular foramen from above or arise inferiorly in the upper neck (Fig. 47-19).133,135 These lesions are typically large CPA or petroclival meningiomas. Small tumors, however, positioned in the lower clivus or along the medial and inferior portions of the posterior petrous bone may also extend to the jugular foramen directly or by invading and destroying the temporal bone. The degree of jugular foramen involvement may vary from minor tumor invasion to extensive extracranial extension into the neck. Jugular foramen meningiomas may directly invade the internal jugular vein and upper neck and extend through the adjacent occipital bone to the foramen magnum. Meningiomas of the jugular foramen can encase individual cranial nerve filaments and spread into the sheaths surrounding the nerves at the skull base. In contrast, the lower cranial nerves are usually compressed against the surface of glomus jugulare tumors.133,135

IAC

Figure 47-18. A sagittal view of a jugular foramen meningioma with both intracranial and extracranial extension. IAC, internal auditory canal; HC, hypoglossal canal. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

HC

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manifestations were present in three of eight (37%) patients. Molony and coworkers found all their patients were women between the ages of 19 to 52 years, with a mean age of 40 years.134 Similar signs and symptoms were reported in two large series on patients with extracranial meningiomas of the temporal bone. In one such series in 1983, Reitz and colleagues reported hearing loss in 83% of patients. An equal distribution of mixed, conductive, and sensorineural hearing loss was found among these patients. A middle ear mass or changes in the tympanic membrane was found in 74% of patients. Tinnitus and otalgia were noted in 42% of patients. The study also reported facial paresis in 32% of patients and the presence of other cranial neuropathies in only 11%.133,136 In a study of 56 patients with extracranial meningiomas of the temporal bone in 1992, Nassif and coworkers noted that an overwhelming majority of patients (85%) exhibited otologic complaints. Hearing loss was found in 54%. Tinnitus, vertigo, and dizziness were some of the other presenting symptoms.133,137 Figure 47-19. Coronal view of a T1-weighted gadolinium-enhanced MRI scan revealing extension of a posterior fossa meningioma into the jugular foramen.

Clinical Presentation The clinical signs and symptoms of patients with meningiomas of the jugular foramen vary due to their proximity to the lower cranial nerves. Hearing loss, pulsatile tinnitus, hoarseness, and dysphagia have been reported as the most common symptoms for these tumors.131,134,136 In a comprehensive chapter on meningiomas of the jugular foramen, Thompson and Cass reviewed the clinical manifestations for 19 primary jugular foramen meningiomas reported in the literature. Mixed conductive and neurosensory-type hearing loss was reported in 15 of 19 (79%) patients. A visible middle ear mass was noted in 11 of 19 (58%) patients. Tinnitus was noted in 9 of 19 (47%) patients with pulsatile tinnitus present in 5 of 9 (55%). Cranial nerve deficits (V through XII) were noted in 10 of 19 (53%) patients, with CN IX and X neuropathies reported in 5 of 10 (50%) patients each. Six of 19 (32%) patients were reported to suffer from multiple cranial neuropathies.133 Patients with meningiomas of the jugular foramen commonly present with multiple cranial nerve deficits; a combination of CN IX, X, and XI neuropathies is known as Vernet’s syndrome and a combination of neuropathies of CN IX, X, XI, and XII is known as Collet-Sicard syndrome.130,131 Headache, facial pain, visual loss/diplopia, vertigo, and ataxia are additional symptoms noted in patients with jugular foramen meningiomas. In contrast, Thompson and Cass noted that secondary jugular foramen meningiomas were more likely to present with a neurosensory hearing loss, a weak voice, and dysphagia, due to their involvement of multiple cranial nerves. In one of the larger series on jugular foramen meningiomas, Molony and coworkers noted that hearing loss accompanied with a middle ear mass was present in 7 of 8 (88%) patients. Six of eight (75%) patients complained of tinnitus, which was pulsatile in four. Lower cranial nerve

Diagnosis A preoperative histologic diagnosis is usually not obtained due to the relative inaccessibility of the jugular foramen region. However, a detailed radiologic study of a suspected lesion in the jugular foramen is necessary to suggest a diagnosis, determine the extent of the disease, and formulate a therapeutic strategy. CT, MRI, and angiography are the primary diagnostic modalities for assessing meningiomas of the jugular foramen. The characteristic findings of meningiomas on CT, MRI, and angiography have been previously described. High-resolution CT images with bone detail in multiple planes are required to adequately visualize meningiomas of the temporal bone. Mild hyperostosis and destruction of bone may be seen well beyond the cortex of the jugular foramen, given the propensity of these meningiomas to spread locally. In contrast, glomus jugulare tumors exhibit far greater bony changes, typically in the form of irregular bony destruction of the jugular fossa. When these changes are present on CT, the surrounding bone is commonly described as looking “moth-eaten.” The difference in the degree of bone destruction may help to differentiate between these two tumors. The intense signal enhancement of the jugular bulb on postinfusion images sometimes prevents identification of the jugular foramen meningiomas. However, meningiomas with significant intratympanic or extracranial extension can be easily discovered with enhancement.133 MRI remains the preferred imaging modality for detecting intracranial and extracranial extension of jugular foramen meningiomas. Identifying tumor extension into the nose, nasopharynx, paranasal sinuses, middle ear, mastoid, parapharyngeal space, infratemporal fossa, and cervical region is important in the preoperative evaluation of the tumor. Angiography with preoperative embolization may be considered for a highly vascular jugular foramen meningioma. When a meningioma is limited only to the jugular foramen, it may not be easily visible with angiography. Angiography, however, may be useful for differentiating meningiomas from glomus jugulare tumors, which demonstrate an intense arterial flow with early venous

Meningiomas of the Posterior Fossa and Skull Base

return.133 Preoperative embolization is used to prevent excessive blood loss for highly vascular lesions.134 Given the presence of otologic symptoms in a majority of patients with jugular foramen meningiomas, audiometry is often performed to determine the type and degree of hearing loss. Conductive hearing loss suggests involvement of the ossicular chain or the tympanic membrane, whereas sensorineural hearing loss suggests involvement of the otic capsule structures, CN VIII, or the brainstem. The precise involvement is important when considering hearing preservation surgery. Auditory brainstem evoked potentials may also be useful for revealing vestibulocochlear involvement. Vestibular testing is usually not performed due to the frequent absence of vertigo in patients with jugular foramen meningiomas. However, vocal cord function, laryngeal and pharyngeal sensation, and swallowing function should be evaluated in all patients with a lesion of the jugular foramen.133 In a comprehensive review of 34 jugular foramen meningiomas, Lustig and Jackler noted a preoperative dysfunction of the lower cranial nerves in approximately 35% of cases (CN IX 38%, CN X 41%, CN XI 32%, CN XII 35%).135

Surgical Approach The surgical approach is primarily determined by the tumor location and extent of disease. The approach may be modified based on the size of the lesion, the likelihood of total resection, and possibility of cranial nerve preservation. Jugular foramen meningiomas with a significant intracranial component must be approached with an intracranial approach. A suboccipital craniotomy provides an excellent exposure to the CPA and jugular foramen. Limited intracranial extension may be addressed with a retrolabyrinthine approach. If the patient has a profound sensorineural hearing loss secondary to a sizable intracranial tumor component, hearing ablation surgery is justified, and the tumor may be managed with a translabyrinthine approach. The transcochlear approach can be used for large anteriorly based meningiomas, which require a wider exposure. Meningiomas extending to the foramen magnum may be approached with a far or extreme lateral approach necessary for exposure of the tumor as well as adequate control of the vertebral artery (Figs. 47-20 and 47-21). Jugular foramen meningiomas extending anteriorly may be approached with a subtemporal-infratemporal approach combined with a transjugular approach. This is necessary to ensure adequate tumor exposure as well as control of the carotid artery. Meningiomas with an extensive intracranial component as well as temporal bone invasion may be approached with a complete petrosectomy and may result in a greater likelihood of complete tumor removal and a decreased chance of recurrence.133 An infratemporal fossa or transpetrosal approach with a transdural extension may also be used for resection of jugular foramen meningiomas. Molony and colleagues used this approach in a majority of their patients to obtain exposure of the lesion and its origin in the jugular bulb. The juxtacondylar approach, which provides an inferior and posterior access to the jugular foramen, may be used to complement the

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infratemporal approach to provide a large exposure of the tumor.130,133,134,138

Surgical Management As with the treatment of all meningiomas, complete surgical excision of jugular foramen meningiomas is preferred. This is difficult given the propensity of these lesions to infiltrate into the surrounding bone and encase the neurovasculature. Wide surgical margins are also required to prevent tumor progression and recurrence. Subtotal resection, however, is often necessary, especially if involvement of the local cranial nerves has occurred. Preservation is especially important if only mild cranial nerve dysfunction is present prior to surgery, given the risk of severe morbidity with surgical procedures attempting complete resection in this region. Aggressive surgical excision of the tumor may be performed if severe cranial dysfunction is present preoperatively.134 Elderly patients with increasing symptoms accompanied by evidence of tumor progression combined with a poor preoperative functional status and a short life expectancy may be treated with radiation therapy. Stereotactic radiation therapy may also be used for patients who fail surgical resection of the tumor. Multiple cranial nerve deficits have been reported following the surgical removal of jugular foramen meningiomas. The tumor location, degree of neurovasculature

Figure 47-20. The skin incision used for the far lateral approach begins above the ear, extends inferiorly in the postauricular region before turning to the midline over the posterior processes of the vertebral bodies. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

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Figure 47-21. A view of the bony exposure of the far lateral approach. The posterior aspect of the sigmoid sinus defines the anterior superior border of the suboccipital craniectomy. Drilling is performed down to the region of the occipital condyle and in this example a C1 and C2 laminectomy have been performed. JV, jugular vein; VA, vertebral artery. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

JV

VA

encasement, infiltration of the lesion, and extent of resection influence the morbidity associated with surgical excision. In a review of 25 patients with jugular foramen meningiomas, Thompson and Cass in 1996 reported the following postoperative cranial nerve neuropathies: CN X in 14 of 25 (56%) patients, CN IX in 13 of 25 (52%), CN XI in 7 of 25 (28%), CN XII in 7 of 25 (28%), and CN VII in 6 of 25 (24%). CSF leaks were reported in 3 of 25 (12%) patients, and hemiparesis was noted in 1 patient (4%).133 The complex relationship between the tumor and the local nerves and vessels in the jugular foramen makes the surgical resection of tumors in this region particularly challenging. Within the jugular foramen, tumors may originate laterally with the jugular vein and bulb, medial to the inferior petrosal sinus, or centrally along the fibroosseous partition on which the cranial nerves lie. Lustig and Jackler noted a unique and consistent relationship between the neurovasculature and each of the three most common tumors of the jugular foramen, namely, glomus jugulare (paragangliomas), schwannomas, and meningiomas. Knowledge of the jugular foramen anatomy combined with characteristic tumor growth patterns help the surgeon assess the risk of cranial nerve injury and accordingly plan the degree of tumor resection leading to the best possible functional outcome.135 Meningiomas are much more variable in their relationship to the lower cranial nerves and vasculature in the jugular foramen than glomus tumors. Meningiomas originating in the lateral aspect of the jugular foramen lend themselves to excellent neural preservation since the tumor lies between the surgeon and cranial nerves. In addition these tumors also occlude the jugulosigmoid

venous complex early in their growth. Complete excision of meningiomas arising in the medial aspect of the jugular foramen are associated with a high risk of CN IX, X, and XI injury.135 Meningiomas deeply penetrating the dural envelope of the jugular foramen, however, are always associated with a high risk of injury to the cranial nerves, regardless of their origin. Sudden injury to CN X may leave the patient with an incompetent larynx and require that the patient undergo a tracheostomy and gastrostomy for airway protection and nutrition.

FORAMEN MAGNUM MENINGIOMAS Introduction The foramen magnum lies within the occipital bone. Multiple structures lie in close proximity to this foramen, including the caudal medulla, rostral spinal cord, cerebellar tonsils, inferior vermis, fourth ventricle, and the lower cranial and upper cervical nerves. The spinal cord is attached to the lateral dura by the dentate ligaments, the most rostral of which serves as an important landmark in the surgery of tumors of the foramen magnum. The lateral aspect of this ligament is in close association with the vertebral artery where it enters the dura with the posterior spinal artery and dorsal root of C1. After entering the dura, the vertebral artery gives rise to the posterior inferior cerebellar artery (PICA) superior to the foramen magnum. The vertebral artery continues superiorly to merge with the contralateral vertebral artery to form the basilar artery.139,140

Meningiomas of the Posterior Fossa and Skull Base

The lower cranial nerves arise from the anterolateral medulla and spinal cord. These nerves are usually affected by tumors of the foramen magnum since they lie in close proximity to this region. Cranial nerves IX through XI arise as rootlets from the anterior medulla and spinal cord and exit the skull base though the jugular foramen. A contribution to CN XI passes through the foramen magnum from C2.139,140

Epidemiology Meningiomas represent the majority of tumors originating at the foramen magnum, yet they are exceedingly rare lesions. In 1953, in a review of Olivecorona’s series of posterior fossa meningiomas, Castellano and Ruggerio noted only three foramen magnum meningiomas.72 In 1971, Lecuire and Dechaume studied a series of 240 posterior fossa meningiomas, only 20 of which were foramen magnum meningiomas.82 In 1980, Yasargil and Mortara reported only three foramen magnum meningiomas in a large series of posterior fossa meningiomas.74 In a chapter review of multiple series of foramen magnum meningiomas in 1991, Scott and Rhoton found these tumors to account for approximately 1.8% of all intracranial meningiomas, 6% to 7% of all posterior fossa meningiomas, and 8% to 9% of all spinal meningiomas.139 A more recent paper by Pirotte and coworkers in 1998 reported that foramen magnum meningiomas account for 0.2% of all intracranial tumors, 1% of all intracranial meningiomas, and 5% of posterior fossa meningiomas.141 Meningiomas represent approximately 70% of all benign tumors arising from the foramen magnum and are the most common tumor entity at this location.140,142 Akin to all other intracranial meningiomas, foramen magnum meningiomas are more common in females than in males. Multiple series have noted a female-to-male ratio of approximately 2:1 to 3.6:1.140 Although the age at presentation varies from the fourth to the sixth decade, the age range ranges from 4 to 88 years.140 Meyer and colleagues reported patients’ ages to range from 12 to 81 years, with an average of 49 years. The average interval from the first symptoms to diagnosis was between 2.5 to 4 years in most series.143

History and Classification In 1929, Elsberg and Strauss reported the first successful removal of a foramen magnum meningioma in a 36-year-old patient with Brown-Sequard syndrome.140 In 1938, Cushing and Eisenhardt defined foramen magnum meningiomas as those tumors located on the margin of the foramen magnum.3 Castellano and Ruggerio defined them as tumors involving the lower third of the clivus.72 Cushing and Eisenhardt divided foramen magnum tumors into two anatomic groups: craniospinal and spinocranial. Craniospinal meningiomas arise in the basilar groove anterior or anterolateral to the spinal cord projecting inferiorly to the foramen magnum. Spinocranial meningiomas originate posterior or posterolateral to the medulla and projecting superiorly to the cerebellar cistern. The authors made this distinction primarily based on the clinical presentation and on the difficulty of surgical excision.3,140 In

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1941, Dandy agreed with the classification and felt that it was important for planning an operative approach.139 In 1953, Castellano and Ruggerio proposed their classification of posterior fossa meningiomas based on their site of dural attachment. Given this criterion, only meningiomas arising from the foramen magnum were considered foramen magnum meningiomas, not meningiomas arising elsewhere that extended through the foramen magnum.72 Recent authors have proposed that all meningiomas passing through the foramen magnum be classified as foramen magnum meningiomas.139 Comparing outcomes between series of foramen magnum meningiomas has been difficult, given their scarcity as well as wide variations in their classification.

Clinical Presentation A wide range of clinical signs and symptoms have been observed for patients with foramen magnum meningiomas. In 1953, Castellano and Ruggerio stated that “the possibility of a meningioma of the foramen magnum should always be considered in the presence of a capricious clinical history with long remissions and illogicalness.”72 In a series of 102 benign extramedullary tumors of the foramen magnum, Meyer and colleagues found that 40% of patients had a normal neurologic exam at initial evaluation.143 The clinical presentation of these tumors has frequently simulated and been diagnosed as cervical spondylosis, multiple sclerosis, demyelinating disease, several degenerative diseases, and even occasionally hysteria.140 A high degree of suspicion is required to make the diagnosis of a meningioma before the tumor has grown to cause significant impingement of the neural axis. In a study of 16 benign extramedullary tumors of the foramen magnum, half of which were meningiomas, Akalan and coworkers reported that only five cases were diagnosed within 6 months of their initial symptoms. Patients with symptoms that began at least a year before admission had multiple incorrect diagnoses prior to their final diagnosis and appropriate treatment.144 Initially, patients often complain of a deep, aching pain in the suboccipital and cervical regions. This pain is often exacerbated by neck movement, coughing, and straining. This symptom is thought to result from tumor involvement of the first three cervical nerves, which innervate the dura covering the anterior aspect of the posterior fossa.139,140 Several sensory and motor deficits develop with an increasing growth of the tumor. The deficits often simulate the relapsing-remitting pattern of multiple sclerosis and therefore are very difficult to diagnose. Cold or burning dysthesias have been described as some of the most common sensory changes in patients with foramen magnum meningiomas. These dysthesias often progress to hypesthesias, diminished temperature sensation, and loss of tactile or position sense. Trigeminal sensory loss in an “onionskin” pattern, hyperesthesia, and trigeminal neuralgia have also been reported as signs of foramen magnum meningiomas.139 Progressive spastic quadriparesis or asymmetrical pyramidal quadriparesis has been described as a common clinical presentation in patients with foramen magnum meningiomas. This symptomatology begins with weakness

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and spasticity in the arm, progressing to the ipsilateral leg, followed by the contralateral leg, and then the arm. This pattern of quadriparesis is observed with anterolaterally growing lesions and has been noted to be more severe on the ipsilateral side. Atrophy and weakness of the sternocleidomastoid and trapezius muscles due to involvement of the spinal accessory nerve have been noted in 25% to 44% of patients.140 Atrophy of the distal upper extremity and intrinsic hand muscles has also been noted in these patients secondary to venous outflow obstruction and subsequent infarction of the spinal cord.140 In cases in which the tumor has progressed to large dimensions, compression of the medulla has resulted in development of a spastic or ataxic gait, sphincter disturbances, and respiratory dysfunction. Patients with foramen magnum meningiomas also exhibit slow and athetotic-like movements of their arms, hands, and particularly fingers when they close their eyes and hold their arms outstretched. This phenomenon, also known as “piano-playing fingers” has been reported in as many as a third of patients with extramedullary foramen magnum tumors.145 In conclusion, signs and symptoms of foramen magnum meningiomas include unilateral neck pain aggravated by coughing, Lhermitte’s sign in the absence of multiple sclerosis, CN XI dysfunction, sensory dyesthesias, progression of motor and sensory deficits, and atrophy of intrinsic hand muscles.130

A

Diagnosis CT and MRI are the primary modalities for diagnosing foramen magnum meningiomas as well as determining their size, extent, and neurovascular involvement. Guidetti and Spallone found the overall diagnostic accuracy of CT without intrathecal contrast to approach 75%.145 In a series of 102 benign extramedullary tumors of the foramen magnum, including meningiomas, Meyer and colleagues found CT with IV contrast to be diagnostic in 75% and suggestive in another 20% of these tumors.143 MRI, however, is widely considered to be the superior noninvasive imaging modality. MRI provides better delineation of the tumor relationship to the surrounding structures, especially the brainstem, upper spinal cord, and neurovasculature (Fig. 47-22).146,147 MRI also aids in providing a better definition of the surrounding vasculature as well as excluding aneurysms of the vertebral artery and its branches. The absence of bony artifacts on MRI also provide a better delineation of the tumor.146 Angiography is useful for revealing the vascular supply to the tumor and defining the position of major vessels surrounding or intimately involving the tumor. These vessels include the anterior spinal artery, posterior spinal artery, PICA, and vertebral artery. Preoperative embolization may be used to decrease the risk of severe intraoperative hemorrhage of highly vascular meningiomas. Angiography is also helpful in elucidating the venous drainage pattern and the dominance and degree of venous involvement by the tumor. This is especially important if sacrifice of the sigmoid sinus or jugular vein is considered necessary intraoperatively.139,140 Angiography may also exclude the possibility of an aneurysm in the posterior circulation.139

B Figure 47-22. A, Coronal T1-weighted gadolinium-enhanced MRI scan revealing a large foramen magnum meningioma compressing the medulla and spinal cord. B, Sagittal view.

Surgical Approach The displacement of the medulla and spinal cord, superior-inferior extent of the tumor, size of the tumor, and size of the dural attachment are all considered in determining the optimal approach for resecting foramen magnum meningiomas. A large number of approaches are designed to access the anterior rim of the foramen magnum by removing functionally less important portions of the skull base.148 Only 20% of these lesions occur posteriorly or posterolaterally. The most common location of these tumors is anterolaterally in the foramen magnum. Anterior routes, such as the transoral and transcervical routes, as well as posterior routes via the suboccipital and retrosigmoid approaches have been taken to resect meningiomas of the foramen magnum.140

Meningiomas of the Posterior Fossa and Skull Base

Preliminary results for the transcervical and transoral approaches were dismal due to injury of the lower cranial nerves and brainstem during tumor removal, resulting in a poor functional outcome for the patient. Although large anterior or anterolaterally located tumors that displace the brainstem may provide enough room for excision of a tumor through posterior routes, the outcomes with these approaches have also been disappointing. The far and extreme lateral approaches were designed through modifications of the posterior approaches to obtain a better exposure for anteriorly placed lesions. These approaches have had better success at visualization of the foramen magnum and may be combined with a variety of transpetrosal approaches (Fig. 47-23).140,149 Some authors have also proposed the use of a dorsolateral transcondylar approach for ventral or ventrolateral meningiomas of the foramen magnum with little or no additional neurologic impairment or craniospinal instability.148,150 In a recent paper studying the role of occipital condyle resection in the far lateral approach, Nanda and coworkers found that this was not necessary for the safe and total resection of anterior intradural foramen magnum meningiomas.151 In a recent report on 17 foramen magnum meningiomas, Goel and colleagues took a conventional posterior suboccipital approach with a midline incision and extension of the craniectomy laterally toward the side of the tumor. With a tumor size ranging from 2.1 to 3.8 cm, and a majority of lesions displacing the brainstem posteriorly, complete tumor resection was achieved in 14 of 17 (82%) patients and a subtotal resection was performed in the other 3. No significant postoperative complications occurred in the majority of patients, with an average followup of 43 months. The authors concluded that a majority

of foramen magnum meningiomas can be resected with a lateral suboccipital approach with microsurgical techniques.142

Surgical Results Dismal results have been reported for the surgical resection of foramen magnum meningiomas. In several early series multiple lower cranial nerve deficits and brainstem injuries were reported for the surgical excision of foramen magnum meningiomas. These patients were often left with severe postoperative deficits, including labile hypertension, aspiration, and respiratory arrest.139,140 Patients who survived surgery were often left with brainstem and lower cranial nerve deficits that often required a tracheostomy and feeding gastrostomy. In a chapter review on foramen magnum meningiomas in 1991, George reported an overall mortality rate of 13% for 161 foramen magnum tumors. Approximately 68% of patients had good results, 10% had fair results, and 9% had poor results.146 In one of the earliest series of 74 foramen magnum meningiomas in 1941, Love and coworkers reported 34 perioperative deaths due to complications.152 In 1980, Yasargil and Mortara reported an overall mortality rate of 13.2% for these meningiomas in a review of 114 surgically treated cases. The overall neurologic outcome was described as good in 79 of 114 (69.3%) patients, fair in 9 of 114 (7.9%), and poor in 11 of 114 (9.6%).74 In 1988, Guidetti and Spallone also noted an operative mortality rate of 11%.139 In a series of 102 benign intradural extramedullary foramen magnum tumors in 1984, Meyer and colleagues reported an operative mortality rate of 5% and a 5% mortality rate from recurrence within 3 years.

FM C1 C C1

C2 O

827

Figure 47-23. A sagittal view of the region of the foramen magnum. Posterior foramen magnum tumors are directly accessible from a posterior approach, whereas anterior foramen magnum tumors that are intradural are best accessed through a far lateral approach. A, anterior; C, clivus; FM, foramen magnum; O, odontoid; P, posterior. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

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Results were excellent in 75% of patients, mildly impaired in 12%, and poor in 13%.143 In a recent series of 40 foramen magnum meningiomas in 1996, George and coworkers achieved complete removal (Simpson grade I or II) in 86% of these lesions and 94% of intradural tumors. The posterolateral approach was used in 31 of 40 (78%) patients. Subtotal resection (Simpson grade III) was accomplished in 11% of cases. Significant intradural extension and bony invasion were the primary reasons for an incomplete resection.153 Clinical improvement, defined by the authors as a better postoperative than preoperative functional status was reported in 90% of patients, with worsening noted in 7.5% of patients. Three patients died as a result of surgery, and no recurrences were noted with a mean follow-up of 4.8 years.153 In another recent series of 40 craniocervical junction meningiomas in 1996, Samii and colleagues reported complete removal in 63% and subtotal removal in 30% of patients. The authors noted that an intracranial origin, infiltrative or en plaque growth, and encasement of the vertebral artery were independent predictors of incomplete tumor removal.154 Complications from surgery were reported in 30% of patients. Postoperative tracheostomies were necessary in four patients, and gastrostomies were required in three. Aspiration secondary to lower cranial nerve dysfunction was noted in four patients, two of whom died after developing pneumonia, resulting in an overall mortality of 6%.154 Other complications included transient worsening of caudal cranial nerve function, facial nerve palsies, and temporary gait ataxia. Three recurrences were reported in this series, two of which were noted in patients 8 years after an incomplete removal of meningiomas. Although preoperative cranial nerve deficits remained postoperatively, sensory changes, dysesthesias, pain, and gait ataxia improved during the first year following surgery. The average Karnofsky score also improved from 63 ± 17 to 73 ± 12 after surgery.154

HEARING PRESERVATION Hearing preservation after the surgical removal of a CPA meningioma has been reported in multiple series to vary between 33% and 100%.41,92,137,155–159 The variation in the rate of hearing preservation is due to the unpredictability of the tumor site in the CPA, the different degrees of auditory nerve involvement as well as the scarcity of literature on hearing preservation, and the inadequate reporting of preoperative and postoperative audiometric data.92,137 In addition, the absence of a universal classification scheme and specific inclusion criteria for hearing results has made

the collection and analysis of hearing preservation data particularly difficult. The Committee on Hearing and Equilibrium guidelines of the American Academy of Otolaryngology has established a classification system by which preoperative and postoperative audiometric data can be reported (Table 47-7). This classification scheme is similar to one proposed by Shelton and Hitselberger in 1991. Class A hearing is defined as socially useful hearing with a PTA (500 Hz and 1, 2, and 4 kHz) of less than 30 dB and an SDS of greater than 70%. Class B is described as serviceable hearing with a PTA of less than 50 dB and an SDS of greater than 50%. Class C hearing is defined as any measurable hearing loss, and class D hearing is equivalent to the absence of any measurable hearing.158 In a series studying the preoperative and postoperative auditory function in patients with CPA meningiomas, Schaller and coworkers proposed a slightly different classification system: Classes I and II correspond exactly to classes A and B of the prior classification scheme. Class III was more specifically defined as a PTA between 51 dB and 90 dB and an SDS between 5% and 49%. Class IV was described as a PTA ranging from 91 dB to 100 dB with an SDS between 1% to 4%. Class V was defined as a PTA and SDS with no response, corresponding to class D. The combination of classes III and IV hearing corresponds to class C.92 Hearing classification schemes have been used by some authors and not by others. Samii and colleagues in 1985, reported measurable hearing in 11 of 15 (73%) patients postoperatively, but they provided no information regarding the quality of the postoperative hearing.62 In a series of 12 patients in 1992, Nassif and coworkers reported an overall hearing preservation in 11 of 12 (92%) patients, with 8 of 12 (67%) patients retaining class A or B hearing.137 Approximately 75% of patients in this series preserved their preoperative hearing after the surgical excision of a CPA meningioma.137 In 1995, Schaller and colleagues also reported favorable hearing preservation data in their series of 13 patients. The authors reported total hearing preservation in 9 of 13 (69%) patients, with 100% of patients maintaining a class A or B level of hearing postoperatively.92 Like Nassif and colleagues,137 Schaller and colleagues92 also reported a similar percentage (69%) for preservation of preoperative hearing. In 1996, in a study of 16 patients, Grey and coworkers reported a hearing preservation in 8 of 16 (50%) patients. However, if serviceable hearing or better (class A or B) was present preoperatively, 8 of 11 (73%) patients achieved preservation of their hearing. Class A hearing, or socially useful hearing, was maintained in 6 of 9 (67%) cases.158 In the most recent study by Batra and coworkers in 2002, hearing preservation was attained in 10 of 11 (91%) patients, and 9 of

TABLE 47-7. Hearing Classification of the American Academy of Otolaryngology Hearing Class

Description

Pure Tone Average (PTA)

Speech Discrimination Score (SDS)

Class A Class B Class C Class D

Good Serviceable Measurable “Dead ear”

PTA ≤ 30 dB PTA ≤ 50 dB

SDS ≥ 70% SDS ≥ 50% Any measurable hearing loss Absence of any measurable hearing

PTA, average of 500 Hz and 1, 2, 4 kHz.

Meningiomas of the Posterior Fossa and Skull Base

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TABLE 47-8. Hearing Preservation for CPA Meningiomas—Series (1982–2002) Preoperative Hearing Author

Year

Total

Laird et al.41 Nedzelski and Tator155 Samii et al.62 Nassif et al.137 Cohen et al.156 Prasad et al.157 Schaller et al.92 Grey et al.150 Batra et al.159

1982 1984 1985 1992 1993 1993 1995 1996 2002

18 3 15 12 8 3 13 16 11

Class A + B

12 2 8 11 10

10 (90%) achieved a class A hearing status after surgery (Table 47-8).159 None of the patients in these studies experienced an improvement in hearing after surgery except those in Schaller and colleagues’s study, who reported an improvement in 2 of 13 (15%) patients.92 The ability to preserve hearing is based on multiple factors: the level of preoperative hearing, quality of hearing in the contralateral ear, location of the tumor, extent of cochleovestibular nerve involvement, size of the tumor, age, and general health of the patient.158,160 Hearing preservation surgery is usually performed via the suboccipital/retrosigmoid, petrosal, middle fossa, extended middle fossa approach, or the petrosal approach (Figs. 47-24, 47-25, and 47-26).155 The retrosigmoid approach provides

Figure 47-24. Surgeon’s view of the floor of the middle cranial fossa. The temporal lobe dura has been retracted, and the superior petrosal sinus can be seen medially. The triangle region over the internal auditory canal designates a safe region of drilling where the superior semicircular canal posteriorly and the basal turn of the cochlea anteriorly would not be entered. The wide anterior posterior identification of the internal auditory canal can be performed medially at the level of the porus acousticus. Drilling should be performed directly over the internal auditory canal when progressing medially to laterally to avoid entering the otic capsule structures. Also note a quadrangular region anteriorly known as Kawase’s quadrangle of the petrous apex. Drilling in this quadrangle allows for the exposure of the ventral portion of the cerebellopontine angle and posterior fossa. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

Postoperative Hearing Total 6 3 11 11 3 1 9 8 10

Class A + B

8 1 8 8 9

Hearing Preservation Total 33% 100% 73% 92% 38% 33% 69% 50% 91%

Class A + B

67% 50% 100% 73% 90%

a wide exposure for the removal of posteriorly but not anteriorly based meningiomas. The middle fossa approach allows for resection of tumors in the IAC as well as the middle cranial fossa. Anteriorly located lesions as well as meningiomas with a significant component in the CPA can be resected with an extended middle fossa approach. Grey and coworkers reported that 6 of the 16 patients required additional exposure with the retrolabyrinthine and middle cranial fossa approaches. Although this indicated the increased size of the tumors and the difficulty encountered in their removal, four of the six patients (66%) retained their preoperative hearing. The authors suggest that additional bony removal did not result in a significant loss of auditory function.158 Maurer and Okawara recommended a suboccipital/retrosigmoid craniotomy to maximize the possibility of hearing preservation.59 Maniglia and coworkers also suggested the use of the suboccipital approach if patients with a preoperative hearing loss were to have a chance of hearing preservation or full restoration.60 Hearing ablative surgery, on the other hand, is performed through the translabyrinthine and transcochlear approaches in patients with nonserviceable hearing. The location of a meningioma has been shown to be the most important determinant in the preservation of hearing. A comparison between retromeatal (posterior to the IAC) and premeatal (anterior to the IAC) meningiomas in several studies showed that the prognosis for hearing preservation is markedly worse when the tumor rests medial to the porus acousticus.57,158 Schaller and colleagues noted a difference in the clinical presentation as well as surgical approach, operative resection, and morbidity and mortality of premeatal versus retromeatal meningiomas.92,161 The authors reported a preservation of class I (class A) hearing in four of six (66%) patients with retromeatal meningiomas. In contrast, all the patients with premeatal tumors had a class IV or V hearing preoperatively.92 The authors considered these patients as having nonserviceable hearing preoperatively and therefore excluded them from being considered for hearing preservation surgery. In the series by Batra and coworkers, hearing preservation surgery was attempted in 10 patients with retromeatal tumors. Class A hearing was preserved in eight of nine (90%) patients, with one patient relegated to class B hearing. Another patient with a class B hearing achieved a class C hearing status postoperatively. Ten of the 11 patients with premeatal tumors did not have serviceable hearing preoperatively, and therefore hearing preservation surgery was

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Figure 47-25. The surgeon’s view of a transtentorial combined middle and posterior fossa anterosigmoid petrosal approach. The vestibular apparatus has been kept intact. The superior petrosal sinus has been divided, exposing a combined view of the cerebellopontine angle and the middle cranial fossa floor. The inferior aspect of the dissection is the region of the jugular bulb. The trochlear nerve and trigeminal nerve are well visualized superiorly. The brainstem can be accessed over a large area. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

VL

VL

Figure 47-26. The petrosal approach may be further enlarged by resecting the bone of the middle fossa floor primarily in Kawase’s quadrangle. This is still a hearing conservation approach as the cochlea, labyrinthine apparatus, and the internal auditory canal are kept intact. (Used with permission from Jackler RK: Atlas of Neurotology and Skull Base Surgery. Philadelphia, Mosby, 1996.)

not attempted in these individuals. Only one patient with a premeatal tumor with class A hearing retained a similar level of auditory function postoperatively.159 The explanation offered for the difference in the hearing preservation between premeatal and retromeatal meningiomas is the hindrance of the CN VII–VIII complex in the line of dissection. Given this intimate relationship, stretch or inadvertent damage to these nerves may occur even in the hands of the most experienced surgeons as the premeatal meningiomas displace the facial-cochlear nerve complex posteriorly.92,161 Grey and coworkers also agreed that stretching of nerves during dissection of the tumor could lead to worse hearing preservation for tumors anteromedial to the IAM.158 In contrast, retromeatal tumors are typically separated from the nerves by an arachnoid layer and therefore are less likely to invade or compress the neurovascular structures of the IAC (Fig. 47-27). Since a good tissue plane can usually be found between retromeatal tumors and the CN VII–VIII nerve bundle, and since the tumor is not obstructed by these cranial nerves, a favorable outcome is expected.57,92 Multiple studies have shown that the size of a CPA meningioma does not appear to affect the preservation of hearing after surgical removal.92,158,159 In a study of 16 patients, Grey and coworkers reported that although two of three patients (66%) with meningiomas less than 2.5 cm retained their preoperative hearing classification, only 6 of 13 patients (46%) with meningiomas greater than 2.5 cm did the same. Although this may seem like a noteworthy difference, the authors did not find this result to be statistically significant (p = 0.54, Mann-Whitney U test).158 Schaller and colleagues also did not find an association between tumor size and preservation of preoperative hearing. In their study

Meningiomas of the Posterior Fossa and Skull Base

Figure 47-27. Axial T1-weighted gadolinium-enhanced MRI scan revealing a large posterior petrous face meningioma, which is posterior to the cranial nerves. Despite the size of this tumor, it is easily accessible since arachnoid planes separate the anterior portion of the tumor from the left-sided posterior fossa cranial nerves.

of 13 patients, all 3 patients with meningiomas less than 2 cm and the 1 patient with a tumor between 2 cm and 3 cm retained their preoperative hearing classification. In contrast, only six of nine patients (66%) with meningiomas larger than 3 cm maintained their preoperative hearing status.92 However, this difference also did not achieve statistical significance. Multiple authors including Nassif and coworkers have not found any relationship between hearing preservation and the size of the a CPA meningioma.137 Several investigators have also studied the effect of tumor extension into the IAC and hearing status. Grey and coworkers discovered that the likelihood of having class D hearing preoperatively was directly related to the presence of tumor in the IAC. If tumor involvement was present in the IAC, the chance of profound hearing loss was 45% versus 5% if no involvement was present.158 The authors noted that the preoperative hearing class was maintained in 2 of 3 (66%) cases when the meningioma occupied the IAC, 1 of 3 cases when the tumor entered the porus acousticus, and 5 of 10 cases when the tumor did not enter the IAC. In agreement with the data presented by Grey and coworkers, Schaller and colleagues also demonstrated that extensive tumor infiltration in the IAC is associated with class D hearing.92 Furthermore, they found that the amount of tumor in the IAC does not necessarily correlate with the presence of hearing. The authors proposed that tumor involvement of the IAC may be an “all or none”

831

phenomenon when total hearing loss may be caused by a small nidus of tumor resulting in vascular compromise.92,158 Batra and coworkers reported six of eight (75%) patients with purely extracanalicular tumors to have class A hearing postoperatively. In the same series, three patients had intracanalicular tumors, but all of them retained their class A hearing postoperatively.159 Dramatic improvements in patients with poor preoperative hearing have been reported after removal of CPA meningiomas.59,60,92,155,160,162,163 In 1950, Baker and Christoferson reported the first case of a 44-year-old female who experienced a return to normal hearing after removal of a CPA meningioma despite a completely dysfunctional acoustic nerve for more than 2 years.164 Maurer and Okawara recently reported the case of a 32-year-old female who presented with a 1-year history of deafness in her right ear. Audiometry demonstrated a profound retrocochlear hearing loss, and CT showed a 3.2-cm enhancing lesion of the right CPA. The authors used a suboccipital approach to remove the lesion, which was confirmed to be a meningioma on histopathology. By the seventh postoperative day, the patient was routinely using her right ear for telephone conversations. Audiometry revealed a normal hearing threshold with an SDS of 100%.59 Similar case reports have been found in the literature. Goebel and Vollmer reported yet another case of hearing improvement of 10 dB in speech reception threshold (SRT) and a remarkable return of SDS from 0% to 86%.160 Nedzelski and Tator reported similar preoperative and postoperative hearing results for all three of their patients with CPA meningiomas. In particular, they described a dramatic hearing improvement in one patient 6 months after surgery.155 Magnilia also reported preservation or improvement in hearing in 3 of 14 (21%) patients who had experienced some preoperative hearing loss.60 Schaller and his colleagues, who recommended not pursuing a hearing preservation approach for patients with less than a class A hearing status, themselves reported an improvement in postoperative hearing in two (15%) of their patients with a poor preoperative hearing status.92 Goebel and Vollmer mention that even when patients have poor preoperative auditory function, a hearing preservation approach should be attempted.160 Maurer and Okawara go so far as to rule out the use of a translabyrinthine approach given the possibility of hearing preservation.59 In a study of CPA meningiomas in 2000, Voss and coworkers suggested that a retromeatal meningioma, with minimal IAC involvement, and absence of inner ear invasion on temporal bone CT scans should prompt hearing preservation surgery despite a poor preoperative hearing status.79 Although several authors agree in part with this assessment, Batra and coworkers correctly point out that more data are required before hearing conservation surgery can be recommended for all patients regardless of their preoperative hearing loss.159 Two theories have been offered for the cause of vestibulocochlear dysfunction even in the presence of an anatomically preserved CN VIII. Vascular compromise of the labyrinth or the nerves themselves is believed to be the most likely cause of auditory and vestibular dysfunction.158 Intraoperatively, the vascular compromise is thought to result from a spasm of the labyrinthine arteries induced by mechanical irritation of the neurovascular bundle or

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SURGICAL NEUROTOLOGY

coagulation of the labyrinthine vessels in the event of a persistently bleeding tumor.92 Belal and coworkers presented evidence that postoperative hearing loss was due to compromise in vascular supply. Stretching and trauma to the nerve have also been postulated to play a lesser role in the loss of function.158 The use of evoked otoacoustic emissions may help to differentiate between the above-mentioned causes of CN VIII dysfunction since emission loss is encountered only with disruption of vascular supply to the cochlea and not retrocochlear nerve damage. Grey and coworkers reported that only one of their patients with class D hearing had evoked emissions preoperatively, and so attributed the profound hearing loss to vascular compromise in the rest of their patients.158 Recent reports have shown the preservation of hearing even after surgical removal of a large meningioma suspected to have caused significant vascular compromise to the labyrinth. A hypothesis for the remarkable postoperative hearing in some patients was recently suggested by Buchheit. The blood supply to the cochlea is usually derived from the internal auditory artery, a branch of the basilar artery. Buchheit believes that some collateral circulation to the cochlea is provided by the stylomastoid artery, a branch of the posterior auricular artery. This is not, however, a universally held belief. Thus, even in cases of severe damage to the internal auditory artery, blood flow would be maintained by the collateral circulation, thereby resulting in hearing preservation. The author lends additional weight to this hypothesis by pointing out the infrequency of hearing preservation in difficult cases even with the most experienced surgeons.59 Although current opinion given case studies of dramatic hearing improvement suggests that hearing preservation surgery should be attempted even in patients with poor preoperative hearing, some authors suggest a hearing ablative approach such as the translabyrinthine or transcochlear approach if the lateral two-thirds of the IAC or vestibule are extensively involved or if massive IAC involvement or encasement by the tumor of the vestibulocochlear complex occurs.160 However, a good level of preoperative hearing and questionable status of the contralateral ear may also prompt the surgeon to attempt hearing preservation surgery at the expense of reduced exposure and increased operative time.160 Grey and coworkers disagreed with Schaller that hearing preservation surgery should be reserved for patients with class A hearing only. These authors felt that class B hearing is still serviceable, whereas Schaller and colleagues believe that preservation of a classes B or C hearing is of little functional importance.92,158 The preservation or recovery of clinical vestibular function after surgical removal of CPA meningiomas was reported by Prasad and colleagues in 1993.157 All three patients in the study experienced an improvement in clinical vestibular function after surgery, despite an absent or minimal caloric function. The vestibular results reported by Grey and coworkers158 also suggested improvement following surgical resection. Eight of 13 patients complained of imbalance preoperatively, whereas only 1 of 16 experienced unsteadiness postoperatively. However, six patients were found to be unsteady postoperatively when the vestibular system was stressed with tests that required the patient to walk in the dark or turn rapidly.

A comprehensive clinical examination including the assessment of cerebellar ataxia, dysdiadochokinesis, Romberg’s test, walking along a line with eyes open (WALEO), and walking along a line with eyes closed (WALEC) were conducted to assess the cerebellar and vestibular function of each patient. Improvement was noted for patients with all tests except the WALEC, signifying the importance of the visual system compensation in patients with vestibular dysfunction.158 Given the possibility of hearing preservation for meningiomas and the poorer relative hearing results associated with vestibular schwannomas, it is imperative to obtain an accurate preoperative diagnosis of any CPA lesion.92 The availability of modern imaging techniques has not only assisted in making the diagnosis of a CPA meningioma but also identifying the precise location of the tumor. The preoperative identification of a meningioma may alter the surgical strategy since the factors influencing the risk of damage to the CN VII–VIII nerve complex are different from those for vestibular schwannomas.92 The position of the meningioma also helps to plan the surgical approach as well as set realistic expectations for hearing and vestibular nerve preservation. Although imaging techniques are still in their infancy, the knowledge collected in these studies serves as encouragement for surgeons to plan and expect to preserve the CN VII–VIII nerve complex.158

FACIAL NERVE PRESERVATION Satisfactory preservation of the facial nerve has been noted in most series in the literature. Facial nerve preservation defined as an absent to moderate postoperative impairment after removal of a CPA meningioma was recently noted in two large series to be 69% and 94%.92,159 Similar to the results available for hearing preservation, minimal preoperative and postoperative data exist for facial nerve function in the literature. The location, and the size of the meningioma play a role in the postoperative function of facial nerve. The degree of tumor involvement in the region of the IAC may also affect facial nerve preservation. In contrast to the data accumulated for hearing preservation, however, surgeons have, of late, consistently used the facial nerve grading system introduced by House and Brackmann to quantify postoperative CN VII function.165 In a recent study, the facial nerve was anatomically preserved in 11 of 13 (85%) patients. Schaller and colleagues reported an HB grade I preservation in 6 of 10 (60%) patients. The other four patients who had no preoperative deficits were noted to have a postoperative CN VII dysfunction of HB grade II, 20%, HB grade III/IV, 10%, and HB grade VI, 10%. All three patients with a preoperative functional weakness (HB grade II–VI) had a total facial nerve deficit (HB grade VI) immediately after surgery.92 A similar percentage of normal facial nerve function was recorded by Batra and coworkers, who reported an HB grade I preservation in 11 of 17 (65%) patients in their series of 21 patients, 17 of whom had facial nerve preservation data available. Two of 17 (11.5%) patients each retained an HB grade II and III, respectively, and 1 of 17 (6%) patients each maintained an HB grade IV and VI, respectively. Overall, 13 of 17, 76%, of patients maintained

Meningiomas of the Posterior Fossa and Skull Base

an HB grade I or II postoperatively. The facial nerve for the patient with a postoperative HB grade VI had to be transected due to encasement of the nerve in tumor. One patient with a preoperative HB grade of VI improved to an HB grade IV after tumor removal (Table 47-9).159 Given these reasonable results, the facial nerve dissection should be attempted in every CPA meningioma case. Size does not appear to have a significant effect on the postoperative CN VII function. Schaller and colleagues noted a preoperative and postoperative total facial nerve paralysis (HB grade VI) in patients with large tumors. One of three (33%) patients with meningiomas less than 2 cm had a worsening of facial nerve function compared with none of the patients with tumors between 2 and 3 cm and three of nine (33%) patients with tumors greater than 3 cm. The facial nerve was transected in 2 of 11 (15%) patients with large meningiomas, leading the author to conclude that the risk of poor facial nerve function increased in large tumors due to a difficult intraoperative dissection.92 Batra and coworkers also noted that size did not statistically influence the postoperative facial nerve function. Two of five (40%) patients with tumor sizes less than 2 cm, 7 of 10 (70%) patients with tumor sizes between 2 and 4 cm, and one of two patients (50%) had normal CN VII function postoperatively. Based on the data, tumor size was not found to statistically affect the postoperative facial nerve function using the Fischer exact test ( p = 0.52).159 Akin to hearing preservation, continuity of CN VII has been reported to vary based on the site of a meningioma. Facial nerve dysfunction was noted to be higher in tumors located anterior to the IAM, thereby displacing the nerve posteriorly, partially obstructing tumor resection primarily due to a difficult intraoperative dissection of nerve. Schaller and colleagues reported a grade I through IV preservation of the facial nerve in all eight meningiomas located posterior to the IAM. However, only one of five (20%) patients with premeatal meningiomas retained grade I through IV facial function.92 The authors reported a preservation of HB grade I in six of eight (75%) patients with retromeatal meningiomas. In contrast, a HB grade I was not seen in either of the two patients (0%) with premeatal tumors.92 Batra and coworkers also reported a statistically significant difference ( p = 0.025) in the preservation of postoperative facial nerve function and retromeatal tumors. All 10 of 10 patients (100%) with retromeatal tumors treated with a retrosigmoid approach retained their HB grade I facial function. In contrast only one of seven patients (14%) with premeatal tumors maintained HB grade I facial function postoperatively. The CN VII function in the rest of their patients was as follows: HB grade II in two patients, HB

TABLE 47-9. Facial Nerve Results for CPA Meningiomas— Five Series; 35 Cases Preoperative HB Grade I–II HB Grade III–IV HB Grade V–VI

30 1 4

Data taken from references 59, 61, 112, 178, and 182.

Postoperative 23 6 6

833

grade III in two patients, HB grade IV in one patient, and HB grade VI in the final patient.159 The causes for the dismal rate of facial nerve preservation in meningiomas located anteromedial to the IAM are similar to those reported for poor hearing preservation for these tumors after surgery. The intimate relationship between premeatal tumors and the neurovascular bundle as well as the presence of the CN VII–VIII complex between the surgeon and the tumor are the primary reasons for the poor facial nerve preservation during dissection of a premeatal meningioma.57,158 Preoperative facial nerve paresis has also been noted as a risk factor for postoperative CN VII dysfunction. Schaller and colleagues reported that all three patients with preoperative facial nerve weakness ended up with HB grade VI postoperatively.92 Batra and colleagues described one patient with HB grade III before surgery declining to HB grade VI after tumor removal. However, the authors also noted the improvement of CN VII function from HB grade VI to grade IV.159

RECURRENCE Although surgical excision is the definitive therapy for the treatment of meningiomas, recurrence and progression of disease have plagued surgeons for decades, despite the seemingly complete removal of these tumors.166 Multiple factors influencing recurrence have been recognized ever since Cushing began operating on patients for the surgical resection of meningiomas.167 In his series of 295 patients, 43 required reoperation for “actual or symptomatic” recurrence. In addition, 76 patients died due to an incomplete removal of the meningioma. Although Cushing did not report a recurrence rate, an analysis of his data by Simpson suggests that it was more than 15%. In 1957, Simpson reemphasized the role of the extent of resection, location, and histology of the tumor in influencing the recurrence of meningiomas.168 Since then, several authors have attempted to elucidate the factors hastening tumor recurrence in order to initiate close follow-up and early postoperative treatment (e.g., radiotherapy) in patients with an increased risk of tumor growth and progression.166 Few papers in the literature have addressed the incidence and causes of recurrence extensively. One of the reasons is that meningiomas are benign tumors that grow slowly and therefore lend themselves to retrospective study. In addition, several early papers oversimplified the statistical analysis required for calculating the recurrence rate. In many cases recurrence was calculated as a proportion of all patients treated without considering the follow-up period, resulting in a gross underestimation of the true recurrence rate.169 Recent papers employ a statistical method used to correct for the differences in the follow-up period known as life-table analysis.166,169 However, this method cannot correct for the quality of postoperative follow-up, which varies tremendously among studies. In many studies, patients are not followed until clinical recurrence has occurred. Also, the rate of late recurrence for meningiomas is unknown because few patients are followed for periods of 15 to 20 years.169 Furthermore, the methods used for detecting recurrence have varied; in early series

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recurrence was defined by a return of clinical symptoms, whereas in others recurrence was measured with modern imaging techniques. Finally, subjective data such as the functional status of a patient is rarely used as a criterion to measure recurrence after surgery; consideration of only objective data such as radiologic evidence or the need for a second operation for assessing recurrence result in an underestimation of the survival and recurrence rates.166 In 1957, Simpson defined recurrence as the reappearance of symptoms due to tumor growth after a period of symptomatic relief.168 In 1983, Adegbite and coworkers introduced the term progression, which implied a “continuance in growth” subsequent to incomplete tumor removal.167 With the advent of modern imaging techniques, the definition of recurrence was modified. Mirimanoff and colleagues in 1975 considered patients to have a recurrence if after a period of time, radiologic studies detected the presence of tumor despite complete excision.166 These authors defined the progression as an increase in tumor size after subtotal removal, confirmed with imaging studies. Using this definition of recurrence, Melamed and coworkers calculated an overall recurrence rate of 29% in a series of 126 patients in 1979. This figure was calculated without life-table analysis.170 In contrast, in 1986 Jaaskelanian estimated the overall recurrence rate to be 19% at 20 years using life-table analysis in a series of 657 patients.169 In a study of 225 patients in 1985, Mirimanoff and colleagues reported an absolute 5-, 10-, and 15-year survival probability of 83%, 77%, and 69%, respectively.166 In 1983, Adegbite and coworkers noted similar recurrence-free rates of 80% at 5 years, 70% at 10 years, and less than 50% at 20 years in their report on 114 patients.167 In the most recent study of 286 patients with intracranial meningiomas in 1999, Ayerbe and coworkers reported recurrence rates of 14%, 37%, and 61% at 5, 10, and 15 years, respectively. All these patients were followed with either CT or MRI from 3 to 17 years since the initial surgery.171 A classification scheme for measuring the degree of surgical excision was proposed by Simpson in 1957. The author introduced five distinct grades of surgical resection: Grade I is defined as a macroscopically complete excision of tumor including its dural attachments and abnormal bone. This includes removal of the sinus wall if infiltrated with tumor. A grade II resection is described as resection of the tumor and its extensions with coagulation of its dural attachments. Grade III is defined as a resection of the intradural tumor without removal or coagulation of its dural attachments. A grade IV resection is described as an incomplete tumor removal, and a grade V excision is a simple decompression with or without a biopsy (Table 47-10).168 The extent of surgical resection has been reported to play a major role in the recurrence rate of meningiomas. Multiple studies in the literature have noted a higher incidence of recurrence/progression with an incomplete or partial resection. In an early series of 126 patients, Melamed and coworkers noted that two-thirds of patients with a radical excision of the tumor remained recurrencefree. The authors defined radical excision as either the complete removal of the tumor with resection of the meninges and invaded bone or total tumor removal with or without cauterization of the meninges. In contrast, nearly one-half (44%) of patients with an incomplete

TABLE 47-10. Simpson’s Grading Scheme for Extent of Tumor Resection Simpson’s Grade

Degree of Removal

Grade I

Macroscopically complete removal of the tumor with excision of its dural and bony attachments Macroscopically complete removal of the tumor and its extensions with endothermy coagulation of its dural attachments Macroscopically complete resection of tumor without removal or coagulation of its extradural extensions Partial removal leaving intradural tumor in situ Simple decompression of the tumor

Grade II Grade III Grade IV Grade V

From Simpson D: The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20:20–39, 1957.

removal of tumor experienced recurrence in this study.170 Simpson noted recurrence rates of 9%, 19%, 29%, and 40% at 10 years for patients with a grades I, II, III, and IV resection, respectively.168 In a more recent series using lifetable analysis, Mirimanoff and colleagues noted a 5-, 10-, and 15-year recurrence-free survival rate of 93%, 80%, and 68%, respectively, following complete tumor removal. In contrast, after a subtotal excision for the same period, the authors reported a progression-free survival rate of 63%, 45%, and 9%, respectively. This difference was highly statistically significant ( p < 0.0001) when assessed with the Mantel-Haenszel test. In addition, patients with subtotally excised meningiomas had a high likelihood of a second operation at 5, 10, and 15 years (25%, 44%, 84%) when compared with 6%, 15%, and 20% for patients with completely resected meningiomas.166 Adegbite and coworkers also noted the grade of the initial surgery to have a statistically significant influence on recurrence. In their series, the percentage of patients free of recurrence 5 years after a grade I, II, III, and IV surgical excision were 86%, 82%, 100%, and 48%, respectively. The number of patients with a grade III removal were too few for an accurate statistical analysis. Nevertheless, the trend suggested that a higher degree of tumor removal was associated with a lesser likelihood of recurrence. The difference in results between patients with a grade I and II surgical removal versus those with a grade IV excision was statistically significant.167 In an analysis of 53 patients, Marks and coworkers found a recurrence rate of 9.5% after complete resection of tumor versus a rate of 18.4% after subtotal removal.172 In a study of 257 patients, similar results were noted by Chan and Thompson in 1984, who reported a frequency of tumor recurrence after a grade I, II, III, IV, and V removal to be 11%, 22%, 50%, 37%, and 100%, respectively. A difference of 3.3 years was found in the average survival time between patients with complete removal versus those with partial removal of the tumor.173 Given these data, a surgeon must balance the extent of resection with the likelihood of recurrence and postoperative functional status of the patient. The likelihood of recurrence or progression of a meningioma has also been reported to vary based on the location of the tumor. Parasagittal meningiomas were noted by Simpson and Melamed and coworkers to have a high rate of recurrence.168,170 Melamed and coworkers suggested that this was most likely due to invasion of the superior

Meningiomas of the Posterior Fossa and Skull Base

sagittal sinus wall.170 Waga and colleagues, on the other hand, found meningiomas of the convexity to be associated with the highest rates of recurrence.167 However, the authors noted that when malignant tumors were excluded, meningiomas of the falx were found to recur most often.167 Contradicting these findings, Mirimanoff and colleagues reported low recurrence and progression rates at 5 and 10 years for meningiomas of the convexity (3% and 25%) and parasagittal area (18% and 24%).166 In an analysis of risk factors for recurrence, Ayerbe and coworkers found tumors at the petroclival and parasaggital locations to correlate with a high degree of recurrence.171 Posterior fossa meningiomas were reported to have a high risk of recurrence by Melamed and coworkers in 1979. These tumors showed a recurrence of 54.5% in one of the earliest series studying the recurrence of intracranial meningiomas. The authors attributed this high rate of recurrence to the incomplete removal of these tumors due to their close proximity to critical neurovascular structures.170 In the series by Mirimanoff and colleagues in 1985, complete excision was noted in only 10 of 31 (32%) posterior fossa meningiomas, with a subtotal resection in the other 68% of these tumors. The lesions displayed overall 5- and 10-year recurrence rates of approximately 20% and 40%, respectively.166 In a study of 257 patients in 1984, Chan and Thompson reported an overall recurrence rate of 20% for posterior fossa meningiomas. They reported no recurrence for patients with a grade I resection 0/7 (0%) and only one recurrence for a patient with a grade II resection. However, 8 (42%) recurrences were noted in the 19 patients that underwent a grade IV or V removal.173 Due to the low rate of total excision in the posterior fossa, meningiomas in this location were associated with intermediate to high rates of recurrence when compared with tumors in other locations. In contrast to these data, Adegbite and coworkers reported no significant influence of location on recurrence. Although differences in the percentage of tumor recurrence were observed between convexity, parasagittal, sphenoid wing, and posterior fossa meningiomas among others, this variation was not statistically significant.167 However, given that the location of a meningioma determines the extent of resection which in turn influences the rate tumor recurrence, the site of a meningioma may be considered an indirect factor in tumor recurrence and progression. The complete removal of tumor also resulted in a longer observed survival time as well as an improved quality of life compared with partial tumor excision. Given the difficulty of complete tumor resection, posterior fossa meningiomas had the lowest observed average survival period of 5.9 years compared with parasagittal, falcine, convexity, olfactory groove, and sphenoidal ridge meningiomas.173 Furthermore, patients with gross total removal of recurrent tumor had a significantly longer duration of subsequent survival with good functional status than those with partial tumor resection. A longer period of survival was also found in patients with meningiomas smaller than 4.5 cm in diameter.173 Patients with smaller meningiomas did not have longer survival rates than individuals with larger meningiomas but led a better quality of life after tumor removal. The most important factor for determining postoperative

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survival, however, remains the preoperative clinical condition of the patient. In a study of 124 intracranial meningiomas in 1989, Kajiwara and colleagues reported an association between meningioma recurrence and the age of the patient, with the majority of recurrences found in patients younger than age 60 years. A particularly high recurrence rate was found in individuals younger than age 40. In addition, the mean age of patients with recurrent tumors was younger than that for patients with no recurrences.174 In contrast, several other studies do not report an association between a patient’s age or gender with an increased rate of recurrence and progression. In the 34 cases of recurrence, Melamed and coworkers in 1979 reported a male-to-female ratio of 3:2, equal to that found in the entire group of 126 patients.170 In 1985, Mirimanoff and colleagues found no association between recurrences or progression of the tumor with such factors as the age, gender, or duration of symptoms. The recurrence or progression-free survival rates at 5 and 10 years for females (83% and 68%) and males (84% and 66%) were nearly identical. There was also no difference in the rates at 5 and 10 years between patients younger than 50 years (83% and 61%) and individuals older than 50 years old (84% and 75%).166 In addition, the time from the onset of symptoms to surgical resection was less than 6 months in 59 patients, 6 months to a year in 54 patients, 1 to 2 years in 60 patients, and more than 2 years in 52 patients. The recurrence- or progression-free rates of 76%, 63%, 65%, and 71% were similar in all four groups at 10 years.166 Melamed and coworkers in 1979, reported no correlation between the consistency of the meningioma defined as hard, friable, “suckable,” necrotic, or vascular and the rate of recurrence.170 In contrast, in a study of 657 patients in 1986, Jaaskelanian reported soft consistency of the tumor to strongly and independently correlate with recurrence (p < 0.01). The author reported that 15 of the 79 meningiomas had been soft and “suckable” during surgery, resulting in a recurrence rate of 34% at 20 years. The author suggested that soft meningiomas tended to recur because they were more apt to tear and be left behind in the tumor bed during surgical removal. In addition to soft consistency of the tumor, the author also found simple coagulation of the tumor base and invasion of bone to be risk factors for recurrence. Approximately 34% to 56% of patients with two of the three risk factors, 15% to 24% of patients with one of the three risk factors, and 11% with no risk factors experienced a recurrence within 20 years.169 Specific histologic types of meningiomas have been noted to correspond to a higher rate of recurrence. In 1970, Crompton and Gauthier-Smith suggested that syncytial meningiomas are most likely to recur, whereas fibroblastic meningiomas are least likely to do so.175 However, recent studies have not found a statistically significant correlation between a particular histology and the duration to recurrence. Simpson in 1957 and Melamed and coworkers in 1979 found no correlation between any particular histology and an increased rate of tumor recurrence.168,170 Adegbite and coworkers did not find any relationship between recurrence and the three most common histologic groups for meningiomas, namely, the syncytial, transitional, and fibroblastic subtypes.167 The authors did, however, find a

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5-year recurrence-free survival rate of only 32% for angioblastic and malignant meningiomas. However, the small sample size of these tumors did not allow for a statistically significant comparison.167 Chan and Thompson reported that the average survival of 3.6 years for patients with malignant tumors was not significantly different from that for benign meningiomas.173 Although no specific histology is associated with an increased recurrence, high cellularity is often observed in recurrent meningiomas. Two early studies by Skullerud and Loken in 1974 and Jellinger and Slowik in 1975 found an increased cellularity and mitotic rate in recurrent tumors.176 Waga and coworkers also noted histologic malignant changes in 6 of 19 recurrent meningiomas.167 Crompton and Gautier-Smith believed that an increased number of mitoses, greater extent of necrosis within the tumor, and infiltration of the tumor into adjacent brain predicted a greater chance of recurrence.175 Melamed and colleagues, in agreement with these authors, also found that cerebral infiltration, numerous mitoses, and cellular pleomorphisms were associated with a higher rate of recurrence.170 The study by Adegbite and coworkers in 1983 noted that 6 of the 21 recurrent meningiomas displayed a greater degree of cellularity or increased mitotic figures.167 Marks and colleagues in 1986 also noted mitoses and areas of focal necrosis to correlate with a higher recurrence rate.172 In a review of 82 cases in 1986, De la Monte and coworkers noted the following histopathologic factors were associated with recurrence: hypervascularity, hemosiderin deposition, growth of tumor in sheets, prominent nucleoli, mitotic figures, single cell or group necrosis, nuclear pleomorphism, and an atypical or malignant tumor grade.177 All these studies suggest a more aggressive cellular histology for recurrent tumors. In a study of 286 patients in 1999, Ayerbe and coworkers found atypical and malignant histologic types, nucleolar prominence, and the presence of greater than 2 mitoses/hpf to correlate with a higher rate of recurrence.171 The assessment of DNA has also been used to predict meningioma recurrence. A high proliferation index determined by flow cytometry analysis has been associated with recurrent meningiomas.178 In a study by May and colleagues in 1989, a higher proliferation index was observed in recurrent meningiomas than in nonrecurring ones. The two groups of patients with recurrent and nonrecurring tumors were matched for age, gender, and length of follow-up. A greater number of mitoses and areas of focal necrosis were noted in the recurrent group. Foci of necrosis were seen in four of the nonrecurring tumors compared with seven of the recurrent ones. In addition, mitotic figures were seen in 4 of nonrecurring tumors compared with 12 for the recurrent group.178 Flow cytometry may play a role in predicting the clinical behavior and therefore recurrence in these cases. This study concluded that a proliferative index of greater than 20% in any tumor suggests that it may recur, despite complete resection and a benign histology.

RADIATION THERAPY The benefit of radiotherapy as an adjunctive treatment for meningiomas has been established in a few limited studies. In a study of 58 patients in 1975, Wara and coworkers

studied the role of fractionated external beam radiotherapy (5000 to 5500 cGy) in treatment of subtotally resected (Simpson grade IV) meningiomas. Approximately 5 years after treatment, the authors found a recurrence rate of 29% in the irradiated group versus 74% in the nonirradiated group.179 In a more recent study of 135 meningiomas not localized to the posterior fossa, Barbaro and coworkers in 1987 noted a similar difference in the recurrence rates between meningiomas receiving and those not receiving radiation treatment. Of the 51 patients who underwent a complete resection and did not receive radiation therapy, only 2 (4%) had a recurrence. Among the 84 patients in the study who underwent an incomplete resection, a recurrence rate of 60% was noted in the 30 patients who did not receive radiation treatment, whereas the 54 patients who were given radiotherapy had a recurrence rate of 32%. The authors also reported a longer median time to recurrence in the irradiated versus the nonirradiated group, with a 125-month hiatus in irradiated patients versus 66 months in patients who did not receive irradiation, (p < 0.05). This large series contained 23 posterior fossa meningiomas, 21 of which underwent subtotal resection. Of these 21 posterior fossa meningiomas, 16 did not receive radiation treatment.180 A more recent study of benign partially resected meningiomas by Miralbell and colleagues in 1992 compared the recurrence rates between 36 patients treated with surgery and radiation therapy versus those in 79 patients treated with surgery alone. The authors found a recurrence rate of 12% for patients treated with subtotal resection and radiation therapy (5000 to 6000 cGy). This compared with a rate of 52% for patients treated only with a subtotal resection. The paper did not reveal the anatomic distribution of meningiomas in this study.181 All these studies suggested that radiotherapy is beneficial as adjunctive therapy for incompletely resected benign meningiomas. However, additional studies need to be performed to prove an unequivocal benefit in these patients.34 Patients with malignant meningiomas, however, have been determined to greatly benefit from radiation therapy. Radiation therapy may also be used for the palliation of inoperable and recurrent tumors.167 Stereotactic photon-beam radiosurgery (gamma knife), which was initially used for a limited number of patients, is now being used with greater frequency. Patients with subtotally resected meningiomas, individuals with recurrent tumors in locations associated with unacceptable surgical morbidity, and elderly patients with poor functional status are some of the groups that have benefited from stereotactic radiosurgery. In a study of 50 patients with intracranial meningiomas, which included six posterior fossa meningiomas, Kondziolka and colleagues reported a 2-year tumor growth rate control of 96%.182 Some of the complications with this treatment modality were reported by Al-Mefty and coworkers in a series of 58 patients who received an average 5000 cGy with a follow-up of 8 years. Complications, including visual deterioration, pituitary dysfunction, brain necrosis, and one case of radiation-induced clival meningioma, were noted in 19% of patients.183 Brainstem and cerebellar necrosis was also noted by Miralbell and colleagues in their series of meningiomas.181 The role of stereotactic radiation therapy is expected to increase in the treatment of meningiomas in the near future.

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147. Wagle VG, Villemure JG, Melanson D, et al: Diagnostic potential of magnetic resonance in cases of foramen magnum meningiomas. Neurosurgery 21:622–626, 1987. 148. Bertalanffy H, Gilsbach JM, Mayfrank L, et al: Microsurgical management of ventral and ventrolateral foramen magnum meningiomas. Acta Neurochir (Suppl) 65:82–85, 1996. 149. Babu RP, Sekhar LN, Wright DC: Extreme lateral transcondylar approach: technical improvements and lessons learned. J Neurosurg 81:49–59, 1994. 150. Bertalanffy H, Seeger W: The dorsolateral, suboccipital, transcondylar approach to the lower clivus and anterior portion of the craniocervical junction. Neurosurgery 29:815–821, 1991. 151. Nanda A, Vincent DA, Vannemreddy PS, et al: Far-lateral approach to intradural lesions of the foramen magnum without resection of the occipital condyle. J Neurosurg 96:302–309, 2002. 152. Love JG, Thelan EP, Dodge HW: Tumors of the foramen magnum. J Int Coll Surg 22:1–17, 1954. 153. George B, Lot G, Boissonnet H: Meningioma of the foramen magnum: a series of 40 cases. Surg Neurol 47:371–379, 1997. 154. Samii M, Klekamp J, Carvalho G: Surgical results for meningiomas of the craniocervical junction. Neurosurgery 39:1086–1094; discussion 1094–1095, 1996. 155. Nedzelski JM, Tator CH: Hearing preservation: A realistic goal in surgical removal of cerebellopontine angle tumors. J Otolaryngol 13:355–360, 1984. 156. Cohen NL, Lewis WS, Ransohoff J: Hearing preservation in cerebellopontine angle surgery. Am J Otol 14:423–433, 1993. 157. Prasad S, Kamerer DB, Hirsch BE, Sekhar LN: Preservation of vestibular nerves in surgery of the cerebellopontine angle: Effect on hearing and balance function. Am J Otolaryngol 14:15–20, 1993. 158. Grey PL, Baguley DM, Moffat DA, et al: Audiovestibular results after surgery for cerebellopontine angle meningiomas. Am J Otol 17:634–638, 1996. 159. Batra PS, Dutra JC, Wiet RJ: Auditory and facial nerve function following surgery for cerebellopontine angle meningiomas. Arch Otolaryngol Head Neck Surg 128:369–374, 2002. 160. Goebel JA, Vollmer DG: Hearing improvement after conservative approach for large posterior fossa meningioma. Otolaryngol Head Neck Surg 109:1025–1029, 1993. 161. Schaller B, Merlo A, Gratzl O, Probst R: Premeatal and retromeatal cerebellopontine angle meningioma. Two distinct clinical entities. Acta Neurochir 141:465–471, 1999. 162. Christiansen CB, Greisen O: Reversible hearing loss in tumors of the cerebello-pontine angle. J Laryngol Otol 89:1161–1164, 1975. 163. Vellutini EA, Cruz OL, Velasco OP, et al: Reversible hearing loss from cerebellopontine angle tumors. Neurosurgery 28:310–312; discussion 312–313, 1991. 164. Baker G, Christoferson L: Proceedings of the Staff Meetings of the Mayo Clinic 25:549, 1950. 165. House JW, Brackmann DE: Facial nerve grading system. Otolaryngol Head Neck Surg 93:146–147, 1985.

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Epidermoid Cysts of the Cerebellopontine Angle Outline Introduction Embryology Pathology Clinical Signs Diagnosis Computed Tomography Magnetic Resonances Imaging

Surgical Treatment Unusual Compllcalions of CPA Epidermoid Cysts Spontaneous Meningitis Lumbar Arachnoiditis Squamous Cell Carcinoma Summary

INTRODUCTION Congenital cholesteatoma, or epidermoid cyst of the temporal bone, may occur in the middle ear, the mastoid, the petrous apex, or in the cerebellopontine angle (CPA). Cruveilhier' in 1829 was among the earliest to identify intracranial epidermoid tumors. After his descriptions of three cases, they were called Cruveilhier's pearly tumors in the literature for the next 100 years. Muller2 first used the word cholesteatoma in reference to three cases he reported, because they contained cholesterol crystals. Virchow! preferred to use the name pearly tumors because cholesterol was not always present in the four cases he presented. In 1897, Bostroem" outlined the embryology of these tumors and dubbed them epidermoid. By 1943, Rand and Reeves' found about 200 cases in their review of the world literature and added 21 cases of their own. Epidermoid cysts comprise 0.2% to 1.5% of all intracranial tumors, and the posterior fossa is the most frequent intracranial site for their appearance." In the CPA, epidermoid cysts are the third most common lesion, constituting 4.6% to 14% of all tumors in this region.Y Other locations by decreasing frequency include the parasellar area, clival area, lateral recess of the fourth ventricle, and petrous apex." Mahoney!" analyzed 142 cases of cranial and intracranial epidermoid cysts and found 53 (37%) in the CPA Yamakawa and colleagues II reported the location of 45 intradural epidermoid cysts: 46% CPA, 15% middle fossa,.15% cerebral hemisphere, 9% suprasellar, 9% third ventricle, and 6% fourth ventricle. Nager" reviewed the literature and concluded that 30% to 40% of epidermoid cysts are found in the CPA, where they account for 6% to 7% of all CPA tumors. The tumors extend linearly along planes of least resistance to the middle fossa, foramen magnum, and to the contralateral CPA; enveloping neurovascular structures along the way.9,12 Multiple epidermoid cysts almost never occur." CPA epidermoid cysts appear in any age group, but the majority are identified in the third and fourth decades.V They present with progression of symptoms after a long period of slow growth. 8

Antonio De la Cruz, MD Karen Jo Doyle, PhD, MD Stephanie Moody Antonio, MD

CPA epidermoid cysts are to be differentiated from extradural (cranial or diploic) epidermoid cysts and from dermoids. Intradiploic epidermoid tumors are slow-growing masses that present as a painless swelling of or defect of the cranium.'! These tumors probably develop from indusion of ectodermal elements during closure of the neural groove.f-!' Dermoid tumors contain hair follicles and gland tissue and tend to occur in the midline" and are four to nine times less common than epidermoid cysts.'?

EMBRYOLOGY In 1854, Von Remak first advanced the view that epidermoid cysts arise from epithelial cell rests early in embryonic development.l" Bostroem" also leaned toward an epithelial origin of epidermoid cysts, suggesting that they arose from embryonic epithelial rests at a fairly late stage of fetal development. Bostroem regarded dermoids as developing from a younger and more primitive cell layer that may give rise to epithelial and mesothelial tissues, unlike epidermoid cysts, which are composed of derivatives of epithelial tissue only." Scholtz'! described the inclusion of ectodermal elements at the time of the closure of the neural groove during the third to fifth week of embryonic life, when the neural ectoderm separates from the cutaneous ectoderm; he surmised that these misplaced cells give rise to dermoid or epidermoid tumors in the midline. Later, other authors added to the epithelial rest theory, hypothesizing that epidermoid cysts layaway from the midline as a result of epithelial misplacement during development of the secondary otic and optic cerebral vesicles in the forebrain and metencephalon during the fourth or fifth week of development.S'? Fleming and Botterel'? hypothesized that epidermoid cysts formed from the proliferation of multipotential embryonic cell rests located more laterally than the neural tube closure site. Migratory properties of CPA epidermoid cells were observed in vitro, similar to acquired cholesteatomas of the middle ear and mastoid. Because this migratory ability is unique to 841

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epithelium derived from the first branchial groove (no other epithelium in the head and neck shares this property), the authors suggest a first branchial groove site of origin for CPA epidermoid cysts.l"

PATHOLOGY Bailey'? gave an almost poetic description of the macroscopic appearance of epidermoid tumors: "Grossly the tumors resemble startlingly mother-of-pearl both in tint and luster. The surface is smooth, silky, with irregular pea-sized or larger elevations and peels away easily from the surroundings. The surface layers are tough, with about the malleability of heavy tin foil. From the surface, with a knife blade, flakesmay easily be separated which show beautifully the characteristic luster."

Microscopically, epidermoid cysts are covered by stratified squamous epithelium overlying a thin layer of connective tissue. The capsule may contain foci of calcification. The superficial layers are usually cornified, and intercellular bridges are occasionally seen.i? Epidermoid cysts contain keratin debris and frequently, cholesterol crystals. This debris is the result of progressive desquamation and breakdown of keratin from the epithelial lining of the cyst, forming concentric lamellae. The interior of the epidermoid is usually soft, white, waxy material. Sometimes the contents are thick, viscid, and dark brown or gray. They are devoid of blood supply, but often are in surface contact with arteries." To further differentiate epidermoid cysts and dermoids, dermoids contain other elements of normal skin, such as sweat glands, sebaceous glands, hairs, or hair follicles, whereas epidermoid cysts have only squamous and sometimes basal epithelium present. Montgomery and Finlayson/? presented an interesting case of a tumor involving the middle fossa as well as the posterior fossa. The middle fossa portion had dermoid features (sebaceous glands and hair follicles), whereas the posterior fossa part exhibited more epidermoid characteristics. They argued that this was evidence that epidermoid cysts and dermoids were the same tumor, but this is the only case of its kind in the literature. The growth rate of epidermoid cysts is linear, like normal skin, unlike the exponential growth demonstrated by most neoplasrns.P This linear rate of growth is expected of tumors derived from a single layer of basal germinal cells spread out over a surface area. The slow growth rate enables adjacent structures to adjust gradually, and epidermoid cysts spread with finger-like projections along preformed clefts and spaces. They tend to engulf nearby blood vessels and cranial nerves and spread along the crevices of the brainstem and cerebellar and cerebral hernispheres.Vr" Ulrich/! described the gross spread of epidermoid cysts as "multilobulated masses that adapt themselves to the available space between the skull and the brain." There are four possible routes of spread from the CPA. Anteriorly tumor may spread to the prepontine cistern, engulfing or displacing the basilar artery, and toward the contralateral side. Inferior extension toward the foramen magnum risks the lower cranial nerves, the vertebral artery, and the posterior

inferior cerebellar artery. Superior extension across the tentorium results in middle fossa involvement. Finally, tumor may extend medially into the foramen of Lushka into the fourth ventricle.i! Yasargil and colleagues-" found that of 22 CPA epidermoid cysts in their series, 5 were directed posterocaudally through the foramen of Luschka into the fourth ventricle, 3 extended anterorostral through the incisura into the parasellar cisterns, and 4 appeared to be supratentorial tumors extending back to the posterior fossa. Samii'? reported the location and extension of CPA epidermoid cysts in 40 patients: 15 were confined to the CPA, 3 had transtentorial extension, 5 had middle fossa extension, 9 had extension to the foramen magnum, and 8 had both transtentorial and foramen magnum extension. The only change to the brain produced by an epidermoid is local atrophy attributable to the pressure exerted by the expanding cyst. 20 Ganglion cells disappear, and frequentlya mild degree of gliosis occurs. No inflammatory reaction is typically seen.

CLINICAL SIGNS Posterior fossa epidermoid cysts, because they are very slow-growing, may be asymptomatic for years. Before imaging techniques became available, patients could exhibit symptoms for decades before diagnosis. In 1964, Ulrich!' recorded patients with intracranial epidermoid cysts whose durations of symptoms were as long as 29 and 53 years. Even with the advent of modern imaging techniques, diagnosis may be delayed more than 20 years. 9,12,26-28 The symptoms of CPA epidermoid cysts include hearing loss, tinnitus, dizziness, and gait disturbance. 12,23 Hearing loss and tinnitus are the usual initial symptoms in 80% of patients, and gait disturbance and headache are the initial complaints in 20%.29 Other less common presenting symptoms are intention tremor, tic douloureux, facial numbness, facial spasm, facial palsy, impaired taste, impaired lacrimation, dysarthria, dysphagia, tongue deviation, nausea and vomiting, and loss of consciousness." Nager" reported that 50% to 75% of patients with epidermoid cysts of the CPA complained of progressive sensorineural hearing loss, tinnitus, unsteadiness, and facial nerve symptoms. He also found that 25% to 50% of tumors manifested as atypical trigeminal neuralgia (atypical because it was of longer duration and might, not have trigeminal nerve impairment). Samii summarized potential mechanisms for tic douloureux: direct compressive effect, indirect pressure by causing vascular compression, or local irritation from cyst content seepage.V The most common cranial nerve abnormalities are VIII (50% to 55%), VII (18% to 45%), V (25% to 43%), and VI (10% to 30%).9,12

DIAGNOSIS Before the advent of computed tomography (CT) and magnetic resonance imaging (MRI), the diagnosis of intradural epidermoid cysts was difficult. Presenting symptoms and signs pointed to CPA tumor, but it was impossible to predict the pathology preoperatively because acoustic neuroma, meningioma, arachnoid cysts, and other lesions

Epidermoid Cysts of the Cerebellopontlne Angle

behave similarly. Plain radiographs, which showed diploic epidermoid cysts as radiolucent areas in the cranium, were of little use in diagnosing CPA epidermoid cysts." In Braclanann and Anderson's series-" of CPA cholesteatoma, 9 of 13 patients had normal internal auditory canals (IACs) on petrous pyramid plain films. "Without a tumor large enough to produce hydrocephalus, a pneumoencephalograph was frequently read as normal. 30 In the pre-CT era, the Pantopaque myelogram was used, on which CPA cholesteatoma exhibited the characteristic appearance of a lobulated or scalloped border, in contrast to the round or smooth contour of meningioma or acoustic neuroma." Braclanann and Anderson performed lumbar puncture as a part of the myelogram and reported that 9 of 10 patients hada normal cerebrospinal fluid (CSF) protein level, despite largeCPA epidermoid cysts, unlike other CPA neoplasms, whichare associated with elevated CSF protein levels.i"

Computed Tomography In the 1970s, CT permitted a more reliable radiologic diagnosis of CPA epidermoid cysts. In a study of nine patients with CPA epidermoid cysts comparing earlier imaging techniques to C'I, skull radiographs were normal in four patients and nonspecific in five, radionucleotide brain scans were normal in seven, and angiography was nondiagnostic in every case. CT detected the lesion in eight of nine cases." On CT, CPA epidermoid cysts are homogeneous and low density (low absorption values from -22 to +18 Hounsfield units: 500 scale) (Fig. 48-1). Bone erosion may be demonstrated (Figs. 48-2 and 48-3). By C'I, a CPA epidermoid may be difficult to distinguish from a subarachnoid cyst, which is also homogeneous and of low density, but the subarachnoid cyst usually has a sharply defined, rounded margin compared with the irregular periphery of the epidermoid tumor. 12,32 Enhancement of the capsule is uncommon.12,33 The appearance of epidermoid cysts may vary on CT. Increased density has been reported for some epidermoid tumors. Braun and coworkers'? reported three cases of posterior fossa epidermoid cysts with increased density

Figure 48-1. CT examination of leftCPA epidermoid (arrow); demonstrates characteristic homogeneous lowdensity without enhancement.

843

Figure 48-2. Normal right lAC.

(80 to 120 Hounsfield units), with two of them demonstrating scattered peripheral densities consistent with calcification (140 to 160 Hounsfield units). They could find no histologic reason for the increased CT density and termed the lesions dense epidermoid cysts. Nagashima and colleagues-" identified four patterns of CT findings: (1) homogeneous low density, (2) homogeneous low density with calcification or small dense nodules, (3) isodense, and (4) homogeneous high density. They were able to find a pathologic correlate in that the low or isodense epidermoid cysts were pearly appearing containing a white, waxy material rich in cholesterol, whereas the high-density epidermoid cysts were cystic and contained brown, viscous fluid with saponification of the debris. Dunn and coworkers" described another CT dense posterior fossa epidermoid cyst where the tumor contained a viscous brown fluid. They also pointed out that all reported cases of dense epidermoid cysts have occurred in the posterior fossa of females. Another interesting finding reported by Laster and colleagues was of freely movable fatty material within the ventricles and subarachnoid space seen in association with a CPA epidermoid, with negative absorption values by CT scan within the CSF space." The authors suggested that this

Figure 48-3. Bone program axial CT of leftCPA epidermoid, with extension to and erosion of petrous bone involving the left lAC (arrow). Compare with normal right lAC in Figure 48-2.

844

SURGICAL NEUROTOLOGY

probably represented rupture of the cyst in to the subarachnoid space, occurring spontaneously or postsurgically."

Magnetic Resonance Imaging Epidermoid tumors have a characteristic appearance on MRI. Generally, they have long Tl recovery times (low signal intensity) and prolonged T2 decay time (high signal intensity) (Figs. 48-4 and 48-5).J7-40 New MRI techniques have provided a better means of differentiating epidermoid from arachnoid cysts, which have identical MRI characteristics. On fluid-attenuated inversion recovery (FLAIR), an arachnoid cyst will be hypointense (similar to CSF), but an epidermoid cyst will be hyperintense (indicating protein content)."! Diffusion-sequence MRI can also be useful in distinguishing these two lesions as the solid nature of the epidermoid leads to a high signal (white) compared with the low signal (black) of the arachnoid cyst." Vion-Dury and colleaguesf highlighted variability in MRI findings among different cases of CPA epidermoid cysts. In their review of the literature, they found that 57% of epidermoid cysts are characterized by an increase and about 15% by a decrease of T2 relaxation time; and in 26% the T2 relaxation time is not different from that of the surrounding parenchyma." Other authors have found some variability in the Tl-weighted appearances of epidermoid cysts.9, 12,43 Horowitz suggested cystic epidermoid tumors with dense capsules had bright signal in Tl images due to high lipid content, whereas classical pearly tumors were hypointense on T'I images.t! Another study demonstrated that 4 of 20 surgically verified epidermoid cysts exhibited hvperintensitv on Tl images and hvpoinrensitv

Figure 48-5. MRI of leftCPA epidermoid. Demonstrates typical T2-weighted appearance (high intensity). This large CPA epidermoid has extended anteriorly to surround the pons.

on T2 images.t" Steffey and coworkers'! emphasized the variability of consistency on MRI of five epidermoid tumors: four of the five showed heterogeneous internal signal intensity; the fifth was homogeneous yet different from brain and CSF. They felt that this variability did not preclude the use of MRI to distinguish epidermoid cysts from subarachnoid cysts, which have the same signal intensity as CSF on both Tl- and T2-weighted images. Arriaga and Brackmann'" stressed the importance of obtaining both CT and MRI to work up petrous apex lesions and to differentiate epidermoid from cholesterol granuloma. These two imaging modalities have added a great deal to the preoperative planning of surgical treatment of CPA epidermoid cysts, with MRI having an advantage in locating the full anatomic extent of tumor for preoperative planning.f? Postoperatively, MRI with its greater anatomic detail is the preferred imaging technique for monitoring residual or recurrent epidermoid tumor." The new MRI techniques will likely playa strong role in preoperative diagnosis.

SURGICAL TREATMENT

Figure 48-4. MRI of leftCPA epidermoid. Typical T1-weighted appearance (low intensity).

The history of surgery for epidermoid tumors is long. Bailey'? in 1920 described successful surgical removal of intracranial epidermoid cysts using the suboccipital approach. In 1943, Rand and Reeves' reported five epidermoid cysts involving the CPA, including one with prepontine origin and spread to both CPAs. They found two tumors at autopsy and attempted removal of three others by the suboccipital approach. Two patients died postoperatively, and the third did well after a second operation in which all tumor was successfully removed. They felt that complete removal of tumor was out of the question when the capsule was intimately involved with cranial nerves or

Epidermoid Cysts of the Cerebellopontine Angle

the circle of Willis. In their 1950 paper, Grant and Austen'" outlined treatment of 22 epidermoid cysts, including 4 of the CPA. They removed these tumors subtotally, via suboccipital craniotomy, but emphasized that their patients did not require further operations. The mortality rate from their entire series was 23 %, and they did not offer separate mortality figures for the CPA epidermoid cysts. MacCarty and coworkers 5a reported 24 intracranial epidermoid cysts treated before 1959, 8 of which were located in the CPA. Four patients had surgery, and three tumors were completely removed. One patient died, one was lost to followup, and two were alive with some neurologic problems and facial paralysis. Surgeons continue to employ the suboccipital craniotomy, but have added other surgical approaches to the armamentarium for removal of CPA epidermoid cysts, including the translabyrinthine, middle fossa, and transcochlear approaches. The choice of approach is based on the hearing, cranial nerve symptoms, and extent of the tumor, including presence of contralateral or middle fossa extension. The retrosigmoid or suboccipital approach provides access to the prepontine region with adequate exposure of cranial nerves V to XI. It may allow hearing preservation. Any extension superiorly over the tentorium will require a middle fossa approach. With the middle fossa approach, division of the superior petrosal sinus and tentorium further widens the operative field." Larger lesions involving the posterior and middle fossa may be approached with a combined extended middle fossa (exposing petrous ridge to clivus) and retrolabyrinthine/retrosigmoid approach, called the petrosal approach. Wide access to the middle fossa, lAC, and posterior fossa is obtained while still preserving the otic capsule and, hence, hearing. Transtemporal approaches to CPA epidermoid cysts are the

translabyrinthine and transcochlear procedures. The translabyrinthine operation permits direct access to the CPA without cerebellar retraction, via extended mastoidectomy, labyrinthectomy, and removal of the bone surrounding the lAC. A translabyrinthine approach is attempted when hearing preservation is not an option and provides good exposure to tumor in the prepontine cistern, contralateral side, and foramen magnum." In cases with tumor involvement of the area anterior to the brainstem, the opposite CPA, and the carotid artery, the transcochlear approach is used. The facial nerve is rerouted posteriorly after the translabyrinthine approach is carried out, and bony removal of the cochlea to the internal carotid artery is completed.51 This enables access to the midline structures, including the clivus, basilar artery, vertebral arteries, cranial nerves V through XI, and the opposite lAC. With microdissection techniques, mortality, morbidity, and recurrence rates have improved. Generally, intracranial epidermoid cysts should be treated by complete surgical excision. However, complete removal can be limited by the encasement of neurovascular structures and the risk of increased morbidity with sacrifice of functioning cranial nerves. In these cases, it may be preferable to perform an incomplete removal, since recurrence may occur slowly and reoperation may not be required for many years. 8, 12 Despite careful technique, postoperative cranial nerve deficits are not uncommon. Mohanty and colleagues reported 40% of their patients had postoperative deterioration in cranial nerve function. 52 It must be kept in mind, however, that rates of preoperative dysfunction may also be high,9,l2,52 and some patients may experience an improvement in function, especially notable for cranial nerve V l2 Table 48-1 summarizes the published surgical results from the treatment of CPA epidermoid cysts, from the

TABLE 48-1. Operations and Surgical Results for the Treatment ofCPA Epidermoid Cysts inthe Premicrosurgical and Microsurgical Eras Patients

Total

Subtotal

Rand and Reeves5 SO Grant and Austin 49 SO MacCarty et also SO

3 4 4

2 0 3

1 4 1

Total Premicrosurgical

11

5

6

Guidetti and Gagliardi SO Brackmann and Anderson 28 TL Hamel et al. 79 SO De la Cruz 55 TC Berger and Wilson 27 SO Sabin etal. 80 SO Yamakawa et al." SO De Souza et al. 53 SO, MF Yasargil et al. 26 SO Lunardi et al. 54 SO Altschuler et al 4 8 SO Samii et al. 12 SO Mohanty et al,52 SO Talacchi et al. 9 SO, ST Moffat et al. 25 SO, MF, TL

7 13 11 6 13 10 15 30 22 16 11 40 25 28 15

3 5 8 6 0 1 7 0 22 5 2 30 12 16 12

4 8 3 0 13 9 8 27

Total Microsurgical

262

129

78

SO,

845

Second Operation

Deaths

1 0

N

N

1

2

3

11 9 10 13 12 3

0 3 0 N 0 2 2 2 0 3 4 3 0 7 1

1 2 2 1 0 1 2 1 0 2 0 0 2 1 0

130

27

15

N

suboccipital; TL, translabyrinthine; Te, transcochlear; MF, middle fossa; ST, subtemporal; N, data not given.

846

SURGICAL NEUROTOLOGY

premicroscopic and microscopic eras. From this table it is noteworthy that subtotal resection remains a common occurrence. Second operations are required in 0 to 36% of patients. The mortality rate has substantially improved. Yamakawa and colleagues!' surgically treated 15 cases of CPA epidermoid cysts from 1963 to 1988. Seven patients had total tumor removal, six were subtotal, and two, subcapsular. There were two deaths, and three patients needed at least one additional operation. Excellent postoperative functioning was reported for 71 % of the patients ("excellent function" was not defined in the study). De Souza and coworkers 53 reported surgical results of patients with 30 CPA epidermoid cysts from 1966 to 1986 in India. The suboccipital approach was used in 27 patients, and the middle fossa was used or added in 4. Incomplete removal was the rule. One patient died, three developed meningitis, and four patients had postoperative facial paralysis. Two patients were reoperated on for recurrence. Six patients had bipolar coagulation of the epithelial remnants, and none of these developed symptoms or signs of recurrence by 3 years after surgery. The most complete surgical excisions reported are those by Yasargil and colleagues.i" who operated on 22 CPA epidermoid cysts via suboccipital craniotomy. Radical removal was possible in nearly every case. No recurrences were reported. Of their patients, 80% had normal neurologic recovery, 6% had minor neurologic sequelae, and the remaining 14% were neurologically worse or expired. These writers recommended total excision of CPA epidermoid cysts by means of the suboccipital approach. Lunardi and coworkers 54 used the suboccipital craniotomy to remove 16 CPA epidermoid cysts and the subtemporal approach in one patient. Eleven patients had subtotal excision (nine with adhesion to the brainstem, and two with past-the-midline extension). Three patients developed meningitis (two after subtotal excision), three had hydrocephalus, and two died. Of the 15 who survived, 3 developed recurrence of tumor requiring second operation. Seven of the 11 patients who received subtotal removal were alive and well with a mean follow-up of 6 years. Based on their results these investigators concluded that total removal could decrease survival owing to greater operative risk and that long-term survival was as likely with subtotal removal. Altschuler and colleaguesf reported on 11 CPA epidermoid cysts, 6 with middle fossa extension. All patients had wide suboccipital craniotomy; two had total excision, five near total, four subtotal. Four patients had second operations from 2 to 10 years later, and each of these required a third operation. No deaths occurred. Complications included two CSF leaks and one case of hydrocephalus requiring a shunt. Samii'? reported the outcome of a series of patients operated on for CPA epidermoid tumors between 1980 and 1993. A retrosigmoid semisitting approach was used. Total resection was accomplished in 75 %, and in the remaining 10 cases, capsule was left behind because of neurovascular adhesions. No recurrences were noted on follow-up in patients who had complete resection, but 3 of 10 patients with subtotal resection developed recurrence. Complications included CSF leak (two patients), aseptic meningitis (one patient), and hydrocephalus requiring ventriculoperitoneal shunt (one patient).

Brackmann and Andersorr" reported results of 12 patients who had translabyrinthine removal from 1964 to 1977. Eight tumors were removed subtotally due to adherence of the capsule to brainstem or vessels. Three patients required additional surgery for recurrences. Two postoperative deaths occurred, one due to bleeding and one from postoperative infection. De la Cruz! reported the use of the transcochlear approach for seven CPA cholesteatomas. Total tumor removal was achieved in all patients. One patient with diabetes died postoperatively of pyelonephritis, and autopsy revealed no residual tumor. Three patients had permanent facial paralysis, one patient had persistent headaches, and one had ongoing facial pain. None had evidence of recurrence from 2 to 5 years postoperatively. In 2002, Moffat and colleagues'! reported a series of 15 patients treated with retrosigmoid, retrolabyrinthine, transotic, or translabyrinthine approaches combined with middle fossa as needed. They based the surgical management on a new classification stage of disease extent. Hearing preservation was attempted and successful in four of nine patients with complete audiologic assessment. Complications include aseptic meningitis, CSF leak, pulmonary embolism, aspiration (requiring tracheostomy and jejunostomy), and increased intracranial pressure (requiring ventriculoperitoneal shunt). Complete removal was performed in 12 patients. One patient developed recurrence at 15 years postoperatively. Regardless of the technique used to remove CPA epidermoid cysts, Conley'? advises good dehydration to assist with brain retraction for better exposure, use of the operating microscope, and "great tenacity on the part of the surgeon to allow more of these tumors to be totally removed in the future." In addition, she recommends meticulous removal of all lining except that which invades the brainstem, with use of good anesthetic monitoring and appropriate cranial nerve monitors. When blood vessels or nerves are involved, careful dissection should be done. Tumor lining neurovascular structures may appear to have a plane, but often erosion has taken place and overzealous dissection may lead to disastrous consequences.F Simple intracapsular debulking is not recommended, since this will likely lead to early recurrence requiring reoperation. Reoperation can be expected to be more difficult due to the scarring of tissue planes and adhesions of tumor to neurovascular structures. 58 Staged surgical resection may improve the extent of resection of giant tumors with extension into multiple areas. 58 During dissection, tumor spillage should be avoided to avert the postoperative consequence of aseptic meningitis, adhesive arachnoiditis, and the associated risk of hydrocephalus.'? Some authors irrigate the CPA with steroid." Postoperative parenteral steroids should be used and gradually tapered over 5 to 10 days. Long-term follow-up should include periodic MRI for the detection of early recurrence and observation of identified recurrences. As recurrences may be late, follow-up should continue beyond 10 years. Incomplete excisions will be especially at risk for recurrence. The timing of subsequent surgery is controversial. Some authors debate intervention should be performed at the first radiologic evidence of recurrence, but others suggest waiting for symptoms. 9,52,59

Epidermoid Cysts of the Cerebellopontlne Angle

In summary, use of the middle fossa, translabyrinthine, petrosal, subtemporal, or suboccipital approaches to CPA epidermoid tumors provides good exposure for microscopic dissection.Total removal is limited in at least one-third to all cases due to neurovascular involvement. Despite incomplete tumor removal, long-term follow-up without clinicallyapparent disease is possible and can be done safelywith periodic MRI. Typical complications include cranial nerve dysfunction, aseptic meningitis, hydrocephalus, and postoperative pain.

847

Lumbar Arachnoiditis Repeated meningitis due to intracranial epidermoid has been reported to produce complete obliteration of the subarachnoid space by fibrous tissue at the lumbar leve1. 63 This condition is manifested clinically by difficulty walking and by lower extremity weakness on neurologic examination. MRI can localize the area of CSF blockage, and treatment consists of high-dose dexamethasone and lumbar laminectomy.

Squamous Cell Carcinoma UNUSUAL COMPLICATIONS OF CPA EPIDERMOID CYSTS Spontaneous Meningitis Meningitis as a complication of surgery for the resection or partial resection of intracranial epidermoid cysts has been discussed." However, meningitis occurring spontaneously in a case of intracranial epidermoid is a very rare occurrence. Dermoid tumors, which may be accompanied by a congenital dermal sinus to the skin, have been associated with meningitis. Epidermoid cysts are not connected to sinuses, thereby decreasing the likelihood of drainage and infection. Our search reveals only four case reports of meningitis occurring spontaneously without surgery in CPA epidermoid cysts. Schwartz and Balentine'" reported two cases of meningitis complicating a CPA epidermoid. The first patient was a girl who was admitted to the hospital a total of nine times between the ages of 14 and 34 months for recurrent meningitis. Because the child was treated before the era of CT, her 2-cm prepontine epidermoid was not discovered until autopsy, despite multiple investigations, including ventriculograms, arteriograms, pneumoencephalograms, myelograms, and even a negative frontal craniotomy performed at age 20 months. The epidermoid cyst was open anteriorly and communicated with the subarachnoid space, and the episodes of meningitis were presumed to be aseptic and due to repeated discharge of the cyst contents into the subarachnoid space with inflammatory response. The repeated bouts of meningitis had produced a communicating hydrocephalus, and a venticuloperitoneal shunt had been performed. Retrospective cytologic analysisof CSF obtained during one of the patient's illnesses revealed keratin debris and epithelial cells that might have assisted in the diagnosis before the child's death. A second child with a similar prepontine/premedullary epidermoid discovered postmortem after repeated bouts of bacterial meningitis was described in the same report. Leal and Miles'" reported a similar case of recurrent aseptic meningitis in a young child who later proved to have a fourth ventricle epidermoid. In 1989, Abramson and colleagues'? described a patient who, over a 5-year period starting at age 34, was admitted 30 times to the hospital for aseptic meningi~s. A CT scan in 1981 was read as normal, but repeat CT In 1985 revealed a CPA mass consistent with. an epidermoid, which was removed by suboccipital cramotomy. They proposed that a high index of suspicion be maintained for the presence of intracranial epidermoid in patients with repeated bouts of aseptic meningitis.

Another rare complication of CPA epidermoid is the ?evelop~ent ~f squa!flous cell carcinoma. Like benign Intracr~mal epidermoid cysts, malignant intracranial epide~OId cysts most commonly appear in the CPA.29 Typical features include onset in middle age, male preponderance, and more severe and rapidly progressing symptoms than those produced by benign epidermoid cysts. Squamous cell carcinoma of the CPA may arise in a benign tumor or may appear de novo as a primary neoplasm. Several cases of primary intracranial squamous cell carcinoma of the CPA have been reported, some of which arose de novo,63--{i6 but most of which were squamous cell carcinoma arising in previously verified CPA epidermoid cysts.29,64,67-76 The three earliest cases64,68,76 were found incidentally on examination at autopsy, and the seven later cases are all surgically proven cases of malignant transformation of previously partially resected epidermoid cysts.21,29,67,68,7o,n,74 A more recent case of a primary surgery of a CPA lesion with the pathologic diagnosis of carcinoma arising from an epidermoid cyst was reported by Kveton and colleagues." The clinical course was stabilized by surgical resection, radiation, and chemotherapy," Another patient with incidental carcinoma found in a preexisting benign epidermoid cyst was treated with surgical resection and radiation with no recurrence at 2.5 years." Squamous cell carcinoma (SCCA) arising in previously resected CPA or parapontine epidermoid cysts has been described more frequently than de novo SCCA.29,67,69,7o,n,74,75 None of these patients had radiation therapy before malignant transformation occurred, but several of them .had at least one bout of aseptic meningitis. N?ne of t:?e patients had.complete resection of their benign epIde~OId cysts. ~he tI~e elapsed between the first epidermoid and the dIagnOSIS of SCCA varied from months to decades. Abramson, Morawetz, and Schlitt'? feel that SCCA appears as a result of chronic inflammatory response, much as It can occur in burn scars or chronic ulcers, and recommend complete excision of intracranial epidermoid cysts to prevent bouts of aseptic meningitis that may predispose to the formation of SCCA.

SUMMARY Epidermoid cysts of the CPA are unusual tumors that present with slowly progressive symptoms of hearing loss and disequilibrium, Their diagnosis on CT and MRI examinations may be difficult due to variations in their

848

SURGICAL NEUROTOLOGY

appearance on these studies. Because of their propensity to surround cranial nerves and blood vessels and their adherence to these structures and the brainstem, surgical removal of CPA epidermoid cysts is usually more difficult than for acoustic neuromas or meningiomas. Incomplete surgical removal is frequently necessary, and surgical and postsurgical complications are common. Epidermoid cysts of the CPA present a great challenge to the neurotologist and neurosurgeon, who should be aware of the unique problems inherent in their diagnosis and treatment.

REFERENCES 1. Cruveilhicr J: Anatomie pathologique du corps humain, vol 1. Paris, JB Bailliere, 1829, p 34I. 2. Muller J: Uber den feineren Bau und die Formen der krankhaften Geschwulste, vol I. Berlin, G Reimer, 1838, p 51. 3. Virchow R: Uber Perlgeschwulste. Virchows Arch Path Anat 8: 371-418, 1855. 4. Bostroem E: Uber die pialen Epidermoide, Dermoide und Lipome und duralen Dermoide. Centralbl allg Path Path Anat 8:1-98, 1897. 5. Rand CW, Reeves DL: Dermoid and epidermoid tumors (cholesteatomas) of the central nervous system. Arch Surg 46: 350-376,1943. 6. Nager GT: Epidennoids involving the temporal bone: Clinical, radiological, and pathological aspects. Laryngoscope 2(Suppl):1-22, 1975. 7. Grey PL, Moffat DA, Hardy DG: Surgical results in unusual cerebellopontine angle tumors. Clin OtolaryngoI21:237-243, 1996. 8. Lalwani AK: Meningiomas, epidermoids, and other nonacoustic tumors of the cerebellopontine angle. Otolaryngol Clin 25(3): 707-729,1992. 9. Talacchi A, et al: Assessment and surgical management of posterior fossaepidermoid tumors: Report of 28 cases.Neurosurg 42:242-252, 1998. 10. Mahoney W: Die Epidermoide des Zentralnervensystems.Z Gesamte Neurol Psychiatrie 155:416-471, 1936. I I. Yamakawa K, et al: Clinical course and surgical prognosis of33 cases ofintracranial epidermoid tumors. Neurosurgery 24:568-573, 1989. 12. Samii M, et al: Surgical treatment of epidermoid cysts of the cerebellopontine angle. J Neurosurg 84:14-19, 1996. 13. Kuzeyli K, et al: Epidermoid tumor of the occipital bone. NeurosurgRev 19:109-112,1996. 14. Von Remak R: Beitrag zur Entwicklungsgeschichte der krebshaften Geschwulste. Deutsche Klinik 6:170-174, 1854. 15. Scholtz E: Einige Bemerkungen tiber das meningeale Cholesteatom in Anschluss an einen Fall von Cholestea-tom des III Ventrikels. Virchow's Arch Path Anat 184:225-273, 1906. 16. Baumann CH, Bucy PC: Paratrigeminal epidermoid tumors. J Neurosurg 13:455-468, 1956. 17. Fleming JFR, Botterell EH: Cranial dermoid and epidermoid tumors. Surg Gynecol Obstet 109:403-411, 1959. 18. Kountakis SE, et al: Migration of intradural epidermoid matrix: Embyrologic implications. Otolaryngol Head Neck Surg 123: 170-173,2000. 19. Bailey P: Cruveilhier's "tumeurs perlees." Surg Gynecol Obstet 31: 390-401,1920. 20. Love JG, Kernohan JW: Dermoid and epidermoid tumors (cholesteatomas) of central nervous system. JAMA 107:1876-1883, 1936. 21. Ulrich]: Intracranial epidermoids: a study on their distribution and spread.] Neurosurg 21:1051-1058,1964. 22. Montgomery GL, Finlayson DIC: Cholesteatoma of the middle and posterior cranial fossa. Brain 57:177-183,1934. 23. Alvord EC: Growth rates of epidermoid tumors. Ann Neurol 2:367-370, 1977.

24. Nagashima C, Takaharna M, Sakaguchi A: Dense cerebellopontine epidermoid cyst. Surg NeuroI17:172-177, 1982. 25. Moffat DA, et al:Staging and management of primary cerebellopontine cholesteatoma.] Laryngol Otol 116:340-345, 2002. 26. Yasargil MG, Abernathey CD, Sarioglu AC: Microneurosurgical treatment of intracranial dermoid and epidermoid tumors. Neurosurgery 24:561-567,1989. 27. Berger MS, Wilson CB: Epidermoid cysts of the posterior fossa. J Neurosurg 62:214-219, 1985. 28. Brackrnann DE, Anderson RG: Cholesteatomas of the cerebellopontine angle. In Silverstein H, Norrell H (eds.): Neurological Surgery of the Ear. Birmingham, AL, Aesculapius, 1979, pp 340-344. 29. Abramson RC, Morawetz RB, Schlitt M: Multiple complications from an intracranial epidermoid cyst: Case report and literature review. Neurosurgery 24:574-578,1989. 30. House WF, Doyle ]B: Early diagnosis and removal of primary cholesteatoma causing pressure to the VIllth nerve. Laryngoscope 72:1053-1063,1962. 31. Mikhael MA, Mattar AG: Intracranial pearly tumors: The roles of computed tomography, angiography, and pneumoencephalography. J Comput Assist Tomogr 2:421-429, 1978. 32. Davis KR, et al: Diaguosis of epidermoid tumor by computed tomography. Radiology 119:347-353,1976. 33. Gao Py, et al: Radiologic-pathologic correlation: epidermoid rumor of the cerebellopontine angle. Am] N euroradiol 13:863-872, 1992. 34. Braun IF, et al: Dense intracranial epidermoid rumors: Computed tomographic observations. Radiology 122:717-719, 1977. 35. Dunn RC, et al: Unusual CT-dense posterior fossa epidermoid cyst. J Neurosurg 55:654-656,1981. 36. Laster DW; Moody DM, BallMR: Epidermoid tumors with intraventricular and subarachnoid fat: Report of two cases. Am] Roentgenol 128:504-507,1977. 37. Davidson lID, Ouchi T, Steiner RE: NMR imaging of congenital intracranial germinal layer neoplasms. Neuroradiology 27:301-303, 1985. 38. Savader S], et al: Maguetic resonance imaging of intracranial epidermoid tumors. Clin Radiol40:282-285, 1989. 39. Tampieri D, Melanson D, Ethier R: MR imaging of epidermoid cysts. Am] Neuroradioll0:351-356, 1989. 40. Yuh wrc, et al: MR of fourth-ventricular epidermoid rumors. Am ] Neuroradiol 9:794-796, 1988. 41. Dutt SN, et al: Radiologic differentiation of intracranial epidermoids from arachnoid cysts. Otol Neurotol 23:84-92, 2002. 42. Vion-Drury}, et al: MR imaging of epidermoid cysts. Neuroradiology 29:333-338, 1987. 43. Horowitz BL, et al: MR of intracranial epidermoid tumors: correlation of in vivo imaging with in vitro I3C spectroscopy. Am ] Neuroradiolll: 299-302, 1990. 44. Li FC, et al: Short TlfT2 epidermoids: Lipid or water sigual. Paper presented at the 28th Annual Meeting of the American Society of Neuroradiologists, Los Angeles, March 19-23, 1990, P 63. 45. Steffey D], et al: MR imaging of primary epidermoid tumors. ] Comput Assist Tomogr 12:438-440, 1988. 46. Arriaga MA, Brackmann DE: Differential diagnosis of primary petrous apex lesions. Am] OtoI12:470-474, 1991. 47. Olson ]], et al: Comparative evaluation of intracranial epidermoid tumors with computed tomography and magnetic resonance imaging. Neurosurg 21:357-360,1987. 48. Altschuler EM, et al: Operative treatment of intracranial epidermoid cysts and cholesterol granulomas: Report of 21 cases. Neurosurg 26:606-614,1990. 49. Grant FC, Austin GM: Epidermoids: Clinical evaluation and surgical results.] Neurosurg 7:190-198, 1950. 50. MacCarty CS, et al: Dermoid and epidermoid tumors in the central nervous system of adults. Surg Gynecol Obstet 108:191-198, 1959. 51. House ~'F, Hitselberger WE: The transcochlear approach to the skull base. Arch Otolaryngol 102:334-342, 1976.

Epidermoid Cysts of the Cerebellopontlne Angle

52. Mohanty A, et al: Experience with cerebellopontine angle epidermoids. Neurosurg 40:24-30, 1997. 53. De Souza CE, et al: Congenital cholesteatomas of the cerebellopontine angle. Am] OtoII0:358-363, 1989. 54. Lunardi P, Missori P, Innocenzi G: Long-term results of surgical treatment of cerebellopontine angle epidermoids. Acta Neurochir 103:105-108, 1990. 55. De la Cruz A: The transcochlear approach to meningiomas and cholesteatomas of the cerebellopontine angle. In Brackman DE (ed): Neurological Surgery of the Ear and Skull Base. New York, Raven Press, 1982, pp 353-360. 56. Conley FK: Epidermoid and dermoid tumors: clinical features and surgical management. In Wilkins RH, Rengachary SS (eds.): Neurosurgery. New York, McGraw-Hili, 1985, pp 668-673. 57. Hitselberger W: Personal communication 2002. 58. Sekhar L, Wright D: Comment. Neurosurgery 42:242-252, 1998. 59. Ebersold M: Comment. Neurosurgery 42(2):242-252, 1998. 60. Cantu RC, Ojemann RG: Glucosteroid trearment of Keratin meningitis following removal of a fourth ventricle epidermoid tumour.] Neurol Neurosurg Psychiatry 31:75, 1968. 61. Schwartz]F, Balentine ]D: Recurrent meningitis due to an intracranial epidermoid. Neurology 28:124-129,1978. 62. Leal 0, Miles J: Epidermoid cyst in the brain stem: Case report. ] Neurosurg 48:811-813,1978. 63. Wong Sw, Ducker TB, Powers ]M: Fulminating parapontine epidermoid carcinoma in a four-year-old boy. Cancer 37:1525-1531, 1976. 64. Garcia CA, McGarry PA, Rodriguez F: Primary intracranial squamous cell carcinoma of the right cerebellopontine angle.] Neurosurg 54:824-828, 1981. 65. Nosaka Y, et al: Primary intracranial epidermoid carcinoma. ] Neurosurg 50:830-833, 1979. 66. Scully RE, Galdabini ], McNeely BU: Case records of the Massachusetts General Hospital. New Engl] Med 296:271-276, 1977.

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67. Dubois P], et al: Malignant change in an intracranial epidermoid cyst: Case report.] Comput Assist Tomogr 5:433-435,1981. 68. Ernst P: Haeufung dysontogenetischer Bildungen am Zentralnervensystem. Verh Dtsch Ges PathoI15:226-234, 1912. 69. Fox H, South EA: Squamous cell carcinoma developing in an intracranial epidermoid cyst (cholesteatoma).] Neurol Neurosurg Psychiatry 28:276-281,1965. 70. Knorr ]R, et al: Squamous carcinoma arising in a cerebellopontine angle epidermoid: CT and MR findings. Am ] Neuroradiol 12:1182-1184,1991. 71. Landers]W, Danielski]: Malignant intracranial epidermoid cyst, Arch Pathol Lab Med 70:419-423, 1960. 72. Matsuno A, et al: Primary intracranial epidermoid carcinoma accompanied with epidermoid cyst in the cerebellopontine angle: A case report. No Shinkei Geka 15:851-858, 1987. 73. Nishio S, et al: Primary intracranial squamous cell carcinomas: report of two cases. Neurosurg 27:329-332, 1995. 74. Nishiura I, et al: Primary intracranial epidermoid carcinoma. Neurol Med Chir 29:600-605,1989. 75. Toglia ]U, Netsky MG, Alexander E: Epithelial (epidermoid) tumors of the cranium: Their common nature and pathogenesis, ] Neurosurg 23:384-393,1965. 76. Yamanaka A, Hinohara S, Hashimoto T: Primary diffuse carcinomatosis of the spinal meninges accompanied with a cancerous epidermal cyst of the base of the brain. Gan To Kagaku Ryoho 46:274-276,1955. 77. Kveton]F, Glasscock ME, Christiansen SG: Malignant degeneration of an epidermoid of the temporal bone. Otol Head Neck Surg 94:633-636, 1986. 78. Guidetti B, Gagliardi FM: Epidermoid and dermoid cysts. ] Neurosurg 47:12-18, 1977. 79. Hamel E, Frowein RA, Karimi-Nejad A: Intracranial intradural epidermoids and dermoids. Neurosurg Rev 3:215-219,1980. 80. Sabin HI, Bordi LT, Symon L: Epidermoid cysts and cholesterol granulomas centered on the posterior fossa: Twenty years of diagnosis and management. Neurosurgery 21:798-805,1987.

Chapter

49 Loren J. Bartels, MD, FACS John R. Arrington, MD

Rare Tumors of the Cerebellopontine Angle Outline Cerebellopontine Angle Syndrome Embryology Anatomy of the Cerebellopontine Angle The Cerebellopontine Angle Syndrome Factors Typical Cerebellopontine Angle Syndrome Course Congenital Rest Lesions Cholesteatomas, Epidermoids, and Dermoids Lipomas Miscellaneous Congenital Rest Lesions

T

he cerebellopontine angle (CPA) is a relatively remote anatomic region that is uncommonly involved in pathology. Only 8% to 10% of intracranial neoplasms involve the CPA. Acoustic neuromas account for 70% to 90% of CPA lesions and have a quite variable pattern of symptoms that can greatly delay and confuse diagnosis.1–5 Meningiomas are the second most common lesion of the CPA, comprising 3% to 15% of CPA tumors.5–7 Less common primary CPA lesions include ectodermal lesions (cholesteatoma, epidermoid, dermoid) and lipomas. Other lesions of the CPA are indeed rare in the realm of human CPA pathology. A compendium of the truly rare lesions of the CPA might fall into several categories as outlined in Table 49-1. A discussion of rare lesions of the CPA, then, involves a review of a great many disorders that pathologically affect the region by a variety of mechanisms. Understanding the presentation of these lesions requires a basic understanding of the CPA anatomy and how its disturbance produces the CPA syndrome. To complicate the picture further, CPA syndromes may arise from infection, autoimmune disorders, and paraneoplastic syndromes.

CEREBELLOPONTINE ANGLE SYNDROME Embryology The embryogenesis of the CPA answers a number of questions about the types of lesions that occur in the area. The neural tube infolds primitive ectoderm to form neural structure. In the process, undifferentiated ectodermal tissue may remain from which a variety of tumors can develop. 850

Primary Brain Neoplasms in the Cerebellopontine Angle Gliomas, Astrocytomas, and Oligodendrogliomas Ependymomas Choroid Plexus Papilloma Cerebellar Lesions Inflammatory and Autoimmune Lesions Other Cranial Nerve Lesions Facial Nerve Schwannoma Trigeminal Nerve Schwannoma Lower Cranial Nerve Schwannoma

Direct Extension of Skull Base Lesions to Cerebellopontine Angle Vascular Lesions Metastic Lesions from Intracranial Sources Metastic Lesions from Extracranial Sources Malignant Degeneration of Congenital Lesions Miscellaneous Summary

The facial and cochleovestibular neural elements project laterally into the otic capsule as insulating Schwann cells grow medially more slowly. Similar insulating cells, such as astrocytes, oligodendrocytes, and microglial cells, grow laterally from the brainstem to compete cover the vestibular and cochlear nerves. The junctional area between central connective and insulating tissue and the Schwann cells consists of glial and connective tissue fibrils. For reasons not apparent, the acoustic nerve seems more prone to primary benign neoplasms. The eighth cranial nerve, among the other cranial nerves of posterior fossa origin, is the only nerve to terminate on primary sense organs of ectodermal origin, and the incidence of primary neoplasm of the remaining cranial base nerves is rare. Neurofibromas or schwannomas of the trigeminal nerve, jugular foramen nerves, and hypoglossal nerves are quite rare except in neurofibromatosis.5

Anatomy of the Cerebellopontine Angle Tumors of the CPA cause symptoms by distorting rather complex anatomy through which the seven more caudal cranial nerves traverse. This basal cistern of the skull is limited superiorly by the tentorium, posteriorly by the pons and cerebellum, and laterally by cerebellar (flocculus) approximation to the petrous bone. Medially, the CPA can be said to connect with an equal contralateral entity. Anteriorly, the CPA abuts the petrous bone and clivus. Inferiorly, CPA lesions may displace the cerebellar tonsil and extend into the foramen magnum. The apex of the CPA is the region of the lateral recess of the fourth ventricle, the region where

Rare Tumors of the Cerebellopontine Angle

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TABLE 49-1. Rare Lesions of the Cerebellopontine Angle 1. Congenital rest associated lesions Cholesteatoma, dermoid, epidermoid Lipoma Respiratory endothelial cyst Enterogenous cyst Choroidal epithelial cyst Salivary gland heterotopia Heteroglial tissue 2. Primary brainstem lesions Glioma Astrocytoma Oligodendroglioma Ependymoma Choroid plexus papilloma Glioblastoma multiforme 3. Primary cerebellar lesions Medulloblastoma Rhabdomyosarcoma Hemangioblastoma Hemangiosarcoma Glioblastoma multiforme Anaplastic astrocytoma 4. Inflammatory lesions Arachnoid cyst Cholesterol granuloma of petrous apex Granuloma Focal arachnoiditis 5. Other cranial nerve lesions Trigeminal neuroma Facial nerve neuroma Glossopharyngeal neuroma Vagal neuroma Hypoglossal nerve neuroma

6. Lesions of direct extension from skull base Glomus tumors Craniopharyngioma Petrous apex cholesteatoma Chondroma Chondrosarcoma Osteosarcoma Adenoma Ceruminous Adenocarcinoma of endolymphatic sac 7. Vascular lesions Fusiform aneurysm Saccular aneurysm Hemangioma Hemangioblastoma Hemangiosarcoma Hematoma 8. Lesions metastatic from other intracranial neoplasms Craniopharyngioma Pineal gland tumor 9. Metastatic lesions from nonintracranial sources Lung Breast Cervix clear cell adenocarcinoma Pharynx squamous cell carcinoma 10. Malignant degeneration of intracranial congenital rests Squamous cell carcinoma Melanoma Adenoid cystic carcinoma Malignant teratoma 11. Miscellaneous

the cochlear nerve and vestibular nerves enter the brainstem at the pontomedullary junction. Since the facial nerve exits the brainstem just anteromedial to the cochleovestibular nerve, the central chord of the CPA is the seventh and eighth cranial nerve complex. The key blood vessel of the CPA is the anterior inferior cerebellar artery (AICA).8 Two branch vessels of the AICA are critical: the internal auditory artery and the recurrent perforating artery. These vessels may become parasitized by pathology or be vulnerable during surgical dissection.8 The choroid plexus sometimes protrudes a tuft of tissue through the foramen of Luschka into the CPA.9,10

hypesthesia and pain, constant or lancinating. Cerebellar dysfunction occurs with larger lesions, up to 45% of schwannomas.11–14 Other effects of CPA tumors include nystagmus and gaze paralysis, which may resolve with decompression of the flocculus of the cerebellum.14–17 Thus, the CPA symptom sequence is hearing loss, balance disturbance, altered facial sensation, facial pain, and—quite late in the process—nystagmus, impaired coordination, facial palsy, vocal cord palsy, swallowing difficulty, impaired vision, and eventually long tract signs. The rate and sequence of symptom development may provide clues to nonacoustic lesions: schwannomas and meningiomas with slow appearance of symptoms, generally sparing the facial nerve, malignant lesions with rapid symptom progression commonly with facial nerve involvement, and intraaxial lesions with more ataxia, long tract signs, or other disturbances.4,18,19 The CPA syndrome, however, does not always imply CPA tumor or mass lesion.20 Neurotologic symptoms of CPA disease may occur in patients with minimal audiometric findings. At least 30% of patients with CPA syndromes do not have diagnosable mass lesions. Among other causes are migraine, multiple sclerosis, sarcoidosis, vascular loop syndromes, ischemic disease, paraneoplastic syndromes, rare infectious lesions, and undiagnosable causes.21 Ischemic disease may be suspected in patients with sudden onset of multiple aspects of the CPA syndrome.21 Falsenegative test results may plague diagnostic regimens for both acoustic schwannoma and nonacoustic schwannoma lesions of the CPA. However, when a mass lesion is found, some aspect of the CPA syndrome is almost always present.3,21,22

The Cerebellopontine Angle Syndrome Factors The CPA syndrome in its varied symptomatology is influenced by several factors5: 1. 2. 3. 4.

Primary point of origin of the lesion Rapidity of lesion growth Width of the CPA Individual susceptibility of affected surrounding anatomy 5. Invasive or noninvasive nature of lesion Since the eighth cranial nerve is roughly in the central chord of the CPA, acoustic schwannoma is the archetypal lesion responsible for the CPA syndrome. Predictably, the most common physiologic effects from CPA lesions are altered hearing and balance. Secondary effects related to larger tumors are trigeminal nerve dysfunction including

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Typical Cerebellopontine Angle Syndrome Course The typical course of the two common CPA lesions, acoustic schwannoma and meningioma, is an insidious development of symptoms. In Denmark where a national system to gather data on a high percentage of acoustic schwannoma patients exists, the average number of years of hearing loss secondary to acoustic schwannoma prior to diagnosis is 7 to 8 years.11,23 The average period of documented high-frequency hearing loss prior to tumor diagnosis is 4 years.24 However, over a 4-year period, only 3 of 21 acoustic neuromas were found to grow.25 A period of up to 30 years may elapse between onset of hearing loss and diagnosis, indicating that some lesions are dormant. Sudden hearing loss accounts for about 13% of acoustic neuromas, and acoustic neuromas are found in about 1% of sudden hearing loss patients.26,27 Since the symptom complex for acoustic schwannoma may be as little as 1 day to 30 years, determining the nature of the lesion by duration of hearing loss is not feasible. In fact, it is not unusual for a diagnosis of a nonacoustic, nonmeningioma pathologic condition to be a surprise when operating on the CPA.4,5,18 Whatever the lesion, development of the CPA syndrome pattern in a time period different from 1 to 8 years often implies a rarer lesion of the CPA.4,5,18,23–25,28–30 When the pattern of symptoms broader than hearing loss is considered, the presence a nonschwannoma lesion can often be suspected, especially if the patient already carries a history of a lesion likely to metastasize.

CONGENITAL REST LESIONS Lesions of the CPA can be categorized by tumor category or by location. Although the three most common lesions are schwannoma, meningioma, and primary CPA cholesteatoma, the range of lesions is broad. Table 49-1 outlines a broad range of rare lesions that may occur in the CPA. Although cholesteatomas are the third or fourth most common lesion, they are indeed rare CPA lesions.

Cholesteatomas, Epidermoids, and Dermoids The most common primary congenital lesion of the internal auditory canal (IAC), petrous apex, and CPA is cholesteatoma or a dermoid of similar origin. Congenital choleasteatomas of the skull base and CPA are discussed elsewhere in the text and are discussed here in brief. Facial pain and hemifacial hypesthesia are common symptoms. Tic douloureux is a frequent feature, the presenting symptom in 10 of 13 cases in a report derived largely from Dandy’s data.31 Facial nerve paresis or paralysis occurs in about half.32,33 Facial nerve dysfunction may be manifested by hemifacial spasm and synkinesis as well. Approximately 15% to 20% of patients with CPA cholesteatoma have hemifacial spasm. However, less than 1% of patients with hemifacial spasm have epidermoids. Those patients with hemifacial spasm who did have cholesteatoma typically had other cranial neuropathy as well, which distinguishes them from similar patients without tumor.34 Hemifacial

spasm in infancy, however, correlates with intrinsic brainstem tumor.35 Hemifacial spasm may also occur in patients with meningiomas, enterogenous cysts, arachnoid cysts, and vascular compression syndromes, among other lesions, and is not a specific sign of CPA tumor nor specific for CPA cholesteatoma.20,36–38 Unilateral sensorineural hearing loss (SNHL) is less often a characteristic, occurring in 25% to 50%.31–33 Episodic vertigo is common, occurring in about 40%.32,33 The left side seems to predominate in Dandy’s data.31 Ipsilateral cerebellar signs may occur with larger lesions. Complete removal of CPA cholesteatoma is not common, accomplished in only 20% to 30% of cases. The death rate prior to surgery may be as high as 10%. The surgery-associated death rate may be quite high as well, from 3% to 20%.32,33,39 Chemical meningitis is not rare postoperatively, but is treatable with steroids. Infectious complications after surgical removal efforts can be extremely difficult to control because of the existence of nonvascular keratin, which may support bacterial growth. Regrowth rates may be as high as 13%.32,33,39 Cholesteatoma in combination with acoustic schwannoma has been reported.40

Lipomas Intracranial lipomas are considered congenital rest in origin and more typically occur elsewhere in the cranial cavity than in the CPA. They occur in about 1 or 2/1000 autopsies, which suggests that symptomatic and extant lesions have substantially different occurrence rates. Similarly, they are found in about 1/1000 computed tomography (CT) scans, but only 1/70 intracranial tumors.41 The most common location is the corpus callosum and the vast majority are supratentorial, but they do rarely present in the CPA (Fig. 49-1). The symptom course for CPA lipomas is somewhat different from IAC lipomas. IAC lipomas have a slowly progressive course often similar in symptom complex to schwannomas. However, the CPA lipoma symptom course is typically quite insidious, often much longer than is the case for schwannomas.42 Fluctuant SNHL and episodic dizziness may be presenting symptoms.43 CPA lipomas may present quite a varied course and nonacoustic nerve

Figure 49-1. Lipoma of internal auditory canal with facial and cochleovestibular nerves transversing the lesion.

Rare Tumors of the Cerebellopontine Angle

symptoms may dominate, such as pain or hemifacial spasm.41–44 IAC lipomas may erode bone but typically do not. Although bone erosion is atypical for CPA lipomas, bone spurs or osteomas may accompany them.45 Occasionally, metaplastic cartilage may be found in intracranial lipomas, more commonly in locations other than the CPA.46 Lipomas are typically low density on CT with specific Hounsfield measurement findings.20 Prior to MRI, cisternography helped with the diagnosis, particularly for small intracanalicular lesions.47 With MRI, the lesions are bright with both T1 and T2 imaging, typical for fat.20,41,48 Pathologically, lipomas are trabeculated, fibrovascular, and often inseparable from brain arachnoid. Mesodermal in origin, their method of growth typically entraps cranial nerve fibers in the CPA. Some nerve fibers may show demyelination from tumor effect. Symptoms are caused by mass effect. Aggressive tumor removal risks not only cranial nerve loss, but inadvertent incursion into the brain. Hence, the usual management is to remove no more tumor than is essential to resolve the symptoms related to brainstem compression. It is not unusual to lose acoustic nerve function with removal of CPA lipomas because the nerve is typically so thoroughly invaded, but the facial nerve may be just as involved without fibers distinguishable from tumor fibrous strands.41,42

Miscellaneous Congenital Rest Lesions Miscellaneous congenital rest lesions include the following: 1. 2. 3. 4. 5.

Respiratory epithelial cyst Enterogenous cyst Salivary gland heterotopia Heteroglial tissue Teratoma

Among extremely rare congenital lesions of the CPA are respiratory epithelial cysts and enterogenous cysts, which are felt to represent embryologic endodermal dysgenesis.38,49–52 In the case of enterogenous cysts, embryogenesis failure occurs at about the third week of gestation when the neurenteric canal and the notochord separation from the primitive gut is supposed to occur. Cuboidal or ciliated columnar epithelium, mucous glands, and smooth muscle may join ependymal or glial tissue in the cysts. The lesions are typically low density and avascular on CT scans. On magnetic resonance imaging (MRI), such cysts would be expected to have water density on T1 and to be bright on T2. However, cysts with high protein concentrations may be bright on T1. Cystic lesions of the CPA may possess xanthogranulomatous reaction, cholesterol clefts, and brownish fluid more typical of cholesterol granuloma.53 Histopathology among cystic lesions in the CPA from extremely rare congenital rest cysts to cystic tumors such as craniopharyngiomas.54–59 The differential diagnosis would include arachnoid cyst, cholesteatoma, lipoma, craniopharyngioma, and cystic acoustic schwannomas, although the last of these should have areas with more typical features. Epithelial cysts of respiratory or enteric character may occur in the CPA, rarely, with fluid of a variable nature.38,49–52,60–69 Xanthogranuloma may occur as a solid tumor with involvement of the contents of the IAC, inseparable from

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nerves (personal experience).67,70–73 Cystic astrocytomas can be confused as such an endodermal lesion.20,74 A case report of a cystic astrocytoma of the CPA found a typical mural nodule in a patient with neurofibromatosis, and deficits of cranial nerves V, VI, VII, VIII, ataxia, and long tract signs. Although the lesion was in the CPA, clearly, the nature of the clinical findings suggested a much more invasive process than a neurofibroma.74 Thus, cysts of the CPA are not always benign lesions. Hamartomas or heteroglial tissue of the CPA do occur on an extremely rare basis.75 In general, they consist of astrocytes and dense neuroglial fibers. Oligodendrocytes and small ependymal canals may accompany them. They are thought to be secondary to glial streaming through a pial defect. Solitary leptomeningeal gliomas are thought to derive from these hamartomatous rests.5,76 Heterotopic glial tissue may also occur independent of hamartomas in the CPA as incidental findings at surgery or at autopsy.76,77 Heterotopic cerebellar tissue may accompany hamartomas of the CPA and IAC.78 Hamartomas may be suspected by the lack of typical acoustic schwannoma features on imaging studies, though, more often, the diagnosis is only made after pathologic study.75,76 Salivary gland heterotopia is a hamartomatous process that more commonly occurs in the region of Meckel’s cave, but may extend to the CPA.79 It may arise in a fashion similar to that for epidermoid cysts. Primary cylindroma (adenoid cystic carcinoma) of the skull base may derive from salivary gland heterotopia and may extend into the CPA.5,79 Combination congenital rest lesions may also occur. A respiratory epithelial cyst with both squamous epithelial and columnar lining has been reported.51 Ciliated epithelium and mucus glands as well as recurrent chemical meningitis complicated the clinical presentation. Teratomas may occur in many locations, including the CPA.18,80 Teratomas may undergo malignant degeneration. Not only is locally invasive growth problematic, but malignant dissemination within the cerebrospinal fluid (CSF) spaces may occur.81 Medullomyoblastoma may be teratomatous in origin.82 Morbidity from teratoma and its removal can be incapacitating, and survival after malignant degeneration may be quite unlikely.18 Colloid cysts, usually a congenital rest found in the third ventricle, have been found in the CPA.83

PRIMARY BRAIN NEOPLASMS IN THE CEREBELLOPONTINE ANGLE Perhaps as few as 0.3% to 2% of lesions of the CPA originate from primary brain tissue, and some may reach the CPA by metastasis.5,18,19,84–86 Symptoms vary tremendously depending on the primary area of growth or invasion. Presenting characteristics may be typical of a CPA lesion, but an intra-axial lesion may be suspected because the rate of development of symptoms is commonly more rapid than would be expected with an acoustic schwannoma or meningioma.18,19 Intracranial hypertension with papilledema is more likely with a lesion growing more rapidly than acoustic schwannoma. CT may not easily distinguish these lesions from schwannomas; MRI may more effectively demonstrate brainstem intra-axial status. Auditory evoked

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potentials, not uncommonly bilaterally abnormal, may, however, be normal in some of these lesions. The auditory brainstem response (ABR) changes may involve latency delays, not easily explained wave absence, or distorted amplitude morphology. In contrast, extra-axial lesions tend to cause predominantly ipsilateral abnormalities in auditory evoked potentials.19 Thus, when the history and physical examination suggest a CPA-brainstem lesion, auditory studies are not as sensitive as in the case of schwannomas. In fact, physical examination evidence of CPA disease in the presence of a normal auditory physiology should arouse suspicion of a nonacoustic neuromatype mass lesion. Primary brainstem lesions include the following: 1. 2. 3. 4.

Gliomas Astrocytomas Choroid plexus papillomas Ependymomas

Gliomas, Astrocytomas, and Oligodendrogliomas CPA gliomatous lesions are said to develop from the lateral medullary vellum in the medial wall of the lateral recess of the fourth ventricle. Ependymal cells and ependymal cell canals surrounded by astrocytes form in the region of the foramen of Luschka through which a tuft of choroid plexus typically protrudes. A free half-moon-shaped edge of glial tissue forms the lateral medullary vellum and rarely contains any neural tissue. The tissue is remarkably similar to the subependymal plate of the lateral ventricles and to the filum terminale.87 The various lesions that arise from these tissues include astrocytomas, ependymomas, and choroid plexus papillomas, perhaps a subclass of ependymoma.5,87 Perhaps as much as 80% of primary brain tumors in the region are glial in origin.87 Approximately 40% to 50% of all solid tumors in children are brain tumors (2 to 5 cases per 100,000 per year), 60% to 70% gliomas, and 60% infratentorial. In the infratentorial compartment, about equal numbers are medulloblastomas, brainstem gliomas, and cerebellar astrocytomas.88 The tumors may greatly distort the local anatomy and wrap the cranial nerves, but do not typically invade the cerebellum, pons, medulla, or cranial nerves. Symptomatology is by compression and secondary obstruction of CSF flow. Stereotactic biopsy may have an accuracy rate of 75% with brain tumors.89 Most common symptoms of gliomas of the CPA are nausea, vomiting, ataxia, and visual disturbance. Abducens palsy, facial paresis, diminished corneal reflexes, papilledema, and rigid neck are more common associated findings. Nystagmus is frequently present as are long tract signs. Unilateral deafness and dysphagia are unusual.5,87 Kernohan and Woltman in 1948 reported that children account for about 70% of CPA gliomas and about 70% of persons so afflicted are females.87 Treatment for malignant glioma is radiotherapy following surgery. Chemotherapy may have some additional beneficial effect although long-term survival rates after diagnosis of high-grade malignant gliomas are quite low.90–92 In childhood, about one-third of brain tumors below the tentorium, thus with some potential to extend into the CPA.93 Recurrent brainstem glioma

or medulloblastoma of childhood may respond variably to cisplatin or carboplatin and other chemotherapy agents.90,92,94,95 The astrocytomas of the lateral recess and CPA are typically similar in variety to those found elsewhere in the brain. Astrocytomas of the cerebellum account for about 4% of all intracranial neoplasms.19 Pathologically, a loose assortment of monopolar cells is easily identified as astrocytes and represents a low-grade malignancy. Astrocytomas may be cystic (Fig. 49-2A and B) with a mural nodule that enhances on CT. With imaging, calcification, tumor density reduced in contrast to cerebellum, and cystic characteristics typify astrocytomas, but do not allow definitive radiologic diagnosis.19 A mixed astrocytoma-ependymoma has been reported as well. Oligodendrogliomas may, on extremely rare occasions, present in the CPA.96 Oligodendrogliomas and anaplastic astrocytomas are more sensitive to chemotherapy than glioblastomas.97

Ependymomas Ependymomas typically arise from ependymal cells in the lateral medullary vellum of the fourth ventricle, from the same region as astrocytomas and choroid plexus papillomas.88 A lateral medullary vellum origin places most ependymomas in the fourth ventricle, but a few arise sufficiently laterally to extend into the CPA.98,99 Relatively early obstruction of the fourth ventricle by tumor causes intracranial hypertension. When the lesion develops more laterally, a variety of symptoms may occur, including those of vestibular and cochlear deficits. Calcification of ependymomas is not rare and may be more common in children. The ability to differentiate cell type—medulloblastoma versus ependymoma versus astrocytoma—is driven primarily by location and cystic tendency (astrocytoma).98 An occasional patient presents with a bleeding posterior fossa or CPA tumor, survival from which is poor.100 Of six patients reported with bleeding posterior fossa ependymomas, four died.100 Other symptoms may include vague disequilibrium, chronic nausea, and headaches. Ependymoma is one of the more common posterior fossa lesions in children with brain tumors. When treated aggressively in childhood, long-term sequelae include central endocrinopathies (growth hormone imbalance), impaired intellectual ability, and neurologic handicap. Radiotherapy may account for a majority of sequelae.101,102 Factors associated with better survival rates include completeness of tumor resection, the noninvasive nature of the lesion, a low-grade histology, age older than 6 years at diagnosis, absence of cranial neuropathy, and absence of signs of parenchymal invasion.101,103 Poorer likelihood of survival is correlated with age younger than 2 years at diagnosis, a more aggressive histology, lower cranial nerve neuropathies, and signs of parenchymal invasion.101 An occasional recurrent childhood ependymoma may respond to carboplatin, although at therapeutic levels ototoxicity is common.104 The long-term survival rate from childhood ependymoma may be as low as 45%. Intracranial metastasis develops in less than 5% of childhood ependymomas.101 Clear-cell variants of ependymoma can be difficult to differentiate from oligodendroglioma and cerebellar hemangioblastoma.105,106 Subependymoma is possibly a

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hamartoma, similar in that it contains ependymal cells, but it also features astrocytes and transitional cells, typical of the mammalian subependymal layer. The mass lesion may be so integral to the brainstem that removal is not safely possible. Shunting to resolve intracranial hypertension and biopsy may be all that can be safely accomplished.107

Choroid Plexus Papilloma

A

B Figure 49-2. Cystic grade II astrocytoma of left middle cerebellar peduncle and brainstem, centered at IAC. Contrast-enhanced CT (A) is compared with T2-weighted MRI (B).

The choroid plexus of the fourth ventricle normally resides within that structure, but tufts of choroid plexus do commonly extend through the foramen of Luschka into the CPA, called Bochdalek’s basket.10,108,109 Rare lesions of the CPA include choroid plexus papillomas and choroidal cysts.10,109–134 Ependymomas and choroid plexus papillomas, perhaps a subclass of ependymoma, are sometimes lumped together as a papillary type of tumor.5,87 Choroid plexus papillomas account for about 0.5% of intracranial neoplasms. They are one of several types of lesions that may arise in the region of the lateral recess of the fourth ventricle, including lipomas, heterotopias, and ependymomas.5 In the posterior fossa, the lesions more typically present as fourth ventricle tumors with rather vague symptoms such as nonspecific dizziness. However, intracranial hypertension tends to occur relatively early when papillomas occur primarily in the fourth ventricle. When the lesion occurs primarily in the CPA, dysfunction of hearing, facial movement and sensation, headache, ataxia, dysarthria, speech disturbance, papilledema, and blindness may become progressively apparent. These tumors may also present in the CPA with hearing loss and dizziness as the presenting symptoms. A rare presentation is subarachnoid hemorrhage.10,108,124,127,131,135 Choroid plexus papilloma is more common in the fourth ventricle in adults, in the lateral ventricle in children.10,48,72,131,136–139 The age-related distribution of posterior fossa papillomas slightly favors both early and middle ages, but does not vary a great deal by age. In contrast, lateral ventricle papillomas are most common in childhood, but are also more common at all ages than posterior fossa papillomas.137 Destruction of the petrous bone and erosion of the IAC are possible. In CPA papillomas, blood supply is virtually exclusively from the AICA, providing a clue to diagnosis. An enlarged AICA on angiography is considered a strong indicator of the diagnosis. This vascular pattern is not found in meningiomas, acoustic neuromas, lipomas, or cholesteatomas. The lesions may calcify and otherwise appear similar to meningiomas on imaging studies. When visualized in the CPA, the lesion may broadly attach to dura in a manner similar to meningiomas.10,79 Choroid plexus papillomas are vascular lesions and may be physically quite difficult to separate from the brainstem. Adherence to the brainstem may make total tumor removal imprudent. The tumors may be locally invasive of the brainstem and surrounding structures.119,140 Exuberant bleeding may make tumor extirpation quite hazardous. Tumor consistency may be papillary and fragile or, alternatively, quite firm.10,79 Although total tumor removal is a reasonable goal, aggressive tumor removal can result in a high mortality and morbidity rate.10,124 Recurrent tumor growth after partial removal does occur, making total

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tumor removal preferable in most cases.10,124 Radiotherapy may have a favorable effect on these lesions. The prognosis depends on the combination of tumor compressive effects and surgically induced complications. Histopathologically, choroid plexus papillomata are characterized by a papillary appearance. A single layer of columnar epithelium covers delicate vascular connective tissue. A relationship with the choroid plexus is common, but not always demonstrable. Typically, some of the columnar epithelial cells have vacuoles and mucus. Microvilli, but not cilia, are typically present on the columnar cells. Junctional complexes are notable. The lesions may be difficult to distinguish from papillomatous ependymomas.10,124 A single report was found of a choroidal epithelial cyst whose description is similar to some aspects of choroid plexus papilloma: a cyst wall with a basement membrane and a single layer of epithelial cells with microvilli.69 An occasional patient with CPA choroid plexus papilloma may develop intracranial metastases; thus, malignant degeneration may occur.115,118,119,141,142 A case of multiple lesions, lateral ventricle and CPA, was followed by widespread intracranial and spinal column dissemination. Death occurred within 2 years of the initial diagnosis despite radiotherapy.118 A response to combination chemotherapy by recurrent choroid plexus tumor has been reported.143 Radiotherapy and stereotactic radiosurgery have been reported with some success.130 Choroid plexus papilloma has been reported as a rare part of the von Hippel-Lindau disease.46

CEREBELLAR LESIONS Cerebellar lesions are most commonly intra-axial, but some do extend into the CPA. Thus we review cerebellar lesions with the potential to reach the CPA. Primary lesions of the cerebellum are much more common in children than adults. Medulloblastomas, an embryonal tumor originating from neuroepithelial cells in the roof of the fourth ventricle, are the most common childhood posterior fossa tumor.19,144 Their origin more laterally may be explained by the migration route of the primitive cell lines. It is the eccentric medulloblastoma that can be found in the CPA. Although it most commonly occurs as a midline posterior fossa tumor in children, it may also arise more laterally with a CPA component in adults. Thus, eccentric locations are more typical of adult medulloblastomas, but also occur in children.144 Since medulloblastomas do not routinely present as typical CPA lesions, hearing loss is uncommon, but an altered sense of balance may occur. More typically, medulloblastoma patients have symptomatic obstruction of CSF flow. Symptom duration is typically relatively short compared with acoustic neuromas, commonly days to months. When the lesions do extend to the CPA, disequilibrium not typical of a labyrinthine disorder seems characteristic. Rather than intermittent or fluctuant vertigo, chronic disequilibrium out of proportion to any other findings is described. More characteristic are symptoms of cerebellar dysfunction.19 Marked abnormalities in the ABRs may be found.19 These lesions do not commonly cause seventh and eighth cranial nerve symptoms, but may appear in the CPA on imaging studies.19,144

On CT, medulloblastomas are typically intra-axial lesions denser than surrounding brain. Occasionally, calcification or intratumoral hemorrhage may vary the picture. Calcification may occur in 10% to 15% of medulloblastomas.145 With CT, an unusual tumor may be isodense or hypodense relative to surrounding brain. MRI with gadolinium-diethylenetriamine pentaacetic acid (Gd-DPTA) is superior to CT and other imaging methods in diagnosing medulloblastoma in finding metastases and in following tumor progress with therapy. With T1weighted Gd-DPTA, the degree of invasiveness of the medulloblastoma and metastases, including neural foraminal invasion, can also be assessed.146 On MRI, medulloblastomas are typically hypointense on T1 studies. On T2 images, signal intensity is quite variable depending on cystic, hemorrhagic, and spinal fluid seeding of the tumor. Exophytic invasion of the CPA may be found in some. The tumor may seed spinal fluid, intraventricular spaces, and bone. Typically, the lesions are well demarcated and occur in younger persons and may be confused with meningioma.147 Relative hypovascularity and invasion of cerebellar cortex tend to distinguish these tumors from acoustic schwannomas and meningomas.148 Contrast enhancement of medulloblastoma is commonly homogeneous, but may be heterogeneous in about 20%.149 Intracranial metastases may also be found with this lesion.150 Cystic features occur in about three-fourths of cases and extension through the fourth ventricle foramina occurs in about 15%. The CPA is involved directly in about 10%.149 Medulloblastomas may be part of the familial Gorlin’s syndrome, with brain tumors such as medulloblastoma and astrocytoma occurring in successive generations.151,152 Gorlin’s syndrome occurs in 1% to 2% of medulloblastoma patients.150,152 These tumors plus multiple invasive basal cell carcinomas typify this syndrome.151,152 Medulloblastoma was reported in 4 of 105 Gorlin’s syndrome patients (nevoid basal cell carcinoma syndrome).153 Recurrent medulloblastoma of childhood may respond variably to cisplatin. Ototoxicity is common among these patients.154 Rhabdomyosarcoma, on an extremely rare basis, occurs as a primary cerebellar neoplasm, which may extend from a cerebellar hemisphere into the CPA. Tumors may occur in adults, but childhood disease predominates.5,155 Rhabdomyosarcoma may also be associated with a CPA teratoma or a medullomyoblastoma and may occur primarily in the CPA.5,156 Along with teratomas and medullomyoblastomas, rhabdomyosarcomas are thought to be derived from a neural crest-derivative ectomesenchyme.155 Some hypothesize that medullomyoblastoma is a form of rhabdomyosarcoma.157 Genetic similarities between medulloblastoma and rhabdomyosarcoma have been shown, indicating that both have evidence of similar genetic mutant genes in tumor-derived in vitro cell lines.158 A combination of surgical debridement, radiotherapy, and chemotherapy appears to offer the best chances for long-term survival.155 In children, hyperfractionated radiotherapy under multiple daily anesthetics is feasible in management of the lesion.159 Gallium nitrate appears to be active against cell lines derived from rhabdomyosarcoma.160–164 Hemangioendotheliomas, hemangioblastomas, and hemangiosarcomas are typically solitary vascular neoplasms of the cerebellum or spinal cord. These lesions of

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blood vessel origin may rarely present in the CPA. The three related lesions appear to represent a graded variability of aggressive behavior, with the sarcomatous variety being quite malignant.5 In contrast, hemangioblastomas are cystic, benign vascular neoplasms. When associated with ophthalmic and visceral lesions, criteria for von Hippel-Lindau disease may be met.19,165 Hemangioblastomas can cause polycythemia, which may be secondary to release of erythropoietin from tumor stromal cells. In the autosomal-dominant disorder, von Hippel-Lindau disease, hemangioblastomas may be associated with renal cell carcinoma and pheochromocytoma.165,166 Specific genetic abnormalities can be found in some tumors of patients with von Hippel-Lindau’s disease.165,167 Approximately 23% of patients with hemangioblastoma have von Hippel-Lindau’s disease. Von Hippel-Lindau patients may present with unilateral or bilateral primary papillary tumors of the endolymphatic sac with extension to the CPA. These tumors are commonly mistaken to be ceruminomas (see section on Direct Extension of Skull Base Lesions to the CPA). Glioblastomas involving the posterior fossa may be derivative of astrocytomas and are quite uncommon.19 Multicentric glioblastomas, accounting for 2.4% of intracranial gliomas, may present with a lesion in the CPA.168 The tumor can represent a late malignant degeneration of cerebellar astrocytoma.169 A rapidly deteriorating course from diffuse intracranial metastases has been reported.170,171 Glioblastoma multiforme arising above the tentorium can metastasize to a variety of locations, including the CPA, causing multiple lower cranial neuropathies.172 Glioblastomas have been reported as a late complication of radiotherapy.171,173,174 With both focal and whole brain irradiation, long-term survival with cerebellar glioblastoma is reportedly best with highdose focal irradiation.175 With glioblastoma multiforme, chemotherapy has less than dramatic effects on survival.81,176 In children, both glioblastoma multiforme and malignant astrocytic tumors have an unremittingly poor prognosis in spite of aggressive radiotherapy and chemotherapy.177 Astrocytomas may occur not only in the brainstem, as noted earlier, but also in the cerebellum. Cerebellar pilocytic astrocytoma is a slow-growing lesion that can metastasize within spinal fluid spaces on a relatively long delayed basis.178 Recurrences may appear up to 30 or more years after first diagnosis. The potential to degenerate into anaplastic astrocytoma exists, perhaps increased in probability with radiotherapy.179 Astrocytoma in children can be characterized as juvenile and adult in type, with approximately 60% being the juvenile type. The other approximately 40% of astrocytomas that occur in children are of the adult type. The survival rate for adult type astrocytoma occurring in children is 15% at 5 years, 75% for the juvenile type.180 The overall incidence is approximately 9.3 per million person-years. Approximately 7.5% of these tumors occur in children with neurofibromatosis. Enough of these children have strong family histories of tumors, prompting the notion that astrocytoma in childhood has a genetic basis for some.180 A benign cerebellar astrocytoma can, on a rare basis, recur as a glioblastoma multiforme with CPA presentation.67 Five-year survival rates are poor with both glioblastoma multiforme and anaplastic astrocytoma: 1% for glioblastoma multiforme and less than 20% for anaplastic astrocytoma. Complete cranial radiotherapy of

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children younger than age 7 appears to correlate with lowered intellectual performance, among other neuropsychological deficits.181 The vast majority of these lesions recur at the primary site. Chemotherapy prolongs survival marginally without improving overall survival.176

INFLAMMATORY AND AUTOIMMUNE LESIONS Arachnoid cysts, among the rare disorders of the CPA, occur with some regularity, perhaps as often as 1% of CPA lesions. Prior to the advent of MRI, arachnoid cysts were easily confused with acoustic schwannoma.4,18,53,182,183 MRI now allows accurate preoperative diagnosis of the lesion and its extent.184–186 Most are thought to be congenital, but some may be acquired, for example, after intracranial surgery.187 The CPA is the second most common intracranial site for arachnoid cysts and can cause obstructive hydrocephalus. Though commonly asymptomatic, arachnoid cysts can cause progressive neurologic or audiovestibular impairment, even in children. The most common symptoms are those of CPA lesions: hearing loss and imbalance. Less common symptoms include facial pain, hemifacial spasm, facial paresis, and headache. However, hemifacial spasm in conjunction with an arachnoid cyst can be accompanied by arterial compression of the facial nerve independent of the arachnoid cyst.183 Surgery is often curative. Case reports outline stabilization of progressive auditory decline and tinnitus after surgery, relief of unusual vertigo patterns, resolution of trigeminal neuralgia, and even spastic hemiparesis.188–191 Some patients with CPA symptoms attributable to arachnoid cysts may improve spontaneously. Some describe successful shunting of the cysts. Definitive management remains somewhat controversial, but recent literature favors surgical excision.184,186,192 Sarcoidosis may present with a CPA syndrome and MRI evidence of involvement of the seventh and eighth cranial nerves.193–198 Lyme disease, sarcoidois, aspergillosis, and tuberculosis may present with CPA syndromic features. Lyme disease, caused by Borrelia burgdorferi, is a spirochetal disease, as is syphilis, which, in its tertiary phase, may cause facial paresis/palsy. Especially, when the facial paresis is bilateral, Lyme disease is more likely. Other cranial nerves may be involved. The diagnosis is based on clinical suspicion and the results of IgG and IgM Lyme titers. Quite commonly, at the time of onset of facial paresis/palsy, CSF is involved, even if without symptoms of meningitis. Treatment with tetracyclines such as doxycycline is recommended. Other borrelial organisms can cause similar syndromes. The specific species of Borrelia is geographically dependent. Unusual presentations of infectious diseases may present as posterior fossa, CPA disorders. Aspergillomas may erode into the posterior fossa as well as other parts of the skull base. Tuberculoma as a mass lesion in the CPA is more common in countries where tuberculosis is endemic. Reports of solitary tuberculoma of the temporal bone and CPA appear among the differential diagnosis lists of such places. Long-term management with antitubercular therapy is necessary.37,199–201 Syphilis in its late stages may produce gummas that can grow in many intracranial loci, including

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the CPA.202,203 Cysticerosis may present with a CPA lesion and hemifacial spasm, treatable with albendazole.204 The IAC may appear widened on CT. Typically, arachnoid cysts are of low density on CT scans.183 MRI would show spinal fluid density on T1 and T2 imaging (Fig. 49-3A and B). In cystic lesions of the CPA, the differential diagnosis includes astrocytomas, enterogenous cysts, respiratory endothelial cysts, cholesterol granuloma, and other lesions.53,183 Acoustic neuromas can be largely cystic as well. Arachnoid cysts do not enhance with contrast in either MRI or CT scans. They do not fill immediately with contrast cisternography but may enhance on a delayed basis. Not uncommonly, a heralding arachnoid cyst accompanies acoustic schwannoma and needs no special management. A curious series of patients with chronic, widespread arachnoiditis including significant CPA findings has been reported. The disease was largely surgically managed with significant morbidity and mortality.205 For more extensive disease, CSF shunting may variably provide necessary relief from symptoms of increased intracranial pressure.205 Widespread adhesive arachnoiditis may complicate thorium dioxide myelography.206 Radioactive gold has been used intrathecally for treatment of medulloblastoma, but has resulted in a high incidence of focal arachnoiditis in spinal fluid cisterns, including the CPA. In addition, patients treated with intrathecal gold have shown late-onset aneurysms.207 Lyme disease is a spirochetal infection spread by tick bite and is known for its atypical patterns of disease. An expansive granuloma of the CPA has been reported as associated with Lyme disease.208 The patient had documented infection with Borrelia burgdorferi. When cerebellar compression

A

developed, decompression with removal of much of the granulation tissue was undertaken in spite of florid meningitis. Identification of the disease process afforded patient survival from this extraordinarily rare complication of Lyme disease.208 Other inflammatory processes in the CPA include infectious disorders and abscesses, not the subject of this discussion. Apparent inflammatory mass lesions in the CPA do appear in several manners (Fig. 49-4A and B). Neurosyphilis can cause a CPA syndrome from a gumma in the CPA, which may be either vascular or avascular.203 Osteoradionecrosis of the temporal bone can project inflammatory disease into the CPA.209 Cholesterol granuloma may extend into the CPA from temporal bone sources (Fig. 49-5A and B) or may complicate primary intracranial cholesteatoma.5,67,210–212 A postsurgical granuloma has been reported following posterior fossa surgery.213 Granulomas of the posterior fossa may occur without obvious explanation.214 Osteoradionecrosis may extend to the CPA and present as a lesion.209

OTHER CRANIAL NERVE LESIONS Schwannomas appear to be the primary lesions of cranial nerves V, VII, and VIII through XI. The symptoms tend to reflect the nerve affected. The overall incidence of schwannoma of cranial nerves other than the acoustic nerve is approximately 2% to 3% of CPA tumors.31,183 Additional malignant tumors that may arise in skull base cranial nerves include neurofibrosarcomas and fibrosarcomas, typically a complication of neurofibromatosis type 2 (NF2).215,216

B

Figure 49-3. Arachnoid cyst of right CPA and prepontine cistern. CT (A) and T1-weighted MRI (B) demonstrate CSF density with mass effect.

Rare Tumors of the Cerebellopontine Angle

A

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B

Figure 49-4. Otogenic cerebellar abscess. Enhanced T1-weighted MRI shows sigmoid sinus phlebothrombosis and meningeal thickening extending into the CPA and porous acousticus.

Facial Nerve Schwannoma The facial nerve is commonly involved in CPA syndromes, either as part of the initial presentation of the disease process or as a complication of treatment. Facial schwannoma is one of the few lesions primary to the facial nerve and rarely presents with an apparent initial nidus in the CPA.217 Facial nerve neuromas commonly involve extension superior to the geniculate ganglion into the middle cranial fossa in addition to extension into the CPA. These characteristics make many facial nerve neuromas distinct on CT. Earlier generation, lower resolution MRI studies may underestimate the degree of facial nerve involvement by tumor, but significant enlargement with enhancement has a high correlation with tumor.218,219 However, MRI is felt to give the operator the best opportunity to diagnose the lesion preoperatively, and it assists in preoperative planning.220 Additional features include widening of the fallopian canal in the temporal bone, often with additional mass lesions in the middle ear or mastoid. Facial paresis, either obvious or subtle, is frequently present, often with synkinesis. Facial nerve symptoms (paresis, synkinesis, paralysis, tearing dysfunction) in some patients may exceed 10 years. Facial palsy can be transient, mimicking Bell’s palsy. Diagnosis may be elusive because symptoms may be minimal for many years. Even with audiometric evidence of retrocochlear pathology, ABRs may be normal.221 The mass lesion may involve any portion of the nerve from the CPA to the parotid gland, and multiple contiguous portions of the nerve are commonly involved. These several features make possible the preoperative diagnosis in a high percentage of the lesions.222

Subclinical involvement of the facial nerve by tumor includes not only diminished electrical response,223,224 but also diminished tear concentration of lysozyme.85 These changes are identifiable with multiple mass lesions and are not specific for tumor type, but rather are indicative of facial nerve compromise. After removal of the facial nerve, repair by cable graft or rerouted end-to-end facial nerve to facial nerve anastomosis is recommended. Fisch and colleagues suggest the use of fenestrated, collagen tubes for the purpose.225 Barrs and coworkers suggest that the most reliable technique is suture anastomosis, recommending that a single suture be used in the CPA.226 Rerouting of the facial nerve is preferred to cable grafting when possible.225,226 Along with facial nerve schwannoma is the rarer lesion—a nervus intermedius primary schwannoma. Subtle changes in taste perception, eye, and nasal dryness may be the only subtle facial nerve complaints. Otherwise, when these tumors present in the internal auditory canal and CPA, they appear to be acoustic schwannomas.227,238 Malignant facial schwannoma has been reported. Malignant neuromas may occur as part of the NF2 syndrome, more typically involving nonskull base nerves. Isolated malignant neuromas of the skull base also occur on a solitary basis, independent of NF2. Skull base involvement with malignant schwannoma carries a particularly poor prognosis.229,230

Trigeminal Nerve Schwannoma Trigeminal ganglion neuromas often present in the CPA (Fig. 49-6). The comparative incidence, reported by Revilla31

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Figure 49-6. Trigeminal neuroma in cerebellopontine angle with extension from the Meckel’s cave.

A

B Figure 49-5. Cholesterol granuloma originating in the petrous apex. With CT (A) and T1-weighted MRI (B), an expansile mass extends to left CPA. Hyperintensity on T1 is consistent with microhemorrhage.

at all. Some trigeminal nerve tumors appear first with seventh and eighth nerve root effects.183 In one of 16 patients who had a CPA tumor and normal hearing, a fifth nerve schwannoma was found.3 CT with bone imaging often demonstrates petrous apex erosion. Imaging of neuromas is independent of location: neuromas enhance with contrast on both CT and MRI. On CT, neuromas tend to be hypodense, isodense, or may be even mildly hyperdense without contrast.183 With MRI, the lesions tend to be isointense on TI-weighted images enhanced brightly with Gd-DPTA and are therefore more easily detected on MRI. Removal of lesions in this region can follow the usual retrosigmoid approach, but can also be accomplished through a newer transpetrosal, middle fossa route.232 A malignant schwannoma originates extremely rarely in the trigeminal ganglion and may extend into the CPA. The tumor tends to occur in younger individuals, and a significant number occur as a malignant neurofibroma in patients with NF2.233 Melanotic schwannoma of the trigeminal, acoustic, or other cranial nerves is possible.234-236 At surgery, a melanotic schwannoma appears intensely black, reminiscent of melanoma, and may either act benign or malignant. Tumor regrowth rate is unusually rapid and intracranial metastases may be aggressive. Pathology appears to behave like melanoma and prognosis is guarded. Treatment with chemo-radiotherapy for melanoma may provide palliation.236

Lower Cranial Nerve Schwannoma was 3 of 205 CPA lesions, or as often as 3 of 64 CPA tumors.37 The mass tends to involve either the ganglion or the nerve root or both. Fifth nerve symptoms tend to occur prior to auditory nerve symptoms by more than 4 years.31 Symptoms may include those of trigeminal neuralgia.31,231 The pain of trigeminal schwannoma tends to be chronic burning as opposed to typical trigeminal neuralgia, and pain usually precedes weakness of the masticatory muscles.31,183 Up to half of trigeminal neuromas may cause eye muscle deficits, and some may arise with no fifth nerve symptoms

Schwannomas of the glossopharyngeal, vagus, and spinal accessory nerves account for less than 1% of CPA lesions and may be isolated or occur with NF2. Hoarseness and hearing loss tend to be presenting symptoms. Palatal weakness and a diminished gag reflex with unilateral decreased pharyngeal sensation are typical physical features.4,31,183 The jugular foramen may be widened because these lesions may be transcranial, extending from the posterior fossa through the jugular foramen into the upper neck (Figs. 49-7A and B; and 49-8A and B). When approached

Rare Tumors of the Cerebellopontine Angle

only via a suboccipital technique, failure to remove the jugular foramen and cervical components may result in recurrence. Occasionally, the lesion is found incidentally on imaging without apparent related symptoms. On a rare basis, it may occur only in the posterior fossa without skull base involvement. A case has been reported of a spinal accessory neuroma, which grew intra-axially, arising from the intra-axial portion of the nerve.237

DIRECT EXTENSION OF SKULL BASE LESIONS TO CEREBELLOPONTINE ANGLE Skull base neoplasms such as glomus tumor, osteoma, lowgrade adenocarcinoma, chordoma, craniopharyngioma, chondroma (Fig. 49-9), chondrosarcoma, and cholesterol granuloma may reach the CPA by direct extension.

A

A

B Figure 49-7. Spinal accessory nerve neurilemmoma. T1-weighted sagittal (A) and coronal (B) MRI demonstrate an extra-axial mass in left CPA with extension into the foramen magnum and jugular fossa. The cerebellar cyst accompanied lesion.

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B Figure 49-8. Jugular foramen neuroma postradiation from a childhood cerebellar tumor. Contrast enhance T1-weighted coronal MRI (A) demonstrates enhancing mass extending from left CPA to neck. CT (B) shows widening of left jugular foramen.

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Figure 49-9. Chondroma of petrous apex extending through the cerebellopontine angle into cerebellum.

Glomus jugulare tumors (Fig. 49-10A and B) extend with some regularity into the CPA.5,183 CPA extension is classified differently by Fisch and Mattox238 and Jackson.239 The larger lesions may parasitize the vertebral artery system and may substantially increase the difficulty of tumor removal (Fig. 49-11A and B). Cranial nerves involved in glomus tumors include those of the jugular foramen, glossopharyngeal, vagus, and spinal accessory. Less commonly, the hypoglossal and facial nerves demonstrate tumorrelated paresis. With major intracranial extension, surgical approaches may vary from single to staged. For most glomus tumors, even with some intracranial extension, singlestage removal is possible.240 Ceruminous adenomas of the external auditory canal typically spring from the cerumen gland areas of the external auditory canals.5,138,241 However, another CPA tumor with its center of growth located between the sigmoid sinus and the IAC may errantly be called ceruminous adenoma. Such tumors arising from the endolymphatic sac or surrounding tissue tend to be slow-growing, locally aggressive lesions, which sometimes erode bone. They may also erroneously be called middle ear adenomas. Other misapplied diagnoses for this tumor include choroid plexus papilloma, metastatic thyroid carcinoma, and metastatic renal cell carcinoma, among others.242,243 First reported as a primary endolymphatic sac lesion by Hassard, the lesion has been thoroughly characterized by Heffner as a papillary-cystic, low-grade adenocarcinoma.242,244,245 In a report that reviewed the histology and prior literature reports of 20 adenomatous lesions that centered on the posterior fossa face between the sigmoid sinus and the IAC, Heffner extrapolated the origin of the tumor as the endolymphatic sac. Of the 20 lesions, 17 extended into the CPA. With subtotal removal, recurrence rates were quite high: five of six survived surgery. With aggressive removal of contiguous bone and soft tissue around the tumor, recurrence was virtually eliminated (11 of 12). A number of features of the normal endolymphatic sac also appear in the tumor. The term carcinoma is applied because of its locally aggressive

A

B Figure 49-10. Small glomus jugulare tumor. Noncontrast T1-weighted sagittal MRI (A) and contrast enhanced T1-weighted axial MRI (B) demonstrate small enhancing CPA extension of glomus tumor. Absence of signal voids raises question of meningioma or neuroma.

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A

863

Fibrous histiocytoma, also known as aggressive fibromatosis or fibrocytoma of the skull base, may extend to the cerebellopontine angle. The lesion is largely discovered in childhood and, although it is usually benign, it commonly recurs locally without aggressive removal. The lesion may extend both to the CPA and to the base occipital condyle, destabilizing the skull-cervical spine relationship. Although the lesion may appear benign, degeneration to a sarcoma may occur. The lesion has been variously called fibrocytoma, aggressive fibromatosis, and fibrous histocytoma.139,216,246,247 In addition, histiocytosis, perhaps a similar lesion, may appear as an isolated intracranial lesion.214 Chondromas and chondrosarcomas of the skull base are exceedingly rare, generally isolated lesions with an incidence of less than 1/1000 intracranial lesions. From their origin in the skull base at the petro-occipital junction, the lesions may extend into the CPA. Mottled destruction of the petrous apex is similar to the radiographic changes that occur in analogous lesions in digits and is a suggestive radiographic feature. The tumors may be bilateral.248 Patients with Oilier’s disease and Maffucci’s syndrome may develop skull base chondromas. Multiple enchondromas characterize Oilier’s disease, and Maffucci’s syndrome adds hemangiomatosis. Chondrosarcoma may complicate the picture.248,249 A brainstem glioma-type lesion occurs with some frequency in patients with Oilier’s syndrome.249 Chordoma, as a tumor derivative of the primitive notochord, typically occurs in the clivus. Extension to the posterior fossa and CPA does occur.250 Tumor removal is often incomplete and recurrences can be problematic. Chordoma removal can be challenging by any approach, whether posterolateral, transoral, frontolateral, or through the temporal bone and retrosigmoid region in a true lateral perspective. When approachable from a true lateral perspective, an advantage is relatively early control of the vertebral arteries, brainstem, and spinal cord.249 Craniopharyngioma from suprasellar areas may extend directly through the skull base to the CPA, even from a remotely removed suprasellar source.56,58 Craniopharyngioma may appear to arise primarily in the CPA without apparent pituitary lesion.56 An osteoma can present as a CPA mass lesion (Fig. 49-12).31 Both fibrosarcoma and osteosarcoma of the temporal bone have been reported as a complication years after radiotherapy for cerebellar malignant astrocytoma.251,252

B Figure 49-11. Left glomus jugulare tumor. Noncontrast T1-weighted sagittal MRI (A) and contrast-enhanced axial T1-weighted MRI (B) demonstrate massive involvement of skull base, posterior fossa, and neck. Signal void areas indicate a highly vascular mass.

behavior and its propensity for recurrence.138 Short of aggressive removal, recurrence is troublesome, but metastasis does not characterize the disorder.5,241,242,244,245 A fairly large experience with papillary adenomas of the endolymphatic sac is available in the literature. An association with von Hippel-Lindau disease has been found in some. Since von Hippel-Lindau disease is a syndrome that may lead to malignancies of multiple organs, its presence should be sought in patients with primary endolymphatic sac tumors, especially if bilateral endolymphatic sac tumors exist.

VASCULAR LESIONS Aneurysms of the posterior circulation can simulate tumors. In the posterior fossa, aneurysms may be either saccular (Fig. 49-13A and B) or fusiform, but the fusiform type predominate.253–255 Atypically, large aneurysms may present as a mass lesion rather than with subarachnoid hemorrhage.183,256 Saccular aneurysms are less common than fusiform ones in the posterior fossa and typically arise at major vessel branching points, presumably secondary to an elastic membrane defect. Although saccular aneurysms of the posterior fossa are more likely of AICA origin, an occasional one may arise from the posterior inferior cerebellar artery.257 Saccular aneurysms may be more likely to present in the posterior fossa with subarachnoid hemorrhage

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Figure 49-12. Internal auditory canal osteoma occluding the meatus.

than are fusiform aneurysms. The fusiform aneurysms are thought to be secondary to atherosclerosis and may cause a mass effect on lower cranial nerves.5,183 Aneurysm may present as a late complication of intrathecal radioactive gold for treatment of medulloblastoma. The complication

appears to be related to nonhomogeneous deposition of the gold in subarachnoid spaces.207,258 A tortuous basilar artery may present with the CPA syndrome and retrocochlear findings with audiometry and electrophysiologic measures. The diagnosis can be suspected from CT or MRI.259 An arteriovenous malformation can generate a mass effect in the CPA. A patient with secondary facial pain has been reported. The pain was relieved with removal of the lesion.260 Also, arteriovenous malformations of the CPA may present with acute subarachnoid hemorrhage.183,260,261 Hemangiomas may involve the facial nerve in the IAC with or without extension into the CPA.183,262 Capillary hemangioma may grow in the IAC without audiometric changes and can be discovered based primarily on patient complaints.263 The preferred imaging process for hemangiomas is MRI with contrast because many of these lesions are not as readily or completely assessable without contrast.264,265 The density of hemangiomas may vary from hypointense to hyperintense, depending on flow and hemorrhage.261 In a review of eight cases involving the IAC and facial nerve, the nerve and geniculate ganglion in five were so intimately involved with tumor that the facial nerve required grafting.243 A potential clue to hemangioma is facial palsy in conjunction with a primarily IAC tumor that is comparatively small,266 though differentiation from facial nerve schwannoma may be difficult. When IAC

A Figure 49-13. Vertebral-posterior inferior artery junction aneurysm. T2-weighted axial MRI (A) shows signal void in right CPA aneurysm and a nearby ecstatic basilar artery. Aneurysm was confirmed with angiography (B).

B

Rare Tumors of the Cerebellopontine Angle

lesions appear to extend to the geniculate ganglion, complementary CT imaging is recommended because MRI and CT together might provide some information on the possible existence of hemangioma.267 Most hemangiomas involving the facial and cochleovestibular nerves are limited to the IAC and geniculate ganglion, but some are more extensive, involving the CPA. Among other vascular neoplasms that can extend to the CPA, hemangiopericytoma has been reported as an entity separate from, but sometimes confused with, meningioma.268 Hemangiopericytoma, hemangioblastoma, and related lesions were discussed earlier. Cerebellar angiomata can produce cerebellar hematomas.222 Primary brainstem vascular malformation may cause an apparent CPA tumor presenting as a hemorrhage.269 Hemorrhage into an acoustic schwannoma may precipitate the diagnosis of a CPA lesion.270 Repeated hemorrhage into an acoustic schwannoma has been postulated to explain a clinical course suggestive of repeated apparent subarachnoid hemorrhage.271 An organizing hematoma, postsurgical or otherwise, can present as a CPA mass lesion, even on a much delayed basis.272,273 Cryptic vascular malformations can cause pontine hemorrhage, which can present both as a hemipontine hematoma and a CPA mass lesion.269 Choroid plexus papilloma of the CPA has been reported to present with subarachnoid hemorrhage.125

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METASTATIC LESIONS FROM INTRACRANIAL SOURCES A variety of primary intracranial tumors can spread to the CPA directly or via CSF movement in subarachnoid spaces.148 The majority of these lesions are glial in origin and fall into three categories: astrocytoma, medulloblastoma, and brainstem glioma.88 Most such primary brain tumors can arise in the posterior fossa and extend primarily into the CPA. Many of the same cell types can metastasize to the CPA among other destinations. Pineal yolk sac lesions may spread within the subarachnoid system to involve the CPA.129 Mentioned previously is the potential for primary intracranial squamous cell carcinoma to disseminate and secondarily involve the CPA.274 Also discovered was a prolactin-secreting pituitary tumor, which was felt to have metastasized via venous channels to the CPA.275

METASTATIC LESIONS FROM EXTRACRANIAL SOURCES Metastatic lesions to the CPA are so rare that the combination of a prior malignant lesion and a secondarily discovered, isolated CPA mass should not presume the notion of a metastasis to the CPA.183 In addition, women with breast cancer are more likely to develop a meningioma.183,276–281 Sources of adenocarcinoma to the CPA (cerebellum, brainstem, subarachnoid spaces, meninges) or facial nerve include breast (Fig. 49-14A and B), prostate, lung, and ovary.18,282–285 Adenocarcinoma from the breast and prostate have been seen as metastases to skull base

B Figure 49-14. Breast adenocarcinoma. Metastatic tumor to left CPA is shown with T1-weighted axial (A) and T2-weighted axial (B) MRI. (Courtesy of Robert Jackler, MD).

diploic bone with extension into the CPA (Fig. 49-15). Among the unusual lesions reported to metastasize to the CPA is a malignant fibrous xanthoma.286 Lung cancer metastases to the intracranial cavity usually appear above the tentorium.282 Anaplastic carcinoma of the lung has been reported to metastasize to the CPA with the radiographic appearance of an acoustic schwannoma (Figs. 49-16, 49-17, and 49-18).18,287–292 A role may exist for successive removal of an isolated intracranial metastasis in addition to removal of the primary pulmonary lesion.292

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Figure 49-15. Adenocarcinoma of the breast metastatic to petrous apex (arrows) with extension into the cerebellopontine angle.

Paraneoplastic syndromes may arise primarily from adenocarcinomas, small-cell carcinoma of the lung, melanoma, and other malignant tumors. Involvement of the lower cranial nerves in a rapidly progressive unilateral or especially bilateral neuropathy should raise a question of paraneoplastic syndrome. It is to be distinguished from Guillain-Barré syndrome with its primarily motor involvement. Paraneoplastic syndromes may have associated with them elevated antibody levels: anti-Hu, anti-Ri, anti-Yo, anti-Ma, anti-Ya, and anti-Tr.293 However, paraneoplastic phenomena may include hearing loss without apparent antibody abnormality and may arise prior to identification of a primary malignancy. Lyme disease may cause a paraneoplastic syndrome-like disorder as well. Plasmapharesis may be helpful in reversing the cranial neuropathies but may not alter the course of the disease.294 Clear-cell adenocarcinoma (diethylstilbestrol-related) of the cervix and vagina has been reported to metastasize to the cerebellum (hence, CPA) after a long delay.295 Dysgerminoma, a malignant male reproductive tissue lesion, has been found as bilateral CPA lesions (personal communication, Derald Brackmann).296 Oropharyngeal squamous cell carcinoma has been reported to appear in the CPA.18 In the event of metastatic carcinomas, facial paralysis seems to occur fairly early, particularly with respect to tumor size and symptom duration.18 In addition, the lesion may spread by perineural invasion along the mandibular nerve or other divisions of the trigeminal nerve to the CPA.297

MALIGNANT DEGENERATION OF CONGENITAL LESIONS Primary epidermoid carcinoma may occur in the CPA without obvious cutaneous primary origin.5,210,274,298–305 Most primary intracranial squamous cell carcinomas, at least 25 reported, are thought to originate in epidermoids,

A

B Figure 49-16. Large cell anaplastic carcinoma of the lung, metastatic to right cerebellum and CPA. T2-weighted axial (A) and coronal (B) MRI show intra-axial heterogeneous mass extending to right CPA.

but 1 each may have originated in a dermoid and in a craniopharyngioma.274 In one case report, a multiply recurrent epidermoid eventually degenerated into a primary intracranial squamous cell carcinoma.304 The technical term is primary intracranial squamous cell carcinoma, or PISCC. The PISCC is differentiated from a squamous cell carcinoma that is metastatic, for example, from pharyngeal sources.18,297 The tumor may spread to the CPA along the trigeminal nerve by means of perineural invasion.297 Several additional histologic types that occur as primary congenital rest lesions may degenerate into malignant lesions. Melanoma is thought on extremely rare occasion to arise as an apparent primary lesion in the CPA.306,307 Teratoma of the CPA has been previously reported on

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Figure 49-18. Anaplastic carcinoma of lung metastatic to internal auditory canal.

A

Hyperreflexia, gaze paresis, and gaze nystagmus completed the grim findings found to be secondary to a metastatic, systemic, malignant lymphoma. Associated with acquired immune deficiency syndrome, malignant lymphomas may arise in the cerebellum and cause CPA symptoms.308 Diffuse histiocytic lymphoma has a reputation for central nervous system metastases.309 A high-grade lymphoma of the cerebellum can be a complication of chronic lymphocytic leukemia with secondary symptoms of a CPA syndrome.305 In addition, plasmacytomas may arise primarily in the subarachnoid spaces, including the CPA.296,311,312

SUMMARY

B Figure 49-17. Leptomeningeal carcinomatosis. Contrast-enhanced axial T1-weighted MRI of IACs (A) and brain (B) demonstrate abnormal enhancement in both IACs and left parieto-occipital meninges.

extremely rare occasions. The condition is generally malignant with poor prognosis.18 Medullomyoblastomas may arise from teratoma.18,82 Adenoid cystic carcinomas may form in the CPA, perhaps from salivary gland heterotopia.5

MISCELLANEOUS Unilateral hearing loss, facial paralysis, diminished corneal reflex, and contralateral hemiparesis presaged a mass lesion in the CPA with associated internal auditory meatus erosion.

The range of lesions that can involve the CPA is quite broad. Of all of the lesions that involve the CPA, however, fewer than 5% will come from this broad group of truly rare lesions. Acoustic neuroma, meningioma, cholesteatoma (epidermoids, dermoids), and lipoma, taken together, account for more than 95% of CPA lesions. Because so many different lesions can involve the CPA, preoperative diagnosis of each is quite unlikely. However, several features will clue the physician to the possibility of a nonacoustic, nonmeningioma, nonlipoma, noncholesteatoma lesion (Table 49-2). Malignant lesions, for example, more commonly involve a shorter course, an atypical age group, and more dramatic symptoms and physical findings, often in conjunction with atypical radiographic characteristics. Additional radiographic clues might include an apparent intra-axial brain source, unusual extension within the CPA, atypical skull base erosion, cystic features, and uncommon blood vessel features. The presence of other history of genetic abnormalities, prior intracranial tumors, prior radiotherapy to the brain or skull base, or other systemic disorders may offer clues to CPA pathology. In evaluating patients with symptoms and physical findings suggestive of CPA disease, the imaging modality of first resort is contrast-enhanced MRI. In comparison with CT, MRI offers superior soft tissue contrast, greater lesion enhancement, and absence of beam hardening artifacts. CT has a role in imaging bony skull base tumor effects and fat when suspected. Arterial angiography or

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TABLE 49-2. Rare Cerebellopontine Angle Tumors Acoustic Neuroma

Other Mass Lesions Typical Initial Presentation

87% prolonged duration, typically 4–8 years, 13% sudden hearing loss Hallmark feature 1st, 2nd division, large tumors Vague dizziness to vertigo Rare Only with larger tumors, mild compared with size Only with large tumors

Duration of symptoms

Widened in 85% to 90% lesion centered on IAC CPA portion of tumor enhances Extra-axial

Internal auditory canal IV contrast Axial, extra-axial

>90% apparent Less dess than spinal fluid Strong enhancement Extra-axial

T1 iages T2 images Gadolinium DPTA Axial, extra-axial

Hearing loss Trigeminal loss Vertigo, dizziness Other cranial neuropathy Cerebellar function impairment Headache, increased intracranial pressure

Variable: long for lipoma, cholesteatoma, meningioma; often short for malignant and intra-axial near midline lesions Minor feature 1st, 2nd, 3rd division Imbalance common, not vertigo Not rare Common, particularly with malignant lesions 4th ventricle blocked in early near midline, intra-axial lesions

Computed Tomography Usually not widened, lesion eccentric to IAC Variable enhancement Either

Magnetic Resonance Imaging Variable intensity signal Hypo, isodense, or hyperdense Variable Variable

CPA, cerebellopontine angle; DPTA, diethylenetriamine pentaacetic acid; IAC, internal auditory canal.

MRI angiography may be helpful in specific lesions when looking for displacement of vessel, vessel hypertrophy, or aneurysms. In most situations, imaging will allow the physician to predict with reasonable certainty the presence of typical CPA lesions. With rarer lesions, an imaging differential diagnosis may be less certain. Even with modern diagnostic modalities, precise tumor diagnosis may elude the most astute physicians until the sanctum of the CPA is breached.4

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Outline Medulloblastomas Brainstem Gliomas Cerebellar Astrocytomas Ependymomas Choroid Plexus Tumors

I

Chapter

Intrinsic Posterior Fossa Brain Tumors

Hemangioblastomas Metastatic Tumors in the Posterior Fossa Conclusions

n classical clinical neurology, all processes between the neuron and an end organ that could best explain a patient’s symptoms and signs are considered when arriving at an anatomic and pathologic diagnosis. Impaired hearing and dizziness are common symptoms of vestibular schwannomas or cerebellopontine meningiomas but are uncommon with intrinsic tumors of the posterior fossa. Yet the neurotologist should have a working knowledge of intrinsic posterior fossa tumors’ clinical features, just as a neurosurgeon should have of inner and middle ear disorders. This helps establish the correct neurotologic or neurologic diagnoses for these patients. This knowledge is increasingly relevant. Epidemiologic studies have showed increased primary intrinsic brain tumor incidence over the past 2 decades.1–4 This increase correlates with improved neuroimaging with computed tomography (CT) and magnetic resonance imaging (MRI). Populationbased autopsy studies suggest that this increase reflects improved premorbid diagnosis, not a true increase in incidence.5 The implications for clinicians are similar, regardless. The increases are greatest in the elderly population, more than fivefold for patients older than 85 in the period 1973 to 1985.3 Malignant primary brain tumors occur in 6 to 7 per 100,000 persons per year in the United States.6 Their prevalence in the United States has been estimated to be 29.5 per 100,000.7 Between 1991 and 1995, malignant brain tumors accounted for 1% of newly diagnosed adult cancers but 2% of all adult cancer-related deaths.8 They are the most common solid organ tumor of childhood, occurring in up to 1 in 1300 children before age 20.8 They are the second most common cause of cancer-related death in children younger than 15 years.9,10 Intrinsic posterior fossa tumors may be more important differential diagnostic considerations for neurotologists in the pediatric population. Sixty percent to 70% of childhood intrinsic brain tumors are in the posterior fossa. In adults, most tumors are supratentorial. The clinical presentation and tumor types are different for posterior fossa and supratentorial tumors. The Childhood Brain Tumor Consortium evaluated almost 3300 children with brain tumors and found that in a significant percentage there

Ian F. Parney, MD, PhD, FRCSC Lawrence H. Pitts, MD Michael W. McDermott, MD, FRCSC

was involvement of both the brainstem and the cerebellum at the time of diagnosis.11 In addition, more than 10% had spread into the spinal canal. The most common intrinsic tumors in the posterior fossa in childhood are medulloblastoma, cerebellar astrocytomas, brainstem glioma, and ependymoma.12,13 Hemangioblastoma, cerebral metastases, choroids plexus papilloma, and dermoid/ epidermoid cysts are less common.14 In adults, metastatic disease is by far the most common intrinsic posterior fossa brain tumor, although the same spectrum of pathology exists. Clinical presentation with these tumors commonly reflects either cerebrospinal fluid (CSF) obstruction and hydrocephalus or direct brain parenchymal invasion. Hydrocephalus is often accompanied by headache, nausea and vomiting, false localizing signs such as abducens palsy, and/or decreased level of consciousness. Direct brain parenchymal involvement may lead to cerebellar symptoms (gait and/or appendicular ataxia), brainstem symptoms (double vision, facial numbness or weakness, swallowing difficulties), or long tract signs (sensory deficits, pyramidal signs). As noted, impaired hearing and dizziness are uncommon but can occur. In this chapter, we outline the clinical features of the common intrinsic posterior fossa tumors. The epidemiology, pathology, clinical presentation, imaging studies, management, and prognosis for these tumors are discussed.

MEDULLOBLASTOMAS Medulloblastomas are small blue cell tumors arising in the posterior fossa. They account for approximately 20% of all brain tumors in childhood but only 1% of tumors in adults.15–18 The most tumors occur in children between the ages of 5 to 10 years and are rare in patients younger than 1 or older than 40 years of age.12,17,19 Male patients outnumber female patients in most series by 1.3:1 or 2:1.20 In a minority of cases, medulloblastomas are associated with specific genetic syndromes such as Turcot’s syndrome and Gorlin’s syndrome.21 875

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Bailey and Cushing first described these tumors.22 They felt the cell of origin was a primitive medulloblast. These cells were thought to reside in the subependymal zone in the roof of the fourth ventricle. Their existence has never been demonstrated directly, although the identification of widespread subependymal neural stem cells leads credence to this theory.23 At a molecular level, medulloblastomas have been associated with abnormalities of the sonic hedgehog signaling pathway, including patched and smoothened genes.21,24 Microscopically, medulloblastomas consist of densely packed, poorly differentiated, small, blue cells.25 Desmoplastic variants with areas of dense intercellular reticular network have been described, as have medulloblastomas with neuronal and myocytic differentiation. Classifying medulloblastomas is still a subject of debate. They are frequently referred to as a primitive neuroectodermal tumor (PNET), a designation that includes other poorly differentiated and highly malignant small cell central nervous system (CNS) tumors.9,26 Tumor location and clinical presentation may differ slightly with age of presentation. In children, most (65%) arise in the midline cerebellar vermis. In adults, lateral tumors are more common.12,27 The tumor grows into the fourth ventricle and often fills it. The cerebellar peduncles and medulla may be invaded. Extension into the cerebellopontine angle (CPA) is rare. Symptom duration before diagnosis is usually less than 3 months. Most patients have hydrocephalus at presentation. Infants are irritable and experience vomiting and an enlarged head due to hydrocephalus, while 80% of children and adults have the symptom complex of headache, nausea, vomiting, and gait disturbance.17 Magnetic resonance imaging (MRI) has replaced computed tomography (CT) scanning as standard imaging for posterior fossa intrinsic brain tumors (Fig. 50-1). On T1weighted images the tumors are of low signal intensity and of increased intensity of T2 studies. Gadolinium-enhanced T1-weighted images usually show homogeneous enhancement, but an irregular pattern with cyst formation is not uncommon. Leptomeningeal spread of tumor is identified more readily on MRI than on CT. Sagittal MRI helps show the tumor’s fourth ventricular location and axial images may help define invasion of surrounding brain. Management for patients with medulloblastomas requires a coordinated multidisciplinary approach. The current surgical morbidity with microsurgical techniques is low. Surgical goals are to confirm a pathological diagnosis, remove more than 75% of the tumor mass, and reestablish CSF drainage pathways. Significant hydrocephalus may require a temporary external ventricular drain (EVD), although many patients ultimately do not require permanent CSF shunts after definitive surgery for the tumor.28,29 Following surgical treatment, craniospinal axis staging is required with CSF cytology and whole brain and whole spinal axis imaging. Staging should be delayed at least 2 weeks after posterior fossa surgery to avoid postsurgical blood products that can confound CSF and MRI interpretation. Even complete surgical removal does not guarantee cure. Adjunctive treatment includes craniospinal axis irradiation and, in some cases, chemotherapy. In patients older than 3 years, radiation doses to the posterior fossa of 54 Gy and 36 Gy to the remaining craniospinal axis have been advocated with lower doses (45 Gy and 23.4 Gy) for

younger (ages 2 to 2.9 years) children.20 However, these doses have been associated with significant intellectual impairment in children (up to 40% of treated patients with IQ < 80 at 5 years).30 As a result, efforts have been made to reduce the craniospinal axis dose in children to 24 Gy. When combined with chemotherapy, this is associated with similar outcome to higher doses but has reduced intellectual impairment.31–33 Radiation therapy to the whole brain can produce severe neuropsychological deficits so that in very young children (0 to 24 months), chemotherapy alone is used initially. For the neurooncologist it is not uncommon to see patients complaining of reduced hearing after craniospinal irradiation, from either impacted cerumen in the external canal or a delayed radiation effect on structures of the inner ear. Chemotherapy is recommended for all children younger than 2 years (by itself), for all children between ages 2 and 16 years (in combination with irradiation), for all poor risk (<75% resection, disseminated disease) adult patients at diagnosis, and for all patients at recurrence. Furthermore, tumors may recur in even good-risk newly diagnosed adult patients after surgery and irradiation19,34 and are increasingly treated with chemotherapy as well. Typical chemotherapeutic agents employed include vincristine, CCNU (chloroethyl-cyclohexyl-nitrosourea, or lomustine), and cisplatin. These regimens could be ototoxic and audiologic follow-up is necessary. The postoperative management of the condition is complex and best done by a coordinated neurooncologic team experienced in treating this disorder. Optimum management now leads to 50% to 80% 5- and 10-year survivals.19,20,31,33–35 In general, patients may divided into good risk and poor risk categories at diagnosis. Poor outcome is predicted for patients with (1) age less than 2 years, (2) less than 75% of tumor resected, (3) leptomeningeal spread, (4) positive CSF cytology more than 2 weeks after surgery, and (5) systemic metastatic disease.19,31,36 It has also been suggested that presence of more than 1.5 cm2 tumor on any single MR image is independently associated with poor outcome,20 though this is controversial in patients receiving modern therapy.37 Molecular factors such as ErbB2 expression and chromosome 17p deletion have also been reported to denote poor prognosis, even in otherwise good-risk patients.38 Treatment of recurrence is difficult with few long-term survivors. Features of medulloblastomas are summarized in Table 50-1.

BRAINSTEM GLIOMAS Intrinsic brainstem gliomas are a heterogeneous group of astrocytic tumors with diverse pathology, presentation, and outcome. They comprise approximately 10% to 15% of childhood brain tumors and 2% of adult brain tumors.16,39,40 There is no gender predominance.41,42 There are typically no predisposing factors, although brainstem gliomas can occasionally be associated with neurofibromatosis type 1. As stated, brainstem gliomas are a heterogeneous group of tumors that may include pilocytic astrocytomas and diffuse fibrillary astrocytomas of varying grades. They have been classified in the past based on anatomic and neurodiagnostic features as diffuse, focal, cystic, exophytic,

Intrinsic Posterior Fossa Brain Tumors

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B

A

D Figure 50-1. A, Axial contrast-enhanced CT scan showing midline, homogeneously enhancing medulloblastoma; axial T1 with gadolinium (B) revealing much better anatomical detail; similar plane T2 image (C) showing increased signal intensity of tumor. Sagittal T1 image (D) demonstrates plane between floor of the fourth ventricle and tumor mass posteriorly.

C and cervicomedullary.43 The diffuse tumors have acted in a malignant manner, while focal, cystic, exophytic, and cervicomedullary tumors have tended to have a more benign course.43–45 It has been suggested more recently that in children these distinctions largely reflect differences in pathology with diffuse pontine tumors usually representing diffuse fibrillary astrocytomas and all others often representing pilocytic astrocytomas.41 The situation is further complicated

in adults. In this case, diffuse fibrillary tumors again predominate but are associated with sufficiently better prognosis to suggest that they may be biologically distinct from their childhood counterparts despite histologic similarity.46 The constellation of clinical symptoms and signs, as well as their duration, indicates the category of brainstem tumor.41,43 Patients with characteristically diffuse fibrillary brainstem glioma present with multiple cranial nerve

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TABLE 50-1. Features of Medulloblastomas Characteristic

Features

Epidemiology Pathology Molecular abnormalities Presentation Imaging

Most common in children; male to female = 1.3 to 2:1 Small blue cell tumor Altered sonic hedgehog pathway (patched, smoothened) Hydrocephalus, raised ICP, cerebellar signs Midline vermis (children), lateral cerebellum (adults); hypo-T1, hyper-T2, enhance To confirm diagnosis, remove >75% tumor, reestablish CSF drainage Craniospinal axis radiation; dose-reduced (+chemo) in children Increasing role; CCNU, vincristine, cisplatin 50%–80% 5-year survival

Surgery Radiation Chemotherapy Outcome

CCNU, chloroethyl-cyclohexyl-nitrosourea; CSF, cerebrospinal fluid; ICP, intracranial pressure.

B

A

Figure 50-2. A, Axial T1 with gadolinium of diffuse brainstem glioma. Pontomedullary junction is enlarged, distorting anatomy of fourth ventricle. Sagittal T1 images with contrast (B) and T2 second echo (C) demonstrate paucity of enhancement and diffuse infiltrating nature of these tumors.

C

palsies, ataxia, and long tract signs and the symptom duration before diagnosis is short. The sixth and seventh cranial nerves are most commonly involved, followed by the ninth, tenth, and fifth nerves, causing diplopia, facial weakness, and/or swallowing difficulties.45 Focal tumors (whether tectal, posterior exophytic, or cervicomedullary) produce more focal deficits or hydrocephalus. The duration of symptoms before diagnosis is long. MRI is the imaging procedure of choice. For patients with classical MRI findings for diffuse brainstem gliomas, it is often advocated as the only diagnostic test necessary (i.e., in lieu of biopsy).43,47 On T2-weighted images, diffuse lesions show increased signal intensity extending up and down the brainstem. There may be patchy or no gadolinium enhancement on T1 images. Typical MRI findings for a diffuse brainstem glioma are shown in Figure 50-2. Focal tumors show a localized area of abnormality on both T1 and T2 images, and the lesions show focal contrast enhancement. They may occur throughout the brainstem, but most commonly occur in posterior exophytic, cervicomedullary,

Intrinsic Posterior Fossa Brain Tumors

or tectal plate locations.39 Typical MRI findings for a focal cervicomedullary glioma are shown in Figure 50-3. Anterolaterally exophytic tumors may mimic meningioma or acoustic neuroma in the CPA. Distinguishing between intra- and extra-axial tumors can be difficult in this location and depends on ascertaining the tumor origin. Note

that in children with neurofibromatosis, without brainstem tumors, areas of increased signal intensity on T2 images are frequently seen and may represent white matter not fully myelinated. This may help to explain the improved prognosis of neurofibromatosis patients with what appear to be diffuse brainstem tumors.48

A

B

Figure 50-3. Sagittal T1 image without contrast (A) demonstrating isointense cervicomedullary dorsally exophytic tumor. Both T1 (B) and T2 (C) axial images reveal intrinsic nature of tumor not compromised by bony artifact.

C

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When required, surgical goals for brainstem gliomas are to establish a diagnosis and reestablish CSF pathways. This is not usually the case with diffuse brainstem gliomas. In addition, tectal gliomas are not typically biopsied. However, patients with dorsal exophytic tumors may undergo open operation for biopsy and/or partial removal. Enlarging tumor cysts can be drained stereotactically or at open operation, as symptoms and tumor location warrant. With cervicomedullary tumors, gross total resection of the cervical and subtotal resection of the medullary components of the tumor is possible. For surgically amenable tumors, even subtotal resection may be adequate to control symptoms for long periods without adjuvant therapy.39 If CSF pathways are obstructed and cannot be reestablished by tumor resection, CSF shunting or ventriculoscopic third ventriculostomy may be required.49,50 External beam radiotherapy is the mainstay of treatment for diffuse brainstem gliomas. This has been associated with temporarily improved neurologic function, although not with improved survival.51 Hyperfractionated radiotherapy was not associated with improved survival in a randomized phase III trial.52 Although objective responses have been seen, chemotherapy’s impact on diffuse brainstem tumors has been minimal or possibly detrimental.53,54 For more focal tumors, adjuvant radiation and/or TABLE 50-2. Features of Brainstem Gliomas Characteristic

Features

Focal Brainstem Gliomas Epidemiology Pathology Molecular abnormalities Presentation Imaging Surgery Radiation Chemotherapy Outcome

Children and young adults Pilocytic astrocytoma Possible NF-1 association Focal deficits, hydrocephalus; long duration Focal enhancing mass; exophytic; midbrain, medulla Biopsy, debulk dorsal exophytic tumor; reestablish CSF paths Only for progressive tumors Only for progressive tumors Survival >7 years

Diffuse Brainstem Gliomas (children) Epidemiology Pathology Molecular abnormalities Presentation Imaging Surgery Radiation Chemotherapy Outcome

Children and young adults Diffuse fibrillary astrocytoma Not well defined Cranial neuropathies, ataxia, long tract signs; short duration Diffuse, enhancing; pontine Typically not indicated Standard to posterior fossa Role uncertain Survival <1 year

Diffuse Brainstem Gliomas (adults) Epidemiology Pathology Molecular abnormalities Presentation Imaging Surgery Radiation Chemotherapy Outcome CSF, cerebrospinal fluid.

Adults Diffuse fibrillary astrocytoma Not well defined Cranial neuropathies, ataxia, long tract signs; short duration Diffuse, enhancing; pontine Typically not indicated Standard to posterior fossa Role uncertain Survival 4–5 years

chemotherapy are usually reserved for rare progressive tumors.39 Prognosis for patients with brainstem gliomas varies with age and tumor type. Diffuse intrinsic brainstem gliomas in children (the most common brainstem glioma) have a poor prognosis with a median survival of approximately 1 year.39,41,54 More focal brainstem tumors in both children and adults have a much better outlook with median survival longer than 7 years.39 Interestingly, several recent reports suggest that adults with diffuse low-grade brainstem gliomas also have a relatively good prognosis (median survival 4 to 5 years) despite histologic and imaging similarities to diffuse brainstem gliomas in children.42,46 However, there also appears to be a subpopulation of adult patients with diffuse brainstem tumor with high-grade histology and poorer prognosis.46 Features of brainstem gliomas are summarized in Table 50-2.

CEREBELLAR ASTROCYTOMAS Astrocytomas that affect the cerebellum are relatively heterogeneous and include pilocytic astrocytomas and both low- and high-grade astrocytomas. They account for 10% to 20% of all posterior fossa intrinsic tumors15 and for 12% to 18% of all pediatric brain tumors.55 Mean age at diagnosis is between 7and 9 years but there is a tail extending into the adolescent and young adult population.55,56 There is no clear gender predominance.55 Most cerebellar astrocytomas are either pilocytic astrocytomas or low-grade (grade II) fibrillary astrocytomas.12,55 High-grade astrocytomas are uncommon. Pilocytic astrocytomas are classically cystic tumors with a mural nodule and often arise in the cerebellar hemisphere. Rarely, they arise in the CP angle and mimic an acoustic schwannoma.57 Fibrillary astrocytomas are more commonly solid, midline, and infiltrating tumors. They occur more frequently in patients with neurofibromatosis type I. Most patients present to medical attention with nonspecific symptoms and signs of raised intracranial pressure. Headache, nausea and vomiting, and papilledema occur in more than 80%.55,58,59 Cerebellar signs vary with tumor location. Truncal ataxia is common with midline tumors, and limb dysmetria is seen with hemispheric lesions. Midline solid tumors are more common in young children, and laterally placed cystic tumors are seen more frequently with increasing age.58 Classically, cerebellar pilocytic astrocytomas have a lowdensity cystic component and a contrast-enhancing mural nodule on imaging studies60 (Fig. 50-4). However, a recent large series reported this finding in only 16% of patients.55 If the cyst wall enhances (Fig. 50-5), the wall itself is felt to be neoplastic. The cyst wall is usually surgically removed in such cases, although this is controversial.61 More often, fortunately, there is a solid nodule in the cyst’s wall that represents the entire neoplasm, which can be removed surgically after drainage of the cyst. Cerebellar fibrillary astrocytomas are usually solid, heterogeneously enhancing midline tumors. Both pilocytic and fibrillary cerebellar astrocytomas commonly cause noncommunicating hydrocephalus. Surgery for cerebellar astrocytomas is generally rewarding. Long-term survival or even cure can follow complete excision

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B A

Figure 50-4. A, Classic cerebellar cystic JPA with enhancing mural nodule on T1 images. B, T2 images show that nodule is hyperintense compared to surrounding brain, while sagittal image (C) shows the extent of cystic change in these tumors and associated hydrocephalus.

C

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A

B

Figure 50-5. A, Pathologically confirmed JPA, similar to previous case, as seen on axial T1 study. However, lower axial (B) and sagittal (C) studies reveal neoplastic involvement of the cyst wall, which must be excised at surgery.

C

Intrinsic Posterior Fossa Brain Tumors

TABLE 50-3. Features of Cerebellar Astrocytomas Characteristic

Features

Epidemiology Pathology Molecular abnormalities Presentation Imaging

Children, young adults Pilocytic more than fibrillary astrocytoma Possible NF-1 association Hydrocephalus, raised ICP, cerebellar signs Cystic mass with enhancing nodule (and occasionally cyst wall) Resect nodule (and cyst wall if enhances) For recurrent/residual tumor For recurrent tumors Ten-year survival ≈ 90%

Surgery Radiation Chemotherapy Outcome ICP, intracranial pressure.

of pilocytic astrocytomas.12,55,62,63 Five-, ten-, and twentyfive-year survivals of 92%, 88%, and 88% (respectively) have been reported.58 Pilocytic astrocytomas can be removed entirely after draining the cyst. The solid, infiltrating nature of a fibrillary astrocytoma makes total removal less likely. Hydrocephalus often resolves with tumor removal and reestablishment of CSF pathways. Few patients require permanent CSF shunting. When total tumor removal has been accomplished and verified by postoperative imaging, no further treatment is required except for periodic follow-up imaging studies. If postoperative studies show continued enhancement, consideration should be given to reresection.64 If this cannot be done because of tumor infiltration into critical areas, outcome might be improved with focal irradiation of the remaining tumor.65 Bloom and colleagues reported 5- and 10-year survival rates of 70% and 63% for unfavorable tumors treated by postoperative radiation.15 Chemotherapy is generally reserved for unresectable recurrent tumors, such as pilocytic astrocytomas with diffuse leptomeningeal spread.66,67 Despite the many reports of good clinical outcomes as judged by physicians, some children with cerebellar astrocytomas or other posterior (and supratentorial) tumors have motor and cognitive deficits after treatment.68 The prognosis for patients with malignant cerebellar astrocytomas is uniformly poor despite aggressive local resection and postoperative radiation therapy, with median survivals of 20 to 30 months and long-term survivals of only 30%.15,69,70 Features of cerebellar astrocytomas are summarized in Table 50-3.

EPENDYMOMAS Ependymomas account for 1.2% to 9% of all brain tumors and 9% to 12% of pediatric tumors.12,71–73 Nearly twothirds of all ependymomas occur in the posterior fossa and of all tumors in this location, 75% occur in children.71,73 Ependymomas form a significant subset of pediatric brain tumors but are not as common as medulloblastomas, brainstem gliomas, and cerebellar astrocytomas. They might be slightly more common in females than males,74 although this is not a universal finding.73 Ependymomas are thought to arise from ependymal cells around the cerebral ventricles or aqueduct of Sylvius. Most arise in periventricular locations, most commonly around the

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fourth ventricle.73,75 Both benign and malignant forms are described pathologically, but controversy exists regarding grading these tumors and its influence on outcome.12,74,76,77 Malignant forms are seen more commonly in the supratentorial compartment and in younger children.75,78 Ventricular obstruction and resulting hydrocephalus are almost universal at presentation for patients with posterior fossa ependymomas. Prediagnosis symptom duration is somewhat longer in adults than children, but headache, nausea and vomiting, and cerebellar dysfunction are common to both.78 Tumor extension into the foramen magnum and upper cervical spine is relatively common73 and may produce severe suboccipital and upper neck pain. Lower cranial nerve palsies are seen in up to 20% of patients. They result from either direct invasion of the fourth ventricular floor or tumor extension into medullary cisterns.78,79 Other neurologic signs include papilledema, ataxia, and nystagmus. CT scan images of ependymomas demonstrate calcification in 20% to 50%.78,80 MRI studies with and without enhancement, although not sensitive for calcification, clearly define the rostral-caudal tumor extent and extension outside the fourth ventricle (Fig. 50-6). The tumors are usually hypointense on T1 compared to surrounding brain, and cystic change is rare. Staging the craniospinal axis to rule out disseminated disease is an important component of diagnostic imaging. Like staging in patients with medulloblastomas, this should be performed either preoperatively or at least 4 weeks postoperatively to avoid postsurgical artifact. Less than 50% of posterior fossa ependymomas can be resected completely (as verified on postoperative MRI).73,81 Their tendency to invade posterior fossa arachnoid cisterns, blood vessels, cranial nerves, or the floor of the fourth ventricle often prevents gross total resection. When possible, however, complete resection is an important prognostic factor.81,82 Current acceptable surgical morbidity is 5% to 10%. Localized benign ependymomas are treated with focal external beam irradiation to the posterior fossa to a dose of 54 Gy.73,81 Tumors with spinal axis dissemination are treated with additional craniospinal irradiation to 30 Gy. Radiosurgery may have a role for recurrent or anaplastic ependymomas.83,84 Chemotherapy’s role at first diagnosis is questionable because it does not appear to improve survival compared to surgery and radiation or even meaningfully postpone radiotherapy for young children.81,82 It may have a role in recurrent or disseminated disease.81 Overall, survival figures appear better for adults than children, presumably due to the higher number of highgrade tumors in the latter. The 5-year survivals for benign tumors are 60% to 90%, and 0% to 30% for malignant forms.15,75,77,78,82,85 When a tumor recurs, it does so at the original site and isolated spinal failure is uncommon.73 Features of ependymomas are summarized in Table 50-4.

CHOROID PLEXUS TUMORS Choroid plexus tumors account for less than 1% of all brain tumors but as many as 8% of neonatal brain neoplasms.86–88 In one series, 82% of papillomas in children occurred in those younger than 24 months.89 This was supported by a recent metanalysis that showed a marked preponderance of supratentorial choroid plexus tumors in

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B A

Figure 50-6. A, Axial contrast CT scan revealing calcification within nonhomogeneously enhancing ependymoma. Axial (B) and sagittal (C) T1 contrast-enhanced MRI images show variable enhancement and no separation of floor of fourth ventricle from tumor.

C

Intrinsic Posterior Fossa Brain Tumors

TABLE 50-4. Features of Ependymomas Characteristic

Features

Epidemiology

75% in children; females slightly more than males Cuboidal cells with pseudorosettes Chromosome 22q loss Hydrocephalus, raised ICP, cerebellar signs Hypo-T1, hyper-T2, enhance Attempt GTR, but frequently not possible Standard to posterior fossa May have role at recurrence Five-year survival 50%–90%

Pathology Molecular abnormalities Presentation Imaging Surgery Radiation Chemotherapy Outcome ICP, intracranial pressure.

patients younger than 5 years.88 Choroid plexus tumors appear to affect both genders equally.88 Choroid plexus tumors can occur in the lateral ventricles, third ventricle, fourth ventricle, or CP angle. Tumors can occur in any of these locations at any age, but supratentorial tumors are much more common in children.88 Fourth ventricular tumors are more uniformly distributed between children and adults. CP angle tumors are relatively uncommon and are largely restricted to adults.88,90,91 Although most choroid plexus tumors are benign choroid plexus papillomas, up to 30% may show anaplastic features suggestive of choroid plexus carcinoma.88 Classically, patients with choroid plexus tumor present with increased intracranial pressure secondary to hydrocephalus. The hydrocephalus is related to CSF overproduction, blocking CSF pathways by tumor, and/or blocking CSF absorption at the arachnoid granulations because of recurrent small intraventricular hemorrhages. The tumors can protrude through the foramina of Luschka and Magendie, causing lower cranial nerve deficits. CT scans may show punctuate areas of calcification within the choroid plexus tumors. On noncontrast T1-weighted MRI, they are lobulated and isointense to normal brain. Homogeneous enhancement is seen on both CT and MRI (Fig. 50-7). Choroid plexus papillomas are treated by complete surgical removal, which can be associated with outright cure.88 Complete resection is associated with 85% 10-year survival, compared to 56% for partial resections and 50% 1-year survival for biopsy-only patients.88 It is not clear that radiation or chemotherapy plays any role in managing choroid plexus papilloma even at recurrence, where prognosis may be similar to first presentation.88 For choroid plexus carcinoma, the 5-year survival rate is only 50%.92 This may be improved by adjuvant radiation and/or chemotherapy and the role for these therapies is being explored. Features of choroid plexus tumors are summarized in Table 50-5.

HEMANGIOBLASTOMAS Hemangioblastomas are benign vascular central nervous system neoplasms. They are found primarily in the cerebellum, occasionally in the spinal cord, and rarely above the tentorium.93 They account for 1.1% to 2.4% of all intracranial tumors and about 7% of posterior fossa tumors

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in adults.12,93,94 The tumors are most common in young and middle-aged adults, and males outnumber females. They can occur as solitary or multiple tumors. They may be associated with von Hippel-Lindau ( VHL) disease but most (60% to 80%) are sporadic.12,93 VHL is an autosomal-dominant disorder that involves loss of the tumorsuppressor gene VHL on the short arm of chromosome 3. This finding is demonstrated in a variety of tumors from patients with the syndrome,95,96 including retinal and CNS hemangioblastoma, kidney and liver cysts, renal cell carcinoma, pheochromocytoma, and pancreatic cancer. Sporadic hemangioblastomas tend to occur in older patients while tumors associated with VHL are seen in younger patients. Genetic screening for VHL loss in the offspring of patients with VHL is now routine. Approximately 60% of hemangioblastomas are cystic. They generally lie in the paramedian cerebellum but can arise from the vermis or lateral hemispheres.12,97 When they occur in the brainstem, the area postrema in the medulla is a common site.94 The tumors usually have a pial attachment. Thus, a small portion of the tumor abuts the brain surface, typically along a sulcus. Presenting symptoms include limb clumsiness, ataxia, and symptoms of raised intracranial pressure (ICP) including headache, nausea, vomiting, and lethargy. Tumors in the brainstem or cerebellar peduncles may cause prominent vertigo.94 The average symptom duration before diagnosis is 13 months. CT and MRI demonstrate cystic lesions with an enhancing mural nodule. Hemangioblastomas can be distinguished from cystic cerebellar astrocytomas on imaging by increased numbers of large blood vessels97 (Fig. 50-8). Cerebral angiography is helpful in defining blood vessels that supply the tumor. It can also disclose other lesions in the cerebellum or the cervical spinal cord (if the neck is included in the imaging films). Solid tumors that are lateral in the cerebellar hemisphere and abut the petrous ridge may resemble CPA tumors. They can be distinguished by vascular flow voids on MRI and by their vascular pattern at angiography.95 Solid tumors are particularly difficult to treat and those that arise in the medulla have a substantial operative mortality. Some cerebellar hemangioblastoma patients present with erythrocytosis secondary to erythropoietin production by the tumor.98 Erythrocytosis resolves after tumor removal. Its reappearance usually indicates tumor recurrence. Treatment of hemangioblastomas is primarily surgical resection, although this may be aided by endovascular embolization when appropriate.93,99 A recent series reported symptomatic improvement after hemangioblastoma resection in 88% at 1 year.93 Recurrence occurred in 17% of lesions and up to 30% of patients required multiple operations. Radiation’s role is not well defined, although both standard fractionated radiotherapy and radiosurgery have been proposed to decrease the risk of recurrence.100,101 Radiosurgery is best suited for treating new, small tumors in patients who have VHL to try to prevent symptomatic enlargement. Tumors with associated cysts are best dealt with by surgical resection for documented growth or symptoms. Chemotherapy does not have a standard place in hemangioblastoma management but has been proposed experimentally for patients with VHL disease.99 There is inadequate recognition of the full spectrum of tumors that occur in VHL, which leads to incomplete

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A B

Figure 50-7. A, Axial CT scan without contrast of choroid plexus papilloma demonstrates extensive calcification not uncommon with these tumors. Axial T2 (B) image reveals the tumor is hypointense compared to surrounding brain, while on the T1 image (C) a portion of the lobulated tumor is isointense posteriorly.

C TABLE 50-5. Features of Choroid Plexus Tumors Characteristic

Features

Epidemiology Pathology Molecular abnormalities Presentation Imaging

All ages; relatively common in neonates Cuboidal, papillary tumors; up to 30% anaplastic Not well defined Hydrocephalus, raised ICP Supratentorial (children), infratentorial (adults); enhancing intraventricular mass Curative for papillomas Role unclear Role unclear 85% 10-year survival after GTR

Surgery Radiation Chemotherapy Outcome ICP, intracranial pressure.

Intrinsic Posterior Fossa Brain Tumors

887

TABLE 50-6. Features of Hemangioblastomas Characteristic

Features

Epidemiology Pathology Molecular abnormalities Presentation Imaging Surgery Radiation Chemotherapy Outcome

Young to middle-aged adults Vascular tumor similar to renal cell carcinoma VHL loss Raised ICP, cerebellar signs Cystic mass with enhancing nodule GTR potentially curative Role not well defined Role not well defined Recurrence in 17% after GTR

ICP, intracranial pressure; VHL, von Hippel-Linday.

A

screening for associated systemic tumors. The National Institutes of Health screening protocol includes urinary catecholamine screen, formal funduscopic examination, and an abdominal CT and ultrasound.102 Family members of patients with VHL also should be screened to identify treatable lesions before they cause irreparable damage or malignancies develop.103 Although the cerebellar lesions often can be totally removed, they might recur in up to 25% of cases, so that patients should be followed with periodic CT or MRI studies after surgery.104 In cases of VHL, family members should be offered genetic counseling. Features of hemangioblastomas are summarized in Table 50-6.

METASTATIC TUMORS IN THE POSTERIOR FOSSA

B

C

Metastatic brain tumors are secondary tumors spread hematogenously from primary tumors at distant sites. They are the most common brain neoplasms. Autopsy reports indicate that 20% to 50% of patients who die of cancer have brain metastases and about 40% of these tumors are solitary.105–108 Brain metastases incidence detected before death may be increasing due to increased access to sensitive imaging studies and improved primary tumor control. Eighty percent of metastatic tumors occur in the cerebral hemispheres, 16% in the cerebellum, and 3% in the brainstem.107 This is roughly proportional to the size and blood flow of each region. Primary lung, breast, and gastrointestinal tract tumors and melanoma account for more than 75% of intracranial metastases. Non-smallcell lung carcinoma, breast carcinoma, and melanoma account for most solitary metastases.105,107 In addition, small-cell lung carcinoma metastasizes to brain in approximately 70%. Uterine and prostatic tumors uncommonly metastasize to central nervous system structures but when they do, they tend to localize to the cerebellum.106 The presentation of patients with brain metastases in the posterior fossa is not particularly different from that of patients with other mass lesions in this location. Headaches, lethargy, nausea, and vomiting suggest hydrocephalus and

Figure 50-8. Coronal (A) and sagittal (B) images reveal an enhancing tumor with an associated cyst laterally (arrows). On coronal images circular signal voids are consistent with large vascular channels within the tumor. The cerebral angiogram (C) demonstrates the typical vascular pattern of hemangioblastoma.

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increased ICP. Focal cerebellar tumors can produce limb clumsiness (dysmetria) and ataxic gaits. Spontaneous hemorrhage into a vascular metastasis (e.g., thyroid or renal cell carcinoma, melanoma) can cause abrupt deterioration in a patient’s clinical condition. Tumor spread to the leptomeninges can cause cranial nerve deficits and meningeal signs. Although 50% of brain metastases present within a year of diagnosis of the primary tumor, malignant melanoma is renowned for the long latent period (sometimes years) between diagnoses of the primary and secondary tumor.108 Gadolinium-enhanced T1-weighted MRI images are the best way to confirm the diagnosis radiologically and rule out multiple metastases (Fig. 50-9). CT scans using a double-dose contrast-delayed imaging technique are also useful, but scatter from surrounding bone in the posterior fossa frequently degrades the images and makes interpretation difficult. Both CT and MRI images usually demonstrate marked edema surrounding the lesion. This feature makes initial treatment with glucocorticosteroids particularly beneficial to reducing mass effect and symptoms. Treatment of brain metastases in the posterior fossa depends on (1) tumor location, presentation, and pathology, (2) number of metastases, and (3) systemic disease status. Options for treatment include surgical resection, radiosurgery, and standard fractionated radiotherapy. Some metastatic tumors such as small-cell lung carcinoma and lymphoma are exquisitely radiosensitive and are usually treated with radiation alone. For other tumor types, there is clear evidence that surgically resecting a single accessible metastases followed by external beam radiation therapy is superior to radiation alone for patients younger than 70 years with controlled systemic disease, good performance status, and a life expectancy longer than 3 months.109,110 Posterior fossa metastases can be removed surgically if they are superficial or subcortical within the cerebellar hemisphere and do not extend into the cerebellar peduncle. Resection is also often indicated for cerebellar metastases to quickly alleviate obstructive hydrocephalus. Traditionally, multiple metastases have been a contraindication to surgery. However, increasing evidence suggests that prognosis for patients who have up to five cerebral metastases completely resected at one sitting is similar to patients who have resection of a single metastasis, provided that these patients meet other criteria for surgery (age <70, controlled systemic disease, good performance status, life expectancy >3 months).111 Increasingly, stereotactic radiosurgery with or without standard external beam radiotherapy is being employed for both single and multiple metastases.112–114 Prognosis for patients treated in this fashion appears similar to that for patients treated with surgery and standard radiation therapy, but no randomized clinical trials have compared these treatments directly. In the absence of such studies, surgery may be more attractive for patients with cerebellar metastases because it can also alleviate hydrocephalus. Chemotherapy that makes use of agents with demonstrated activity against the known primary tumor may provide some palliation. Survival after diagnosis of cranial metastatic disease varies according to tumor type, degree of systemic involvement, and neurologic status at the time of diagnosis. Median survivals of 9 to 14 months are found with breast,

A

B Figure 50-9. Multiple metastases from breast carcinoma. A, T1 images with contrast show two convexity lesions in both cerebellar hemispheres. B, T2 image shows greater area of signal abnormality, consistent with surrounding vasogenic edema.

Intrinsic Posterior Fossa Brain Tumors

TABLE 50-7. Features of Metastases Characteristic

Features

Epidemiology Pathology

Most common posterior fossa tumor in adults Small-cell lung, NSC lung, breast, GI tract, renal cell, melanoma Variable Hydrocephalus, raised ICP, cerebellar signs Enhancing mass with marked edema Resect single radioresistant mets in good candidates Standard to posterior fossa +/− radiosurgery Variable Median survival 9–14 months

Molecular abnormalities Presentation Imaging Surgery Radiation Chemotherapy Outcome

GI, gastrointestinal; ICP, intracranial pressure; NSC, non-small-cell.

kidney, colon, and lung metastatic to brain; metastatic melanoma has a 6-month median survival.106 Features of posterior fossa metastases are summarized in Table 50-7.

CONCLUSIONS Intrinsic posterior fossa tumors include both benign and malignant lesions with variable recommended treatment regimens and expected outcomes. For the practicing neurotologist, awareness of these tumor types is important, especially for tumors that may extend into the CP angle (ependymoma, choroid plexus papilloma). All neurotologists should understand the clinical and imaging features, recommended treatments, and expected outcomes reviewed here.

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Chapter

51 Mitchell K. Schwaber, MD

Vascular Compression Syndromes Outline Anatomic Considerations Microsurgical Anatomy of the Cerebellopontine Angle Vascular Anatomy of the Cerebellopontine Angle Microscopic Anatomy of the Cranial Nerve Pathophysiology Ectopic Excitation of a Nerve Mechanically Induced Ectopic Excitation Reflection of Impulses Ephaptic Transmission Afterdischarge and Autoexcitation Neuroplasticity or Reorganization of the System Theories of Pathophysiology Hemifacial Spasm Trigeminal Neuralgia Cochleovestibular Nerve Compression Syndrome Histopathology of Vascular Compression Syndromes Microvascular Decompression Surgical Technique The Controversy Surrounding Microvascular Decompression

ascular compression syndrome is the term used to classify a group of conditions thought to be caused by the compression of a cranial nerve by a vessel. These conditions include hemifacial spasm (HFS), trigeminal neuralgia (TN), glossopharyngeal neuralgia (GPN), geniculate neuralgia (GN), and cochleovestibular nerve compression syndrome (CNCS). These syndromes have some common features, including (1) anatomy, (2) theories of pathophysiology, (3) histopathology, and (4) surgical treatment, that is, microvascular decompression. In this chapter, these common features are reviewed, as are the individual vascular compression syndromes. The surgical technique of microvascular decompression is described and illustrated, and the controversy surrounding the procedure is discussed.

V

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Vascular Compression Syndromes Hemifacial Spasm History Clinical Features Site of Lesion Diagnostic Evaluation Treatment Trigeminal Neuralgia History Clinical Features Site of Lesion Diagnostic Evaluation Treatment Glossopharyngeal Neuralgia History Clinical Features Site of Lesion Diagnosis and Treatment Tic Convulsif and Geniculate Neuralgia History and Clinical Features Site of Lesion Cochleovestibular Nerve Compression Syndrome History Clinical Features Site of Lesion Diagnostic Evaluation Treatment Summary

ANATOMIC CONSIDERATIONS In this section, the normal anatomy and vascular supply of the cerebellopontine angle (CPA) and the microscopic anatomy of the cranial nerves are reviewed.

Microsurgical Anatomy of the Cerebellopontine Angle Matsushima and colleagues1 reviewed the microsurgical anatomy of the CPA and the surrounding structures, and the reader is referred to this reference for greater detail. The petrosal or anterior surface of the cerebellum faces the posterior surface of the temporal bone, the brainstem,

Vascular Compression Syndromes

and the fourth ventricle. The lateralmost portion of this surface is retracted to expose the CPA during surgery. As viewed from the retrosigmoid approach, the brainstem structures are the midbrain superior, the pons in the center of the field, and the medulla inferior. Three fissures are created by the cerebellum overlapping these brainstem structures. Superior is the cerebellomesencephalic fissure, in the center is the cerebellopontine fissure, and inferior is the cerebellomedullary fissure. The cerebellopontine fissure borders the middle cerebellar peduncle. A major artery and vein is found in each fissure. In the cerebellomesencephalic fissure the superior cerebellar artery (SCA) and the vein of the cerebellomesencephalic fissure are found. In the cerebellopontine fissure the anterior inferior cerebellar artery (AICA) and the vein of the cerebellopontine fissure are found. The posterior inferior cerebellar artery (PICA) and the vein of the cerebellomedullary fissure are found in the cerebellomedullary fissure. The cerebellopontine fissure has superior and inferior limbs that communicate with the adjacent fissures. The flocculus is also located on the cerebellar surface, and it overlies the root entry zone of the cochleovestibular and facial nerves (Fig. 51-1). Inferior to the root entry zone of the cochleovestibular nerve (CVN), overlying the entry zone of the lower cranial nerves, is the choroid plexus. Superiorly, the trigeminal nerve exits the pons and travels obliquely in an anterosuperior direction toward the petrous apex. The trigeminal nerve consists of two roots: the sensory root is called the portio major, and the motor root is called the portio minor. Inferior, glossopharyngeal, vagus, and accessory nerves are visible as they exit the posterior fossa through the jugular foramen. The glossopharyngeal nerve exits the medulla oblongata in a sulcus along the dorsal border of the inferior olive and consists of five or six filaments that unite to form a single nerve. The exit zone of the lower cranial nerves is not usually well visualized during retrosigmoid vestibular nerve section. The vagus and the cranial accessory nerve fibers arise from the dorsal border of the inferior olive, immediately below

Figure 51-1. Illustration of the microsurgical anatomy of the CPA. The cochleovestibular nerve is retracted to expose the facial nerve and AICA giving off several small branches. The open arrow indicates the trigeminal nerve. The dark arrow indicates the glossopharyngeal nerve and the immediately adjacent vagus and accessory nerves. The curved arrow indicates the flocculus. The AICA is shown in its most frequent location.

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the glossopharyngeal exit zone. Both of these nerves arise as multiple filaments and, as they travel peripherally, the filaments unite to form three or four major bundles. The vagus and the accessory nerves exit the posterior fossa together in a sleeve of dura through the jugular foramen. A spinal accessory branch joins the cranial accessory filaments to form the spinal accessory nerve. The facial nerve exits the pons immediately anterior to the roots of the cochlear and vestibular nerves. The facial nerve travels in parallel with the CVN to the internal auditory canal (IAC). For the facial nerve, the myelin transition zone (TZ) from the central nervous system (CNS) to peripheral myelin is found 0.8 mm from the brainstem.2,3 The nervus intermedius is situated between the vestibular portion of the CVN and the facial nerve and may be incorporated into the vestibular nerve in some cases.4 The CVN exits the pons and travels to the IAC in an inferolateral course. Its length in the CPA is from 8 to 15 mm, depending on where the nerve is measured. The average length of the entire eighth nerve is 20 mm.5 The TZ of CNS and peripheral myelin has been reported2,6,7 at between 8.2 and 13.0 mm, depending on the investigator. The TZ is located outside the porus in 56% of cases, at the porus in 18%, and inside the porus in 26% of cases.8 A groove, or raphe, can be appreciated on the posterior surface of most CVNs, and this groove usually indicates the division of the cochlear and vestibular segments. A small vessel often travels in this groove. In the surgical position for retrosigmoid vestibular nerve section, the flocculus hides the medialmost 5 to 7 mm of the CVN.

Vascular Anatomy of the Cerebellopontine Angle The SCA arises near the apex of the basilar artery and encircles the brainstem near the pontomedullary junction, passing below the oculomotor and trochlear nerves and above the trigeminal nerve. The SCA then enters the cerebellomesencephalic fissure, where it sends several perforators into the deep cerebellar matter and then travels to the tentorial surface of the cerebellum. The PICA arises from the vertebral artery near the inferior olive and then passes posterior to the medulla. At the anterolateral margin of the medulla, the PICA passes among the rootlets of the hypoglossal, vagus, glossopharyngeal, and accessory nerves. The PICA then courses around the cerebellar tonsil where it enters a series of fissures and ultimately supplies the suboccipital surface of the cerebellum. The AICA arises from the basilar artery and encircles the pons near the abducens, facial, and CVNs. The AICA sends small branches into the IAC and to the lateral segment of the choroid plexus and then passes the flocculus on the middle cerebellar peduncle to supply the petrosal surface of the cerebellum. The AICA is divided into three segments: (1) The premeatal segment begins medially at the basilar artery and courses laterally around the brainstem to reach the seventh and eighth cranial nerves. (2) The meatal segment is located in the vicinity of the IAC and is usually characterized as a convex loop, directed toward or through the meatus. (3) The postmeatal segment begins

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distal to the cranial nerves and courses medially to supply the brainstem and the cerebellum. The major veins of the region are the vein of the cerebellopontine fissure and the middle cerebellar peduncle vein.9 The cerebellopontine fissure vein is formed from the union of the anterior hemispheric veins that converge on the lateral end of the middle cerebellar peduncle near the apex of the cerebellopontine fissure. It courses rostrally to the flocculus and to the root entry zone of the facial and CVNs and rarely is found to make contact with the CVN. The vein then drains into either the superior petrosal sinus or joins with the middle cerebellar peduncle vein prior to entering the superior petrosal sinus. The middle cerebellar peduncle vein usually runs caudal to the flocculus, then superiorly between the facial and CVNs. It then drains superiorly, either joining the cerebellopontine fissure vein or draining directly into the superior petrosal sinus. Sunderland10 studied the vascular anatomy of the base of the brain and reported that the vertebral and basilar arteries were significantly shifted from the midline in 46 of 210 (22%) autopsies. When present, this finding was usually associated with looping of the SCA. Hardy and Rhoton11 studied the relationship of the SCA to the trigeminal nerve. Among 50 specimens, 26 showed contact of the SCA to the trigeminal nerve. In six specimens, the SCA contacted the trigeminal root entry zone. Kim12 recently reported that in every specimen in his study, the premeatal segment of AICA was nerve-related, that is, the premeatal segment of AICA made contact with the facial or the CVN. The relationships of the AICA to the facial nerve, the CVN, and the internal auditory meatus have been the subject of at least 20 publications, according to Oaknine.13 However, after excluding multiple reports of the same data and reports in foreign languages, five investigators have addressed the subject of the use of microsurgical dissection techniques. The data from these five anatomic studies is reviewed in later sections of this chapter and in Tables 51-1 and 51-2. The number of specimens studied by each investigator is as follows: Sunderland,5 264; Mazzoni and Hansen,14 100; Martin and colleagues,15 50; Oaknine,13,16 65; and Kim,12 52. Table 51-1 summarizes the relationship of the meatal segment of the AICA to the internal auditory meatus. Oaknine13,16 found a vessel either at the orifice or within the meatus least often, in 44% of specimens, whereas Mazzoni and Hansen14 found this relationship most often, in 67%. Sunderland5 found the AICA related to the TABLE 51-1. Location of AICA Loop Relative to Internal Auditory Canal—Percent of Specimens Demonstrating Finding Investigator Oaknine13,16 Mazzoni14 Sunderland5 Martin15 Kim12

Outside IAC

In the IAC

At the Opening of IAC

19 40 39 34 14

25 27 25 20 34

56 33 36 46 52

AICA, anterior inferior cerebellar artery; IAC, internal auditory canal.

TABLE 51-2. Relation of Meatal AICA to the Facial and Cochleovestibular Nerve—Percent of Specimens Demonstrating Finding Investigator Oaknine13,16 Mazzoni14 Sunderland5 Martin15 Kim12

Anterior to Facial Nerve

Posterior to CVN

Between

52 51 26 N/A 27

9 6 22 N/A 22

36 43 49 16 50

AICA, anterior inferior cerebellar artery; CVN, cochleovestibular nerve.

internal auditory meatus in 64% of dissections, Martin and colleagues15 found this relationship in 54% of dissections, and Kim12 found this relationship in 48% of specimens. Table 51-2 summarizes the relationship of the AICA to the facial nerve and CVN. The relationships are presented with respect to the surgical position for a retrosigmoid vestibular nerve section. The meatal segment of the AICA passed between the facial nerve and the CVN in 40% to 50% of specimens in the majority of studies. In about half of the specimens, the meatal segment passed either anterior or posterior to the facial-CVN complex. Kim12 has summarized the most frequent relationship of the AICA to the facial and CVN as follows: The premeatal segment travels anteroinferior to the nerves, the meatal segment travels between the facial and the CVN near the meatus, and the postmeatal segment travels posteroinferior to the nerve bundle.

Microscopic Anatomy of the Cranial Nerve Peripheral nerve tissue is characterized by nerve fibers that are suspended in a collagen-rich extracellular or endoneurial space.17 A peripheral nerve fiber consists of a basement membrane-axon-Schwann cell unit. Each fiber travels in an undulating, somewhat redundant fashion, which provides elasticity and protection from traction during movement. Peripheral nerve fibers are collected into bundles of funiculi.18 Within a funiculus, nerve fibers frequently divide and branch, creating a funicular plexus. Three types of supporting tissues are associated with peripheral nerve fibers—endoneurium, perineurium, and epineurium. Endoneurium is a delicate, collagen-rich connective tissue that surrounds each nerve fiber and fills the funiculi. Perineurium is the thin sheath that compartmentalizes each funiculus. Perineurium acts as a barrier to diffusion and infection and imparts tensile strength to the nerve. Epineurium is a loose areolar tissue that surrounds the funiculi and forms a nerve trunk.18 In contrast, CNS tissue is characterized by a small extracellular space in which collagen is lacking, that is, CNS tissue lacks an endoneurial space. In CNS tissue, the axons are imbedded in a complex network of oligodendrogliocytes and astrocytes. CNS nerve fibers are collected into a bundle and travel in a more parallel course, that is, the nerve fibers lack a funicular plexus. In addition, the perineurium and the epineurium are absent. These factors combine to

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make the intracranial or CNS portion of a cranial nerve more susceptible to injury than the peripheral portion.18 The TZ between peripheral nerve tissue and CNS tissue does not take place at the level at which the cranial nerve emerges from the brainstem, but rather at a site more peripheral along the course of the nerve. Skinner7 and Tarlov2 studied the light microscopic findings of the TZ and noted that the distance from the brainstem in which the TZ occurred varied significantly among cranial nerves and that the sensory component of a nerve usually had a much longer CNS segment than the motor component. The cranial nerve, as it travels toward the brainstem, splits from a larger nerve trunk into several thinner components, called rootlets, and then further divides into smaller minirootlets (Fig. 51-2). The TZ between peripheral nerve and CNS tissue occurs within the minirootlets, that is, each minirootlet has a TZ. Central to the TZ, the cranial nerve then enters the brainstem as a mass of compact white matter.17,19,20 In the CVN the CNS portion of the minirootlet is convex in shape and bulges into the peripheral nerve portion of the minirootlet (see Fig. 51-2). This accounts for the arch-shaped TZ noted by Tarlov.2 The apex of the bulging CNS tissue is completely surrounded by components of the peripheral minirootlet, creating two compartments at the TZ.21 The inner compartment consists of the elements of a CNS nerve fiber and the outer compartment consists of the elements of a peripheral nerve, the major difference between the two being the absence or presence of the endoneurial space, respectively. As axons pass between these two compartments, a node of Ranvier is usually found, and it is called the borderline node.17 Each compartment can be further subdivided into two subcompartments, so that four distinct subcompartments can be identified. These four distinct areas have been named as follows (from outside to in): the outer zone, the glial fringe zone, the mantle zone, and the core zone.17,19 The endoneurial space of the peripheral nerve ends in a cul-de-sac. As a result, blood vessels that had coursed

Figure 51-2. Illustration shows the TZ of the CVN. The TZ actually consists of numerous minirootlets. Also note that the CNS segment is convex, creating an arch into the zone. A cross-section through the TZ shows the outer peripheral portion of the nerve (white) and the inner CNS portion of the nerve (shaded). (Modified from Berthold C-H, Carlstedt T, and Corneliuson O: Anatomy of the nerve root at the central-peripheral transition region. In Dyck PJ et al [eds.]: Peripheral Neuropathy, vol 1. Philadelphia, WB Saunders, 1984, pp 156–170.)

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within the endoneurial space can no longer follow the axons. The blood vessels then travel to the outside surface of the nerve root where they join vessels from the CNS.22 Several authors have suggested that the poor vascularization makes this segment of the nerve more susceptible to injury, creating a locus minoris resistae or “Achilles heel.”17,23 Others, however, have suggested that a deficiency in CNS myelin is the reason for the increased susceptibility. Obersteiner and Redlich24 studied the core zone where nerve fibers actually entered the spinal cord and observed what they thought was a depletion of myelin. They interpreted17 this finding as indicating that all nerve fibers lacked a myelin sheath for a distance of about 50 μm. Levi25 also noted this lack of myelin in the core zone. It is now known that this apparent lack of myelin was, in fact, a preservation artifact.18,20,26 Despite this fact, because of their work, the TZ is often referred to as the ObersteinerRedlich zone. The myelin sheath of the CNS portion is thinner than the peripheral portion,18 causing some investigators to suggest that the CNS portion of a nerve is more susceptible to injury.27,28 Moller29 has recently clarified the point that, in his opinion, it is the entire CNS segment that is more susceptible to compression injury, not just the TZ.

PATHOPHYSIOLOGY The current theory of pathophysiology of the various vascular compression syndromes suggests that the condition begins when a vessel adheres to the cranial nerve and then causes chronic ectopic excitation of the nerve. As a result of this chronic excitation, the cranial nerve nucleus undergoes reorganization or neuroplastic changes. This neuroplastic change then causes hyperfunctioning of the nerve.

Ectopic Excitation of a Nerve Ectopic excitation refers to the development of a site within a nerve that spontaneously generates impulses. Nerve impulses are usually initiated in the cell body or at the peripheral receptor. However, ectopic excitation implies that the initiation of an impulse occurs in the midportion of an axon, at a site that does not ordinarily generate impulses. Experimentally induced focal demyelination of axons results in a lowering of the threshold of excitation of that segment, and if the threshold is sufficiently low, the site can spontaneously discharge and create an action potential. Focal demyelination can be induced by injecting various foreign substances into the nerve, which causes inflammation, granuloma formation, and microneuromas. The ectopic activity may arise as a single action potential or as a burst of activity.30 Rasminsky31 has stated that ectopic excitation is manifested in four ways: (1) mechanically induced or spontaneous ectopic excitation, (2) reflection of impulses, (3) ephaptic excitation, or “crosstalk,” between fibers, and (4) afterdischarge or autoexcitation. Each of these aspects is briefly reviewed. Mechanically Induced Ectopic Excitation Following the creation of experimental focal lesions in a nerve, nerve fibers become exquisitely sensitive to both acute

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and static compression at the site of injury.32 Rasminsky31 has stated that in these experiments “even minimal pressure results in prolonged bursts of impulses propagated in at least one direction away from the lesion site.” Reflection of Impulses Normal nerve impulses are slowed as they pass through a site of injury. In addition, an extra-axonal flow of current occurs normally as the impulse passes through the nerve. If the threshold of excitation is sufficiently low at the injury site, a nerve fiber might be recovering from refractoriness while the extra-axonal flow is still in the region. The sensitive nerve fibers might then be reexcited, creating a focus of ectopic excitation that travels antidromically. This phenomenon has also been called the cascade effect, enabling the injured nerve fiber to serve as a pathologic amplifier of normal neuronal activity.30 Ephaptic Transmission Ephaptic transmission is the term used to describe the phenomenon in which an axon develops cross-excitation with another axon, usually after an injury. In this circumstance it is now thought that a demyelinated or bare axon excites a myelinated one, rather than two bare axons interacting.31,33,34 Ephaptic transmission can result in orthodromic transmission, antidromic transmission, or both (Fig. 51-3). For example, in an ephaptically transmitting motor nerve at the ephapse, cross-excitation and stimulation of a second axon occurs. The second axon’s impulse then travels peripherally, which results in the movement of muscles innervated by the second axon. This type of ephaptic transmission is one of the explanations given for synkinesis. Compression increases ephaptic transmission by increasing interstitial tissue resistance, making it more likely that the current will be shunted to a nearby axon. Afterdischarge and Autoexcitation Afterdischarge refers to the presence of repeated firing by a nerve fiber after a priming stimulus. This phenomenon has been shown to occur in nerves demyelinated by the formation of experimental granulomas.34 Numerous electrophysiologic studies on patients have suggested that ectopic excitation and ephaptic transmission are present in HFS. Moller35,36 has proposed that ectopic excitation of the facial nerve is an essential feature

Figure 51-3. Illustration shows the development of ephaptic transmission, or “cross-talk,” between nerve fibers.

of HFS, based on his findings using interoperative electromyography (EMG) during microvascular decompression. Following elevation of the vessels, instantaneous changes were observed in ephaptic transmission in the facial nerve. These findings suggested to Moller that the vessels were responsible for the problem. A major premise of vascular compression syndromes is that a vessel cross-compresses a nerve, which results in chronic ectopic excitation and stimulation of the nerve. Ectopic excitation of a nerve has been clearly demonstrated following various experimental injuries and in certain diseases such as multiple sclerosis. In the experimental animal, mechanical stimulation and minimal compression of the injury site cause markedly increased activity from the focus of ectopic excitation. These data also suggest that a vessel might be able to trigger ectopic excitation, although it should be clearly stated that there is no proof that a vessel can actually cause the initial nerve injury.

Neuroplasticity or Reorganization of the System Topographic organization of sensory receptors is a basic feature of the major sensory systems, and several reports have documented the organizational changes that occur in the somatosensory and visual cortex following denervation of peripheral receptors.37–41 In particular, the topographic representation within the somatosensory cortex has been altered by the removal of skin sensation following the amputation of digits and by the transection of peripheral nerves. The deprived area of the somatosensory cortex then becomes progressively responsive to adjacent skin areas. This phenomenon is called neuroplasticity, and most sensory and motor systems undergo these changes in response to changes in the peripheral receptors. Although this review is limited to examples of the neuroplastic changes that have been found in the facial and vestibular nuclei, similar changes have also been shown in the trigeminal (barrel receptors) and glossopharyngeal (altered taste perception) nuclei. Facial nucleus reorganization has been shown not only with facial nerve stimulation but also deafferentation. Moller and Jannetta35 and Moller and Sen42 have studied the effects of chronic electrical stimulation of the facial nerve root entry zone in rats. After a month of daily, brief stimulation of this region, the rats developed EMG activity that resembled the findings usually seen in HFS patients. These findings did not occur in animals that were implanted with electrodes but were not stimulated. In addition, stimulation anywhere along the length of the facial nerve caused these EMG changes. From this study, Moller concluded that it is not injury but chronic stimulation of the facial nerve that results in HFS. His theory of kindling is reviewed in this section. Recently, Ishikawa has reported that his electrophysiologic studies of f-waves indicate that neuroplasticity of the facial nucleus occurs in HFS.43 The facial nucleus is somatotopically organized and, like other motor systems, undergoes reorganization following deafferentation. Facial nerve regeneration induces sprouting of axons from motor neurons within the facial nucleus and causes dramatic changes in the cellular organelles of

Vascular Compression Syndromes

the facial neuron, including increased ribosomes, RNA, and enzymes.44 With respect to the neuroplasticity of the vestibular nucleus, a deafferenting lesion such as that from a labyrinthectomy is most familiar to otolaryngologists. To summarize the course of vestibular compensation after labyrinthectomy: After acute unilateral labyrinthectomy, the contralateral vestibular nucleus still receives normal input from the contralateral end organ. This imbalance is perceived as motion, causing the sensation of vertigo in addition to a host of autonomic side effects. Within hours, the cerebellum perceives sensory information that is in conflict with the vestibular inputs. The cerebellum then begins to exert an inhibitory influence on the vestibular nuclei, reducing the activity of the nuclei bilaterally. After a period of several weeks, the deafferented nucleus begins to discharge spontaneously once again. After several months, the neuronal activity of the contralateral nucleus increases to about the same as the injured side. Rotation testing results in increased activity in the normal nucleus but not the nucleus on the labyrinthectomized side. Other studies regarding neuroplasticity of the vestibular system are primarily concerned with the adaptability of the vestibulo-ocular reflex (VOR) gain, that is, the ability of the VOR to change its response characteristics during rotational stimulation. Lesions of the cerebellar flocculus abolish VOR adaptation and result in decreased gain of the VOR. Alternatively, O’Leary and Davis45 found that patients with active Ménière’s disease have increased gains on vertical autorotation tests, and Hamid46 reported that increased gain appears to accompany the development of motion intolerance. Melvill Jones47 has published several reports regarding adaptive changes induced in the VOR with visual alterations. His best known experiments studied the effects of left-right reversing prism glasses, which cause extreme changes in the manner in which the eyes move during head movement. Normally, the eyes move in the opposite direction of head movement; the VOR then corrects the visual input with a nystagmus beat. Melvill Jones found that after wearing the reverse prism glasses for just a few minutes, the eyes begin immediately to move in the same direction as the head movement. These data indicate that altering the external relationships between visual and vestibular stimuli gradually, but substantially, changed the parameters of the reflex pathway. O’Leary48 found that repeated or prolonged applications of low-frequency sinusoidal stimuli cause a gradual decline in VOR gain. This phenomenon has been called rotational habituation and indicates another form of neuroplasticity. Neuroplasticity of the facial and vestibular systems can occur in response to both increased activity or to deafferentation. Elements of both probably occur in the vascular compression syndromes.

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muscles of the lower face. The spasms are characterized as involuntary bursts of tonic and clonic muscle spasms that become more or less constant over time. The patient usually develops a significant weakness on the affected side. HFS is thought to be caused by a vascular loop compressing the root entry zone of the facial nerve near the brainstem, at the segment of the nerve covered by CNS myelin. The currently accepted theory of pathophysiology is called the kindling theory.42,49,50 The kindling theory states that the PICA loop compresses the nerve, thus causing demyelination and creating a focus of ectopic excitation (Fig. 51-4). Ectopic excitation causes chronic stimulation of the facial nerve, and the impulse then travels antidromically back to the facial nucleus. Chronic stimulation of the facial nucleus causes reorganization of the neuronal pathways and results in hyperactivity of the nucleus. Facial movements are unique among motor systems because of a diversity of inputs into the facial nucleus, including voluntary, emotional, and reflexive. Reorganization might cause unmasking of reflexive movements that are normally inhibited. As a consequence of this hyperactivity, bursts of spasms are seen in the facial muscles. Considerable clinical and experimental evidence suggests that the kindling theory is likely, although it is unclear how a vessel actually initiates these events. Trigeminal Neuralgia A similar mechanism to HFS has been proposed for TN. TN is characterized by severe, lancinating facial pain that is triggered by tactile stimulation of the face or of the gums. Idiopathic TN is thought to be due to a loop of the superior cerebellar artery compressing the trigeminal nerve on its root entry zone.28 Like HFS, a theory of pathophysiology has been proposed.51 Compression of the nerve root by a vascular loop results in demyelination and deactivation of the inhibitory fibers of the trigeminal nerve. Tactile stimuli on the face or gums then causes increased activity of the trigeminal nucleus, because of the loss of the inhibitory fibers. The increased nuclear activity results in increased discharge of the trigeminal nerve. Further amplification of the nerve impulses occurs at the site of the demyelination and subsequently these impulses are reflected back to the trigeminal nucleus. The activity of the nucleus increases further, reaching a point where severe and intense pain is perceived by the patient.

Theories of Pathophysiology Hemifacial Spasm HFS is a condition characterized by involuntary unilateral facial spasms. HFS usually begins with twitching of the orbicularis oculi muscle and then progresses to involve the

Figure 51-4. Illustration demonstrates the features of the kindling model. (1) A vessel makes contact with the nerve, which causes ectopic excitation. (2) Antidromic impulses are then transmitted back to the nucleus. (3) In the nucleus, reorganization results in increased discharge of the nucleus. (4) Increased discharge of the nucleus is transmitted orthodromically down the nerve and results in symptoms.

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Cochleovestibular Nerve Compression Syndrome 52

Schwaber has recently proposed a theory of pathophysiology for the CNCS. This syndrome, sometimes referred to as vascular loop syndrome, is characterized by recurrent vertigo spells and positional vertigo spells, constant disequilibrium, and acquired motion intolerance. These patients often demonstrate a unilateral high-frequency sensorineural hearing loss, prolonged interwave latencies on ABR recordings, and spontaneous nystagmus on electronystagmography (ENG). Air contrast computed tomography (CT) scans of the IAC will often show a vessel seemingly fixed to the CVN. This theory of pathophysiology52 suggests that the syndrome begins with an episode of vestibular neuritis, which causes axonal loss and nerve swelling. A vessel might become attached to the CVN at this time. Following deafferentation of the vestibular neuritis as well as the intermittent excitation of the vestibular nerve by the vessel, the vestibular nucleus undergoes reorganization and develops increased or hyperfunctioning activity. As a result, each of the interactions of the vestibular system is changed, including the vestibulospinal system, the visual system, and the reticular formation. Motion, head positioning, and visual stimuli each cause progressively greater symptoms as a result of this organizational change. Arbusow has demonstrated herpes simplex virus-1 in the vestibular nerve in patients with suspected vestibular neuritis. This finding confirms the suspected pathophysiology of recurrent viral neuritis of the vestibular nerve and furthermore suggests that this condition might be treated with antiviral drugs.53 With respect to these theories, the common theme is that the cranial nerve is injured and possibly chronically stimulated. As a result, changes in the cranial nerve nucleus occur, resulting in a hyperfunctioning system. It is this increased activity that accounts for the symptomatology.

Histopathology of Vascular Compression Syndromes In 1965, Beaver and coworkers54 reported their study of trigeminal nerve specimens obtained during trigeminal nerve section for idiopathic TN. The specimens were studied with electron microscopy and demonstrated focal areas of hypermyelination, hypomyelination, and overgrowth of myelin into great axis cylinders. Similar findings were also reported by Kerr.55 However, these pathologic findings were not readily accepted, because many could be attributed to artifact. Thickening and irregularity of the myelin sheaths and segmental demyelination have also been described in autopsy cases of older patients without a history of TN.55 Hilton56 has reported the findings from nerve biopsy of the trigeminal nerve at surgery for TN. He found focal loss of myelin, as well as axonal loss. These findings support the concept of ephaptic transmission. Ruby and Jannetta57 performed biopsies of the facial nerve at the root entry zone in a case of HFS. A biopsy of the portion of the nerve that had been compressed by a vessel was studied with electron microscopy. Jannetta reportedly found nerve fibers that were partially or totally demyelinated, although the histopathologic materials were

not illustrated. These authors proposed that demyelination allows naked axons to make contact with one another. They also found hypertrophied myelin sheaths intermingled with normal fibers. Iwakuma and colleagues58 reported similar findings in an autopsy case of HFS. Specifically, these investigators found focal fascicular demyelination accompanied by Schwann cell proliferation at the root entry zone. Kumagami59 reported segmental demyelination of the facial nerve at the stylomastoid foramen in two cases where he performed neurotomy of the peripheral facial nerve for hemifacial spasm. Kumagami also found myelin thickening in some histologic sections. Despite the fact that the specimens were obtained at a site far distal to the supposed site of compression, the same histopathologic features were present. Brihaye and coworkers60 reported autopsy findings in a case of GPN, where the glossopharyngeal and the vagus nerves were compressed by an atheromatous vertebral artery. Demyelination of the ninth and tenth cranial nerve was reportedly found. Ishii61 studied the nerve section specimens following pharyngeal and cervical resection of the glossopharyngeal nerve for GPN. Despite the fact that these specimens were obtained extracranially, marked degeneration of the myelinated fibers, disorganization, and thickening of the myelin were observed. Degeneration was localized in some cases, but more often was diffuse. Hypermyelination was also found in these specimens. The histologic findings in TN, HFS, and GPN are remarkably similar, given the wide variation in the site of the biopsy, the nerves involved, and the number of investigators. Unfortunately, in none of these studies were there any controls nor any reported attempt to conceal the diagnosis from the neuropathologist. Collan and colleagues,62 specifically referring to the work of Beaver54 and Kumagami,59 states that these changes are very difficult to distinguish from artifacts. Hypermyelination and demyelination have not been found in cases of CNCS. Helms and coworkers,63,64 in a double-blind controlled fashion, found that nerves affected by Ménière’s disease often had increased connective tissue or endoneurial fibrosis compared with normal cadaver nerves. The Ménière’s nerves also demonstrated increased lipofuscin and vascular changes on electron microscopy. Other investigators65–68 have reported similar findings. Ylikoski and colleagues68 found perineurial and endoneurial fibrosis in one-third of 150 consecutive Ménière’s cases. They suggested that the fibrosis seen in these specimens might lead to a relative constriction of the nerve, although the true pathologic significance of these findings remains unknown. Quijano and coworkers,69 however, have reported no increase in fibrosis in a study of 11 cases of classic Ménière’s disease obtained from their autopsy temporal bone series. Belal and Ylikoski70 reported a case that appears to be the first histopathologic study of CNCS. The report details the autopsy temporal bone findings in a case of Ménière’s disease in which endolymphatic hydrops was not found. The patient had previously failed endolymphatic sac surgery and had undergone middle fossa vestibular nerve section. Endoneurial fibrosis, myelin thickening, and increased lipofuscin were found in the vestibular nerve.

Vascular Compression Syndromes

In reviewing the literature, endoneurial fibrosis was repeatedly identified in cases that resemble CNCS, including cases that were diagnosed as vestibular neuritis, chronic vestibular neuritis, and post-traumatic vertigo. Schwaber and Whetsell52 specifically studied the histopathology of the vestibular nerve in CNCS. In this study, vestibular nerve specimens were obtained during suboccipital vestibular nerve section for vertigo and disequilibrium. The CNCS nerves were intermingled with vestibular nerves obtained in cases with other disorders. The nerves were prepared, sectioned, and interpreted by the neuropathologist in a single-blind study fashion. In this study, the nerves from cases with CNCS were characterized by marked endoneurial fibrosis and axonal loss, whereas the nerves obtained from the Ménière’s cases were not involved with significant endoneurial fibrosis. No degeneration of myelin was found in any case. Schwaber interpreted these findings as showing that a deafferentation occurs as the initial event in CNCS. The most plausible explanation for a deafferenting lesion is vestibular neuritis.

MICROVASCULAR DECOMPRESSION Surgical Technique Microvascular decompression is the surgical procedure used to elevate a compressing vascular loop from the affected cranial nerve. Jannetta71 has argued that microvascular decompression is preferred over denervation. Jannetta stated that denervation of an end organ is not a physiologic procedure, and patients may experience difficulty as they age because of decompensation. As a result, Jannetta does not recommend trigeminal nerve section or CVN section. The procedure is performed through a retrosigmoid suboccipital approach. Prior to the surgery, the patient is counseled regarding the benefits and risks of the procedure, with a special emphasis on facial weakness, hearing loss, cerebrospinal fluid (CSF) leakage, meningitis, and headache. Operative permits are obtained after the patient has received this information. To perform microvascular decompression, the patient is placed under general, endotracheal anesthesia in the supine position. Electrodes for facial nerve monitoring, electrocochleography, and ABR monitoring are placed, and a Foley catheter is placed for urinary drainage. The ipsilateral shoulder is elevated and the patient’s head is then placed in Mayfield pinions. The head is turned so that the occiput is uppermost in the field. Excess tension on the neck is avoided. The incision site is injected with a mixture of 2% lidocaine (Xylocaine) with 1:100,000 epinephrine for hemostasis and then prepped using iodophor solution. While the drapes are being placed, baseline values are obtained for the various monitors. A curvilinear incision is made over the subocciput region, and the periosteum and soft tissues are incised to expose the bony suboccipital region of the skull. The soft tissue dissection usually requires the control and ligation of the occipital artery and the control of several venous emissarium from the skull. While beginning the bony exposure, the patient is given intravenous mannitol, 1.0 g/kg

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body weight, to achieve a rapid diuresis. Bony dissection is performed by means of suction-irrigation and an airpowered drill system. The bone over the subocciput is removed to expose the dura and the bony defect measures 4 to 5 cm in diameter. A cruciate dural incision is fashioned to expose the CPA (Fig. 51-5). Several 5–0 sutures are placed to provide retraction of the dura. The cerebellum is gently retracted posteriorly, with particular attention to the inferior portion of the CPA. The basilar cistern is opened first and the CSF allowed to egress. This maneuver usually allows much easier retraction of the cerebellum, which is held in place by a self-retaining retractor. The various adhesions surrounding the trigeminal, cochleovestibular, facial, and glossopharyngeal nerves are then dissected, and the flocculus of the cerebellum is retracted to further visualize the root entry zone of the nerves. Jannetta71 has also stated that the vessels must crosscompress the nerve at right angles (Fig. 51-6); vessels that run parallel to the nerve do not compress it. The author prefers to decompress all vessels making contact or in the vicinity of the nerve in question. The various vessels, arteries, veins, arterioles, and venules are carefully elevated from the surface of the affected nerve. This usually requires the division of arachnoidal adhesions as well as the blunt dissection of the major vessels. Jannetta71 has reported that the vessels often retract a few millimeters on opening of the dura and removal of the CSF. Therefore, the pathologic vessel may not always be in contact with the nerve, but when found, grooving or indentation of the nerve is considered significant. The author decompresses the cranial nerve from the brainstem to its exit from the CPA, that is, the entire CPA segment of the nerve. Small Teflon tufts or slips of muscle are then insinuated between the nerve and the vessel to prevent recontact (Fig. 51-7). After ensuring hemostasis, the CPA is irrigated with saline and the retractor is removed. The dura is closed with interrupted 5–0 Surgilon sutures. In cases in which

Figure 51-5. After opening the dura, the cochleovestibular and facial nerves can be seen. Note, the course of the nerves is from superior to inferior in the field.

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Figure 51-6. Operative photograph that shows a large AICA loop that cross-compresses the cochleovestibular nerve (arrow).

the mastoid air cells are opened, bone wax is used to seal them. The soft tissues are closed with interrupted absorbable sutures and the skin is closed with skin staples. A light dressing is applied after removing the monitor electrodes. The patient is monitored overnight in the neurosurgical intensive care unit. Early ambulation is encouraged, and most patients undergoing microvascular decompression are discharged on the third postoperative day. The skin staples are removed within the first 2 weeks of the postoperative period. Each patient is then followed until all acute symptoms are stabilized. Postoperative visits are determined by the severity of the symptoms, as is the need for additional medicines. Microvascular decompression of the CVN has been relatively free of reported complications. The most significant complication of this procedure has been hearing loss.

Figure 51-7. Operative photograph obtained during microvascular decompression of the vascular loop. Note the insertion of Teflon to prevent readherence of the vessel to the nerve.

Because the labyrinthine arteries arise from the apex of a vascular loop within the IAC, attempts to dissect the loop out of the canal usually cause avulsion of these tiny vessels from the AICA. The loss of circulation to the labyrinth then results in profound hearing loss. Excessive manipulation of the cochlear nerve can also cause a moderate sensorineural loss. Microvascular decompression of other cranial nerves has a reported mortality of 1% and a 10% incidence of other complications.72 These figures have prompted some to advise extreme caution with regard to the procedure.73 These other complications include cranial nerve deficits, headaches, and CSF rhinorrhea. Fortunately, no reported mortality is associated with microvascular decompression of the CVN. Recently, Badr-El-Dine and coworkers74 have described the use of endoscopy in performing minimally invasive microvascular decompression. In this report the endoscope was helpful in identifying the sites where a vessel contacted the nerve and in determining if the Teflon sponge was correctly positioned to prevent the vessel from attaching to the nerve. Similar findings were reported by King and colleagues,75 who used endoscopy during a variety of procedures in the posterior fossa.

The Controversy Surrounding Microvascular Decompression Although several authors have raised serious questions concerning the validity of the entire vascular loop concept, the most comprehensive review article concerning this question is the one by Adams76 on microvascular decompression. The first part of this review reflects primarily Adams concerns regarding TN and HFS. The controversy regarding CNCS is then reviewed. Jannetta27,28,71,77–80 has written extensively regarding his opinion that the vascular loop compression must be at the root entry zone of the cranial nerve, at the junction of peripheral and CNS myelin. Adams76 has raised the issue that the actual TZ of the myelin is only 1 to 3 mm long and that the TZ can only be seen histologically, that is, it cannot be seen by the surgeon. Therefore, the surgeon cannot know if a vessel is on the TZ or not. Moller29 has responded to this criticism by clarifying that the susceptible segment is that covered by CNS myelin, not specifically at the TZ. Adams76 voiced his concern regarding the compression and grooving caused by vessels on a nerve and whether this in fact represents pathology. Adams noted that he often saw grooving of the optic nerve at surgery without perceivable deficits. Adams also questioned the significance of vessels that “fall away” from the nerve on opening the dura. Apfelbaum81 classified vascular loops into “definite” compressing vessels and “possible” compressing vessels, based on adherence, proximity, and grooving, among others. Apfelbaum believes that in cases of TN where a “possible” vessel is found, the trigeminal nerve should be sectioned to achieve beneficial results. Adams76 noted that nearly 100% of patients demonstrate some sort of vascular contact at surgery and that there is a need for a better method to determine if a specific vessel is responsible for nerve root compression. A number of other investigators have reported finding no evidence of vascular loop compression at exploratory

Vascular Compression Syndromes

surgery. The negative exploration rate for TN76,81 varies from 4% to 90%, and that for HFS82 approximates 25%. However, despite a negative exploration, many patients improve after the procedure.82–84 Adams,76 Auger and coworkers,84 Kaye and Adams,82 and Fabinyi and Adams85 have suggested that the effects of microvascular decompression are nonspecific and that the success of the procedure is a result of manipulation of the nerve. Microvascular decompression may cause fibrosis or chronic trauma to a sensitive portion of the nerve, resulting in decreased nerve function and decreased inputs into the nucleus. This possibly explains the numerous reported cases of TN and HFS that improve dramatically for long periods with “stroking” or “controlled neurolysis” of the nerve.86 Adams76 has stated that Jannetta and Moller have used several untenable arguments to defend microvascular decompression. Adams noted that their first argument is to claim that other surgeons do not know how to expose the nerve root or to identify a vessel, an argument that deserves no further comment. The second is to claim that delayed recovery is evidence of the effects of microvascular decompression, rather than some other mechanism. Adams noted that a facial palsy often develops several days after head trauma or after acoustic tumor surgery. Therefore, delayed recovery might just be a reflection of a delayed onset of a palsy. The third argument discussed by Adams involves the use of electrophysiology to document the site of the lesion. Adams stated that it is difficult for him to believe Moller’s data regarding HFS, given the proximity of the brainstem, the nerve root, and the TZ, in addition to the variability of electrophysiologic tests. In fact, Auger and colleagues84 have interpreted Moller’s data to indicate that die changes caused by microvascular decompression in HFS could be due to mild trauma. Specifically regarding microvascular decompression of the CVN, Adams76 stated that Jannetta’s early reports do not provide the necessary data to define his patient population. Adams also noted that the episodic vertigo of Ménière’s disease is eradicated by vestibular nerve section. Since Jannetta has reported his best results with microvascular decompression in Ménière’s patients, this strongly suggested to Adams that the effect of the surgery was to denervate the vestibular organ partially. During the course of this literature review, the author could not find a single reference by Moller or by Jannetta where postoperative ENG results were reported to rebut this argument. Following Jannetta’s New England Journal of Medicine report concerning “Disabling positional vertigo,”78 number of letters to the editor of the journal voiced concern over the lack of controls in his work, the difficulty in assessing the outcome of vertigo procedures, and the lack of a clear definition of his patient population.87,88 Snow89 noted that Jannetta’s results are approximately those that have been reported with a variety of treatments for Ménière’s disease, that is, a 75% success rate in controlling vertigo. Snow advised caution in overinterpreting the effects of microvascular decompression of the CVN. Thomsen90 recently stated that the evidence for vascular compression is anecdotal at best, and that the basis for decompressing the CVN is “speculative.” Brandt91 recently reviewed positional vertigo, including peripheral, nerve,

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and central causes. In this report, Brandt states that the term disabling positional vertigo is a “misleading and confusing description for a most heterogeneous collection of signs and symptoms, far from a reliably diagnosable entity. The lack of a well-defined syndrome and of a diagnostic test, make it difficult for the nonsurgical clinician to believe in this interesting disease.” Brandt suggested that many of Moller’s patients might have “phobic postural vertigo.” Brandt also noted that neither close vessel contact nor the surprisingly high improvement rate following microvascular decompression confirms that vessels are indeed related to the symptoms. Citing Thomsen,90 Brandt91 noted that the results of surgery in this condition may be entirely due to placebo effects. Brandt’s conclusions succinctly summarize this chapter. Further information is required if the clinical picture presented by vascular compression of the CVN is to be accurately defined. Since this report, Brandt92 has further stated that four criteria must be met for vascular compression of the CVN: (1) short attacks of rotational vertigo, (2) dependence on head positions, (3) hyperacusis, and (4) a measurable deficit on audiovestibular testing.

VASCULAR COMPRESSION SYNDROMES Hemifacial Spasm History HFS as a symptom was first described by Schultze93 in 1875, in a case involving a vertebral artery aneurysm. HFS was first recognized as a disease entity in 1888 by Gowers94 who carefully differentiated it from other movement disorders and tics involving the face. Clinical Features HFS usually begins with intermittent twitches around the eye and, in particular, in the inferior portion of the orbicularis oculi muscle. The condition then progresses to involve the muscles of the lower face. HFS is nearly always unilateral and is characterized by involuntary bursts of tonic and clonic movements of the facial muscles. When fully developed, the patient may experience daily spasms, with severe long-lasting tonic contraction.95 The spasms can be provoked by facial expressions and can occur during sleep.77 As HFS progresses, a mild weakness of the face is often noted, along with the development of synkinesis with voluntary movement. Position-dependent HFS77,96 as well as increased salivary flow97 associated with HFS have both been reported. Demographically, HFS is more prevalent in females, representing 65% of cases in most reported series,30,95,98,99 and the left side is more often involved than the right. The condition occurs mostly in middle-aged and older patients, with a mean age of onset of 45 years.95 The average duration of symptoms prior to surgical treatment is 5 years.77 Of 229 patients operated on by Jannetta, 205 (89%) were classical in presentation, as described earlier. The remainder were atypical, beginning in the lower face, and then involving the orbicularis oculi muscle. Many patients have a period of remission within the first 2 years after onset.100

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Site of Lesion A number of sites have been proposed as the “site of the lesion” in the past, including the facial nucleus101–104 and the nerve root entry zone near the brainstem.27,28,71,105 McCabe106 suggested that the site of the lesion in HFS is area 4-S in the cortex. A fourth proposed site is within the fallopian canal. This site is primarily based on surgical observations of segmental edema, made during total facial nerve decompression for HFS.107 Evidence that the nerve root entry zone is the site of the lesion in HFS is based on both electrophysiologic data and on surgical observations.

present? In a patient with facial spasm, a complete history and neurotologic exam should be performed, with the specific aim of determining if a tumor or mass is present involving the facial nerve in its course from the brainstem to the peripheral muscles. The diagnostic tests needed to evaluate HFS patients include a gadolinium-contrast magnetic resonance imaging (MRI) scan of the head and temporal bones, an audiogram with acoustic reflexes, and an auditory brainstem response (ABR). Also an EMG exam is usually obtained and the characteristic findings in HFS include a prolonged trigeminofacial (eye blink) reflex latency and a rapid discharge rate (greater than 200 bursts/min) of the involved muscles.

Electrophysiologic Data Esslen100 stated that the characteristic EMG finding in HFS is a rhythmic repetition of firing in different facial muscles, at a rate of up to 350 bursts or volleys per second. Esslen has also stated that the discharge pattern in HFS resembles the spontaneous firing rate of nerve muscle preparations with experimentally induced unstable membrane conditions. Based on these findings, Esslen concluded that in HFS the lesion must be in the facial nerve. Moller and Jannetta,35,36,49,50 by means of intraoperative EMG recordings, demonstrated that ephaptic transmission instantaneously decreased when the nerve was decompressed. If this decrease was not seen, the recurrence rate was very high. Mooij108 used intraoperative EMG with electrical stimulation to determine the site and adequacy of the facial nerve decompression in patients with hemifacial spasm. He found that the use of intraoperative EMG was beneficial in 87% of cases. Surgical Observations Digre and Corbett95 reviewed the world’s literature and found 1688 reported cases of HFS. In these cases, the following pathologies were identified and reported: vessels (509), tumor (19), bony abnormalities (7), other (4), not specified (986), unknown (163). Among the tumor cases, meningiomas were the most frequent, followed by CPA epidermoid tumors. Among the cases due to vessels, 92% were due to arteries and 8% were due to veins. Among the arteries found, the following were identified: AICA (34%), PICA (18%), IAC artery (7%), and vertebral/basilar artery (22%). Following decompression of these vessels, 85% of patients were free of spasms, although the success rate varied considerably with the surgeon performing the procedure. These findings are somewhat at variance with those of Jannetta.66 Of Jannetta’s 229 surgical cases, 210 were due to an artery, 4 were due to a vein, and 10 were mixed. The PICA was the predominant vessel in this series. Jannetta stated that PICA must cross-compress the root entry zone at right angles to cause HFS, and in his opinion parallel vessels do not cause HFS.

Treatment Following diagnosis, the patient is initially started on a course of baclofen (Lioresal), which in some patients lessens the frequency of the spasm. Baclofen is administered in a progressively increasing dose, beginning with 5 mg tid and increasing to 40 to 80 mg/day. The majority of patients do not respond to this therapy, however, and the spasm is then treated with botulinum toxin injections to the facial muscles, avulsion of peripheral nerve branches, or microvascular decompression of the facial nerve root entry zone. Botulinum toxin is injected into the inferior portion of the orbicularis oculi muscle and into the zygomaticus and levator anguli oris muscles. The botulinum toxin paralyzes the facial muscles and will significantly decrease the spasm. The effect, however, lasts only 3 to 4 months and must be repeated at that time. Avulsion of peripheral nerve branches is used only in cases of limited spasm, that is, spasms confined to the lower lip or one specific region of the face. The most often applied treatment for HFS is microvascular decompression of the facial nerve root entry zone. Microvascular decompression is performed through a suboccipital exposure of the CPA. It is most important to decompress vessels that cross-compress the facial nerve, particularly the PICA compressing the facial nerve on its inferior surface. After decompressing the vessels, a tuft of felt is insinuated between the vessel and the facial nerve to prevent reattachment. Microvascular decompression is successful in eliminating the facial spasm in 80% to 85% of cases.95 Note that microvascular decompression for HFS is not without significant complications. Jannetta71 has reported complications in 37% of a series of 229 cases. These complications included permanent facial paralysis (3%), profound sensorineural hearing loss (5%), aseptic meningitis (6%), and CSF leak (4%). Other less frequent complications included pneumonia, pulmonary embolism, serous otitis media, and temporary facial paralysis.

Trigeminal Neuralgia Diagnostic Evaluation

History

During the initial evaluation of a patient with HFS, it is important to characterize the nature of the facial spasm: Does it involve the entire face or only a segment? Is it a spasm or is it synkinesis? Or is facial weakness also

Although Avicenna first described a case of severe recurring facial pain in the early part of the 11th century,51 most authors attribute the first description of TN to Jurjani, who described the condition a century later. The term tic

Vascular Compression Syndromes

douloureux was coined by Andre in 1756 and today is used synonymously with idiopathic TN. TN became a recognized clinical entity when Fothergill gave the first clear description of 14 cases in 1773.51

Clinical Features TN is a condition characterized by paroxysms of intense facial pain usually confined to the distribution of the divisions of the trigeminal nerve. The pain is usually characterized as lancinating, often as a severe burning or as an electric shock in the face. Usually there is no warning or prodrome. Each paroxysm of facial pain lasts from a few seconds to a few minutes. After an episode, there is a short period when the pain cannot be triggered. However, the pain may then recur after a short time, so that it may appear to be continuous for several weeks. The painful paroxysms tend to occur in bouts or cycles that last for a few weeks to months. Pain-free remissions, also lasting from weeks to months, follow the pain cycle. Over time, the duration of the painful episodes tends to be longer, and the pain-free remissions tend to be shorter. Most cases of TN have a defined trigger, that is, eating, rubbing, or touching some area of the face or brushing the teeth triggers the pain. The trigger is usually located within the area of pain distribution. In general, minimal tactile stimuli precipitate the attacks. Painful or deep pressure stimuli do not usually trigger the pain. Rarely, the pain can be precipitated by loud noise, movement of the eyes, or from intense emotional stimuli. Most patients are pain-free during sleep, perhaps because of a lack of triggering stimuli. The vast majority of cases are unilateral, with a right-left predominance of about 3:2. Bilaterality occurs in just 5.3% of cases. Localizing the pain can be very difficult for most patients. Initially, the pain is usually confined to a small area, and later begins to radiate up and down the face. The pain may involve more than one division of the trigeminal nerve, most frequently involving second and third divisions together (34%), followed by the second divisions alone (19%), the first and second divisions together (16%), and the third division alone (16%). The ophthalmic division is least often affected (3%).51 Henderson,109 in describing the location of the facial pain, has defined a mouth-ear zone and a nose-orbit zone. In two-thirds of his cases, the pain involved the former. The prevalence of TN has been estimated by Penman110 to be 155 cases per million, with a 1.6:1 female to male predominance. The mean age of onset is about 50 years, although childhood onset has been reported. Occasionally TN is found in association with HFS, a combination known as tic convulsif. GPN has also been reported in association with TN, and Selby51 has estimated that this combination occurs in 0.5% of cases of TN. Tic convulsif and GPN are reviewed further later in this chapter. Few physical findings are associated with TN. Reddening of the face, watering of the eye, and nasal congestion often accompany the facial pain. If anesthesia of a particular division is detected, a tumor or vascular malformation involving the trigeminal nerve should be suspected.

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Site of Lesion TN has been divided into two categories: symptomatic and idiopathic. Symptomatic TN includes cases with defined pathologic lesions, that is, traumatic, tumorous, vascular, and demyelinating diseases. Harris63 favors trauma to the dental nerves as an important pathogenic mechanism for symptomatic TN, citing a case that appeared to follow a difficult dental extraction. Harris also reported five cases of TN that developed 3 to 12 years after an apparent viral TN associated with facial hemianesthesia. Krohel and colleagues111 also reported a case of TN in the second and third divisions after multiple attacks of herpes simplex neuralgia. Slow-growing tumors and documented vascular anomalies can compress, deform, or stretch the sensory root of the trigeminal nerve and result in symptoms that are indistinguishable from those found with idiopathic TN. TN cases secondary to acoustic neuromas, meningiomas, cholesteatomas, and metastatic tumors have all been reported. Cholesteatomas are more likely to cause TN symptoms than are the other tumors. However, unlike idiopathic TN, most tumor cases have objective sensory deficits due to tumor compression of the trigeminal nerve. In addition, in tumor cases there is rarely any remission from the facial pain. Multiple sclerosis may also cause TN, and in the cases reported, a plaque was found in the sensory root of the trigeminal nerve.112 These cases of a TN due to multiple sclerosis lend some credence to the theory that the CNS segment of the nerve is the site of the lesion. Idiopathic TN has also been called primary, essential, or major TN. A number of sites have been proposed as the “site of the lesion” including the trigeminal sensory root and the brainstem trigeminal nucleus.113 Chronic latent infection of the gasserian ganglion with herpes simplex has also been proposed as the cause of idiopathic TN, but this seems unlikely given the large number of cases of herpes cold sores and the relative infrequency of TN. Several neurosurgeons have proposed that the source of irritation in the vast majority of cases is due to a vessel crosscompressing the trigeminal sensory nerve root at the root entry zone. These surgical observations are reviewed in greater detail in the following paragraphs. Surgical Observations In 1934, Dandy114 reported 215 posterior fossa procedures performed for the relief of TN. Dandy performed trigeminal sensory root section at the pons in these cases and, during the course of the procedure, noted aberrant branches of the SCA or other vessels in contact with the nerve root in 66 cases. He also found six aneurysms and five angiomas in contact with the nerve root.114 In 1968 Gardner115 reported 18 cases of typical TN that had recurred after a middle fossa dural decompression. Through a posterior fossa approach, six had vessels that compressed or transfixed the nerve root and an additional case had a basilar aneurysm. Jannetta and Rand79 reported that in five consecutive operations for TN, the trigeminal root was compressed by the SCA. The vessels were so small as not to be visible to the naked eye. Haines and coworkers116 compared the findings of 20 consecutive cadavers and 40 operative cases of TN, and

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found vessels in 17.5% of the cadavers compared with 92.5% of the surgical cases. The most frequent finding in the surgical cases was a deep caudal loop of the SCA116 that passed between the trigeminal nerve and the pons. They also noted that the vessel cross-compressed at least half of the nerve trunk, usually on the superomedial side. Haines and coworkers116 reported an autopsy case of TN, which showed grooving and compression of the affected side but not the unaffected side. Jannetta27 in 1979 reported 465 cases of idiopathic TN treated with a suboccipital exposure and decompression of the trigeminal sensory root. According to Jannetta, in nearly every case, vessels were found cross-compressing the nerve, although many were too small to be appreciated without the benefit of high-power magnification. The following pathologies were specifically reported: artery (242), vein (57), mixed (96), arteriovenous malformation (1), tumor (15), and no pathology (1). Based on surgical observations, Jannetta28 postulated that a vessel comes in contact with a cranial nerve as a result of aging; that is, as the brain ages, it shrinks and sags, while arteries, over time, dilate as a result of arteriosclerosis. By chance, a vessel comes in contact with the trigeminal nerve at the CNS segment. According to Jannetta, the pulsatile vessel gradually compresses the nerve, which leads to demyelination and abnormal conduction. Other investigators have reported similar results. Petty and Southby117 found vascular compression of the root entry zone in 14 of 19 cases of idiopathic TN. Zhang and colleagues118 recently reported that in every one of their 200 cases of idiopathic TN, vascular compression was found near the pons. Zhang and colleagues found, however, that the offending vessel was the SCA in just 117 cases. In addition, another unspecified artery was found in 69 cases, an aneurysm in 2 cases, and a venous plexus in 12 cases. Diagnostic Evaluation After obtaining a history, a complete head and neck and neurotologic exam is performed with the specific aim of finding a cause for the facial pain, such as temporomandibular joint disease, a parotid lesion with neural involvement, or maxillary sinusitis. Following the examination, a gadolinium-contrast MRI scan is obtained, in an effort to rule out tumors or multiple sclerosis involving the trigeminal nerve. Other studies necessary to determine the cause include coronal CT scans of the sinuses and fineneedle aspiration biopsy of a palpable lesion. CT scans of the skull base and the various foramina can also be helpful in the evaluation for a tumor in this region. Treatment Once the diagnosis of TN is established, the patient is treated with carbamazepine (Tegretol), beginning at 200 mg bid. The dose of the carbamazepine is increased by 200 mg/day until the symptoms are controlled. A positive response to carbamazepine is considered virtually diagnostic of TN, and this finding is used as a diagnostic test by some clinicians. The maximum dose of carbamazepine is approximately 1200 mg/day, but in the author’s experience,

most patients complain of drowsiness at 800 to 1000 mg/day. During the administration of carbamazepine, a complete blood count should be obtained weekly to avoid the complication of agranulocytosis. Patients with TN that is not adequately controlled on carbamazepine are considered candidates for surgical therapy. This therapy consists of two types: radiofrequency lesioning of the trigeminal nerve root and microvascular decompression of the trigeminal nerve root entry zone. Radiofrequency lesioning consists of the introduction of a thin needle-like probe into the foramen ovale. The mandibular nerve and semilunar ganglion are then lesioned by high-frequency energy, which leaves the lower face anesthetized. This procedure is preferred when the patient’s age or medical status precludes an intracranial procedure. Microvascular decompression is performed through a suboccipital approach. In this procedure, the arteries and veins that contact the trigeminal nerve are elevated and small tufts of cardiac felt are placed to prevent reattachment of the vessels. The most frequent vessel that causes TN is the SCA. When no clear vascular compression is found, most neurosurgeons prefer to section partially the sensory root of the trigeminal nerve (portio major). Although microvascular decompression is initially beneficial in 75% to 85% of cases, the long-term success of this procedure is closer to 50%. Many of the complications associated with microvascular decompression of the trigeminal nerve are the same as those that occur with microvascular decompression of the facial nerve, including aseptic meningitis, pneumonia, pulmonary embolus, and CSF leak. Compared with microvascular decompression of the facial nerve, the incidence of permanent facial palsy and hearing loss is much less (less than 1%). Surgery for TN, however, has specific, unique complications—anesthesia dolorosa and keratitis neuroparalytica— that merit further discussion. Anesthesia dolorosa119 is a particularly troublesome complication of TN surgery, and as the name indicates, includes both anesthesia and pain of the face. Anesthesia dolorosa occurs following the creation of a trigeminal lesion, most often following radiofrequency lesioning of the nerve; less so after partial section of the sensory root. Anesthesia dolorosa can also occur after microvascular decompression of the trigeminal nerve, but much less often. (A search of the literature after 1980 failed to disclose the exact incidence of this problem.) Although hypoesthesia of a trigeminal branch can be readily demonstrated, the patient complains of a constant, burning sensation of the face. Anesthesia dolorosa is thought to be due to the development of a traumatic neuroma of the trigeminal nerve, after which ephaptic transmission occurs in the nerve. Increased trigeminal nerve firing then causes the same pathophysiologic sequence described earlier for the development of TN; thus the development of this complication in TN patients is not too surprising. The initial treatment consists of carbamazepine. Surgical treatment for more severe cases includes tractotomy, vertical nucleotomy, and more recently the implantation of deep brain stimulators into the thalamus. A second and equally serious complication of TN surgery is keratitis neuroparalytica. This condition occurs as a result of the development of corneal anesthesia following

Vascular Compression Syndromes

lesioning of the trigeminal nerve. The cornea develops progressive ulceration, even in cases where tearing and blinking remain normal. These patients should be referred for immediate ophthalmologic consultation. In most cases, a tarsorrhaphy or canthoplasty is performed to protect the cornea.

Glossopharyngeal Neuralgia History The symptoms of GPN were first described by Weisenberg120 in 1910 in a case associated with an acoustic neuroma. Harris63 first described GPN as a distinct clinical entity in 1921. Clinical Features GPN is characterized by a unilateral pain usually situated in the base of the tongue and in the tonsillar fossa, but the pain may radiate outward into the pharynx. In some cases the pain may also be felt in the external auditory canal and beneath the angle of the jaw. The pain is a severe lancinating pain, much like that described for TN. A cough may accompany the pain, in addition to salivation, flushing, sweating, tinnitus, and vertigo. Tachycardia, hypertension, and asystole have also been reported to accompany the paroxysms of GPN. The painful paroxysms last from 30 seconds to several minutes and tend to occur in bouts or cycles. Initially, the bouts of pain occur two to three times a year, but over time, the bouts tend to be more frequent and to last longer. The pain of GPN may be triggered by swallowing, talking, or pressure on the tragus. The clinician can trigger the paroxysm by placing a cotton swab on the base of the tongue or in the external auditory meatus. Site of Lesion Demographically, GPN occurs much less often than idiopathic TN, at a rate of approximately 0.3% to 0.5% of cases of TN. Like TN, GPN has been divided into symptomatic GPN and idiopathic GPN. Dandy121 estimated that one-fourth of GPN cases are due to tumor. Other symptomatic causes include local infection, trauma to the neck, elongation of the styloid process, occlusion of the internal carotid artery, and tortuosity of the vertebral artery or the posterior cerebellar artery.122,123 The origin of idiopathic GPN remains unknown, and like HFS and idiopathic TN, the mechanism of ephaptic transmission or cross-talk has been proposed. Ishii61 reported the presence of demyelination in the peripheral glossopharyngeal nerve in seven cases of idiopathic GPN and proposed that the “site of the lesion” of idiopathic GPN can be anywhere along the nerve, from the brainstem to the periphery. Kunc124 speculated that the lesion is in the brainstem, because of the frequent association of TN with GPN, and because the trigeminal tract and the glossopharyngeal tract are very near each other. Brihaye and coworkers60 reported the autopsy findings of a case of GPN. They found an atheromatous vertebral artery compressing cranial nerves IX, X, and XI.

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Diagnosis and Treatment Like TN, the history, physical examination, and radiologic evaluation are aimed at excluding identifiable lesions of the pharyngeal region. Having done so, most patients are initially started on carbamazepine in an attempt to control the symptoms. Surgical therapy is reserved for only the most severe cases and consists of avulsion of the glossopharyngeal nerve.

Tic Convulsif and Geniculate Neuralgia History and Clinical Features The combination of severe facial or ear pain with HFS is called tic convulsif, a term first suggested by Cushing125 in 1920. The reported incidence95 of this entity among patients with TN varies from 0.2% to 11%. Tic convulsif appears to be more frequent in women, with a female to male predominance of 2:1. Initially tic convulsif may present as either TN or as HFS. As the condition develops, the facial spasms become more frequent, and when they occur, facial pain usually accompanies them. Both components tend to undergo remission at the same time.

Site of Lesion Cook and Jannetta126 have proposed that tic convulsif is due to vascular loop compression of both the facial and trigeminal nerves. In reviewing the world literature on the subject, they found 15 cases with adequate operative documentation for study. Ten of these 15 cases had vascular abnormalities, and 5 had tumors compressing the cranial nerves. These authors reported 11 of their own operative cases, and at surgery 21 of the 22 involved cranial nerves (both V and VII) had vessels compressing the root entry zone. As a consequence of vascular decompression, 73% of their cases were pain-free and 73% had no HFS. An additional 18% of patients had only mild spasms of the face. Yeh and Tew127 have suggested that tic convulsif is actually the combination of geniculate neuralgia and HFS. These authors reported a case of tic convulsif due to a dolichoectatic anterior inferior cerebellar artery compressing the root entry zone of the motor and sensory portions of the facial nerve. Following decompression of the nerve root entry zone, the symptoms were relieved. Yeh and Tew127 further suggested that geniculate neuralgia is due to compression of nervus intermedius at the brainstem. Geniculate neuralgia is a very rare disorder, characterized by paroxysms of severe lancinating pain involving the ear, which may or may not be accompanied by profuse tearing of the ipsilateral eye. The term geniculate neuralgia was coined by Ramsey Hunt in 1907 to describe a case of postherpetic facial palsy with persistent severe ear pain. Geniculate neuralgia is now used to denote both symptomatic and idiopathic cases of recurring paroxysms of severe, deep ear pain. No obvious trigger site for the pain has been reported. A number of authors have proposed that the disorder involves the nervus intermedius128–130 and have recommended section of the nerve as treatment. Recently, however, the concept of vascular compression of

Vascular Compression Syndromes

Based on Applebaum and Valvassori’s report, if the site of the lesion is the TZ, only a limited number of symptomatic individuals could possibly have CNCS. Also, if the site of lesion in CNCS is in the porus acousticus, the only way to safely decompress the vessel would be to drill the bony canal and then open the dura to allow the vessel to expand away from the nerve. Moller29 has recently proposed that the site of lesion can be anywhere on the glial segment of the CVN in the CPA. Just how the vessel makes contact and then injures the CVN is unclear from the reported literature. One possible mechanism is ectasia, or elongation, of the vessels as a result of aging or arteriosclerosis.156 Most of the supporting data for this site of lesion are based on either surgical observations or on the response to microvascular decompression of the nerve. It should be reiterated here that vessels are normally found in contact with the CVN, so that surgical observations are of little value in proving the site of the lesion. Also, the results of microvascular decompression surgery do not constitute scientific proof either; it is unknown if trauma on the nerve or the placebo effect play a role in the improvement these patients may describe. Moller’s reports of ABR abnormalities,152,153,157–159 however, do suggest a retrocochlear site of lesion, most probably in the cochlear nerve. These data do not specify just what the cause of the abnormality is, only the site. Schwaber and Whetsell52 have recently proposed a third site of lesion—that CNCS begins with an episode of vestibular neuritis. This site is based on a study of the histopathology of the nerve, which revealed marked axonal loss in CNCS cases. Schwaber has stated that the role of vessels at this time remains undetermined. Diagnostic Evaluation The evaluation of patients with recurrent vertigo and disequilibrium begins with a complete history and neurotologic examination. When taking the history, features that should suggest the possibility of CNCS are the recent onset of motion intolerance, a sensation of constant floating or unsteadiness, optokinetic symptoms, worsening of symptoms with fatigue, and recurrent vertigo in the absence of fluctuating hearing loss. Auditory symptoms include tinnitus and either unilateral or bilateral hearing loss. Physical examination of the ears, nose, throat, and head and neck is usually normal. Neurotologic exam is often characterized by spontaneous or gaze nystagmus. Another finding that suggests the possibility of CNCS is the presence of a rotatory nystagmus, which can be elicited when the patient lies down, a sign that might ordinarily be called a nonclassical Dix-Hallpike test. In addition to the history and the neurotologic examination, the author obtains an audiogram, acoustic reflex test, ABR test, and ENG in patients with recurrent vertigo. Rotational testing is obtained in selected patients, particularly those with signs, symptoms, and test findings that suggest the possibility of CNCS. Laboratory tests, including reactive protein reagent (RPR), microheamgglutination-Treponema pallidum (MHA-TP), sedimentation rate, antinuclear antibody (ANA) titers, rheumatoid factor, cholesterol, triglycerides, serum glucose levels, and thyroid function tests, are obtained. Gadolinium-enhanced

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MRI scans of the head and IACs are also obtained. The results of these studies are then reviewed in an effort to define the cause of the patient’s symptoms. Patients with Ménière’s disease, benign paroxysmal positional vertigo, acoustic tumors, acute vestibular neuritis, perilymph fistula, or other systemic diseases are treated. Patients without an obvious vestibular diagnosis are considered possible cases of CNCS. Based on the test data obtained, suggestive cases are referred for air contrast CT scans. Simultaneous intravenous and air contrast CT scanning enables the vessels and nerves of the CPA to be visualized clearly. McCabe has suggested that the only vessels that can be imaged are those that are fixed to the nerve bundle and that therefore cause the symptoms. Both CPAs should be studied and compared. If a fixed vessel is found in this group of patients, the diagnosis of CNCS is very likely. In contrast, Parnes160 studied the relationship of the vasculature in the CPA to the cochleovestibular bundle on MRI scan. Vessels were seen in 60% of cases, and vessels were observed in 40% of cases. Contact of the vessels and the nerves was observed in 12% of cases. Similar results were reported by Makins and colleagues,161 who also noted that the presence of vessels on MRI did not support the diagnosis of vascular loop compression. Treatment Some patients with symptoms of CNCS can be treated conservatively with vestibular suppressants such as diazepam (Valium), alprazolam (Xanax), or clonazepam (Klonopin). Vestibular rehabilitation therapy with platform posturography may also be helpful in these cases. Patients who are so symptomatic that they cannot work or carry on daily functions are considered surgical candidates. Vestibular nerve section controls the episodic vertigo in the majority of CNCS cases, but this procedure has not altered the constant disequilibrium and unsteadiness seen in these patients.155 On the other hand, microvascular decompression of the CVN eliminates the disequilibrium in approximately half of the cases and improves the symptoms in another one fourth of cases. Microvascular decompression fails to control the symptoms in approximately

Figure 51-9. Air contrast CT scan of the left CPA showing a vascular loop extending into the IAC.

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one fourth of cases. The long-term results of microvascular decompression are unknown at this time.

SUMMARY The vascular compression syndromes are a group of conditions thought to be caused by the compression of a cranial nerve by a vascular loop. The current theory of pathophysiology states that through both deafferentation and chronic stimulation, the cranial nerve nucleus undergoes reorganization and becomes hyperfunctioning. This hyperfunction is responsible for the symptoms seen in these patients. The technique of microvascular decompression is described as well as the controversy surrounding it. Microvascular decompression is most effective in the management of HFS; less so in the management of TN and CNCS. The clinical features, diagnosis, and treatment of each vascular compression syndrome is reviewed.

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Chapter

52 J. Gail Neely, MD

Facial Nerve and Intracranial Complications of Otitis Media Outline Introduction Epidemiology History Pre-1920s 1920s and 1930s 1940s to Present Relative Frequency of Complications General Pathophysiology Acute versus Chronic Otitis Media Role of Cholesteatoma Predisposing Factors Microbiology of Complications Microbial Virulence Factors Anaerobic Bacteria Bone Resorption and Biofilms Bone Resorption Biofilms Subtle Signs of Impending or Early Complications

INTRODUCTION Complications of otitis media occur when infection extends beyond the pneumatized spaces of the temporal bone and their mucosa.1,2 Fourteen intratemporal (extracranial, aural) complications of otitis media are hearing loss, perforation of the tympanic membrane, mastoiditis, apical petrositis, facial nerve paralysis, labyrinthitis, atelectasis of the middle ear, aural acquired cholesteatoma, cholesterol granuloma, ossicular discontinuity, adhesis otitis media, tympanosclerosis, ossicular fixation, and infectious eczematoid dermatitis. Seven intracranial complications are extradural abscess, dural sinus thrombophlebitis, brain abscess, encephalitis, hydrocephalus, meningitis, and subdural empyema.3 In this chapter, the complication of facial nerve paralysis and six intracranial complications of otitis media are discussed. Because encephalitis is one of the four stages of brain abscess, brain abscess/encephalitis are discussed as one complication. Additionally, because the pathophysiology of development and consequences of extradural granulation tissue are the same as the rarer extradural abscess, extradural abscess/granulation tissue were discussed as a single complication. 912

Facial Paralysis Specific Pathophysiology Clinical Presentation Diagnosis Treatment Epidural Abscess/ Granulation Tissue Specific Pathophysiology Clinical Features Diagnosis Treatment Dural Venous Sinus Thrombophlebitis Specific Pathophysiology Clinical Features Diagnosis Treatment Brain Abscess/Cerebritis Specific Pathophysiology Clinical Features Diagnosis

Treatment Otitic Hydrocephalus Specific Pathophysiology Clinical Features Diagnosis Treatment Meningitis Specific Pathophysiology Clinical Features Diagnosis Treatment Subdural Empyema Specific Pathophysiology Clinical Features Diagnosis Treatment

The order in which the intracranial complications are discussed is clinically significant. Multiple complications are not unusual and may be sequentially grouped by pathophysiology to facilitate diagnosis. The progression of extradural granulation tissue, as a consequence of mastoiditis or apical petrositis, adjacent to a dural venous sinus may result in sinus thrombophlebitis, which in turn may lead to brain abscess/encephalitis or otitic hydrocephalitis. Meningitis is characteristically the most common and usually single complication. Epidural empyema is rare, but can be a sequela of meningitis.

EPIDEMIOLOGY Considering that health care costs from otitis media exceed $5 billion a year in the United States alone,4 it is astonishing that complications are not more common. The particular issue of why only select individuals develop complications continues to challenge medical interest and requires better answers. Antibiotics have certainly played a significant role; however, even in the preantibiotic era, the curiosity of biologic selectivity remains.

Facial Nerve and Intracranial Complications of Otitis Media

History Pre-1920s Before the 1900s, intracranial complications of otitis media were nearly always fatal.5 Barr accurately described subdural empyema complicating otitis media and recommended mastoid drainage.6 However, only the rare surgeon, such as Macewen, successfully treated otogenic intracranial complications.7 1920s and 1930s Despite the development of the radical mastoidectomy for exteriorization of cholesteatoma, 6% of patients with acute or chronic otitis media developed an intracranial complication in the 1920s and 1930s,8 and 1 out of every 40 deaths at Los Angeles County Hospital was due to an intracranial complication of otitis media.9 The mortality rate for meningitis, the most dreaded complication, was 90%,10 and for brain abscess was 80%.11 Mosher developed the concept of draining otogenic brain abscesses through a source distant from the mastoid, an improvement over earlier procedures, but mortality rates continued to be high.12 1940s to Present With the advent of the sulfonamides and penicillins, the incidence of and the mortality from intracranial complications from otitis media dropped dramatically. Courville found a 90% decrease in the death rate from complications of otitis media.13 Dawes found that in the 1940s, 25 of 67 patients with central nervous system (CNS) complications of otitis media died, compared with 4 of 62 in the 1950s; these data were statistically significant and the comparison had excellent power (chi-square p < 0.001, power 0.988).14 Proctor reported 129 cases of intracranial complication of otitis media with 39 deaths from 1934 to 1943 at the University of Michigan, whereas only 27 cases with 1 death occurred during the period 1953 to 1962.15 These data represent a 79% proportional decrease in complications over the two 10-year comparative intervals, and the decrease in death rates were statistically significant (chi-square p = 0.009). Because the aural complications of mastoiditis, apical petrositis, facial paralysis, and labyrinthitis, and especially the

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intracranial complications since antibiotics were introduced, have become less frequent, complacency, which can result in delayed or incomplete diagnosis, is a danger.10 Complacency may be premature. Two recent systematic reviews of patient data in two large medical centers suggest: (1) complications may be more common than generally recognized16 and (2) proportional increases in antibiotic resistance may be responsible for increasing numbers of patients with complications; this could represent a partial return to the preantibiotic era.17 Greenberg and Manolidis16 found more than one-third (33 of 90) of consecutive operations for chronic ear disease had complications discovered during surgery.

Relative Frequency of Complications Most studies that look at the frequency of CNS complications of otitis media find that meningitis is the most common (Table 52-1). Exceptions include Pennybacker’s review of 200 cases of intracranial complications of mastoiditis, in which he found that brain abscesses and otitic hydrocephalus outnumbered cases of meningitis.18 Lund found brain abscess to be more common than meningitis in his review of 50 patients.19 Proctor found sigmoid sinus thrombosis to be slightly more common than meningitis in his preantibiotic series, but this finding changed in his postantibiotic data.15 The other five postantibiotic studies find meningitis to be the most prevalent intracranial complication of otitis media.14,20–23 After meningitis, sigmoid sinus thrombosis, brain abscess, and extradural abscess generally occur more commonly than the two most unusual complications, otitic hydrocephalus and subdural empyema. Missing from these data is a differential between acute middle ear infections and chronic infections. Meningitis is by far the most common complication from acute suppurative otitis media and rare in chronic suppurative otitis media; the other complications are predominantly the result of chronic infections, especially in the presence of cholesteatoma. Detection and definition bias may account for dural venous sinus thrombophlebitis and brain abscess outnumbering extradural abscess in Table 52-1. Extradural granulations, which might not be counted as an extradural abscess, are much more common than dural venous sinus thrombophlebitis and brain abscess and are prerequisite to sinus thrombophlebitis and most otogenic brain abscess. The remaining numbers are consistent with experience.

TABLE 52-1. Relative Frequencies of Intracranial Complications of Otitis Media in the Antibiotic Era

Dawes14 Proctor15 Juselius and Kaltiokallio21 Wolfowitz23 Fisch96 Gower and McGuirt20 Samuel et al.22 Total of columns (n = 724)

Meningitis

Sinus Thrombus

Brain Abscess

Epidural Abscess

Otitic Hydrocephalus

Subdural Empyema

98 11 19 26 21 76 83 334

97 3 5 11 3 5 39 163

40 8 2 3 6 6 53 118

Not given 1 16 8 Not given Not given 49 74

5 4 Not given 4 3 5 Not given 21

6 0 0 5 0 3 Not given 14

Modified from Neely JG, Doyle KJ: Facial nerve and intracranial complications of otitis media. In Jackler RK, Brackmann DE (eds.): Neurotology. St Louis, Mosby, 1994, pp 905–918.

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GENERAL PATHOPHYSIOLOGY

Microbial Virulence Factors26

Acute versus Chronic Otitis Media

Virulence is the capability of a pathogen to cause disease. Virulence factors are the properties, for example, gene products, enabling a microbe to establish in a host and to cause disease. Pathogens may be organized into two groups: (1) principal pathogens, which cause disease even when the general host defenses are intact, and (2) potential pathogens (e.g., Pseudomonas aeruginosa), which do not usually invade and cause disease in an intact host but may cause devastating disease in a compromised one. Principal pathogens can be further subdivided into: (1) opportunistic organisms, which are those that require some local breakdown or host impairment for them to cause disease (e.g., Staphylococcus aureus or pneumococcus), and (2) those that cause disease in a completely intact host. Most principal pathogens seem to be opportunistic. Pathogenic organisms are capable of creating their own opportunistic advantage by overcoming host defenses. These are (1) antiphagocytic capsules, (2) toxins, and (3) enzymes; these act on the host immune cells and to break down local anatomic barriers. Pathogenic organisms have additional more subtle mechanisms for avoiding or subverting host defenses. These are (1) immunoglobulin-specific proteases, such as IgA protease by H. influenzae, (2) iron sequestration mechanisms, and (3) coating themselves with host proteins. Microbes have the objective of replication and persistence; death of the host is counterproductive to this end. Disease is a “byproduct” of the organisms’ effort to achieve their objective.26 Not only do individual organisms exert adaptive mechanisms within the host in order to survive, they may share “virulence-associated genes” with other organisms within the species. Local changes about the organisms in temperature; ionic conditions; oxygen concentration; pH; and concentrations of calcium, iron, and other metals “exert profound effects on expression of virulence determinants.”26 A genetic control mechanism within the microbial organism, called a regulon, coordinates pathogenicity. These regulons are groups of individual genes controlled by a common regulator, such as a protein or a receptor. A “regulon provides a means by which genes can respond in concert to a particular stimulus.”26

Proctor pointed out that in the preantibiotic era, most intracranial complications of otitis media (52%) developed as a result of acute infection. After the introduction of antibiotics, the trend reversed, and more complicated ear cases were associated with chronic ear disease (76%) than with acute middle ear disease.15 Role of Cholesteatoma Mathews and Marus discussed the important role played by cholesteatoma in the genesis of intracranial complications, particularly in developing nations. Of their 74 patients with cholesteatoma-associated mastoiditis, 44% had intradural spread of infection, with a 12% mortality rate. In contrast, only 7% of their patients having mastoiditis without cholesteatoma showed intracranial spread, with only one death.24 Predisposing Factors Several obvious factors may alter the host’s resistance to microorganisms causing acute and chronic otitis media, making them more susceptible to complications.1 These may include systemic diseases such as diabetes, leukemia, immunodeficiencies, malnutrition, and medications such as steroids that suppress the immune system. In addition, temporal bone fractures, congenital dehiscences, or chronic infection may remove anatomic barriers to infection, thus permitting its spread to the labyrinth, facial nerve, or intracranially. However, the issue of why a small number of seemingly healthy individuals develop complications is a question worthy of more serious thought. Tissue invasiveness, bone destruction, and thrombophlebitis seem to be important processes by which transient or persistently inadequate host resistance or microbial virulence may result in complications. Microbial molecular biology may assist in generating some answers.

Microbiology of Complications An extensive review of cellular biology, molecular biology, biochemistry, microbiology, and immunology of otitis media is available in the report of the seventh research conference on otitis media.3 Readers are encouraged to study this supplement. The common organisms found in acute mastoiditis, with or without osteitis, are Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae. Anaerobic bacteria are predominant in brain abscesses; however, pneumococcus, Bacteroides fragilis, Peptostreptococcus species, Proteus species, and Pseudomonas species are also found in intracranial complications.25 These data would suggest that local breakdown of host defenses, especially those that create anaerobic environments, may be particularly important in the development of intracranial complications.

Anaerobic Bacteria27 Virtually all anaerobic organisms within anaerobic infections come from indigenous flora. Anaerobic organisms employ three major virulence factors: (1) ability to adhere to or invade epithelial surfaces, (2) production of toxins and enzymes, and (3) presence of surface capsular polysaccharides or lipopolysaccharides. Anaerobic infections are characterized by suppuration, abscess formation, and tissue destruction. Pathogenicity is enhanced by “the breakdown of anatomic barriers, especially mucosa, and factors lowering oxidation-reduction potential.”27 The following infections commonly involve anaerobic organisms: brain abscess, subdural empyema, chronic otitis

Facial Nerve and Intracranial Complications of Otitis Media

media and mastoiditis, and chronic osteomyelitis, whereas anaerobes are seldom involved with meningitis, acute otitis media, and acute osteomyelitis. Clinical clues of anaerobic infections are: (1) foul odor, (2) abscess formation, (3) septic thrombophlebitis, (4) previous treatment with antibiotics with poor activity against anaerobes, and (5) “no growth” in “sterile pus.” Failure to treat anaerobic organisms in a mixed aerobicanaerobic infection may lead to treatment failure. Surgical drainage and debridement is important in most anaerobic infections.

Bone Resorption and Biofilms Bone resorption “Most of the morbidity associated with chronic otitis media is due to pathological, localized resorption and remodeling of bone.”28 In an extensive review of the biology of bone resorption, Chole described the microenvironments of bone destruction in chronic otitis media, with or without cholesteatoma. In brief, bone resorption is the result of osteoclasts, which derive from mononuclear bone marrow precursors and are recruited to sites of inflammation and stimulated into activity by a series of cascades of inflammatory mediators. Pressure and the presence of keratinizing epithelium enhance this bone resorption. Bone-lining cells are simultaneously induced to retract from local areas, which allows recruited osteoclasts open access to bone matrix. Osteoclasts tightly attach to bone by a peripheral clear, or “sealing,” zone, which separates the metabolically active ruffled-border microenvironment against the bone from the remaining extracellular spaces. The osteoclastic cellular proton pump acidifies the ruffled-border isolated microenvironment to a maximally active pH of 4.0, and bone resorptions follows. A dynamic struggle between bone resorption and bone formation is mediated by a complex array of cytokines, lymphokines, growth factors, ecosanoids (arachidonic acid metabolites), neuropeptides, and enzymes. A principal ingredient in this balance seems to be plasmin. As tissue-type and urokinase-type plasminogen activators, serine proteases, which are present in many cell types, are stimulated, thereby converting plasminogen to plasmin. The dichotomous cascade that may follow determines the outcome. If plasmin activates procollagenase toward collagenase, osteoclasts are recruited and bone resorption ensues. However, if plasmin activates latent transforming growth factor beta to the active form, bone formation occurs. This normally occurring control mechanism may be significantly perturbed by chronic infection, especially in the presence of pressure-inducing, keratin-excessive cholesteatomas.28

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placement.29 Exactly what role biofilms play in the development of adverse microenvironments leading to complications remains to be seen. An exciting new discovery suggests that lactoferrin, a ubiquitous and abundant substance in mucosal secretions, especially in breast milk, can inhibit the formation of biofilms at the critical juncture of their development. Lactoferrin has been shown to prevent bacteria from adhering to mucosal surfaces by chelating iron and causing “twitching,” a special form of surface motility. The concentrations of lactoferrin necessary for twitching are considerably less than the levels at which these substances kill or retard bacterial growth.30 It is tempting to consider mucosal ulceration and granulation tissue development as significant perturbations of natural defense mechanisms, including the reduction of lactoferrin-induced twitching, leading to increased osteoclast activity and biofilm formation, which could predispose to complications of suppurative otitis media, with or without cholesteatoma.

SUBTLE SIGNS OF IMPENDING OR EARLY COMPLICATIONS The subtle signs of a potentially impending complication tend to be the clinical reflection of the above-mentioned pathophysiology. Evidence of persistence of an acute infection or fetid exacerbation of a chronic infection are hallmarks of an impending complication. Evidence of signs or symptoms unusual to the expected clinical course suggests the development of a potential complication. Some of these subtle signs and symptoms are (1) persistent pain over several days or recurrent pain within 2 weeks of a treated acute suppurative otitis media, (2) persistent or recurrent fetid discharge in a chronically draining ear following 2 weeks of vigorous treatment, or (3) local ear pain or systemic fever in a patient with a chronically draining ear without other reasons for the fever. Early signs and symptoms of an established complication are (1) retro-orbital pain; (2) lethargy, irritability, or headache; (3) dull boring ear pain during, or following, an ear infection; (4) blurred vision or diplopia; and (5) dizziness in a patient with an ear infection. These symptoms are not usually volunteered; they must be specifically elicited, especially in children, but often even in adults. The late signs and symptoms of intracranial complications of otitis media are altered mental status, fever, cranial nerve palsies, neck stiffness, subperiosteal abscess, cerebellar findings, emesis, headache, auricular cellulites, and suppurative labyrinthitis.31

Biofilms

FACIAL PARALYSIS

A biofilm is an amorphous extracellular matrix of exopolysaccharides on a surface surrounding “sessile” bacteria. These bacteria are alive, but inactive, not culturable, and resistant to antibiotics. Bacteria may leave the biofilm to become active, free-floating “planktonic” bacteria. Post demonstrated biofilms on the middle ear mucosa in chronically draining ears following tympanostomy tube

Specific Pathophysiology It had long been recognized that facial paralysis could have an otogenic cause, but it remained for Kettel to describe the incidence, clinical features, treatment, and outcome of facial palsy of otitic origin. From 1906 to 1938, 105 out of 13,125 patients treated for acute or chronic otitis media

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had peripheral facial weakness (0.8%). Chronic otitis media accounted for more than three times the facial paralysis than did acute otitis media; and 80% of facial palsy due to chronic otitis media was in patients with cholesteatoma.32 In the postantibiotic era, the frequency of facial paralysis in acute otitis media has decreased, but still occurs, more commonly in children than in adults.21 However, the incidence of facial palsy from chronic otitis media may not have changed drastically. Sheehy and colleagues analyzed 1024 cases of surgically treated cholesteatoma and found preoperative facial paralysis in 11 patients.33 Pfaltz reported facial palsy in 13 of 500 (2%) cases of otitis media (6 with cholesteatoma).34 The data from these historical biased samples suggest that not only did antibiotics not reduce the incidence of facial nerve injury in chronic otitis media; but the incidence may have increased. This assertion is based on the calculation that Kettle’s finding are not significantly different from those of Sheehy and colleagues (chi-square p = 0.449); however, Pfaltz’s data show an overall 69% proportional increase and a significantly greater incidence of facial paralysis in comparison with Kettle’s observations (chi-square p < 0.001). The development of facial paralysis in acute otitis media is presumably due to direct extension of inflammatory products and toxins to the fallopian canal by three possible routes: (1) congenital dehiscences in the canal, (2) physiologic canaliculi between the middle ear (e.g., stapedial muscle, chorda tympani nerve), or (3) vascular connections between the fallopian canal and the mastoid air cells.35,36 Acute neuritis results, with edema, compression, and ischemia leading to neurapraxia. In chronic otitis media, facial paralysis may occur due to osteitic erosion and invasion of the fallopian canal by granulation tissue or cholesteatoma. Cholesteatoma most commonly involves the facial nerve at the second genu or tympanic segment, producing direct compression or compression of the venous supply of the nerve (or both).

Clinical Presentation Although sudden facial palsy may occur in either acute or chronic otitis media, the usual picture is one of gradual weakness.37 Facial paralysis due to acute infection progresses over 2 to 3 days, often occurs about 7 to 10 days after the onset of acute otitis media, and occurs most often in children.38 In one study, only 37% of patients with facial paralysis due to acute otitis media had complete paralysis.39 Neumann’s sign, in which an individual branch of the nerve is weak and may progress to other branches, is an indicator of cholesteatoma.40 Lacrimal function is rarely affected in facial palsy produced by otitis media because the location of the lesion is usually distal to the takeoff of the greater superficial petrosal nerve.41

Diagnosis A history and physical examination serve to differentiate between acute and chronic otitis media, and careful assessment of each branch of the facial nerve is necessary to evaluate for Neumann’s sign. Lacrimal function testing with the Schirmer test helps to rule out more proximal coexisting lesions.

Cases of incomplete facial palsy with acute otitis medial usually require no further testing, because complete recovery is the rule. In cases of complete facial paralysis with acute otitis media, sequential maximal electrical stimulation testing should be performed to monitor any progression that might be obscured by the complete paralysis.42 Computed tomography (CT) with intravenous contrast is reserved for cases in which intracranial complications are suspected; high-resolution computed tomography (HRCT) of the temporal bones without contrast is important in those advanced cases of acute otitis media in which surgery is considered or planned and in all cases of subacute or chronic otitis media with facial paralysis.

Treatment Intravenous antibiotics and myringotomy are required for treating facial paralysis from acute otitis media. In cases of complete paralysis from acute otitis media and in those in which responses to maximum stimulation are lost, complete mastoidectomy is indicated. In these cases a facial recess approach from the mastoid to the middle ear and a large myringotomy or placement of a tympanostomy tube is wise. The objective is to clear the infection as rapidly as possible and to explore the fallopian canal in search of invading granulation tissue. Incising the facial nerve epineurium and perineurium is not wise because it exposes the vulnerable nerve fibers to destructive infection. Facial palsy from chronic otitis media requires immediate surgical treatment after institution of local and systemic antibiotics. The objective is to clear the infection and explore the nerve. If no cholesteatoma is present, complete intact-wall mastoidectomy should be performed with exploration of the facial nerve from the geniculate ganglion to the stylomastoid foramen; if cholesteatoma is present, the surgeon must determine if a canal wall-down or canal wall-up procedure should be performed. When granulation tissue or cholesteatoma is found in contact with the epineurium, bone should be removed widely to expose normal nerve sheath proximal and distal to the involved segment. Granulations and cholesteatoma may be carefully removed from the epineurium. The perineurium acts as a barrier to infection and should not be opened even if granulation tissue penetrates it; following granulations into the nerve is not recommended because granulations intersperse between nerve fibers and attempts to remove the granulations will result in loss of fibers. The perineurium can be opened to determine the need for later nerve resection and grafting only in rare cases where the nerve is necrotic and electrical testing indicates complete degeneration. Resection and grafting should not be done during the infection. Prognosis for recovery of function is excellent for partial facial nerve paralysis due to acute or chronic otitis media. However, a retrospective study by Silberman and Lewis found that 30% of patients with complete facial paralysis due to acute otitis media had an unsatisfactory recovery.39 Kettel noted better results in facial paralysis complicating acute suppurative otitis media. However, in 18 cases of facial palsy with osteitis found as mastoidectomy, 6 had

Facial Nerve and Intracranial Complications of Otitis Media

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complete recovery, 10 had incomplete recovery or synkinesis, and 2 had permanent complete paralysis. Of 27 patients who had mastoidectomy without exploration or decompression of the facial nerve for chronic otitis media with granulation tissue or cholesteatoma, 11 had an unsatisfactory result, with complete paralysis of the mouth or an inability to close the eye.32

EPIDURAL ABSCESS/ GRANULATION TISSUE Specific Pathophysiology Epidural abscesses are collections of pus external to the dura. More commonly, however, granulation tissue, rather than pus, is found at surgery. They occur at three sites: (1) between the tegmen and the middle fossa dura, (2) between the bone overlying the sigmoid sinus and the sinus itself (perisinus abscess), and (3) between Trautmann’s triangle and the posterior fossa dura.43 Epidural abscesses may be found incidentally at mastoidectomy and represent a relatively early intracranial complication of subacute or chronic otitis media.44 Epidural abscess occurs as a consequence of bone destruction, either in coalescent mastoiditis or in chronic otitis media with granulation tissue or cholesteatoma. Coalescent mastoiditis and chronic suppurative otitis media without cholesteatoma more likely results in posterior cranial fossa epidural abscess, often adjacent to the sigmoid sinus, whereas cholesteatoma may produce epidural abscesses in either the middle or posterior fossa.43 Epidural abscesses or granulation tissue are often precursors to and concomitant with sigmoid sinus thrombophlebitis, brain abscesses/cerebritis, and otitic hydrocephalus. If the sigmoid sinus is occluded and inflamed, otitic hydrocephalus may occur. If retrograde thrombophlebitis extends from the transverse or sigmoid sinus along cerebral veins, especially the vein of Labbé, temporal lobe or cerebellar brain abscesses or cerebritis, remote from direct contact with the temporal bone, may occur. In other words, epidural abscess or granulation tissue are frequently the precursors to the other, more severe complications of otitis media.

Figure 52-1. Axial postcontrast CT showing posterior fossa otogenic epidural abscess with rim enhancement (arrow).

Epidural abscess appears hyperintense relative to CSF on both T1- and T2-weighted MRI, unlike sterile effusions or blood (Fig. 52-3). CSF pressure and cell count are usually normal in epidural abscess. When imaging confirmation is not possible, the epidural abscess may be found at operation. Surgical discovery by careful dissection to view dura through thin bone remains the most accurate means of diagnosing cases otherwise requiring surgery for suppurative disease.

Treatment The treatment of epidural abscess is surgical. Discovery at mastoidectomy of granulation tissue overlying the dura establishes the diagnosis of epidural space invasion, with or without pus. Ritter found 12 patients with pathologic dural exposure in 152 patients with cholesteatoma, the precursor of epidural abscess.46 The bone should be thinned over the sigmoid sinus, posterior fossa dura, and middle fossa dura to inspect for granulations or abscess. When either is found, bone should be removed until normal dura is found circumferentially.41

Clinical Features Epidural abscess is most often clinically silent. Deep ear pain, however, may be present. Profuse, creamy, pulsatile otorrhea is usually present in chronic otitis media with epidural abscess.

Diagnosis CT with intravenous contrast may demonstrate epidural abscess of the posterior fossa on axial cuts or of the middle fossa on coronal views (Fig. 52-1). Bone program CT may reveal erosion of the bone commonly over the lateral surface of the sigmoid sinus or middle fossa tegmen and rarely over the posterior fossa at Trautman’s triangle (Fig. 52-2). MRI may also be used to diagnose epidural abscess and is considered to be more sensitive for this purpose than CT.45

Figure 52-2. Bone program coronal CT demonstrating erosion of bone at the right tegmen (arrow) at the site of a middle fossa epidural abscess.

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inflammation of the dural outer wall of the sinus is induced. As inflammation (phlebitis) reaches the inner wall of the sinus, mural thrombus forms, which progressively becomes larger, eventually obliterating the lumen of the sinus. As infection progresses, the thrombus propagates anterograde down the jugular bulb to the jugular vein, retrograde through the superior or inferior petrosal sinus to the cavernous sinus, posteriorly through the torcular, or through the mastoid emissary vein. The second route by which sigmoid sinus thrombosis forms is in acute otitis media by osteothrombophlebitic extension via small venules that thrombose and propagate into the sinus. In such cases, the bone over the sigmoid sinus is likely to be intact and the outer wall of the sinus may appear normal. Figure 52-3. T1-weighted coronal MRI in the same patient as Figure 52-2, demonstrating middle fossa epidural abscess, which appears as a bright signal (arrow).

DURAL VENOUS SINUS THROMBOPHLEBITIS Specific Pathophysiology Infectious thrombophlebitis of the sigmoid sinus is a wellknown intracranial complication of otitis media. Politzer5 in 1883 accurately described the pathology and clinical features of lateral sinus thrombosis, stating that the disease was, with few exceptions, fatal. By 1934, the prognosis of otogenic lateral sinus thrombosis was still grave; Coureville and Nielsen found dural sinus thrombosis in 69 of their 303 autopsy cases of otitis media intracranial complications.9 By the 1950s the prognosis was far more favorable, and the condition more rare. Jensen47 reported that sinus thrombosis as the cause of death in Denmark was down from 0.3% of total postmortems to just 0.01%. Dawes found 97 cases of sinus thrombosis out of 252 cases of intracranial complications, of whom 16 died.14 In his series, sinus thrombosis and meningitis occurred with equal frequency. Sigmoid sinus thrombosis was a more common otitic complication than meningitis in Proctor’s review.15 In the modern series by Gower and McGuirt in the United States, all of the nonmeningitic complications of otitis media are rare, with lateral sinus thrombosis being no more common than brain abscess or otitic hydrocephalus.20 In another review from the United States, Teichgraeber and coworkers described six cases seen over a 10-year period, with a single death.48 In contrast, Seid and Sellars in South Africa treated 13 cases of lateral sinus thrombosis due to ear disease in just 2.5 years, with a mortality rate of 23%.49 Septic thrombosis of the sigmoid sinus may occur with chronic or acute infection, with chronic infection being responsible more frequently in some series14,15,49 and acute/subacute infections predominating in others.20,50 Shambaugh presented two pathophysiologic mechanisms for the formation of lateral sinus thrombosis.51 The first and more common pathway is by erosion of bone from coalescent mastoiditis or cholesteatoma with formation of perisinus granulation tissue, or abscess. Gradually,

Clinical Features Wolfowitz and Teichgraeber and coworkers outlined the clinical features of septic lateral sinus thrombosis.23,48 Fever is the most common sign and may have either the typical spiking curve or a more level pattern. Ear pain and neck stiffness are the next most common symptoms. Papilledema appears in a minority of cases in which total occlusion of the sinus with otitic hydrocephalus has taken place. Weight loss and anemia may also occur. Additional clinical signs would suggest propagation of thrombosis. In retrograde progression to the cavernous sinus, proptosis, ptosis, chemosis, and opthalmoplegia are possible.52 Anterograde propagation into the jugular vein produces further neck stiffness, a palpable cord, and eventually evidence of pulmonary septic emboli. Thrombosis laterally to the mastoid emissary vein produces the classic Griesinger’s sign of tenderness and edema over the posterior mastoid. Finally, posterior propagation through the torcular to the sagittal sinus may be the mechanism of otitic hydrocephalus, which is considered to be a separate complication of otitis media and is discussed in the next section.

Diagnosis In the past, lateral sinus thrombosis was extremely difficult to identify. The symptoms and signs are so nonspecific as to preclude accurate diagnosis. Clinical diagnosis became apparent only when further extension of thrombus occurred to the jugular vein, cavernous sinus, or superior sagittal sinus. Lumbar puncture was not helpful, because it was usually sterile, and the Queckenstedt test (failure of spinal fluid pressure to rise after the compression of the jugular vein on the side of the diseased ear) and Toby-Ayer test (rise in spinal fluid pressure when the opposite jugular vein is compressed) were considered unreliable and dangerous because of the threat of inducing brain herniation.14 The venous phase of cerebral angiography has been used to diagnose lateral sinus thrombosis, but has not been strongly recommended due to its potential to dislodge clot, thus spreading infection.48 CT has become a routine test in the investigation of intracranial complications. In sinus thrombosis, the socalled delta sign, a low-intensity central region surrounded by a high-intensity rim, may be seen.53 The delta is created by clot surrounded by contrast-enhanced dura. The delta

Facial Nerve and Intracranial Complications of Otitis Media

sign on CT has been used to diagnose superior sagittal, transverse, and sigmoid sinus thrombosis,54 but MRI has proven to be a superior means of assessing septic dural sinus thrombosis in any location.55 Early MRI studies found that flowing blood on spinecho images appears as a signal void, but vessel thrombosis emits a signal.56 Freshly formed thrombi, rich in deoxyhemoglobin, appear as intermediate density on T1-weighted images and low intensity on T2-weighted images; as clot matures and methemoglobin forms within it, MRI characteristics change so that it becomes hyperintense on both T1- and T2-weighted images56,57 (Fig. 52-4). The introduction of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) contrast enabled radiologists to look for the delta sign on MRI, and special flow images generated by gradient echoes permitted differentiation between slowly flowing blood and clot.58,59 This technology has been applied to otogenic sigmoid sinus thrombosis.60 Magnetic resonance angiography is the most recent development; it provides superior visualization of vessels and can estimate blood flow direction and velocity.55 Its advantages include its reduced risk and ability to provide images in multiple planes with a single data acquisition.61 It is now the imaging technique of choice in otogenic dural sinus thrombosis.55

Treatment Intravenous antibiotics and surgery are indicated in the treatment of sigmoid sinus thrombosis. The surgical approach has not changed greatly from 100 years ago. This consists of mastoidectomy with skeletonization of the sigmoid sinus by removal of sigmoid sulcus bone, exposure of the dural venous sinus, and gentle removal of overlying granulations. Opening of the sinus is rarely necessary, except to remove any pus or necrotic material.48 Free blood flow is not a surgical goal; complete clot removal is not necessary and may be dangerous. In the past, ligation of the jugular vein was advocated to prevent the anterograde propagation of thrombus, a process still used in advanced cases with evidence of spread.62 In current practice, ligation is recommended only when signs of advancing infection into the neck or pulmonary circulation appear.63

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Anticoagulation, which can arrest the propagation of thrombosis, but may increase the risk of venous infarct and intracranial hemorrhage, is recommended only in the presence of cavernous sinus thrombosis.52 Antibiotic coverage must be broad spectrum and should cover the mixed flora that typically appear in sigmoid sinus thrombosis, including streptococci, proteus, pseudomonas, and anaerobes.48 The variety of pathogens found in the mastoid in lateral sinus thrombosis cases make cultures obtained at surgery a necessity to guide the selection of antibiotics.

BRAIN ABSCESS/CEREBRITIS Specific Pathophysiology Brain abscess is defined in this section as an accumulation of pus surrounded by a region of encephalitis within the cerebrum or cerebellum.41 In the past, otitis media was an important cause of brain abscess, but today, ear infections account for less than 20% of brain abscesses.64 Brain abscess is even rarer in children than in adults, and most are in congenital heart disease, with only rare otogenic brain abscess being reported.65 However, one study reports an otogenic source of brain abscess in 35% of children with brain abscess.62 Twenty percent of otogenic brain abscesses are due to acute otitis media, whereas 80% develop from chronic ear infection.66 The mortality rate from otogenic brain abscess in the antibiotic era is about 25%.66,67 Samuel and colleagues found cerebral otogenic abscess to be four times more common than that arising in the cerebellum.22 Otogenic brain abscess usually originates from venous thrombophlebitis rather than direct dural extension.41 Acute or chronic otitis media with granulation tissue or cholesteatoma may involve the dura of the middle fossa or posterior fossa.67,68 Brain abscesses progressively develop and terminate in four pathologic steps: (1) Retrograde thrombophlebitis from dural vessels involved with local infection may extend to terminal white matter vessels, which produces encephalitis. (2) This localized encephalitis progresses to necrosis and liquefaction of brain tissue, with surrounding edema.67 (3) Within 10 days to several weeks, an abscess capsule consisting of fibrous tissue surrounded by granulation tissue forms. (4) As the abscess expands, rupture may occur into the ventricles or subarachnoid space, depending on the site of the abscess. The bacteriology of otogenic intracranial abscess usually includes gram-positive and gram-negative aerobic organisms, as well as anaerobes.41 Most otogenic brain abscesses contain multiple organisms.69 Of gram-positive aerobic organisms, Streptococcus and Staphylococcus species are common, but Proteus, Escherichia coli, Klebsiella, and Pseudomonas species may also be found. Haemophilus influenzae is rarely found in otogenic brain abscess.68 The most common anaerobic organisms found in brain abscesses are Peptococcus, Peptostreptococcus, and Bacteroides fragilis.41

Clinical Features Figure 52-4. T1-weighted axial MRI of right mature sigmoid sinus thrombosis (hyperintense on T1, arrow).

The clinical stages in the development of brain abscess have been well described and include (1) invasion (cerebritis),

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(2) localization (quiescent abscess), (3) enlargement (manifest abscess), and (4) termination (abscess rupture).41 In the first stage, patients have headache, fever, drowsiness, and malaise, which resolves over a few days. The second stage is clinically silent and may last several weeks. Fever, lethargy, and headache recur in the third stage, and focal neurologic symptoms or seizures may occur. Papilledema is found in 70% of stage 3.68 Finally, when the abscess ruptures in stage 4 the disease often becomes rapidly fatal.

Surgical treatment of chronic ear disease follows stabilization of the patient. The patient is usually quite stable, and both neurosurgical and otologic surgery may be done at the same time and as early as possible. Aspiration for culture of the brain abscess through a separate burrhole may be considered. Also, medications for seizure prophylaxis may be considered in cases of abscess or cerebritis.

Diagnosis

OTITIC HYDROCEPHALUS

CT with contrast can readily demonstrate cerebral or cerebellar abscess. The brain abscess appears as a hypodense area surrounded by an enhancing ring, which is in turn surrounded by hypodense edema (Fig. 52-5). For patients identified during the stage of cerebritis, imaging can be used to monitor medical treatment or to decide on the timing of surgical intervention.70 MRI can be used as well and is probably superior for revealing cerebellar abscess or for detecting any spread of the abscess to the ventricle or subarachnoid space.71

Specific Pathophysiology

Treatment Treatment of brain abscess requires, at least, intravenous antibiotics. Two controversies exist over the surgical treatment of otogenic brain abscess. The first controversial area in the treatment of brain abscess is whether neurosurgical intervention is needed at all; some data support the use of antibiotic therapy alone for resolution of small brain abscess.72 The second controversy pivots around the neurosurgical decision regarding drainage versus excision of the abscess. Some evidence suggests that aspiration of brain abscess or open evacuation of pus with antibiotic irrigations of the cavity results in fewer permanent neurologic sequelae.73 On the other hand, other evidence supports complete excision of the abscess resulting in lower mortality.64 The best position for the clinician regarding such controversies is to review the most current evidence and follow the direction of the best local neurosurgical consultation for a particular case.

Quincke was the first to describe otitic hydrocephalus as increased intracranial pressure associated with clear CSF.74 He believed it to be caused by increased secretion of CSF by the choroid plexus in response to infection. Symonds coined the term otitic hydrocephalus in 1931, defining it as the signs and symptoms of increased intracranial pressure (headache, vomiting, and papilledema), without abscess formation, with clear CSF findings, associated with otitis media.75 With the advent of ventriculography, it was learned that the ventricles are not enlarged in otitic hydrocephalus, but the name has persisted.76 Otitic hydrocephalus is a rare consequence of ear infection, with only a slightly higher incidence than subdural abscess in most series, and it may occur in acute or chronic otitis media.19,20 The prognosis, relative to mortality, is favorable compared with other intracranial otitis media complications; however, blindness can be a serious complication of papilledema. Foley76 reported only 6 deaths in 44 cases; in four more modern articles, no deaths were reported in a total of 19 patients.15,19,20,34 The exact mechanism producing increased intracranial pressure in otitic hydrocephalus is unclear, but Symonds provided the most plausible explanation.75 Using clinical and postmortem information, he deduced that the syndrome was caused by retrograde extension of thrombophlebitis from the lateral sinus to the superior sagittal sinus, with resultant blockage of the arachnoid villi. Because otitic hydrocephalus always occurs with lateral sinus thrombosis, but not all cases of lateral sinus thrombosis exhibit otitic hydrocephalus, Symonds’ theory is usually cited as the correct one. Lenz and McDonald argued against Symonds’ theory on the basis that sagittal sinus thrombosis is associated with further neurologic deficits, ventricular enlargement, and higher mortality than otitic hydrocephalus.77 Symonds felt that in otitic hydrocephalus the thrombus extended only to the posterior sagittal sinus and did not completely occlude it.

Clinical Features

Figure 52-5. Contrast-enhanced axial CT of a large brain abscess in a patient with chronic otitis media with cholesteatoma.

The presenting symptoms of otitic hydrocephalus include headache, lethargy, nausea, vomiting, visual blurring, and diplopia in combination with acute or chronic otitis media.77 Physical examination reveals papilledema, occasional sixth nerve palsy (unilateral or bilateral), and variable reduction of mental status. There is a potential for severe visual loss with otitic hydrocephalus.

Facial Nerve and Intracranial Complications of Otitis Media

921

Diagnosis History and physical examination and MRI are usually sufficient to make the diagnosis, which is made on the basis of intracranial hypertension as manifested by papilledema, ear infection, no meningitis signs, and no brain abscess on MRI. Lumbar puncture, showing increased pressures and clear CSF is risky in this condition because of the hazard of brain herniation and sudden death. If lumbar puncture is necessary, it should be performed only in the immediate presence of a neurosurgeon. CT has been recommended to demonstrate normal ventricular size and to rule out other accompanying intracranial infections.77,78 However, MRI is replacing CT as the method of choice in the evaluation of otitic hydrocephalus, because of its superior evaluation of the extent of dural sinus thrombosis79 (Figs. 52-6 and 52-7).

Figure 52-7. Sagittal MRI with gadolinium contrast-enhanced venogram, demonstrating narrowing of the distal superior sagittal sinus (arrow) in the same patient as Figure 52-6 with otitic hydrocephalus

Treatment The treatment of otitic hydrocephalus has two goals; eradication of otologic disease and the alleviation of intracranial pressure.77 It is important to remember that the cause of this type of intracranial hypertension is the inflammatory thrombophlebitis of the sigmoid sinus, with total occlusion. Treatment is mastoidectomy (with additional indicated procedures to eradicate disease), and exposure of the lateral surface of the sigmoid sinus (with gentle removal of granulations). Again, opening the dural sinus is not indicated and can be dangerous. Alleviation of intracranial pressure is usually first attempted with medication. Intravenous steroids, acetazolamide, furosemide, and mannitol have all been used in otitic hydrocephalus to decrease intracranial pressure.77 CSF drainage procedures including serial lumbar puncture, lumbar drainage, and long-term lumboperitoneal shunting may become necessary. Treatment is aimed at preventing visual deterioration. Recently, optic sheath surgical decompression has been employed successfully to

Figure 52-6. T1-weighted axial MRI demonstrating a clot filling the right sigmoid and transverse sinuses, with extension into the torcula (arrow) in a patient with otitic hydrocephalus.

reverse the visual deficit associated with increased intracranial pressure.80

MENINGITIS Specific Pathophysiology Meningitis due to otitis media was the most dreaded and deadly of all complications before the era of antibiotics. Within several years after their introduction, antibiotics improved recovery from meningitis from 10% to 86%.10 In the postantibiotic era, otogenic meningitis in adults resulted from chronic otitis media twice as frequently as from acute otitis media.81 However, otogenic meningitis in children is predominantly from acute otitis media. Friedman and coworkers82 found meningitis was the most common CNS complication of otitis media. They found 92 of 259 cases of CNS infections were associated with otitis media and 91% were from meningitis. The majority of the patients were younger than 1 year of age. The mortality rate from otitic meningitis was 3%. In acute otitis media leading to meningitis, there is good evidence that bacteremia leads to meningitis, rather than direct extension of infection through the dura. In cases of Haemophilus influenzae type B bacteremia, 65% of children demonstrated otitis media.83 This indicates that otitis media may produce a bacteremia that spreads to the meninges. Eavey and colleagues also provided evidence that otitic meningitis in children has a hematogenous origin.84 Sixteen temporal bones from 8 children who died of meningitis were studied, and 14 of them demonstrated concurrent otitis media with no evidence of a direct pathway from the middle ear or mastoid to the intracranial cavity. Furthermore, when the inner ear was involved, the spread of acute infection to the labyrinth was from the CSF, via the internal auditory canal or cochlear aqueduct, rather than from the middle ear directly. This was seen in four patients with early suppurative labyrinthitis. On the other hand, otitic meningitis as a result of chronic ear disease can have as high as a 30% mortality

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rate and results from direct extension of infection from the ear.20 The bacteria cultured from patients with chronic otitis media producing meningitis are Proteus, Klebsiella, diphtheroids, and a mixture of anaerobes. Proctor felt that the pathophysiologic mechanism in meningitis due to chronic ear disease was direct spread of infection via the labyrinth, petrous apex cells, dural sinuses, or mastoid.15

the patient’s clinical condition is too poor to withstand surgery. However, remembering that in chronic otitis media direct extension of middle ear infection is often the cause, surgery in these cases should be considered as quickly as possible and should be focused as carefully as possible on the specific site of lesion.

SUBDURAL EMPYEMA Clinical Features Cawthorne described the clinical features of otitic meningitis.85 He noted that the progression of symptoms tends to be more rapid when meningitis is associated with acute otitis media than with chronic ear disease. The earliest symptom is headache, followed quickly by fevers and chills. Vomiting may follow, particularly in children, as well as restlessness in adults and irritability in children. Neck stiffness is another early sign. As the disease progresses, the headache becomes unbearable and photophobia appears. Neck stiffness increases to rigidity, Kernig’s and Brudzinski’s signs become positive. Fever continues to rise. Untreated, meningitis progresses to coma and neurologic deficits.

Diagnosis Early examination of the CSF verifies the clinical diagnosis, reveals the severity of the infection, and provides cultures to guide in the selection of antibiotics. HRCT with and without contrast is of use, particularly in patients with chronic ear disease, to look at bony architecture and to rule out epidural abscess, cerebritis, brain abscess, and large subdural collections requiring drainage.86 In children with rapid onset of meningitis with acute otitis media or repeated bouts of otitic meningitis, CT should be performed to diagnose a Mondini malformation or other congenital ear malformations that permit CSF leakage through inner ear fistulae. In adults, temporal lobe meningoencephalocele into the mastoid or middle ear should be suspected. Middle ear needle aspiration confirms the diagnosis of CSF leak, and CT confirms osseous defects; however, neither MRI nor CT always show the meningoencephalocele.87,88

Treatment Medical therapy is the mainstay for otitic meningitis. Antibiotics should be targeted to the suspected and, when known, the specific offending organism(s). The rapidity with which bacteria that commonly cause meningitis overcome host defenses necessitates the use of bactericidal rather than bacteriostatic antibiotics.89 Because rapid bacteriolysis releases high concentrations of inflammatory bacterial fragments, anti-inflammatory agents such as dexamethasone are needed to decrease the neurologic and audiologic sequelae of meningitis.90 Other antiinflammatory agents are being investigated, such as nonsteroidal drugs and monoclonal antibody directed against human adhesion molecules that serve as receptor sites for certain bacteria.89 Other than myringotomy, surgical therapy is reserved for cases of chronic otitis media and may be postponed if

Specific Pathophysiology Subdural empyema is a fulminating, purulent bacterial infection between the dura and arachnoid. Ear infection is an uncommon cause of subdural empyema seen more commonly with frontal sinusitis in children and adults and as a consequence of meningitis in infants.91 In nearly every reported series of intracranial complications of otitis media, subdural empyema is the least common, in both the preantibiotic and antibiotic eras.9,15 More recently, subdural empyema remains the rarest of otitis media complications.20,22,24 Only one study from a South African general hospital reports subdural empyema as being slightly more prevalent than brain abscess.23 Otogenic subdural empyema occurs more frequently in children than adults.20 Subdural empyema occurs more frequently as a complication of chronic otitis media than from acute otitis media or acute mastoiditis. In one study, two cases of posterior fossa subdural empyema and four cases of supratentorial empyema were all associated with chronic otitis media with cholesteatoma, and none with acute infection.25 The mortality from subdural empyema in the antibiotic era remains high compared with that from other intracranial complications of otitis media. Otogenic subdural empyema has a significantly higher mortality rate than that due to sinusitis.92 Courville and Nielsen in autopsy studies found three mechanisms for the formation of subdural empyema.9 The first was by direct spread of infection through bone and dura, usually at the tegmen tympani, by granulations or cholesteatoma. The second mechanism was retrograde extension of infection by small venous channels to the subdural space. The third was rupture of brain abscess into the subdural space. In otogenic subdural empyema, once pus reaches the subdural space, it may spread over the temporal and parietal lobes supratentorially, or over the cerebellum in the posterior fossa. The bacteriology of the subdural empyema depends on the site and chronicity of the primary infection. The neurologic deficits found in subdural empyema are felt not to be the result of mass effect, because the empyema is small, but rather are due to cerebral inflammation, vasculitis, and edema, with eventual venous infarction. Left untreated, mass effect from an edematous brain causes transtentorial herniation and death.93

Clinical Features The early signs and symptoms of subdural empyema include headache, nausea, vomiting, meningismus, and fever. Patients with delayed presentation progress to altered mental status, focal neurologic deficits, and focal or

Facial Nerve and Intracranial Complications of Otitis Media

generalized seizures.93 The time of onset of symptoms to presentation is short, averaging 4 days.

Diagnosis CT is usually the only study needed to diagnose subdural empyema and should be obtained immediately. Subdural empyema appears as a thin, low-density collection over the cerebral convexity, with a rim of contrast enhancement and inward displacement of the gray matter/white matter interface. Sometimes multiple discrete loculated subdural collections may be found.94 MRI is superior at detecting the presence and extent of all collections and more specific at differentiating epidural from subdural collections.45 MRI of epidural abscess demonstrates a hypointense rim, which represents displaced dura at the interface between the lesion and the brain, which would be absent in subdural abscess. Lumbar puncture is contraindicated because of increased intracranial pressure and the danger of tonsillar herniation. Physical examination combined with CT will reveal a sinus or otogenic source of infection.

Treatment Emergency neurologic surgery and intravenous antibiotics are the treatment for otogenic subdural empyema. Bannister and coworkers recommend craniotomy for drainage of the empyema, rather than burrhole drainage with aspiration, because burrhole treatment is frequently inadequate and needs to be repeated.95 They obtained a survival rate of 92% with primary craniotomy treatment. However, Bok and Peter found a mortality rate of 7.7%, with 86% of 90 patients making a good recovery in their review of patients with subdural empyema, the majority of whom had burrhole treatment based on CT scan localization of abscess.96 They concluded that in most cases, burrhole craniotomy has a place in the treatment of subdural empyema. Broad-spectrum antibiotics should be used initially, and operative cultures and localization of the source of infection will guide further antibiotic choices. If the patient is stable, mastoidectomy may be performed at the time of craniotomy, with eradication of cholesteatoma, if present.

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7. Macewen W: Pyogenic Infective Diseases of the Brain and Spinal Cord. Glasgow, James MacLehose, 1893. 8. Kafka MM: Mortality of mastoiditis and cerebral complications with review of 3225 cases of mastoiditis with complications. Larygoscope 45:790–822, 1935. 9. Courville CB, Nielsen JM: Fatal complications of otitis media. Arch Otolaryngol 19:451–501, 1934. 10. House HP: Acute otitis media: A comparative study of the results obtained in therapy before and after the introduction of the sulfonamide compounds. Arch Otolaryngol 43:371–378, 1946. 11. Ballantine HT, White JC: Brain abscess: Influence of the antibiotics on therapy and mortality. New Eng J Med 248:14–19, 1953. 12. Mosher HP: The wire gauze brain drain. Surg Gynecol Obstet 23:740–741, 1916. 13. Courville CB: Intracranial complication of otitis media and mastoiditis in the antibiotic era. Larygoscope 65:31–46, 1955. 14. Dawes JD: Discussion on intracranial complications of otogenic origin. Proc Roy Soc Med 54:315–319, 1961. 15. Proctor CA: Intracranial complication of otitic origin. Larygoscope 76:288–308, 1966. 16. Greenberg JS, Manolidis S: High incidence of complications encountered in chronic otitis media surgery in a U.S. metropolitan public hospital. Otolaryngol Head Neck Surg 125:623–627, 2001. 17. Zapalac JS, Billings KR, Schwade ND, Roland PS: Suppurative complication of acute otitis media in the era of antibiotic resistance. Arch Otolaryngol Head Neck Surg 128:660–663, 2002. 18. Pennybacker J: Discussion on intracranial complications of otogenic origin. Proc Roy Soc Med 54:309–315, 1961. 19. Lund WS: A review of 50 cases of intracranial complications from otogenic infection between 1961 and 1977. Clin Otolaryngol 3: 495–501, 1978. 20. Gower D, McGuirt WF: Intracranial complication of acute and chronic infectious ear disease: A problem still with us. Larygoscope 93:1028–1033, 1983. 21. Juselius H, Kaltiokallio K: Complication of acute and chronic otitis media in the antibiotic era. Acta Otolaryngol 74:445–450, 1972. 22. Samuel J, Fernandes CM, Steinberg JL: Intracranial otogenic complications: A persisting problem. Larygoscope 96:272–277, 1986. 23. Wolfowitz BL: Otogenic intracranial complications. Arch Otolaryngol 96:220–222, 1972. 24. Mathews TJ, Marus G: Otogenic intradural complications: A review of 37 patients. J Laryngol Otol 102:121–124, 1988. 25. Bluestone CD, et al: Treatment, complications, and sequelae. Ann Otol Rhinol Laryngol 11 (Suppl) 188 (3, Pt 2):102–124, 2002. 26. Relman DA, Falkow S: A molecular perspective of microbial pathogenicity. In Mandell GL, Bennett JE, Dolin R (eds.): Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Disease, 5th ed, vol I. Philadelphia, Churchill Livingstone, 2000, pp 2–12. 27. Finegold SM: Anaerobic bacteria: General concepts. In Mandell GL, Bennett JE, Dolin R (eds.): Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Disease, 5th ed, vol II. Philadelphia, Churchill Livingstone, 2000, pp 2518–2575. 28. Chole RA: The molecular biology of bone resorption due to chronic otitis media. Ann N Y Acad Sci 830:95–109, 1997. 29. Post JC: Direct evidence of bacterial biofilms in otitis media. Larygoscope 111:2083–2094, 2001. 30. Singh PK, Parsek MR, Greenberg EP, Welsh MJ: A component of innate immunity prevents bacterial biofilm development. Nature 417(May 30):552–555, 2002. 31. Schwaber MK, Pensak ML, Bartels LJ: The early signs and symptoms of neurotologic complications of chronic suppurative otitis media. Larygoscope 99:373–375, 1989. 32. Kettel K: Facial palsy of otitis origin. Arch Otolaryngol 37:303–348, 1943. 33. Sheehy JL, Brackmann DE, Graham MD: Cholesteatoma surgery: Residual and recurrent disease. A review of 1024 cases. Ann Otol, Rhinol, Laryngol 86:451–454, 1977.

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62. Mathews TJ: Lateral sinus pathology (22 cases managed at Groote Schuur Hospital). J Laryngol Otol 102:118–120, 1988. 63. Jackson CG, Dickins JR: Lateral sinus thrombosis. Am J Otol 1:49–51, 1979. 64. Le Beau J, et al: Surgical treatment of brain abscess and subdural empyema. J Neurosurg 38:198–203, 1973. 65. Spires JR, Smith RJ, Catlin FI: Brain abscesses in the young. Otolaryngol Head Neck Surg 93:468–473, 1985. 66. Meyers EN, Ballantine HT: The management of otogenic brain abscess. Larygoscope 75:273–288, 1965. 67. Kornblut AD: Cerebral abscess: A recurrent otologic problem. Larygoscope 82:1541–1556, 1972. 68. Maniglia AJ, et al: Intracranial abscesses secondary to ear and paranasal sinuses infections. Otolaryngol Head Neck Surg 88:670–680, 1980. 69. Ingham HR, Selkon JB, Roxby CM: Bacteriological study of otogenic brain abscesses: Chemotherapeutic role of metronidazole. Brit Med J 2:991–993, 1977. 70. Freeman J: Changing concepts in the management of otitic intracranial infection: Use of computerized axial tomography in detection and monitoring of cerebritis. Larygoscope 94:907–911, 1984. 71. Maniglia AJ: Intracranial abscesses secondary to nasal, sinus, and orbital infections in adults and children. Arch Otolaryngol Head Neck Surg 115:1424–1429, 1989. 72. Brand B, Caparosa RJ, Lubic LG: Otorhinological brain abscess therapy: Past and present. Larygoscope 94:483–487, 1984. 73. Maurice-Williams RC: Open evacuation of pus: A satisfactory surgical approach to the problem of brain abscess? J Neurol Neurosurg Psychiatry 45:697–700, 1983. 74. Quincke H: Über meningitis serosa und verwandre. Zustande Deutsche Atschr Nervenh 9:149–168, 1897. 75. Symonds CP: Otitic hydrocephalus. Brain 54:55–71, 1931. 76. Foley J: Benign forms of intracranial hypertension—“toxic” and “otitic” hydrocephalus. Brain 78:1–41, 1955. 77. Lenz RP, McDonald GA: Otitic hydrocephalus. Larygoscope 94:1451–1454, 1984. 78. O’Connor AF, Moffat DA: Otogenic intracranial hypertension. J Laryngol Otol 92:767–775, 1978. 79. Nadel L, et al: MRI of intracranial sinovenous thrombosis: The role of phase imaging. Mag Res Imaging 8:315–320, 1990. 80. Horton JC, et al: Decompression of the optic nerve sheath for vision-threatening papilledema caused by dural sinus occlusion. Neurosurg 31:203–212, 1992. 81. McLay K: Otogenic meningitis. J Laryngol Otol 68:140–146, 1954. 82. Friedman EM, McGill TJ, Healy GB: Central nervous system complications associated with acute otitis media in children. Larygoscope 1001:149–151, 1990. 83. Anderson AB, Ambrosino DM, George RS: Haemophilus influenza type B unsuspected bacteremia. Pediatrics 32:82–85, 1987. 84. Eavey RD, et al: Otologic features of bacterial meningitis of childhood. J Pediatrics 106:402–407, 1985. 85. Cawthorne T: Otogenic meningitis. J Laryngol Otol 54:444–470, 1939. 86. Mafee M, et al: Otogenic intracranial inflammations: Role of CT. Otolaryngol Clin North Am 21:245–263, 1988. 87. Neely JG: Classification of spontaneous cerebrospinal fluid middle ear effusion: Review of 49 cases. Otolaryngol Head Neck Surg 93:625–634, 1985. 88. Neely JG: Intratemporal and intracranial complications of otitis media. In Bailey BJ (ed.): Head and Neck Surgery— Otolaryngology. Philadelphia, JB Lippincott, 1993, pp 1607–1622. 89. Quagliarello V, Scheld WM: Bacterial meningitis: Pathogenesis, pathophysiology, and progress. New Eng J Med 327:864–872, 1992. 90. Odio C, et al: The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. New Eng J Med 324:1525–1531, 1991.

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91. Farmer TW, Wise GR: Subdural empyema in infants, children, and adults. Neurology 23:254–261, 1973. 92. Beekhuis GJ, Taylor M: Ear and sinus aspects of intracranial complications of intracranial suppurative disease in cranial and intracranial suppuration. In Gurdjian ES (ed.): Cranial and Intracranial Suppuration. Springfield, IL, Thomas, 1969, pp 42–58. 93. Wackym PA, Canalis RF, Feuerman T: Subdural empyema of otorhinological origin. J Laryngol Otol 104:118–122, 1990.

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94. Weisberg L: Subdural empyema: Clinical and computed tomographic correlations. Arch Neurol 43:497–500, 1986. 95. Bannister G, Williams B, Smith S: Treatment of subdural empyema. J Neurosurg 55:82–88, 1981. 96. Bok AP, Peter JC: Subdural empyema: Burr holes or cranitomy? A retrospective computerized tomography-era analysis of treatment in 90 cases. J Neurosurg 78(4):574–578, 1993.

Chapter

53 Ronald A. Hoffman, MD Dennis Pappas, MD

Cerebrospinal Fluid Leak of Temporal Bone Origin Outline Etiology Postoperative Cerebrospinal Fluid Leak Temporal Bone Trauma Tumors and Infection Labyrinthine and Perilabyrinthine Abnormalities Spontaneous Leaks Diagnosis Treatment Postoperative and Post-traumatic Cerebrospinal Fluid Leaks

C

erebrospinal fluid (CSF) leak of temporal bone origin implies an abnormal communication or series of communications between the subarachnoid space and the aircontaining spaces of the temporal bone. The anatomic integrity of the tympanic membrane and the functional status of the eustachian tube will dictate the clinical presentation. If the tympanic membrane has been violated, as might occur following temporal bone fracture, otorrhea may ensue. If the tympanic membrane is intact, which is usually the case after skull base surgery, ear fullness, hearing loss, or rhinorrhea may be the presenting symptom. Occasionally, CSF leak can be occult and intermittent, and meningitis will be the presenting symptom. CSF leaks can be classified as congenital and acquired (Table 53-1). Acquired leaks, which are far more common, are usually due to blunt or surgical trauma, less often infection or neoplasm. Congenital leaks may be due to labyrinthine abnormalities,1 patent or enlarged preformed perilabyrinthine pathways,2 or dural defects adjacent to the otic capsule.3,4

ETIOLOGY Postoperative Cerebrospinal Fluid Leak CSF leaks have been reported following tympanomastoid surgery for chronic ear disease, translabyrinthine approaches to the posterior cranial fossa and internal auditory canal (IAC), middle and posterior cranial fossa surgery, cochlear implantation,5 and various lateral skull 926

Spontaneous Cerebrospinal Fluid Leaks Cerebrospinal Fluid Leak with Cochlear Dysplasia Postinfectious/Neoplastic Adjunctive Measures Continuous Lumbar Cerebrospinal Fluid Drainage Intraoperative Glue Intraoperative Fluorescein Antibiotic Prophylaxis Conclusion

base procedures. The majority of postoperative CSF leaks are associated with acoustic tumor removal. CSF leaks following acoustic tumor surgery present as incisional (wound), rhinorrhea, or otorrhea.6 Anatomically, incisional leaks are straightforward. Otorrhea occurs when CSF gains access to the external auditory canal, which implies compromise of the external auditory canal wall or tympanic membrane. Rhinorrhea occurs when CSF reaches and finds egress through the eustachian tube to the nasopharynx. Following translabyrinthine surgery, CSF can gain access to the mastoid through the dural opening created for access to the posterior cranial fossa. From the mastoid, CSF can then track to the middle ear via the aditus ad antrum, facial recess cells, sinus tympani cells opened during facial nerve skeletonization, or retrofacial air cells. CSF can also gain access to the temporal bone via surgically exposed air cell tracts above or below the IAC. These air cell tracts can communicate with the middle ear via anterolateral extensions, hypotympanic extensions, or directly to the eustachian tube orifice via an anterosuperior extension. Finally, CSF can gain access to the vestibule through compromise in the fundus of the IAC and, if the stapes has been accidentally subluxed, directly into the middle ear.7 Following retrosigmoid removal of an acoustic neuroma, CSF can gain access to the pneumatized temporal bone via three potential routes: retrosigmoid air cells; the lateral end (fundus) of the IAC; or perilabyrinthine air cell tracts that can extend above, below, and into the posterior bony wall of the IAC. CSF leak via the lateral end of the IAC is theoretical, with no documented case following suboccipital surgery in the literature. The retrosigmoid air cells (perisinus tract) are often opened during suboccipital

Cerebrospinal Fluid Leak of Temporal Bone Origin

TABLE 53-1. Acquired Blunt trauma Surgical Infectious Neoplastic Congenital Labyrinthine-cochlear dysplasia associated with footplate dehiscence Perilabyrinthine Patent petromastoid canal Enlarged and patent cochlear aqueduct Patent Hyrtl’s fissure Enlarged facial nerve canal Dehiscent lamina cribrosa of IAC Distant from otic capsule Spontaneous IAC, internal auditory canal.

craniotomy (Fig. 53-1). The dura must be tightly closed and the exposed cells carefully sealed during surgical closure to prevent leakage of CSF into the mastoid via this route. Finally, a variable degree of pneumatization occurs above, posterior to, and below the IAC. Lang and Kerr8 demonstrated a pneumatized air cell tract in the posterior lip of the IAC in 22% of temporal bones examined histopathologically. These cell tracts are opened in the routine removal of the posterior bony wall of the IAC necessary to expose and remove intracanalicular tumor. Despite many technical modifications over the years, CSF leaks following acoustic tumor removal continue to be a clinical challenge. Bryce and colleagues,9 in a 1991 review of 319 cases, reported a 10% incidence after suboccipital surgery and an 11% incidence after translabyrinthine surgery. Brennan and colleagues10 reported a series of 624 cases in 2001, with a 10% incidence of leak following both translabyrinthine and retrosigmoid approaches. Leonetti and coworkers11 reported on 589 skull base surgeries

Figure 53-1. Axial high-resolution computed tomography scan (HRCT) demonstrating mastoid compromise (c) following suboccipital craniotomy. Note surgical mesh plate (p) used in operative closure. CSF leak was controlled by mastoid obliteration with abdominal fat.

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between 1988 and 1999 with an 8% incidence of CSF leak following retrosigmoid approach and a 4% incidence after translabyrinthine approach.

Temporal Bone Trauma CSF leak is common following temporal bone trauma. Hicks and coworkers12 studied 40 temporal bone fractures and noted that CSF leak occurred in 29% of longitudinal fractures and 44% of transverse. Ghorayeb and Rafie13 reported a 21% incidence of CSF otorrhea in 123 cases of temporal bone fracture and Lui-Shindo and Hawkins14 reported a 26% incidence following basilar skull fractures in children under 18 years of age. Lee and colleagues15 reviewed 72 children with 79 temporal bone fractures and found 58% to have otorrhea suggestive of a CSF leak. All resolved without active intervention. Dahiya and colleagues16 reassessed the classic characterization of fractures and their being longitudinal or transverse and found that the most critical factor predisposing to CSF leak was whether the otic capsule was violated or spared. The incidence of CSF leak was four times greater in otic capsule-violating fractures.

Tumors and Infection Tumors and chronic ear disease are unusual causes of CSF leak. The association of CSF leak with infection, however, is particularly onerous due to the potential for life-threatening intracranial infectious complications. Postmortem studies17 have demonstrated a tegmen defect in 21% of temporal bone specimens, with 6% having multiple defects. Although bony defects do not necessarily correspond with dural compromise and CSF leaks, infection adjacent to exposed dura poses a clear risk.

Labyrinthine and Perilabyrinthine Abnormalities The most common labyrinthine abnormality associated with CSF leak is cochlear dysplasia associated with a defect in the footplate of stapes. The lateral end of the IAC is usually dehiscent in these cases, allowing for direct communication of CSF with the cochlear cavity (Figs. 53-2 and 53-3). At surgery CSF may be noted to be welling or “gushing” from a central defect in the stapes footplate. Alternatively, an arachnoid “bleb” may be prolapsing through the footplate defect with an intermittent CSF leak. CSF leak associated with cochlear dysplasia usually is manifested in childhood as recurrent meningitis and is associated with a common cavity dysplasia, unilateral profound sensorineural hearing loss, and a unilateral vestibular deficit.18,19 CSF leak associated with cochlear dysplasia must be differentiated from idiopathic perilymph fistula of childhood. Reilly20 considered the CSF gusher associated with cochlear dysplasia to be one end of a continuum with idiopathic perilymph fistula (as seen in children with progressive sensorineural hearing loss). MacRae and Ruby21 referred to small and large perilymph fistulas: “small perilymph fistulas may present as progressive sensorineural hearing loss … Large perilymph fistulas in children usually present as recurrent bacterial meningitis …”

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Figure 53-2. Axial HRCT of 15-year-old female with sensorineural hearing loss AD (right ear) and recurrent meningitis. Note deformity of cochlea (a) and opacification of mastoid air cells (b). CSF leak surgically confirmed from dehiscence of stapes footplate.

The diagnosis, incidence, and even existence of idiopathic perilymph fistula in children is a subject of ongoing controversy.22 CSF is not synonymous with perilymph. CSF leak via a footplate fistula in a child with a cochlear malformation should be viewed as a distinct clinical entity, not synonymous with idiopathic perilymph fistula of childhood. Congenital perilabyrinthine pathways that remain patent and account for CSF leak are rare. Hyrtl’s fissure is a bony cleft inferior to the round window niche that extends medially, inferior to the cochlea, toward the posterior fossa. A patent Hyrtl’s fissure is due to lack of ossification between the otic capsule and the jugular bulb. The petromastoid canal extends from the posterior fossa surface of the temporal bone, through the arch to the superior semicircular canal and communicates with the mastoid air cell system (Fig. 53-4). The subarcuate artery traverses this canal, which is quite large in the fetus. CSF has been reported to leak from the fallopian canal, surrounding the facial nerve.23 Gacek24 studied anatomic variations in the distal extent of the subarachnoid space surrounding the facial nerve and found that the subarachnoid

Figure 53-4. Axial temporal bone section demonstrating superior semicircular canal (a) and petromastoid canal (b).

space ended in the intralabyrinthine segment in 88% but extended into the tympanic segment in 12%. Other potential perilabyrinthine pathways would include a patent cochlear aqueduct and a dehiscent cribriform plate in the fundus of the IAC. To be clinically relevant, however, these potential routes would have to be associated with a communication between the cochlea and middle ear, such as a round or oval window compromise or a fracture of the otic capsule.

Spontaneous Leaks Spontaneous CSF leaks constitute a distinct clinical subgroup that occurs distant from the otic capsule, usually along the middle fossa, less commonly along the posterior fossa plate.3 Occasionally, spontaneous leaks are due to multiple skull base defects.25 Gacek26 has argued that spontaneous leaks are secondary to herniation of aberrant arachnoid granulations located in the dural surfaces of the temporal bone. Increased age and intermittent spinal fluid pressure changes are hypothesized to cause progressive enlargement of these granulations, with subsequent bone erosion and communication of the CSF space and pneumatized temporal bone. Spontaneous CSF leaks may, therefore, bridge the distinction between congenital and acquired causes. Spontaneous CSF leaks that occur without evident precipitating cause are most common in the sixth decade and usually present as a unilateral middle ear effusion with associated conductive hearing loss. CSF rhinorrhea is less commonly the presenting symptom. The diagnosis is virtually certain when profuse clear otorrhea occurs following a myringotomy.

DIAGNOSIS

Figure 53-3. Coronal HRCT of patient depicted in Figure 53-1. Note continuity of IAC with vestibule (c).

The diagnosis of CSF leak of temporal bone origin is predicated upon a high index of suspicion. A history of clear, profuse rhinorrhea suggests a CSF leak but does not differentiate between a leak of anterior skull base and temporal bone origin. The presence of a middle ear effusion or

Cerebrospinal Fluid Leak of Temporal Bone Origin

a history of prior temporal bone, middle fossa, or posterior fossa surgery is more localizing. Often, a CSF leak will be intermittent and occult, and only recurrent meningitis will suggest the diagnosis. This is typically the case in the child with a cochlear malformation and a footplate dehiscence. Bryce and colleagues9 reported that 7% of leaks following acoustic tumor surgery presented as meningitis and Pappas and colleagues3 noted that 20% of spontaneous CSF leaks presented as meningitis. Physical findings may be few. Rhinorrhea, if not obvious, can sometimes be elicited by having the patient lean forward and perform a Valsalva maneuver. A middle ear effusion is nonspecific. However, clear and profuse otorrhea following a myringotomy is virtually pathognomonic. Temporal bone fractures may cause a tympanic membrane perforation, in which case otorrhea will ensue. Laboratory analysis may be of value if a specimen of fluid can be obtained. A glucose level 50% that of serum and a protein level of less than 1 to 2 g/L is suggestive of CSF. However, contamination of the specimen with blood, wound secretions, tears, or saliva can lead to a false-positive result. Definitive laboratory diagnosis, with as little as 100 μm of CSF, is possible by means of immunofixation techniques that demonstrate a characteristic β2-transferrin band found only in CSF. Intrathecally injected radionuclides can be helpful in establishing the presence of a leak, but when detected intranasally they do not differentiate between the anterior skull base and temporal bone as the source. Imaging studies remain the cornerstone of the accurate diagnosis and localization of CSF leaks. CSF leaks that complicate a temporal bone surgical procedure do not generally require imaging because the site and mechanism of the leak can be anticipated. Nonsurgical trauma, blunt or penetrating, is often imaged by high-resolution computed tomography (HRCT) to examine the extent of associated injury, in addition to the origin of a CSF leak. In contrast, the diagnosis and localization of occult or intermittent leaks may rely solely on imaging techniques. When CSF leaks present as rhinorrhea, the entire skull base must be imaged. HRCT remains the most effective imaging modality in demonstrating labyrinthine abnormalities, bony dehiscence, bony erosion (Figs. 53-5 and 53-6), or fracture. When intrathecal contrast is added to HRCT, the precise location of the leak can often be determined, if the leak is active during the study (Fig. 53-7). Magnetic resonance imaging (MRI) of the brain is of limited utility in the evaluation of CSF leaks. Herniated neural tissue can be quantified and characterized, but the point of CSF leakage is rarely identified. MR cisternography, performed with fat-suppressed, heavily T2-weighted images and high-resolution matrices, is a noninvasive alternative to intrathecal contrast HRCT, particularly when the clinical manifestations of CSF leak are intermittent. The conspicuity of extravasated CSF may be increased when MR cisternographic images are viewed with video reversal, so that the extravasated CSF appears black against an otherwise bland background. El-Gammal and colleagues27 reported a sensitivity of 87% and a specificity of 78% with MR cisternography in 37 consecutive patients with CSF rhinorrhea. Shetty and colleagues28 reported that HRCT

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Figure 53-5. Coronal HRCT of 74-year-old female with spontaneous CSF leak. Note middle cranial fossa defect (d) anteromedial to ampullated end of superior semicircular canal, confirmed at surgery.

alone had a diagnostic accuracy of 93%, MR cisternography alone 89%, and that combining the two had an accuracy of 98% (Fig. 53-8).

TREATMENT Postoperative and Post-traumatic Cerebrospinal Fluid Leaks The treatment of CSF leak depends on the cause. Dura accidentally compromised during chronic ear surgery should be repaired promptly with a muscle or fascia plug. Large defects can be reinforced with a pedicled temporalis muscle flap. Nonviable materials, such as bone wax, should not be used during chronic ear surgery as they may act as a foreign body nidus for continuing infection. Culture and sensitivities should be performed intraoperatively and appropriate postoperative antibiotics instituted. These patients must be observed carefully for intracranial complications.

Figure 53-6. Coronal HRCT of 76-year-old female with CSF leak in chronically infected radical mastoid bowl. Note bony middle fossa plate dehiscence (b) at site of leak.

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A

Figure 53-7. Coronal view of CT cisternogram demonstrating metrizamide in right temporal bone (m) and eustachian tube (m).

The majority of traumatic leaks heal uneventfully with expectant observation or with the use of continuous lumbar spinal fluid drainage. Hicks and coworkers12 observed spontaneous closure in all of the longitudinal fractures that occurred in ears free of previous underlying otologic pathology (six of nine) and in two of four transverse fractures. Goodwin29 and Lee and colleagues15 also observed that the majority of post-traumatic leaks resolved without active intervention. Brennan and colleagues10 reported that 18% of CSF leaks following acoustic tumor removal resolved with expectant management, and an additional 49% with lumbar CSF drainage. Fishman and coworkers30 reported that continuous CSF drainage resolved 87% of postoperative CSF leaks not responsive to conservative measures. Postoperative CSF leaks unresponsive to continuous CSF drainage mandate surgical revision. Translabyrinthine leaks are managed by repacking of the mastoid/ labyrinthectomy defect. Suboccipital leaks should be managed with extracranial repair whenever possible. A complete mastoidectomy is performed and the posterior fossa plate skeletonized. CSF can usually be identified to be welling from specific perisinus or perilabyrinthine air cell tracts. The specific tracts are obliterated with fascia. The remainder of the mastoid bowl is then covered with a second layer of fascia and the bowl filled with abdominal fat. Rarely, a CSF leak will persist despite initial surgical revision or repair. In such instances total obliteration of the middle ear cleft and eustachian tube may be necessary. This is usually performed by sacrificing the external auditory canal wall, packing the eustachian tube orifice and middle ear, and oversewing the external auditory canal. As an adjunctive measure, the eustachian tube orifice can be closed transorally or transnasally in the nasopharynx.31,32

B Figure 53-8. A, Axial HRCT image at the level of the IAC demonstrating a bony defect involving the posterior aspect of the IAC (white arrow) associated with a spontaneous CSF leak. An air-fluid level can be seen within the mastoid air cell system (black arrow). A cell tract connects the defect to the mastoid air cell system (series of small black arrows). The opposite side shows a similar air cell tract that does not communicate with the IAC (series of small white arrows). B, Axial MRI cisternogram image corresponding to HRCT image. CSF appears black. IAC defect (large white arrow) demonstrates extravasation of CSF into adjacent air cell tract (series of small white arrows).

Spontaneous Cerebrospinal Fluid Leaks Spontaneous CSF leaks, which do not resolve without surgical intervention, and post-traumatic leaks that have not healed spontaneously can be addressed by several surgical approaches. The approach of choice depends on the location of the defect, the size of the defect, hearing status, and the operating surgeon’s technical skills. The transmastoid approach is least invasive and most familiar to the majority of otologic surgeons. This approach provides access to both the middle and posterior cranial fossa plates, which may be necessary when preoperative imaging has not identified a specific site of leakage. Herniated brain tissue should be gently excised by means of bipolar

Cerebrospinal Fluid Leak of Temporal Bone Origin

coagulation. The dural defect should be packed with a dumbbell-shaped piece of soft tissue. A second layer of fascia should be tucked between the dura and edges of the bony cranial defect. This can be further reinforced by a temporalis muscle flap, adipose packing the mastoid, or fibrin glue. A middle cranial fossa approach is indicated for larger tegmen tympani attic defects and less accessible leak sites along the petrous apex and overlying the eustachian tube. Middle fossa repair of attic defects avoids compromising the ossicular chain, with subsequent conductive hearing loss. The middle fossa approach also allows for additional primary dural closure and bony reinforcement of the floor of the middle cranial fossa. A combined approach offers the advantages of both and can often be accomplished with a “minicraniotomy.” In a nonhearing ear, virtually all leaks can be managed from the transmastoid approach. Patients should be counseled preoperatively about the possible need for a combined surgical approach.

Cerebrospinal Fluid Leak with Cochlear Dysplasia CSF leak secondary to cochlear dysplasia can be managed with a transcanal tympanotomy. If associated with a CSF gusher and a nonhearing ear, the usual case, the stapes should be removed and the vestibule tightly packed with pericranial tissue, fascia, or muscle. Postoperative continuous lumbar CSF drainage can be a useful adjunct.

Postinfectious/Neoplastic CSF leaks associated with chronic otitis, with or without cholesteatoma, represent a difficult therapeutic challenge. Prior to surgery, culture and sensitivity studies should be obtained and appropriate antibiotics administered in an attempt to resolve the infection. If the site of the CSF leak allows for preservation of the canal wall, the mastoid can be obliterated. If the underlying disease necessitates sacrificing the posterior canal wall, or if a leak occurs in a previously performed radical cavity, the entire ear can be obliterated with a Rambo-type procedure.33 All external auditory canal and mastoid bowl epithelium must be meticulously removed to prevent secondary cholesteatoma formation. If the cavity is free of infection, it can be packed with abdominal fat for better obliteration. Obliteration in the face of persistent infection or osteonecrosis is best managed with a vascularized regional flap. The sternocleidomastoid muscle works well in this situation. Regardless of precise surgical technique, the patient should be kept on postoperative antibiotics for an appropriate time.

ADJUNCTIVE MEASURES Continuous Lumbar Cerebrospinal Fluid Drainage Continuous lumbar CSF drainage is an important adjunct in treating postoperative CSF leaks. A continuous lumbar drain can be placed at the bedside under local anesthesia or after induction of anesthesia, prior to surgery. CSF should

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be drained via a sterile, closed system at a rate of 10 mL/h. Gravity drainage, placing the collection vehicle at the level of or slightly above the lever of the leak, should be avoided because of the risk of excess drainage at too rapid a rate. This can lead to a siphon effect with air entering the skull via the site of leak, creating a tension pneumocephalus. Graff and colleagues34 reported three such cases, all of whom had a clinical course marked by rapidly progressive obtundation, stupor, and coma. CT readily demonstrated intracranial air. Treatment consists of clamping off the CSF drain, placing the patient in a flat or slightly Trendelenburg position, and the administration of 100% oxygen. A pneumocephalus contains ambient air that is 78% nitrogen. Inhaling concentrated oxygen flushes nitrogen from the bloodstream, which causes nitrogen to diffuse out of the intracranial compartment. All of Graff’s patients experienced a prompt resolution of their neurologic symptoms with this treatment. CSF should be drained a set amount per hour, with the drain closed at other times. An alternative technique is the use of an IV infusion pump, working in reverse, at a set rate. Continuous spinal drainage, properly performed, is highly efficacious and well tolerated. The majority of postoperative leaks will resolve with 4 to 5 days of drainage. Headache is common if CSF is drained too rapidly. Meningitis is unusual and can be avoided by careful attention to the sterility of the drainage system. A culture and sensitivity of CSF should be performed after 2 or 3 days of drainage so that infection can be anticipated and treated promptly.

Intraoperative Glue Intraoperative glue is a valuable adjunct in sealing CSF leaks. The concept of fibrin glue as a biologic adhesive, sealant, and hemostatic agent evolved in the early 1970s when techniques for the isolation and concentration of human fibrinogen were perfected. The mechanism of fibrin glue formation is based on the final steps of coagulation. When concentrated fibrinogen is combined with thrombin, fibrinopeptides are cleaved from the fibrinogen molecule, which results in the formation of fibrin monomers. The fibrin monomers become cross-linked in the presence of ionized calcium and factor XIII and form a firm, nonfriable clot, “glue.” The concentration of fibrinogen dictates the strength of the tissue bond while the concentration of thrombin dictates the rapidity with which the fibrinogen is converted to fibrin. Autologous fibrin glue can be prepared by preoperative cryoprecipitation of a patient’s plasma. Fibrin glue prepared from pooled human plasma is now commercially available in the United States (TisseelVH, Baxter Healthcare, Glendale, CA). This pooled human fibrinogen has been carefully treated and screened for potential communicable disease. Kveton and Goravalingappa35 have reported on the efficacy of hydroxyapatite cement (HAC)(Bone source, StrykerLeibinger, Kalamazoo, MI) in the treatment of CSF leaks of temporal bone origin. HAC is easily sculpted, can be used in small amounts, and dries rapidly. Kveton and Goravalingappa retrospectively reviewed 13 consecutive cases of transmastoid repair of temporal bone defects, all successful.

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Intraoperative Fluorescein Intrathecal fluorescein can be a useful intraoperative adjunct in localizing a CSF leak if preoperative imaging has not been specific. After insertion of a CSF drain, 10 mL of CSF is removed and mixed with 0.5 mL of 5% fluorescein. Five milliliters of this solution is then reinjected intrathecally. Only a small amount of dilute fluorescein is necessary to visualize the area of the site of origin of the leak. Rare but potentially serious side effects include seizures and transverse myelitis.

Antibiotic Prophylaxis The use of prophylactic antibiotics to prevent meningitis in the presence of a CSF leak is controversial. In 1991 Rathore36 reviewed all previously published studies in the English literature regarding prophylactic antibiotics and basilar skull fracture. Prior to 1970 a significantly greater percentage of patients developed meningitis if they received prophylactic antibiotics than if they did not. Since 1970 no difference was observed with or without antibiotics. Friedman and colleagues,37 in 2001, reported a decrease in the frequency of meningitis following basilar skull fracture from 21% without antibiotic prophylaxis to 10% with antibiotic prophylaxis. Streptococcus pneumoniae is the most frequent bacterial pathogen identified when meningitis occurs. Ignelzi and VanderArk38 demonstrated that patients who receive prophylactic antibiotic experience a change in nasopharyngeal bacterial flora, that the microorganisms isolated have increased antibiotic resistance, and that the risk of drugresistant infection may be increased. In light of these conflicting data in the literature, prophylactic antibiotics are not routinely used.

CONCLUSION CSF leak of temporal bone origin is unusual but not rare. The diagnosis will be overlooked if the clinician does not maintain a high index of suspicion. A thorough understanding of temporal bone anatomy allows for an appreciation of the potential pathways by which CSF can gain access to and leak from the temporal bone. Diagnostic evaluation centers on accurate imaging techniques. Conservative management is desirable, and continuous CSF lumbar drainage is an important adjunct in this regard. The surgical approach to repair will depend on the site of temporal bone compromise. A favorable outcome will be maximized by flexible and individualized therapy.

REFERENCES 1. Neely GG: Classification of spontaneous cerebrospinal fluid middle ear effusion: Review of forty-nine cases. Otolaryngol Head Neck Surg 93:625, 1985. 2. Gacek RR, Leipzig B: Congenital cerebrospinal fluid otorrhea. Ann Otol 88:358, 1979. 3. Pappas DG, Hoffman RA, Cohen NL, Pappas DL Sr: Spontaneous temporal bone cerebrospinal fluid leak. Am J Otol 13:6:534, 1992.

4. Pappas DG Jr, Hoffman RA, Holliday RA, et al: Evaluation and management of spontaneous temporal bone cerebrospinal fluid leaks. Skull Base Surg 4:181, 1994. 5. Page EL, Eby TL: Meningitis after cochlear implantation in Mondini malformation. Otolaryngol Head Neck Surg 116(1):104, 1997. 6. Hoffman, R: Cerebrospinal fluid leak following acoustic neuroma removal. Laryngoscope 104:40, 1994. 7. Clemis JD: Microsurgical treatment of acoustic neuroma (results and complications). Laryngoscope 81:1191, 1971. 8. Lang J, Kerr AG: Pneumatization of the posteromedial air-cell tract. Clin Otolaryngol 14:425, 1989. 9. Bryce GE, Nedzilski JM, Rowed DW, Rappaport JM: Cerebrospinal fluid leaks and meningitis in acoustic neuroma surgery. Otolaryngol Head Neck Surg 104:81, 1991. 10. Brennan JW, Rowed DW, Nedzilski JM, Chen JM: Cerebrospinal fluid leak after acoustic neuroma surgery: Influence of tumor size and surgical approach on incidence and response to treatment. J Neurosurg 94(2):217, 2001. 11. Leonetti J, Anderson D, Marzo S, Moynahan G: Cerebrospinal fluid fistula after transtemporal skull base surgery. Otolaryngol Head Neck Surg 124(5):511, 2001. 12. Hicks GW, Wright WJ Jr, Wright WJ III: Cerebrospinal fluid otorrhea. Laryngoscope 80(Suppl 25):1, 1980. 13. Ghorayeb BY, Rafie JJ: Fractures of the temporal bone. Evaluation of 123 cases. J Radiol (Fr) 70(12):703, 1989. 14. Lui-Shindo M, Hawkins DB: Basilar skull fracture in children. Int J Pediatr Otolaryngol 17(2):109, 1989. 15. Lee D, Honrado C, Har-El G, Goldsmith A: Pediatric temporal bone fractures. Laryngoscope 108:816, 1998. 16. Dahiya R, Keller JD, Litofsky NS, et al: Temporal bone fractures: Otic capsule sparing versus otic capsule violating—Clinical and radiographic considerations. J Trauma 47(6):1079, 1999. 17. Ahren C, Thulin CA: Lethal intracranial complications following inflation in the treatment of serous otitis media due to defects in the petrous bone. Acta Otolaryngol 60:407, 1965. 18. Hirakawa F, Kurokawa M, Yajin K, Harada Y: Recurrent meningitis due to a congenital fistula in the stapedial footplate. Arch Otolaryngol 109:697, 1982. 19. Ryczko B, Brodsky L, Stanievich JF, Pordell R: Spontaneous cerebrospinal fluid otorrhea in a deaf infant. Int J Pediatr Otolaryngol 16:244, 1988. 20. Reilly JS: Congenital perilymphatic fistula: A prospective study in infants and children. Laryngoscope 99:393, 1989. 21. MacRae DL, Ruby RF: Recurrent meningitis secondary to perilymph fistula in young children. J Otolaryngol 19(3):222, 1990. 22. Friedland DR, Wackym PA: A critical appraisal of spontaneous perilymphatic fistulas of the inner ear. Am J Otol 20(2):261, 1999. 23. Isaacson JE, Linder TE, Fisch U: Arachnoid cyst of the fallopian canal: A surgical challenge. Am J Otol 23(3) (Suppl 1):49, 2002. 24. Gacek RR: Anatomy and significance of the subarachnoid space in the fallopian canal. Am J Otol 19(3):358, 1998. 25. Pappas DG Jr, Pappas DG, Hoffman RA, Harris S: Spontaneous cerebrospinal fluid leaks originating from multiple skull base defects. Skull Base Surg 6(4):227, 1996. 26. Gacek R: Arachnoid granulation cerebrospinal fluid otorrhea. Ann Otol Rhinol Laryngol 99:854, 1990. 27. El-Gammal T, Sobol W, Wadlington VR: Cerebrospinal fluid fistula: detection with MR cisternography. Am J Neuroradiol 19:627, 1998. 28. Shetty PG, Shroff MM, Dushyant VS: Evaluation of high resolution CT and MR cisternography in the diagnosis of cerebrospinal fluid fistula. Am J Neuroradiol 19:633, 1998. 29. Goodwin JW: Temporal bone fractures. Otolaryngol Clin North Am 16(3):651, 1983. 30. Fishman A, Hoffman R, Roland JT, et al: Cerebrospinal fluid drainage in the management of CSF leak following acoustic neuroma surgery. Laryngoscope 106(8):1002, 1996.

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31. Kwartler JA, Schulder M, Baredes S, Chandrasekhar S: Endoscopic closure of the eustachian tube for repair of cerebrospinal fluid leak. Am J Otol 17(3):470, 1996. 32. Sataloff RT, Zavod MB, Myers DL: Otogenic cerebrospinal fluid rhinorrhea: A new technique for closure of cerebrospinal fluid leak. Am J Otol 21(2):240, 2000. 33. Meyerhoff WL, Stringer SP, Roland PS: How I do it—Otology and neurotology: Rambo Procedure: Modifications and application. Laryngoscope 98:795, 1988. 34. Graf CJ, Gross CE, Beck DW: Complications of spinal drainage in the management of cerebrospinal fluid fistula: Report of three cases. J Neurosurg 54:392, 1981.

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35. Kveton JF, Goravalingappa R: Elimination of temporal bone cerebrospinal fluid otorrhea using hydroxyapatite cement. Laryngoscope 110:1655, 2000. 36. Rathore HR: Do prophylactic antibiotics prevent meningitis after basilar skull fracture? Pediatr Infect Dis 10:87, 1991. 37. Friedman JA, Ebersold MJ, Quast LM: Post-traumatic cerebrospinal fluid leakage. World J Surg 25(8):1062, 2001. 38. Ignelzi RJ, VanderArk GD: Analysis of the treatment of basilar skull fractures with and without antibiotics. J Neurosurg 43:721, 1975.

Chapter

54 Robert A. Williamson, MD Newton J. Coker, MD

Arteriovenous Malformations Outline Classification Location and Arterial Sources Pathogenesis and Pathophysiology Grading Systems and Natural History

CLASSIFICATION Intracranial vascular malformations can be classified as telangiectasias, varices, cavernous malformations, venous malformations, or arteriovenous malformations.1 A telangiectasia is a small network of thin-walled capillaries separated by normal parenchyma. A varix is a single dilated vein surrounded by normal tissue. Cavernous malformations are masses of sinusoidal vascular spaces without intervening parenchyma. One of the most common vascular malformations of the central nervous system, the venous malformation, consists of a mass of abnormal venous channels draining into a common vein. This type of malformation, however, has no direct arterial supply, and the venous channels are often separated by normal tissue. Arteriovenous malformations (AVMs) are fistulas of the intracerebral or extracerebral vessels in which arteries and veins communicate directly or through pathologic vascular channels without an intervening capillary plexus.1 AVMs are described according to cause (congenital, traumatic, or acquired), site (intracranial, extracranial, or intracranial and extracranial), or type (pial, dural, and mixed pial and dural).2 The most common AVMs encountered by otologists are dural arteriovenous fistulas (DAVFs) and carotid-cavernous fistulas. DAVFs are true fistulas void of the nidus or mass of vessels common to intraparenchymal lesions, and they represent 10% to 15% of all intracranial arteriovenous fistulas.2,3 DAVFs usually involve the walls of a dural sinus or an adjacent cortical vein and can involve any of the dural-based sinus structures of the cranial vault.4 Fistulas involving the transverse-sigmoid sinus region are the most common subtype, accounting for approximately 38% of all DAVFs,5 and are of primary importance to the practicing otologist. Their clinical presentation can vary, ranging from relatively innocuous pulsatile tinnitus to new-onset neurologic deficit and intracranial or intraparenchymal hemorrhage. Carotid-cavernous fistulas (CCFs) differ from DAVFs in several important aspects, including their epidemiology and origin, pathophysiology, presentation, and treatment; 934

Clinical Presentation Radiographic Evaluation Treatment References

many experienced clinicians regard them as separate entities.6 They are broadly divided into direct or indirect (dural) subtypes and are classified separately according to the Barrow classification, based on the pattern of arterial supply and shunt characteristics (see later discussion).7 CCFs are frequently a consequence of head trauma,8,9 but can be spontaneous or associated with Ehler-Danlos syndrome and other collagen-vascular diseases, osteogenesis imperfecta, or fibromuscular dysplasia.8–11 Other forms of extracranial arteriovenous communications in the head and neck causing pulsatile tinnitus include traumatic aneurysms of the internal maxillary artery,12 cervical angiomas,13 giantcell tumors of the mandible,13 AVMs of the mandible,14 and AVMs of the cervical region and scalp.

LOCATION AND ARTERIAL SOURCES Most DAVFs are located in the basal aspect of the dura mater.3,15 Multiple arteries often supply these lesions. Branches of the external carotid artery are the most common; however, branches of the internal carotid artery and vertebral artery may produce or supplement the fistulas. Dural AVFs are commonly found in the occipitomastoid region. If CCFs are grouped separately as distinct entities, fistulas involving the transverse and sigmoid sinus regions, superior and inferior petrosal sinuses, and the marginal sinus combined account for approximately 63% to 75% of all DAVFs.16–18 Within this subgroup, DAVFs of the transverse and sigmoid sinus represent the great majority (75%), with fistulas involving the petrosal and marginal sinuses accounting for approximately 25%.17,18 CCFs represent between 12% and 34% of all intracranial AVFs.5,16 Posterior fossa DAVFs typically receive their blood supply from transmastoid perforators of the occipital artery, posterior auricular artery, and posterior branches of the middle meningeal and superficial temporal arteries. In addition, meningeal branches of the ascending pharyngeal and ipsilateral vertebral arteries may contribute blood supply,

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remaining indirect, or dural, CCFs (types B, C, and D) are usually slow-velocity fistulas involving the dural walls of the cavernous sinus and are often spontaneous in nature. Type B fistulas are supplied by dural branches of the cavernous ICA and are considered to be exceedingly rare.8,9 Type C CCFs are supplied by dural branches from the external carotid artery, and type D CCFs, which are the most common, are supplied by branches from both the internal and external carotid arteries.8 Tomsick further subdivides type D CCFs into those with unilateral supply (type D1) and those with bilateral supply (type D2).22 Venous drainage from the cavernous sinus occurs through the superior and inferior petrosal sinuses, the anterior and posterior intercavernous (circular sinus) channels, emissaries draining into the pterygoid plexus, and the basilar (clival) plexus. Venous inflow into the cavernous sinus occurs through the superior and inferior ophthalmic veins and the superficial middle cerebral (sylvian) veins.

PATHOGENESIS AND PATHOPHYSIOLOGY Figure 54-1. Subtraction angiography: left external carotid injection, lateral view, demonstrates dural arteriovenous fistula (AVM) that involves the transverse and sigmoid sinus (SS). Fistula is supplied by the occipital (OA), posterior auricular, and posterior branches of the meningeal arteries.

as can small tentorial branches of the meningohypophyseal trunk of the internal carotid artery (Fig. 54-1).17,18 Larger and more extensive fistulas may receive direct parenchymal blood supply from adjacent pial arteries; this phenomenon can also occur after interventions that occlude proximal, feeding dural arteries.17 Fistulas in the parasellar area are vascularized by branches of the middle meningeal, infraorbital, ophthalmic, meningohypophyseal, or ascending pharyngeal arteries.19 Tentorial AVFs are usually localized to the petrous ridge and involve the superior petrosal sinus; their blood supply may be similar to that of parasellar20 or posterior fossa lesions. Dural AVFs in the anterior cranial fossa are rare and typically emanate from the basal dura mater, anterior portion of the falx cerebri, or the frontal convexity.21 Arterial contributions include the ophthalmic, ethmoidal, superficial temporal, or the anterior branches of the middle meningeal arteries. These DAVFs typically drain into the superior sagittal sinus or the dural and cortical veins. Of those involving the superior sagittal sinus, the middle third is most commonly affected, followed by the posterior third.17 Blood supply is often bilateral and symmetrical, and posteriorly located lesions may also receive a variable supply from the posterior meningeal branch of the vertebral artery.17 CCFs, often considered as separate clinical entities, consist of abnormal arteriovenous communication between the carotid artery and the cavernous sinus (Fig. 54-2). They are broadly divided into two main categories—direct and indirect—and further categorized according to the Barrow classification, which describes the arterial supply and shunt velocity.7,8 The Barrow type A CCF is a direct fistula, usually post-traumatic, which develops from a tear or rupture in cavernous segment of the ICA allowing high-velocity shunting into the cavernous sinus. The three

Many hypotheses have been advanced to explain the development of DAFVs; most agree that they are acquired lesions. However, Vidyasagar proposes a congenital origin due to the persistence of embryonic veins.23 Although this theory may account for the rare lesion seen in infants and young children,24 it fails to explain the manifestation of DAVFs in adults. Dural sinus thrombosis and subsequent venous hypertension are consistent findings that likely contribute to the development of DAVFs.17,25–27 Dural shunting in the region of the thrombosis then ensues, and venous hypertension is thought to enlarge or dilate normally present but microscopic arteriovenous shunts, resulting in the clinical lesion.17 This relationship has been

Figure 54-2. Subtraction angiography: left internal carotid artery (ICA) injection, AP view, demonstrates a dural carotid cavernous fistula (CCF ), type D. Dural feeders from the ICA shunt into both cavernous sinuses (CS). (ACA, anterior cerebral artery; MCA, middle cerebral artery.)

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Figure 54-3. Pathogenesis and pathophysiology of dural arteriovenous malformations. (Adapted from Awad IA, Little JR, Akarawi WP, et al: Intracranial dural arteriovenous malformations: Factors predisposing to an aggressive neurological course. J Neurosurg 72:839–850, 1990.)

demonstrated in an animal model.28 Several investigators have also proposed an important role for angiogenic growth factors, especially basic fibroblastic growth factor (bFGF)29,30 and vascular endothelial growth factor.31 The exact role of these angiogenic factors requires further investigation.17,32 Trauma is accountable for the pathogenesis of most type A CCFs8,9 and may play a role in the formation of some dural AVFs17,25 by initiating sinus thrombosis or disrupting veins and arteries in close proximity. Rupture of a cavernous ICA aneurysm or congenitally weakened ICA wall in Ehler-Danlos syndrome or fibromuscular dysplasia may also cause type A CCFs, as can surgical trauma.11,33–35 Thrombosis has been proposed as a causative factor in CCFs types B–D8; these types demonstrate a marked female predominance and often present in the sixth and seventh decades of life.33 The pathophysiology of dural AVFs is demonstrated in Figure 54-3. Regardless of location or cause of the fistula, it is the pattern of venous drainage that accounts for clinical manifestations and the risk of hemorrhage or neurologic deficit.3,4,36,37 When the venous drainage is through antegrade pathways, the volume of shunting determines the clinical picture. High-volume shunting can lead to recruitment of additional arterial sources, venous hypertension, and subsequent signs and symptoms. When venous drainage is retrograde due to obstruction or highvolume shunting, leptomeningeal and cortical venous drainage pathways develop, resulting in an increased tendency to develop hemorrhage or neurologic deficits.16,18,38 Many investigators consider cortical venous drainage an indication for emergent treatment.6 Variceal distension and venous ectasia then follow and are also known to be significant risk factors for hemorrhage.17,38 Arterial steal has been implicated in the pathophysisology of cranial nerve deficits,37 but the volume of shunting in DAVFs is considered insufficient to produce ischemia.3 Other mechanisms may lead to elevated intracranial pressure, including impaired venous drainage, aneurysmal dilatation of the vein of Galen with subsequent occlusion of the aqueduct

of Sylvius, and subarachnoid hemorrhage followed by communicating hydrocephalus.3 Low-frequency sensorineural hearing loss (SNHL) has been reported in association with AVFs.39 This phenomenon is presumed to be a result of the masking effect of objective tinnitus or of vascular compromise of the cochlea. Improvement in the hearing following treatment of the AVF may occur. The papilledema and optic atrophy leading to visual deficits develop as a result of increased intracranial pressure. With CCFs, direct ophthalmologic signs and symptoms are the most common manifestation. Pulsating exophthalmos; ophthalmoplegia with or without associated palsies of cranial nerves III, IV, or VI; conjunctival chemosis; reduced visual acuity; elevated intraocular pressure; periorbital bruit; and pulsatile tinnitus may all occur.6,40,41 Intraorbital and retinal hemorrhage may occur. Trigeminal (especially first division) and facial nerve dysfunction (though rare) have also been reported.42–44 The clinical presentation can vary depending on fistula type and duration and the pattern of venous drainage.

GRADING SYSTEMS AND NATURAL HISTORY Several classification systems have been proposed for categorizing DAVFs and as a means of evaluating their severity, describing their high-risk features, and estimating their clinical behavior. Each system describes the common features of venous drainage pattern, presence of cortical venous drainage, and occurrence of sinus obstruction or thrombosis. The most commonly used classification schemes are summarized in Table 54-1. It is important to note that DAVFs are dynamic lesions and may progress from relatively benign type 1 lesions to more aggressive type 2 or 3 lesions, either gradually or abruptly. Such progression is often heralded by a change in symptomatology, and repeat evaluation, including angiography, is mandatory for determining transition to a higher risk category.17,47 Spontaneous thrombosis may also occur

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TABLE 54-1. Grading Systems for Dural Arteriovenous Fistulas Classification

Grade

Venous Drainage Pattern

Djindjian et al.45

1 2 3 1 2 3 4 I II

Drainage to ipsilateral sinus Drainage to contralateral sinus Drainage via cortical veins Normal antegrade without restriction or cortical venous drainage Antegrade or retrograde with or without cortical venous drainage Retrograde or cortical venous drainage without antegrade drainage Cortical venous drainage only Venous drainage into sinus, normal antegrade flow Venous drainage into sinus, insufficient antegrade flow/reflux A Retrograde venous drainage into sinus only B Retrograde venous drainage into cortical vein only A+B Retrograde venous drainage into sinus and cortical vein Venous drainage into a cortical vein without ectasia Venous drainage into cortical vein with venous ectasia (>5 mm diameter, three times larger than draining vein) Venous drainage into spinal perimedullary veins

UCSF (Lalwani et al.)46

Cognard et al.199547

III IV V

Adapted, with permission, from Malek AM, Halbach VV, Higashida RT, et al: Treatment of dural arteriovenous malformations and fistulas. Neurosurg Clin North Am 11(1):147–166, 2000.

in some cases17,48 and has been reported following diagnostic angiography in between 5% and 43% of cases.49–51 The natural history of AVFs has not been completely elucidated; each lesion is best evaluated in terms of its angiographic appearance and presence of high-risk features. Aggressive angiographic characteristics, as mentioned earlier, include leptomeningeal or cortical venous drainage, aneurysmal venous dilations and variceal distension, and galenic venous drainage.16,21,38 Hemorrhage can occur in the subarachnoid or subdural spaces, or intraparenchymally. Although an AVF at any site may potentially develop serious neurologic sequelae, lesions involving the transverse and sigmoid sinuses typically exhibit the least aggressive behavior. Right and left sides are affected equally; involvement of the torcula Herophili is rare.21 Lesions in these locations may be entirely asymptomatic or present with combinations of pulsatile tinnitus; headache that varies in intensity with head elevation, activity level, and Valsalva’s maneuver; or hemorrhage and subsequent neurologic deficit. Overall risk of hemorrhage has been estimated at 1.5% per year.38 AVFs in the anterior cranial fossa are felt to have more aggressive clinical courses; DAVFs located along the floor commonly present with hemorrhage. There is a distinct male predominance, and headache is also a common presenting feature.21 Lesions located in the orbital and ethmoid regions are known to have higher rates of spontaneous hemorrhage, as are lesions involving the tentorial incisura.21,37,52

CLINICAL PRESENTATION The clinical presentation of DAVFs is highly variable, and the importance of the pattern of venous drainage and other high-risk features and location cannot be overemphasized. DAVFs may remain asymptomatic or cause troublesome or disabling pulsatile tinnitus and headache. Other lesions can present with transient ischemic attacks, seizures, motor weakness and other focal deficits, or with brainstem and

cerebellar findings.3,37 Vertigo and forms of ataxia can be presenting features53 as can signs of intracranial hemorrhage. Normal, laminar blood flow in the region of the ear is not normally perceived as tinnitus. Turbulent vascular flow is audible54 and results from either an increase in volume or flow through and irregular lumen.55 Lesions in the transverse and sigmoid sinus regions account for the majority of DAVFs and most often present with pulsatile tinnitus, which is characteristically worse at night.37,56 Venous drainage of any AVF in proximity to the temporal bone may cause tinnitus.37 Table 54-2 outlines the differential diagnosis of lesions that cause pulsatile tinnitus. AVFs of the cavernous sinus more commonly present with ophthalmologic findings. Proptosis, ophthalmoplegia, cranial nerve palsy, chemosis, elevated intraocular pressure, hemorrhage, and pulsatile exophthalmos dominate the clinical picture. Periorbital bruit and pulsatile tinnitus may also occur.6 These patients may be misdiagnosed with Graves’ disease, reactive or allergic conditions, or conjunctivitis. Thorough physical examination, often in conjunction with an ophthalmologist, is indicated. A careful microscopic examination of the external auditory canal, tympanic membrane, and middle ear is imperative in the evaluation of pulsatile tinnitus. A middle ear mass denotes temporal bone pathology, such as a vascular tumor or congenital vascular anomaly. The former are most commonly paragangliomas (glomus tympanicum or jugulare); the latter can be persistent stapedial arteries, aberrant or aneurysmal ICAs, or any one of a number of jugular bulb anomalies (e.g., diverticuli, dehiscent or enlarged). Turbulent flow in the jugular bulb (which may be enlarged)57 commonly generates a venous hum and pulsatile tinnitus. On physical exam, the hum is intensified by deep breathing and reduced by Valsalva’s maneuvers, rotation of the head toward the tinnitus, or gentle compression of the ipsilateral internal jugular vein. Auscultation of a bruit in the postauricular area suggests a lesion of the occipitomastoid region, but bruits from the middle ear, mastoid, and jugular fossa can be transmitted to the same location.3 Bruits may also be noted in the

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TABLE 54-2. Differential Diagnosis of Pulsatile Tinnitus Cardiovascular Disease Vascular Disease Arteriovenous fistula/malformation (AVM) Carotid-cavernous fistula ICA atheroma ICA thrombosis ICA dissection Ectasia or stenosis Fibromuscular dysplasia Intrapetrous carotid aneurysm Intracranial aneurysm Cardiac valvular disease Cardiac high-output states Anemia Thyrotoxicosis Beriberi Pregnancy

Vascular Tumor of Temporal Bone or Cranium Paraganglioma Meningioma Hemangioma Vestibular schwannoma Vascular metastatic carcinoma Parenchymal AVM

fossa, carotid canal, and petrous apex can be obtained. In addition, brain CT sequences, especially with contrast, may demonstrate parenchymal edema, subarachnoid hemorrhage, subdural hematoma, or intraparenchymal hemorrhage. Dilated cortical veins may also be noted.17 Magnetic resonance imaging (MRI) may be useful for demonstrating parenchymal edema, infarction, hemorrhage, or an uncommon mass lesion with similar presenting symptoms. Dilated cortical veins are also effectively detected on MRI.62 Newer MR angiography and venography techniques, though useful in certain situations, may fail to detect relatively benign type I DAVFs and smaller, higher grade lesions, and are therefore considered inadequate screening tools.17 Selective, high-resolution digital angiography with late venous study is considered the standard diagnostic modality for detecting and evaluating DAVFs.21 Characterization of each lesion should include location and extent, arterial supply, pattern of venous drainage, and documentation of other high-risk features. Additionally, any alteration in symptomatology or clinical signs warrants repeat angiographic evaluation to assess alteration in venous drainage and transition to a higher risk lesion.21,47

Other Disorders of the Temporal Bone Paget’s disease Otosclerosis (osteolytic phase)

Congenital or Developmental Anomalies Anomalous ICA of middle ear Congenital arterial shunts Persistent stapedial artery Primitive otic artery Primitive hypoglossal artery Eagle syndrome13 Jugular megabulb57 Dehiscent jugular bulb Posterior condylar emissary vein58

Other Conditions Benign intracranial hypertension59 ICA, internal auditory canal.

temporal, periorbital, convexity, or cervical regions, depending on lesion location.6 AVFs of the transverse sinus may be associated with hypertrophic occipital or posterior auricular arteries, or a thrill in their location. Compression of these vessels or the carotid can soften the bruit. Further testing, including audiometry, formal ophthalmologic evaluation, and imaging studies including angiography are indicated depending on the clinical picture.

RADIOGRAPHIC EVALUATION Discovery of pathology responsible for tinnitus is most likely when the tinnitus is objective or coexists with middle ear disease; however, imaging studies are indicated in any case where the source of the tinnitus, whether objective or subjective, is unclear.60,61 Computed tomographic (CT) scanning is the most appropriate initial imaging modality, including thin-section, high-resolution, axial and coronal views of the temporal bone. Important information about the middle ear, jugular

TREATMENT Treatment alternatives for DAVFs include observation, endovascular management, surgical excision, and combined endovascular and surgical management.17 In addition, radiotherapy and radiosurgery protocols have been developed to treat selected DAVFs.20,63 Risks are inherent in the choice of any treatment option and must be weighed against the patient’s symptoms, lesion grade, and angiographic features.17,46 Accepted indications for treatment include (1) pulsatile tinnitus that is intolerable or of sufficient degree to produce insomnia, (2) new-onset or progressive neurologic deficit, (3) hemorrhage or infarction, (4) visual loss, (5) elevated ICP, and (6) presence of high-risk features (especially cortical venous drainage) on angiography.17,47,64 Patients who are asymptomatic or unbothered by their symptoms and have angiographically documented low-risk AVFs can be observed without treatment. It is important that they be informed that any change in symptomatology may indicate transition to a more aggressive grade of lesion, and repeat angiography, at a minimum, is warranted. Some investigators feel that the majority of DAVFs of the transverse and sigmoid sinus region have a benign clinical course, but the true incidence of these lesions is unknown. Compression therapy may be useful for some patients with indirect CCFs7 and atherosclerosis-free carotid arteries, or with DAVFs of the transverse-sigmoid region supplied primarily by the occipital artery. Full angiographic evaluation should be performed prior to therapy; the presence of high-risk features or severe symptoms are considered contraindications to compression. Compression is applied to the ipsilateral carotid-jugular area (for CCFs) or the ipsilateral mastoid and retrosigmoid area (for transversesigmoid DAVFs) for 30 minutes per session. Successful thrombosis of fistulas may occur in up to 27% of appropriately selected cases.17,65,66 Compression therapy may

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involve significant discomfort and requires a highly motivated patient.17 Endovascular (or interventional neuroradiologic) management has become the treatment of choice for most DAVFs.6,16,53,64,67 Rapid technological development has occurred in imaging capacity, catheter systems, and various embolic agents and materials over the last two decades, and endovascular procedures have become safe and highly successful in treating these lesions. A large array of catheter systems is available for safe navigation to most points within the intracranial vasculature.68 Typically, a guiding catheter is employed for access to lesions and to allow passage of a microcatheter system (either steerable or flow-directed) for direct endovascular management. Embolic materials available for use include liquid agents (the adhesive N-butyl-cyanoacrylate [NBCA], and 95% ethanol); particle agents (most commonly polyvinyl alcohol particles sized 150 μm to 1 mm); and coil systems, which are either thrombogenic, fibered platinum, or electrolytically detachable (Guglielmi detachable coils).68,69 In addition, balloon systems (silicone or latex, detachable or nondetachable) are available. Selection and deployment of agents is decided on for each patient based on operator experience, shunt characteristics, and angiographic anatomy. The goals of endovascular management include reduction or elimination of clinical symptoms or neurologic deficits, and prevention of future neurologic deterioration or hemorrhage. Generally, endovascular management is performed in the neuroangiography suite with the patient under neuroleptanesthesia (with an anesthesiologist and cardiopulmonary monitoring) or local anesthesia with sedation when continuous neurologic monitoring is advantageous. Access to the right femoral artery is achieved using the Seldinger technique, and a long 6 French sheath is placed. An initial heparin bolus and continuous infusion are administered and monitored using the activated clotting time (ACT). A guiding catheter system is placed, and a coaxial microcatheter system (steerable or flow-directed) is then positioned and navigated to the vascular territory of interest. The lesion is then thoroughly evaluated (usually including both carotid and vertebral systems) using highresolution digital subtraction angiography equipment, and the treatment approach is finalized. Transvenous access is gained through the femoral or internal jugular vein. In most cases, a combination of transarterial and transvenous technique is used; transarterial embolization is employed first to reduce or occlude arterial supply to the lesion, improve success of transvenous embolization, and occasionally preoperatively as an adjunctive method before surgical resection.17 Superselective embolization of the arterial supply is performed typically with either NBCA or polyvinyl alcohol (PVA). A single, proximal feeder artery is usually left patent to allow for later evaluation of the lesion and prevent the development of collateral arterial supply. Transvenous embolization, usually with coil systems, then follows after careful evaluation of venous drainage pathways. As a general rule, second and third treatments may be required, depending on the expertise of the endovascular team and the character of the lesion being treated. Results vary with lesion grade, size, and location. Reported success rates for endovascular management of CCFs range

939

between 59% and 90%,18,33,52,64,70 depending on whether success is defined clinically or angiographically. Success rates for DAVFs vary more widely by site and range between 35% and 96%.3,18,67,70,71 Combined endovascular and surgical management is often used to treat DAVFs involving the ethmoid, superior petrosal, deep venous (vein of Galen) and superior sagittal sinuses,11,17 and DAVFs with direct leptomeningeal drainage.64 Complications of endovascular management include those related to catheterization of the cranial vasculature (spasm, rupture, intimal injury, etc.) and those related to material placement and properties within the vasculature. Distal embolization (NBCA or PVA) may induce cerebral edema, hemorrhage or ischemia, cranial nerve deficits (either new-onset or exacerbation of existing symptoms), or venous infarction and hemorrhage. Cranial nerve deficits may include vertigo,64 vestibular dysfunction, SNHL,64 lower cranial nerve deficits, or ophthalmoplegia and blindness in the treatment of CCFs; many deficits are transient, however, and steroids are often beneficial in reducing the inflammatory response. Rates of occurrence of transient complications vary from 5% to 33%.6,33,52,64 Permanent or serious complications are rarer and have been estimated to occur in between 1% and 9.4% of cases.6,33,51,52,69 Coil systems and detachable balloons generally cause fewer complications, but can migrate downstream, inadvertently divert venous flow and exacerbate cortical drainage, or occlude normal cerebral venous outflow and result in venous infarction.52,68,72 Surgical excision is generally less commonly employed as a first-line treatment modality, but is important in cases that require combined-modality treatment, in difficult cases refractory to endovascular management, and in the management of certain specific lesions (e.g., DAVFs along the anterior cranial floor, some deep DAVFs in the region of the vein of Galen).17,38 In general, the surgical management of AVFs consists of exposure of the lesion and feeding vessels, ligation of feeding vessels, and excision of the malformation.73,74 Complete eradication of AVFs involving the transverse and sigmoid sinus requires excision of the sinus and all involved dura.49,75,76 Simple ligation of feeding vessels from the external carotid system may provide temporary symptomatic relief in some patients56 but fails to effect a definitive long-term cure since AVFs will recruit new arterial supplies medially from the internal carotid or vertebral artery systems.77,78 Preoperative digital angiography maps the arterial supply to the lesion. For dural AVFs involving the transverse and sigmoid sinus, three areas of regional supply to the lesion should be delineated: the external group of vessels that supply the dura through perforations in the mastoid and occipital bone, the medial group or meningeal arteries, and the internal vessels of the tentorium, the medial and lateral tentorial arteries, and branches of the middle and posterior cerebral arteries.48 The preoperative study should confirm the patency of the contralateral transverse and sigmoid sinus in order to avoid compromising the cerebral venous drainage; additionally, embolization can be employed to reduce intraoperative blood loss. The operative technique49,75,76 for excising AVFs of the occipitomastoid region is illustrated in Figure 54-4. The transverse and sigmoid sinus, the dura over the cerebellum

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Figure 54-4. Surgical excision of dural arteriovenous fistula involving the transverse sinus. A, Curvilinear skin incision extends over temporal and occipital areas into neck. B, Large, osteoplastic flap is removed to expose occipital and cerebellar dura mater and AVF. Dural incisions are made parallel to the transverse sinus through the fistulous communications. C, Cross section of transverse sinus (TS) demonstrates relationship of dural incisions to occipital lobe, cerebellum, and tentorium cerebelli. D-E, Third incision through tentorium isolates sinus. Continued

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Figure 54-4. Cont’d. F, Division and ligation of medial transverse sinus at the confluence of incisions. When necessary, superior petrosal sinus is divided and sigmoid sinus resected. G, Ligation of sigmoid sinus. H, Closure with fascia or dural homograft. Mastoid air cells are occluded with bone wax.

and occipital region, and the tentorium are accessed via a large osteoplasic flap developed with a high-speed drill and diamond burrs in order to obliterate the intraosseous perforators. The significant potential for hemorrhage on removal of the bone flap necessitates patient elevation and use of bipolar electrocautery, application of pressure and clotting agents, and rapid administration of blood products. A partial mastoidectomy exposes the sigmoid sinus, sinodural angle, and dura overlying the posterior surface of the temporal bone between the sinus and semicircular

canals. Dural incisions in two planes encompass the fistulas and obliterate feeding arteries. Feeding vessels are cauterized or closed with hemostatic clips. The first dural incision in the occipital region begins near the midline, parallels the transverse sinus, and terminates at or distal to the superior petrosal sinus. Ligation of the superior petrosal sinus at its entry into the transverse sinus depends on the size of the AVF and the drainage pattern of the vein of Labbé, which should be preserved. The vein of Labbé may drain into the superior petrosal sinus or the inferior

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cerebral veins. The second incision is made in the cerebellar dura parallel to the incision above the sinus. The third incision in the tentorium encompasses the AVF and begins and ends at the confluence of the first and second dural incisions with the transverse sinus. The cut ends of the transverse and sigmoid sinuses are ligated or packed. The purpose of in toto dural sinus resection is to remove all fistulous communications with the transverse sinus. Conservative management is warranted when dural fistulas are small, uncomplicated, and without any of the aggressive angiographic features listed earlier. Surgical excision of AVFs in older patients carries increased risks. Those AVFs with benign angiographic features may warrant careful observation and serial angiography. Radiotherapy and radiosurgery have been employed in the management of AVFs, but published data in the literature are relatively limited. Gamma-knife radiosurgery with stereotactic angiography and MR angiography has been used to manage indirect CCFs with a success rate of 80%,63 and small DAVFs have also been successfully treated with radiosurgery.79 Other investigators have used radiotherapy, including total brain irradiation, with success rates up to 75%.20,80 These modalities require further study, but may be appropriate when other treatment options have failed.17

REFERENCES 1. McCormick WF: The pathophysiology of vascular (“arteriovenous”) malformations. J Neurosurg 24:807–816, 1966. 2. Newton TH, Cronqvist S: Involvement of dural arteries in intracranial arteriovenous malformations. Radiology 93:1071–1078, 1969. 3. Houser OW, Baker HL Jr, Rhoton AL Jr, et al: Intracranial dural arteriovenous malformations. Radiology 105:55–64, 1972. 4. Barnwell SL, Halbach VV, Higashida RT, et al: Complex dural arteriovenous fistulas. J Neurosurg 71:352–358, 1989. 5. McDougall CG, Halbacc VV, Dowd CF, et al: Dural arteriovenous fistulas of the marginal sinus. Am J Neuroradiol 18:1565– 1572, 1997. 6. Phatouros CC, Meyers PM, Dowd DV, et al: Carotid artery cavernous fistulas. Neurosurg Clin North Am 11(1):67–84, 2000. 7. Barrow D, Spector R, Landman J, et al: Classification and treatment of spontaneous carotid cavernous fistulas. J Neurosurg 62:248–256, 1985. 8. Debrun GM, Vinuela F, Fox AJ, et al: Indications for treatment and classification of 132 carotid-cavernous fistulas. Neurosurg 22:285–289, 1988. 9. Francis PM, Flom RA, Zabramski JM, et al: Treatment of carotidcavernous fistulas: Part I, interventional neuroradiology. BNI Quarterly 7:2–8, 1991. 10. Fox R, Pope F, Narcisi P, et al: Spontaneous carotid cavernous fistula in Ehler-Danlos syndrome. J Neurol Neurosurg Psychiatr 51:984–986, 1988. 11. Halbach VV, Higashida R, Dowd C, et al: Treatment of carotidcavernous fistulas associated with Ehlers-Danlos syndrome. Neurosurgery 26:1021–1024, 1990. 12. Binns PM, Read RC: Traumatic arteriovenous aneurysm arising from the internal maxillary artery. J Laryngol Otol 84:843–847, 1970. 13. Ward PH, Babin R, Calcaterra TC, et al: Operative treatment of surgical lesions with objective tinnitus. Ann Otol Rhinol Laryngol 84:473–482, 1975. 14. Babin RW, Osbon DB, Khangure MS: Arteriovenous malformations of the mandible. Otolaryngol Head Neck Surg 91:366–371, 1983.

15. Houser OW, Campbell JK, Campbell RJ, et al: Arteriovenous malformation affecting the transverse dural venous sinus—An acquired lesion. Mayo Clin Proc 54:651–661, 1979. 16. Awad IA, Little JR, Akarawi WP, et al: Intracranial dural arteriovenous malformations: Factors predisposing to an aggressive neurological course. J Neurosurg 72:839–850, 1990. 17. Malek AM, Halbach VV, Higashida RT, et al: Treatment of dural arteriovenous malformations and fistulas. Neurosurg Clin North Am 11(1):147–166, 2000. 18. Halbach VV, Higashida RT, Hieshima GB, et al: Dural fistulas involving the cavernous sinus: Results of treatment in 30 patients. Radiology 163:437–442, 1987. 19. Van Berkel JP, Matrical B, Batchelor DA: Occipital dural arteriovenous fistulas. Diagn Imag Clin Med 54:240–250, 1985. 20. Lewis AI, Tomsick TA, Tew JM Jr: Management of tentorial dural arteriovenous malformations: Transarterial embolization combined with stereotactic radiation or surgery [see comments]. J Neurosurg 81:851–859, 1994. 21. Waga S, Fujimoto K, Morikawa A, et al: Dural arteriovenous malformation in the anterior fossa. Surg Neurol 8:356–358, 1977. 22. Tomsick TA: Types B, C, & D (Dural) CCF: Etiology, prevalence, and natural history. In Tomsick TA (ed.): Carotid Cavernous Fistula. Cincinnati, Digital Educational Publishing, 1997, pp 59–73. 23. Vidyasagar C: Persistent embryogenic veins in arteriovenous malformations of the dura. Acta Neurochir (Wein) 48:199–216, 1979. 24. Chan S-T, Weeks RD: Dural arteriovenous malformation presenting as cardiac failure in a neonate. Acta Neurochir (Wein) 91:134–138, 1988. 25. Chaudhary MY, Sachdev VP, Cho SH, et al: Dural arteriovenous malformation of the major venous sinuses: An acquired lesion. Am J Neuroradiol 3:13–19, 1982. 26. Kutluk K, Schumacher M, Mironov A: The role of sinus thrombosis in occipital dural arteriovenous malformations—development and spontaneous closure. Neurochir 34:144–147, 1991. 27. Picard L, Bracard S, Mallet J, et al: Spontaneous dural arteriovenous fistulas. Semin Intervent Radiol 4:219–240, 1987. 28. Terada T, Higashida RT, Halbach VV, et al: Development of acquired arteriovenous fistulas in rats due to venous hypertension. J Neurosurg 80:884–889, 1994. 29. Terada T, Higashida RT, Halbach VV, et al: The role of angiogenic factor bFGF in the development of dural AVFs. Acta Radiol 138:877–883, 1996. 30. Lawton MT, Jacobowitz R, Spetzler RF: Redefined role of angiogenesis in the pathogenesis of dural arteriovenous malformation. J Neurosurg 87:267–274, 1997. 31. Folkman J: Seminars in Medicine of the Beth Israel Hospital, Boston: Clinical applications of research on angiogenesis [see comments]. N Engl J Med 333:1757–1763, 1995. 32. O’Reilly MS, Boehm T, Shing Y, et al: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277–285, 1997. 33. Barnwell SL, Oisin RO: Endovascular therapy of carotid cavernous fistulas. Neurosurg Clin North Am 5(3):485–495, 1994. 34. Day AL, Rhoton AL: Aneurysms and arteriovenous fistulae of the intracavernous carotid artery and its branches. In Youmans JR (ed.): Neurological Surgery, vol 3, ed 3. Philadelphia, WB Saunders, 1990. 35. Lach B, Nair S, Russell N, et al: Spontaneous carotid-cavernous fistula and multiple arterial dissections in type IV Ehlers-Danlos syndrome [case report]. J Neurosurg 66:462–465, 1987. 36. Hiramatsu K, Utsumi S, Kyoi K, et al: Intracerebral hemorrhage in carotid-cavernous fistula. Neuroradiology 33:67–71, 1991. 37. Lasjaunias P, Chiu M, terBrugge K, et al: Neurological manifestations of intracranial dural arteriovenous malformations. J Neurosurg 64:724–730, 1986. 38. Hoh BL, Choudhri TF, Sander CE, et al: Surgical management of high-grade intracranial dural arteriovenous fistulas: Leptomeningeal venous disruption without nidus excision. Neurosurgery 42: 796–806, 1998.

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39. Weider DJ, Kuo A, Spiegel PK, et al: Objective tinnitus of vascular origin with hearing improvement after treatment. Am J Otol 11: 437–443, 1990. 40. Martin JD Jr, Mabon RF: Pulsating exophthalmos: Review of all reported cases. JAMA 121(5):330–335, 1943. 41. Dandy WE, Follis RH: On the pathology of carotid-cavernous aneurysms (pulsating exophthalmos). Am J Ophthalmol 24: 365–385, 1941. 42. Kapur A, Parikh NK, Sanghave NG, et al: Spontaneous carotidcavernous fistula with ophthalmoplegia and facial palsy. Postgrad Med J 58:773–775, 1982. 43. Madsen PH: Carotid cavernous fistulae: A study of 18 cases. Acta Ophthalmol 48:731–750, 1970. 44. Moster ML, Sergott RC, Grossman RI: Dural carotid cavernous sinus vascular malformation with facial nerve paresis. Can J Ophthalmol 23:27–29, 1988. 45. Djindjian R, Cophignon J, Theron J: Embolization by superselective arteriography from the femoral route in neuroradiology, 1: Review of 60 cases: Technique, indications, complications. Neuroradiology 6:20–26, 1973. 46. Lalwani AK, Dowd CF, Halbach VV: Grading venous restrictive disease in patients with dural arteriovenous fistulas of the transverse/ sigmoid sinus. J Neurosurg 7:11–15, 1993. 47. Cognard C, Gobin YP, Pierot L, et al: Cerebral dural arteriovenous fistulas: Clinical and angiographic correlation with a revised classification of venous drainage. Radiology 194:671–680, 1995. 48. Kuhner A, Krastel A, Stoll W: Arteriovenous malformations of the transverse dural sinus. J Neurosurg 45:12–19, 1976. 49. Phelps CD, Thompson HS, Ossoinig KC: Carotid-cavernous fistula (red-eye shunt syndrome). Am J Ophthalmol 93:423–436, 1982. 50. Mani RL, Eisenberg RL: Complications of catheter cerebral angiography: Analysis of 5000 procedures. II: Relation of complication rate to clinical and arteriography diagnoses. Am J Radiol 131:867–869, 1978. 51. Meyers PM, Halbach VV, Dowd CF, et al: Dural carotid cavernous fistula: Definitive endovascular management and long-term followup. Am J Ophthalmol 134:85–92, 2002. 52. Lownie SP: Intracranial dural arteriovenous fistulas: Endovascular therapy. Neurosurg Clin North Am 5(3):449–458, 1994. 53. Branco G, Takahashi A, Ezura M, et al: Dural arteriovenous shunt involving the superior petrosal sinus: Presentation and treatment by transvenous embolisation via the occipital and transverse sinuses. Neuroradiology 39:67–70, 1997. 54. Holgate RC, Wortzman G, Noyek AM, et al: Pulsatile tinnitus: The role of angiography. J Otolaryngol (Suppl) 3:49–62, 1977. 55. Vallis RC, Martin FW: Extracranial arteriovenous malformation presenting as objective tinnitus. J Laryngol Otol 98:1139–1142, 1984. 56. Obrador S, Soto M, Silvela J: Clinical syndromes of arteriovenous malformations of the transverse-sigmoid sinus. J Neurol Neurosurg Psychiatr 38:436–451, 1975. 57. Buckwalter JA, Sasaki CT, Virapongse C, et al: Pulsatile tinnitus arising from jugular megabulb deformity: A treatment rationale. Laryngoscope 93:1534–1539, 1983. 58. Lambert PR, Cantrell RW: Objective tinnitus in association with an abnormal posterior condylar emissary vein. Am J Otol 7:204–207, 1986. 59. Sismanis A: Otoloic manifestations of benign intracranial hypertension syndrome: Diagnosis and management. Laryngoscope 97:1–17, 1987. 60. Harris S, Brismar J, Cronqvist S: Pulsatile tinnitus and therapeutic embolization. Acta Otolaryngol 88:220–226, 1979.

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61. Sila CA, Furlan AJ, Little JR: Pulsatile tinnitus. Stroke 18:252–256, 1987. 62. DeMarco KJ, Dillon W, Halbach VV, et al: Dural arteriovenous fistulas: Evaluation with MR Imaging. Radiology 175:193–199, 1990. 63. Guo WY, Pan DH, Wu HM, et al: Radiosurgery as a treatment alternative for dural arteriovenous fistulas of the cavernous sinus. Am J Neuroradiol 19:1081–1087, 1998. 64. Roy D, Raymond J: The role of transvenous embolization in the treatment of intracranial dural arteriovenous fistulas: Technique assessment. Neurosurgery 40(6):1133–1144, 1997. 65. Halbach VV, Higashida RT, Hieshima GB, et al: Dural fistulas involving the transverse and sigmoid sinuses: Results of treatment in 28 patients. Radiology 163:443–447, 1987. 66. Higashida RT, Hieshima GB, Halbach V, et al: Closure of carotid cavernous sinus fistulae by external compression of the carotid artery and jugular vein. Acta Radiol 369(Suppl):580–583, 1986. 67. Dawson RC, Joseph GJ, Owens DS, et al: Transvenous embolization as the primary therapy for arteriovenous fistulas of the lateral and sigmoid sinuses. Am J Neuroradiol 19:571–576, 1998. 68. Khayata MH, Dean BL, Spetzler RF: Materials and embolic agents for endovascular treatment. Neurosurg Clin North Am 5(3): 475–484, 1994. 69. Guglielmi G, Vinuela F, Dion J, et al: Electrothrombosis of saccular aneurysms via endovascular approach, Part 2: Preliminary clinical experience. J Neurosurg 75:8–14, 1991. 70. Higashida RT, Halbach VV, Tsai FY: Interventional neurovascular treatment of traumatic carotid and vertebral artery lesions: Results in 234 cases. Am J Roentgenol 153:577–582, 1989. 71. Jansen O, Dorfler A, Forsting M, et al: Endovascular therapy of arteriovenous fistulae with electrolytically detachable coils. Neuroradiology 41:951–957, 1999. 72. Qureshi AI, Luft AR, Sharma M, et al: Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: Part II-Clinical aspects and recommendations. Neurosurgery 46:1360–1376, 2000. 73. Gamache FW Jr, Patterson RH Jr: Surgical management of cranial arteriovenous malformations. In Schmidek HM, Sweet WH (eds.): Operative neurosurgical techniques: indications, methods, and results. Orlando, Grune & Stratton, 1988. 74. Maw AR: Some features of arteriovenous malformations in the head and neck. Laryngoscope 82:785–795, 1972. 75. Hugosson R, Bergstrom K: Surgical treatment of dural arteriovenous malformation in the region of the sigmoid sinus. J Neurol Neurosurg Psychiatr 37:97–101, 1974. 76. Sundt TM Jr, Piepgras DG: The surgical approach to arteriovenous malformations of the lateral and sigmoid dural sinuses. J Neurosurg 59:32–39, 1983. 77. Arenberg IK, McCreary HS: Objective tinnitus aurium and dural arteriovenous malformations of the posterior fossa. Ann Otol Rhinol Laryngol 80:111–120, 1971. 78. Courteney-Harris RG, Ford GR, Innes AJ, et al: Pulsatile tinnitus: Three cases of arteriovenous fistula treated by ligation of the occipital artery. J Laryngol Otol 104:421–422, 1990. 79. Chandler HC, Friedman WA: Successful radiosurgical treatment of a dural arteriovenous malformation: Case report. Neurosurgery 33: 139–144, 1993. 80. Hirai T, Korogi Y, Baba Y, et al: Dural carotid cavenous fistulas: Role of conventional radiation therapy: Long-term results with irradiation, embolization, or both. Radiology 207:423–430, 1998.

Chapter

55 Louis J. Kim, MD C. Phillip Daspit, MD, FACS

Neurotologic Aspects of Posterior Fossa Arachnoid Cysts Outline Introduction Pathology and Pathogenesis Classification Clinical Signs and Symptoms

INTRODUCTION This chapter describes the classification, clinical signs, imaging characteristics, and treatment options pertinent to posterior fossa arachnoid cysts. Although these are relatively rare entities, they frequently present with an array of symptoms initially seen by the neurotologist or otolaryngologist. Symptoms can include headache, gait disturbances, vertigo, hearing loss (progressive or fluctuating), and tinnitus. Although a high index of suspicion is required to diagnose an arachnoid cyst, the current diagnostic modalities allow this to be accomplished with ease.

PATHOLOGY AND PATHOGENESIS Arachnoid cysts compose 1% of all intracranial lesions. The most common location is the middle fossa. In the literature, however, about 10% of arachnoid cysts occur in the posterior fossa, with most of these found in the cerebellopontine angle. The most accurate description of the development of arachnoid cysts is by Starkman, Brown, and Linell.1 They propose that duplication of the arachnoid membranes as a result of a developmental aberration in the flow of cerebrospinal fluid (CSF) leads to their pathogenesis. In a review by Rengachary and colleagues, light and electron microscopic analysis supported the intra-arachnoid location of these cysts.2 The lining is usually composed of flattened arachnoid cells split along its membrane to enclose the cyst (Fig. 55-1). Ependymal cells are occasionally discovered but are not believed to be causative. Histologic evidence of inflammation, hemorrhage, or trauma is usually lacking. Therefore, these cysts are most commonly believed to represent congenital malformations of the arachnoid.2,3 Cyst growth has been accounted for by several hypotheses.4 Intracystic hemorrhage can produce an osmotic gradient that leads to cyst enlargement. Active secretion of fluid by the cyst itself has been reported. In a similar mechanism, ectopic choroid plexus has been encountered in rare cases of arachnoid cysts.5 Finally, and most popular, is the ball-valve mechanism, whereby intermittent cerebrospinal fluid 944

Diagnosis and Imaging Management Summary

trapping gradually enlarges the cyst. Symptoms subsequently can develop from local mass effect, obstructive hydrocephalus, hemorrhage into the cyst, or focal or nonlocalizing neurologic symptoms.

CLASSIFICATION Little’s group proposes a classification of cysts based on their location in the posterior fossa arachnoid.6 However, a more practical classification has been developed by Vaquero’s group.7 This anatomic classification categorizes these lesions into the following types: supracerebellar, retrocerebellar, laterocerebellar, clival, and mixed arachnoid cysts. Supracerebellar cysts are located in the tentorial notch. They usually originate from the quadrigeminal cistern and extend toward the posterior fossa and can present with hydrocephalus (Fig. 55-2). Retrocerebellar cysts include all cysts of the superior and inferior midline and of the cerebellar hemispheres. Such cysts compress the cerebellum, which causes the

Figure 55-1. Histopathology of an arachnoid cyst wall.

Neurotologic Aspects of Posterior Fossa Arachnoid Cysts

Figure 55-2. MRI of a supracerebellar cyst.

appearance of cerebellar hypoplasia on imaging studies. After cyst fenestration or shunting, the cerebellum often reexpands to occupy the potential space (Fig. 55-3). Laterocerebellar cysts occupy the cerebellopontine angle. They may be the most difficult category to diagnose because they are usually small. Until the advent of highresolution MRI, epidermoids in this anatomic region were often confused with arachnoid cysts (Fig. 55-4). Clival cysts are located entirely ventral to the brainstem along the clivus and are quite rare entities.

Figure 55-3. CT of a retrocerebellar cyst.

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Figure 55-4. MRI of a laterocerebellar cyst.

Cysts that occupy more than one of these categorized locations do occur, and these are classified as mixed locations (Fig. 55-5).

CLINICAL SIGNS AND SYMPTOMS The hallmark of posterior fossa arachnoid cysts is their variability in presenting signs and symptoms, which tend to be vague and usually related to the location of the cyst.8–13 Patients typically complain of headaches, ataxia, hearing loss, tinnitus, seizures, focal cranial nerve palsies, or other neurologic disturbances that can be associated with space-occupying lesions. The symptoms can be fleeting, making the diagnosis on clinical grounds alone problematic. Among symptomatic patients, headache is the most common

Figure 55-5. MRI of an arachnoid cyst encompassing both retrocerebellar and supracerebellar locations.

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finding, with or without associated neurologic disturbances. Careful recording of history in this population usually reveals a long antecedent history of vague symptoms, and the clinician should be admonished that headache is not always attributable to arachnoid cysts. Asymptomatic cysts are discovered with increasing frequency in the modern imaging era during evaluation for head trauma or other unrelated neurologic workup.14

DIAGNOSIS AND IMAGING Current neurotologic diagnostic procedures such as audiograms, balance testing, evoked potentials, and plain films of the skull serve little clinical importance in the diagnosis of an arachnoid cyst. However, Lanzino and colleagues describe an interesting case of a cerebellopontine angle arachnoid cyst with preoperative hearing loss and normal otoacoustic emission measurements that predicted postoperative hearing preservation following arachnoid cyst marsupialization.15 The utility of otoacoustic emissions for hearing preservation assessment remains to be proved. Computed tomography (CT) of arachnoid cysts demonstrates a hypodense, well-demarcated, noncalcified, spaceoccupying mass that is indistinguishable from cerebrospinal fluid. High-resolution CT can reveal the degree of mass effect and anatomic distortion as well. Contrast administration should not demonstrate cyst wall enhancement, and it raises the suspicion of a neoplastic or inflammatory process. After administration of intrathecal dye, cisternography can demonstrate whether the cyst communicates with normal CSF pathways. Cysts can be both communicating and noncommunicating with respect to the cerebral cisterns. The role of cisternography is discussed further in the section about management of these lesions. Magnetic resonance imaging (MRI) of the brain is the most useful diagnostic tool for arachnoid cysts.16–21 By definition, the fluid in an arachnoid cyst is CSF, therefore the signal characteristics of these cysts mimic those of pure CSF. Normally, arachnoid cysts are hypointense on T1weighted images (Fig. 55-6), hyperintense on T2-weighted images (Fig. 55-7), and nonenhancing after gadoliniumcontrast administration.22 As with CT, any deviation from the classic imaging findings suggests another etiology. A diagnostic quandary can occur in the differentiation of cerebellopontine angle (CPA) arachnoid cysts from epidermoids on MRI. This is because epidermoids can exhibit similar T1- and T2-weighted imaging characteristics as described for arachnoid cysts. However, radiographic differentiation can be obtained using fluid-attenuated inversion recovery (FLAIR) and diffusion weighted image (DWI) sequences. Epidermoids typically appear hyperintense on FLAIR and DWI sequences, and arachnoid cysts remain hypointense.16 The greatest advantage of MRI is the extraordinary soft tissue detail. The effects of cysts on surrounding brain tissue, cranial nerves, and vascular structures can be readily identified. Compared with CT, MRI images of anatomic relationships in the posterior fossa are well-visualized, enabling precise localization of cysts. On sagittal MRI, the presence of a separate fourth ventricle can exclude the diagnosis of a Dandy-Walker cyst. Classically, large

Figure 55-6. T1-weighted image of an arachnoid cyst in the posterior fossa.

retrocerebellar cysts had been distinguished from mega cisterna magna. However, current opinions characterize the two conditions as one entity along a continuum from small to giant cyst.7 One shortcoming of MRI is poor bony definition. For bony anatomy, CT remains the optimal study. Remodeling of adjacent bone is typical, with scalloping of the inner table of the posterior fossa and thinning of the overall bone thickness. These findings indicate that pressure is exerted by the cyst along the bony borders. This is exemplified best in young patients with more malleable skulls. Burgeoning arachnoid cysts that exert pressure can lead to gross anatomic distortions of adjacent

Figure 55-7. T2-weighted image of an arachnoid cyst in the posterior fossa.

Neurotologic Aspects of Posterior Fossa Arachnoid Cysts

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bone. Cysts along the cerebellopontine angle may erode into the petrous apex or mastoid air cells, producing otorrhea or rhinorrhea.

MANAGEMENT Management of arachnoid cysts of the posterior fossa remains nonstandardized.4,6,11,14,23–25 In general, asymptomatic cysts should be followed conservatively with serial MRI scans to evaluate for cyst growth. For patients with neurologic symptoms, the clinician should take care to correlate symptoms with cyst location and mass effect. That is, patients with nonlocalizing symptoms such as headaches often pose the difficult problem of deciding whether the arachnoid cyst is truly responsible. Here clinical acumen is required to give special attention to the degree of brain compression, cranial nerve displacement, ventricular outflow obstruction, and adjacent bone remodeling. Once the arachnoid cyst is deemed symptomatic or the cyst has demonstrated marked growth over time, several treatment options are available. Cisternography can determine whether the cyst is communicating or noncommunicating. For noncommunicating cysts, some authors advocate cystoperitoneal shunting.23,26,27 For communicating cysts and associated hydrocephalus, some advocate ventriculoperitoneal or lumboperitoneal shunting because the cyst contents can drain via normal CSF pathways.4,23,26 If symptoms of hydrocephalus fail to resolve, an open procedure can be undertaken. Open procedures have the distinct advantage of providing direct treatment and shunt independence (Fig. 55-8). Open procedures include cyst fenestration into adjacent cisterns, cyst resection, and endoscopic fenestration. Samii and colleagues recommend cyst resection or maximal cyst fenestration as the optimal treatment for CPA posterior fossa arachnoid cysts4 (Figs. 55-9 and 55-10). In their series of 12 cases, perioperative morbidity occurred in one case (seventh and eighth cranial nerve palsies) and long-term follow-up showed marked improvement or disappearance of symptoms in all patients. Similarly, Jallo and colleagues present a series of CPA arachnoid cyst in five pediatric patients who underwent microsurgical fenestration of cyst walls with excellent long-term follow-up results. One

Figure 55-8. Intraoperative view of the bulging cyst wall prior to fenestration.

Figure 55-9. Intraoperative view of cyst fenestration.

patient initially underwent cystoperitoneal shunting that failed and subsequently required open surgery.28 An emerging operative technique for posterior fossa arachnoid cysts is endoscopic fenestration. Here the endoscope is inserted via a small burr hole into the cyst itself, often with the concomitant use of frameless stereotactic guidance. Instruments designed for the endoscope’s working channels are employed for cyst fenestration. The major advantages include a minimally invasive approach and unparalleled illumination and visualization of the cyst and adjacent structures. Hopf and Perneczky report their series of endoscopic arachnoid cyst fenestration, including nine cases involving the posterior fossa. Complication occurred in a single case, with a 78% favorable outcome overall.24 Certainly, as this technique develops, it will be an important part of the treatment armamentarium. Overall, the ablation of neurotologic symptomatology is quite variable after treatment. Hearing fluctuation may cease but usually does not improve. Mild dysequilibrium may continue and headaches usually are alleviated. Treatment of arachnoid cysts must be individualized. Routine follow-up by clinical examination and MRI scanning must be performed at appropriate intervals to assess the patient’s response to treatment. Careful follow-up is

Figure 55-10. Intraoperative view of fenestrated cyst.

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the only reasonable way to offer effective, long-term care to patients with arachnoid cysts.

SUMMARY Arachnoid cysts of the posterior fossa can be difficult to diagnose based on clinical grounds alone. For patients with complaints referable to the inner ear or posterior fossa, the usual neurotologic workup should be obtained. If the workup proves unhelpful, a high index of suspicion should lead to imaging studies that facilitate diagnosis of an arachnoid cyst. Treatment paradigms are not standardized. These include cyst shunting and open or endoscopic cyst fenestration or resection.

REFERENCES 1. Starkman SP, Brown TC, Linell EA: Cerebral arachnoid cysts. J Neuropathol Exp Neurol 17:484–500, 1958. 2. Rengachary SS, Watanabe I, Brackett CE: Pathogenesis of intracranial arachnoid cysts. Surg Neurol 9:139–144, 1978. 3. Hirano A, Hirano M: Benign cystic lesions in the central nervous system. Light and electron microscopic observations of cyst walls. Childs Nerv Syst 4:325–333, 1988. 4. Samii M, et al: Arachnoid cysts of the posterior fossa. Surg Neurol 51(4):376–382, 1999. 5. Schuhmann MU, et al: Ectopic choroid plexus within a juvenile arachnoid cyst of the cerebellopontine angle: Cause of cyst formation or reason of cyst growth. Pediatr Neurosurg 32(2):73–76, 2000. 6. Little JR, Gomez MR, MacCarty CS: Infratentorial arachnoid cysts. J Neurosurg 39:380–386, 1973. 7. Vaquero J, et al: Arachnoid cysts of the posterior fossa. Surg Neurol 16:117–121, 1981. 8. Bengochea FG, Blanco FL: Arachnoidal cysts of the cerebellopontine angle. J Neurosurg 12:66–71, 1955. 9. Galassi E, et al: Intratentorial arachnoid cysts. J Neurosurg 63:210–217, 1985. 10. Haberkamp TJ, et al: Diagnosis and treatment of arachnoid cysts of the posterior fossa. Otolaryngol Head Neck Surg 103(4):610–614, 1990.

11. Hadley MN, et al: Otolaryngologic manifestations of posterior fossa arachnoid cysts. Larynogscope 95:678–681, 1985. 12. Pagni CA, Canavero S, Vinci V: Left trochlear nerve palsy, unique symptom of an arachnoid cyst of the quadrigeminal plate. Case report. Acta Neurochir (Wien) 105:147–149, 1990. 13. Pappas DG, Brackmann DE: Arachnoid cysts of the posterior fossa. Otolaryngol Head Neck Surg 89:328–332, 1981. 14. Garcia-Bach M, Isamat F, Vila F: Intracranial arachnoid cysts in adults. Acta Neurochir Suppl 42:205–209, 1988. 15. Lanzino G, et al: Recovery of useful hearing after posterior fossa surgery: The role of otoacoustic emissions: Case report. Neurosurgery 41:469–473, 1997. 16. Dutt SN, et al: Radiologic differentiation of intracranial epidermoids from arachnoid cysts. Otol Neurotol 23:84–92, 2002. 17. Gandy SE, Heier LA: Clinical and magnetic resonance features of primary intracranial arachnoid cysts. Ann Neurol 21(4):342–348, 1987. 18. Heier LA, et al: Magnetic resonance imaging of arachnoid cysts. Clin Imaging 13:281–291, 1989. 19. Valvassori GE, Guzman M: Magnetic resonance imaging of the posterior cranial fossa. Ann Otol Rhinol Laryngol 97:594–598, 1988. 20. Weiner SN, Pearlstein AE, Eiber A: MR imaging of intracranial arachnoid cysts. J Comp Assist Tomogr 11(2):236–241, 1987. 21. Rock JP, et al: Arachnoid cyst of the posterior fossa. Neurosurgery 18:176–179, 1986. 22. Wilner HI, Kashef R: Unilateral arachnoid cysts and adhesions involving the eighth nerve. Am J Roentgenol Radium Ther Nucl Med 115(1):126–132, 1972. 23. Ciricillo SF, et al: Intracranial arachnoid cysts in children. A comparison of the effects of fenestration and shunting. J Neurosurg 74:230–235, 1991. 24. Hopf NJ, Perneczky A: Endoscopic neurosurgery and endoscopeassisted microneurosurgery of the treatment of arachnoid cysts. Neurosurgery 43:1330–1337, 1998. 25. Lange M, Oeckler R: Results of surgical treatment in patients with arachnoid cysts. Acta Neurochir (Wien) 87:99–104, 1987. 26. Harsh GR IV, Edwards MSB, Wilson CB: Intracranial arachnoid cysts in children. J Neurosurg 64:835–842, 1986. 27. Mason TB II, et al: Massive intracranial arachnoid cyst in a developmentally normal infant: Case report and literature review. Pediatr Neurosurg 35(4):220–224, 2001. 28. Jallo GI, et al: Arachnoid cysts of the cerebellopontine angle: Diagnosis and surgery. Neurosurgery 40(1):31–37, 1997.

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Outline Introduction Historical Perspective Indications and Contraindications Anatomy Surgical Technique Nerve Monitoring and Anesthesia Middle Fossa Vestibular Neurectomy General Points to Posterior Fossa Vestibular Neurectomy

Chapter

Vestibular Neurectomy

Nerve Identification and Nerve Section Technique Retrolabyrinthine Approach Retrosigmoid-Internal Auditory Canal Approach Combined RetrolabyrinthineRetrosigmoid Approach Postoperative Care Results Retrolabyrinthine Vestibular Neurectomy

Retrosigmoid-Internal Auditory Canal Vestibular Neurectomy Combined RetrolabyrinthineRetrosigmoid Vestibular Neurectomy Complications Conclusion

INTRODUCTION A wide variety of medical and surgical treatments have been developed for the management of endolymphatic hydrops since the syndrome’s first description by Prosper Ménière in 1861. When vertigo is refractory to dietary changes and medical treatment, selective vestibular neurectomy (VN) is the treatment of choice for patients who wish to preserve functional hearing. Elimination of vertigo and hearing preservation are the two principle objectives of selective vestibular nerve section (VNS). This chapter focuses on the surgical indications and techniques of VN.

HISTORICAL PERSPECTIVE Modern-day vestibular neurectomy developed from the early work of Walter Dandy, who began performing complete (cochlear and vestibular) eighth nerve sections for the treatment of vertigo due to Ménière’s disease.1 The surgical technique was refined by McKenzie, who performed the first selective VNS in 1931.2 Dandy popularized the surgery when he adopted selective VNS, and he used the suboccipital approach to accumulate the world’s largest case series at 624.3 Without the aid of microscopes or modern surgical equipment, there was a 10% incidence of facial nerve paralysis, and approximately half of the patients actually underwent complete eighth nerve section. Following the death of Walter Dandy in 1946, VN diminished in popularity and was largely replaced by endolymphatic sac surgery and destructive procedures of the labyrinth. Factors contributing to this change included the potentially significant complications that can occur from

Seth I. Rosenberg, MD, FACS Herbert Silverstein, MD, FACS

intracranial surgery, as well as increased familiarity and comfort level among otologists with transmastoid surgery. The modern era of VN began in 1961 when William House described the microsurgical extradural approach to the internal auditory canal (IAC) through the middle fossa for sectioning of the superior vestibular nerve.4 Later modifications were made to this surgery, such as sectioning the inferior vestibular nerve in addition to the superior vestibular nerve, and removal of Scarpa’s ganglion.5–7 Results were excellent; however, the technically demanding middle fossa approach remained an obstacle to widespread use. Seeking a safe and reliable alternative to the middle fossa approach, in 1978 Silverstein and Norell developed the retrolabyrinthine (and later retrosigmoid) approaches to expose the eighth nerve complex in the cerebellopontine angle (CPA).8 Subsequent histologic studies confirmed that complete vestibular nerve section could be performed at the CPA through a posterior fossa approach. 9 Today, due to its advantages, the posterior fossa approach has become the most common technique for VNS in the United States.10

INDICATIONS AND CONTRAINDICATIONS The most common inner ear disorder treated by VNS is classic unilateral Ménière’s disease. However, it is also useful in treating select cases of recurrent vestibular neuronitis, traumatic labyrinthitis, and vestibular Ménière’s disease. The classic elements of Ménière’s disease include fluctuating hearing loss, tinnitus, and aural fullness, but episodic vertigo is usually the most disturbing to patients. The principle behind VNS is to prevent vestibular afferent 949

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impulses from reaching the brain. Although it does not cure the underlying disease process, VN is intended to eliminate the disease’s most disabling symptom, vertigo. Subjective complaints of recurrent disabling vertiginous attacks are mandatory to warrant the scope of this surgery. Some patients who have many attacks per year may find that their lifestyles are not affected enough to warrant a major surgical procedure. Other patients who have only a few vertigo episodes per year may find their lives severely affected, continually living in fear of the next attack, and yet others may find the attacks occupational hazards that may put themselves, their coworkers, and the public at risk. Of course, the surgery is recommended for these latter individuals. Attempts at conservative management, including dietary salt restriction and diuretic therapy, should be tried before considering surgical intervention. Although patients are frequently able to tell which ear is causing their symptoms, it is still important to document objective evidence of unilateral inner ear disease. Often this can be demonstrated on audiogram, electronystagmography (ENG), and/or electrocochleography (ECOG). Patients who have signs of ataxia or who are unable to perform tandem gait should not undergo ablative surgery because they have a high risk of postoperative persistent disabling imbalance. Patients who already have severe or profound nonserviceable hearing loss should be considered for labyrinthectomy rather than VN, depending on the degree of residual benefit that they derive from the affected ear. The patient need have only minimal residual hearing is for hearing preservation VN surgery, considering that preservation of serviceable hearing in patients with a speech reception threshold greater than 50 dB and/or a speech discrimination less than 50% is frequently achieved. In fact, it has been found that in 19 patients with profound hearing loss who had been offered a labyrinthectomy for Ménière’s disease but chose vestibular neurectomy, 68% had hearing improvement with an average postoperative pure tone average of 60.2 dB and 59.5% speech discrimination at a mean of 22.3 months after surgery. At a mean of 30.6 months postoperatively, 16% improved to better than 50 dB pure tone average and 50% speech discrimination.11 Elderly patients may have a longer recuperation and slower adaptation, but VN has been successfully performed on patients in their late seventies with excellent results and no additional morbidity. Previous mastoid surgery such as an endolymphatic sac procedure is not a contraindication. Obviously, VNS should never be performed on an only hearing ear or if there is no vestibular function in the contralateral ear. Before surgery, a thorough discussion of the surgery, associated risks, and alternatives should be discussed with the patient and family. The surgical aim to relieve vertiginous attacks and attempt hearing preservation should be explained. However, hearing loss and even deafness can occur. The procedure is not designed to eliminate tinnitus and aural fullness, and the patient must be aware that these symptoms may remain. The patient should be counseled to expect postoperative short-lasting vertigo followed by more prolonged dysequilibrium. Dysequilibrium can usually be shortened by postoperative vestibular

rehabilitation therapy. Other rare complications including facial nerve paralysis, cerebrospinal fluid leakage, and meningitis should be discussed.

ANATOMY The vestibular nerve’s location within the cochleovestibular nerve bundle was first identified by McKenzie.2 Since then, our understanding of the cochleovestibular anatomy has been further elucidated.12 It is imperative for the surgeon to understand the dynamic anatomic relationships of the cochlear, vestibular, facial, and intermediate nerves, their branches throughout their courses from the brainstem to the fundus of the IAC, and the proximity of cranial nerves V, IX, and X in the CPA. At the labyrinthine end (fundus) of the IAC, six separate branches of the seventh and eighth nerves enter the temporal bone: the facial nerve, nervus intermedius, superior vestibular nerve, inferior vestibular nerve, posterior ampullary nerve to the posterior semicircular canal (singular nerve), and cochlear nerve (Fig. 56-1). The transverse (falciform) crest divides the lateral IAC into the superior and inferior compartments. A bridge of bone, the vertical crest (Bill’s bar), separates the superior compartment into an anterosuperior quadrant, which contains the facial nerve and the nervus intermedius, and a posterosuperior quadrant, which contains the superior vestibular nerve. Anterior and inferior to the falciform crest is the cochlear nerve. The inferior vestibular nerve lies posterior to the cochlear nerve in the lateral portion of the IAC. The posterior ampullary nerve lies in a separate canal (the singular canal), which enters the IAC from the posteroinferior quadrant approximately 2 mm medial to the falciform crest.

Figure 56-1. Anatomy of the IAC contents after removal of the posterior bony lip. (From Haberkamp TJ, Silverstein H: Vestibular neurectomy from the posterior fossa approaches: A summary of the techniques. Operative Tech Otolaryngol Head Neck Surgery 12:116–121, 2001; with permission.)

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The singular nerve serves as a useful landmark to avoid entry into the labyrinth, specifically the posterior semicircular canal, when drilling the medial portion of the IAC via a retrosigmoid approach. Anatomic and radiographic studies have shown this distance to be variable, and a thinsection computed tomography (CT) scan of the labyrinth is routinely obtained preoperatively to identify the location of the singular canal and its distance from the porus acusticus. The inferior vestibular nerve is formed by the confluence of the posterior ampullary nerve and the saccular nerve just medial to the falciform crest. The inferior vestibular nerve branches innervate the saccule (saccular nerve) and the posterior semicircular canal (posterior ampullary nerve). The superior vestibular nerve innervates the superior semicircular canal, lateral semicircular canal, and utricle, with a small contribution to the saccule. The cochleovestibular cleavage plane, the separation between the cochlear and vestibular nerves, lies in the coronal plane at the fundus of the IAC. The vestibular nerves occupy the posterior half of the canal. In the lateral IAC there is a constant well-delineated cleavage plane between the superior and inferior vestibular nerves. Between the falciform crest and the porus acusticus, in the middle section of the IAC, the superior and inferior vestibular nerve fibers fuse into a common nerve bundle. At the lateral end of the IAC the facial nerve lies anterior to the superior vestibular nerve, and the cochlear nerve lies anterior to the inferior vestibular nerve. The cochlear and inferior vestibular nerves fuse within the IAC, just medial to the falciform crest. The cochlear and vestibular nerves then rotate 90 degrees so that the cochlear nerve, which at first lies anterior to the inferior vestibular nerve, rotates to lie inferior to the vestibular nerve at the porus acusticus and within the cerebellopontine angle (Fig. 56-2). The majority of the 90-degree rotation occurs in the IAC; only slight rotation occurs in the cerebellopontine angle. The cochlear nerve emerges from the brainstem caudal and slightly dorsal to the vestibular nerve. The flocculus of the cerebellum obscures 5 mm of the eighth nerve at the brainstem. After the vestibular and cochlear nerves fuse in the IAC, the cochleovestibular cleavage plane usually persists grossly and histologically. The vestibular fibers remain segregated and are cephalad; the cochlear fibers are caudal. Occasionally, inferior vestibular nerve fibers run with the cochlear nerve, whereas the efferent cochlear fibers run in the inferior vestibular nerve.13 In the cerebellopontine angle, the cochleovestibular cleavage plane appears grossly as a fine septum along the eighth nerve in approximately 75% of patients. Typically, the vestibular nerve is grayer and the cochlear nerve is whiter. This is a reflection of the nearly 2:1 ratio of cochlear fibers (average 31,000) to vestibular fibers (average 18,000), and the more compact arrangement of the cochlear fibers. Frequently, a fine arteriole runs along the posterior surface of the eighth nerve overlying the cochleovestibular cleavage plane. The facial nerve lies ventral to the eighth cranial nerve in the posterior fossa and is thus hidden for much of its course. The facial nerve exits the brainstem at the pontomedullary junction approximately 3 mm ventral and caudal to the eighth nerve root entry zone. The facial nerve emerges with a more slender nerve, the nervus intermedius,

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Figure 56-2. The anatomy of the seventh and eighth cranial nerves and their branches seen from the supine otologic surgical position after the posterior wall of the IAC has been removed during a right retrosigmoid/IAC approach. The 90-degree rotation of the cochlear and vestibular nerves is illustrated. (From Haberkamp TJ, Silverstein H: Vestibular neurectomy from the posterior fossa approaches: A summary of the techniques. Operative Tech Otolaryngol Head Neck Surgery 12:116–121, 2001; with permission.)

which gets its name from its position as it courses across the cerebellopontine angle between the seventh and eighth nerves. Eventually, the nervus intermedius becomes incorporated in the sheath of the facial nerve. In the IAC, the facial nerve is connected to the superior vestibular nerve by the vestibulofacial fibers of Rasmussen; in the cerebellopontine angle, the facial nerve is adjacent to but distinct from the eighth nerve. Although it is hidden from the surgeon’s view by the eighth nerve, the facial nerve can usually be seen with gentle retraction of the superior vestibular nerve in the IAC or the eighth nerve in the cerebellopontine angle. Sometimes, a small mirrored instrument or a rigid endoscope is necessary to visualize the facial nerve. The nervus intermedius may consist of a single nerve or multiple bundles and runs between the seventh and eighth nerves throughout its course. Usually, it delineates the cochleovestibular cleavage plane on the ventral surface of the eighth nerve. This landmark can be identified with the aid of a mirrored instrument or a rigid endoscope in cases of a poorly defined cleavage plane. Another valuable landmark in the posterior fossa is the jugular dural fold (“Herb’s fold”) to aid in identification of the lower cranial nerves.14 This fold of dura appears as a white linear structure extending from the foramen magnum across the sigmoid sinus, attaching to the posterior aspect of the temporal bone anterior to the vestibular aqueduct. The midpoint of the fold lies approximately 1 cm dorsal to the ninth cranial nerve, and the eighth nerve enters the IAC approximately 7 to 10 mm ventral to the cephalad aspect of the fold.

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SURGICAL TECHNIQUE Nerve Monitoring and Anesthesia Regardless of the approach, continuous monitoring of the facial nerve is performed during VNS. The anesthesiologist should be alerted to this so that muscle relaxants can be withheld. During drilling and dissection of the nerve bundles, electrified instruments are used, which diminish risk to the facial nerve. Auditory brainstem response (ABR) monitoring may also be employed. However, the risk of hearing loss remains low with or without it, and the authors no longer use ABR routinely for VN. Intravenous antibiotics are administered in the perioperative period, and mannitol is given (1.5 g/kg up to 100 g) when drilling begins. This is an important aspect of intracranial surgery because it minimizes the need for brain retraction. Blood pressure should be closely monitored in the perioperative period as well to reduce the risk of intracranial hemorrhage.

Middle Fossa Vestibular Neurectomy The middle fossa approach for VN has been largely supplanted by posterior fossa surgery. Nevertheless, although the landmarks can be difficult to identify and the temporal lobe retraction may be contraindicated in older patients, it remains a useful technique. Middle fossa surgery may be used if the posterior fossa approach has failed (e.g., due to absence of a visible partition between the cochlear and vestibular nerves in the posterior fossa), and hearing preservation remains a priority. Vertigo cure rates have been higher than 90%.15,16 In contrast to mastoid and posterior fossa surgery where the surgeon sits at the side of the table, for middle fossa surgery the surgeon is at the head of the table facing inferiorly. The patient is placed in the supine position with the head turned to the contralateral side. The hair is shaved from just anterior to 5 cm posterior to the auricle and 9 cm above. One percent lidocaine with epinephrine 1:100,000 is injected along the planned incision. A preauricular incision is made from the lower edge of the zygomatic root and extended above the auricle, angling anteriorly by approximately 30 degrees for a length of approximately 7 cm. The muscle is incised along its posterior and superior attachments so that it can be reflected anteriorly. A craniotomy measuring 3 × 4 cm is made. Two-thirds of the bone flap is situated anterior to the external auditory canal, and onethird posterior. The inferior cut is made 1 cm above the temporal line, and the residual bone is removed with rongeurs to approximate the floor of the middle cranial fossa. After removal of the bone flap, dural elevation proceeds, lifting it off the arcuate eminence and the meatal plane in a posterior to anterior direction. The greater superficial petrosal nerve (GSPN) may be partially dehiscent along the floor of the middle fossa, and great care must be exercised during this part of the elevation. A middle fossa retractor is placed against the groove for the superior petrosal sinus to retract the temporal lobe and provide better exposure. The arcuate eminence is an important landmark along the floor of the middle fossa, but its relationship to the underlying superior semicircular canal varies. For this reason, it is advisable to identify the superior semicircular

canal from posterolaterally, where the contrast between pneumatized bone and otic capsule bone is most apparent. The IAC’s course runs approximately 60 degrees anteromedial from the plane of the superior semicircular canal. In addition to aiding in localization of the IAC, blue lining the superior semicircular canal and geniculate ganglion allows for maximal bone removal around the lateral IAC. The facial nerve monitor can simplify the identification of the geniculate ganglion by allowing more rapid positive identification of the GSPN. Stimulation of the GSPN may require slightly higher stimulus intensities than direct facial nerve stimulation. Once identified, the GSPN is traced into the geniculate ganglion, which is skeletonized. After all landmarks are appreciated, the bony roof of the IAC is opened. The IAC drill-out proceeds in a medial to lateral direction. The widest area of bone removal is medially, which narrows laterally toward the fundus (located between the superior semicircular canal and the cochlea). Once the vertical crest is identified and palpated, it can be used to begin sharp separation of the nerves in the facial-vestibular plane. After exposure of the fundus and division of connecting fibers between the facial and vestibular nerves, the superior vestibular nerve is divided (Fig. 56-3). Next, the inferior aspects of the fundus are inspected. The horizontal crest and acute angle of view of the IAC limit visualization of the inferior nerves. The singular nerve is sectioned by sliding a right-angle hook along the posterior edge of the inferior vestibular nerve and avulsing the nerve from the singular canal (Fig. 56-4). Following completion of the nerve section, the depression in the middle fossa floor is filled with a plug of temporalis muscle. Temporal lobe retraction is released, and the bone plate is replaced. The wound is then closed in multiple layers, starting with the temporalis muscle.

Figure 56-3. Drawing illustrating middle fossa exposure of the nerves in the IAC after the bone has been removed and the dura opened in a right ear. The superior semicircular canal and the greater superficial petrosal nerve (GSPN) provide landmarks in localization of the IAC. The vestibulofacial anastomoses should be divided before neurectomy. (From Haberkamp TJ, Silverstein H: Middle fossa vestibular neurectomy: A simplified approach. Operative Tech Otolaryngol Head Neck Surgery 12:122–123, 2001; with permission.)

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Figure 56-4. Drawing after the superior vestibular nerve has been sectioned via a middle fossa approach. Since the transverse crest obscures view of the lateral IAC, the singular nerve is sectioned, leaving the inferior vestibular nerve intact. A right-angle hook is used to divide the singular nerve. (From Haberkamp TJ, Silverstein H: Middle fossa vestibular neurectomy: A simplified approach. Operative Tech Otolaryngol Head Neck Surgery 12:122–123, 2001; with permission.)

General Points to Posterior Fossa Vestibular Neurectomy An injection of 1% lidocaine with epinephrine 1:100,000 is used along the planned incision. The skin is incised to create an anteriorly based, U-shaped, postauricular skinmuscle flap measuring 5 cm in craniocaudal width and 4 cm in anteroposterior length. The skin, postauricular muscles, and periosteum are elevated in a single layer to prevent seroma formation postoperatively. Abdominal fat is harvested from the left lower abdominal quadrant and is used to obliterate the postauricular bony surgical defect at the conclusion of the operation. Alternatively, a cranioplasty may be performed. To do this, the dura is covered with a large sheet of Gelfoam. Next, the skull contour is restored with cranioplasty material such as methylmethacrylate. Bleeding from the sigmoid sinus, jugular bulb, or dural vessels is often encountered. Hemorrhage from the dural sinuses is high volume but low pressure, and precisely applied pressure is almost always all that is needed for hemostasis. Pressure can be applied by using compressed Avitene or Gelfoam placed directly on the bleeding point and held in place with a cottonoid sponge. Some patients have a large emissary vein arising from the sigmoid sinus. If this is encountered, it is wise to complete the remainder of the mastoid and retrosigmoid drilling before completely exposing the emissary vein. Once the other drilling is completed, the bone over the emissary vein can be thinned down with a diamond drill, and the eggshell covering of bone can be gently removed with a blunt elevator. At that point, the venous branch can be easily controlled with bipolar cautery or ligation. If significant bleeding from a large

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mastoid emissary vein occurs before all of the overlying bone is removed, it may not be possible to stop with cautery alone. In that case, the overlying bone should be drilled away while applying pressure with a cottonoid sponge. Once the bone is removed, bleeding is stopped by cauterizing the vein stump. Before the dura is opened, bipolar cautery is used to score the planned incision. Lifting the dura as it is cut with scissors also helps to prevent injury to underlying vessels on the cerebellar cortex. Mannitol is used to induce contraction of the cerebellum and improve exposure of the brainstem. Once the dura is incised, it is necessary to release cerebrospinal fluid (CSF) from the cerebellopontine cistern. This allows the cerebellum to further retract and provides excellent exposure of the CPA. Damage to the surface of the cerebellum is prevented by using a large Penrose drain placed against the cortex. The Penrose drain is carefully advanced toward the cistern while the cerebellum is gently retracted. Once the arachnoid is incised and CSF is released, it is usually no longer necessary to retract the cerebellum. The Penrose drain is left in place to protect the cerebellar surface until the conclusion of the nerve section. If brain swelling occurs from trauma to the cerebellum and the CPA cannot be easily exposed, it is best to withdraw and close the wound (although we have not had to do this in any case). The surgeon should be aware that with the measures taken to decrease brain swelling, the petrosal veins near the tentorium become stretched as the cerebellum falls away. These veins are vulnerable to injury, but bleeding can be controlled with Avitene and electrocautery.

Nerve Identification and Nerve Section Technique When the cerebellum falls away with the release of CSF, the jugular dural fold is a helpful landmark to identify the eighth cranial nerve, which lies 7 to 10 mm medial to its anterior aspect.14 It is also important to locate cranial nerves V, IX, and X for orientation to the eighth nerve. To prevent injury, the facial nerve is first visualized inferiorly and then followed as it runs anterior to the vestibular nerve by gently retracting the eighth cranial nerve. If necessary, the facial nerve can also be seen using a 30-degree or 70-degree endoscope.17 Occasionally, the facial nerve is adherent to the anterior surface of the eighth nerve. In that case, it must be separated from the vestibular nerve with a round knife. As previously described, several landmarks are helpful in finding the cleavage plane between the cochlear and vestibular nerves. The cochlear nerve appears whiter and the vestibular nerve appears grayer. Frequently, a fine blood vessel is visible between the cochlear and vestibular fibers. Sometimes the cleavage plane is more visible anteriorly, along which the nervus intermedius runs, and can be viewed with a small mirror or an endoscope. If a cleavage plane is still not visible, then the superior half of the eighth nerve is divided near the brainstem where the vestibular and the cochlear fibers are separated more distinctly. With this technique, the majority of the vestibular fibers are divided and most of the cochlear fibers are preserved. A cleavage plane that is not initially apparent usually can be found near the brainstem.

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The safest way to transect the vestibular nerve is to divide the posterior 80% of the nerve with Luetje microscissors and to complete the transection with an electrified sickle knife, while ensuring that the facial nerve is free of the dissection. The nerve separator should be visualized passing anterior to the vestibular nerve and separating it from the facial and cochlear nerves before completing the transection. When the transection is complete, the surgeon will observe the cut ends of the nerve retract away from each other like a rubber band on stretch. Most intraoperative complications are prevented by careful, gentle microsurgical techniques. However, total hearing loss can occur even if the cochlear nerve is not interrupted because of damage to the internal auditory artery that causes ischemic cochlear injury. Several approaches have been developed to gain access to the CPA via the posterior fossa; the specifics for each will now be addressed.

Retrolabyrinthine Approach The retrolabyrinthine approach was developed in 1978. The exposure is limited anteriorly by the facial nerve and otic capsule, posteriorly by the sigmoid sinus, inferiorly by the jugular bulb, and superiorly by the middle fossa. To achieve the best exposure, it is necessary to identify and skeletonize each of these structures. After the skin-muscle flap is elevated, a complete mastoidectomy is performed, the sigmoid sinus is identified, and its overlying bone is removed. The endolymphatic sac, the vertical portion of the facial nerve, the posterior wall of the external auditory canal, and the posterior semicircular canal are identified and preserved. The retrofacial air cells are then opened, and the dura over the posterior fossa is exposed from the middle fossa to the jugular bulb and from the sigmoid sinus to the posterior semicircular canal (Fig. 56-5). The sigmoid sinus is collapsed and retracted posteriorly using the Silverstein lateral sinus retractor.18 In contrast to the retrosigmoid approach, the dura is incised anterior to the sigmoid sinus, creating an anteriorly based flap around the endolymphatic sac. A Penrose drain is placed over the cerebellum, which is gently retracted as the arachnoid is opened with a blunt instrument to allow the CSF to escape. The vestibular nerve section is then performed under high-power magnification. The dura is closed using interrupted 4–0 silk sutures; however, in the retrolabyrinthine approach a watertight closure is generally not possible. Temporalis fascia is placed over the dura with fibrin glue, the mastoid cavity is filled with adipose tissue, and the wound is closed in layers. The skin is closed with staples. Because of the 10% incidence of CSF leak with this approach, the retrolabyrinthine exposure was discontinued at our institution in favor of the retrosigmoid approach, which allows a watertight closure of the dura and less direct communication with the mastoid air cells.

Retrosigmoid-Internal Auditory Canal Approach The retrosigmoid-internal auditory canal (RSG-IAC) approach was developed in 1985 in an attempt to improve vertigo control rates and decrease the incidence of

Figure 56-5. A right retrolabyrinthine approach—posterior fossa dura exposed from the sigmoid sinus to the otic capsule. (From Haberkamp TJ, Silverstein H: Vestibular neurectomy from the posterior fossa approaches: A summary of the techniques. Operative Tech Otolaryngol Head Neck Surgery 12:116–121, 2001; with permission.)

CSF leak.19 The principle behind this modification is that the cochlear and vestibular fibers are more clearly separated into different nerve bundles in the IAC. Exposure of the nerves in the IAC could allow a more thorough vestibular neurectomy without increasing the risk of hearing loss. A posterior fossa craniotomy 3 cm in diameter is performed immediately behind the lateral sinus. After the dura is opened with a posteriorly based, U-shaped incision, the CSF is released and the cerebellum is retracted with a self-retaining retractor blade. The seventh and eighth cranial nerves and IAC are identified as described earlier. An anteriorly based, U-shaped dural flap is elevated from the posterior surface of the temporal bone between the operculum and the porus acusticus. The posterior wall of the IAC is drilled with a diamond burr to the singular canal. Measurements can be made from the preoperative high-resolution CT scan, allowing the surgeon to determine how much bone of the IAC can be removed before reaching the singular canal, and thus avoiding entering the vestibule and posterior semicircular canal (SCC). Next, the dura in the IAC is incised. The superior vestibular nerve and the singular nerve (the branch of the inferior vestibular nerve to the posterior SCC) are sectioned at this point. The inferior vestibular nerve fibers to the saccule are preserved because of their close association with the cochlear fibers. The saccule has no known vestibular function in humans and sectioning it would place hearing unnecessarily at risk. Bone wax is used to seal exposed air cells in the IAC. The dura is closed in a watertight fashion, and no abdominal fat is needed to fill the defect. The retrosigmoid approach minimized the complication of CSF leak. However, because of the frequent incidence of severe headaches, this approach was discontinued in 1987.

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The headaches were thought to be related to drilling the bone over the IAC, causing a bone dust arachnoiditis.

Combined RetrolabyrinthineRetrosigmoid Approach The combined retrolabyrinthine-retrosigmoid vestibular neurectomy (RRVN) was developed in 1987 and remains our preferred technique. This approach was developed to incorporate the advantages of both the retrolabyrinthine and RSG-IAC approaches, which include shorter operating time, watertight closure of the dura, minimal cerebellar retraction, and elimination of the need for IAC drilling with its associated incidence of headache (but allowing exposure for drilling the IAC when necessary) (Table 56-1).20–22 Through complete exposure of the sigmoid sinus, it can be retracted anteriorly after the dura is incised and allows improved visualization of the nerve bundle at the CPA. In this approach, a limited mastoidectomy is performed to expose 3 cm of the sigmoid sinus from the transverse sinus inferiorly. Few mastoid air cells need to be opened. The posterior fossa dura is exposed at least 1.5 cm posterior to the sigmoid sinus. It is important that the bone be removed along the course of the sigmoid sinus inferiorly, near its junction with the jugular bulb. This is necessary to expose the cerebellar cistern, which is approached in a near vertical direction from superior to inferior. A dural incision is made 3 mm behind and parallel to the sigmoid sinus after the line of incision is cauterized with bipolar cautery. The sigmoid sinus is retracted forward using stay sutures placed along the dural cuff. This affords visualization of the posterior wall of the temporal bone and the jugular dural fold (“Herb’s fold”), and it allows wide exposure of the cerebellopontine angle without retraction of the cerebellum. A Penrose drain is placed against the cerebellum and gentle retraction is performed with a Penfield elevator until the cerebellopontine angle cistern is opened and CSF is released. At that point, the jugular dural fold and cranial nerves are identified (Fig. 56-6). The vestibular nerve is sectioned near the brainstem (Fig. 56-7). In cases with a poor cleavage plane, the superior half of the eighth nerve is sectioned near the brainstem. Although the IAC can be opened and the nerve sectioned as outlined under the RSG-IAC approach, we no longer drill the IAC. Even when the cleavage plane is not readily apparent, excellent results have been obtained by cutting the superior half of the eighth nerve at the brainstem. Once the procedure is completed, the dura is closed in a watertight fashion with interrupted silk sutures. Abdominal fat or

Figure 56-6. Exposure provided by the combined retrolabyrinthineretrosigmoid approach to the cerebellopontine angle. (From Haberkamp TJ, Silverstein H: Vestibular neurectomy from the posterior fossa approaches: A summary of the techniques. Operative Tech Otolaryngol Head Neck Surgery 12:116–121, 2001; with permission.)

cranioplasty is used to fill in the bony defect. This not only provides a better cosmetic result than not filling in the defect, but it also prevents adhesions between the scalp and dura, which can induce headaches.

Postoperative Care A mastoid dressing is applied in the operating room at the conclusion of the procedure and is generally left in place for 24 to 48 hours. Patients are admitted to the neurosurgical

Table 56-1. Advantages of the Combined Retrolabyrinthine-Retrosigmoid Approach Shorter operating time Wide exposure of the CPA No cerebellar retraction Drilling of the IAC usually unnecessary Postoperative headaches generally avoided Ability to open IAC if cochleovestibular cleavage plane obscured at CPA Watertight dural closure and minimal exposure of mastoid air cells, minimizing chances of CSF leak High hearing preservation rates (80%)

Figure 56-7. Right vestibular nerve after it has been sectioned near the brainstem. (From Haberkamp TJ, Silverstein H: Vestibular neurectomy from the posterior fossa approaches: A summary of the techniques. Operative Tech Otolaryngol Head Neck Surgery 12:116–121, 2001; with permission.)

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intensive care unit for the first 24 hours and blood pressure and neurologic status are monitored. They are encouraged to sit in a chair on the first postoperative day, ambulate on the second postoperative day, and can usually go home on the third to sixth day. Patients should receive instructions about vestibular rehabilitation prior to surgery, and begin exercises on postoperative day 1. Exercises including eye movement saccades, tracking gaze stabilization, and vertical and horizontal head movements can start even before the patient is able to get out of bed. A common complaint in the early postoperative period is that the patient notices a subtle difficulty with focusing vision at a distance. This phenomenon is related to unilateral deafferentation of the vestibulo-ocular pathway and usually resolves in 7 to 14 days.

RESULTS Retrolabyrinthine Vestibular Neurectomy In a review of 78 patients who underwent retrolabyrinthine vestibular neurectomy, 88% were completely cured of the vertigo, and an additional 7% were substantially improved. With regards to hearing, data is available on 65 patients. At 1 month, 37% of patients were within 10 dB of their preoperative PTA and/or 15% of their preoperative speech discrimination, while an additional 23% had a improvement in PTA greater than 10 dB and/or greater than 15% improvement in speech discrimination scores. Hearing preservation as good as or better than the preoperative level was accomplished in at least 60% of patients.11

Retrosigmoid-Internal Auditory Canal Vestibular Neurectomy Of the 14 patients who underwent RSG-IAC vestibular neurectomy, 90% were completely cured of the vertigo. At 1 month, 50% of patients were within 10 dB of their preoperative PTA and/or 15% of their preoperative speech discrimination. An additional 21% had a greater than 10 dB improvement in PTA and/or a 15% improvement in speech discrimination scores. Hearing preservation at least at the preoperative level was accomplished in 71% of patients.11

Combined RetrolabyrinthineRetrosigmoid Vestibular Neurectomy More than 126 combined RRVN procedures have been performed. The results are very similar to those of the retrolabyrinthine approach with regards to the control of vertigo. However, the hearing preservation results have been better. Complete vertigo cure is accomplished in 85%, with substantial improvement in another 7%. Hearing data is available on 73 patients. At 1 month postoperatively, 44% of patients were within 10 dB of their preoperative PTA and/or 15% of their preoperative speech discrimination. An additional 36% had an improvement in PTA at greater than 10 dB and/or an improvement in speech discrimination scores greater than 15%. Hearing preservation

at least at the preoperative level was accomplished in 80% of patients. Hearing was statistically better (p < 0.05) in the RRVN group for all follow-up periods (1 week, 1 month, 1 year, and 18 to 24 months) compared to patients who had retrolabyrinthine vestibular neurectomy.11 This is attributed to sectioning the vestibular nerve close to the brainstem and greater experience gained over time, as well as the wide exposure possible with the combined RRVN approach. The results of this surgery have been particularly successful in terms of patient satisfaction and functional ability. Most patients are able to return to activities they had given up because of Ménière’s disease. When objectively rating functional ability on a six-point scale according to the 1995 Committee on Hearing and Equilibrium guidelines,23 4.2 was the average preoperative functional level and 1.3 was the average postoperative functional level in our series following RRVN. Other authors have reported similar vertigo control rates (= 85%) with their experience of vestibular neurectomy by various approaches.24,25

COMPLICATIONS Complications have been infrequent. No cases of facial paralysis or weakness have occurred in our series of posterior fossa vestibular neurectomy. Facial nerve monitoring and the use of electrified instruments have played a key role in preventing injury to the facial nerve. Early postoperative intracranial bleeding requires neurosurgical assessment, and if signs of herniation are evident, opening the wound emergently is necessary. We have not seen this in our experience. Meningismus with mild temperature elevation early in the postoperative period is usually due to small amounts of blood in the CSF producing chemical meningitis. No treatment other than close monitoring is required in such cases. All wound infections have been superficial and have resolved rapidly with local wound care and antibiotics. With perioperative antibiotics such as nafcillin and elevation of the flap in a single layer from the skin down to the periosteum (to avoid seroma formation), wound infection has been essentially eliminated. Meningitis generally presents several days postoperatively with a spiking temperature, headache, and nuchal rigidity. This requires an immediate lumbar puncture for culture and sensitivity studies and appropriate antibiotic treatment. This very rare complication has not occurred in our experience. With retrolabyrinthine vestibular neurectomy, the most common complication was CSF leak, which occurred in 10% of cases. This complication has become very unusual since a watertight closure is possible with the combined RRVN approach. We have found that most CSF leaks can be stopped with continuous lumbar drainage for 3 to 4 days. Headaches have been a very significant problem with the RSG-IAC approach; they occur early in 75% and persist for years in about 25% of patients. The exact etiology of the headaches is unknown but appears to be related to arachnoiditis caused by extensive drilling in the posterior fossa and IAC. With the combined RRVN approach we currently use, drilling of the IAC can be avoided along with the postoperative severe headaches seen with the RSGIAC approach.

Vestibular Neurectomy

About 5% of patients continue to have vertigo after posterior fossa vestibular neurectomy. Usually, the vertigo is mild and the patient still notes a marked improvement in quality of life. Patients who undergo vestibular nerve section for pathology other than classical Ménière’s disease have a higher failure rate. In preserving hearing, some persistent vestibular fibers may remain in the cochlear nerve.26 If some vestibular function remains on electronystagmography and the patient continues to have severe episodic vertigo, inner ear perfusion with gentamicin or labyrinthectomy with or without transcochlear eighth nerve section is an option.

CONCLUSION For patients with vertigo resulting from Ménière’s disease, which is refractory to medical and less invasive surgical management, selective vestibular neurectomy represents a hearing preservation technique with high success in controlling vertigo. Since first introduced over a century ago, the concept of vestibular neurectomy has undergone an evolution. Microsurgical combined retrolabyrinthine-retrosigmoid vestibular neurectomy has been our standard approach since 1987. The technique provides a direct approach with excellent results and minimal incidence of complications.

REFERENCES 1. Dandy WE: Ménière’s disease: Its diagnosis and method of treatment. Arch Surg 16:1127–1152, 1928. 2. McKenzie KG: Intracranial division of the vestibular portion of the auditory nerve for Ménière’s disease. Can Med Assoc J 34:369, 1936. 3. Dandy WE: Treatment of Ménière’s disease by section of only the vestibular portion of the acoustic nerve. Bull Johns Hopkins Hosp 53:52–55, 1933. 4. House WF: Surgical exposure of the internal auditory canal and its contents through the middle cranial fossa. Laryngoscope 71:1363, 1961. 5. Fisch U: Vestibular and cochlear neurectomy. Trans Am Acad Ophthalmol Otolaryngol 78:252–254, 1977. 6. Glasscock ME: Vestibular nerve section. Arch Otolaryngol 97: 112–114, 1973. 7. Glasscock ME, Kveton JF, Christiansen SG: Middle fossa vestibular neurectomy: An update. Otolaryngol Head Neck Surg 92:216–220, 1984. 8. Silverstein H, Norrell H: Retrolabyrinthine surgery: A direct approach to the cerebellopontine angle. Otolaryngol Head Neck Surg 88:462–469, 1980.

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9. Silverstein H: Cochlear and vestibular gross and histologic anatomy (as seen from the postauricular approach). Otolaryngol Head Neck Surg 92:207–211, 1984. 10. Silverstein H, Wanamaker H, Flanzer J, et al: Vestibular neurectomy in the United States–1990. Am J Otol 13:23–30, 1992. 11. Rosenberg S, Silverstein H, Hoffer M, et al: Hearing results after posterior fossa vestibular neurectomy. Otolaryngol Head Neck Surg 114:32–37, 1996. 12. Silverstein H, Norrell H, Haberkamp T, et al: The unrecognized rotation of the vestibular and cochlear nerves from the labyrinth to the brainstem: Its implications in surgery of the eighth cranial nerve. Otolaryngol Head Neck Surg 95:543–549, 1986. 13. Rasmussen AT: Studies of the VIIIth cranial nerve in man. Laryngoscope 50:667, 1940. 14. Jackler RK, Whinney D: A century of eighth nerve surgery. Otol Neurotol 22:401–416, 2001. 15. Silverstein H: Indications and results of middle fossa vestibular neurectomy. In Silverstein H, Norrell H (eds.): Neurological Surgery of the Ear. Birmingham, Ala, Aesculapius, 1977, pp 124–130. 16. Silverstein H, Rosenberg S, Arruda J, et al: Surgical ablation of the vestibular system in the treatment of Ménière’s disease. Otolaryngol Clin North Am 30:1075–1095, 1997. 17. Rosenberg S: Endoscopic otologic surgery. Otolaryngol Clin North Am 29:291–300, 1996. 18. Silverstein H: Silverstein lateral venous sinus retractor. Otolaryngol Head Neck Surg 89:303. 19. Silverstein H, Norrell H, Smouha E: Retrosigmoid-internal auditory canal approach versus retrolabyrinthine approach for vestibular neurectomy. Otolaryngol Head Neck Surg 97:300–307, 1987. 20. Silverstein H, Norrell H, Smouha E, et al: Combined retrolabretrosigmoid vestibular neurectomy: An evolution in approach. Am J Otol 10:166–169, 1989. 21. Silverstein H, Norrell H, Smouha E, et al: Vestibular neurectomy through combined retrolab-retrosigmoid approach. In Fisch U, Valavanis A, Yasargil MG (eds.): Neurological Surgery of the Ear and Skull Base. Amsterdam, Kugler & Ghedini Publications, 1989, p 481. 22. Silverstein H, Rosenberg S: Combined retrolabyrinthineretrosigmoid vestibular neurectomy. Operative Tech Otolaryngol Head Neck Surg 2:26–27, 1991. 23. Monsell EM, Balkany TA, Gates GA, et al: Committee on hearing and equilibrium guidelines for the diagnosis and evaluation of therapy in Ménière’s disease. Otolaryngol Head Neck Surg 113:181–185, 1995. 24. Pappas DG Jr, Pappas DG Sr: Vestibular nerve section: Long-term follow-up. Laryngoscope 107:1203–1209, 1997. 25. Thomsen J, Berner B, Tos M: Vestibular neurectomy. Auris Nasus Larynx 27:297–301, 2000. 26. Rosenberg S, Silverstein H, Norrell H, et al: Audio and vestibular function after vestibular neurectomy. Otolaryngol Head Neck Surg 104:139–140, 1991.

Chapter

57 Charles D. Yingling, PhD, D ABNM Yasmine A. Ashram, MD, D ABNM

Intraoperative Monitoring of Cranial Nerves in Skull Base Surgery Outline Introduction History and Context Scope of This Chapter Neurophysiology in the Operating Room Personnel Instrumentation: Technical Considerations Instrumentation Recording Electrodes Stimulating Electrodes Constant Voltage versus Constant Current Stimulus Duration Recording Electrodes and Patient Preparation Electrical Safety Cranial Nerve Monitoring: Quality Control Anesthesia Communication and Report Generation Facial Nerve Monitoring Vestibular Schwannoma, Other Cerebellopontine Angle Tumors Modalities for Facial Nerve Monitoring Activity Evoked by Electrical Stimulation

Spontaneous and Mechanically Elicited Activity Limitations of Electromyography Microvascular Decompression Parotidectomy Middle Ear Surgery Facial Nerve Preservation Other Motor Nerve Monitoring Extraocular Muscles Latency Criteria to Distinguish Nerves VI and VII Placement of Electrodes for Monitoring Extraocular Muscles Trigeminal Nerve Lower Cranial Nerves Cochlear Nerve Monitoring Auditory Brainstem Response Recording in the Operating Room Stimulus and Recording Parameters, Electrodes, and Placement Reducing Electrical and Acoustic Interference

INTRODUCTION History and Context The first published description of cranial nerve monitoring during posterior fossa surgery was more than a century ago. On July 14, 1898, Dr. Fedor Krause, during a cochlear nerve section for tinnitus, noted that “unipolar faradic irritation of the (facial) nerve-trunk with the weakest possible current of the induction apparatus resulted in contractions of the right facial region, especially of the orbicularis oculi, as well as of the branches supplying the nose and mouth. . . .”1 The patient awoke with a transient facial paresis, which was mostly resolved by the next day. Krause also noted contractions of the shoulder, which he thought were due to stimulation of the spinal accessory nerve that “had undoubtedly been reached by the current, 958

Analogue versus Digital Filtering Interpretation of Responses in Surgical Context Typical ABR Findings in Vestibular Schwannoma Surgery Correlation of Intraoperative ABR with Postsurgical Auditory Function Direct VIII Nerve Action Potentials Placement of Electrodes Stimulus and Recording Parameters Detection and Interpretation of Changes Intraoperative Electrocochleography Electrode Placement Interpretation of Waveforms Evoked Potentials to Stimulation of the Vestibular Nerve Cochlear Nerve Preservation Future Directions and Conclusions

because it was, together with the acousticus, bathed in liquor (i.e., cerebrospinal fluid [CSF]) that had trickled down. . . .” Krause was thus not only the first to describe the use of electrical stimulation to locate cranial nerves but also the first to encounter the confounding problem of artifactual responses from current spread! In 1912 Frazier2 used a similar technique during an operation for relief of vertigo; he pointed out the importance of preserving the facial nerve, which he noted could be identified by “galvanic current.” Subsequently, Olivecrona,3,4 Hullay and Tomits,5 Rand and Kurze,6 Pool,7 and Albin and colleagues8 described similar methods. At one time, several surgeons even performed resection of vestibular schwannomas (acoustic neuroma) under local anesthesia to facilitate assessment of facial function.3,5 The basic technique of observing the face for visible contractions after electrical stimulation remained the state of the art for facial nerve

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monitoring until 1979, when intraoperative facial electromyography (EMG) was introduced.9 In contrast to the long history of facial nerve monitoring, the advent of cochlear nerve monitoring is a relatively recent development. The availability of techniques for signal averaging and the discovery of the human auditory brainstem response (ABR) by Jewett and Williston in 197110 were necessary preconditions for attempts to monitor cochlear nerve function. Also, during the early days of vestibular schwannoma surgery, tumors were generally quite large by the time they were diagnosed. Given the relatively crude state of early microsurgical techniques, mortality rather than cranial nerve preservation was usually the main concern. With the advent of more sensitive diagnostic measures, including ABR, computed tomography (CT), and later gadolinium-enhanced magnetic resonance imaging (MRI) scanning, earlier diagnosis of smaller tumors became more common. Together with advances in microsurgical techniques, posterior fossa surgery has become much safer, and thus increasing emphasis has been placed on preservation of cranial nerve function. This has in turn stimulated the development of techniques for monitoring cranial nerves during surgery. Monitoring nerve VII during vestibular schwannoma surgery has now become routine at most major medical centers, and anatomic preservation of the facial nerve has been achieved in more than 95% of cases in most recently published series.11 Although facial motility is often compromised in the immediate postoperative period, the long-term prognosis is good if the nerve can be electrically stimulated after tumor removal. A recent National Institutes of Health (NIH) consensus conference on vestibular schwannoma12 concludes that “the benefits of routine monitoring of the facial nerve are established.” Preservation of hearing has been more difficult to achieve because of the more intimate relationship of such tumors with the cochleovestibular nerve, but is now often achieved in smaller tumors with monitoring of the eighth nerve. Finally, the techniques developed for facial nerve monitoring can be readily adapted for monitoring other cranial motor nerves. Several books13–17 contain extensive discussion of many of these topics.

Scope of This Chapter This chapter considers the issues and techniques of cranial nerve monitoring primarily from the surgical neurophysiologist’s point of view. Thus, the emphasis is on the practical aspects of instrumentation, electrode placement, adaptation of neurophysiologic techniques to the operating room, artifact identification, types of responses encountered, and the relationship between intraoperative recordings and clinical outcome. Specific clinical syndromes and their relation to cranial nerve anatomy are not considered in detail. Somatosensory evoked potential (SEP) recording is also not treated here, although SEP recording can be useful in monitoring large posterior fossa tumors with significant brainstem compression; discussions of SEP monitoring can be found in Nuwer,16 Møller15 and Desmedt.13 This chapter is based on our experience at the University of California–San Francisco (UCSF) with more than 500 posterior fossa procedures, as well as a review of the literature through 2002. We describe the methods currently

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available for cranial nerve monitoring, emphasizing facial and cochlear nerve monitoring during vestibular schwannoma surgery but also including extension of these techniques to other nerves encountered in a variety of skull base procedures.

NEUROPHYSIOLOGY IN THE OPERATING ROOM Personnel Successful intraoperative monitoring requires more than simply bringing another piece of equipment into the operating room (OR). The OR, unlike the typical clinical neurophysiology laboratory, presents a time-pressured and electrically hostile environment. Providing technically adequate recordings in the OR requires professional personnel with specialized skills and experience. Reliance on equipment without such personnel might result in failure, or even worse, inadequate monitoring with inaccurate and misleading feedback to the surgeon. A new specialty field of intraoperative neurophysiologic monitoring has evolved, with its own professional organization, the American Society of Neurophysiological Monitoring (ASNM). Surgical monitoring professionals come from diverse backgrounds, including neurophysiology, audiology, biomedical engineering, neurology, and anesthesiology; regardless of background or professional degree, monitoring personnel require a common fund of knowledge that includes neuroanatomy and neurophysiology, biomedical instrumentation, specific intraoperative monitoring techniques with their uses and limitations, and practical experience performing these techniques and interpreting their results in the surgical context. Since inappropriate application of monitoring techniques has potentially catastrophic consequences, the participation of professional monitoring personnel is necessary, despite the additional costs. Third-party reimbursement in the United States is now facilitated by a specific CPT code (95920) for intraoperative neurophysiologic monitoring. Two national organizations in the United States now offer professional certification for surgical neurophysiologists. At the technologist level, the American Board of Registered Electrodiagnostics Technologists (ABRET) offers a Certification in Neurophysiological Intraoperative Monitoring (CNIM), which is awarded on the basis of a written examination offered to technologists who can document a minimum experience of 100 surgical cases monitored. The American Board of Neurophysiologic Monitoring (ABNM) offers board certification to monitoring professionals who hold advanced degrees and have a minimum of 3 years’ experience with 300 cases monitored. The ABNM exam consists of a written portion covering such areas as anatomy, physiology, instrumentation, and specific monitoring techniques, followed by an oral exam that stresses interpretation and judgment in simulated clinical scenarios. At the time of this writing (early 2003), more than 400 professional are qualified with CNIMs and approximately 60 are diplomates of the ABNM. This is still a relatively small number, given the explosive growth of monitoring in many other types of surgical cases as well as

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skull base surgery. There is a growing need for training programs to ensure an adequate supply of qualified personnel; the demand for monitoring services is growing rapidly.

Instrumentation: Technical Considerations Instrumentation The basic instrumentation requirements for monitoring cranial nerves with EMG are an isolated electric stimulator that can be precisely controlled at low levels; several low-noise EMG amplifiers; a multichannel display; and an audio monitor with a squelch circuit to mute the output during electrocautery. The earliest commercial systems, such as the Grass NL-1 and Xomed NIM-2, had only one or two channels and were thus unsuitable for use in complex cases where multiple cranial nerves are at risk. Also, it is highly recommended that more channels be used even in smaller vestibular schwannoma resections where only the facial nerve is at risk; the extra channels provide a valuable control for nonspecific increases in EMG activity resulting from light anesthesia or other nonsurgical factors. The availability of more channels also allows simultaneous monitoring of multiple divisions of the facial (VII) nerve independently, as well as other cranial motor nerves such as the motor component of the trigeminal nerve (V3m) and the spinal accessory nerve (XI), which are often involved in posterior fossa tumors. The NIM-Response (Nerve Integrity Monitor), manufactured by Medtronic Xomed ( Jacksonville, FL), offers four EMG channels and appropriate stimulation and squelch circuits (Fig. 57-1). The constant current stimulator can be

set to as low as 0.01 milliamperes (mA) to allow precise threshold determinations, and there are inductive probes that can be clamped around the output wires of electrocautery equipment, sensing when they are activated and automatically squelching the audio output. This system does not include signal averaging capability and thus cannot be used to monitor ABR. Monitoring ABR requires an averaging computer with high-gain, low-noise electroencephalogram (EEG) amplifiers, which can be synchronized to an acoustic generator capable of delivering clicks of calibrated intensity, with control of polarity (condensation, rarefaction, or alternating) and repetition rate. Most commercial evoked potential systems have such capabilities and can be readily adapted to use in the operating room. Typical clinical systems include at least four-channel, high-gain (100K to 500K) differential amplification with multipole, bandpass filtering capabilities, acoustic stimulus intensity ranging from threshold to at least 70 dB above normal hearing threshold (dBHL), signal averaging with real-time display of the evolving averages as well as the input signal, and permanent disk storage with the option of printing hard copies. There are, however, several desirable features for operating room use that differ from features of most commercial systems designed for diagnostic use. In the OR, the emphasis is on continuous and rapid data collection, simultaneous display of baseline traces and recent trends, as well as the current trace to facilitate continuous monitoring and assessment of intraoperative changes. Simultaneous collection of ABRs from left and right ears (with responses to alternating ear stimuli automatically directed to the proper channels) is also desirable to control for nonspecific effects such as anesthesia, acoustic artifact, and patient temperature. For complex surgical cases, when more EMG channels or ABR averaging capability are needed, there are several commercial multichannel systems designed for intraoperative use. Cadwell Laboratories (Kennewick, Wash.) offers the 16-channel Cascade system with a flexible software package and low-level stimulators appropriate for intracranial stimulation. The Cascade is available in either console or portable versions (Fig. 57-2), and the 16 channels can be assigned as desired to averaged, free-run, or stimulustriggered modes. Similar systems include the Epoch 2000 from Axon Systems (Hauppauge, NY ), Viking Select and Endeavor from Nicolet Biomedical (Madison, Wis.), and the EP16 from XLTEK (Toronto, Ont.). All of these systems allow multiple independent time bases and functions to operate simultaneously; for example, some channels may be devoted to free-running EMG at slow sweep speeds, others to stimulus-triggered EMG at a faster sweep, while still others can be used for collection of averaged ABRs. These systems are also adaptable for other types of surgical monitoring (i.e., spinal surgery) by creating appropriate software templates. Recording Electrodes

Figure 57-1. The Medtronic Xomed NIM-Response, a four-channel monitoring system specially designed for cranial nerve monitoring.

Both surface and needle electrodes have been used. The surface electrodes most commonly employed are small discs of the type used for scalp EEG recording. A variety of needles are employed, including standard EMG electrodes,

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B

Figure 57-2. The Cadwell Cascade, a 16-channel general purpose intraoperative monitoring system that can be flexibly configured to record averaged evoked potentials, triggered EMG, and free running EMG simultaneously. It can be used to monitor many types of surgical procedure other than neurotologic, but is readily programmable for simultaneous ABR and multichannel EMG recording for complex skull base procedures. It is available in both console (A) and portable (B) versions. Similar systems are available from several manufacturers (see text).

A subdermal EEG electrodes, and a variety of custom designs. Each type has advantages and disadvantages for OR use. Surface electrodes pick up EMG activity from a relatively large number of muscle fibers, so they may provide better coverage and greater probability of detecting activity if only a few fibers are active. However, surface electrodes are less specific, more prone to artifact, and more time-consuming to apply, so their use has largely been supplanted by needle electrodes, which can be quickly inserted and taped into place. Furthermore, surface electrodes are useful only for recording from superficial musculature; needles are required for monitoring cranial nerves that innervate deeper muscles such as the extraocular muscles or larynx. Probably the most popular recording electrodes for cranial nerve monitoring are platinum or stainless-steel subdermal needles designed for EEG (available from several suppliers); these have a larger uninsulated surface than electrodes designed for single-fiber EMG and thus are more likely to detect activity arising anywhere in the desired muscle. Prass and Lüders18 advocate the use of intramuscular

hook wire electrodes that are inserted with a hypodermic needle; these are more delicate, have higher impedance and are thus more prone to artifact, and offer no practical advantage for routine recording from facial muscles. In some applications, the use of insulated needles is desirable to avoid cross-talk from overlying muscles, for example, when recording from extraocular muscles where the electrodes must pass through the orbicularis oculi muscle and will thus respond to facial nerve activity as well. The first reports of facial EMG monitoring used a single recording channel, with one electrode of the bipolar pair in orbicularis oculi and the other in orbicularis oris.9,19 This montage is sensitive to activity in muscles innervated from either superior or inferior branches of the facial nerve. However, use of a single channel has major disadvantages. First, wider spacing between two electrodes leads to greater sensitivity to electrical artifacts, which in the electrically noisy environment of an operating room can lead to difficult or erroneous interpretations. Second, mechanical trauma to the seventh nerve often causes

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sustained EMG activity, making identification of the facial nerve with electrical stimulation more difficult. With two or more closely spaced bipolar channels, at least one is usually quiet enough to allow responses to stimulation to be identified without signal averaging even with high tonic EMG activity. It is thus desirable to use at least two channels of facial EMG, even for simple cases. Furthermore, a third channel should be used to monitor EMG from a noninvolved region, such as the trapezius or contralateral face, even if the facial nerve is the only one at risk. This channel serves as a control for nonspecific EMG activity resulting from light anesthesia and other nonsurgical causes. To record the ABR in hearing-conservation procedures, one electrode is placed in the ipsilateral ear canal and another on the forehead or vertex. The placement of the second electrode is not critical if it is near the midline. If the averaging computer has the capacity to record simultaneously from both ears, the contralateral ear ABR provides a control for nonspecific effects. (Note, however, that the two ears must be stimulated alternately, not simultaneously, with separate averages for each ear.) Figure 57-3 shows the positioning of recording electrodes for a retrosigmoid craniotomy for vestibular schwannoma with an effort to preserve hearing. For a translabyrinthine approach, the same configuration is used, with the exception of the earphone and electrodes for ABR recording because hearing conservation is not possible with this approach. Stimulating Electrodes Both monopolar and bipolar stimulating electrodes have been employed. In theory, a bipolar electrode might provide more precise localization because the likelihood that current will spread to adjacent structures is lower than with a monopolar configuration using a distant reference. The practical reality, however, is different. The threshold for bipolar stimulation depends strongly on the orientation of the two contacts with respect to the axis of the nerve.20 Bipolar electrodes are inherently more bulky, making maintenance of a specific orientation difficult in the close confines of the posterior fossa. Monopolar electrodes do not have this disadvantage, and if the stimulus intensity is near the threshold level, can provide spatial resolution of less than 1 millimeter. With any monopolar electrode, the tip should be connected to the cathode of the stimulator; the anodal return can be a clip attached to a retractor or a needle inserted in the periphery of the wound. If a needle is used, it should be placed on the posterior margin of the incision, away from the recording electrodes to minimize stimulus artifact; this is especially important when recording from extraocular muscles, which have small amplitude and short latency responses that can easily be swamped by electrical artifacts. Several types of monopolar electrodes have been described. Møller and Jannetta19 used a short length of malleable wire on a rigid handle with the distal tip bared of insulation. Prass and Lüders21 developed a similar electrode, with the insulation continuous to a flush-tip, which could be bent so that only the central portion of the tip contacted the desired tissue. They showed that this design minimizes

Figure 57-3. Diagrammatic representation of electrode placement for monitoring vestibular schwannoma surgery with attempted hearing conservation. Pairs of needle electrodes are placed in the following muscles: temporalis (V3m), orbicularis oculi and orbicularis oris (CN VII), and trapezius (CN XI). Click stimuli from a small transducer on the chest are fed through a plastic tubing into the ipsilateral ear through a foil-covered sponge insert that also serves as a recording electrode, referred to a needle electrode on the forehead or vertex. An electrocautery ground pad is placed on the arm as a signal ground. A flexible-tip probe is used to stimulate cranial motor nerves, with a needle electrode as the stimulator ground placed in the margin of the craniotomy. (From Jackler RK, Pitts LH: Acoustic neuroma. Neurosurg Clin North Am 1:199–223, 1990. Redrawn for Jackler RK, Brackmann DE: Neurotology. St. Louis, Mosby, 1994.)

the spread of current to adjacent structures. Yingling and Gardi22 developed a probe with a flexible platinumiridium tip, insulated except for a 0.5-mm ball on the end (Fig. 57-4). This electrode can be used to stimulate within dissection planes or even behind the tumor, out of the surgeon’s view, without concern for inadvertently damaging unseen neural or vascular structures (Fig. 57-5). With this probe, the facial nerve can frequently be located electrically even before it can be seen; dissection can then proceed in the most advantageous manner to avoid neural damage. These probes are all used exclusively for stimulation, and thus dissection must be halted each time stimulation is used. Kartush and colleagues20 developed a set of Rhotontype dissecting instruments that are insulated except at the cutting surface. They can be interchangeably connected to the electric stimulator, allowing simultaneous dissection with constant stimulation. Kartush and colleagues20 note that sharp dissection, as opposed to traction or prolonged dissection, may elicit little or no EMG response even if

Intraoperative Monitoring of Cranial Nerves in Skull Base Surgery

Figure 57-4. Flexible-tip probe used for intracranial stimulation. The entire probe and the flexible wire are insulated except for the 0.5-mm ball on the end in order to achieve localized stimulation. (From Yingling C, Gardi J: Intraoperative monitoring of facial and cochlear nerves during acoustic neuroma surgery. Otolaryngol Clin North Am 25:413–448, 1992.)

a nerve is completely transected. These “stimulus dissectors” are particularly useful for removing the last portions of tumor capsule that are closely adherent to a nerve. They can also be used for intermittent stimulation during dissection in other regions. Constant Voltage versus Constant Current The issue of whether constant current or constant voltage stimulators should be used is a source of continuing

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controversy. Transmembrane current is ultimately the effective stimulus for a nerve axon. Constant current stimulators have generally been preferred for transcutaneous stimulation, since the applied current remains constant despite changes in electrode impedance. However, for intracranial stimulation the degree of shunting by blood, CSF, or irrigant may vary widely from one second to the next and thus the same considerations may not apply. Møller and Jannetta19 state the case for the use of constant voltage, rather than constant current, stimulation. Consider a nerve immersed in a conducting fluid. According to Ohm’s law (I = E/R, or current = voltage/resistance), most of the current from the stimulator will flow through the fluid, rather than through the higher resistance neural membrane. To depolarize the nerve effectively, a constant current stimulator may have to be turned up to a relatively high level. If the fluid is suddenly removed (i.e., by suction) or a drier portion of the nerve is contacted, the same total current will flow through and possibly damage the nerve. Conversely, the current delivered from a constant voltage stimulator depends on the resistance of the nerve itself, according to Ohm’s law, independent of the degree of shunting. Paradoxically, the total current delivered varies as the nerve and fluid environment changes, but the current delivered to the nerve itself is more constant with a constant voltage stimulator. Prass and Lüders,21 however, advocate the use of constant current stimulation because their flush-tip probe design eliminates the problem of current shunting by fluids. Kartush and colleagues20 compare bare-tip with flush-tip probe designs and show significantly greater response amplitudes with flush-tip stimulators. Note, however, these latter results were obtained with constant current stimulators; it is not clear whether the same results would be obtained with constant voltage devices. Research in animal models will probably be necessary to finally resolve this issue. Meanwhile, most groups will probably continue using whichever method they have the most experience and feel most comfortable with. Whether constant voltage or constant current is used, the question remains as to what actual level of stimulation is most appropriate. Some argue for a “set it and forget it” approach. However, more useful information can be gained by varying the stimulation intensity in different surgical contexts. Stimulus Duration

Figure 57-5. Surgical view of large vestibular schwannoma (retrosigmoid approach) showing use of flexible-tip probe to locate the facial nerve on the medial surface of the tumor, out of direct view. Tumor is drawn as if transparent to show details of anatomy on the hidden surface. (From Yingling C, Gardi J: Intraoperative monitoring of facial and cochlear nerves during acoustic neuroma surgery. Otolaryngol Clin North Am 25:413–448, 1992.)

Stimulus duration is an important parameter that can affect responses during intraoperative monitoring. Various stimulus durations have been used during intraoperative monitoring and there is still no consensus on which duration is most appropriate. The optimum stimulus duration should provide reliable information to the surgeon while maintaining electrical safety. Selesnick23 conducted a study to determine the optimum stimulus duration to be used in intraoperative monitoring. He suggested that a 50-μs duration would be electrically safer to the nerve. However, animal studies24,25 and extensive clinical experience using currently accepted stimulus parameters26 do not support the assumption that a shorter stimulus duration is electrically safer to the nerve. We recently compared three stimulus durations: 50 μs, 100 μs, and 200 μs during intraoperative

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Figure 57-6. Responses from orbicularis oris after suprathreshold facial nerve stimulation at three stimulus durations. (Vertical lines indicate features picked for quantitative analysis.) Note the more robust response at longer stimulus durations (see text for details).

electrical stimulation of the facial nerve in vestibular schwannoma surgery (Ashram and colleagues, in preparation). The facial nerve was stimulated distally with each duration at the fundus of the internal auditory canal (IAC), after opening the dura and before tumor dissection, and the recorded compound muscle action potential (CMAP) was measured. The mean stimulation threshold decreased by 33.3% as the stimulus duration increased from 50 μs to 100 μs and decreased by 20% as the stimulus duration increased from 100 μs to 200 μs. The mean amplitude of the suprathreshold response increased 48% as the stimulus duration increased from 50 μs to 100 μs, and a further 35% as it increased from 100 μs to 200 μs. The total area of the suprathreshold response increased 43% from 50 μs to 100 μs, and 136% from 100 μs to 200 μs. Therefore, as the stimulus duration was increased, the threshold of the recorded CMAP became progressively lower, and the suprathreshold response amplitude and area under the curve were increased (Fig. 57-6). Since larger responses are easier to detect in real time, particularly when a response to stimulation must be obtained during periods of ongoing tonic EMG activity, the use of a stimulus of 200 μs therefore provides a higher degree of effectiveness and reliability. Recording Electrodes and Patient Preparation Several types of needle electrodes are available for recording EMG activity. The needle electrodes most commonly used in clinical EMG are insulated except at the tip and designed for recording activity from a few muscle fibers. In the context of intraoperative monitoring, however, uninsulated needles are preferred because they have lower impedance and their larger surface area records activity from a larger proportion of the muscle. Of course, in the age of human immunodeficiency virus (HIV), presterilized needles should be used only once and then discarded in an appropriate sharps container.

The recording electrodes are best attached after the patient is anesthetized, positioned on the operating table, and placed in a Mayfield or similar head support if one is used. This avoids both patient discomfort and the possibility of wires being dislodged during positioning. The electrodes must be carefully placed and taped into position so that the leads are directed away from the surgical field and secured so that they do not move during draping. It is desirable to use different colored wires for each muscle. The input connector to the amplifiers should be attached to the head of the operating table so that it moves with the bed as it is raised and lowered during the case. It is placed on the side opposite to the surgeons to allow access in case of intraoperative problems; we use a Mayo stand attached to the bed, which provides a tunnel to the patient’s face for access to the endotracheal tube as well as the electrode input box. The electrode leads should be tightly twisted; this helps cancel undesired pickup of 60 Hz or other electrical noise. Pretwisted electrode pairs in different colors are available from Medtronic Xomed. At this point, patients are typically still paralyzed from the short-acting agent given at induction, and thus no EMG activity will be seen. However, the traces should be quiet, with no excessive 60-Hz activity, which would result from high electrode impedance or an open connection. So-called notch filters, designed to remove only 60-Hz activity, should generally not be employed because they could mask a noise problem that is best corrected. Electrode impedance can be checked at this point, ideally from the recording instrument itself to ensure continuity of the connecting cables as well. This is the time for compulsive system checkout procedures; it may be impossible to replace a bad electrode or repair a connection once the patient has been draped. The layout of the OR setup we use for skull base procedures is shown in Figure 57-7. Electrical Safety A detailed discussion of electrical safety considerations is beyond the scope of this chapter. Most hospitals have a biomedical engineering department responsible for periodic testing of equipment used in patient care to ensure adequate grounding and minimal leakage current delivered to the patient. Monitoring equipment should probably be inspected more often than most clinical equipment, given the potential to deliver dangerous current levels intracranially. Problems might also arise from the interaction of different systems connected to the same patient; such problems must generally be debugged in the actual context in which they occur because they are difficult to anticipate or simulate in the laboratory. Such testing should be entrusted to a competent biomedical engineer.

Cranial Nerve Monitoring: Quality Control In contrast to clinical EMG and evoked potentials, which are performed in a special laboratory, surgical monitoring is done in an electrically hostile environment. Every effort must be made to eliminate or reduce 60 Hz mains interference (50 Hz in Europe), as well as the (frequently broadband) noise originating from OR equipment such as

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can easily be made to match the input of the monitoring equipment. All equipment should be grounded to the same spot with heavy-duty cables in order to avoid ground loops. A detailed analysis of these issues is beyond the scope of this chapter; Møller provides an excellent tutorial.15

Anesthesia

Figure 57-7. Floor plan of operating room setup for posterior fossa craniotomies.

electrocautery, lasers, ultrasonic aspirators, microscopes, anesthesia machines, electrified beds, light dimmers, patient warmers, compression stockings, and so on (the list goes on and on). The 60 Hz notch filters found on most equipment are of limited utility because they remove only 60 Hz sinusoidal activity. More commonly, noise consists of complex spikes that recur at the line frequency but have a high fundamental frequency not affected by notch filters. Every effort must be made to identify such sources and eliminate their interference. This can often be done by grounding these items, plugging them into a different AC outlet, rerouting cables away from monitoring equipment, or even disconnecting them during crucial periods for monitoring. However, it is not always possible to eliminate or even identify some sources of interference (one particularly noisy OR turned out to be upstairs over an MRI scanner; the large pulsatile magnetic fields were of sufficient strength to cause problems a floor away). Techniques for distinguishing residual artifact from physiologic activity are discussed below in Distinguishing Artifacts from EMG. It is also important that the patient be adequately grounded to the recording apparatus through a single cable, with no alternate ground paths. The patient ground should be placed close to the recording electrodes, and care must be taken to obtain a low-impedance ground by removing surface oils with alcohol, then rubbing conductive paste into the skin before applying a ground pad. An electrocautery ground pad works very well because of the large surface area; an adapter

Cortical evoked potentials are notoriously sensitive to many anesthetic agents, so careful adjustment of anesthesia levels is necessary in applications such as spinal cord monitoring with somatosensory evoked potentials. Fortunately, the ABR and EMG responses, which are monitored during skull base surgery, are not significantly affected by any common anesthetics. The major anesthetic consideration is a contraindication to the use of muscle relaxants, since blockade of the neuromuscular junction interferes with monitoring of EMG activity. Two recent reports27,28 have suggested that partial blockade can be used to prevent patient movement without blocking the ability to elicit EMG responses with facial nerve stimulation. However, in our experience, although electrically evoked EMG is relatively preserved, both spontaneous and mechanically elicited EMG activity are obliterated by these agents. This compromises two of the more important indicators of facial nerve injury. Therefore, no paralytic agents should be used during skull base surgery with cranial nerve monitoring, other than shortacting agents given to facilitate intubation. This, however, creates its own problems for anesthetic management since patient movement could have disastrous consequences; it must be prevented by maintaining an adequate depth of anesthesia. Fortunately, since the ABR and EMG are not significantly affected by routine concentrations of common anesthetics, such as nitrous oxide, opiates, and halogenated agents, no other constraints on anesthetic technique are generally necessary. A final note of caution concerns the injection of local anesthetic at the incision site, which presents the theoretical possibility of anesthetizing the facial nerve at the start of the procedure and invalidating subsequent attempts to monitor either spontaneous or stimulus evoked activity. Care must be taken to avoid injection near the stylomastoid foramen to eliminate this problem. Alternatively, since the local anesthetic (usually lidocaine) is used primarily as a vehicle for epinephrine to aid hemostasis, Jones and Mellert29 suggest the use of 1:100,000 epinephrine with no local anesthetic to avoid this problem.

Communication and Report Generation Rapid feedback to the surgeon is necessary if monitoring is to make any practical difference; the neurophysiologist should be stationed where he or she can converse easily with the surgeon. We place the neurophysiologist at the foot of the operating table on the same side as the surgeon, with the scrub nurse on the opposite side of the patient’s head. It is important that noisy instruments such as power drills and ultrasonic aspirators be positioned so that they do not interfere with communication. The surgeon should be able to hear the audio monitor; however, since many extraneous intraoperative events produce audible artifacts,

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the neurophysiologist should inform the surgeon concerning which events are true EMG potentials and which are not. We find it useful for the neurophysiologist to have a small video monitor connected in parallel with the main monitor for the microscope camera. This makes it possible to observe the EMG screen and the operative field simultaneously in order to correlate EMG activity with the surgical events causing it and to keep oriented to the anatomy of different sites being stimulated. Developing precise terminology is very important for communication between the surgeon and neurophysiologist. Each team should agree on a set of terms for using electrical stimulation; we distinguish between search and threshold modes depending on whether a fixed stimulating voltage is to be used to determine whether a motor nerve is within the area being dissected or whether a variable voltage is used to determine the voltage necessary to activate an identified nerve. The exact voltage being used is specified as well, in either search or threshold mode. Detailed notes on the monitoring events are kept on each procedure. The patient’s neurologic status and the nature of the procedure being done are briefly described, together with a specific description of the monitoring setup, including location of recording electrodes, parameters used for stimulation and recording, and so forth. The baseline conditions are described (any spontaneous EMG activity before incision, ABR latencies, etc.). A running log is then kept during the case, with the time noted for major surgical stages (incision, opening dura, retracting cerebellum, etc.) and any monitoring events (mechanically elicited EMG, electrical stimulation, changes in ABR, etc.). The thresholds and ABR parameters are noted at the end of the case and also entered in the surgeon’s operative note. These reports provide a valuable database for retrospective study, as well as the necessary documentation for billing.

FACIAL NERVE MONITORING Vestibular Schwannoma, Other Cerebellopontine Angle Tumors Several techniques for intraoperative facial nerve (VII) monitoring have made their way to clinical use. However, EMG is by far the most widely used technique.15,18–20,22,30–49 There are three distinct ways in which EMG recordings are used to monitor cranial motor nerve activity. First, spontaneous EMG is continuously monitored to detect changes in activity related to mechanical, thermal, or electrical irritation of the nerves by intraoperative events such as retraction,50 tumor dissection, use of electrocautery, lasers,51,52 or ultrasonic aspiration. Second, intracranial electrical stimulation is used to identify and map the course of the nerves with evoked EMG activity. Finally, noting the threshold, amplitude, and latency of evoked EMG responses can help determine the functional integrity of a nerve. Modalities for Facial Nerve Monitoring Prior to the development of EMG techniques in the late 1970s, the facial nerve was monitored visually. Someone

(usually the anesthesiologist or a nurse) watched the patient’s face for movement related to intraoperative events or electrical stimulation. This technique has relatively low sensitivity and would likely leave many traumatic surgical maneuvers undetected. As a result, recent efforts have been directed toward developing more sensitive measures of facial activity. One option for detecting facial nerve activity is to use sensitive detectors of facial motion, employing photoelectric devices, strain gauges, or accelerometers mounted on the face.53,54 A commercial device that utilizes this technique is available.55,56 A paper whimsically entitled “Bells against Palsy”57 describes a low-tech version of this method with small “jingle bells” sutured at points of maximum excursion of the facial musculature. A technique that measures pressure variations in air-inflated rubber sensors placed beneath the upper lip has also been described.45,58 There is controversy about the sensitivity of EMG versus mechanical pressure for facial nerve monitoring. Dickens and Graham59 compared postoperative facial function in three groups of cerebellopontine angle (CPA) surgery cases: those unmonitored, those monitored with mechanical pressure devices, and those monitored with EMG appliances. The authors conclude that by using EMG monitoring, a greater percentage (87%) of cases had normal or near normal facial nerve function as compared to 56% of those monitored by the mechanical pressure device. Uziel and colleagues60 report that 86% of those monitored with a pneumatic sensor during acoustic neuroma surgery had good early postoperative outcome and 94.5% by 1 year postoperative. A recent study compared both EMG and mechanical pressure monitoring techniques.61 The results demonstrate that EMG has a higher sensitivity (lower response threshold) to both electrical and mechanical facial nerve stimulation than mechanical pressure monitoring. However, EMG tends to have more false-positive responses because of current spread from variable electric sources to the electrodes inserted in the facial muscles. In recent years, the old visual method proposed by Krause1 was reintroduced with the application of the new technology of video-analysis. Filipo and colleagues62,63 advocate the use of video monitoring to detect facial movement. Contraction of the zygomatic muscle moves the labial commissure up and back, therefore they used the shifting along a line from labial commissure to zygomatic bone for measurement of facial movement. Zygomatic muscle action was found to have a lower threshold to electrical stimulation in comparison to other facial muscles because it is the only muscle inserted in a bone segment. They also compared video monitoring to EMG63 and found that the responses obtained by the two systems nearly overlapped, confirming the validity of such a method. EMG had a higher sensitivity; however, it was less specific because of false-positive results. They conclude that video monitoring is a reliable method with the advantages of being noninvasive, being easy and quick to set up, and having a natural specificity since it responds only to muscle contraction. Furthermore, it can give evidence for different levels of neural stimulation, thus providing not only qualitative but also quantitative evaluation of responses. A method for recording compound nerve action potentials (CNAPs) from the facial nerve at the stylomastoid

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foramen after intracranial stimulation is described by Schmid and colleagues.64 Conversely, Richmond and Mahla65 utilized antidromic recording (opposite to the normal direction of impulse conduction), by stimulating the distal facial nerve and recording the CNAP from the nerve within the surgical field using a bipolar electrode. This technique was further updated by Colletti and Fiorino,66 using low-intensity stimulation of the mandibular branch of the facial nerve and monopolar recording techniques. The higher intensities used by Richmond and Mahla65 are probably strong enough to activate trigeminal fibers in the stimulated area and require bipolar recording for more selectivity. Methods based on CNAP rather than EMG recording have the advantage that they can be used even if the patient is paralyzed, which prevents coughing and allows the use of lower levels of narcotics or other anesthetic agents. Another advantage is that these methods allow actual continuous monitoring of facial nerve function, in contrast to EMG, which provides information only when the facial nerve is mechanically or electrically stimulated. Therefore other types of injury (such as ischemic) might not be immediately detected. On the other hand, the CNAP cannot be easily made audible for direct feedback to the surgeon and it is not known whether it is sensitive to facial nerve activity due to injury or manipulation of the nerve. Further investigation of these techniques is warranted. Another technique that has been used for facial nerve monitoring is intraoperative recording of nasal muscle F wave.67 The F wave is a late muscle potential that is believed to be a result of recurrent discharge of a small percentage (approximately 1% to 5%) of the motor neurons. It occurs due to antidromic spread of excitation that reaches the motor neurons and then again propagates orthodromically, producing a delayed muscle contraction. It is recorded as a bi- or polyphasic voltage signal that is preceded by a direct (M) muscle response. The intraoperative recording of an F wave should reflect the functional continuity of the facial nerve motor axons from the axon hillock to the motor endplate. Wedekind and Klug,68 in a study on 33 patients with CPA tumors, found that a permanent loss of nasal muscle F wave appears to indicate a severe dysfunction of the facial nerve postoperatively. All patients with latency or amplitude changes or even a transient loss of the F wave achieved good or moderate facial nerve outcomes. Although the F wave may be an appropriate tool for intraoperative facial nerve function, its use has been limited by its sensitivity to anesthesia and the fact that it may be normally absent in healthy adults.69 The remainder of this section focuses on the EMG technique, which is the most common and the one that we have primarily used. Activity Evoked by Electrical Stimulation Use of Stimulation to Identify and Map Nerves in Relation to Tumor Electrical stimulation is used in two main ways: (1) to identify the facial or other cranial motor nerves in relation to the tumor or other pathologic process and (2) to confirm the nerves’ functional integrity. The relations among the

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various cranial nerves in the normal posterior fossa are relatively constant, so identification is not a major problem in cases with relatively undistorted anatomy such as microvascular decompression or vestibular neurectomy. However, the presence of a space-occupying lesion in the posterior fossa may make identification based on anatomical relationships difficult or impossible. For example, with a large vestibular schwannoma, the facial nerve frequently becomes stretched and widened until it is visually indistinguishable from arachnoid; vasculature on the brainstem surface may even be seen through a gossamer-thin yet functionally intact nerve. In such situations, the only way to identify and trace the facial nerve is with electrical stimulation. The procedures used for monitoring during removal of vestibular schwannomas or other similarly placed cerebellopontine angle tumors are illustrative of the general principles of cranial motor nerve monitoring and are easily adapted to other types of cases involving different cranial nerves. Figure 57-3 illustrates the placement of recording electrodes for a 4-channel montage for vestibular schwannoma surgery. As described, two channels are devoted to the facial nerve itself, with electrode pairs placed in orbicularis oculi and orbicularis oris muscles. One of the electrodes in the orbicularis oculi pair is placed at the lateral canthus, where it will also record volume-conducted activity from the lateral rectus muscle (cranial nerve VI). One channel is used to record from the masseter or temporalis muscle (V3m) and the fourth channel is connected to electrodes in the ipsilateral trapezius muscle (XI). The latter two channels serve two functions. First, larger tumors might expand to involve these nerves and thus monitoring could help in their identification and preservation. Second, even with smaller tumors, the extra channels serve as a control for nonsurgical causes of increased EMG activity, particularly light anesthesia. After placement of the electrodes and connection of the equipment, baseline recordings are taken and any spontaneous EMG activity noted. (In hearing-conservation approaches, baseline ABR recordings are also made at this point.) Any problems with electrodes or connections should be identified at this time because troubleshooting becomes more difficult once the patient is draped and the actual operation begins. Sources of 60 Hz interference should be identified and eliminated at this point if possible; 60 Hz notch filters should be used only if necessary. Once the incision is made, high-amplitude interference from electrocautery generally makes it necessary to turn off the audio monitor and suspend ABR collection. Once the craniotomy is completed and the dura opened to expose the CPA, monitoring begins in earnest. Correct functioning of the stimulating and recording system must be confirmed as soon as possible to avoid potentially catastrophic false-negatives. The presence of a stimulus artifact is not an unequivocal test; it is possible to have a stimulus artifact with only one lead (either the anodal return or the cathodal stimulator) connected. However, the absence of artifacts usually indicates an open circuit somewhere in the system. To avoid ambiguity, we try to confirm the operation of the entire system before commencing tumor dissection. In a retrosigmoid approach, the 11th nerve can usually be stimulated at the jugular foramen as soon as the dura has been opened and the cerebellum retracted; an EMG response in the trapezius muscle

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confirms that the system is operating correctly. This confirmation is usually possible before tumor resection begins, except in very large acoustic tumors. We prefer to use monopolar constant-voltage stimulation, stimulating with cathodal pulses of 0.2 ms duration at a rate of 5 to 10 per second. With these parameters, the threshold for an evoked EMG response from normal nerves is usually between 0.05 and 0.2 V, averaging about 0.1 V. (Thresholds reported for constant-current stimulation have ranged from less than 0.1 to 0.5 mA. Yokoyama and colleagues49 report that the spread of current was about 1 mm at 0.5 to 0.6 mA.) If the 11th nerve is not visible at the outset, the stimulating electrode can be placed directly on a muscle and a direct muscular response obtained, although muscle requires higher stimulation levels than nerve. In translabyrinthine procedures, the facial nerve can be stimulated within the mastoid bone in the course of the labyrinthine dissection (before the tumor is exposed), although the threshold will be higher (usually 0.6 to 1.0 V, although up to 2 V may be needed), depending on the thickness of the overlying bone. Once system function has been verified, we then attempt to locate and stimulate the facial nerve. In smaller tumors (CPA component of 1 cm or smaller), the nerve can usually be located at its brainstem entry and an electrical response confirmed before dissection begins. Once a threshold has been established, the voltage is increased to at least 3X threshold and the stimulator swept across the exposed surface of the tumor to confirm that there are no facial nerve fibers before beginning dissection. In larger tumors, the location of the facial nerve may not be immediately apparent. In such cases, we start with 0.3 V and map the accessible region, and if no response is obtained, repeat the search at 0.5 and 1.0 V. If no response is obtained at 1.0 V, it can be safely assumed that the facial nerve is not on the exposed surface and dissection can proceed. The most common site of intraoperative injury to the facial nerve is just medial to the porus acousticus, where it frequently is compressed and flattened against the temporal bone by the tumor, making it difficult to separate the tumor from the nerve without damage. If the lateral region is dissected first, the nerve could be compromised and develop a conduction block in the more distal segment. This can in turn make it impossible to identify it at the brainstem with electrical stimulation. To avoid this problem, we recommend that tumor dissection be done primarily in a medial to lateral direction. It is useful to identify the facial nerve in the IAC relatively early, but extensive dissection of the lateral aspect of the tumor should be avoided at this point. Once the facial nerve is identified at the brainstem and traced as far laterally as possible, with the tumor-nerve interface under direct vision, then the dissection can move to the lateral end, working back toward the mid-CPA until the nerve is freed from both ends. During dissection, the stimulator is used repeatedly to scan the operative field for the presence of facial nerve fibers as the tumor is mobilized, using suprathreshold stimulus intensities as described previously. The flexibletip probe is particularly useful during this phase because it can be used to probe within dissection planes, often allowing identification of the general location of the nerve

before it can be seen directly. The major advantage of the flexible tip is that it can be used to probe areas of the capsule that are out of view on the deep side of the tumor. (The seventh nerve usually courses on the anterior surface of the tumor and the most common surgical approaches are from posterior.) Once a response is obtained, stimulus intensity is reduced to 0.1 to 0.2 V and the responsive region is narrowed. When the nerve is in sight, the electrode is placed directly on the nerve and a threshold is obtained by slowly increasing the stimulus level from zero until a response is obtained. Further stimulation for mapping the location of the nerve is carried out at approximately 3X this threshold, which should be checked periodically as dissection proceeds. The spatial resolution of electrical mapping is determined partly by stimulus intensity, particularly with monopolar stimulation. For the most accurate localization, the stimulus is kept at a relatively low level, as just described. At just suprathreshold levels, the spatial resolution is less than 1 mm, allowing the facial nerve to be easily distinguished from the adjacent vestibulocochlear complex. Conversely, to confirm that the nerve is not in an area about to be cut or cauterized, higher levels of stimulation (up to 1.0 V) are used to reduce the likelihood of false-negatives. As more and more tumor is removed, the course of the facial nerve can be mapped from brainstem to IAC. The nerve may be relatively cylindrical at each end, but it is frequently compressed by the tumor in the CPA and may present as a broad, flat expanse of fibers splayed across the surface of the tumor. Frequently, the only way to identify the nerve and distinguish it from arachnoid tissue is with electrical stimulation. Another advantage of multichannel monitoring is that in larger tumors, cranial motor nerves other than the facial nerve might be encountered in unexpected locations. It is usually possible to distinguish among several nerves and gain more insight into the anatomic relationships by carefully noting the distribution and latency of responses in the various channels as the field is mapped with stimulation. The facial response to stimulation of the seventh nerve in the CPA has a typical onset latency of 6 to 8 msec with an intact nerve. (The exact latency varies depending on the site of stimulation and the condition of the nerve.) Stimulation of the motor fibers of the trigeminal nerve, which are part of the V3 root ( V3m), produces EMG responses in the masseter and temporalis muscles. Since these larger muscles are close to the facial muscles, there is typically considerable cross-talk between channels. Activity elicited by stimulation of nerve VII may be seen in the masseter channel, and that from stimulation of V3m may be seen in facial channels. When only spontaneous or mechanically elicited activity is considered, this cross-talk leads to ambiguity in the identification of the source. With electrical stimulation, however, responses to V3m versus nerve VII stimulation can be readily distinguished from one another by their different onset latencies. Stimulation of V3m produces EMG responses that are of a considerably shorter latency (3 to 4 msec to onset) than those to nerve VII stimulation (6 to 8 msec), allowing these nerves to be distinguished despite overlap in the responding channels. (A mnemonic for remembering this: VII about 7, V less than 5.) Stimulation of the 11th cranial nerve

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produces responses restricted to the trapezius muscle; because of the greater distance, there is generally no crosstalk between channels with stimulation of nerve XI. Finally, the sixth nerve is occasionally encountered in vestibular schwannoma surgery. Stimulation of nerve VI produces a short latency response (≈2 msec) in the lateral rectus muscle, which can be recorded as a small deflection that is volume conducted to the orbicularis oculi channel. Recall that one of the bipolar electrodes in orbicularis oculi is positioned near the lateral canthus to optimize pickup of this response. (The section on Other Motor Nerve Monitoring considers direct recordings from the lateral rectus and other extraocular muscles in cases where the third, fourth, and sixth cranial nerves are more directly involved.) The patterns of response distribution and latency encountered in typical vestibular schwannoma cases are indicated schematically in Figure 57-8.70 Assessment of Functional Status of Nerves following Tumor Removal The primary utility of intraoperative stimulation is in localizing and mapping the course of cranial nerves in relation to CPA tumors. However, electrical stimulation is also used to determine changes in the functional status of these nerves, and it is a useful predictor of postoperative function. Although it is not always possible to obtain threshold measurement at the brainstem before tumor resection, especially of large tumors, it may be of value because it gives an idea about the baseline threshold. Change of

Figure 57-8. Schematic representation of responses obtained in four-channel montage (see Fig. 57-3) with intracranial stimulation of different motor nerves. Despite cross-talk in the fifth and seventh cranial nerve channels, these nerves can be clearly distinguished by the shorter latency of the responses to fifth-nerve stimulation. Stimulation of the sixth nerve produces a short latency response localized to the orbicularis oculi channel, due to volume conduction from the lateral rectus to the electrode at the outer canthus; stimulation of CN XI produces responses restricted to the trapezius (see text for details). (From Jackler RK, Pitts LH: Acoustic neuroma. Neurosurg Clin North Am 1:199–223, 1990.)

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threshold from baseline after an episode of spontaneous activity is a guideline as to whether manipulation has caused a change in the functional status of the nerve. It is the change of threshold rather than its absolute value that is of significance, since no consistent relation was found between tumor size and threshold measurement before tumor by dissection. This was attributed to the variability of compression of the facial nerve by tumors, which is not directly related to tumor size. The volume of the intrameatal rather than the extrameatal tumor may more closely correlate with threshold before tumor removal.71 After total tumor resection, the ability to elicit facial EMG responses by low-threshold stimulation of the seventh nerve at the brainstem is a good but not infallible predictor of postoperative function, since a low threshold may be recorded despite a bad postoperative facial nerve function and high threshold may be obtained despite good outcome. 72–74 Inconsistency between low threshold and poor postoperative function was attributed to (a) the presence of sporadic fibers that are physiologically intact and depolarized in response to low threshold levels in patients in whom the majority of facial nerve fibers had undergone axonal injury or (b) intraoperative events (nerve edema or vasospasm) subsequent to the final threshold measurement, which may affect postoperative facial nerve outcome. On the other hand, the recording of a high threshold despite good outcome may result from nonuniform injury to facial nerve fibers or the presence of fluid in the operative field (cerebrospinal fluid, blood, and irrigation fluid) acting to shunt the stimulating current away from the nerve fibers.75 The amplitude of the CMAP response obtained might also be an indicator of postoperative facial nerve function; Beck and colleagues report that patients who exhibited at least a 500 μV contraction when stimulated with 0.05 mA at the brainstem after tumor removal were likely to have an excellent immediate facial nerve result (grade I or II).76 Conversely, a substantially elevated threshold or the inability to elicit a response with stimulation up to 1 V carries a significant likelihood of postoperative facial dysfunction, particularly in the short run. Mandpe and colleagues report that 89% of patients with an amplitude greater than or equal to 200 μV had a grade I or II early postoperative function, whereas only 41% of patients with an amplitude less than 200 μV had a grade I or II early postoperative facial nerve function.71 Because absolute amplitude is quite variable among patients and may be partially determined by nonspecific factors such as precise electrode placement and amount of subcutaneous fat,32 measures based on amplitude ratios were proposed. Taha and colleagues77 measured the ratio of the amplitude of CMAP produced by stimulating the facial nerve at the brainstem proximally and at the internal auditory meatus near the transverse crest distally after total tumor excision in 20 patients. They found that all patients with proximal-to-distal amplitude ratios greater than 2:3 had grade III or better initial function and grade I final facial nerve function; and all patients with amplitude ratios less than 1:3 had grade IV or worse initial and final facial nerve function. Mandpe and colleagues71 measured the amplitude ratio of the facial nerve stimulation at the brainstem before and after tumor resection, proposing that a large number would suggest an

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intact facial nerve and a low number would indicate few functional facial nerve fibers. However, their data did not uphold these predictions and they found no statistical significance with immediate postoperative facial nerve outcome using these guidelines. It is possible that uncontrolled factors contribute to the high variability among measures obtained before versus after resection; ratios obtained within a short time frame may be more stable and should reflect the proportions of fibers still conducting through the tumor bed. Prediction of long-term rather than short-term facial nerve function is the surgeon’s major concern; it is essential for planning rehabilitative treatment and counseling the patient in a more informed manner.78 It has been suggested that low threshold recorded at the brainstem after tumor resection is a good predictor of long-term facial nerve function;73,79,80,81 however, the ability of threshold to accurately predict long-term function has been questioned.82,83 Recently, Fenton and colleagues84 assessed the predictive factors of long-term facial nerve function in a series of 67 patients undergoing vestibular schwannoma surgery. They suggest that the best predictor of long-term facial nerve outcome is the clinical grade of early postoperative facial function rather than electrophysiologic variables. They also demonstrated that all patients with a recordable EMG response to proximal stimulation after tumor dissection, irrespective of the threshold or amplitude, recovered to a follow-up grade III or better facial nerve function. Although this had been reported previously,71,74,80,85,86 its relevance has been unnoticed. Therefore, it is now accepted that whenever there is a recordable response to electrical stimulations of whatever amplitude or threshold, the facial nerve is most likely to show signs of improvement with follow-up and intervention is therefore not recommended within the first year.84 On the other hand, the absence of response to stimulation at the end of surgery does not doom the patient to a bad outcome. If the nerve is anatomically preserved, even with an immediate postoperative palsy, there is still a good possibility of eventual return of function as functional nerve fibers regenerate. Partial recovery of function in patients with unrecordable responses after surgery has been reported.87 The earlier the onset of recovery the better its quality; however, if there is no evidence of recovery at 12 months, then it is unlikely.88 Intraoperative Identification of the Nervus Intermedius Anatomic identification of the nervus intermedius during CPA surgery may not be a straightforward task. Although the nervus intermedius usually crosses the CPA as a single trunk passing between the seventh and eighth cranial nerves, it may sometimes be composed of as many as four rootlets and may cling to the eighth nerve in the CPA, then gradually cross between the eighth and seventh nerves as it approaches the internal auditory meatus.89 From our experience (Ashram and colleagues, submitted for publication), electrical stimulation of the nervus intermedius during CPA surgery produces a characteristic response in the orbicularis oris channel only: long latency, low amplitude, and higher in threshold than the facial nerve response (Fig. 57-9). It is important to recognize the nervus intermedius response during electrical stimulation

Figure 57-9. Responses in orbicularis oris to stimulation of nervus intermedius (top) and facial nerve (bottom). Note that the n. intermedius response is smaller, of longer latency, and seen only in the lower facial nerve channel. (From Ashram and colleagues, submitted for publication.)

and to avoid confusing it for a facial nerve response since both are recorded from the orbicularis oris channel (the facial nerve–monitoring channel). Initial confusion between the nervus intermedius and a facial nerve strand at the time of stimulation may occur since the whole course of the facial nerve may not be visible by the surgeon because it courses anterior to the tumor and most common surgical approaches are from posterior. Furthermore, tumor growth causes the facial nerve to be stretched and widened so it often cannot be identified as a solitary trunk but rather a wide ribbon. Knowledge of the electrophysiologic features of nervus intermedius stimulation can help protect the facial nerve during CPA surgery. The surgeon must recognize that stimulation of the nervus intermedius can cause EMG activity in the facial nerve–monitoring channels (at least in the orbicularis oris), but that the main trunk of the facial nerve may lie in an entirely different location within the CPA (Fig. 57-10). It is imperative for the surgeon to locate the facial nerve itself by stimulation to protect this critical structure. Misidentification of the nervus intermedius response can lead to inadvertent injury of the facial nerve by dissection in other areas if stimulation is not used in the mistaken belief that the facial nerve has already been located. Avoiding this pitfall may be the most important reason for knowing the characteristics of the nervus intermedius response. Spontaneous and Mechanically Elicited Activity EMG responses to intracranial stimulation are the most specific indicators of cranial nerve localization and functional status. However, spontaneous EMG activity and mechanical EMG responses related to intraoperative events are also useful in preserving neural function. As the facial nerve is compressed by a growing tumor, local irritation of nerve fibers as well as demyelination can occur, resulting in increased sensitivity to mechanical stimulation and early

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A

B

C

D

generation of spontaneous activity.47,90 This abnormal activity is attributed to an increase of sodium channels, which occurs in compressed nerve fibers.91 Removal of a tumor that is adherent to the facial nerve thus results in a clear and strong EMG activity that can give a prompt warning to the surgeon to stop or modify manipulation. Some patients, particularly those with significant preoperative facial deficits, have a baseline tonic facial EMG activity; this often decreases as the nerve is decompressed with opening of the dura and draining of CSF. Virtually all patients exhibit some mechanically evoked facial EMG activity during tumor dissection, retraction, irrigation, or other intraoperative events. An increase in EMG activity associated with a particular surgical maneuver is often the earliest indicator of the location of the facial nerve. When such activity is elicited, the stimulator should then be used to search the area in question to positively identify the nerve if possible. Frequently, operative manipulations elicit EMG activity even if the nerve is not in the immediate areas as a result of traction or pressure being transmitted to the nerve from the tumor. In such cases, a negative response to electrical stimulation indicates that dissection can proceed. In other cases, stimulation following mechanically elicited activity results in identification of the nerve, which can then be localized precisely, as described previously. Finally, ongoing EMG activity is often an indirect indicator of depth of anesthesia, which is of particular concern when no muscle relaxants can be used. A simultaneous increase in spontaneous EMG activity on all channels is unlikely to result from localized dissection. When such a generalized increase occurs, the anesthesiologist should be notified immediately; overt patient movement often occurs within a few seconds.

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Figure 57-10. Anatomic variants in the relationship between nervus intermedius and the facial and vestibulocochlear nerves. A, N. intermedius joining the cranial nerve VII/VIII complex near the brainstem root’s entry zone. B, N. intermedius joining cranial nerves VII and VIII in mid-cerebellopontine angle. C, N. intermedius joining CNs VII and VIII near the porus acousticus. D, N. intermedius taking a separate course through the CPA, where it can be misidentified as the facial nerve unless its unique response characteristics are recognized. (From Ashram and colleagues, submitted for publication).

Distinguishing Artifacts from EMG Most of the activity encountered on the monitor screen or loudspeaker is artifactual, rather than representative of true muscle activity. There are numerous sources of intraoperative artifact, and it is important to distinguish artifact from true EMG. Some artifacts are obviously associated with electrocautery equipment, ultrasonic aspirators, lasers, drills, and so on, and can be readily identified by their appearance during use of these devices and generally large amplitude. Such artifacts should be rejected from the audio monitor by use of interlock devices or squelch circuitry, which mutes the audio if signals above a preset threshold are encountered. More troublesome are smaller artifacts produced by bimetallic potentials due to contact between surgical instruments made of different metals; since these may be associated with intraoperative events similar to those producing true EMG responses, they can be difficult to distinguish (Fig. 57-11). Some useful criteria include the fact that artifacts are typically higher in frequency content than EMG and thus sound more “crackly” than true EMG, which has more of a “popping” sound; and the tendency for artifacts to appear simultaneously on several channels, which is unlikely with EMG. Experienced monitoring personnel are in a better position to make such decisions than surgeons who are focused on the operative field. Patterns of Mechanically Evoked EMG Activity Prass and Lüders18 distinguished two types of EMG activity associated with intraoperative events. They suggested that the phasic “burst” pattern, characterized by short, relatively synchronous bursts of motor unit potentials, corresponded to a single discharge of multiple facial nerve axons.

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A

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C Figure 57-11. A, Artifact produced by contact of different metallic instruments in the surgical field. Note the sharp edges on waveforms (top) with exponential decay (may be confused with spike activity). Single EMG spike (bottom) with a low-amplitude EMG background and no exponential decay. B, Regular sinusoidal artifact (top) produced during drilling of the IAC. Irregular EMG activity (bottom) occurring while drilling the IAC. C, Regular artifact with two time scales, 200 msec/cm and 5 msec/cm (top two traces). EMG activity on the same two time scales (bottom two traces). At 200 msec/cm, it can be difficult to differentiate between true EMG activity and artifact. However, with the faster 5 msec/cm time base, trace 2 shows that the artifact waveform is regular and synchronized while trace 4 reveals the irregularities that characterize true EMG activity.

This type of activity was elicited by direct mechanical nerve trauma, free irrigation, application of pledgets soaked with lactated Ringer’s solution over the facial nerve, or electrocautery, and could be easily associated with such events. The second pattern, tonic or “train” activity, consisted of episodes of prolonged asynchronous grouped motor unit discharges, which could last up to several minutes. These were most commonly associated with facial nerve traction, usually in the lateral-to-medial direction. They further divided such train activity into higher-frequency trains (50 to 100 Hz), dubbed “bomber potentials” due to their sonic characteristics, and lower-frequency discharges (1 to 50 Hz), which were more irregular and had a sound resembling popping popcorn. The onset and decline of “popcorn” activity was more gradual than the more abrupt onset and decline of “bomber” activity. More recently, Romstock and colleagues92 classified train activity into three distinct patterns: A trains are characterized by a sinusoidal symmetrical sequence of high-frequency and low-amplitude signals that have a sudden onset; B trains are regular or irregular sequences of repeated spikes or bursts with maximum intervals of 500 msec; and C trains are characterized by continuous irregular EMG responses that have many overlapping components. Whereas B and C trains did not correlate with postoperative function, the authors suggested a relation between the occurrence of “A trains” and poor postoperative facial nerve function. Nakao and colleagues93 classified train activity that occurred during the last stage of tumor resection into an irritable pattern with frequent EMG responses to the slightest stimuli; a silent pattern with few or no EMG responses; a stray pattern with persistent train responses up to 20 minutes despite temporary discontinuance of surgical manipulation; and an ordinary pattern related to mechanical stimulation of the nerve but not easily elicited. They found an association between the occurrence of silent or stray EMG patterns and poor postoperative outcome. Figure 57-12 shows samples of types of EMG activity often encountered in vestibular schwannoma removal. In Figure 57-12A, a dense tonic activity has a sinusoidal pattern. Such activity often results from retraction or rotation of the tumor, and presumably reflects stretching of the nerve. Figure 57-12B shows a less intense pattern of tonic activity, with repetitive bursts often described as “popcorn” activity. Figure 57-12C shows a single transient burst, often associated with specific intraoperative maneuvers involving direct contact with the nerve. Such events are relatively common and generally do not imply significant damage unless they are of large amplitude and occur during critical stages of dissection. Finally, Figure 57-12D demonstrates burst activity superimposed on ongoing background EMG activity. It is important to recognize such events overlapping on background activity because they may pass unnoticed despite their significance. Recall that tonic EMG activity can be observed even in baseline recordings, particularly in larger tumors where there is significant compression of the facial nerve. A high level of tonic activity complicates the detection of changes in EMG associated with intraoperative events, as well as the use of stimulus-evoked EMG for nerve identification and mapping. As discussed, the use of multiple channels

Intraoperative Monitoring of Cranial Nerves in Skull Base Surgery

Figure 57-12. Examples of three types of EMG activity often seen during vestibular schwannoma surgery. A, Dense tonic (sustained) activity, often associated with nerve stretch and having a sinusoidal pattern. B, Lower tonic activity, called popcorn activity. C, Phasic (transient) burst activity, typically associated with direct contact with the nerve. Such events are not of major significance unless they are of large amplitude and occur during critical stages of dissection. D, Burst activity superimposed on ongoing small-amplitude train. It is important to recognize such events overlapping on background activity because they might pass unnoticed despite their significance.

helps in identification of changed patterns of tonic activity or of stimulus-evoked activity. Can Mechanically Evoked EMG Activity Predict Postoperative Outcome? Prass and Lüders18 suggested that episodes of “burst” activity were probably due to the mechanoreceptor properties of nerve axons, since they tended to be directly associated with intraoperative compression of the facial nerve. Such mechanically evoked activity was thought to be distinct from injury discharges and to have no necessary relationship to nerve injury. They further pointed out that the ability to elicit burst activity with mechanical stimuli indicates functional integrity of the nerve distal to the site of stimulation, and that a trend of decreasing burst activity despite continued mechanical stimulation may indicate nerve injury has already occurred. In contrast, they argued that frequent and prolonged “train” responses, especially of the “bomber” type, were more likely to be associated with either nerve ischemia or prolonged mechanical deformation and thus possibly correspond to injury potentials and poor postoperative function. In fact, the “bomber” pattern is one familiar to cellular

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neurophysiologists, who recognize it as the “swan song” of dying neurons. Daube and Harper32 described cases in which prolonged train activity was associated with both inability to electrically stimulate the nerve after tumor removal and lack of postoperative facial motility. Nakao and colleagues94 analyzed train activity in a series of 51 patients and compared responses with postoperative outcome. Their results were promising but somewhat disconcerting. They found low-amplitude train activity to be of little concern, because 17 of 18 patients with this pattern had relatively good postoperative function. On the other hand, high-amplitude activity (more than 250 μV) was associated with severe facial nerve dysfunction. However, no definite conclusion was reached, because seven of nine patients with no train activity also showed severe facial nerve dysfunction, implying that some events that are detrimental to facial nerve function do not elicit EMG activity. Romstöck and colleagues92 could not demonstrate a significant relationship between amplitude of EMG potentials and postoperative outcome and therefore resorted to waveform pattern (described earlier) as a main criterion for predicting new postoperative motor deficits. In a series of 50 patients operated on for vestibular schwannoma, we have recently reviewed the effect of tumor size on the response of the facial nerve to mechanical stimuli, and whether the prognostic value of burst and train activity could be redefined based on tumor size (Ashram and colleagues, in preparation). Patients were divided into two groups based on tumor size: group A consisted of 33 patients with tumor size less than or equal to 3 cm and group B consisted of 17 patients with tumor size greater than 3 cm. Small-amplitude burst activity occurred in 100% of patients in both groups. Small-amplitude train activity occurred in 88% of group A and 76.5% of group B patients. As for large-amplitude activity, we found that in group A (smaller tumors) large-amplitude trains occurred during dissection in 5.2% of patients with good outcome, 75% with moderate outcome, and 100% of patients with poor outcome and were significantly correlated to postoperative outcome. In group B (large tumors), large-amplitude train activity occurred in 33% of patients with good outcome, 50% of patients with moderate outcome, and 42% of patients with poor outcome (stated differently, there was no relation between large-amplitude trains and outcome in patients with large tumors). When the prognostic value of spontaneous activity was assessed in groups A and B combined, we failed to find a relation between large-amplitude spontaneous activity and postoperative outcome. These data illustrate several important points. First, in small tumors where the nerve is more responsive to mechanical stimuli, large-amplitude spontaneous activity during dissection was significantly related to poor postoperative facial nerve outcome; therefore, their occurrence suggests injury to the facial nerve. The surgeon should be warned promptly and consider changing the surgical technique. On the other hand, in large tumors, there was no correlation between large-amplitude spontaneous activity and postoperative outcome. Large tumors result in significant facial nerve compression. The nerve axons become stretched, partially damaged, and less responsive than healthy ones, therefore producing little EMG activity

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despite significant manipulation.95 Second, the absence of large-amplitude spontaneous activity in patients with large tumors is not always an indication of safe dissection, so spontaneous activity is not a reliable a criterion for warning the surgeon in this group. Thus, frequent use of electrical stimulation in large tumors is important to map the tumor surface and measure thresholds, which can give an idea about the condition of the nerve. Third, in five patients (in group A and B) there was large-amplitude spontaneous activity recorded during the early stages of tumor resection; however, at the final stage of resection, spontaneous activity tended to be less frequent and of low amplitude despite significant surgical manipulation of the facial nerve. This decline in burst activity may give a false sense of security, causing more vigorous dissection with the possibility of permanent damage to the nerve. Therefore, the change of pattern of EMG from a responsive to a silent one should be considered an ominous sign signifying a certain degree of nerve injury. Fourth, the occurrence of burst or train activity of small amplitude, although not of major concern, does indicate the proximity of the facial nerve to the region of dissection. Fifth, the failure to find a significant relationship between large-amplitude burst and train activity when groups with small and large tumors were combined explains the discrepancy between our data and previous studies that could not reach a consensus about the prognostic value of spontaneous activity. Limitations of Electromyography Despite the wide use of intraoperative EMG monitoring, it still has its limitations. A major problem with EMG is its relatively low specificity. EMG channels can easily pick up artifacts, and the distinction between them and true EMG may sometimes be difficult. During electrocautery, EMG becomes virtually useless, when the facial nerve is at high risk. Attempts to reduce the artifact from bipolar cautery have met with limited success, since such devices generate high-amplitude, broadband noise that is difficult to filter out. Techniques based on detection of motion, which are not subject to electrical interference, such as video monitoring, may provide an important adjunct to EMG monitoring despite their relatively lower sensitivity. In our experience, the practical way to deal with this problem is to use electrical stimulation before bipolar electrocoagulation to confirm that the area to be cauterized is free from facial nerve fibers. The absence of a response to higher levels of electrical stimulation (up to 1 V) in an area about to be cauterized is an indication that electrocautery can proceed safely. Another problem with EMG is that facial nerve integrity with stimulation cannot be assessed unless the nerve is accessible in the surgical field. However, with large tumors the facial nerve is at risk of being traumatized before it is visually apparent to the surgeon, and it may not be responsive to mechanical manipulation. In this situation, the facial nerve location can be anticipated by using a flexible-tip probe to stimulate within dissection planes or even behind the tumor, out of the surgeon’s view, without concern for damaging unseen vascular or neural structures. The development of continuous facial nerve monitoring methods that do not rely on visual identification of the nerve remains one of the major challenges for future research.

Microvascular Decompression Jannetta96 first demonstrated that many cranial nerve dysfunctions can be caused by compression of the nerves by vascular loops and can be treated by moving the offending vessel off the nerve and placing a soft cushion between it and the nerve. This technique, known as microvascular decompression, is now widely used for treatment of conditions such as trigeminal neuralgia and hemifacial spasm. Since these procedures involve possible damage to cranial nerves in the posterior fossa, EMG and ABR monitoring techniques are frequently used97 with the same procedures described elsewhere in this chapter. In the specific case of microvascular decompression for hemifacial spasm (HFS), however, a different procedure has been described by Møller and Jannetta.44 This method is based on the finding of an abnormal muscle response in patients with HFS, in whom muscles innervated by one branch of the facial nerve respond when another branch is stimulated. This response is caused by abnormal spread of activity from one branch on the facial nerve to another on the affected side. Since it is not suppressed by anesthesia, it can be recorded intraoperatively as long as the patient is not paralyzed. For a typical procedure, recording electrodes are inserted into the mentalis muscle (innervated by the marginal mandibular branch of VII) and the orbicularis oculi (temporal branch). Subdermal needle electrodes are also inserted adjacent to the marginal mandibular and temporal branches of VII for stimulation. Note that the stimulation voltage required is higher (4 to 20 V ) than for direct stimulation of the nerve intracranially. Figure 57-13 shows typical results from such a procedure. In Figure 57-13A, the upper channel shows the normal response in orbicularis oculi to stimulation of the temporal branch, before microvascular decompression; note the short latency (≈3 ms) due to the peripheral site of stimulation. The lower channel of Figure 57-13A shows the abnormal response in mentalis at a latency of ≈9 ms; this reflects the time taken for the response to travel antidromically to the intracranial site of the abnormal crossover and back out again. Figure 57-13B, recorded a few minutes after removal of the offending vessel, illustrates the loss of the abnormal mentalis response while the normal orbicularis oculi response is unchanged. If the abnormal response is not seen at the outset, it can generally be triggered by a brief train of stimuli at a high frequency (50 Hz). The amplitude of the abnormal response is typically lower than that of the normal response, and may drop even further after opening the dura, presumably because of a shift in the relation of the vessel to the nerve. Nevertheless, an abnormal response at some amplitude can generally be seen until the nerve is decompressed; Møller and Jannetta44 recommend that the decompression be carried out until no abnormal response can be seen. They state that the abnormal response disappears immediately when the offending vessel is removed from the nerve, a finding also reported by Halnes and Torres,33 although in our experience it may take a few minutes for the abnormal response to disappear completely. Intracranial stimulation as described previously can of course also be used to ensure the integrity of the facial nerve in procedures for HFS.

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(zygomatic), upper orbicularis oris (marginal mandibular), and mentalis (buccal). The pattern of responses obtained with electrical stimulation can be used to determine which branch is being stimulated; methods for recording both mechanically elicited activity and responses to electrical stimulation are similar to those used intracranially; however, note that since the intracranial portion of the facial nerve lacks the thick epineurium found distally, thresholds within the parotid gland are typically higher than those in the posterior fossa. More information can be found in Schwartz and Rosenberg.99

Middle Ear Surgery

Figure 57-13. Responses during intraoperative monitoring of microvascular decompression for hemifacial spasm. Stimulating electrodes are in the temporal branch of the facial nerve; recording channels are in orbicularis oculi (top) and mentalis (bottom). A, Before decompression: abnormal response at prolonged latency in mentalis to stimulation of temporal branch. B, After decompression: abnormal response in mentalis is no longer seen and normal response in orbicularis oculi is unchanged.

Hatem and colleagues98 evaluated the prognostic value of the persistence or suppression of the abnormal muscle response at the end of microvascular decompression of the facial nerve in 33 patients with HFS. Their results question the prognostic value of abnormal muscle responses; clinical cure was observed whether or not the abnormal muscle response disappeared at the end of surgery. More work is necessary to firmly associate persistence or disappearance of the abnormal muscle response to ultimate clinical outcome.

Parotidectomy Detailed consideration of facial nerve monitoring for parotidectomy is outside the scope of this chapter. Briefly, the idea is to use as many EMG channels as are available to record from different peripheral branches of the facial nerve, distal to the pes anserinus. A typical 4-channel montage might include closely spaced bipolar electrode pairs in frontalis (temporal branch of VII), lower orbicularis oculi

Although facial nerve monitoring has become accepted as the standard of care in CPA surgery, its use in middle ear surgery is still controversial. In 1994 Roland and Meyerhoff 100 surveyed all members of the American Otological Society and American Neurotology Society regarding the routine use of facial nerve monitoring for all tympanomastoid surgery; 4% of respondents thought that facial nerve monitoring should be used for all tympanomastoid surgery, whereas 95% believed it should be reserved for procedures that entail a high risk of facial nerve injury. The odds of iatrogenic injury of the facial nerve increase when the normal anatomic landmarks of the temporal bone are altered. Previous surgery, granulation tissue, and cholesteatoma distort the normal anatomy and place the nerve at a higher risk of injury. Facial nerve dehiscence is an additional factor that renders the nerve more vulnerable. Moreano and colleagues,101 in a histopathologic study of 1000 temporal bones without evidence of middle ear disease or inflammation, found that 56% presented with at least one facial nerve dehiscence. Selesnick and Lynn-Macrae,102 in a study on 67 surgical procedures for cholesteatoma, found facial nerve dehiscence in 33%, twice the rate found in an older study by Sheehy and colleagues,103 underscoring the fact that this is an underestimated finding. Noss and colleagues104 suggested that the electrical stimulation threshold of the facial nerve is more reliable in identifying a facial nerve at risk than surgical observation alone. In their series of 262 cases, the surgeon judged the nerve to be dehiscent in 13% of the cases. This figure is comparable to other estimates by surgical observation in the published literature, but is much less than that observed by histologic and light microscopy. The discrepancy may be explained in part by the limited view of the surgeon during surgery. Usually, direct surgical view of the facial nerve is available only for the lateral surface of the tympanic portion and the second genu; the oval window surface of the nerve with the highest incidence of dehiscence is not always visible. The authors found that a facial nerve stimulation threshold of less than 1 V identifies a nerve that is electrophysiologically dehiscent and thus should be considered at increased risk of injury. With this criterion, there was a 62% incidence of electrophysiologic dehiscence in their series, in good agreement with anatomic studies. The assessment of risk versus cost of cranial nerve monitoring in middle ear surgery and mastoid surgery was not directly addressed by this study and will require additional clinical research.

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Facial Nerve Preservation Several studies have compared postoperative facial nerve function in series of cases with and without facial nerve monitoring. Leonetti and colleagues41 compared 23 unmonitored with 15 monitored infratemporal approaches to the skull base, all of which involved rerouting of the facial nerve in the temporal bone. In the unmonitored group, 11/23 (48%) showed a poor outcome (House grade V or VI facial palsy) at discharge. None of the monitored group fell into this category, whereas 12/15 (80%) had a good outcome (House grade I or II). Niparko and colleagues47 reported outcome for 29 monitored and 75 unmonitored translabyrinthine vestibular schwannoma removals. A nonsignificant trend for better facial function in the monitored group was seen at the end of the first postoperative week. At 1-year follow-up, satisfactory facial function was significantly associated with monitoring (p < 0.05). This effect was only significant for tumors larger than 2.0 cm, although there was a nonsignificant trend (p = 0.08) in the same direction for smaller tumors. Kwartler and colleagues39 compared a group of 89 monitored translabyrinthine vestibular schwannoma removals with an unmonitored group of 155 cases and reported better facial function at both immediate and 1-year follow-up in the monitored group, although the results were not statistically significant at 1-year; the difference was found only for larger tumors (>2.5 cm). Hammerschlag and Cohen34 reported a 3.6% incidence of facial paralysis in 111 consecutive CPA cases with EMG monitoring compared with 14.7% in 207 previously unmonitored cases. Harner and colleagues35 reported outcome data from 91 consecutive vestibular schwannoma removals with facial nerve monitoring. The unmonitored control group consisted of 91 patients, selected from a larger pool of 173 to match the monitored group on the basis of (in order): (1) tumor size (median 3 cm); (2) year of operation; and (3) age (median 54 yr). The facial nerve was anatomically preserved in 92% of the monitored group and 84% of the unmonitored group, a nonsignificant difference. However, at 3 months, 46% of the monitored and 20% of the unmonitored group had normal (grade I) function; 15% of the monitored and 35% of the unmonitored group had a grade VI palsy. At 1 year, 45% of the monitored and 27% of the unmonitored group had no deficit (grade I), while only 2% of the monitored but 6% of the unmonitored group had no facial function whatsoever (House grade VI). Several features have become apparent from such studies. First, most series report a good outcome in the majority of cases, regardless of whether monitoring was employed. Second, there is a higher incidence of grade I or II outcomes and a lower incidence of grade V or VI in the monitored cases. It is evident that although there is a small increase in the proportion of subjects with good outcomes (grades I or II), the main effect of monitoring was to greatly decrease the incidence of poor outcomes (grades V or VI). This undoubtedly reflects the relative ease of locating and preserving the facial nerve in smaller tumors, and thus the greater impact of monitoring on larger tumors where the nerve is more likely to be stretched and distorted and thus more difficult to identify on anatomic criteria alone.

A potential confound in all such studies is the fact that the unmonitored cases were operated on earlier than the monitored ones; it is thus arguable that the improvements in outcome could be due simply to the surgeons’ greater experience. However, Harner and colleagues35 note that part of the surgeons’ technical improvement is a direct result of the advent of monitoring. As surgeons become more aware of maneuvers that produce EMG discharges, they naturally adapt their operative technique to avoid such maneuvers as much as possible. Intraoperative monitoring may thus contribute to improved cranial nerve preservation in more than one way. A quote from Harner’s paper typifies the attitude of most surgeons who have used intraoperative monitoring: “I don’t think I could convince anybody at our institution (the Mayo Clinic) with experience to give up monitoring under any circumstances.” Similarly, the surgical team at UCSF refuses to schedule a vestibular schwannoma operation unless cranial nerve monitoring is available; our results show a 99.2% anatomic preservation of the facial nerve with the use of EMG monitoring.73 As noted earlier, the NIH consensus conference on vestibular schwannoma12 concluded “The benefits of routine intraoperative monitoring of the facial nerve have been clearly established. This technique should be included in surgical therapy for vestibular schwannoma.” In summary, facial nerve monitoring for vestibular schwannoma surgery is now clearly established as the standard of care. While less formal data is available concerning monitoring of other cranial motor nerves, the techniques and applications are virtually identical and should have similar benefits. The same NIH consensus panel concluded “Routine monitoring of other cranial nerves should be considered.” It is thus unequivocally recommended that EMG monitoring with as many simultaneously recorded channels as necessary be employed during any skull base surgery in which cranial motor nerves are at risk.

OTHER MOTOR NERVE MONITORING Extraocular Muscles Monitoring of the oculomotor (III), trochlear (IV), and abducens (VI) nerves, which innervate the various extraocular muscles, is frequently necessary in surgery for more anterior skull base lesions. These may include, for example, cavernous sinus tumors, prepontine tumors, or petrous apex lesions with a significant anterior or medial extension. The basic principles are the same as for facial nerve monitoring; however, the relative inaccessibility of the target muscles causes special difficulties. Latency Criteria to Distinguish Nerves VI and VII Because of its relative proximity to the vestibulocochlear and facial nerves, the abducens nerve (VI) is probably the most frequently encountered of these three nerves in neurotologic surgery, since it may be seen during removal of moderate to large vestibular schwannomas. In this context, there may not be an electrode already placed in the lateral rectus muscle. Nevertheless, it is generally possible to identify VI with electrical stimulation by careful observation of

Intraoperative Monitoring of Cranial Nerves in Skull Base Surgery

the distribution and latency of electrically evoked responses. As described previously, the electrodes for monitoring the upper branches of the facial nerve are placed in the orbicularis oculi muscle in such a way that one electrode of the pair is near the outer canthus. This electrode is close enough to the lateral rectus muscle that it can pick up activity from the lateral rectus by volume conduction. Of course, since this electrode pair also responds to stimulation of the facial nerve, it is necessary to determine whether a response is due to stimulation of VI or VII. The easiest criterion is latency; the response from stimulation of VI generally has an onset of 2 to 3 msec, in contrast to 6 to 8 msec for the facial nerve. The response can only be seen in the orbicularis oculi channel, whereas stimulation of VII typically produces responses in both orbicularis oculi and orbicularis oris. Finally, the amplitude of the volume-conducted response from VI is typically much smaller than the direct response from orbicularis oculi. Despite the general utility of these criteria, they are not 100% foolproof. A sixth nerve that has been significantly stretched by the tumor or damaged during dissection may not conduct as rapidly, causing an increased latency. Similarly, a damaged seventh nerve may produce a response in only the upper channel, and the response may be of low amplitude, thus mimicking a VI response. In vestibular schwannoma surgery, the distinction between VI and VII is usually clear on anatomic criteria. However, in cases that more directly involve cranial nerves III, IV, and VI, it is desirable to achieve more specificity by direct recording from the extraocular muscles.

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Figure 57-14. Placement of electrodes in extraocular muscles for monitoring cranial nerves III, IV, and VI. Electrodes are inserted through closed eyelids (drawn as if transparent), against the inner surface of the bony orbit, to record from inferior rectus/inferior oblique (CN III), superior oblique (CN IV), and lateral rectus (CN VI). (See text for details.)

Placement of Electrodes for Monitoring Extraocular Muscles Clinical electromyography of the extraocular muscles is generally performed with fine-gauge monopolar or bipolar needles from 2.5 to 4 cm long, insulated except at the tip. These long electrodes are necessary to reach the belly of the muscles for single muscle unit recording. However, such recordings are typically performed for brief periods in awake patients. During prolonged surgery under general anesthesia, however, significant safety considerations argue against the use of such long needles where they cannot be visualized. Fortunately, for monitoring purposes, it is not necessary to record directly from the belly of the extraocular muscles; thus, shorter electrodes that are easier to insert and that carry less risk of inadvertent perforation of the globe can be employed. Although good results have been obtained with subdermal EEG electrodes, paired hook wire electrodes are preferred for this purpose because they are flexible and less likely to traumatize the eye; the bipolar recordings obtained have greater specificity than referential recordings to noninsulated needles. The hook wire electrodes are inserted through the eyelids near the tendons of the target muscles, where they pick up volume-conducted activity from the muscles themselves (Fig. 57-14). The tendons are attached to the globe about 0.5 to 1.0 cm from the margin of the cornea. All that is required for selective monitoring is to place the electrodes where they will respond to stimulation of only one specific nerve. Depending on the specific muscle, this may be easier said than done.

The oculomotor nerve (III) is perhaps the easiest from which to obtain specific responses because it innervates all of the extraocular muscles except the lateral rectus and superior oblique. Placement of an electrode at the infraorbital margin, roughly one-third of the distance out from the inner canthus, results in pickup of activity from the inferior oblique and/or inferior rectus muscles, both of which are innervated by nerve III (see Fig. 57-14). The lower rim of the orbit should be palpated through the eyelid; the infraorbital foramen can generally be felt and the electrode inserted slightly medially. The hook wire electrodes are inserted from just above the rim with a hypodermic needle angled downward so that it can be felt to slide along the bony floor of the orbit. After insertion to the desired depth, the needle is removed while the wires are held in place and taped to prevent movement. Similarly, activity in the lateral rectus muscle, innervated by the abducens nerve (VI), can be detected by an electrode inserted from the lateral canthus and angled so that the inserting needle can be felt to slide along the inside of the lateral wall of the orbit. As long as the electrode remains at the lateral margin of the orbit, any EMG responses obtained will be specific to nerve VI activity, since there are no other extraocular muscles in this area. The trochlear nerve (IV) is the most difficult to monitor because the superior oblique muscle does not connect to the eyeball in the same straightforward fashion as the other extraocular muscles. The superior oblique arises

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medially from the body of the sphenoid bone and runs along the medial wall of the orbit almost to the margin, superior to the medial rectus. Near the orbital margin its tendon passes through the fibrous trochlea and then bends posteriorly at an acute angle to attach beneath the superior rectus muscle on the lateral side of the upper surface of the eyeball. Attempts to place an electrode near the tendon insertion would thus result in pickup from the superior rectus (III) and give erroneous indications. On the other hand, attempts to place an electrode near the belly of the muscle are likely to result in pickup of activity from the medial rectus and again give erroneous readings in the fourth nerve channel with third nerve activity. There is no easy solution to this problem. The best compromise is to place an electrode along the superior orbital ridge, about one-quarter out from the inner canthus, and angled upward and medially so that it ideally passes the tendon of the superior oblique with the tip near the superior oblique muscle itself. The supraorbital foramen can be palpated and used as a rough landmark, with the electrode inserted slightly medially (see Fig. 57-14). It should be recognized that as a result of cross-talk among the extraocular muscles, identification of the specific nerve giving rise to spontaneous or mechanically elicited EMG activity might be difficult. Stimulus-evoked activity, where the anatomic relations among the nerves and other intracranial structures can be used as additional indicators, might have greater specificity. The latency of responses in the extraocular muscles to stimulation of the third, fourth, or sixth nerves is typically 2 to 3 msec, much shorter than that of responses to stimulation of the seventh nerve. This short latency helps prevent confusion of true III, IV, or VI responses with nerve VII activity, a common contaminant of recordings from these muscles. It should be kept in mind that the placement of electrodes near the globe is not without risk. Diagnostic ocular electromyography has been associated with rare occurrences of ecchymoses of the conjunctiva, subcapsular hemorrhage, and exposure keratitis, all of which clear without sequelae. Of more concern is inadvertent perforation of the globe, which is more likely in the presence of undetected glaucoma.75 Recently, new methods of electrode placement were introduced for exact anatomic localization and to decrease the risk of complications. Single-shafted bipolar needle electrodes are placed under the guidance of B-mode ultrasound to visualize the needle within the target muscle.105 Another method is to use neuronavigation for image-guided electrode placement. In this method, needle electrodes are inserted percutaneously into the ocular muscles along the axis of a handheld pointer or by means of an electrode applicator to allow direct tracking with the navigation system.106

Trigeminal Nerve The trigeminal nerve (V3m) is the largest of the cranial nerves. Its function is primarily that of sensory supply to the face, but it also supplies motor innervation to the muscles of mastication, primarily masseter and temporalis. Most efforts at intraoperative monitoring of the seventh nerve have concentrated on the motor portion (V3m), which is a

branch of V3. There have been very few attempts to monitor the sensory branches, largely because of the technical problems encountered in overcoming stimulus artifact in trigeminal SEP recording, which is both due to the short latency of trigeminal SEPs and the proximity of the stimulation and recording sites.107,108 However, Soustiel and others109 obtained good results by using alternating polarity stimuli to cancel the stimulus artifact, and showed evoked potential changes correlating with surgical manipulations in 10 of 17 patients. The principles of monitoring V3m are the same as for the seventh nerve: Record from appropriate muscles, look for mechanically elicited activity during dissection, and use electrical stimulation to elicit evoked CMAP for positive identification and establishment of activation thresholds. Once again, however, the problem of cross-talk between channels complicates the situation in practice. The masseter and temporalis are relatively large and powerful muscles and have a coarser innervation than facial muscles. Thus, stimulation of V3m can produce large-amplitude CMAP responses because of the bulk of muscle innervated. Furthermore, there is extensive overlap between facial muscles and the muscles of mastication. The masseter (V3m) is overlaid by various mimetic muscles, including the platysma, zygomaticus major, and the risorius (VII). There is thus the potential for cross-talk in both directions: Activity in the masseter may be picked up through volume conduction to electrodes in orbicularis oris, and activity in facial muscles may be seen in the masseter electrodes. Similarly, the broad, flat temporalis muscle (V3m) overlaps with the occipitofrontalis and temporoparietalis muscles (VII), again creating the possibility of cross-talk in both directions. This overlap is a major problem in interpreting the origin of mechanically elicited EMG activity, although in most instances the region of surgical dissection helps to determine which nerve is being activated. Another frequent reaction encountered with surgical manipulation near the fifth nerve is bradycardia, presumably a result of painful somatosensory input; this reaction is not seen with mechanical stimulation of VII, although a similar response may be seen to activation of the vagus (X) nerve (see below in the section on Lower Cranial Nerves). One possible solution to the cross-talk problem is to attempt a placement of V3m recording electrodes that will be minimally affected by facial muscle activity. We currently use hook wire electrodes placed in the temporalis muscle underneath the zygomatic arch, unless this is impossible because of the surgical approach (i.e., subtemporal or middle fossa), when the electrode should be placed in the masseter. Cross-talk presents less of a problem with the use of electrical stimulation, although the responses to stimulation of either cranial nerve (CN) V3m or VII are still seen in the other channels just as for mechanically elicited activity. However, the latency of responses to stimulation of CN V3m versus CN VII is a robust indicator of which nerve has been stimulated. Stimulation of CN VII, as already indicated, produces CMAP with an onset latency that typically varies between 6 and 8 msec, depending on the exact site of stimulation, although it may be as short as 5 msec with stimulation in the far lateral IAC or delayed as long as 20 msec if the nerve has been severely compromised by the

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tumor. On the other hand, stimulation of V3m produces responses of significantly shorter latency, ranging from around 3.5 to 5 msec. (Remember: V less than 5, VII about 7). Figure 57-8 shows the differential pattern of responses seen in a typical vestibular schwannoma case.

Lower Cranial Nerves Larger vestibular schwannomas with a significant inferior extension may involve the lower cranial nerves and benefit from more specific monitoring of these nerves than is typically done (we routinely monitor CN XI even in small tumors as a control for light anesthesia or other nonspecific causes of EMG activity). More commonly, cranial nerves IX through XII are involved in tumors of the posterolateral cranial base such as glomus jugulare tumors, meningiomas, or schwannomas of the 9th, 10th, or 11th nerves. The morbidity associated with removal of tumors in this region is primarily caused by neural damage, which may result in deterioration of voice, swallowing difficulties, or weakness and pain in the shoulder. These nerves can be monitored with EMG techniques analogous to those already described, with appropriate placement of recording electrodes.110–113 The glossopharyngeal (IX) nerve primarily mediates sensation to the upper pharynx and taste to the posterior third of the tongue. The only muscle innervated by this nerve is the stylopharyngeus, which is not easily accessible for insertion of EMG recording electrodes. Electrodes in the posterior part of the soft palate ipsilateral to the tumor, however, will pick up volume-conducted activity from the stylopharyngeus (Figs. 57-15 and 57-16). The electrodes are inserted intraorally after intubation, and are best sutured in place to prevent accidental dislodgment. In contrast to other lower cranial nerves, there is typically little EMG activity produced in the ninth nerve by

Figure 57-15. Placement of paired needle electrodes in the soft palate to monitor cranial nerve IX and in the tongue to monitor cranial nerve XII. (From Lanser M, et al: Regional monitoring of the lower (ninth through twelfth) cranial nerves. In Kartush J, Bouchard K [eds.]: Intraoperative Monitoring in Otology and Head and Neck Surgery. New York, Raven, 1992.)

Figure 57-16. Sagittal view of placement of needle electrodes into the muscles used for lower cranial nerve monitoring. Needle electrode pairs are placed into the soft palate (CN IX), false vocal cord (CN X), trapezius (CN XI), and tongue (CN XII). (From Lanser M, et al: Regional monitoring of the lower [ninth through twelfth] cranial nerves. In Kartush J, Bouchard K [eds.]: Intraoperative Monitoring in Otology and Head and Neck Surgery. New York, Raven, 1992.)

mechanical stimulation during dissection, and it is thus the most often lost. Fortunately, the deficits produced by isolated ninth-nerve damage are relatively minor. Electrical stimulation of this nerve produces EMG responses at a latency of about 5 to 7 ms, which are generally of low amplitude because recording electrodes are not placed directly in the stylopharyngeus. Similar responses are often seen with stimulation of the 10th nerve; however, it is easy to distinguish between CNs IX and X with multichannel recordings since stimulation of CN X, but not CN IX, also produces responses in the vocalis muscle. The vagus (X) nerve is one of the most complex cranial nerves, with myriad functions affecting the cardiac, respiratory, and gastrointestinal systems as well as providing motor innervation to pharyngeal and laryngeal musculature. There is also a significant sensory component. Isolated paralysis of the ninth nerve creates a significant functional deficit, a hoarse and breathy voice, which can be remedied at least partially with intracordal polytetrafluoroethylene (Teflon) injections. However, a paralysis of both the 9th and 10th nerves, a common combination given their anatomic proximity, is much more serious because it can lead to recurrent aspiration or dysphagia and the necessity for tracheotomy or gastrostomy. These severe complications are more likely in patients who had normal preoperative function, whereas previous damage may have allowed gradual compensation and thus less serious postoperative deficits. The 10th nerve was formerly monitored with electrodes placed in the supraglottic larynx (false vocal cords) after intubation with a standard endotracheal tube.111 Although this provided satisfactory recordings, placement of electrodes was technically difficult and they were easily dislodged. This technique has been rendered obsolete by the development of an endotracheal tube with integral EMG electrodes (Xomed, Jacksonville, Fla.), so that bipolar

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recordings can be obtained from left and right vocalis muscles without additional electrodes (Fig. 57-17A). Another option for tenth nerve monitoring is a laryngeal surface electrode (RLN system, Jefferson City, Mo.), which is inserted intraorally, posterior to the larynx, after intubation with a standard endotracheal tube (Fig. 57-17 B). It has a flat contact surface that records from the posterior cricoarytenoid muscle. The handle of the electrode is bent forward and held against the roof of the mouth with intraoral gauze sponges so that the contact surfaces rotate forward to ensure a stable contact. The latency of EMG responses to electrical stimulation of CN X varies with the site of stimulation. Intracranial stimulation in the posterior fossa or jugular foramen produces response latencies ranging roughly from 4 to 6 ms. Stimulation of the recurrent laryngeal nerve in the neck, such as during thyroid surgery, produces a much faster response (2 to 3 ms latency).

Figure 57-17. A, Electromyographic (EMG) endotracheal tube. Two pairs of wires contact vocalis muscles bilaterally to record EMG activity resulting from activation of the recurrent laryngeal nerve, a component of CN X. B, Laryngeal surface electrode. After intubation the electrode is inserted into the postcricoid space with a standard endotracheal tube to record from the posterior cricoarytenoid muscles (CN X). (From Yingling CD: Intraoperative monitoring of cranial nerves in neurotologic surgery. In Cummings VW, et al [eds.]: Otolaryngology, Head and Neck Surgery, 3rd ed. St. Louis, Mosby, 1998. A, Courtesy of Medtronic Xomed, Jacksonville, Fl; B, Courtesy of RLN Systems, Jefferson City, Missouri.)

Another concern with stimulation of the vagus nerve is cardiac effects; we have experienced bradycardia and even asystole with traction on the 10th nerve in both the posterior fossa and jugular foramen regions. Fortunately, this effect is generally not seen with threshold-level electrical stimulation; however, during surgery in this region, the anesthesiologist should be prepared to administer anticholinergic agents on short notice if necessary. Monitoring of CN XI with electrodes in the trapezius muscle (see Fig. 57-16) has already been briefly considered; this muscle is the easiest marker for identifying the nerves of the jugular foramen in removal of large vestibular schwannomas or other cerebellopontine angle tumors. During monitoring for tumors of the jugular foramen region itself, it may also be useful to place electrodes in the sternocleidomastoid muscle if extra channels are available, especially if there are preexisting 11th nerve deficits and wasting of the trapezius.

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Responses elicited by stimulation of CN XI have a typical latency of 5 to 7 ms, depending on the exact site of stimulation. One concern with stimulation of CN XI is that the large size of the trapezius, in comparison with muscles innervated by other cranial nerves, can lead to significant patient movement, especially with higher levels of stimulation. This can be dangerous, particularly if the patient is immobilized in a Mayfield or similar three-point head holder. For this reason, it is important to start at low intensity when stimulating CN XI and to keep the stimulation as close to the threshold level as possible. If a higher stimulation level is used to ensure that no nerves are in a region about to be dissected, the neurophysiologist should be prepared to rapidly lower the intensity if CN XI is unexpectedly encountered. Finally, the 12th cranial nerve provides motor innervation to the muscles of the tongue. Damage to this nerve produces the well-known sign of ipsilateral deviation when the tongue is stuck out, due to the predominance of the genioglossus muscle on the intact side, but in isolation damage does not usually produce major functional problems. However, damage to this nerve can lead to problems with chewing and swallowing, particularly in combination with deficits in the 9th and 10th nerves. This should be taken into account when considering facial reanimation with CN XII–VII anastomoses in patients with lower cranial nerve deficits. Monitoring CN XII is straightforward; electrodes are inserted into the lateral aspect of the anterior third of the ipsilateral tongue (see Figs. 57-15 and 57-16). Again, this is best done after intubation, and the electrodes should be sutured into place to prevent accidental dislodgment, with the suture tails left long and taped to the cheek to aid in removal at the end of the procedure. The characteristic response to stimulation of the 12th cranial nerve has a latency of approximately 6 ms111 and is of course largest in the tongue EMG channel. Note, however, that responses may also be seen in the 9th and 10th nerve channels, presumably representing movement artifacts from the leads in the mouth. Although EMG monitoring proved to be a safe tool for intraoperative identification and localization of the lower cranial nerves contributing to their anatomic and functional preservation, the predictive value of intraoperative EMG is limited. The occurrence of spontaneous EMG activity does not appear to predict postoperative lower cranial nerve deficit.114

COCHLEAR NERVE MONITORING The cochlear nerve is one of the very fragile cranial nerves, and in the case of vestibular schwannomas it is usually much more intimately involved with the tumor. Thus, preservation of hearing is generally a more difficult task and less likely to succeed than preservation of facial nerve function. However, recent advances in surgical and monitoring techniques have made preservation of hearing an attainable goal in removal of many smaller vestibular schwannomas. Furthermore, the cochlear nerve is at risk in many other posterior fossa procedures, including resection of meningiomas and other non-vestibular-schwannoma (VS) tumors, vestibular neurectomies for disabling vertigo,

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microvascular decompression of the fifth nerve for trigeminal neuralgia or of the seventh nerve for hemifacial spasm, to mention a few of the most common. The method most employed for cochlear nerve monitoring has been intraoperative recording of the auditory brainstem response.22,42,115–133 ABR recording from the contralateral ear may be useful in cases with brainstem compression due to large tumors, even if there is no hearing on the operated side.134 More recently, direct eighth nerve action potentials15,22,42,51,135,136 electrocochleography (ECoG)42,137–140 and recordings from the cochlear nucleus141 have also been employed. Finally, the use of evoked otoacoustic emissions, a newly developed diagnostic technique, has been proposed as a method for monitoring cochlear function.142

Auditory Brainstem Response Recording in the Operating Room Since the ABR was first described in 197110 it has become one of the most common neurophysiologic diagnostic tests because of its ease of administration, relatively low cost, and ability to localize lesions in the peripheral auditory pathway.143 Since most clinical ABR systems are readily adaptable to use in the OR, application of ABR techniques to intraoperative monitoring is relatively straightforward. Details on ABR recording procedures can be found elsewhere in this volume. This section discusses only special considerations in adapting ABR recording to the operating room. Stimulus and Recording Parameters, Electrodes, and Placement In clinical settings, stimuli for eliciting the ABR are typically delivered at rates around 10 to 15 per second. For OR use, higher rates of 20 to 30 per second are desirable to reduce averaging time, although this may reduce response amplitude in cases with poor preoperative hearing. Stimulus intensity is maintained at a high level, usually at 95 dB peak sound pressure level (SPL) or higher, to obtain the best possible signal-to-noise ratio (S/R) (this is at least 60 dB above subjective click threshold levels). Although this is a high level for continuous stimulation, it does not appear to pose a problem; we are not aware of any reports of compromised hearing traceable to ABR recording over extended periods. Nevertheless, it is prudent to set the stimulus intensity at the lowest level that produces consistent waveforms. Standard audiometric earphones are not useful in the OR because they would interfere with surgical access; it is thus necessary to use miniature earphones that fit within the ear and do not compromise the surgical field. Møller and colleagues15,97 have successfully used small in-the-ear transducers designed for use with portable cassette players. However, inexpensive earphones may vary considerably in the acoustic waveform delivered for a given electrical input,144 affecting ABR waveforms and latencies. Higherquality transducers that duplicate the frequency response of standard audiometric earphones offer a more consistent, although expensive, alternative. For OR use, the main concern is obtaining clear definition of wave I, which is often the only useful ABR component with patients who have vestibular schwannoma. Any earphones meeting this criterion can be used with good success.

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Unless expensively shielded earphones are used, stimulus artifact can be a major problem. Careful lead placement and grounding can help minimize artifact. However, the best solution is to use plastic tubing to conduct sound into the ear from a transducer placed a few inches away; this reduces stimulus artifact production due to both the distance between recording leads and the earphone’s magnetic field, and because the acoustic delay isolates the electrical artifact from the actual acoustic stimulus and the subsequent response. The tube is terminated with a foam plug covered with a conductive gold foil (TipTrode, Nicolet Biomedical, Madison, Wis.), which also serves as one of the recording electrodes. In addition to providing acoustic isolation from OR background noise, this electrode provides improved definition of wave I compared to the earlobe or mastoid placement routinely used in clinical ABR testing, as a result of closer proximity to the distal eighth nerve generator of wave I. The other electrode for ABR recording is placed at the vertex (Cz) or any point along the mid-sagittal plane between mid-forehead (Fpz) and vertex, and connected to the noninverting input of the amplifier. Subdermal needle electrodes are preferred because of their ease of placement and stable impedance over the long course of surgery. The ground can be placed at any convenient location; large ground pads, like those used for electrocautery equipment, are easily applied and their broad contact area reduces interference from the 50- to 60-Hz power lines. For optimal recording of all components of the ABR, a bandpass of 10 to 3000 Hz is often recommended for clinical recording. In the OR, however, such a wide bandpass is likely to result in greater sensitivity to interference. Since most of the power in the ABR is concentrated between 400 and 1400 Hz,145 narrower filter settings (i.e., 300 to 1500 Hz) produce more stable waveforms and thus facilitate rapid data collection. Although such settings may produce slight latency shifts, this is not a problem in surgical monitoring where the emphasis is on detecting changes from the baseline that can be related to surgical manipulations, not judgments of normal versus abnormal (most ABRs recorded from patients with eighth nerve tumors are abnormal in any event). Digital filtering is another promising development, which is considered in the section “Analog versus Digital Filtering.” It is also desirable to collect a control ABR from the contralateral ear at the same time as from the operated ear. This can be done by delivering stimuli alternately to the left and right ears, and separately averaging the left and right ear trials. This allows immediate comparison of the ABR from the operated side with that obtained from the contralateral ear, a useful control for nonspecific effects from factors such as anesthesia and temperature. Both ears should not be stimulated simultaneously because the response from the contralateral ear could mask the loss of a response on the operative side. Reducing Electrical and Acoustic Interference It is imperative to take whatever steps are possible to minimize both electrical and acoustic artifacts. Electrical artifacts, which are of concern for both EMG and ABR monitoring, have already been covered. In addition,

acoustic interference becomes a significant problem when either ABR or direct eighth cranial nerve action potentials are recorded. Drilling of the temporal bone to open the IAC can pose serious obstacles to auditory nerve monitoring as a result of acoustic masking, which can degrade or even obliterate the ABR or CNAP. Unfortunately, the cochlear nerve, as well as the inner ear itself, is at great risk during this period in typical retrosigmoid approaches. It might be necessary to deliberately halt drilling periodically in order to obtain valid readings. Alternatively, the neurophysiologist can manually start and stop the averaging process in order to collect data during intervals in the drilling, for example, when changing drill burrs. An automatic interlock to halt data collection whenever the drill is activated is another possibility. Because time is a major concern, efforts have been made to develop monitoring techniques that greatly reduce datacollection times. The two major approaches that have been advocated are (1) emphasizing near-field recording techniques and (2) the use of digital in addition to analogue filtering. Near-field recordings, obtained from an electrode placed directly on the cochlear nerve, can produce reliable CNAP recordings within 5 to 10 seconds compared to much greater times (1 to 2 minutes) for conventional ABR averages. Therefore, the capability to perform both far- and near-field recordings during attempts at hearing conservation in vestibular schwannoma surgeries is desirable. These methods are considered in a subsequent section on Direct VIII Nerve Action Potentials. Analogue versus Digital Filtering The other approach to decreasing averaging time is to employ strategies of optimal digital filtering.15,145,146 In this technique, traditionally recorded (vertex to mastoid) ABR baseline waveforms are established postinduction and their spectral characteristics determined to develop optimum filtering parameters for subsequent data collection. It is important that filter characteristics be individually determined for each patient because the baseline ABR in patients with vestibular schwannoma is typically abnormal and filters based on normative data are unlikely to be optimal. After patient-specific filtering parameters are determined, ABRs are acquired by applying this unique filter to each single trial before averaging. This can produce a dramatic reduction in the number of sweeps necessary to obtain stable waveforms and identify critical changes in amplitude or latency. With digital filtering, ABRs can be collected with as few as 128 sweeps, producing a new average every 10 seconds or faster. They also have the advantage over near-field recording techniques that placement of an electrode within the surgical field is unnecessary. Although these techniques are computationally intensive, and generally not yet available in commercial devices, they might ultimately aid in obtaining successful hearing preservation, particularly in patients with larger tumors that cannot be monitored easily using near-field recordings. Interpretation of Responses in Surgical Context ABRs are relatively unaffected by the level of anesthesia or the type of anesthetic agent used, provided normal brain

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temperature is maintained. Core temperature rarely drops below 32°C during the course of surgery. Within this range ABR absolute and interpeak latencies increase as a function of decreasing temperature at a rate of about 0.17 to 0.2 msec/°C,147,148 so that below 32.5°C the values become statistically abnormal.149 Below 27°C waveforms can be difficult to identify149 or even disappear,150 although amplitudes can also increase before being lost at about 18°C.120 Even though core temperature is maintained near normal values, brainstem temperature may still decrease, especially in tissue bordering the exposed CPA, especially if it is irrigated with saline that is cooler than body temperature. If core temperature is not maintained, recording ABRs from the contralateral ear can help determine whether any changes are systematic or localized. Another factor that typically affects the ABR is the craniotomy itself. New pathways for current flow as a result of the craniotomy, changes in the local environment of the cochlear nerve with removal of CSF and exposure of the nerve to air, and insertion of metallic retractors into the opening all create differences in the relationship between the sites of ABR generation in the eighth nerve and brainstem and the recording electrodes. These changes are of no clinical significance, but they can lead to shifts in ABR amplitude, latency, and waveform as large as those associated with intraoperative events that significantly affect auditory pathways. Fortunately, most of these changes occur in the early stages of the procedure before the cochlear nerve is in serious jeopardy; it is, however, important to obtain a new intraoperative baseline after opening and placement of retractors rather than rely on the no longer appropriate preincision baseline.

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Typical ABR Findings in Vestibular Schwannoma Surgery Intraoperative Changes in ABR Latency and Amplitude Figure 57-18A shows typical ABR results from a posterior fossa craniotomy for removal of a small (<1.0 cm) intracanalicular vestibular schwannoma. The postanesthesia, preincision baseline shows well-defined ABRs with reproducible wave I, III, and V peaks to both right and left ear stimulation. There is almost always a significant difference in interpeak I–III and I–V latency values from the ear ipsilateral to the tumor (left in Fig. 57-18A) compared to those from the opposite ear. Baseline ABRs are often much worse than this example, depending on the degree of preoperative hearing loss and the extent to which the cochlear nerve is compromised by the tumor. Figure 57-18B shows the baseline ABR from a patient with a larger tumor; wave V is desynchronized and greatly reduced in amplitude, wave III is absent (presumably due to asynchronous neural firing) and the I–V interpeak latency is significantly increased (>5 ms). In the majority of vestibular schwannoma surgeries, ABR recordings from the operated side progressively deteriorate over the course of surgery, as shown in Figure 57-18C. Cerebellar retraction, trauma from dissection, acoustic trauma, decreased local temperature, and disruption of cochlear perfusion can all affect ABR peaks I, III, and V amplitude and latency values.115,128 Retraction of the cerebellum, particularly in the medial to lateral direction124 is thought to be one of the principle maneuvers responsible for significant ABR deterioration.115,116 Every effort should be made to reverse such effects by adjustment of the cerebellar retractor, by

Figure 57-18. Representative examples of intraoperatively recorded ABRs from three patients undergoing surgery for removal of vestibular schwannoma. Recordings in A and B were obtained after induction but before first incision. A, Thirty-eight-year-old woman with 0.8-cm L-sided tumor, mild high-frequency hearing loss, and speech discrimination scores of 92% (L ear) and 100% (R ear). B, Fifty-two-year-old woman with 1.8-cm tumor, moderate to moderate-severe sloping hearing loss, with speech discrimination scores of 56% (L ear) and 90% (R ear). Stimuli were alternating polarity, 100-μs clicks, presented at 80 dB nHL, 33.3/sec; 0.9-ms acoustic delay; averaged responses (N = 4000) were recorded from ipsilateral ear canal to vertex. Duplicate averages are overlaid. C, Forty-eight-year-old woman with intracanalicular R-sided tumor and nearly normal hearing, operated on via middle fossa approach. Top traces are preincision baseline and bottom traces show preservation of ABR after total removal of tumor, although a slight increase in latencies of waves IIII and V can be seen. Alternating polarity 100-μs clicks, 80-dB nHL, 21/sec; 0.9 ms acoustic delay; averaged responses (N = 1024) recorded from ipsilateral ear canal to mid-forehead. Four consecutive averages are overlaid. (A and B, From Yingling C, Gardi J: Intraoperative monitoring of facial and cochlear nerves during acoustic neuroma surgery. Otolaryngol Clin North Am 25:413–448, 1992.)

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temporarily halting dissection, or by attempting dissection from a different angle or direction.122 Occasionally, wave I amplitude is acutely enhanced, possibly due to mechanical trauma to auditory efferent (inhibitory) fibers, which travel with the vestibular nerve. This is often followed by a rapid decrease in wave I amplitude, suggesting disruption of the blood supply to the cochlea.

CORRELATION OF INTRAOPERATIVE ABR WITH POSTSURGICAL AUDITORY FUNCTION If ABR wave V is preserved after the tumor has been completely removed, preservation of useful hearing is usually achieved. However, even with such favorable intraoperative findings, hearing may still be lost. Sometimes hearing is present in the immediate postoperative period but disappears within 2 or 3 days. The mechanism of this delayed loss is unclear, but may involve vasospasm of the cochlear artery.151 If only wave I of the ABR is intact, preservation of useful hearing is much less likely. In several cases, an intact wave I could be recorded for more than an hour after the cochlear nerve was known to be transected at the brainstem, an event that is unlikely to be compatible with hearing preservation! Complete loss of waves I and V is almost always associated with total loss of hearing; however, even this indicator is not infallible, and a surgeon should not decide to transect the cochlear nerve, even to facilitate tumor removal, solely on the basis of ABR findings. Matthies and Samii152 reported that loss of wave V, although the most definite sign of postoperative hearing loss, is the least helpful in hearing preservation because its occurrence is a late indication of compromise of hearing. On the other hand, wave III is the earliest and most sensitive sign of cochlear nerve affection. Change or loss of wave III is an early sign that is usually followed by wave V loss. Wave III changes must therefore attract special attention to warn the surgeon promptly. Even in patients who report subjectively unchanged hearing and in whom a reproducible ABR wave V peak is maintained, postsurgical hearing can be adversely affected. Psychoacoustic tests of central auditory function, especially dichotic listening tasks (which rely on preservation of neural synchrony) are more likely to pinpoint these deficits than pure tone audiometry. Little effort has been directed at such questions since most surgical and monitoring teams (as well as their patients) are pleased if there is little change from presurgical to postsurgical pure tone thresholds and speech discrimination scores.

64 to 128 trials or fewer, compared with the 1000 or more usually required to record a reproducible ABR. This reduces the averaging time from nearly 1 minute to roughly 5 seconds, permitting virtually online feedback to the surgeon provided the averaging computer can be programmed to automatically collect sequential averages and display the results so that changes can be readily identified. Three basic types of electrode have been employed for intraoperative CNAP recording. Two are monopolar: a cotton wick sutured on the end of a malleable wire and a flexible ball-tipped wire (usually platinum-iridium) as described previously for the flexible-tip stimulating probe. In either case, the electrode is held in place by a separate adjustable clamp, the cerebellar retractor, or brain cotton and/or bone wax restraint15,42,51,136 (Fig. 57-19). The placement of the reference electrode, which is usually connected to the wound musculature, is not critical, but for least sensitivity to artifact it should be near the edge of the craniotomy to minimize the distance to the active electrode. The second type of near-field electrode that has been employed is a bipolar electrode with two closely spaced contacts, both of which are positioned on or near the cochlear nerve at the root entry zone. In theory, such a bipolar arrangement should provide greater spatial selectivity than a monopolar electrode. In practice, this is not necessarily the case since the amplitude and waveform of the CNAP can change if the orientation of the electrode in relation to the nerve is not held absolutely constant. Bipolar electrodes are also inherently bulkier and more difficult to correctly position within the tight confines of the posterior fossa. The greater spatial selectivity of a bipolar electrode may be useful when the issue is positive identification of cochlear versus vestibular nerves, as in vestibular neurectomy procedures for disabling vertigo.

Direct VIII Nerve Action Potentials Placement of Electrodes To provide more rapid feedback on the functional status of the cochlear nerve, the rate of data acquisition can be enormously speeded by recording near-field auditory CNAPs with an electrode placed directly on the cochlear nerve near the brainstem root entry zone.135,153,154 With this configuration, clear averages can be obtained with

Figure 57-19. Surgical view of retrosigmoid approach to a small vestibular schwannoma, showing flexible-tip electrode in place on the cochlear nerve at brainstem for recording of action potentials elicited by click stimuli to the ipsilateral ear. A malleable solid-core wire, attached rigidly outside the craniotomy, is attached to the flexible tip and used to hold the tip in place, slightly indenting the surface of the nerve. (From Yingling C, Gardi J: Intraoperative monitoring of facial and cochlear nerves during acoustic neuroma surgery. Otolaryngol Clin North Am 25:413–448, 1992.)

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However, for routine monitoring of cochlear nerve function during removal of posterior fossa tumors, the simpler monopolar configuration is preferred. A more recent development is the Cueva cranial nerve electrode (Ad-Tech, Racine, Wis.), a horseshoe-shaped monopolar electrode with a special application tool so that the electrode can be atraumatically placed on and removed from the nerve (Fig. 57-20). The C shape of the electrode allows for stable positioning on the nerve, and the open area of the ring allows an escape route for the nerve in case the electrode is pulled out of position. This design avoids cochlear nerve injury.155 Direct CNAP recordings proximal to the tumor cannot begin until the brainstem root entry zone has been exposed; in smaller tumors this may be soon after opening the posterior fossa dura but in attempts at hearing conservation with larger tumors some tumor removal may be necessary first. For middle fossa surgery, in which the brainstem entry zone is not typically exposed, Roberson and others156 describe the use of an electrode secured between the floor of the IAC and the dura adjacent to the cochlear nerve in an extradural location. (A commercial version of this electrode is available from Ad-Tech.) Although it records from the cochlear nerve at or distal to the tumor location, this technique may be useful. Finally, Møller141 describes placement of an electrode in the lateral recess of the fourth ventricle to record directly from the surface of the cochlear nucleus.

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Stimulus and Recording Parameters The same stimuli used to elicit the ABR (brief clicks of fixed or alternating polarity) are also suitable for CNAP recording. Since the direct signal from the nerve is of higher amplitude than the ABR, however, the amplifier gain should be 5 to 10 times lower than for ABR recording; filter settings can remain the same. Usually 64 to 128 trials per average produces an adequate waveform; at a stimulus rate of 20/sec, a new average can thus be obtained in roughly 5 seconds. Detection and Interpretation of Changes It is important to determine the inherent amplitude and latency variability of the CNAP before undertaking operative manipulations that might affect the cochlear nerve, because this variability forms the background against which meaningful changes must be assessed. With an accurate and stable placement of the recording electrode with respect to the nerve, the response can be quite repeatable from one average to the next. However, if the electrode position changes slightly, the variance could increase substantially. Unfortunately, some of the manipulations that may jeopardize the cochlear nerve (i.e., movement of a retractor) are among the most likely to move the electrode. Figure 57-21 shows a typical reversible change in CNAP amplitude.

Figure 57-20. Cueva cranial nerve electrodes. The circumferential electrodes (2- and 3-mm sizes shown) are positioned on the eighth nerve with a special applicator to record direct cochlear nerve compound action potentials. The applicator holds the electrode open until it is released, when it closes most of the way around the nerve. The flat electrode (left) is designed to be inserted between the bone and dura of the internal auditory canal during middle fossa procedures for recording of cochlear nerve action potential. (From Yingling CD: Intraoperative monitoring of facial nerves in neurotologic surgery. In Cummings CW, et al [eds.]: Intraoperative monitoring in Otology and Head and Neck Surgery. New York, Raven, 1992. A, Courtesy of Medtronic Xomed, Jacksonville, Fla.; B, Courtesy of RLN Systems, Jefferson City, Mo. Photo courtesy of Ad-Tech, Racine, Wis.)

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canal electrode,157 either needle or TipTrode, although the amplitudes are much lower (<1 μV compared to 4–20 μV for a promontory electrode).158 Interpretation of Waveforms

Figure 57-21. Representative changes in cochlear nerve compound action potentials, recorded with electrode as shown in Figure 57-19, over the course of 30 seconds during removal of an 0.6-cm intracanalicular vestibular schwannoma. A, Just before mobilization of tissue adherent to cochlear nerve. B, Mobilization of tumor caused a sharp reduction (≈50%) in CNAP amplitude. C, Partial recovery of response after release of traction on nerve. Stimuli as described for Figure 57-18; 100 trials per average, duplicate averages overlaid (From Yingling C, Gardi J: Intraoperative monitoring of facial and cochlear nerves during acoustic neuroma surgery. Otolaryngol Clin North Am 25:413–448, 1992.)

Intraoperative Electrocochleography Electrode Placement Another approach to speeding data collection is to use a transtympanic electrode on the promontory of the cochlea, referred to a scalp electrode, rather than the earlobe or ear canal electrode usually used for ABR recording.138,139 This achieves a higher signal-to-noise (S/N) ratio for wave I as a result of the greater proximity of the recording electrode to its site of generation in the distal cochlear nerve. The promontory electrode can also be used to record the cochlear microphonic (CM) and summating potential (SP) of the electrocochleogram (ECoG). If one electrode is placed at the root entry zone and the other on the promontory, simultaneous collection of CNAPs and the CM and SP can be achieved.42 However, we prefer not to puncture the tympanic membrane; a postoperative CSF leak could become contaminated with the bacteria that reside in the external auditory canal. To avoid this problem, ECoG potentials can be recorded from an ear

The CM is generated primarily by outer hair cells near the base of the cochlea and, as its name implies, it follows the waveform of the eliciting sound. Note that to record the CM, it is necessary to avoid alternating polarity stimuli because the waveforms would cancel each other; this eliminates one of the most useful methods for reducing stimulus artifact. (On the other hand, better definition of the ABR is sometimes obtained with rarefaction clicks only.) Since the CM decreases only slowly when the blood supply to the cochlea is compromised,159 its usefulness as an indicator of when the cochlea might be at risk is limited. In contrast to the CM, the summating potential, which is thought to reflect stimulus-induced depolarization of hair cells, is of the same polarity regardless of stimulus waveform and follows the envelope of a tone burst stimulus. The SP can also be elicited by click stimuli, which elicit a brief potential just before the CNAP. The SP can be thought of as the presynaptic response, and the CNAP as the postsynaptic response. In recording the SP, alternating polarity not only cancels out the stimulus artifact, but also eliminates the CM, leaving the isolated SP appearing as a shoulder on the leading edge of the CNAP (Fig. 57-22). In clinical electrocochleography, the SP/AP amplitude ratio is often calculated.160 In patients with Ménière’s disease, this ratio is typically much larger than normal and increases with the severity of the symptoms. Several lines of evidence suggest that the SP/AP ratio is a measure of the endolymphatic pressure.140 Thus, the SP/AP ratio has been monitored during endolymphatic sac surgery,137 with changes in the SP/AP ratio accompanying decompression or drainage of the endolymphatic sac. Possible complications with either of these techniques include infection and CSF leaks resulting from the violation of the eardrum. However, the ability to independently assess cochlear versus neural function may add potentially useful new information. For example, if the CM or SP is preserved but the CNAP is lost, the likely site of damage is the nerve itself, with little that can be done to reverse the

Figure 57-22. Representative example of intraoperatively recorded electrocochleogram (ECoG). The large downward deflection represents the action potential (N1) in the distal cochlear nerve, which is also recorded as wave I of the ABR. The shoulder on the initial edge of N1 is the sustained potential (SP), representing depolarization of cochlear hair cells. Recordings obtained from foil-covered sponge electrode (Nicolet TipTrode, Madison, Wis.) in external auditory canal, referred to needle electrode in earlobe. Stimuli were 100-μs clicks, alternating polarity, 22/sec, 75-dB nHL, 512 trials per average, four consecutive averages overlaid.

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deficit. (Note, however, that Wang161 observed preservation of the CM and AP for several minutes after transection of the cochlear nerve.) On the other hand, if the CM and/or SP are also lost, then transient cochlear ischemia is another possible mechanism, which might be reversible by raising systemic blood pressure or administering vasodilators.

Evoked Potentials to Stimulation of the Vestibular Nerve Recently, Hausler and colleagues162 have described a new technique for identifying the vestibular nerve with intraoperative electrical stimulation. They used a bipolar stimulating electrode (biphasic current pulses, 100 μs/phase, 0.75 to 1.0 mA, 20/s) and recorded from electrodes on the forehead and ipsilateral ear, averaging 1000 trials, as is done for ABR recording. A consistent vertex-negative 0.5-μV potential with a latency of approximately 2 ms was recorded in all nine patients, which response disappeared with selective vestibular neurectomy proximal to the stimulation site. Simultaneous acoustic masking did not affect the response, and no facial EMG response was seen. A similar technique has been described in an animal model.163 Used in conjunction with facial EMG and ABR or cochlear action potential recording, this technique may provide yet another method for unequivocal differentiation of the various parts of the CN VII/VIII complex.

Cochlear Nerve Preservation There is no unequivocal consensus concerning the utility of cochlear nerve monitoring. To date, there are at least five confounding issues in the literature, which makes it difficult to clearly determine the value of intraoperative monitoring in preserving hearing. 1. The definition of hearing preservation varies widely. Some authors have defined preservation as any useful speech discrimination or pure tone thresholds less than 70 dB between 0.5 and 2.0 kHz,164 while others require pure tone thresholds lower than 50 dB and speech discrimination scores greater than 50%.165 Another alternative is a classification scheme with hearing preservation expressed as a percentage of patients whose postoperative hearing fell in one of three categories: (1) good = speech reception threshold (SRT) lower than 30 and speech discrimination score (SDS) greater than 70%; (2) serviceable = SRT lower than 50 and SDS greater than 50%; (3) measurable = any measurable hearing.166 One qualitative scheme for classification of hearing following vestibular schwannoma surgeries can be found in Silverstein and colleagues.167 The issue of hearing preservation has been critically reviewed by Sanna and colleagues.168 2. Many reports on attempts at hearing preservation have not correlated intraoperative electrophysiologic data with postsurgical behavioral data.119,169 3. Well-designed studies comparing presurgical and postsurgical behavioral data may lack intraoperative correlates.170 4. Many electrophysiologic reports pool hearing preservation results from vestibular schwannomas with other

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surgeries of the posterior fossa in which the relationship of the cochlear nerve to the tumor may be very different.132,169 5. The likelihood of hearing preservation is highly correlated with presurgical hearing status and tumor size; comparisons of results are difficult across studies unless there are controls for these independent variables. Therefore, cautions must be used in drawing conclusions from the literature on intraoperative monitoring and hearing conservation. The most useful studies contain both intraoperative electrophysiologic data and postsurgical behavioral follow-up data, with tumor size and preoperative hearing status well documented. In studies where tumor size was restricted to less than 2.0 centimeters, useful to adequate hearing preservation was maintained in roughly 30% to 45% of patients, as determined by pre- and postoperative pure tone audiometry and speech discrimination.46,132,164,167,170,171 Most studies with intraoperative ABR recording agree that if waves I and V are preserved, there is an excellent chance of hearing preservation,132,164,172 although exceptions have been noted.139 Conversely, if waves I and V are lost, there is little or no chance of hearing preservation,46,132,164 although rare exceptions have been reported. If wave I is preserved but wave V lost, hearing conservation cannot be accurately predicted. Furthermore, transient changes in wave I and the cochlear microphonic, even if the response recovers over the course of surgery, may reflect pathogenic changes to the nerve with poor long-term prognosis.42,139 Recently, Neu and colleagues173 characterized four patterns of intraoperative brainstem auditory evoked potentials based on a consecutive series of 70 patients with acoustic neuroma in whom hearing preservation was attempted. These patterns corresponded with early and late postoperative hearing outcome. They found that all patients with stable wave V (pattern 1) showed definite hearing preservation, and all patients with irreversible abrupt loss of ABR (pattern 2) lost their hearing, despite early hearing preservation in two cases. All patients with irreversible progressive loss of either wave I or V (pattern 3) eventually suffered from definite postoperative hearing loss, despite early hearing preservation in two cases. Those cases with intraoperative reversible loss of ABR (pattern 4) showed variable short- and long-term hearing outcome: In 34% hearing was preserved, 44% suffered postoperative hearing loss, and the remaining 22% showed postoperative hearing fluctuation, either as delayed or reversible hearing loss. The authors concluded that patients at risk for delayed hearing loss can be identified during surgery by a characteristic ABR pattern and may benefit from vasoactive treatment. Attempts to compare CNAP and ABR monitoring techniques during vestibular schwannoma surgery have revealed that although both ABR and CNAP were useful for predicting postoperative hearing, CNAP was more frequently obtainable and CNAP monitoring was associated with a higher chance of hearing preservation.174 Furthermore, CNAP is possible in patients who have unrecordable ABR waveforms and may minimize cochlear nerve trauma.175 Colletti and colleagues176 compared the value of ABR, ECoG, and directly recorded CNAPs in detecting damage to auditory structures during acoustic neuroma surgery.

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Their results revealed that CNAPs had the highest predictive score for postoperative hearing. In particular, when a permanent loss of CNAPs occurred, the sensitivity and specificity were 100%. It was noted that ECoG was recorded in patients with lost CNAPs. This discrepancy was attributed to the capability of cochlear nerve damage to disconnect the ear from the central auditory pathways, causing persistence of peripheral auditory function without propagation of the neural input. ABR monitoring was highly sensitive in detecting auditory damage but its prognostic utility was marred by its poor specificity. To summarize, ABR monitoring has several possible outcomes, with different prognoses for hearing preservation. If both waves I and V are intact after total tumor removal, even with increased I–V interpeak latency, then the cochlea, eighth nerve, and lower auditory brainstem pathways are intact, and at least some hearing should be preserved postoperatively. Even in these most favorable cases, however, there still may be delayed hearing loss. Preservation of wave I with loss of wave V is more common in our experience, and more problematic. Most patients with irreversible progressive loss of wave V usually suffer from postoperative hearing loss. However, wave V may be lost simply due to desynchronization of the volley entering the brainstem, and preservation of postoperative hearing may still be possible. On the other hand, wave I, which is generated in the distal cochlear nerve, can be preserved even if the eighth nerve is transected at the brainstem. Thus, prognoses based on only wave I preservation should be made cautiously, with reference to the degree of anatomic preservation of the cochlear nerve. Finally, loss of all ABR waves is generally incompatible with preservation of hearing; but even this seemingly straightforward prediction is not foolproof. If wave I is gradually lost during a long and difficult dissection, it may only represent desynchronization of the afferent volley with intact transmission into the brainstem and some postoperative recovery of hearing. However, sudden and precipitous loss of wave I is more likely a result of compromise of the cochlear artery, and usually results in loss of any useful hearing.

FUTURE DIRECTIONS AND CONCLUSIONS It is clear that facial nerve monitoring has had a marked impact on preservation of function in acoustic neuroma surgery. Although there are fewer published data for other cranial motor nerves, the benefits are likely to be similar since the principles are identical. The impact of monitoring on hearing preservation is less clear-cut, although the results thus far are promising and improving. It is equally clear that there is still much room for improvement. We hope the next decade will see improved techniques in a variety of areas, including better methods for automatic identification and rejection of artifacts; procedures for quantification of ongoing EMG activity; development of more sensitive non-EMG-based methods; and perhaps most important, development of a technique for assessing facial nerve integrity without direct electrical stimulation. Techniques for automatic artifact rejection have been explored extensively in the context of quantitative EEG,

and many of these may be easily adapted to EMG recordings from muscles innervated by cranial nerves. Some commercial systems already feature automatic hardware interlinks with known sources of artifacts (i.e., bipolar cautery); this should become standard practice as it is much easier to eliminate artifacts before they are recorded than to remove them after they have contaminated the data stream. With the computational power now available, it is also feasible to develop real-time digital filters based on the different power spectra of EMG versus artifacts, or to use online discriminant functions, which could be either prespecified or trained on appropriately tagged data from an individual case. Neural network models, whether implemented in hardware or software, are another promising approach to artifact identification and rejection. Relatively little work has been done in quantification of ongoing (as opposed to stimulus-triggered) EMG activity. Again, however, rapid progress should be possible by adapting techniques that have been developed for quantitative analysis of clinical EMG recordings. The first step, as already mentioned, is automatic identification and elimination of non-EMG artifacts. “Burst,” or phasic, events could be identified and distinguished from “train,” or ongoing, tonic activity. Within each category, quantitative features could be extracted, such as peak-to-peak amplitude, burst duration, integrated area, and power spectra. Correlation of such features with short- and long-term clinical outcome should lead to identification and automatic discrimination of intraoperative events that can be safely ignored versus those that should lead to modification of surgical procedures to avoid neural damage. No matter how much EMG methods are improved, there will still be a need for more sensitive non-EMG methods that can be used during bipolar cautery, when EMG is obliterated but nerves may be at risk for thermal damage. Again, borrowing from related disciplines (e.g., biomedical engineering and image analysis) may lead to rapid progress. More sensitive methods for detection of subtle facial movements are needed, such as specialized strain gauges that change electrical resistance with surface deformation. Automated analysis of digital video, perhaps looking for slight movements of temporary fiducial marks, could add a modern twist to the early technique of peering under the drapes to look for facial movements. Probably the most important single advance would be a method for continuously assessing facial nerve integrity without the need for the surgeon to directly stimulate the nerve, analogous to continuous ABR recordings for assessing cochlear nerve function. This would be especially important in larger tumors, when the nerve may be inaccessible for stimulation until extensive dissection has been done. Ongoing stimulation with an intracranial electrode on the facial nerve proximal to the tumor is conceptually appealing but technically difficult, particularly if the nerve is initially inaccessible. A more recent development, now widely used in spinal surgery, elicits motor responses by transcranial electrical stimulation of the motor cortex with recording of EMG responses from appropriate muscles (transcranial motor evoked potential, or tcMEP). However, such stimulation causes significant contraction of scalp musculature, so this technique may not be appropriate for delicate intracranial surgery.

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and routine inclusion of professional monitoring personnel in the surgical team, coupled with advances in early diagnosis and microsurgical techniques, will continue to improve the prognosis for preservation of cranial nerve function in patients undergoing skull base surgery.

REFERENCES

Figure 57-23. Blink reflex recorded intraoperatively. Ipsilateral (R1) response (top) recorded from orbicularis oculi after three pulse train stimulus to supraorbital nerve. Habituation of reflex response (middle) after repeated train stimulation. Restoration of reflex amplitude (dishabituation) after train stimulation of contralateral supraorbital nerve (bottom).

A more appealing possibility is to use the well-studied blink reflex,75 which is elicited by stimulation of the supraorbital nerve (trigeminal afferents) and consists of an early ipsilateral EMG response (R1) and a later bilateral response (R2), both mediated by the facial nerve. Despite the utility of the blink reflex in clinical testing, it has not yet been reliably elicited in surgery because the reflex activity is suppressed by general anesthetics. It may become possible to overcome this problem by greater reliance on intravenous anesthetics such as propofol together with repetitive train stimulation like that used for tcMEP (Fig. 57-23). Further improvements will likely come as techniques become more refined and integrated. Some of this improvement will come as more sophisticated hardwaresoftware systems, optimized for intraoperative monitoring, become commercially available. Computerized systems with capacity for rapid data collection with online digital filtering, automated artifact rejection, software control of stimulation and recording parameters, user-friendly interfaces, and displays of current data as well as trends during the operation will bring the full range of currently available techniques into more widespread use. Finally, there is still much to be learned about the relationship between intraoperative recordings and long-term clinical outcome. More controlled studies, with carefully characterized patient populations and standardized monitoring techniques with quantification of response parameters, are needed to address many of the issues discussed here. The only certainty is that improvements in monitoring techniques

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51. Silverstein H, et al: Simultaneous use of CO2 laser with continuous monitoring of eighth cranial nerve action potential during acoustic neuroma surgery. Otolaryngol Head Neck Surg 92:80–84, 1984. 52. Wiegand D, et al: Detection of intraoperative laser injury to the facial nerve by electromyographic monitoring of facial muscles. Laryngoscope 101:771–774, 1991. 53. Jako GJ: Facial nerve monitor. Trans Am Acad Opthalmol Otolaryngol 69:340–342, 1965. 54. Sugita K, Kobayashi S: Technical and instrumental improvements in the surgical treatment of acoustic neurinomas. J Neurosurg 57:747–752, 1982. 55. Silverstein H: Microsurgical instruments and nerve stimulator: Monitor for retrolabyrinthine vestibular neurectomy. Otolaryngol Head Neck Surg 94:409–411, 1986. 56. Silverstein H, et al: Routine intraoperative facial nerve monitoring during otologic surgery. Am J Otol 9:269–275, 1988. 57. Williams JD, Lehman R: Bells against palsy. Am J Otol 9:81–82, 1988. 58. Zini C, Gandolfi A: Facial-nerve and vocal-cord monitoring during otoneurosurgical operations. Arch Otolaryngol Head Neck Surg 113:1291–1293, 1987. 59. Dickens JRE, Graham SS: A comparison of facial nerve monitoring systems in cerebellopontine angle surgery. Am J Otol 12:1–6, 1991. 60. Uziel A, Benezech J, Frerebeau P: Intraoperative facial nerve monitoring in posterior fossa acoustic neuroma surgery. Otolaryngol Head Neck Surg 108:126–134, 1993. 61. Bendet E, Rosenberg SI, Willcox TO, Gordon M, Silverstein H: Intraoperative facial nerve monitoring: A comparison between electromyography and mechanical-pressure monitoring techniques. Am J Otol 20:793–799, 1999. 62. Filipo R, De Seta E, Bertoli GA: Intraoperative videomonitoring of the facial nerve. Am J Otol 21(1):119–122, 2000. 63. Filipo R, Pichi B, Bertoli GA, De Seta E: Video-based system for intraoperative facial nerve monitoring: Comparison with electromyography. Otol Neurotol 23:594–597, 2002. 64. Schmid UD, et al: Orthodromic (intra/extracranial) neurography to monitor facial nerve function intraoperatively. Neurosurg 22:945–950, 1988. 65. Richmond IL, Mahla M: Use of antidromic recording to monitor facial nerve function intraoperatively. Neurosurg 16:458–462, 1985. 66. Colletti V, Fiorino FG: Advances in monitoring of seventh and eighth cranial nerve function during posterior fossa surgery. Am J Otol 19:503–512, 1998. 67. Wedekind C, Klug N: F-wave recordings from nasal muscle for intraoperative monitoring of facial nerve function. Zentralbl Neurochir 57:184–189, 1996. 68. Wedekind C, Klug N: Recording nasal muscle F waves and electromyographic activity of the facial muscles: A comparison of two methods used for intraoperative monitoring of facial nerve function. J Neurosurg 95:974–978, 2001. 69. Wedekind C, Klug N: Nasal muscle F-wave for peri- and intraoperative diagnosis of facial nerve function. Electromyogr Clin Neurophysiol 38:481–490, 1998. 70. Jackler RK, Pitts LH: Acoustic neuroma. Neurosurg Clin North Am 1:199–223, 1990. 71. Mandpe AH, Mikulec A, Jackler RK, Pitts LH, Yingling CD: Comparison of responses amplitude versus stimulation threshold in predicting early postoperative facial nerve function after acoustic neuroma resection. Am J Otol 19:112–117, 1998. 72. Kirkpatrick PJ, Tierney P, Gleeson MJ, Strong AJ: Acoustic tumor volume and the prediction of facial nerve functional outcome from intraoperative monitoring. Br J Neurosurg 7:657–664, 1993. 73. Lalwani AK, Butt FY, Jackler RK, et al: Facial nerve outcome after acoustic neuroma surgery: A study from the era of cranial nerve monitoring. Otolaryngol Head Neck Surg 111:561–570, 1994. 74. Silverstein H, Willcox TO Jr, Rosenberg SI, Seidman MD: Prediction of facial nerve function following acoustic neuroma

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58

Outline General Anatomy Muscles Veins Arteries Nerves Surgical Anatomy Level 1 Level 2

Chapter

Anatomy of the Lateral Skull Base

Level 3 Level 4 Level 5 Jugular Foramen and Cavernous Sinus The Cranial Base from Above

U

nderstanding the anatomy of the skull base is critical to management of lesions in this difficult but fascinating area of the head and neck. The ability to interpret diagnostic procedures and plan operative or other treatment in this area depends on a fundamental knowledge of the complex relationship of structures adjacent to the lesion to be treated. This chapter presents the basic anatomy and the surgical approach to the skull base and its adjacent soft tissue structures. Figure 58-1 is presented as orientation to the skeletal landmarks of this area. Figure 58-1A demonstrates the skull base intracranially from above. This area consists of the irregular union of portions of three bones—occipital, petrosal, and sphenoidal—as well as overlapping soft tissue structures. Figure 58-1B demonstrates the skull base extracranially from below. Note the extensive suture lines between the three separate cranial bones, and note that this can make intraoperative localization of bony landmarks difficult. The various foramina, the canal for the carotid artery, and the jugular foramen are demonstrated.

GENERAL ANATOMY Muscles Figures 58-2 demonstrates the important muscles of the infratemporal fossa and adjacent skull base. The temporalis muscle is a fan-like structure that originates from the temporal fossa and inserts onto the coronoid process of the mandible. The masseter muscle originates from the zygoma and attaches to the angle and lateral mandibular ramus. The lateral pterygoid muscle originates from the greater The authors would like to acknowledge the unparalleled artistry of Steve Moon who executed the artwork for this chapter. They also are grateful to Jacqueline Burns for her dedicated assistance in preparation of the manuscript.

Robert A. Goldenberg, MD John P. Leonetti, MD

sphenoid wing and the lateral pterygoid plate and inserts into the front neck of the mandibular condyle. The medial pterygoid muscle arises from the palatine bone, the tuberosity of the maxilla, and the medial pterygoid plate and attaches to the posteromedial surface of the ramus and angle of the mandible. The posterior belly of the digastric muscle originates in the digastric groove of the mastoid tip and inserts onto the hyoid bone via its intermediate tendon. The sternocleidomastoid muscle originates on the sternum and clavicle and inserts onto the lateral surface of the mastoid process. The stylohyoid, stylopharyngeus, and styloglossus muscles originate on the styloid process and insert onto the hyoid bone, thyroid cartilage, and lateral tongue, respectively. The tensor veli palatini originates in the scaphoid fossa of the medial pterygoid plate, the sphenoid bone, and the cartilaginous eustachian tube and inserts on the horizontal portion of the palatine bone. The levator veli palatini originates on the petrous portion of the temporal bone and cartilaginous eustachian tube and inserts into the palatine velum. The longissimus muscle originates by four tendons attached to the third through the sixth cervical vertebrae and it inserts onto the mastoid tip. The anterior rectus of the head originates on the lateral atlas and inserts onto the occipital bone anterior to the foramen magnum. The lateral rectus originates on the transverse process of the atlas and inserts on to the jugular process of the occipital bone.

Veins Figure 58-3 (see Color Plate 3) illustrates the basic venous drainage of the lateral skull base. The extracranial veins encountered are tributaries of the retromandibular, external, or internal jugular veins. Mastoid and occipital emissary veins often connect the dural sinus system with branches of the occipital, postauricular, or retrofacial veins, 997

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Figure 58-1. Skeletal landmarks. A, The skull base intracranially from above. B, The skull base extracranially from below.

but the pterygoid venous plexus is highly variable in its pattern. The structures of most concern to the surgeon are the lateral and sigmoid sinuses, the jugular bulb, and the internal jugular vein. The superior and inferior petrosal sinuses drain from the cavernous sinus anteriorly to the lateral sinus and the jugular bulb, respectively. The occipital and petrosquamous sinuses may also be encountered.

atlanto-occipital membrane to enter the intracranial space. The basilar artery, formed by the intracranial junction of both vertebral arteries, gives rise to the posterior fossa blood supply. These structures include the posterior inferior cerebellar artery, the anterior inferior cerebellar artery, the internal auditory artery, the superior cerebellar artery, the posterior cerebral artery, and multiple pontine and medullary perforating branches.

Arteries

Nerves

The lateral skull base arterial supply is shown in Figure 58-4 (see Color Plate 3). The extracranial blood supply to the scalp and cervical neck is derived from the facial, superficial temporal, occipital, and postauricular branches of the external carotid artery. The deep temporal and middle meningeal branches of the internal maxillary artery, along with the ascending pharyngeal artery, are encountered during infratemporal fossa dissection. Transcranial arterial structures consist of the internal carotid and vertebrobasilar systems. The cervical portion of the internal carotid artery ascends vertically from the bifurcation and is located deep to the sternocleidomastoid, digastric, and stylohyoid muscles. The petrous carotid segment initially ascends vertically in the temporal bone, anterior to the jugular bulb and cochlea, then curves horizontally in an anteromedial direction, medial to the eustachian tube and caudal to the middle meningeal artery and the mandibular division of the trigeminal nerve. The horizontal segment of the carotid artery exits the temporal bone at the petrous apex, where it then forms the more medial cavernous portion. The vertebral artery enters the transverse process of the sixth cervical vertebra and ascends vertically through the

The neural structures encountered during lateral skull base procedures are illustrated in Figure 58-5 (see Color Plate 4). Cranial nerves III, IV, and VI are often identified during cavernous sinus dissection. The trigeminal ganglion gives rise to the trigeminal nerve, which immediately branches into the ophthalmic, maxillary, and mandibular nerves that course through the superior orbital fissure, foramen rotundum, and foramen ovale, respectively. The first two divisions of the trigeminal nerve provide sensory innervation to the face, but the mandibular division provides both sensory innervation to the lower face and motor innervation to the muscles of mastication. The seventh cranial nerve enters the internal auditory canal with the eighth cranial nerve, transverses the temporal bone, exits at the stylomastoid foramen, and branches within the parotid gland to innervate the muscles of facial expression. Prior to exiting, it gives off a postauricular branch that divides into the occipital, auricular, digastric, and stylohyoid nerves and a communicating nerve to the glossopharyngeal nerve. The chorda tympani and stapedius branches of the facial nerve arise in the temporal segment of the nerve, and the greater petrosal nerve, which originates at the geniculate ganglion, passes along

Anatomy of the Lateral Skull Base

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Figure 58-2. A and B, Important muscles of the infratemporal fossa and adjacent skull base.

the floor of the middle cranial fossa prior to traversing the foramen lacerum. The greater petrosal nerve exits at the facial hiatus and joins the deep petrosal nerve to become the vidian nerve. The lesser petrosal nerve exits at the foramen ovale or the petrosal foramen and communicates with the otic ganglion and tympanic plexus. The chorda tympani nerve, which joins the lingual nerve, supplies taste to the anterior two-thirds of the tongue. The ninth cranial nerve exits from the jugular foramen and has the following branches: meningeal, auricular,

pharyngeal, carotid body, superior laryngeal, cardiac, esophageal plexus, and anterior and posterior vagal trunks. The 10th cranial nerve also exits from the jugular foramen and has the following branches: meningeal, auricular, pharyngeal, carotid body, superior laryngeal, cardiac, esophageal plexus, and anterior and posterior vagal trunks. The 11th cranial nerve exits through the jugular foramen and is the primary component of the spinal accessory nerve. The 12th cranial nerve exits through the hypoglossal canal and divides into lingual and muscular branches.

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SKULL BASE DISEASES

SURGICAL ANATOMY Level 1 Figure 58-6 (see Color Plate 4) serves as the initial dissection level displaying the lateral skull base orientation. A radical mastoidectomy has been performed along with a standard modified neck dissection. Deep mastoid dissection allows identification of the dural plate, sinodural angle, sigmoid sinus, and the entire transtemporal course of the facial nerve. The parotid gland has been anteriorly mobilized from the external auditory canal, and the styloid base has been identified following reflection of the styloid musculature, the posterior belly of the digastric muscle, and the sternocleidomastoid muscle. Cervical neck dissection allows identification of the basal cranial nerves (IX through XII), the internal jugular vein, and the carotid artery. This will assist in the retrograde dissection of the cranial nerves during tumor removal, as well as vascular control of the great vessels.

Level 2 Figure 58-7 (see Color Plate 5) demonstrates the enhanced infratemporal exposure gained by the anterior transposition of the facial nerve.1 Mobilization of the seventh nerve in this fashion requires bony decompression from the geniculate ganglion to the stylomastoid foramen, sharp dissection of the investing periosteum at the stylomastoid foramen, and soft tissue (parotid) dissection to the level of the pes anserinus. Bone removal must be complete prior to attempted facial nerve mobilization in order to avoid traction injury. Particular care must be taken to avoid fenestration of the lateral semicircular canal and the stapes. The nerve to the stapedius muscle and any investing periosteum should be sharply sectioned under microscopic control. The internal carotid artery enters the carotid canal anteromedial to the styloid base. The carotid artery is consistently identified following anteroinferior mobilization of the styloid musculature and resection of the styloid process.2 The cartilaginous capsule around the mandibular condyle has been exposed by removing the anterosuperior bony external auditory canal. Additional medial and anterior exposure can be obtained by resecting the cartilage of the glenoid fossa, by downward displacement of the mandible, or by resecting any or all of the condylar process.

Level 3 The jugular foramen and carotid canal have been exposed in Figure 58-8 (see Color Plate 5). The petrous carotid artery enters at the carotid canal, medial to the styloid base, courses vertically, anteromedial to the cochlea, and curves in an anteromedial direction just medial to the middle ear orifice of the eustachian tube. The bony spur or crotch, which separates the vertical petrous carotid artery from the jugular bulb, may be eroded or absent in patients with large tumors that involve the jugular foramen. The transcochlear approach provides lateral exposure to midline skull base lesions.3 In this technique, the facial nerve is posteriorly rerouted following transsection of the

greater petrosal nerve. Complete removal of the cochlea allows skeletonization of the jugular bulb and petrous carotid artery. Dissection medial and inferior to the carotid canal provides access to the petroclival, petrooccipital, and periclival regions.4 The posterior limits of this dissection are the transverse and sigmoid sinuses with the adjacent dura. Communications with extracranial vessels may occur at any level from the transverse sinus to the jugular bulb.5 Anterior displacement of the mandibular condyle requires division of the temporomandibular, sphenomandibular, and stylomandibular ligaments.6 The spine of the sphenoid bone points to the middle meningeal artery at the foramen spinosum where it crosses the eustachian tube’s bony-cartilaginous junction. Dissection of the styloid musculature and the anterior inferior crest of the tympanic bone leads directly to the spine of the sphenoid. The internal maxillary branch of the external carotid artery passes through the space between the sphenomandibular ligament and the neck of the mandibular condyle. Preservation of this vessel may be necessary to maintain adequate arterial supply to the temporalis muscle, which may be used in defect reconstruction.

Level 4 Deeper dissection along the petrous portion of the carotid artery is shown in Figure 58-9 (see Color Plate 6). The horizontal segment of the petrous carotid artery is demonstrated following removal of the bony and cartilaginous eustachian tube. The foramen ovale is seen just anterior and medial to the foramen spinosum.4 The mandibular branch of the trigeminal nerve, the lesser petrosal nerve, an accessory meningeal artery, and pterygoid emissary veins also pass through the foramen ovale. The medial wall of the eustachian tube is a very thin, at times dehiscent, shell of bone covering the carotid artery.7 The cartilaginous eustachian tube can be obliterated or oversewn following tumor removal to prevent cerebrospinal fluid (CSF) rhinorrhea and nasopharyngeal wound contamination. The roof of the carotid canal runs horizontally across the petrous pyramid prior to its entrance into the posterolateral portion of the foramen lacerum.8 The greater petrosal nerve courses over the roof of the carotid canal, while the middle meningeal artery and mandibular nerve cross perpendicular to the horizontal segment of the petrous carotid artery.9 The tensor tympani muscle and eustachian tube are lateral to the carotid artery in this segment. The periosteal arteries and the artery of the pterygoid canal arise from the horizontal portion of the petrous carotid artery, while the caroticotympanic branch usually arises from the carotid genu.2 These vessels become clinically significant if they provide arterial supply to skull base tumors or if they are abnormally enlarged from backflow engorgement. The ascending ramus of the mandible has been removed at this level of dissection and the middle meningeal artery and mandibular nerve have been divided. The middle fossa dura has been exposed following complete removal of the bone of the glenoid fossa. Additional exposure of the middle cranial fossa floor can be achieved following

Anatomy of the Lateral Skull Base

downward displacement of the zygomatic arch, which is left attached to the masseter muscle. The relationship of the lateral pterygoid plate to the anterior margin of the foramen ovale is consistent. The lateral margin of the foramen lacerum along with the medial and lateral pterygoid muscles are displayed.

Level 5 The most medial extent of the surgical dissection is shown in Figure 58-10 (see Color Plate 6). The posterolateral surface of the maxilla is in close proximity to the terminal branches of the internal maxillary artery. Troublesome bleeding may be encountered from these vessels as a result of pterygoid muscle or pterygoid plate manipulation.10 It is useful to identify the landmark of the lateral pterygoid plate in order to avoid troublesome bleeding from the associated venous plexus. The infratemporal plate of the maxilla and the infraorbital fissure form the anterior limit of the dissection. The maxillary branch of the trigeminal nerve may be seen at the foramen rotundum in the greater sphenoid wing. Superior orbital fissure exposure may require division of the maxillary nerve.4 The anterior margin of the foramen ovale is adjacent to the posterior portion of the lateral pterygoid plate. The margin of the medial pterygoid plate is somewhat variable. The petrous bone around the foramen lacerum has been removed to show the course of the internal carotid artery. The dura over the middle cranial fossa floor may be elevated in order to follow the horizontal portion of the petrous carotid artery medially.11 The trigeminal impression (Meckel’s cave) is located at the anteromedial petrous tip and is superior to the carotid canal and the foramen lacerum. The foramen lacerum has been described as a jagged space between the pars basalis of the occipital bone, the temporal portion of the sphenoid bone, and the petrous apex of the temporal bone.12 No structures pass out of the foramen lacerum, but only through it. Exposure of the basal portion of the occipital bone can be achieved by dissection deep to the foramen lacerum. Clival tumors may be approached following division of the buccopharyngeal fascia, prevertebral fascia, and superior pharyngeal constrictors.13 The styloid process is an important landmark during deep parapharyngeal space dissection. The stylopharyngeal septum may be traced to the lateral pharyngeal wall, and the parapharyngeal space can thus be delineated from the retropharyngeal space.14 The pterygomaxillary fissure joins the pterygopalatine and infratemporal fossae. The skull base can be divided into a midline and two lateral compartments separated by the petro-occipital fissure.15 The sphenoid body, clivus, occipital condyle, and hypoglossal canal are midline. The temporal bone and greater sphenoid wing constitute the lateral compartment. The occipital condyle, as it abuts the first cervical vertebra, along with the surrounding musculature and fascia represent the posterior medial limit of the dissection. Important landmarks in this area are the occipitomastoid suture line and the stylomastoid foramen. The vertebral artery and the transverse process of the first cervical vertebra are demonstrated.

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Jugular Foramen and Cavernous Sinus The complex neurovascular anatomy encountered during dissection near the jugular foramen and cavernous sinus is displayed in Figure 58-11 (see Color Plate 7). The jugular foramen can be divided into the pars nervosa and the pars venosa with the neural component situated medially and the vascular compartment located laterally.16 A fibrous or bony septum can often be found between the jugular spine of the petrous bone and the jugular spine of the occipital bone. The right jugular foramen is usually larger in diameter than the left and seems to correspond with the size of the lateral venous sinus. The size of the pars nervosa is more consistent. The inferior petrosal sinus occupies the medial pars venosa, and the jugular bulb fills the lateral space. These structures are separated by a fibrous septum through which course cranial nerves IX, X, and XI. The inferior petrosal sinus enters the medial wall of the jugular bulb at various locations and usually consists of multiple, separate channels. The inferior petrosal sinus, which is usually located just medial to the internal carotid artery above the hypoglossal canal, may be the source of profuse bleeding following tumor removal from the jugular foramen.17 Packing of the inferior petrosal sinus to control bleeding may result in temporary or permanent paralysis of cranial nerves IX, X, or XI, which are located in the fibrous sheath medial to the jugular bulb. The hypoglossal canal is situated inferior to the jugular foramen, although the proximal segment of the hypoglossal nerve is medial and posterior to the vagus nerve.18 The location of the hypoglossal nerve in relation to the jugular bulb will vary according to its bony canal’s relationship to the occipital condyle and the jugular foramen. The cavernous sinus extends from the superior orbital fissure to the apex of the petrous portion of the temporal bone. As viewed from a lateral perspective, the cavernous sinus lies anterior and superior to the foramen lacerum. The carotid artery and a portion of the sixth cranial nerve are surrounded by the cavernous sinus.19 Cranial nerves III and IV and the second division of cranial nerve V are found in the lateral wall of the cavernous sinus.20 Each cavernous sinus receives the superior petrosal sinus, the inferior petrosal sinus, and the pterygoid venous plexus and are themselves joined by the large basilar (intercavernous) sinus. The three branches of the carotid artery found within the cavernous sinus are the meningohypophyseal trunk, the artery of the inferior cavernous sinus, and the McConnell capsular arteries.21 The carotid artery is relatively mobile within the cavernous sinus. The third cranial nerve enters the dural roof anterior and lateral to cranial nerve VI. Both nerves are medial to and beneath the free tentorial margin. Cranial nerve III enters above the meningohypophyseal trunk, while cranial nerve VI bends around the proximal portion of the intracavernous carotid artery. The maxillary nerve courses anteriorly within the inferior wall of the cavernous sinus or within the inferior compartment of the sinus itself.22 This nerve may therefore be injured if the cavernous sinus is entered in a lateral to medial direction.

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SKULL BASE DISEASES

Brisk bleeding may be encountered during dissection along the medial floor of the middle cranial fossa. Dural venous sinuses exist between the cavernous sinus, the foramen ovale, and the pterygoid venous plexus. Judicious placement of packing material is suggested to avoid inadvertent injury to the nerves within the cavernous sinus.

THE CRANIAL BASE FROM ABOVE An intracranial view of the skull base and related neurovascular structures is shown in Figure 58-12 (see Color Plate 7). A variety of foramina and fissures exist in the region of the middle cranial fossa. The optic canals, each transmitting an optic nerve and an accompanying ophthalmic artery, are located between the body and the lesser wings of the sphenoid and anterior to the anterior clinoid processes. The midline portion of the middle cranial fossa behind the optic canals is the sella turcica (pituitary gland). The tip of the petrous portion of the temporal bone fits between the body and the greater wing of the sphenoid at the jagged foramen lacerum. The internal carotid artery leaves the petrous tip to run in the carotid sulcus to the undersurface of the anterior clinoid process where it turns medially toward the tuberculum sellae. Much of the floor of the middle cranial fossa is formed by the greater wing of the sphenoid bone. Anteriorly, lateral to the anterior clinoid process, is the superior orbital fissure, which transmits the ophthalmic vein, the ophthalmic division of the trigeminal nerve, and cranial nerves III, IV, and VI. The foramen rotundum, which transmits the maxillary branch of the trigeminal nerve, is located behind the base of the superior orbital fissure at the level of the sella turcica. Posterior to the foramen rotundum is the foramen ovale, which provides a pathway for the mandibular division of the trigeminal nerve into the infratemporal fossa. The middle meningeal artery passes through the foramen spinosum, which is located posterolateral to the foramen ovale. The petrous portion of the temporal bone forms the posteromedial margin of the middle cranial fossa. The gasserian ganglion of the trigeminal nerve is located in a bony depression (Meckel’s cave) of the petrous tip where the internal carotid artery enters the cavernous sinus just above the foramen lacerum. The greater petrosal nerve is located in a groove along the middle cranial fossa floor that is perpendicular to the course of the middle meningeal artery and parallel to the horizontal petrous portion of the internal carotid artery. The greater petrosal nerve enters the middle fossa floor at the facial hiatus, which is located just anterior to the geniculate ganglion of the facial nerve. The very thin roof of the middle ear, the tegmen tympani, is located lateral and posterior to the facial hiatus, while the arcuate eminence (superior semicircular canal) is seen more posteriorly. The internal auditory canal, which transmits cranial nerves VII and VIII is located along the line that bisects the angle formed by lines drawn through the greater petrosal nerve and the arcuate eminence. Removal of the tegmen tympani allows exposure to the ossicles, the tensor tympani muscle, the eustachian tube orifice, and the tympanic segment of the facial nerve. Extreme caution must be exercised in removing bone

anterior and inferior to the lateral margin of the internal auditory canal because fenestration of the cochlea will lead to inadvertent loss of hearing. The vertical portion of the petrous carotid artery and the carotid genu can be exposed by dissection medial to the eustachian tube and anteromedial to the cochlea. The midline anterior margin of the posterior cranial fossa is the dorsum sellae, and the lateral margin is the superior margin of the petrous portion of the temporal bone. The lateral posterior cranial fossa is roofed by a layer of dura matter that is attached anterolaterally to the superior margins of the two petrous bones and posteriorly to the occipital bones (tentorium cerebelli). The internal auditory meatus, found on the posteromedial face of the petrous bone, is the opening of the internal auditory canal, which transmits the seventh and eighth cranial nerves. The jugular foramen is located behind and below the internal auditory meatus and is formed by the fissure between the temporal and occipital bones. The sulcus for the sigmoid sinus is found on the medial aspect of the temporal and occipital bones, providing a path for the sigmoid sinus to the jugular foramen. The jugular foramen can be divided into the pars venosa (jugular vein) and pars nervosa (cranial nerves IX, X, and XI). The foramen magnum is the largest foramen in the posterior fossa and through it the brain and the spinal cord are continuous with each other. The two vertebral arteries ascend through this foramen as well as cranial dural and spinal cord venous plexuses. The anterior foramen magnum is bordered by the clivus, which is a downwardly slanting midline bone formed by the fusion of the body of the sphenoid bone to the basal portion of the occipital bone. The sulci for the inferior petrosal sinuses, ending posteriorly at the jugular foramina, are found along the lateral aspects of the clivus. The superior petrosal sinus connects the cavernous sinus with the transverse or sigmoid sinus and is located in a groove along the superomedial petrous ridge. The basilar plexus (sinus) is between the two inferior petrosal sinuses extending downward on the clivus to the foramen magnum.

REFERENCES 1. Fisch U: Infratemporal fossa approach for glomus tumors of the temporal bone. Ann Otol Rhinol Laryngol 91:474–479, 1982. 2. Gossman JR, Tarsitano JJ: The styloid-stylohyoid syndrome. J Oral Surg 35:555–560, 1977. 3. House WF, De la Cruz A: Transcochlear approach to the petrous apex and clivus. Trans Am Acad Ophthalmol Otolaryngol 84: 927–931, 1977. 4. Fisch U, Pillsbury HC: Infratemporal fossa approach to lesions in the temporal bone and base of the skull. Arch Otolaryngol 105: 99–107, 1979. 5. Woodhall B: Anatomy of cranial blood sinuses with particular reference to the lateral. Laryngoscope 49:966–1009, 1939. 6. Friedman WH, et al: Stylohamular dissection: a new method for en bloc resection of malignancies of the infratemporal fossa. Laryngoscope 91:1869–1880, 1981. 7. Hybels RL, Friedberg SR: Combined otolaryngologic and neurosurgical approaches to tumors of the temporal bone and skull base. Surg Clin North Am 60:609–628, 1980. 8. Gacek RR: Evaluation and management of primary petrous apex cholesteatoma. Otolaryngol Head Neck Surg 88:519–523, 1980.

Anatomy of the Lateral Skull Base

9. Glasscock ME III: Exposure of the intra-petrous portion of the carotid artery. In Hamberger CA, Wersall J (eds.): Proceedings of the Tenth Nobel Symposium: Disorders of the Skull Base Region. New York, John Wiley & Sons, 1968, pp 135–143. 10. Arena S: Tumor surgery of the temporal bone. Laryngoscope 84:645–670, 1974. 11. Fisch U: Infratemporal fossa approach to tumors of the temporal bone and base of the skull. J Laryngol Otol 92:949–967, 1978. 12. Gacek RR: Diagnosis and management of primary tumors of the petrous apex. Ann Otol Rhinol Laryngol 84:1–20, 1975. 13. Stevenson GC, et al: A transcervical transclival approach to the ventral surface of the brain stem for removal of a clivus chordoma. J Neurosurg 24:544–551, 1966. 14. Som PM, Biller HF, Lawson W: Tumors of the parapharyngeal space: Preoperative evaluation, diagnosis and surgical approaches. Ann Otol Rhinol Laryngol (Suppl) 90:3–15, 1981. 15. Som PM, Shugar JMA, Parisier SC: A clinical-radiographic classification of skull base lesions. Laryngoscope 89:1066–1076, 1979. 16. DiChiro G, Fisher RL, Nelson K: The jugular foramen. J Neurosurg 21:447–460, 1964. 17. Jenkins HA, Fisch U: Glomus tumors of the temporal region: Technique of surgical resection. Arch Otolaryngol 107:209–214, 1981. 18. Gejrot T: Jugular foramen syndromes. In Hamberger CA, Wersall J (eds.): Proceedings of the Tenth Nobel Symposium: Disorders of the Skull Base Region. New York, John Wiley & Sons, 1968, pp 279–283. 19. House WF: Middle cranial fossa approach to the petrous pyramid: Report of 50 cases. Arch Otolaryngol 78:460–469, 1963. 20. Parkinson D: A surgical approach to the cavernous portion of the carotid artery. J Neurosurg 23:474–483, 1965. 21. Wallace S, et al: The cavernous branches of the internal carotid artery. Am J Roentgenol Radium Ther Nucl Med 101:34–36, 1967.

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22. Henderson WR: A note on the relationship of the human maxillary nerve to the cavernous sinus and to an emissary sinus passing through the foramen ovale. J Anat 100:905–908, 1966. 23. Morantz RA, Kirchner FR, Kishore P: Aneurysms of the petrous portion of the internal carotid artery. Surg Neurol 6:313–318, 1976.

BIBLIOGRAPHY Anson BJ, Donaldson JA: Surgical Anatomy of the Temporal Bone, 3rd ed. Philadelphia, WB Saunders, 1981. Counter RT: Color Atlas of Temporal Bone Surgical Anatomy. Chicago, Yearbook Medical Publishers, 1980. Ferner H, Stanbesand J: Sobotta Atlas of Human Anatomy, vol 1. Baltimore and Munich, Urban and Schwartzenberg, 1983. Goldenberg RA: Surgeon’s view of the skull base from the lateral approach. Laryngoscope (Suppl) 36(12), part 2, 1984. Grant JCB: Grant’s Atlas of Anatomy. Baltimore, Williams & Wilkins, 1962. Gray H: Gray’s Anatomy of the Human Body, 17th ed. CM Goss, editor. Philadelphia, Lea & Febiger, 1959. McMinn RMH, Hutchings RT, Logan BM (eds.): Color Atlas of Head and Neck Anatomy. Chicago, Yearbook Medical Publishers, 1981. Naumann H (ed.): Head and Neck Surgery, vol 3. Philadelphia, WB Saunders, 1982. Nelson RA: Temporal Bone Surgical Dissection Manual. Los Angeles, House Ear Institute, 1982. Unsold R, et al: Computer Reformations of the Brain and Skull Base: Anatomy and Clinical Applications. New York, Springer-Verlag, 1982. Waddington MM: Atlas of the human skull, Rutland, VT, 1981, Academy Books.

PLATE 3

Figure 58-3. Basic venous drainage.

Figure 58-4. Arterial supply.

PLATE 4

Figure 58-5. Neural structures encountered during lateral skull base procedures.

Figure 58-6. Initial dissection level displaying the lateral skull base orientation.

PLATE 5

Figure 58·7. Enhanced infratemporal exposure gained by the anterior transposition of the facial nerve.

Figure 58-8. Exposed jugular foramen and carotid canal.

PLATE 6

Figure 58-g. Deeper dissection along the petrous portion of the carotid artery.

Figure 58-10. The most medial extent of surgical dissection.

PLATE 7

Figure 58·11. Complex neurovascular anatomy encountered during dissection near the jugular foramen and cavernous sinus.

Figure 58-12. Intracranial view from above of the skull base and related neurovascular structures.

Chapter

59 Michael J. O’Leary, MD, FACS Sanjay Ghosh, MD Richard E. Hayden, MD

Soft Tissue Reconstruction in Skull Base Surgery Outline Historical Perspectives Classification of Skull Base Defects Reconstructive Techniques Local Transposition Flaps Anterior Galeal-Pericranial Flap Temporoparietal Pericranial Flap Other Local Transposition Flap Choices Temporalis Muscle Flap Scalp and Forehead Flaps Regional Transposition Flaps

Latissimus Dorsi Myocutaneous Flap Other Regional Transposition Flaps Lower Trapezius Myocutaneous Flap Pectoralis Major Flap Microvascular Free Flaps Radial Forearm Fasciocutaneous Flap Rectus Abdominis Free Flap Other Microvascular Flap Alternatives Gastro-Omental Free Flap Latissimus Dorsi Free Flap

T

he dramatic advances in skull base surgery over the past 2 decades have largely been possible because of advances in reconstructive surgery. Without the ability to consistently and reliably separate the contaminated sinonasal cavities from the sterile intracranial compartment, skull base surgery could not evolve. This separation required viable vascularized tissue transfer, sometimes of significant volume, and as such awaited the development of predictable flaps to the skull base. Free flaps have provided the most reliable and most versatile tools for this reconstruction. Over the past 20 years, they have provided the “safety net” of recovery from skull base surgery, minimizing the morbidity and maximizing cosmetic and functional returns. With success rates exceeding that of pedicle transposition flap, the microvascular reconstructive surgeon represents an integral part of any modern skull base surgery team.

HISTORICAL PERSPECTIVES The evolution of flap reconstruction to the head and neck and, in particular, to skull base defects has been protracted. The oldest known flap, the midline forehead flap, originates in the head and neck and was reported by Sushruta in 700 BC.1 Interest in tissue transplantation by vessel anastomoses was fostered by Carrel as early as 1902.2 The concept of a tubed pedicled skin flap was advanced by Filatov in 1917 and by 1920, Gillies had transferred these flaps from the trunk to the head and neck. These were laborious staged procedures that required weeks and often 1004

Lateral Upper Arm Flap Lateral Thigh Free Flap Reconstructive Choices by Site Anterior Skull Base Middle Skull Base Posterior Skull Base Posterior Cranial Vault Reconstruction Future Developments “Janus” Double-Surface Flaps Stereotactic Skull Base Navigation Biopolymers Summary

months to deliver a skin flap with tenuous vascularity to the region. As such, they could not be candidates for reconstruction of skull base defects and were actually used into the 1960s for head and neck defects with only limited success. Owens3 is credited with describing a more reliable skin flap, based on the sternocleidomastoid muscle in 1955. This flap could not reach the skull base. In 1959, Seidenberg4 demonstrated that clinical organ transplantation was possible by the successful transfer of a segment of jejunum to the pharynx with vessel reapproximation. This led to rapid advances in microsurgery in the 1960s. Jacobsen and Saurez pioneered modern microvascular surgical techniques in 1960 and by 1959 Chinese surgeons in Shanghai had successfully replanted a severed hand. Krizek showed that vessels could be anastomosed end-toside and by 1966 Buncke5 had mastered the techniques of anastomoses in vessels less than 1 millimeter in diameter. These advances in replantation stimulated research and development in instrumentation, optics, sutures, and techniques. Pedicled skin flaps were revolutionized in 1959 when McGregor6 described his axial pattern forehead flap based on the superficial temporal vessels. The concept was adopted by Bakamjian7 in 1965 for the deltopectoral flap based on the internal mammary perforators. These flaps became the workhorse flaps for head and neck cancer surgery but did not facilitate ablation of the skull base. The pedicled galeal-periosteal flap, described by Sharif8 in 1978 provided for the first time a reliable source of vascularized tissues that could be used to separate the intra- and

Soft Tissue Reconstruction in Skull Base Surgery

extracranial compartments. Although its utility was limited to midline anterior cranial floor defects, undoubtedly this flap was responsible for a jump forward to modern anterior cranial base surgery. It remains a valuable tool for reconstructing defects in this region but is not possible in many patients because of previous surgery, radiation, or extensive ablation. In the 1970s microvascular free tissue transfer came of age. Harii9 first described microvascular augmentation to the vascularity of a flap in 1971 and McLean and Buncke10 are credited with performing the first microvascular free flap in 1972 with the transfer of the omentum to cover a scalp defect. Taylor and Daniel11 published a report of the first free skin flap in 1973. Panje12 and Harashina13 both described the transfer of this same groin flap by microvascular technique to the head and neck in 1976. Although these advances, like McGregor’s pedicled forehead flap, provided the potential for delivering vascularized flaps to the skull base, that potential was not fulfilled. The 1970s also represented a watershed in pedicled musculocutaneous flap development. Conley14 introduced the superior trapezius flap in 1972. Olivari15 rediscovered Tansini’s pedicled latissimus dorsi flap in 1976 and, within 2 years, Quillen16 showed how it could be reliably transferred to the head and neck. In 1977 the concept of musculocutaneous flaps was clearly delineated by McGraw. A free latissimus dorsi flap transfer was described by Watson17 by 1979. Although Ariyan’s18 pectoralis major flap revolutionized head and neck surgery in 1979, it would not reliably cover skull base defects. Certainly, both the free and the pedicled latissimus dorsi flaps as well as the lower island trapezius flap introduced by Baek19 in 1980 could have provided such coverage if only that potential had been realized at the time. The modern era of free-flap surgery came after 1978, when a wave of new flap discoveries provided the reconstructive surgeon with a vast array of flap options. Various combinations of skin, bone, muscle, fat, and viscera were now available, often with long vascular pedicles and largecaliber vessels. Taylor20,21 introduced osseous and osseocutaneous fibula and iliac crest flaps in 1979. In the same year, Baudet22 described the free gastro-omental flap. The scapular flap,23 parascapular flap,24 and lateral arm flap25 provided new skin flaps. Pennington26 introduced the rectus abdominis free musculocutaneus flap in 1980. This free flap was popularized for skull base reconstruction by Jones and remains a workhorse for reconstruction of skull base defects. The large surface area of free muscle offered by the latissimus dorsi and rectus flaps make them ideal for reliable adhesion and consequent closure of potential cerebrospinal fluid (CSF) leakage. The omentum also has this advantage, although the free omental flap never gained wide popularity for closing skull base defects. Baudet’s gastro-omental flap was popularized for head and neck reconstruction by Panje27 in 1987 and was subsequently described by Jones and Schramm28,29 for skull base reconstruction. Free flaps provide significant advantages over pedicled musculocutaneous flaps in this region. They are not limited by an arc of rotation with the potential for distal flap necrosis in the most critical area. Gravity also combines with the pedicle to produce a downward traction on the repair greater than that found with free flaps. Without the

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limitations in flap placement dictated by an attached pedicle, the free flap can be more easily contoured to maximize coverage of the defect while also providing, if required, the potential for midfacial skeletal, facial, or scalp replacement. Hesitation regarding margin adequacy becomes less of a concern, facilitating oncologically sound en bloc resection of skull base lesions. The continuous evolution of head and neck reconstructive surgery has provided the innovative skull base surgeon with many tools to reconstruct the range of skull base defects.

CLASSIFICATION OF SKULL BASE DEFECTS Many classifications exist for diseases of the skull base. From a reconstructive viewpoint, we prefer an anatomically derived method paralleling the anterior, middle, and posterior cranial fossa (Fig. 59-1). Further subdivision, into medial and lateral lesions, reflects the varying demands of deep versus superficial defects. Medial and central lesions often require restoration of three-dimensional soft tissue defects, whereas lateral lesions more frequently demand an extensive skin paddle for surface closure. Anterior lesions extend from the nasal region to the posterior orbit and include orbital and sinus tumors medially, with facial skin cancers and parotid neoplasms laterally. Craniofacial surgery for congenital and traumatic defects may exhibit bilateral involvement. The middle region extends from the posterior orbit to the petrous temporal bone and includes midline lesions such as chordomas and nasopharyngeal neoplasms. Temporal bone resections for middle ear and auricular malignancies and other lesions accessed via an infratemporal fossa approach typify lateral lesions of the middle skull base. The posterior region extends from the remainder of the temporal bone to the midline confluence of venous sinuses. Pathology in this

Figure 59-1. Anatomic classification system for skull base.

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area includes vascular and neurogenic lesions of the jugular bulb and posterior scalp malignancies. Meningiomas and sarcomas can affect any of these three anatomic divisions. Some tumor defects are closed primarily, but defects that result from resection of malignancies and advanced benign lesions often require more extensive restorations.

RECONSTRUCTIVE TECHNIQUES Defects following the removal of formerly “unresectable” diseases of the skull base tend toward the large size, and they are often found in a previously irradiated field. These features destine to the historical archives those reconstructions that are based solely on skin grafts and fat and mucosal flaps. Closure with vascularized tissue reduces healing time and morbidity, especially CSF leaks and infection. A hierarchy of vascularized reconstructive options currently available to the skull base surgeon ranges from local to regional transposition flaps to microvascular free flaps (Table 59-1). Here we discuss representative flaps from each tier, and for the more important procedures, we outline specific operative techniques and applications.

Local Transposition Flaps Commonly bypassed for more extensive flap transfers, three local flaps remain of primary importance in the repair of anterior and middle skull base defects. These flaps require meticulous attention during the ablative portion of the case to ensure their viability at closure. A clear understanding of the anatomic layers covering the temporal and parietal regions of the skull is critical (Fig. 59-2).30 The temporoparietal, or “innominate,” fascia is the key layer, which is well vascularized by the superficial temporal vessels.

Figure 59-2. Layered anatomy of the temporal and parietal scalp.

sutured directly to the dural remnant. The subsequent “dural seal” provides a supportive barrier over the cribriform area and ethmoid defect, greatly reducing the propensity for CSF leaks and retrograde infection. In more extensive, orbital defects, a lateral pericranial flap can be elevated based on the deep and middle temporal arteries from the temporalis muscle.32,33 A vascularized outer-table calvarial bone, harvested at the superior aspect of the flap, creates an osseous potential for reconstruction of larger anterior skull base defects.34 Technique and Applications After injection for hemostasis, a standard coronal incision is carried down to the bony calvarium. Dissection proceeds caudally in this avascular plane deep into the periosteum. At approximately 1 cm above the orbital rims, the supraorbital and supratrochlear vessels enter the flap and are

Anterior Galeal-Pericranial Flap Separation of the nasal cavities from the anterior cranial fossa is the key to reconstruction following en bloc resection of sinus malignancies.31 Preservation of the supraorbital and supratrochlear vessels allows elevation of a well-vascularized anterior pericranial flap (Fig. 59-3). This rugged, myofascial “sling” can be folded through the craniotomy defect and

TABLE 59-1. Vascularized Flap Hierarchy for Skull Base Reconstruction Local Transposition Flaps Anterior galeal-pericranial flap Temporoparietal flap Temporalis muscle flap

Microvascular Free Flaps Radial forearm flap Rectus abdominis flap

Regional Transposition Flaps Sternocleidomastoid flap Latissimus dorsi flap Pectoralis major flap Figure 59-3. Anterior galeal-pericranial flap.

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carefully preserved. Following tumor removal, usually through a combined craniofacial approach, a template for the pericranial flap is drawn on the deep surface of the coronal flap. Depending on the size of the defect and the need for a dural graft, flap thickness is improved through inclusion of the galeal layer in the flap. Inserted through the inferior craniotomy gap, the flap is secured by sutures over the orbits bilaterally and the sphenoid medially. A splitthickness dermal graft applied to the airway side of the flap is a useful adjunct to enhance the seal between the nose and the dura. The anterior galeal-pericranial flap carries the welldeserved classification of the “workhorse” flap for anterior skull base defects. Advantages include the relative ease of harvest, excellent vascularity, and minimal cosmetic and functional defect. Minor disadvantages might include the flap’s thin nature and absence of a skin-bearing capability, although that is rarely required for lesions in this area. Temporoparietal Pericranial Flap As an alternative use of the lateral scalp tissue, the temporoparietal flap derives a rich vascular supply from the superficial temporal artery. Composed primarily of the innominate, or “fool’s fascia,” between the subcutaneous layer and the deep temporalis fascia, this extensive flap can be elevated superiorly across the midline for transfer as a bilateral sling with dual blood supply. More commonly, it is used as a unilateral pedicled flap based on the superficial temporal vessels. The temporoparietal flap also can be harvested for free tissue transfer,35 although vessel diameters approximating 1 mm approach the lower limits of applicability. Composite features include the elevation of vascularized, calvarial bone grafts,36,37 and temporalis fascia. Technique and Applications A Doppler probe tracks the course of the superficial temporal vessels from their emergence in the pretragal area to several centimeters above the superior temporal line.38 A preauricular “face-lift” incision posterior to the vascular bundle extends superiorly as a T or Y for better exposure of the fascia (Fig. 59-4). Inferiorly, the superficial temporal vein lies superficial to the artery in the tragal region. Several centimeters superiorly, arterial branches to the occipital and forehead regions are identified and preserved if possible. Careful elevation of the skin in the immediate subfollicular plane is critical to preservation of the innominate fascial layer (Fig. 59-5). A needle-tip Bovie cautery in the cutting mode helps in this bloody plane. Deeper dissection risks injury to the superficial temporal vessels, and a more superficial dissection results in hair follicle damage and possible scalp necrosis (Fig. 59-6). Keep the anterior dissection behind an imaginary line extending 0.5 cm below the tragus to 1.5 cm above the lateral brow. Superiorly the flap can be extended to include vascularized outer-table calvarial bone by leaving the periosteum attached 2 cm above the superior temporal line. The deep aspect of the innominate fascia is commonly dissected free of the temporalis fascia, although, if required, it can be left attached as a dense, vascularized dural patch. Based inferiorly, the arc of rotation extends up to 14 cm for excellent coverage of anterior and middle

Figure 59-4. Blood supply to the temporoparietal flap.

cranial fossa defects. After transfer, close the preauricular incision in a cosmetic fashion. Although commonly confused with the temporalis muscle flap of limited utility, the temporoparietal flap has numerous applications in skull base reconstruction. It offers excellent vascularity and composite bone and fascial features that can be combined with either a pericranial or temporalis muscle flap. Alone, it has minimal cosmetic consequences; the scar is hidden in the hair and along the lines of a face-lift incision. Transfer can be performed as either a rotation or a free flap, although for the latter the small superficial temporal vessels may be a limiting factor. Relative disadvantages include the technical requirements of a precise dissection in a difficult plane and a lack of skin-bearing potential. Despite these minor limitations, the temporoparietal flap remains a favorite for reconstruction in this area.

Other Local Transposition Flap Choices Temporalis Muscle Flap Because of its proximity to the skull base, this muscle flap is frequently called on to provide soft tissue “filler.” Reliance on the temporalis flap should be accompanied by a thorough understanding of its limitations. The temporalis muscle fills the temporal fossa, and rotation of this expendable muscle of mastication leaves a lateral depression, more noticeable in a balding patient. The arc of rotation originates at the level of the zygomatic arch, which provides good lateral coverage and is well suited to the orbital region but limited more medially.39 The frontal branches of the facial nerve travel in a fat pad across the anterior zygomatic arch and must be carefully preserved. Perhaps the most significant limiting feature is the precarious blood supply to this muscle.

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A

B

C

D Figure 59-5. A, Left tegmen erosion with temporal lobe encephalocele. B, Temporoparietal flap elevated on the right superficial temporal artery pedicle. C, Temporoparietal flap inserted inferior to craniotomy bone graft. D, Coronal view of reconstructed middle cranial fossa floor.

The principal arterial supply is via the paired deep temporal branches off the internal maxillary artery, entering the medial muscle surface at the lateral pterygoid.40 During an infratemporal fossa dissection, the internal maxillary artery is often sacrificed, precluding the use of this flap when based only on the deep temporal vessels. Recent injection

studies41 confirm an anastomotic link to the superficial temporal system via the middle temporal artery, which may sustain the muscle without a deep arterial supply. Here the flap elevation includes the innominate fascia with the superficial temporal artery over the temporalis muscle. A temporoparietal flap can be raised in conjunction with

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Figure 59-6. Marginal necrosis exacerbated by curvilinear flap design. A vertical incision from the superior auricular attachment ensures better vascular supply and is preferred.

the temporalis muscle flap and then split to create a bilobate flap with independent rotation arcs. Scalp and Forehead Flaps Once mainstays of soft tissue coverage in this area, these flaps are primarily of historical interest in modern skull base reconstruction due to their limited rotational arc and significant disfigurement.

Regional Transposition Flaps Larger lesions require soft tissue replacement successfully delivered in a single stage. A number of well-vascularized, reliable myocutaneous flaps fill a critical need in skull base reconstruction. Latissimus Dorsi Myocutaneous Flap One of the largest flaps available, the triangular latissimus dorsi muscle arises from the lumbar and lower six thoracic vertebral spines, the sacrum and posterior iliac crest, as well as muscle slips from the ninth through twelfth ribs. Superiorly, the muscle converges as the quadrilateral tendon to a single insertion on the intertubercular sulcus of the humerus. In skull base reconstruction, the latissimus serves as either a pedicled or a free flap. The large skin flap offers a wide arc of rotation that serves the posterior and lateral skull base and, at times, even the anterior region without tension. The vascular supply is the thoracodorsal artery, a reliable branch of the subscapular artery off the subclavian (Fig. 59-7).42 The flap offers one of the largest skin islands available for transfer to the head and neck and may be deepithelialized to bury an even greater volume in deep defects. Suturing the skin island to the cervical skin flaps in a “rat tail” fashion offers support against gravity and avoids tunneling compression. Technique and Applications Typically, the patient must be placed in the lateral decubitus position for flap harvest, often precluding a concomitant

Figure 59-7. Vascular supply to the latissimus dorsi.

“two-team” approach. When a smaller amount of tissue is required, however, the flap can be raised with the patient supine. The skin incision begins at the posterior axillary fold, the paddle directed in either a horizontal or more commonly an oblique orientation. The vascular pedicle can be identified early by proximally tracing the lateral artery superiorly over the serratus anterior to its junction with the subscapular artery. The thoracodorsal artery, supplying the latissimus, is also identified here and traced distally deep to the muscle. Alternatively, the latissimus can be first dissected easily from the underlying ribs with identification of the thoracodorsal artery on the undersurface in a fashion similar to elevation of the pectoralis major muscle flap. Medially, paraspinal musculocutaneous perforators are ligated without flap compromise. A tunnel is prepared between the pectoralis minor and major for delivery to the neck region. The thoracoacromial supply to the pectoralis major is carefully avoided. The wound is drained and usually closed primarily under a fair amount of tension. With large flap elevations, a skin graft might be employed. Even as a regional pedicled flap transfer, the latissimus possesses an arc of rotation that easily covers lateral defects of the middle and posterior cranial fossa (Fig. 59-8).43,44 Functional debility and donor site morbidity are surprisingly low, with primary closure feasible even in flaps up to 10 × 20 cm. The lateral positioning requirement represents the major argument against the latissimus flap. Other negatives include a limited anterior reach in some patients, seroma formation, and the thick, poorly matching skin paddle.

Other Regional Transposition Flaps Lower Trapezius Myocutaneous Flap Another skull base workhorse is the lower (posterior or extended island) trapezius myocutaneous flap, overlying the medial-inferior aspect of this muscle. As one of three trapezius flaps described, early flap failures and questions

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A

B

C

D Figure 59-8. The latissimus dorsi pedicle flap. A, CT scan of recurrent periauricular basal cell carcinoma. B, Posterior skull base defect with large intracranial exposure. C, Latissimus dorsi pedicle flap at harvest. D, Postoperative closure at 1 month.

regarding the arterial supply dampened initial enthusiasm. An excellent series of prosections by Netterville and Wood45 help clarify this confusion. In 30 cadaver dissections, the transverse cervical artery, which is classically described as the principal vascular supply to this muscle46 (Fig. 59-9), was found to be the dominant vessel in less than one-third (9 of 30) of the cadavers. The dorsal scapular artery, previously considered a supplemental vessel, was the dominant supply in half the dissections. The remaining specimens (6 of 30) exhibited equal-diameter vessels, with the transverse cervical artery supplying the territory above the rhomboid minor and the dorsal scapular supplying the territory below the rhomboid minor muscle. Inclusion of the dorsal scapular artery greatly enhances the viability of the lower trapezius, extending 15 cm below the tip of the scapula. The arc of rotation of the lower trapezius flap is

adequate for most posterior and lateral skull base defects; this flap spares the upper trapezius muscle fibers and shoulder elevation is preserved. Limiting aspects of this flap include difficult intraoperative positioning and prior radical neck dissection injury to the transverse cervical artery (Fig. 59-10). Pectoralis Major Flap The undisputed choice of a pectoralis major flap for anterior head and neck defects has been advocated in skull base reconstruction47 (Fig. 59-11). It does not share the large arc of rotation enjoyed by the latissimus, which combined with its thickness and lack of room for a two-team capability limit its applications in the reconstruction of skull base defects48 (Fig. 59-12). Other pedicled flaps described for

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Transverse cervical a. Ascending branch

Descending branch

Figure 59-9. Classical description of the lower trapezius vascular.

skull base reconstruction, including the sternocleidomastoid and deltopectoral flaps, are rarely included in the first echelon of regional transposition flaps. All pedicled flaps suffer from a finite arc of rotation and restricted two-team capability, integral features of our current approach to skull base disorders.

Microvascular Free Flaps The reliability and decreased morbidity of microvascular free tissue transfers relegates the plethora of regional myocutaneous rotational flaps to the cosmetically unappealing archives, documenting the evolution of modern skull base surgery. Beasley and colleagues49 compared their local, pedicled, and free-flap reconstructions for 90 anterior skull base defects performed over 10 years. Free-flap reconstructions exhibited a significantly higher incidence of uncomplicated primary wound healing (95% versus 62.5%) and a much lower incidence of flap loss (0%), cerebrospinal fluid leak (5%), meningitis, and abscess (0%) than did defects reconstructed with pedicled myocutaneous flaps. Temporalis muscle flaps, for example, exhibited a 27% necrosis rate, which likely reflects the tenuous nature of its delicate, paired deep temporal vascular supply. The consequences of even partial flap loss can be disastrous in the skull base, where often the most distal portion of a rotational flap is involved primarily in sealing off the cranial contents. Interestingly, there was no significant extension of operative times for the free-flap group, reflecting a focus on two-team, concomitant ablative, and reconstructive surgeries. Although limited by the largely retrospective nature of the review, they concluded that microvascular

Figure 59-10. Lower trapezius myocutaneous pedicle flap. Gravity and distal flap circulation compromise the use of this flap in skull base surgery.

free-tissue transfer is the safest, most economical procedure when faced with moderate to large composite defects of the cranial base. In our skull base team experience, concomitant free-flap transfers actually accelerate the speed of these extended cases compared to sequential, pedicled flap repair. We prioritize free flaps that accommodate two-team simultaneous surgery (Fig. 59-13). Recipient vessel sites, the major limiting factor in such transfers, are most frequently cervical branches of the external carotid artery and the external jugular vein. Following radical neck dissection, the internal

Thorocoacromial a.

Pectoral branch

Figure 59-11. The pectoralis major myocutaneous flap.

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team and arrives at the defect to find recipient vessels available and prepared for microvascular anastomosis. Through the coordination of a concomitant two-team approach (Fig. 59-14), both teams remain fresh and operating time is reduced, despite closure of considerably larger defects.

Radial Forearm Fasciocutaneous Flap

A

Our most common choice for reconstruction of skull base defects is the radial forearm flap, across all compartments— anterior, middle, and posterior cranial fossa. Ease of harvest with long, redundant pedicles, hardy skin with unparalleled viability, and minimal donor site morbidity make this the workhorse flap in skull base reconstruction. This fasciocutaneous flap was first described by Yang50 in 1981 and was anecdotally referred to as the “Chinese flap.” Supplied by direct septocutaneous perforators from the radial artery via the lateral intermuscular septum, the arterial pedicle may include the entire length of the radial artery (Fig. 59-15). Paired venae comitantes are drained primarily by the cephalic vein that can be extended above the elbow. Featuring this lengthy pedicle, the radial forearm flap can be placed in most skull base locations and still access reliable host vessels in the neck. Almost the entire volar surface of the forearm is available as a skin paddle, although the fascial and subcutaneous tissues may be used alone for deeper skull base defects (Fig. 59-16). The flow-through nature of the vascular pedicle offers the unlikely possibility of additional free-flap “hookups” if necessary. Neurosensory potential also exists with the inclusion of the lateral or medial antebrachial nerves that supply the skin paddle. If necessary, the superficial branch of the radial nerve can also be included as a vascularized nerve graft to bridge an ablative nerve defect. A preoperative Allen test, as the surgeon manually occludes both the radial and ulnar arteries and watches for reperfusion following ulnar artery release, ensures against the rare anomaly in which the ulnar artery fails to provide adequate supply to the hand via both the superficial and deep palmar arches. Morbidity includes a cosmetically unattractive closure of the skin graft donor site with a sensory deficit over the volar aspect of the forearm. The long, reliable vascular pedicle combined with the functional advantages of a large, pliable fasciocutaneous paddle and vascularized nerve graft make the radial forearm a unique reconstructive option. Rectus Abdominis Free Flap

B Figure 59-12. A, Pectoralis major myocutaneous flap with at the limits of its arc of rotation. B, Note the critical closure occurs at the most dependent portion of the flap.

jugular vein, the superficial temporal vascular bundle, the occipital artery, or even a mastoid emissary vein can be used. Preservation of potential vascular supplies must be a clear priority from the onset of the approach. Ideally, the reconstructive team begins simultaneously with the ablative

Introduced as a free flap by Pennington51 in 1980, the rectus abdominis offers many features uniquely suited for reconstruction of the skull base52,53 (Fig. 59-17). The paired rectus abdominis muscles extend from the lower costal cartilages to the pubic tubercle and are supplied on the undersurface by the superior and deep inferior epigastric vessels (Fig. 59-18). The latter is consistently the dominant supply and allows transfer of the entire muscle length because of an extensive intervening anastomotic network. The rectus flap features a long vascular pedicle (up to 15 cm) and large vessel diameters (3 mm), which make it an excellent choice for deep defects. Transverse fascial inscriptions in the rectus abdominis muscle support suspension sutures

Soft Tissue Reconstruction in Skull Base Surgery

Lattissimus Dorsi

Lateral Upper Arm

Radial Forearm

Rectus Abdominus

Gastro-omental

Lateral Thigh

Figure 59-13. Free flaps available for skull base reconstruction.

Figure 59-15. Vascular supply to the radial forearm flap.

1013

Figure 59-14. Sharing the field in concomitant modern skull base surgery.

that can be attached to holes drilled in the bony margins of the defect. Available as either a myocutaneous or pure muscle flap, the rectus offers the flexibility to tailor the reconstruction to a wide variety of defects. Careful donor site closure avoids development of an abdominal hernia, particularly below the arcuate line where both layers of the internal oblique aponeurosis run anterior to the rectus muscle, leaving no posterior rectus sheath below this level. If necessary, an alloplastic mesh screen can be incorporated into the repair to help prevent ventral herniation. Another reported possible morbidity includes inspiratory splinting due to postoperative incisional pain, although this has not been our experience. Flap harvest from the supine position allows a simultaneous team approach and shortens operative times. The safe, reliable, rapid, and versatile features of the rectus abdominis flap make it a leading choice for skull base reconstruction.

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A

C

B

D

Figure 59-16 A, Recurrent postauricular squamous carcinoma AS. B, Radial forearm free flap.C, Postoperative defect. D, Patient external auditory canal remnant.

Technique and Applications A variety of cutaneous paddles can be designed with the rectus flap, which determines incision placement. When the rectus abdominis is elevated solely as a muscular flap, a paramedian or occasionally a midline incision is used (Fig. 59-19). The anterior rectus sheet is opened in the midline over the muscle, but in most cases, it is not harvested to help reinforce a layered abdominal closure. The muscle is freed from the enveloping sheath, and the vascular pedicle is carefully identified at the lateral undersurface of the muscle, about 5 cm superior to the pubic tubercle. The pedicle is then dissected proximally and ligated at its penetration point through the transverse abdominal fascia deep to which it exits the external iliac truck. If possible, the muscle below this point should be left in place because removal below the arcuate line increases the chance for postoperative herniation. Reinforcement of defects below

the arcuate line is enhanced by a contralateral “flip-flop” rotation of the anterior rectus sheet over the defect. Another common alternative involves synthetics reinforcement using Marlex mesh screen sutured over defects below the arcuate line. The remainder of the wound is then closed in a layered fashion over suction drains, which can be removed at 3 days to decrease the odds of seroma collection. The combination of a long pedicle, intercalated fascial strips, and the simultaneous two-team capability make the rectus the most common free flap used for closure of skull base defects. If thickness is a problem when a cutaneous paddle is required, the muscle can be transferred and skingrafted with excellent results. The long pedicle and suspension ability of the muscle make it the best choice for closure of deep, medially based defects, which are among the most difficult in this area. The rectus sheath can also be included as a vascularized graft for dural defects. The disadvantage of a possible abdominal hernia can be

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minimized by meticulous multilayer closure over synthetic reinforcement.

Other Microvascular Flap Alternatives Gastro-Omental Free Flap

A

The greater omentum has historically been transposed locally to cover thoracic and abdominal wounds later with good success. At the Navy Hospital Oakland in 1971 it was introduced as a free flap to cover successfully a large scalp defect with anastomosis to the superficial temporal artery.54 Coupled with a segment of the greater curvature of the stomach,55 the gastro-omental flap has many advantages in reconstruction of skull base defects. The omentum is richly vascularized peritoneal connective tissue that tenaciously seals off leaks, a feature particularly adapted to the closure of intracranial defects. Through a burst of fibroblastic activity, adhesions have been shown to develop within a few hours of intra-abdominal injuries.56 The tissue also contains condensations of fixed macrophages, known as “milky spots,” which impart an antibacterial property missing from cutaneous or muscular flaps. A hemostatic quality is also reported due to the ability of omentum to stimulate prothrombin activation with subsequent conversion of fibrinogen to fibrin.57 Other advantages include the large amount of pliable tissue and distant harvest site, which promotes a simultaneous two-team approach. While the morbidity of a laparotomy is not added lightly, precautions against adhesions and hernia help to minimize complications. Technique and Applications

B Figure 59-17. A, Left rectus muscle with fascial striations. B, The free rectus attached to branches of the external carotid artery and jugular vein.

The stomach with attached omentum is easily approached through either a midline or paramedian abdominal incision. The superior aspect of the greater omentum is delivered into the wound by separating it in an avascular plane from the inferior portion attached to the transverse colon. The gastroepiploic vessels are identified as running along the stomach’s greater curvature from the neck to the pylorus and giving off radial branches to the rich end-arterial arcade of the omentum (Fig. 59-20A). A 3 × 8-cm segment of the greater curvature is isolated and transected by an abdominal stapling device (Fig. 59-20B). This “pouch” can later be opened to a 6 × 8-cm gastric mucosal flap and typically the region lacks the acid-producing parietal cells. The left and right gastroepiploic arteries may be temporarily clamped to evaluate the anastomotic circulation. If adequate, the vessels are divided, the abdominal remnants ligated, and the flap removed for transfer (Fig. 59-20C). Before wound closure, the stapled greater curvature of stomach is oversewn and a pyloroplasty performed. A feeding jejunostomy is placed and the abdomen closed in layers. Vascular pedicle length can be extended to provide for most skull base lesions by selective ligation of radial branches. The right gastroepiploic artery is usually the dominant vessel, with a diameter of 2 to 3 mm. The accompanying vein is in the 3- to 4-mm range with a thin, delicate wall typical of abdominal vessels. If necessary, the flap can be split in two based on the distribution of the right and left gastroepiploic vessels.

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Figure 59-18. Vascular supply to rectus abdominis.

The applications of this reliable and versatile flap are numerous.58 It is particularly well suited to the closure of deep-seated, medial defects.59 The gastric segment also provides an excellent replacement for an associated upper airway mucosal loss in the nasopharynx and oropharynx (Fig. 59-20D). In such cases, the pedicle can be tunneled down to the cervical vessels in a large Penrose drain, which helps to avoid twisting. The rich omental vascularity supports a skin graft for external defects. Overlapping the omentum in layers allows for the restoration of bulk where needed. Soft tissue contour restoration rounds out the various applications.60 Despite the associated abdominal morbidity, the excellent wound-healing characteristics of the gastro-omental flap make it a mainstay for the closure of defects in the skull base region. Latissimus Dorsi Free Flap Harvested as a free flap, the latissimus can be placed anywhere in the skull base for either a myocutaneous or muscular flap closure. Pedicle length and vessel diameters vary depending on the point of harvest along the subscapular arterial tree (Fig. 59-21). Ligation distal to the circumflex scapular branch preserves the supply to the scapular flap territory and yields an 8- to 12-cm pedicle with 2-mm vessel diameters. If necessary, length can be extended by ligation at the subscapular artery takeoff from the axillary artery, which increases vessel diameters to the 3- to 4-mm range. The amount of flat muscle and excellent vascularity of the latissimus flap make it particularly useful in the coverage of alloplastic materials and chronically infected wounds. Donor site morbidity is small, as noted earlier. Two-team access for flap harvest is not as good as with the lateral thigh and rectus flaps.

Lateral Upper Arm Flap This fasciocutaneous flap offers a supple, 8 × 10-cm skin paddle with a neurosensory potential.61,62 Vascular supply is based on the profunda brachii artery and its posterior radial collateral division located in the lateral intermuscular septum (Fig. 59-22). Short pedicle lengths of 6 to 8 cm and vessel diameters of 1 to 2 mm limit the use of this flap. Lateral Thigh Free Flap The proximity of the latissimus and rectus to the head region tests the friendship of even the most familiar ablative and reconstructive teams; the lateral thigh flap described by Baek63 spares such intimacy. Based on the terminal cutaneous perforator of the profunda femoris artery (Fig. 59-23), this reliable fasciocutaneous flap offers up to 25 × 14 cm of skin and subcutaneous tissue.64 The vascular pedicle is long (8 to 12 cm) and the vessel caliber ranges from 2 to 5 mm in diameter. The dominant vascular pedicle rarely is the second or fourth perforator of the profunda system, but these vessels also may be included in a long skin ellipse. The donor site closes primarily with morbidity comprising a small area of hypesthesia with a vertical scar on the lateral thigh. Technique and Applications With the knee flexed and internally rotated, a line is drawn connecting the greater trochanter superiorly with the fibular condyle of the femur, which delineates the long axis of the flap. A long ellipse of skin simplifies closure and allows adjustment of the skin paddle to incorporate additional vascular supplies other than the third perforator if noted. The anterior border is incised first and the dissection is

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B A

C

D

Figure 59-19. The rectus abdominis free flap. A, Large cordoma of medial middle fossa. B, Rectus flap incision. C, Free rectus abdominis flap after pedicle ligation. D, CT scan of defect following flap transfer.

carried down to the prominent fascia lata of the iliotibial tract. The intermuscular septum is identified carefully along the posterior margin of the tract and contains the small distal branches of the perforating arteries. Exposure is greatly enhanced as the insertions of the vastus lateralis are released from the linea aspera of the femur, and the larger diameters of the proximal perforating vessels can be appreciated. The third perforator is located just distal to the adductor brevis, approximately midway along the incision, and it represents the dominant supply in the majority of cases. In 5% of cases, there is also a significant contribution from the fourth or terminal perforator that can be readily included in the flap. The vessels are traced to their origin from the profunda femoris. Flap viability is assessed before harvest. If color and temperature remain adequate, the vessels are ligated

and the flap is transferred in an ice slush to the prepared donor vessels in the head and neck. The arterial microvascular anastomosis is performed with 10–0 continuous sutures and venous approximations with Nakayama ring pin devices if greater than 2 mm in diameter. The donor site is closed primarily in layers and a leg drain is placed for a minimum of 3 days to avoid the frequent occurrence of a seroma. The combination of a long vascular pedicle (longer than 10 cm), large skin paddle, and a two-team donor site make the lateral thigh an excellent choice in the reconstruction of large skull base defects, particularly those involving significant skin loss. Another feature of this underused flap is the potential for restored sensitivity through inclusion of a lateral femoral cutaneous nerve, which can be hooked up to a branch from the trigeminal nerve or a branch from the

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A

B

C

Figure 59-20. The gastro-omental free flap. A, Gastroepiploic supply to the greater omentum. B, Gastro-omental flap ready for harvest. C, Free gastro-omental flap. D, Gastric mucosal closure of oropharyngeal defect.

D

cervical plexus. Inclusion of the fascia lata on the medial surface of the flap offers the possibility of a vascularized graft for a watertight closure of an associated dural defect.

RECONSTRUCTIVE CHOICES BY SITE Anterior Skull Base The workhorse for reconstruction of both medial and lateral defects in the anterior skull base region is the galealpericranial flap (Table 59-2). Sutured to the deepest part of exposed dura, this highly vascularized flap adequately nourishes a dural homograft and provides adequate support for the frontal lobes (Fig. 59-24). The flap acts as a CSF seal and physiologic barrier with excellent viability. Bilateral temporalis suspension flaps may be provided to further support large, central defects. For anterior central

defects in patients with unilateral loss of pericranium and temporalis muscle blood supply, an extended temporoparietal pericranial flap based on the superficial temporal vessels often suffices. When this option is lacking or when more bulk is required anteriorly, free flaps usually present a more attractive option than regional myocutaneous pedicle flaps. The rectus flap’s long pedicle and workable amount of muscle make it a leading choice for deep and complicated anterior reconstructions. Another alternative for more lateral anterior skull base lesions is the temporoparietal flap. External anterior defects that include facial skin can be addressed with a number of free and pedicled skin or myocutaneous flaps, depending on the amount of tissue and vascular pedicle length required. Pedicled myocutaneous flaps usually reach these areas, but these flaps often provide far more bulk and weight than is necessary, resulting in massive, eventually ptotic reconstructions that require debulking and revision surgery.

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Figure 59-21. Pedicle length options with the latissimus dorsi free flap.

Middle Skull Base The middle skull base presents a challenge for flap reconstruction because of the tight space. We routinely keep the temporoparietal flap option alive by preserving the superficial temporal vessels whenever possible. This thin, highly vascular and pliable flap is ideally suited for isolation of the middle cranial fossa from the temporal bone below in

Figure 59-22. Vascular supply to the lateral upper arm flap.

conjunction with free bone, cartilage, and fascia grafts (Fig. 59-25). Repair of the medial defects in the middle cranial fossa following resection of chordomas or other midline lesions involving the nasopharyngeal cavity. Limited access, combined with the high density of vital structures, make soft tissue replacement and dural repair an arduous task. As alluded to earlier, the unique features of the rectus abdominis

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Figure 59-23. Vascular supply to the lateral thigh flap.

ideally suit these rigorous demands. The excellent vascularity accelerates dural patch healing and the long vascular pedicle allows hookup to more laterally situated vessels. Rapid mucosalization characterizes the exposed muscle surfaces and eliminates the need for skin grafting. Muscle bulk is adequate for even the largest defects and slips of muscle may be fashioned to obliterate sinuses and seal crevice defects. The latissimus dorsi free flap performs similarly but does not possess the fascial inscriptions for suspension and often requires a positional change for harvest and closure. Large lateral defects of the middle skull base are amenable to pedicle flap closure with latissimus or trapezius myocutaneous flap. Smaller defects respond well to a temporalis muscle transposition flap. For superficial lesions involving a facial nerve defect, a radial forearm free flap with vascularized interposition nerve graft might be the flap of choice.

Posterior Skull Base Posterior fossa defects after lateral temporal bone resections are best repaired with the radial forearm free flap. The limited arcs of rotation of pedicled myocutaneous flaps, including the pectoralis major, lower trapezius, and even latissimus dorsi are generally inadequate and place TABLE 59-2 Flap Choices by Site Skull Base Defect

Flap selections

Anterior fossa

Galeal-pericranial/temporoparietal/radial forearm/rectus Temporoparietal/rectus abdominis/gastro-omental Radial forearm/rectus abdominis/lateral thigh

Middle fossa Posterior fossa

the most dependent portion of the flap in the area for critical closure. The results are usually less than satisfactory, with partial flap necrosis and wound dehiscence (Fig. 59-26). In contrast, the radial forearm free flap offers the advantages of simultaneous harvest, reliable closure with excellent cosmetic results (Fig. 59-27). A prosthetic auricle is readily fashioned and can be fit with a hearing aid if the cochlea has been spared.

POSTERIOR CRANIAL VAULT RECONSTRUCTION Closure goals following posterior fossa surgery include dural repair, CSF leak prevention, and cranial vault reconstruction. Although all skull base surgeons recognize the importance of dural closure and CSF leakage prevention, the need for cranial vault reconstruction has been somewhat controversial. Traditionally, neurosurgeons have approached the posterior fossa by performing a craniectomy. Following tumor resection, the dura, suboccipital musculature, and skin are closed to prevent CSF leakage, and a bony defect is allowed to remain. Describing the translabyrinthine approach to acoustic neuromas in the 1960s, Hitselberger and House relied first on gel foam and then on an abdominal fat graft to seal the posterior fossa dura. They did not feel it necessary to perform any bony cranial vault reconstruction, and this has been quite common throughout neurosurgery. More recently, surgeons have begun to include cranial vault reconstruction following posterior fossa surgery. We routinely place rigid titanium mesh over the abdominal fat graft covering the dura, followed by fibrin glue application and wound closure (Fig. 59-28). Plate fixation employs

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B

A

D

Figure 59-24. Anterior cranial fossa reconstruction. A, Computed tomography (CT) scan demonstrating an advanced paranasal sinus malignancy. B, Coronal incision performed with isolation of a pericranial flap. C, The pericranial flap is introduced below the inferior limb of the bicoronal bone flap. D, The wound is well healed at 1 month postoperatively with complete skin graft take.

C self-tapping screws, made of an magnetic resonance imaging (MRI) compatible titanium alloy. This step adds approximately 10 to 15 minutes to the operative time and provides rigid reconstruction of the cranial vault. Recent clinical studies have demonstrated some distinct advantages to rigid cranial vault reconstruction, or cranioplasty, following posterior fossa surgery. First, rigid reconstruction of the cranial vault may help prevent cerebrospinal fluid leakage. Gnanalingham and colleagues65 analyzed a series of 110 pediatric patients who had had surgery for posterior fossa tumors. Approximately half the patients had cranial vault reconstruction (craniotomy), and the other half were left with a bony defect or craniectomy. In this series, the authors observed a statistically significant decrease in the incidence of CSF leakage and pseudomeningocele formation in the craniotomy cases. Twenty-seven percent of the patients with craniectomy experienced CSF leakage, while only 4% of the craniotomy group had such leaks. Furthermore, 23% of the craniectomy patients experienced pseudomeningocele formation, while 9% of the patients that had cranial vault reconstruction experienced

this complication. These authors theorize that the replacement of the bone flap may provide counterpressure against the dural suture line and subsequently prevent the egress of CSF from the posterior fossa. Despite the precise mechanism, this study demonstrates a distinct reduction of CSF leakage and pseudomeningocele formation with the reconstruction of the cranial vault following posterior fossa surgery. Cranioplasty following posterior fossa surgery may also reduce the incidence of headaches. Patients who undergo retrosigmoid craniotomy may experience headaches. Schessel and colleagues66 observed significant local discomfort and headache in 59.7% of their patients who underwent retrosigmoid craniectomy for acoustic neuromas. These authors theorize that the suboccipital musculature may become adherent to the dura, and such traction of the occipital musculature on the dura can contribute to significant pain. Furthermore, they propose that cranial vault reconstruction would provide a rigid barrier to separate the occipital musculature from the dura. In support of this methodology, Harner and colleagues67 compared

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A

B

C

D

Figure 59-25. A, Intracerebral abscess complicating chronic otitis media. B, Proximity to fourth ventricle. C, Source of temporal lobe seizures. D, Status post middle cranial fossa approach for incision and drainage with temporoparietal flap for isolation from temporal bone.

the incidence of headache in patients with acoustic neuroma managed with and without cranioplasty. These surgeons observed a 4% incidence of headache in patients who had had cranioplasty, and 17% in a matched group who had not had cranioplasty following acoustic neuroma removal. They hypothesized that the insertion of rigid methylmethacrylate between the dura and the suboccipital musculature reduced the incidence of headaches. Wazen and colleagues68 have provided further clinical evidence to substantiate the theory that cranioplasty can reduce postoperative headaches. These authors analyzed 30 patients

who were managed with retrosigmoid craniectomy for acoustic neuroma surgery and another 30 patients who had had cranioplasty. These clinicians observed a similar incidence of headache in both groups; however, the severity of headache was much greater in the craniectomy group.47 A third advantage of cranioplasty is improved aesthetic appearance with restoration of the normal cranial vault contour. With craniectomy, patients have significant indentation in their cranial vault. With small defects that are covered by hair, such as is seen in most translabyrinthine craniotomies, the bony defect is not a functional or aesthetic

A

B

Figure 59-26. A, Cosmetic disfigurement following pectoralis major flap for posterior fossa closure. B, Right ear defect with dehiscence of dependent end of pectoralis major flap.

A

B

C

D

Figure 59-27. A, En bloc resection of recurrent adenoid cystic carcinoma. B, Branching sural nerve harvest. C, Facial nerve distal branches. D, Radial forearm flap closure.

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A

B

C

D

Figure 59-28. Posterior fossa craniotomy reconstruction. A, Autologous fibrin sealant mixture of human fibrinogen and thrombin (Tisseal, Baxter). B, Titanium plating of the craniotomy bone plate. C, Fibrin glue added subcutaneously. D, Superficial wound closure.

concern. Patients who require large retrosigmoid craniectomies, or who are bald, can experience a dramatic impact on their appearance with such an indentation in their cranial vaults. Such aesthetic considerations are not a primary concern for patients with brain tumors; however, as clinical results continue to improve and patients’ expectations continue to rise, the skull base surgeon will have to face such issues. Cranial vault reconstruction is a simple technique to enhance closure in posterior fossa surgery. Recent clinical studies have demonstrated a decreased incidence of CSF leakage and pseudomeningocele formation following cranial vault reconstruction in pediatric patients. Furthermore, current literature suggests that cranioplasty leads to a reduction in the severity of postoperative headaches.

FUTURE DEVELOPMENTS “Janus” Double-Surface Flaps The most frequent complication of a skull base reconstruction involves an inadequate dural defect repair, with CSF leak and meningitis. Addition of a vascularized covering augments traditional dural repairs using nonvital tissue such as autogenous fascia lata or lyophilized dura. Recently

we have used a vascularized fascial layer for dural patching as part of a double-surface flap, nicknamed after the twoheaded coin depicting the Roman god Janus. Several free flaps offer this potential: the rectus abdominis with the anterior rectus sheath superiorly, the lateral thigh with tensor fascia lata (Fig. 59-29), the temporalis and temporoparietal flaps with temporalis fascia, and the lateral arm flap with brachial fascia. Determination of a significant healing improvement using these vascularized dural patches awaits comparative clinical analysis.

Stereotactic Skull Base Navigation At the turn of the century, Sir Victor Horsley, a neurophysiologist and surgeon, joined Robert Henry Clarke, a mathematician who applied a Cartesian coordinate system to an animal frame, for the first, true “stereotactic” surgical instrument.69 Although never deployed in humans, the concept has evolved over recent years into framed and frameless neuronavigation. In the former category, stereotactic radiosurgery offers alternatives to open surgery for a wide array of benign skull base tumors. In the latter area, a wide array of frameless stereotactic systems have been developed, affording the skull base surgeon the opportunity to determine his precise location as well as that of unseen vital structures that lie in the field through exact radiologic registration in all three planes of space (Fig. 59-30A).

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Figure 59-29. “Janus” double-surfaced lateral thigh flap with undersurface vascularized fascia available for watertight dural closure.

As with the complementary supply and demand forces of economic theory, the concept of minimally invasive surgery dovetails with skull base reconstruction by reducing the extent of the defect and simplifying the demands for closure. In the anterior cranial fossa, adoption of a stereotactic transphenoidal approach significantly reduces the morbidity of the traditional translabial approach and simplifies the surgical equipment required (Fig. 59-30B). Vital landmarks are readily defined and preserved and the fibrin glue closure is rapid and obviates the need for surgical packing, often the most uncomfortable consequence of the transphenoidal approach. Further developments in this nascent field will likely reduce the complexity of reconstructive alternatives for minimally invasive skull base procedures.

A

Biopolymers Numerous synthetic materials have recently entered the medical arena following the “polymer revolution” that swept industry decades ago. Successfully applied to orthopedic and spinal injuries, these biocompatible materials also may serve as slow-release “bioreservoirs” for local deposition of antimicrobials, and so forth. Coupled with the rapid advances in molecular biology featuring an expanding array of growth factors, the clinical potential of these synthetic materials will undoubtedly offer an exciting adjunct to reconstruction of skull base defects.

B Figure 59-30. A, Stereotactic registration of anatomic to radiologic coordinates. B, Stereotactic endoscopic transphenoidal surgery. (From O’Leary MJ: Stereotactic advances in otolaryngology/skull base surgery. In Myers EN [ed.]: Advances in Otolaryngology: Head and Neck Surgery, vol 14. St. Louis, Mosby, 2000, pp 127–161.)

SUMMARY In the past decade, soft tissue reconstruction of the skull base defect has migrated away from traditional pedicled flaps to rely largely on an expanding array of free-flap options. Superior flap success rates, with improved functional and cosmetic results, have enhanced the quality of living for the survivor of skull base trauma. The microvascular reconstructive surgeons play a key role in the maturation of highly specialized teams who perform modern skull

base surgery. Their concomitant work is critical to optimal outcomes in these high-intensity procedures.

ACKNOWLEDGMENTS The authors acknowledge the large clinical contributions by our microvascular colleagues at the Senta Clinic, Dr. Michael Halls and Dr. Diana Briester-Ghosh.

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REFERENCES 1. Hauben DJ: Sushruta Samhita (Sushruta’s Collection) (800–600 BC?). Pioneers of plastic surgery. Acta Chir Plast 26(2):65–68, 1984. 2. Morris DJ, Pribaz JJ: The interrupted-continuous microsurgical suture technique. Microsurgery 13:103–105, 1992. 3. Owens N: A compound neck pedicle designed for the repair of massive facial defects: Formation, development and application. Plast Reconstr Surg 15(5):369–389, 1955. 4. Seidenberg B, Rosenak SS, Hurwitt ES, Som ML: Immediate reconstruction of the cervical esophagus by a revascularized isolated jejunal segment. Ann Surg 149:162–171, 1959. 5. Buncke HJ Jr, Schulz WP: Total ear reimplantation in the rabbit utilising microminiature vascular anastomoses. Br J Plast Surg 19:15–22, 1966. 6. McGregor IA: The temporal flap in intra-oral cancer: Its use in repairing the post-excisional defect. Br J Plast Surg 16:318–335, 1959. 7. Bakamjian VY: A two-staged method for pharyngoesophageal reconstruction with a primary pectoral skin flap. Plast Reconstr Surg 36:173–184, 1965. 8. Sharif A, Aboul-Dahb YW, Abdel-Hafez MS, Ghaly AF, Hussein A: The pericranium flap operation. A new operation for the treatment of progressive infantile hydrocephalus. A preliminary report of 20 cases. Acta Neurochir (Wien) 41(4):335–347, 1978. 9. Harii K: Microvascular free flap transfer in reconstructive surgery. Ann Acad Med Singapore 8(4):425–439, 1979. 10. McLean DH, Buncke HJ Jr: Autotransplant of omentum to a large scalp defect, with microsurgical revascularization. Plast Reconstr Surg 49(3):268–274, 1974. 11. Taylor GI, Daniel RK: The free flap: Composite tissue transfer by vascular anastomosis. Aust N Z J Surg 43(1):1–3, 1973. 12. Panje WR, Bardach J, Krause CJ: Reconstruction of the oral cavity with a free flap. Plast Reconstr Surg 58(4):415–418, 1976. 13. Harashina T, Fujino T, Aoyagi F: Reconstruction of the oral cavity with a free flap. Plast Reconstr Surg 58(4):412–414, 1976. 14. Conley J: Use of composite flaps containing bone for major repairs in the head and neck. Plast Reconstr Surg 49(5):522–226, 1972. 15. Olivari N: The latissimus flap. Br J Plast Surg 29(2):126–128, 1976. 16. Quillen CG, Shearin JC Jr, Georgiade NG: Use of the latissimus dorsi myocutaneous island flap for reconstruction in the head and neck area: Case report. Plast Reconstr Surg 62(1):113–117, 1978. 17. Watson JS, Craig RD, Orton CI: The free latissimus dorsi myocutaneous flap. Plast Reconstr Surg 64(3):299–305, 1979. 18. Ariyan S: Further experiences with the pectoralis major myocutaneous flap for the immediate repair of defects from excisions of head and neck cancers. Plast Reconstr Surg 64(5):605–612, 1979. 19. Baek SM, Biller HF, Krespi YP, Lawson W: The lower trapezius island myocutaneous flap. Ann Plast Surg 5:108–114, 1980. 20. Taylor GI, Townsend P: Composite free flap and tendon transfer: An anatomical study and a clinical technique. Br J Plast Surg 32:170–183, 1979. 21. Taylor GI, Townsend P, Corlett R: Superiority of the deep circumflex iliac vessels as the supply for free groin flaps. Clinical work. Plast Reconstr Surg 64:745–759, 1979. 22. Baudet J: Reconstruction of the pharyngeal wall by free transfer of the greater omentum and stomach. Int J Microsurg 1:53–59, 1979. 23. dos Santos LF: The vascular anatomy and dissection of the free scapular flap. Plast Reconstr Surg 73:599–604, 1984. 24. Nassif TM, Vidal L, Bovet JL, Baudet J: The parascapular flap: A new cutaneous microsurgical free flap. Plast Reconstr Surg 69: 591–600, 1982. 25. Song R, Gao Y, Song Y, Yu Y, Song Y: The forearm flap. Clin Plast Surg 9:21–26, 1982. 26. Pennington DG, Pelly AD: The rectus abdominis myocutaneous free flap. Br J Plast Surg 33:277–282, 1980. 27. Panje WR, Little AG, Moran WJ, Ferguson MK, Scher N: Immediate free gastro-omental flap reconstruction of the mouth and throat. Ann Otol Rhinol Laryngol 96(1 Pt 1):15–21, 1987.

28. Jones NF, Sekhar LN, Schramm VL: Free rectus abdominis muscle flap reconstruction of the middle and posterior cranial base. Plast Reconstr Surg 78:471–479, 1986. 29. Jones NF, Schramm VL, Sekhar LN: Reconstruction of the cranial base following tumor resection. Br J Plast Surg 40:155–162, 1987. 30. Abul-Hassan HS, von Drasek Ascher G, Acland RD: Surgical anatomy and blood supply of the fascial layers of the temporal region. Plast Reconstr Surg 77:17–28, 1986. 31. Schramm VL, Myers EM, Maron JC: Anterior skull base surgery for benign and malignant disease. Laryngoscope 89:1077–1091, 1979. 32. Argenta LC, Freidman RJ, Dingman RO, Duus EC: The versatility of pericranial flaps. Plast Reconstr Surg 76:695–702, 1985. 33. Avelar JM, Psillakis JM: The use of galea flaps in craniofacial deformities. Ann Plast Surg 6:464–469, 1981. 34. Psillakis JM, et al: Vascularized outer-table calvarial bone flaps. Plast Reconst Surg 78:309–319, 1986. 35. Brent B, et al: Experience with the temporoparietal fascial free flap. Plast Reconstr Surg 76:177–188, 1985. 36. Jackson IT, Pellett C, Smith JM: The skull as a bone graft donor site. 37. McCarthy JG, Zide BM: Spectrum of calvarial bone grafting: Introduction of the vascularized calvarial bone flap. Plast Reconstr Surg 74:10–18, 1984. 38. Stock AL, Collins HP, Davidson TM: Anatomy of the superficial temporal artery. Head Neck Surg 2:466–469, 1980. 39. Holmes AD, Marshall KA: Uses of the temporalis muscle flap in blanking out orbits. Plast Reconstr Surg 59:336–342, 1979. 40. Williams PL, Warwick R, Dyson M, Bannister LH, eds: Gray’s anatomy, 37th ed. New York, Churchill Livingstone, 1989, p 741. 41. Gadre AK, et al: The lateral skull base: A vascular perspective with clinical implications. Skull Base Surg 1:110–116, 1991. 42. Bartlett SP, May JW, Yaremchuk MJ: The latissimus dorsi muscle: A fresh cadaver study of the primary neurovascular pedicle. Plast Reconstr Surg 67:591–596, 1981. 43. Bostwick J: Latissimus dorsi flap: Current applications. Ann Plast Surg 9:377–380, 1982. 44. Dinner MI, Peters CR: The arc of rotation of the latissimus dorsi musculocutaneous flap. Ann Plast Surg 3:425–429, 1979. 45. Netterville JL, Wood DE: The lower trapezius flap: Vascular anatomy and surgical technique. Arch Otolaryngol 117:73–76, 1991. 46. Baek S, Biller HF, Krespi YP, Lawson W: The lower island trapezius island myocutaneous flap. Ann Plast Surg 5:108–114, 1980. 47. Ariyan S: Myocutaneous reconstruction of surgical defects following skull base surgery. In Sasaki CT, McCabe BF, Kirchner JA (eds.): Surgery of the Skull Base. Philadelphia, Lippincott, 1987, pp 227–243. 48. Schuller D: Limitations of the pectoralis major musculocutaneous flap in head and neck cancer reconstruction. Arch Otolaryngol 106:709–714, 1980. 49. Beasley NJ, Gilbert RW, Gullane PJ, et al: Scalp and forehead reconstruction using free revascularized tissue transfer. Arch Facial Plast Surg 6:16–20, 2004. 50. Yang G, et al: Forearm free skin flap transposition. Natl Med J China 61:139, 1981. 51. Pennington DG, Lai MF, Pelly AD: The rectus abdominis myocutaneous free flap. Br J Plast Surg 33:277–282, 1980. 52. Jones NF, Sekhar LN, Schramm VL: Free rectus abdominis muscle flap reconstruction of the middle and posterior cranial base. Plast Reconstr Surg 78:471–477, 1986. 53. Yamada A, Harii K, Ueda K, Asato H: Free rectus abdominis muscle reconstruction of the anterior skull base. Br J Plast Surg 45:302–306, 1992. 54. McLean DH, Buncke HJ Jr: Autotransplant of to a large scalp defect with microsurgical revascularization. Plast Reconstr surg 49:268–274, 1972. 55. Panje WR, Pitcock JK, Vargish T: Free omental flap reconstruction of complicated head and neck wounds. Otolaryngol Head Neck Surg 100:588–593, 1989. 56. Ellis H: The aetiology of post-operative abdominal adhesions (an experimental study). Br J Surg 50:10–16, 1962.

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57. Walker FC: The protective function of the greater omentum. Ann R Coll Surg Engl 33:282–306, 1959. 58. Harii K: Clinical application of free omental transfer. Clin Plast Surg 5:273–281, 1978. 59. Yamaki T, et al: Vascularized omentum graft for the reconstruction of the skull base after removal of a nasoethmoid tumor with intracranial extension: Case report. Neurosurgery 28:877–880, 1991. 60. Walkinshaw M, Caffee HH, Wolfe SA: Vascularized omentum for facial contour restoration. Ann Plast Surg 10:292–300, 1983. 61. Katsaros J, et al: The lateral upper arm flap: Anatomy and clinical applications. Ann Plast Surg 6:489–500, 1984. 62. Song R, Song Y, Yuseng Y, Song Y: The upper arm free flap. Clin Plast Surg 9:27–35, 1982. 63. Baek S: Two new cutaneous free flaps: The medial and lateral thigh flaps. Plast Reconstr Surg 71:354–359, 1983. 64. Hayden RE: Lateral cutaneous thigh flap. In Baker SR (ed.): Microsurgical reconstruction of the head and neck, New York, Churchill Livingstone, 1989, pp 211–228.

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65. Gnanalingham KK, Lafuente J, Thompson D, Harkness W, Hayward R: Surgical procedures for posterior fossa tumors in children: Does craniotomy lead to fewer complications that craniectomy? J Neurosurg 97:821–826, 2002. 66. Schessel DA, Nedzelski JM, Rowed D, Feghali JG: Pain after surgery for acoustic neuroma. Otolaryngol Head Neck Surgery 107:424, 1992. 67. Harner SG, Beatty CW, Ebersold MJ: Impact of cranioplasty on headache after acoustic neuroma removal. Neurosurgery 36(6): 1097–1100, 1995. 68. Wazen JJ, Sisti M, Lam SM: Cranioplasty in acoustic neuroma surgery. Laryngoscope 110:1294–1297, 2000. 69. Horsley V, Clarke RH: The structure and functions of the cerebellum examined by a new method. Brain 31:45–125, 1908.

Chapter

60 Sung J. Chung, MD Myles L. Pensak, MD

Tumors of the Temporal Bone Outline Background Anatomy Diagnostic Evaluation Pathobiology Squamous Cell Carcinoma Basal Cell Carcinoma Rhabdomyosarcoma Glandular Tumors Clinical Management

Sleeve Resection Lateral Temporal Bone Resection Subtotal Temporal Bone Resection Total Temporal Bone Resection Radiation Therapy Summary

D

espite recent advances in evaluative methodologies and management strategies, malignancies involving the temporal bone still portend an unfavorable prognosis. Furthermore, while electrophysiologic and neuroradiographic studies have heightened suspicion of an ominous lesion, occult growth and aural symptoms consistent with chronic otitis—and treated as such—have often delayed diagnosis. Several studies have concluded that there is a direct correlation between delay in diagnosis and a poor outcome.1–4 Once a diagnosis has been made, management options are complicated by the irregular and complex osteologic anatomy of the temporal bone and juxtaposing bony skull base. Tumor extirpation often requires the sacrifice of attendant neural and vascular structures, which results in significant morbidity. Furthermore, the intimate relationship of the skull base with intracranial structures further limits the role that adjunctive radiation therapy may play in conjunction with radical surgery. This chapter examines tumors of the temporal bone that require temporal bone resection from an anatomic perspective and the pathobiology of these lesions. The management protocols outlined herein reflect a necessary flexibility in caring for this select patient population.

BACKGROUND Heyer5 is generally credited with the first description of a temporal bone resection for carcinoma. Done in a piecemeal fashion at a time without benefit of magnification or microsurgical instrumentation, this procedure set the operative standard and technique for the next half century. Although numerous surgeons individually performed radical mastoidectomies and variations of the procedure on patients with chronic otitis, it may be presumed that a small number of these patients, in fact, probably had carcinoma of the petrous bone. 1028

In 1969, Hilding and Selker5 referenced Lempert’s 1937 communication wherein he described a one-stage procedure for gaining access to the petrous apex. The importance of this paper is that for the first time the isolation and preservation of the internal carotid artery are clearly described. Future descriptions of temporal bone resection would incorporate this procedure. In 1951, Ward, Loch, and Lawrence6 and Campbell, Volk, and Burkland7 independently described resection of the temporal bone. Within 3 years Parsons and Lewis8 reported for the first time an en bloc removal of the temporal bone, preserving only the petrous apex. Subsequently, several series reported on results of temporal bone resection4,9–15 including total temporal bone resection with the intentional sacrifice of the internal carotid artery.16 Most recently, extensive skull base tumor extirpations have incorporated the complete removal of the temporal bone, although the procedures employed are not generally performed in the traditional fashion reviewed here.

ANATOMY The temporal bone is composed of four distinct elements.17,18 The petrous portion contributes to the skull base of both the middle and posterior cranial fossae. The squamous portion forms the lateral skull, partially enclosing the lateral aspect of both the posterior and middle cranial fossae. The mastoid portion lies inferior and posterior to the squamosa, enlarging and pneumatizing after birth to overhang the stylomastoid foramen laterally. The tympanic portion is poorly developed at birth, but is near full development by 3 years of age. The tympanic ring forms the majority of the bony external auditory canal (EAC). Huschke’s foramen, a developmental defect in the tympanic ring that normally closes, may remain patent, which allows malignant processes access out of the bony ear canal anteriorly into the parotid gland and infratemporal fossa.

Tumors of the Temporal Bone

The pneumatized spaces of the mastoid and petrous portions of the temporal bone are complex and variable with regard to their extent of development. The mesotympanum is the largest pneumatized space in the temporal bone that communicates anteriorly with the eustachian tube. It is laterally bounded by the tympanic membrane and posteriorly by the mastoid central aircell tract via the aditus ad antrum. Violation of the tympanic membrane medially by a neoplastic process permits unimpeded spread to all areas of the petrous bone via the aircell system. The central aircell tract communicates with other pneumatized aircell tracts that invade the petrous portion of the temporal bone in predictable areas. A detailed description of these pathways is beyond the scope of this chapter but can be found in a standard temporal bone surgical atlas.17 An understanding of the three-dimensional relationships of the middle and inner ear structures is essential to the safe operative management of abnormalities of the temporal bone and skull base. The EAC is composed of fibroelastic cartilage in the lateral one-third of its extent. Fissures of Santorini exist in this cartilage, which allows access anteriorly to the parotid gland and posteriorly to the region lateral to the mastoid process. At birth, the bony portion of the canal is poorly developed but reaches adult proportions with growth of the tympanic ring by approximately 3 years of age. The medial two-thirds of the EAC is bony in the adult. There is squamous epithelium directly overlying the periosteum of the bony EAC, with no intervening subcutaneous tissue. Knowledge of the limited lymphatic system associated with the pinna, EAC, and temporal bone is important. Malignancies of this region and associated infectious processes require an overall treatment strategy with application of techniques that address all drainage areas. The external ear follows three distinct drainage pathways. The concha, cartilaginous canal, triangular fossa, and tragus drain anteriorly into the parotid gland and preauricular lymph nodes. The lobule and antitragus drain inferiorly into the infra-auricular lymph nodes and lymph nodes in the parotid gland. The helix and antihelix drain into the postauricular lymph nodes or directly into the deep jugular lymph nodes in the jugulodigastric area or into the spinal accessory lymph node chain. The EAC lymphatics drain into the preauricular and parotid lymph nodes anteriorly, into the upper cervical and deep internal jugular lymph nodes inferiorly, and into the postauricular lymph nodes posteriorly. The mucosa of the middle ear and mastoid contains a fine network of lymphatics draining into channels that surround the eustachian tube, which then drain into the deep upper jugular lymph nodes

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and the retropharyngeal lymph nodes. The inner ear has no known lymphatic drainage system. True lymphatic spread from tumors involving the temporal bone proper occurs in approximately 10% of patients with squamous cell carcinoma. Lymphadenopathy secondary to inflammatory changes associated with these tumors occurs with greater frequency.

DIAGNOSTIC EVALUATION Evaluation of all patients with suspected or biopsy-proved temporal bone malignancy begins with a thorough history and complete physical examination, including an otomicroscopic visualization of the lesion for optimal definition. A careful neurologic examination may suggest regional extension beyond the temporal bone. Audiometric, vestibular electrophysiologic, and neuroradiographic studies will assist in defining the extent of tumor growth. Audiometric studies differentiate between conductive and sensorineural hearing loss. Reflex testing and discrimination scores should be included on the basic audiometric battery. Any suggestion of retrocochlear dysfunction may be further evaluated by testing auditory brainstem response. Impedance audiometry is similarly important and may suggest a vascular tumor or anomaly with a pulsatile tympanogram. Every patient should undergo high-resolution computed tomography (CT) scanning. This test is invaluable in providing the surgeon a sense of the location and extent of the tumor. The architecture of the temporal bone is seen best with CT scanning and should be used to determine the surgical plan for tumor extirpation. In addition to demonstrating bone erosion and the extent of intracranial and cervical involvement, intravenous contrast studies may demonstrate the vascular nature of the lesion. Adjacent structures that cannot be assessed clinically should be studied closely on the films for evidence of tumor involvement. There is no universally accepted staging system for temporal bone malignancies. The American Joint Committee on Cancer uses the same staging system as that for cutaneous malignancies in other locations. Given the unique anatomy of the temporal bone, this staging system is inadequate and fails to provide true prognostic information for tumors that involve the temporal bone. Recently, Arriaga and colleagues19 have proposed a staging system for tumors of the EAC based on CT appearance and clinical examination (Table 60-1). Pensak and colleagues15 have a different staging system, which also relies on CT appearance and clinical findings (Table 60-2).

TABLE 60-1. Pittsburgh Staging System for External Auditory Canal Tumors T1 – Tumor limited to the external auditory canal without bony erosion or evidence of soft tissue extension. T2 – Tumor with limited external auditory canal bony erosion (not full thickness) or radiographic finding consistent with limited (<0.5 cm) soft tissue involvement. T3 – Tumor eroding the osseous external auditory canal (full thickness) with limited (<0.5 cm) soft tissue involvement or tumor involving the middle ear and/or mastoid or patients presenting with facial paralysis. T4 – Tumor eroding the cochlea, petrous apex, medial wall of the middle ear, carotid canal, jugular foramen, or dura, or with extensive (>0.5 cm) soft tissue involvement. N status – Involvement of lymph nodes is a poor prognostic finding and automatically places the patient in an advanced stage (i.e., stage III [T1N1] or stage IV [T2, T3, or T4, and N1]). M status – Distant metastasis indicates a poor prognosis and immediately places a patient in the stage IV category.

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TABLE 60-2. University of Cincinnati Grading System for Temporal Bone Tumors

TABLE 60-3. Lesions of the External Auditory Canal Benign

Grade I – Tumor in a single site, 1 cm or smaller Grade II – Tumor in a single site, larger than 1 cm Grade III – Transannular tumor extension Grade IV – Mastoid or petrous aircell invasion Grade V – Periauricular or contiguous extension (extratemporal) Grade VI – Neck adenopathy, distant anatomic site or infratemporal fossa extension

Magnetic resonance imaging (MRI) is often used in conjunction with CT scanning to provide further information on the soft tissue surrounding the mass in question. Although osteologic invasion is not well addressed by this modality, soft tissue detail is significantly enhanced with MRI scans, which allows improved estimation of the extratemporal extent of the tumor. Dural involvement, frank invasion of brain parenchyma, or involvement of other neural structures can be ascertained. Moreover, the patency of the eustachian tube can be determined most accurately with MRI, as can the proximity of the tumor mass to the carotid artery. Finally, signals from the carotid artery, sigmoid sinus, and jugular bulb give information suggestive of their patency. MRI studies can further be performed to evaluate flow through these major vessels. Angiography is not routinely used unless there is a question of tumor invasion of the carotid artery or there are highly vascular lesions. Identification of principal and subordinate arterial vessels feeding the tumor and the efferent venous channels draining the mass may help in planning surgical intervention.20–22 This, in turn, may permit preoperative embolization to decrease hemorrhage and tumor bulk before surgical excision of selected lesions. Balloon occlusion studies and xenon flow dynamic studies can be performed to assess the collateral flow available should sacrifice of the carotid artery be required either as part of the resection or, unexpectedly, as a result of hemorrhage. Finally, radionuleotide studies have occasionally been employed to differentiate between a neoplastic process and an inflammatory process such as necrotizing external otitis.

PATHOBIOLOGY The surgical literature reflects an agreement among authors that the most common lesion requiring a temporal bone resection is squamous cell carcinoma, accounting for roughly 85% of the tumors cited. Basal cell carcinomas, glandular tumors associated with the temporal bone, regional skull base lesions, and metastases account for the remainder of tumors. Tables 60-3, 60-4, and 60-5 list common lesions associated with the petrous bone. For many of these tumors, formal temporal bone resection is not required for adequate management. Table 60-6 lists common signs and symptoms at the time of presentation with temporal bone tumors from the Cincinnati experience.15

Squamous Cell Carcinoma Squamous cell carcinoma predominantly arises during the fifth decade of life. Common symptoms include aural

Osteoma Neurofibroma Paraganglioma

Malignant Squamous cell carcinoma Basal cell carcinoma Ceruminous gland tumor Rhabdomyosarcoma Melanoma Chloroma

fullness, pruritus, and otorrhea. More advanced lesions manifest with the more ominous signs of serosanguineous drainage, deep-seated otalgia, and cranial neuropathies. Any granulation tissue that is resistant to routine medical management requires a tissue biopsy. Proper diagnosis at the earliest stages will make a lesion most amenable to surgical resection and will maximize survival. Squamous cell carcinomas of the EAC and middle ear are associated with chronic otorrhea, chronic external otitis, and cholesteatoma. Squamous cell carcinoma of the pinna is related to solar radiation and local trauma. The presence of lymphadenopathy is uncommon, but assessment of especially the posterior regions of the neck is important.

Basal Cell Carcinoma Basal cell carcinomas (BCC) generally originate from the periauricular regions according to Batsakis.23 They represent 11% of the tumors of the EAC and temporal bone. Beginning as painless, indolent ulcers, these lesions spread and infiltrate locally. Prolonged growth results in a lesion that often becomes secondarily infected and ultimately violates the perichondrium and periosteum of the EAC. Rarely, growth violates the tympanic annulus and the pneumatized spaces of the temporal bone. Several variants of BCC can predict the aggressiveness of a given tumor. Nodular BCC is the most common variant and also the least aggressive type. Superficial and ulcerative BCC are similar to nodular BCC in aggressiveness but are less common. The two variants of BCC that seem to be more aggressive are morpheaform and basaloid squamous BCC. TABLE 60-4. Lesions of the Middle Ear Space Benign Paraganglioma Adenoma Schwannoma Hemangiopericytoma Chordoma

Malignant Squamous cell carcinoma Adenocarcinoma Chondrosarcoma Acinic cell carcinoma Rhabdomyosarcoma

Tumors of the Temporal Bone

Current staging systems differ from those used elsewhere for head and neck malignancies. The final stage of the tumor depends on the adequacy of surgical resection. The treatment of RMS of the temporal bone in the past consisted of radical surgery with adjuvant chemotherapy and occasional radiation therapy, which resulted in low cure rates and excessive morbidity. Since 1970, however, three intergroup studies have been completed that have shown that the standard treatment for head and neck RMS should be surgical biopsy to confirm the diagnosis and classify the subtype followed by chemotherapy and radiation therapy for definitive treatment. This approach has improved 5-year survival rates to 65%.25–27

TABLE 60-5. Lesions of the Inner Ear Benign Schwannoma Paraganglioma Hemangiopericytoma Lipoma Arachnoid cyst

Malignant 1° neural glioma Medulloblastoma Astrocytoma

Rhabdomyosarcoma Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood, with head and neck involvement in 38% of the patients. Involvement of the temporal bone occurs in 4% to 7% of patients, and 20% of patients have metastatic disease at the time of their diagnosis. The majority of auricular RMS arise from the middle ear. Patients with RMS frequently have symptoms of chronic otorrhea and granulation tissue. RMS localized primarily to the petrous bone, however, may present with cranial neuropathies and headaches without associated aural symptoms.24 The natural history of RMS in the temporal bone is aggressive local destruction with a propensity for distant metastases. From the middle ear, RMS can quickly invade the fallopian canal, resulting in facial paralysis, and can spread proximally into the internal auditory canal. It can also spread by direct destruction of the tegmen or along the eustachian tube. Four subtypes of RMS have been identified: embryonal, pleomorphic, alveolar, and botryoid. The embryonal variant accounts for nearly all of the head and neck RMS. The type of RMS is prognostically significant. Botryoid RMS has the best survival rates and embryonal RMS are more favorable than alveolar RMS, which has the worst prognosis. TABLE 60-6. Signs and Symptoms at the Time of Presentation in 46 Patients with Temporal Bone Tumors Sign and Symptoms

Incidence

Signs Canal mass or lesion Aural discharge Periauricular swelling Facial paralysis Neck nodes Temporal mass

88% 84% 25% 18% 8% 8%

Symptoms Pain Hearing loss Pruritus Bleeding Headache Tinnitus Facial numbness Vertigo Hoarseness

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74% 62% 40% 28% 18% 18% 12% 10% 4%

Pensak ML, et al: Temporal bone carcinoma: Contemporary perspectives in the skull base surgical era. Laryngoscope 106:1234–1237, 1996.

Glandular Tumors Glandular tumors may arise from a primary focus in the EAC as seen with ceruminous gland lesions. Others originate in regional foci, infiltrating the temporal bone secondarily such as occurs with parotid neoplasms. Irrespective of the primary site of origin, the combination of tumor biology and location ultimately determine the management protocol. Benign lesions may be safely extirpated with local excision and malignant tumors are dealt with more aggressively. Adenoid cystic carcinoma with a propensity for neural invasion, high-grade mucoepidermoid carcinomas, and adenocarcinomas with gross petrous invasion are managed in a fashion similar to squamous cell carcinoma.

CLINICAL MANAGEMENT Despite recent advances in neuroradiographic diagnostic imaging techniques, the anatomic extent of tumors of the temporal bone remain difficult to define preoperatively. Radiographic techniques currently have limited ability to discriminate among tumor, cholesteatoma, cholesterol granuloma, or other chronic infectious processes in the aircell system of the petrous pyramid. Visualization of gross boundaries is often impossible to determine adequately due to tumor obstruction, the presence of purulent exudates, and associated surrounding inflammation. Extension of the tumor anteriorly into the parotid gland infrequently can be established on palpation and the medial and superior extension of growth remains clinically inaccessible. Cognizant of the aforementioned limitations, it remains axiomatic that for optimal management of temporal bone carcinoma, an en bloc resection requires an accurate assessment of tumor invasion to prevent inadvertent violation of the mass at the time of resection. Because of the previously stated qualifiers in preoperative tumor assessment, an operative algorithm must be followed to permit surveillance of tumor extension and to prevent an inadequate resection, which would allow unrecognized pathology to be left behind. Five standard options for treatment of temporal bone carcinoma are described next.

Sleeve Resection Only lesions that arise in the cartilaginous portion of the EAC without extension medially to invade bone are amenable to sleeve resection (Fig. 60-1A). A postauricular

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Figure 60-1. A, Lesions confined to the cartilaginous canal may be amenable to a sleeve resection. B, Lesions situated between the bony canal and the tympanic membrane require a lateral temporal bone resection, and all tumor that extends medial to the tympanic annulus requires a subtotal temporal bone resection. (From Pensak ML: Benign vascular and malignant tumors of the ear. In Lee KJ [ed.]: Textbook of Otolaryngology and Head and Neck Surgery. New York, Elsevier Science, 1989, pp 125–140.)

approach cortical mastoidectomy is performed. The EAC is thinned carefully as surgeons look for signs of tumor invasion into the bone of the EAC. If any areas are suspicious for tumor invasion, the operation is converted to a lateral temporal bone resection without compromising the resection. If the bony canal is free of disease, the cartilaginous canal is transected at the bony-cartilaginous junction, and an adequate rim of tissue is taken from the meatus. The simplest way to reconstruct this defect is to place a split thickness skin graft between the retained auricle laterally and the skin of the osseous meatus. Tumors amenable to this type of resection are unusual because they rarely present prior to bony canal erosion. The survival rate2,4,13,14 of patients with these limited tumors is excellent, ranging from 57% to 95%.

Figure 60-2. Meatal incision with extended postauricular incision. (From Pensak ML: Skull base surgery. In Glasscock ME, Shambaugh GE Jr [eds.]: Surgery of the Ear. Philadelphia, WB Saunders, pp 502–533, 1990.)

can be left pedicled on the temporal bone and taken to ensure the margin. A cortical mastoidectomy is then performed, which skeletonizes the facial nerve. Close examination of the EAC for signs of invasion of the tumor into the mastoid cavity is imperative. Should this be found, the lateral temporal bone resection is not an adequate procedure. An extended facial recess is then performed with the middle ear being evaluated for possible violation by tumor. If the middle ear space is involved, the lateral temporal bone

Lateral Temporal Bone Resection Any tumor that involves bone of the EAC and remains lateral to the tympanic membrane is amenable to a lateral temporal bone resection (Fig. 60-1B). A superficial parotidectomy, pedicled on the bony canal anteriorly, ensures eradication of all microscopic disease that might spread anteriorly. The cartilaginous meatus is widely circumscribed, including the tragus, and is then oversewn. Through a postauricular incision or a Y-shaped superiorly based flap, the pinna is elevated and reflected, which leaves the “apple core” lesion with the osseous canal (Fig. 60-2). A limb is extended into the neck along a prominent skin crease, as would be performed for a parotidectomy. The facial nerve is then identified and traced to the pes anserinus (Fig. 60-3). If suspicion exists as to extension of the tumor anteriorly, beyond the limits of the temporal bone, the parotid gland

Figure 60-3. Anterior and posterior flaps developed to show exposed parotid gland and facial nerve at the stylomastoid foramen. A mastoidectomy with extended facial recess approach has been performed. (From Pensak ML: Skull base surgery. In Glasscock ME, Shambaugh GE Jr [eds.]: Surgery of the Ear. Philadelphia, WB Saunders, pp 502–533, 1990.)

Tumors of the Temporal Bone

Figure 60-4. A, The EAC and the tympanic membrane have been mobilized from the temporal bone. The specimen remains attached to the lateral lobe of the parotid gland. A lateral parotid lobectomy is then completed. B, Appearance of defect following removal of specimen. (From Pensak ML: Skull base surgery. In Glasscock ME, Shambaugh GE Jr [eds.]: Surgery of the Ear. Philadelphia, WB Saunders, pp 502–533, 1990.)

resection is then an inadequate treatment modality and a subtotal procedure must be undertaken. With the middle ear being cleared, the incudostapedial joint is separated and the incus removed. The dissection is carried anteriorly across the hypotympanum inferiorly, which skeletonizes the jugular bulb, carotid crest, and carotid artery. Superiorly, the dissection is carried through the zygomatic root to the temporomandibular joint. A straight chisel may be placed lateral to the facial nerve to complete the bony cuts below and into the zygomatic root above to free the bony EAC specimen (Fig. 60-4). In cases where palpable adenopathy exists or direct extension grossly into the parotid gland is noted, a neck dissection and parotidectomy is required to control possible metastatic disease. Reconstruction of the defect is begun by obliterating the eustachian tube, after which a split thickness skin graft can be used to line the middle ear and mastoid cavities. Temporalis muscle flaps can also be used to obliterate dead space, and a skin graft is applied over the muscle (Figs. 60-5 and 60-6). With combined surgical and radiation therapy, 5-year survival rates of 45% to 67% can expected. 3,4,9–14,20,21,28–31

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Figure 60-5. Obliteration technique using temporalis and sternocleidomastoid rotated muscle flaps. (From Pensak ML: Skull base surgery. In Glasscock ME, Shambaugh GE Jr [eds.]: Surgery of the Ear. Philadelphia, WB Saunders, pp 502–533, 1990.)

define an intracranial margin to establish respectability of the tumor mass. If the tumor extends through dura, the dura can be resected free from the temporal lobe. If, however, extension of the tumor into the temporal lobe is found, the lesion would generally be considered inoperable. Adequate exposure requires identification of the foramen spinosum anteriorly and the lateral sinus exposed in the posterior fossa. After the determination of the potential for resectability, the great vessels are controlled in the neck and a total parotidectomy is performed. The parotid is left pedicled on the EAC anteriorly. The facial nerve is traced to the stylomastoid foramen, tagged, and severed. The ascending

Subtotal Temporal Bone Resection Tumors that violate the middle ear or mastoid cavities or violate the medial layer of the tympanic membrane require subtotal resection of the temporal bone (see Fig. 60-1C). This resection encompasses the temporal bone lateral to the internal carotid artery, through the internal auditory canal (IAC), and through the jugular foramen inferiorly. Only the petrous apex is left, attached to the clivus. By either a Y-shaped incision or a large C-shaped incision, a skin flap is elevated widely to permit a temporal craniotomy. This maneuver will

Figure 60-6. A skin graft is used to close the meatal opening over the obliterated cavity. (From Pensak ML: Skull base surgery. In Glasscock ME, Shambaugh GE Jr [eds.]: Surgery of the Ear. Philadelphia, WB Saunders, pp 502–533, 1990.)

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Total Temporal Bone Resection

Figure 60-7. Subtotal resection of the temporal bone. A, The major neurovascular structures in the neck have been identified. The ascending ramus of the mandible is removed along with a subtotal parotidectomy. The common carotid artery is isolated and the branches of the external carotid are sacrificed. The posterior and middle fossae dura are exposed. B, Appearance following removal of the specimen. The ICA has been exposed throughout its intratemporal course. The eustachian tube is obliterated with Proplast, and the cavity may be lined with split thickness skin grafts. (From Pensak ML: Skull base surgery. In Glasscock ME, Shambaugh GE Jr [eds.]: Surgery of the Ear. Philadelphia, WB Saunders, pp 502–533, 1990.)

ramus of the mandible is transected to allow access to the mandibular fossa. It is important to resect the mandibular fossa because extension of tumor into this area is very difficult to determine preoperatively. A mastoidectomy is then performed, which skeletonizes the sigmoid sinus and the jugular bulb. Continuing anteriorly, the carotid artery is skeletonized anterior to the jugular bulb. Working through the subtemporal exposure, the internal carotid artery is exposed in its vertical and horizontal petrous segments and may be mobilized anteriorly. From a subtemporal or middle fossa exposure, the IAC is identified and opened with cranial nerves VII and VIII divided. Any remaining bony connections are freed with a curved osteotome. The lines of resection are through the carotid canal at the lateral aspect of the IAC, through the cochlea, and exiting the jugular foramen1,5,22 (Fig. 60-7). Attempts are made to preserve cranial nerves IX, X, and XI in the pars nervosa portion of the jugular foramen. To ensure adequate removal of all affected tissue, the promontory must be included with the specimen. Reconstructive efforts must obliterate dead space, seal the cranial cavity from possible cerebral spinal fluid (CSF) leaks, and minimize tension to prevent breakdown. Reconstruction can be accomplished by means of regional flaps, myocutaneous flaps, abdominal fat grafts, or free vascular flaps. The 5-year survival for patients with tumors extending medial to the tympanic membrane after combined surgical and radiation therapy is between 25% and 30%.10,13,31–33

Total temporal bone resection includes the petrous apex with the main temporal bone specimen. The petrous apex is isolated from the cavernous sinus at the anterior medial aspect of the petrous internal carotid artery. An osteotome is then used to fracture the posterior lip of the IAC. The carotid artery should be mobilized anterior and medially during removal of the petrous apex. The carotid artery is routinely preserved in this resection, but there are reports of taking the carotid en bloc with the specimen. The 5-year survival rate after total temporal bone resection is no different from the survival rate after subtotal temporal bone resection. Total temporal bone resection may be associated with significant complications including the potential for significant blood loss. The carotid artery may be lacerated inadvertently or may thrombose secondary to manipulation in the mobilization procedures, which leads to stroke and possibly death. Multiple cranial neuropathies may occur either secondary to sectioning of the nerves or secondary trauma due to the packing used to control bleeding from the inferior petrosal sinus and cavernous sinus. Because of difficulties in establishing the extent of disease accurately preoperatively, coupled with the dismal prognosis of medial extension into and beyond the middle ear, treatment protocols have arisen to maximize survival and palliation while minimizing morbidity. Total temporal bone resections have not yielded improved survival, but they do account for a significant increase in morbidity. Subtotal temporal bone resection often requires additional piecemeal removal of residual tumor. We believe that an en bloc lateral temporal bone resection followed by radical mastoidectomy and petrosectomy with high-speed drills may extirpate disease adequately to maintain local control and palliation when coupled with high-dose postoperative radiation therapy.

Radiation Therapy At most institutions, radiation therapy is an adjunctive modality and not the primary treatment of choice. Sometimes, however, the patient refuses surgery or is not a surgical candidate and, therefore, radiation therapy is employed. Achieving adequate doses of radiation deep in the temporal bone is complicated by poor vascularity of the bone and an infected tissue bed. Higher doses are also limited secondary to the toxic effects to the surrounding brainstem. When radiation is given, the protocol must be individualized for the specific tumor. Most commonly, a wedged pair photon radiation field is used at a total dosage of 7000 rads with brain exposure held to 6000 rads. Zhang and colleagues reported a 5-year cure rate with radiation alone of 28.7% compared to a rate of 59.6% for patients who received radiation and surgery.34 In his series of 132 patients, Lewis found postoperative radiation increased the 5-year survival rate from 28.5% to 35.5%.35 There is, however, no conclusive, extensive randomized study on the survival benefits of radiation therapy at this time. In an extensive review of published series of temporal bone malignancies, Prasad and Janecka concluded that radiation therapy offered no survival benefit for tumors

Tumors of the Temporal Bone

confined to the external auditory canal and that the side effects may outweigh any advantage. For tumors involving the middle ear and mastoid, radiation improved survival over mastoidectomy alone but no conclusions could be drawn when it was used as an adjuvant treatment with more extensive resections.36 The complications of radiation therapy include central nervous system damage, osteoradionecrosis, cranial nerve damage, and wound breakdown.

SUMMARY Temporal bone resection remains a formidable challenge despite advances in microsurgical techniques. Because it is not possible to determine preoperatively the absolute extent of tumor infiltration, the salient factor that determines survivorship is the confinement of tumor to the EAC. This latter fact is reflected in statistics of long-term survival of those who undergo lateral versus subtotal temporal bone resection. Unfortunately, despite appropriate cuts, fracture lines may occur during dissection that violate the tumor bed and result in the premature removal of the gross lesion. Establishment of clean margins is further encumbered by inadequate tumor volume in a frozen section specimen, sampling error, and significant quantities of bone in the sample specimen. In cases where it is not established that a complete resection has been accomplished, adjunctive radiation therapy may be employed. Radiation therapy in the postoperative setting has been shown to increase survivorship in patients who had gross tumors removed. The morbidity that could result from temporal bone resection results from injury to neural or vascular structures. Furthermore, dural violation may result in intracranial complications including meningitis and CSF leakage. From an otoneurologic perspective, a lateral temporal bone resection results in a conductive hearing loss, and a subtotal resection leaves the patient with anacusis and often significant early vestibular dysfunction. Furthermore, the latter procedure results in total facial paralysis, which may secondarily cause ophthalmologic problems. Nevertheless, because of its rarity and frequent delay in diagnosis, surgery and radiation therapy represent a lifesaving attempt at management. Although the risks are serious, the patient often has little choice because an untreated carcinoma of the temporal bone is a painful and very noxious way to die.

REFERENCES 1. Arena S: Tumor surgery of the temporal bone. Laryngoscope 84:615–670, 1974. 2. Kinney SE: Clinical evaluation and treatment of ear tumors. In Thawley SE, Panje WR (eds.): Comprehensive Management of Head and Neck Tumors. Philadelphia, WB Saunders Company, 1987, pp 181–206. 3. Krespi YP, Levine TM: Management and therapy of tumors of the temporal bone. In Alberti PW, Reuben RJ (eds.): Otologic Medicine and Surgery. New York, Churchill-Livingstone, 1988, pp 1409–1422.

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4. Spector JG: Management of temporal bone carcinomas: A therapeutic analysis of two groups of patients and long term follow-up. Otolaryngol Head Neck Surg 104:58–66, 1991. 5. Hilding D, Selker R: Total resection of the temporal bone for carcinoma. Arch Otolaryngol 89:636–645, 1969. 6. Ward GE, Loch WE, Lawrence W: Radical operation for carcinoma of the external auditory canal and middle ear. Am J Surg 82:69–178, 1951. 7. Campbell EH, Volk BM, Burkland CW: Total resection of the temporal bone for malignancy of the middle ear. Ann Surg 134: 397–403, 1951. 8. Parsons J, Lewis JS: Subtotal resection of the temporal bone for cancer of the ear. Cancer 7:995–1001, 1954. 9. Arriaga M, et al: Squamous cell carcinoma of the external auditory meatus (canal). Otolaryngol Head Neck Surg 101:330–337, 1988. 10. Conley JJ, Schuller DE: Malignancies of the ear. Laryngoscope 86:1147–1163, 1976. 11. Crabtree JA, Pierce MK: Carcinoma of the external auditory canal. Laryngoscope 867:405–415, 1976. 12. Gacek R, Goodman M: Management of malignancy of the temporal bone. Laryngoscope 87:1622–1634, 1977. 13. Goodwin WJ, Jesse RH: Malignant neoplasms of the external auditory canal and temporal bone. Arch Otolaryngol 106:675–679, 1980. 14. Kinney SE: Squamous cell carcinoma of the external auditory canal. Amer J Otol 10:111–116, 1989. 15. Pensak ML, et al: Temporal bone carcinoma: Contemporary perspectives in the skull base surgical era. Laryngoscope 106: 1234–1237, 1996. 16. Graham M, et al: Total en bloc resection of the temporal bone and carotid artery for malignant tumors of the ear and temporal bone. Laryngoscope 94:528–533, 1984. 17. Anson BJ, Donaldson JA (eds.): Surgical Anatomy of the Temporal Bone. Philadelphia, WB Saunders, 1981. 18. Hollingshead WH: Anatomy for Surgeon: The Head and Neck. Philadelphia, Harper & Row, 1982, pp 159–221. 19. Arriaga M, et al: Staging proposal for external auditory meatus carcinoma based on computer tomography findings. Ann Otol Rhinol Laryngol 99:714–721, 1990. 20. Beldman JE, et al: Early detection of asymptomatic hereditary chemodectoma with radionucleotized cineangiography. Arch Otolaryngol 106:547–552, 1980. 21. Curtain HD: Radiologic approach to paragangliomas of the temporal bone. Radiology 150:837–838, 1984. 22. Irving JD: Angiography in the investigation of tumors of the ear. J Laryngol Otol 97:319–331, 1983. 24. Wiatrak BJ, Pensak ML: Rhabdomyosarcoma of the ear and temporal bone. Laryngoscope 99:1188–1192, 1989. 23. Batsakis JG (ed.): Tumors of the Head and Neck, 2nd ed. Baltimore, Williams & Wilkins, 1979. 25. Crist W, et al: Prognosis in children with rhabdomyosarcoma: A report of the intergroup rhabdomyosarcoma studies I and II. J Clin Oncol 8:443–452, 1990. 26. Crist W, et al: The third intergroup rhabdomyosarcoma study. J Clin Oncol 13:610–630, 1995. 27. Maurer JM, et al: The intergroup rhabdomyosarcoma study I: A final report. Cancer 61:209–220, 1988. 28. Feldman BA: Rhabdomyosarcomas of the head and neck. Laryngoscope 92:424, 1982. 29. Lesser RW, Spector GS, Devineni VR: Malignant tumors of the middle ear and external auditory canal: A 20-year review. Otolaryngol Head Neck Surg 96:43–47, 1987. 30. Lewis JS: Squamous carcinoma of the ear. Arch Otolaryngol 97:41–42, 1973. 31. Pensak ML: Skull base surgery. In Glasscock ME, Shambaugh GE (eds.): Surgery of the Ear. Philadelphia, WB Saunders, 1990, pp 503–533.

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32. Kinney SE, Wood BE: Surgical treatment of skull base malignancy. Otolaryngol Head Neck Surg 92:94–99, 1984. 33. Lewis JS, Page R: Radical surgery for malignant tumors of the ear. Arch Otolaryngol 83:114–119, 1966. 34. Zhang B, et al: Squamous cell carcinoma of temporal bone: Reported on 33 patients. Head Neck 21:461–466, 1999.

35. Lewis JS: Surgical management of tumors of the middle ear and mastoid. J Laryngol Otol 97:299–311, 1983. 36. Prasad S, Janecka IP: Efficacy of surgical treatments for squamous cell carcinoma of the temporal bone: A literature review. Otolaryngol Head Neck Surg 110:270–280, 1974.

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Outline Anatomy of the Jugular Foramen Tumors of the Jugular Foramen Glomus Jugulare

Chapter

Tumors of the Jugular Foramen

Schwannoma Meningioma Other Tumors

M

anagement of lesions involving or originating in the jugular foramen remains one of the most challenging problems for neurotologic and neurologic surgeons. Neoplasms originating in the region of the jugular foramen are less common than those found in the cerebellopontine angle (CPA) and present unique technical difficulties attributable to their pathologic nature and sites of origin. Indeed, management of tumors in this region was a significant driving force behind the multidisciplinary concept of skull base surgery. Frequently, tumors in this area involve intracranial as well as extracranial structures and mandate surgical approaches designed to address both areas if the expectation is cure of these generally histologically benign lesions. Intimate microscopic anatomic familiarity, developed in the laboratory, is a prerequisite to safe operation in the region of the jugular foramen. In addition, the surgeon must be aware of anatomic variants and the effect of mass lesions, which may envelop as well as deform adjacent anatomic structures. In the last two decades many advances have been made in diagnostic and therapeutic technology. New diagnostic imaging techniques, improvements in anesthetic agents and monitoring techniques, and refinements in surgical approaches to the skull base have permitted removal of lesions that have in the past been considered inoperable. Neoplasms originating in the jugular foramen are now frequently resected with the realistic expectation of cure and acceptable postoperative morbidity. This chapter discusses the biology, clinical presentation, evaluation, and management of the tumors frequently originating in the jugular foramen.

ANATOMY OF THE JUGULAR FORAMEN The jugular foramen is the bony opening through which the sigmoid sinus exits the skull to become the internal jugular vein. The sigmoid sinus does not follow a direct course through the skull base, but rather makes an S-shaped

Karl L. Horn, MD Hal L. Hankinson, MD

curve before exiting the skull base. The area of this curve is defined as the jugular foramen. The jugular foramen is bound anterolaterally by the temporal bone and posteromedially by the occipital bone.1,2 The superior extent of the jugular foramen varies and may be in direct relationship with the middle ear and the otic capsule and, on rare occasions, with the medial external auditory canal. The carotid artery lies anterior to the jugular foramen, and the descending segment of the facial nerve lies lateral to the jugular foramen. The jugular foramen is often described as having a larger vascular compartment, the pars vascularis, and a smaller compartment, the pars nervosa. In fact, although the foramen is indeed divided into two compartments by a fibrous or bony bridge connecting the jugular spine of the petrous temporal bone to the jugular process of the occipital bone, each compartment usually has both vascular and neural elements.3 The pars nervosa is occupied by cranial nerve IX and the inferior petrosal sinus, whereas the pars vascularis is occupied by cranial nerves X and XI and the jugular bulb.4 The jugular bulb, which is the area of transition between the sigmoid sinus and the internal jugular vein, is the major vascular structure of the jugular foramen. The term jugular bulb is unfortunately frequently used inappropriately in the literature to refer to the jugular foramen. Although the neural and vascular relationships are somewhat variable in the jugular foramen, the cranial nerves are always surrounded by fibrous tissue and are always outside the lumen of the jugular bulb.5,6 Medially, the dura over the jugular foramen has two openings (Fig. 61-1). The superior opening is occupied by the 9th cranial nerve, which passes into the pars nervosa, and the lower opening is occupied by the 10th and 11th cranial nerves, which pass into the anteromedial portion of the pars vascularis. Within the jugular foramen, the ninth cranial nerve initially passes anterolaterally through a bony canal for 5 to 6 mm, then through connective tissue for several millimeters before exiting the skull base. Cranial nerves X and XI may or may not pass through a small bony canal within the jugular foramen. Cranial nerves X and XI are frequently separated from the ninth 1037

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Figure 61-1. Dural openings into the jugular foramen for cranial nerves IX, X, and XI.

cranial nerve in the jugular foramen by a branch of the inferior petrosal sinus. The cranial nerves, particularly the vagus, remain fasciculated within the foramen.7 All three nerves are surrounded by fibrous connective tissue as they exit the jugular foramen. The nerves are in close proximity to one another as they exit the skull base (Fig. 61-2).8 The glossopharyngeal nerve is the most anterior of the three nerves as it exits the jugular foramen into the neck to travel anteriorly over the internal carotid artery (ICA). The spinal accessory is usually the most posterior as it exits the skull base to travel posteriorly over the internal jugular vein. The vagus nerve lies medial to cranial nerves IX

Figure 61-2. Exit of cranial nerves IX, X, and XI from the jugular foramen into the neck.

and XI as it extends inferiorly between the ICA and the internal jugular vein in the neck. The internal jugular venous system represents the main venous drainage of the cranium. The largest vessel to empty into the jugular bulb is the inferior petrosal sinus. This sinus is the major drainage vessel for the clival region. Although the inferior petrosal sinus is frequently described as passing medial to the ICA between cranial nerves IX and X as it enters the medial jugular bulb, this relationship is variable, and multiple venous channels usually empty into the jugular bulb. The condylar emissary vein empties into the posteroinferior jugular bulb.

Tumors of the Jugular Foramen

TUMORS OF THE JUGULAR FORAMEN Glomus Jugulare Chemodectomas, or nonchromaffin paragangliomas, are not only the most common benign tumor of the middle ear, they are the most common tumor occurring in the jugular foramen.9 Chemodectomas that are found in the jugular foramen are termed glomus jugulare tumors. In 1945, Harry Rosenwasser described the first carotid body-like tumor occurring in the temporal bone.10 Prior to that time, glomus tumors in the temporal bone were incorrectly identified as endotheliomas or hemangioendotheliomas.11 In 1941, Guild described glomus tissue formation along the jugular system, which he termed the glomus jugulare.12 This tissue is identical histologically with the carotid body and other chemoreceptors along the carotid arteries and aortic arch. Glomus bodies have now been identified in several areas of the temporal bone. They have been recognized along the course of glossopharyngeal nerve, the tympanic branch of the glossopharyngeal nerve, and auricular branch of the vagus nerve, Arnold’s nerve, the promontory, and the jugular bulb. It is thought that glomus jugulare tumors arise from the areas of glomus formation in the floor of the middle ear or the jugular bulb.11 The histology of glomus jugulare tumors is similar or identical to carotid body tumors.9 Endocrinologically active tumors occur in 1% to 3% of glomus tumors.13,14 These tumors have been found to secrete epinephrine, norepinephrine, and dopamine, which may be screened for preoperatively by urinary vanillylmandelic acid (VMA) and metanephrine.14,15 The marked vascularity of these tumors may be related to the presence of angiogenic growth factors. Both vascular endothelial growth factor and plateletderived endothelial cell growth factor are expressed in paragangliomas.16 Most glomus jugulare tumors are histologically benign, but cases of metastasis have been reported.17 The incidence of metastasis is low and is thought to approximate 3%. Although glomus tumors have been identified in adolescents, they occur most frequently in middle age. The average age at diagnosis is 52 years.18 They are more common in women by a 6:1 ratio.19 The incidence of multiple glomus tumors is 7% to 10%.20,21 Familial glomus tumors have been recognized, and an autosomal-dominant heredity pattern with incomplete penetration has been proposed.22,23 The overall familial incidence may be as high as 20%.24 Both sporadic and familial paragangliomas are associated with deletions at chromosomes 11q13 and 11q22–23.24,25 As with other jugular foramen tumors, the clinical presentation may vary depending on the site of origin in the jugular foramen and routes of extension from the primary site. Glomus jugular tumors grow along neural and vascular pathways as well as through the aircell tracts, skull base foramina, fissures, and recesses.26 Growth away from the site of origin is along the path of least resistance. Multiple pathways may be taken simultaneously. The most common presenting symptom is hearing loss, which occurs in approximately 80% of patients with glomus tumors.11 This is usually a conductive hearing loss due to middle ear effusion or impingement of the tumor mass on the tympanic membrane or ossicular chain. Sensorineural hearing loss may be seen when either the

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cochlea or the eighth cranial nerve is involved. Tinnitus, which is pulsatile in nature, is the next most common presenting symptom, and is found in nearly 60% of patients.11 Pulsatile tinnitus may not be present in patients with tumors with increased fibrous tissue stroma and less vascularity. Aural discharge, otalgia, vertigo, and bleeding are less frequent symptoms. Cranial neuropathies are seen in only 10% of glomus tumors.11 The facial nerve may be involved by tumor in the middle ear. Multiple combinations of lower cranial neuropathies may be present as the tumor erodes and expands the jugular foramen. The site of lower cranial neural involvement is usually within the jugular foramen, rather than the CPA or cervical region. Increased neural involvement in the jugular foramen is due to the bony confines of the foramen and the persistent fasciculated anatomy of the cranial nerves in the foramen.7 The incidence of involvement of cranial nerves IX, X, XI, and XII is roughly equal.27 Although descriptions of these palsies may be recognized as various clinical syndromes such as Vernet’s, Hullings-Jackson, and Schmidt’s, they are of little benefit in determining the extent of the lesion, planning treatment, or predicting surgical outcome. High-resolution computed tomography (HRCT) remains the most valuable preoperative imaging study of glomus jugulare tumors.28 The bone algorithm with contrast provides accurate determination of bone erosion and delineation of the soft tissue mass. Computed tomography (CT) typically demonstrates an irregularly shaped homogeneous soft tissue mass centered on the jugular foramen.29 The degree of soft tissue enhancement is slightly greater than a schwannoma. The jugular foramen is frequently enlarged, but unlike the jugular foramen schwannoma, the bony rim of destruction is irregular, with a “moth-eaten” appearance (Fig. 61-3). Due to poor bone definition, the role of magnetic resonance imaging (MRI) in glomus jugulare tumors is less important than CT. MRI is, however, beneficial in

Figure 61-3. Computed axial tomogram demonstrating irregular erosion (arrows) of the jugular foramen from a glomus jugulare.

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Although helpful in delineating the blood supply to glomus tumors, angiography is typically only used for imaging tumors in which preoperative embolization is planned, or when sacrifice of the carotid artery or major venous sinus is a possibility. In the latter instance, trial balloon occlusion of the ICA is important.33,34 The tumor blush of a glomus jugulare tumor is usually best seen from injections of the external carotid artery (Fig. 61-6). Glomus jugulare tumors frequently have multiple feeding vessels from the external carotid, internal carotid, and vertebral arteries.35,36 The small caliber of the vessels from the internal carotid and the vertebral arteries, as well as the risk of intracranial embolization, frequently makes preoperative embolization of branches from these vessels difficult and impractical. Embolization of the branches from the external carotid artery is often of benefit in decreasing operative blood loss.37–39 Magnetic resonance angiography (MRA) and venography (MRV) may be used in lieu of traditional angiography. However, these studies are generally not considered to be as accurate as traditional angiography.40

Figure 61-4. T1-weighted MRI scan of a glomus jugulare.

delineating intracranial extension of the neoplasm.30 The tumor appears as an irregular soft tissue mass centered on the jugular foramen.31 The tumors are isointense with the brainstem on T1-weighted images and usually demonstrate high signal intensity on T2-weighted images (Fig. 61-4).32 On T1weighted images, the tumor enhances brightly after gadolinium (gadopentetate dimeglumine) administration (Fig. 61-5). Prominent vessels within the tumor do not enhance and give rise to flow voids that are typical of this tumor.

Figure 61-5. Enhanced T1-weighted MRI scan of a large glomus jugulare. Note multiple tumor flow voids.

Figure 61-6. External carotid angiogram demonstrating tumor blush in a small glomus jugulare.

Tumors of the Jugular Foramen

The chief advantage of MRA and MRV compared with angiography is decreased morbidity.41 MRA and MRV are most helpful in screening for vascular malformations and vascular occlusion. Scintigraphy using various radionuclide imaging agents has been used to evaluate several head and neck tumors including glomus and carotid body tumors. Imaging agents include 99mTc-methoxy-isobutyl-isonitrile (MIBI), indium 111-octreotide, and iodine-131/132 metaiodobenzylguanidine. Radionuclide scanning may be helpful in evaluating patients with monoamine active tumors, suspected metastasis, and metachronous tumors.42–44 As glomus jugulare tumors have become more clearly defined and surgically accessible, various methods of tumor classification may have been suggested. In 1969, McCabe and Fletcher suggested a relatively simple method of classification based on bony destruction.45 In 1981, Jenkins and Fisch presented a more detailed classification of glomus tumors that was consistent with newly described surgical approaches.46 The tumors are divided into four categories: A, B, C, and D. Type A tumors are limited to the middle ear. Type B tumors involve the middle ear and mastoid without infralabyrinthine involvement. Type C tumors extend into the infralabyrinthine area and petrous apex. Type D tumors have intracranial extension and are subclassified according to size. Fisch and Mattox have subsequently refined this classification.47 Type A tumors are not only isolated to the middle ear, but involve only the promontory. Type B tumors are isolated to the hypotympanum, but do not involve the bony plate over the jugular bulb. Type C tumors originate in the jugular bulb and erode the cortical bone overlying the jugular bulb. Type C1 may erode the carotid foramen, but does not invade the carotid artery. Type C2 involve the vertical carotid canal. Type C3 invade the vertical and horizontal carotid canal, but do not reach the foramen lacerum. Type C4 involve the entire intrapetrous carotid artery from the foramen to the cavernous sinus. Type D tumors have intracranial extension. Type De tumors have intracranial extension, but are extradural. They are further classified according to size as De1 (less than 2 cm) or De2 (greater than 2 cm). Type Di tumors have intracranial and intradural extension. They are similarly further defined by size, with Di3 identifying unresectable intracranial extension. The most recent classification system for glomus tumors has been proposed by Jackson and colleagues.48 The tumors are classified as either glomus tympanicum or jugulare. Tympanicum type I tumors involve only the promontory. Type II tumors involve the middle ear space, whereas type III lesions involve the middle ear and mastoid. Finally, type IV tumors involve the middle ear, mastoid, and external auditory canal. Glomus jugulare type I tumors involve the jugular bulb, middle ear, and mastoid. Type II extend beneath the internal auditory canal. Type III involve the petrous apex, and type IV involve the clivus or infratemporal fossa. Type II, III, or IV may have intracranial extensions. Management of Fisch type A and B glomus tumors is complete surgical excision through a standard middle ear or mastoid procedure. Management of glomus jugulare tumors is somewhat more controversial. The slow growth and relative infrequency of these tumors has made determination of treatment efficacy difficult. Usually, unless

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there are other contraindications to surgery, the treatment for glomus jugulare tumors is complete surgical removal. Small Fisch type C1 tumors may be removed via a hypotympanic approach as described by Shambaugh and Farrior.49–51 This approach is only applicable to small tumors with little extension into the jugular bulb and does not provide wide exposure of the ICA or proximal and distal control of the jugular system. In the main, Fisch type C and D tumors are best approached via skull base techniques as described by Gardner and colleagues or Fisch.39,52–54 The type A infratemporal fossa exposure described by Fisch and Mattox is best used for type C1 and C2 tumors. This approach provides wide exposure of the jugular bulb, proximal and distal vascular control of the jugular bulb, and exposure of the carotid canal to the horizontal segment. Cochlear function is also spared; however, closure of the external auditory canal and obliteration of the middle ear yields a maximal conductive hearing loss. The main shortcoming of the infratemporal approach is the failure to provide complete exposure of the petrous apex medial to the ICA. A posteroinferior trans-sigmoid approach first described by Mann and coworkers affords exposure to the jugular foramen for type C1 and C2 tumors with rerouting of the facial nerve or removal of the middle ear.55 This exposure combines a retrolabyrinthine and infralabyrinthine mastoidectomy with the suboccipital approach. Several variations of the technique have been described.56–59 Wide exposure in this area is best accomplished by a modified or widened transcochlear approach, which is usually used for Fisch type C3 and C4 tumors.60–62 The modified transcochlear approach allows for removal of the anterior petrous apex with facial nerve preservation by posterior rerouting. Skeletonization of the carotid artery may be carried into the cavernous sinus, and exposure of the jugular bulb is similar to that in the infratemporal fossa technique. The petrous carotid artery may be displaced laterally for further exposure in the lower and middle clival regions. The most significant disadvantage of this approach is the loss of aural function and the resulting synkinesis from posterior rerouting of the facial nerve. Intracranial extension of the tumor is either removed after the extracranial portion of the procedure has been completed, or the intracranial removal may be staged. This decision is usually based on the length of the procedure or on blood loss. The blood supply to the intracranial extension is usually discrete and controlled with bipolar electrocautery. Larger tumors with anterior extension into the CPA are best exposed through a modified transcochlear approach. The role of radiation therapy in glomus jugulare tumor treatment is controversial.63 The glomus tumor cell is not radiosensitive. However, conventional fractionated external beam radiation therapy does reduce tumor vascularity. This effect may be seen at lower doses (2000 to 3000 rad) than traditionally used by radiation oncologists (4000 to 5000 rad).64 Radiation therapy has also been used preoperatively for large tumors to reduce tumor vascularity. Irradiation as the primary treatment modality is used for elderly patients, patients with residual tumor, or patients refusing surgery. As Leksell gamma knife units have become more readily available, stereotactic radiosurgery for glomus jugulare

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tumors has been increasingly reported in the literature.65–69 The indications for stereotactic radiosurgery are the same as for conventional fractionated external beam radiation. The high incidence of mortality associated with radiationinduced malignancy is certainly a concern for the use of either conventional external beam radiation or stereotactic radiosurgery in the young healthy patient without surgical contraindications.70

Schwannoma The second most frequently occurring tumor in the jugular foramen is the schwannoma or neurilemmoma of cranial nerve IX, X, or XI. These tumors are thought to arise from Schwann cells that surround the axons of these nerves as they leave the central nervous system.71 Perineural or perineurothelial cells may also be a cell of origin for some schwannomas. The perineural cell is identical to the Schwann cell, except for the lack of close relationship to the axon. The histologic pattern of schwannomas is divided into two types: Antoni A and Antoni B. In Antoni A type, the cells are elongated and form bundles or palisade and may be confused histologically with a fibrous meningioma. Antoni B type is found in association with the Antoni A type cells, but forms a much looser pattern with pleomorphic cells. The palisades and bundles found in Antoni A are lacking in Antoni B. Although schwannomas account for 8% of all primary intracranial tumors, schwannomas of the jugular foramen are uncommon tumors, and no author can report extensive experience in the diagnosis and management of these lesions.72 They are thought to represent approximately 3% of all intracranial schwannomas, and only approximately 100 cases have been reported in the literature.73 Most jugular foramen schwannomas are thought to originate from the 10th cranial nerve, and this incidence has been reported as high as 50%.74 The presentation of schwannomas involving the jugular foramen varies. The site of origin along cranial nerves IX, X, and XI determines the pattern of growth and presentation. Three different growth patterns have been described.75 More proximal lesions grow mainly intradurally into the posterior fossa. The more distal lesions enlarge the jugular foramen and extend inferiorly through the skull base into the cervical region. Tumors arising in the middle region may expand primarily in the bone of the skull base; however, this presentation is relatively uncommon. Tumors with primarily intradural extension may present without palsies of cranial nerves IX, X, and XI.75 Hearing loss or vertigo may be the only significant presenting symptoms. Pure tone and speech audiometry may demonstrate retrocochlear hearing loss, although a conductive component may be seen if the tumor extends into the middle ear. Auditory brainstem response testing may demonstrate absence of response or increased I–V latency on the involved side from tumor displacement of the eighth cranial nerve. In addition, contralateral increased III–V latency may be seen in large tumors with brainstem compression. Electronystagmography may demonstrate reduced or absent caloric response on the involved side, consistent with tumor displacement of the eighth cranial nerve. Large tumors may present with gait disturbance, ataxia, or papilledema.

Figure 61-7. Enhanced T1-weighted MRI scan of a jugular foramen schwannoma (x).

Tumors occurring more laterally with enlargement of the jugular foramen and extending through the skull base frequently present with palsies of cranial nerves IX, X, and XI.75 Multiple combinations of cranial nerve palsies have been noted in such tumors. Classification of these patterns into clinically named syndromes is of little benefit for either diagnosis or treatment. MRI demonstrates a smooth contoured soft tissue mass nearly isointense with the brainstem on T1-weighted images and usually shows high signal intensity on T2weighted images.76 Gadolinium enhancement is similar to that seen in glomus tumors, but the flow voids noted in the glomus tumors are absent (Fig. 61-7). CT is helpful in differentiating a jugular foramen schwannoma from a glomus jugulare tumor. CT characteristically shows a smooth tumor capsule and smooth bony erosion of the jugular foramen (Fig. 61-8).77 By contrast, glomus jugulare tumors tend to show irregular intracranial margins and irregular (“moth-eaten”) bony destruction of the jugular foramen. Schwannomas are less homogeneous than glomus tumors and are less enhancing after contrast compared with glomus tumors. Angiography is helpful in determining the vascularity of the lesion and displacement of adjacent blood vessels. However, the main indication for angiography is to evaluate carotid system involvement. Unlike glomus tumors, schwannomas are relatively avascular and may produce little if any tumor blush.78,79 The choice of surgical approach is determined by the size and pattern of the tumor growth. Tumors that are mainly intradural with little extension into the jugular foramen may be managed with either suboccipital, trans-sigmoid, or extended retrolabyrinthine (presigmoid) approaches.80 All of these approaches should provide wide exposure of the CPA and adequate exposure of the medial jugular foramen.

Tumors of the Jugular Foramen

Figure 61-8. Computed axial tomogram demonstrating smooth bony erosion of the jugular from a jugular foramen schwannoma (x).

Tumors that are centered in the jugular foramen or that extend into the cervical region may be exenerated through an infratemporal fossa approach or the trans-sigmoid approach. These techniques are the same as those used for Fisch type C1 and C2 glomus jugulare tumors. These approaches offer excellent exposure of all the bony confines of the jugular foramen. The posterolateral approach through the jugular process that is used in the transsigmoid approach avoids transposition of the facial nerve and obliteration of the middle ear and mastoid. Very large tumors with extension into the anterior CPA may require extended translabyrinthine or modified transcochlear approaches. The latter approach offers the widest exposure of the jugular foramen, carotid artery, and CPA. Regardless of the surgical approach used to exenerate these tumors, function of cranial nerves IX, X, and XI is rarely better postoperatively and, in most case, complete removal of the neoplasm is usually associated with complete paralysis of these nerves.75

Meningioma Meningiomas are the third most common tumor arising in the jugular foramen. The term meningioma was coined by Harvey Cushing in 1922, although the tumor had been known since antiquity and had been described under various nomenclatures since the 17th century.81 Meningiomas are extra-axial neoplasms that apparently originate from arachnoidal cap cells and thus occur most predominately in locations containing high concentrations of these cells. Often the site of attachment is near a foramen or venous sinus. In the posterior fossa, they have a predilection for the posterior surface of the petrous bone.82,83 The cause of

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meningiomas is unknown, although their formation has been associated with prior trauma, foreign body retention, previous radiotherapy, genetic predisposition, and other factors.84–86 They are commonly found in association with other neoplasms in the central form of neurofibromatosis (neurofibromatosis type 2). They constitute 13% to 18% of intracranial tumors, 8% to 12% of which are found in the posterior fossa.86 Meningiomas are more common in women by a ratio of 2:1, and although found occasionally in the pediatric population, they become more prevalent in middle and late life.86 Meningiomas are generally considered benign by histologic criteria, but malignant forms exist in approximately 7%, and even benign-appearing tumors may metastasize within the subarachnoid space or remotely via hematogenous spread. There are six histologically distinct types of meningioma: meningiotheliomatous (endotheliomatous), transitional, psammomatous, fibroblastic, malignant, and angioblastic. The majority of skull base meningiomas are identified as meningiotheliomatous. Some meningiomas are quite soft and friable, but others are tenacious and fibrous. Some are quite vascular and others less so. These factors have considerable importance to the surgeon and greatly determine the instrumentation used to remove a specific tumor. The growth of these tumors is usually extra-arachnoid, a phenomenon that affords certain surgical advantages, in that neurovascular structures within cisterns can often be dissected from the tumor with relative safety and facility. They may, however, envelop these structures as well as erode bone. Calcification is often found within the tumors. Cystic areas, necrosis, and hemorrhage are more unusual. They are prone to spread locally, invading dura and producing a fine covering of meningioma cells, which, if not recognized and removed, can lead to clinical recurrence following surgery.87,88 Jugular foramen meningiomas may be narrow or more often broad-based, with the majority originating between the IAC and the jugular foramen. However, some meningiomas originate in the jugular foramen itself and extend extracranially into the neck or middle ear.89,90 Primary extracranial meningiomas are also rarely observed and may involve structures traversing the jugular foramen.91 The blood supply varies with the location, histology, and size of the tumor, but often comes substantially from the external carotid system, including the ascending pharyngeal and occipital arteries. The intracranial branches of the posterior inferior cerebellar artery may also feed the tumor. The jugular bulb and vein may be compressed or invaded. Cranial nerves IX, X, and XI are usually involved within the jugular foramen, and cranial nerve XII is involved as bony erosion includes the hypoglossal foramen. Neural involvement in the jugular and hypoglossal foramina frequently requires resection of these nerves.89 Meningiomas originating in the region of the jugular foramen may present clinically with a diverse array of symptoms ranging from lower cranial nerve dysfunction to cervical mass or middle ear mass. Often, they reach large size before diagnosis and become apparent by virtue of hearing loss, gait disturbance, and other cerebellar or brainstem abnormalities associated with structures remote from the jugular foramen. The presentation, like jugular foramen schwannomas, depends on the site of origin within the jugular foramen. The more medial tumors present with

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cerebellar and brainstem signs; tumors expanding within the jugular foramen present with lower cranial nerve palsies. Meningiomas are best diagnosed and morphologically defined by gadolinium-enhanced MRI.92 T1-weighted images reveal signal intensity similar to the brainstem. Signal intensity is variable on T2-weighted images. Areas of calcification appear as low signal intensity. Gadoliniumenhanced T1-weighted imaging produces bright enhancement similar to or brighter than a schwannoma or glomus tumor (Fig. 61-9). The tumor is typically more irregular or lobulated than a schwannoma. Flow voids seen in large glomus tumors are absent. CT may fail to demonstrate a small meningioma within the jugular foramen because the signal intensity is similar to that for the jugular bulb.89 Contrast enhancement typically demonstrates a very dense, uniform uptake of dye. A small, medially based tumor may produce no bony erosion of the jugular foramen. Larger tumors typically demonstrate erosion of the jugular foramen. Unlike the irregular moth-eaten appearance of a glomus tumor, the osseous erosion from a meningioma is noted as a subtle loss of cortical definition. Adjacent bone may be sclerotic, and hyperostosis may occur. Selective angiography usually demonstrates minimal tumor blush, similar to that seen in a schwannoma.89 This is in marked contrast to the bright tumor blush noted in a glomus tumor.93 Preoperative embolization is often of benefit in decreasing operative blood loss. Evaluation of venous drainage is important in the event that sigmoid sinus occlusion is necessary for tumor removal. The surgical approach to meningiomas involving the jugular foramen is determined by the clinical and, more importantly, by the radiographic assessment of the origin and extent of the tumor. The goal should be complete

surgical removal of the tumor, although some residual meningiomas are known to enlarge slowly or not at all. This is particularly true if the major blood supply to the tumor has been destroyed. The average growth rate of residual tumor is about 5% per year.94 Tumors more medially centered are approachable through a posterior intradural operation, particularly those with predominately or exclusively intradural growth. These approaches include the suboccipital craniotomy, trans-sigmoid, and the combined subtemporal transtentorial approaches with or without occlusion of the transverse sinus.95,96 The advantages of these procedures include familiarity to the neurosurgeon, sparing of auditory and facial nerve function, and wide visualization of the neural and vascular structures of the inferior portion of the CPA. The disadvantages include cerebellar and temporal lobe retraction, the occasional need for sinus ligation, poor exposure of bone around the jugular foramen and petrous apex, and late occlusion of the arterial supply to the tumor. For tumors occupying the jugular foramen and extending laterally through the skull base, a more lateral approach is necessary.97 Tumors that involve only the vertical portion of the petrous carotid canal may be removed via an infratemporal fossa approach as described by Fisch and Pillsbury.98 The subtemporal preauricular infratemporal fossa approach of Sekhar and colleagues avoids rerouting of the facial nerve, but does require resection of the mandibular condyle and carotid artery displacement.99 It does not afford the exposure of the modified transcochlear approach. Tumors that involve the temporal bone medial to the horizontal portion of the petrous carotid canal are best exposed through a modified transcochlear approach. This approach provides full exposure of the jugular foramen, petrous carotid artery, and extension as necessary into the clivus or the suboccipital area. The disadvantages to these techniques are deafness and transient facial paralysis with residual synkinesis. The virtually universal consensus is that the optimal treatment of meningioma is total removal. However, at times, the most judicious decision may be that of nonoperative observation, subtotal resection, or alternative therapy. Elderly patients without severe central nervous system involvement or medically infirm patients may be followed with serial magnetic resonance scanning. Residual tumor left behind at operation may be followed without further immediate treatment, may be resected at a secondary operation, or may be irradiated by one of several means. Stereotaxic radiosurgery appears to hold particular promise in curing or arresting the growth of residual meningioma.100 Although some meningiomas are known to be hormonally dependent, no conclusive evidence currently exists that hormonal manipulation is effective in their treatment. Chemotherapy, likewise, has not been shown to be useful.

Other Tumors

Figure 61-9. Enhanced T1-weighted MRI scan of a meningioma filling the jugular foramen (JF ). Note irregular tumor edge (arrows).

Other masses, both malignant and benign, may enter the differential diagnosis. Aneurysms of the vertebral or posterior inferior cerebellar artery should be considered when evaluating a neoplasm in this region. Various malignant neoplasms, particularly squamous cell carcinomas, chondrosarcomas, and chordomas, may be encountered and are occasionally suitable for surgical extirpation.

Tumors of the Jugular Foramen

REFERENCES 1. Rhoton AL, Buza R: Microsurgical anatomy of the jugular foramen. J Neurosurg 42:541–550, 1975. 2. Rhoton AL: Microsurgical anatomy of the posterior fossa cranial nerves. Clin Neurosurg 26:398–462, 1979. 3. Lustig LR, Jackler RK: The variable relationship between the lower cranial nerves and jugular foramen tumors: Implications for neural preservation. Am J Otol 17:658–668, 1996. 4. Schwaber MK, Netterville JL, Maciunas R: Microsurgical anatomy of the lower skull base: A morphometric analysis. Am J Otol 11:401–405, 1990. 5. Kveton JF, Cooper MH: Microsurgical anatomy of the jugular foramen region. Am J Otol 9:109–112, 1988. 6. Kveton JF: Anatomy of the jugular foramen: The neurotologic perspective. Oper Tech Otolaryngol Head Neck Surg 7:95–98, 1996. 7. Sen C, Hague K, Kacchara R, et al: Jugular foramen: Microscopic anatomic features and implications for neural preservation with reference to glomus tumors involving the temporal bone. Neurosurg 48:838–847, 2001. 8. Goldenenberg RA: Surgeon’s view of the skull base from the lateral approach. Laryngoscope (Suppl) 94:1–20, 1984. 9. Batsakis JG (ed.): Paragangliomas in the head and neck. In Tumors of the Head and Neck. Baltimore, Williams & Wilkins, 1979, pp 369–380. 10. Rosenwasser H: Carotid body tumor of middle ear and mastoid. Arch Otolaryngol 41:64–67, 1945. 11. Rosenwasser H, Parisier SC, Edelsein DR: Glomus Tumors. In English GM (ed.): Otolaryngology, vol 1. pp 1–28. Philadelphia, JB Lippincott, 1991. 12. Guild S: A hitherto unrecognized structure: The glomus jugulare in man. Anat Rec (Suppl) 2:28, 1941. 13. Zak FG, Lawson W: The Paraganglioma Chemoreceptor System. New York, Springer-Verlag, 1982, pp 276–285. 14. Schwaber MK, Glasscock ME, Nissen AJ, et al: Diagnosis and management of catecholamine secreting glomus tumors. Laryngoscope 94:1008–1015, 1984. 15. Duke WW, Boshen BR, Sotenes P: Norepinephrine-secreting glomus jugulare tumor presenting as a pheochromocytoma. Ann Intern Med 60:1040–1047, 1964. 16. Jyung RW, LeClair EE, Bernat RA: Expression of angiogenic growth factors in paragangliomas. Laryngoscope 110:161–166, 2000. 17. Bojrab DI, Bhansali SA, Zarbo RJ: Management of metastatic glomus jugulare tumors. Skull Base Surg 2:1–5, 1992. 18. Ogura JH, Ciralsky GJ, Gado M: Glomus jugulare and vagale. Ann Otol 87:622–629, 1978. 19. Spector GJ: Glomus jugulare tumors: Interpretation of clinical and laboratory findings, selection of therapy. SIPAC Am Acad Ophthalmol Otol, 1978, pp 1–47. 20. Spector GJ, Ciralsky R, Maisel RH, et al: Multiple glomus tumors in the head and neck. Laryngoscope 85:1066–1075, 1975. 21. Bickerstaff EF, Howell JS: The neurologic importance of tumors of the glomus jugulare. Brain 76:576–593, 1953. 22. van Baars F, van den Brook P, Cremers C, et al: Familial nonchromaffinic paragangliomas (glomus tumors): Clinical aspects. Laryngoscope 91:988–996, 1981. 23. Parkin JL: Familial multiple glomus tumors and pheochromocytomas. Ann Otol 90:60–63, 1981. 24. Petropoulos AE, Luetje CM, Camarata PJ, et al: Genetic analysis in the diagnosis of familial paragangliomas. Laryngoscope 110: 1225–1229, 2000. 25. Bikhazi PH, Messina L, Mhatre AN, et al: Molecular pathogenesis in sporadic head and neck paragangliomas. Laryngoscope 110:1346–1348, 2000. 26. Spector GJ, Sobol S, Thawley SE, et al: Panel discussion: Glomus jugulare tumors of the temporal bone: Patterns of invasion in the temporal bone. Laryngoscope 89:1628–1639, 1979. 27. Alford BR, Guilford RR: A comprehensive study of tumors of the glomus jugulare. Laryngoscope 72:765–787, 1962.

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28. Noujaim SE, Pattekar MA, Cacciarelli A, et al: Paraganglioma of the temporal bone: Role of magnetic resonance imaging versus computed tomography. Top Magn Reson Imaging 11:108–122, 2000. 29. Mafee MF, Aimi K, Valvassori GE: Computed tomography in the diagnosis of primary tumors of the petrous bone. Laryngoscope 94:1423–1430, 1984. 30. Daniels DL, Mark LP: MRI of the jugular foramen. In MRI Decisions. Secaucus, NJ, P.W. Publications, 1991, pp 2–11. 31. Rodgers GK, Applegate L, De la Cruz A, et al: Magnetic resonance imaging: Analysis of vascular lesions of temporal bone and skull base. Am J Otol 14:56–62, 1993. 32. Mafee MF, Raofi B, Kumar A, et al: Glomus faciale, glomus jugulare, glomus tympanicum, glomus vagale, carotid body tumors, and simulating lesions. Radiol Clin North Am 38:1059–1076, 2000. 33. Tarr RW, Jungreis C A, Horton JA, et al: Complications of preoperative balloon test occlusion of the internal carotid arteries: Experience in 300 cases. Skull Base Surg 1:240–244, 1991. 34. DeVries EJ, Sekhar LN, Horton JA, et al: A new method to predict safe resection of the internal carotid artery. Laryngoscope 100: 85–88, 1990. 35. Hesselink JR, Davis KR, Taveras JM: Selective arteriography of glomus tympanicum and jugulare tumors: Techniques, normal and pathologic arterial anatomy. Am J Neuroradiol 2:289–297, 1981. 36. Moret J: Vascularization of the ear: Normal variations-glomus tumors. J Neuroradiol 9:209–260, 1981. 37. Riche MC, Cophignon J, Thurel C, et al: Embolization of the cavernous and petrous segments of the internal carotid artery in severe basilar skull and petrous bone lesions. J Neuroradiol 8: 301–315, 1981. 38. Murphy TP, Brackmann DE: Effect of preoperative embolization on glomus jugulare tumors. Laryngoscope 99:1244–1247, 1989. 39. Gardner G, Cocke E, Robertson JH: Skull base approach: Infratemporal approach. Oper Tech Otolaryngol Head Neck Surg 7:118–128, 1996. 40. Rigby P, Jackler RK: Clinicopatholgic presentation and diagnostic imaging of jugular foramen tumors. Oper Tech Otolaryngol Head Neck Surg 7:99–105, 1996. 41. Stewart K, Stilianos EK, Chang J, et al: Magnetic resonance angiography in the evaluation of glomus tympanicum tumors. Am J Otolaryngol 18:116–120, 1997. 42. Kau R, Arnold W: Somatostatin receptor scintigraphy and therapy of neuroendocrine (APUD) tumors of the head and neck. Acta Otolaryngol 116:345–349, 1996. 43. Nilssen E, Wormald PJ: The role of MIBG scintigraphy in the management of a case of metastatic glomus jugulare tumour. J Laryngol Otol 110:373–375, 1996. 44. Kostakoglu L, Elahi N, Uzal D, et al: Double-phase Tc99m-sestamibi SPECT imaging in a case of glomus jugulare tumor. Radiol Med 15:331–334, 1997. 45. McCabe BV, Fletcher M: Selection of therapy of glomus jugulare tumors. Arch Otolaryngol 89:156–159, 1969. 46. Jenkins HA, Fisch U: Glomus tumors of the temporal region. Arch Otolaryngol 107:209–214, 1981. 47. Fisch U, Mattox D (eds.): Classification of glomus temporale tumors. In Microsurgery of the Skull Base. Stuttgart, Georg Thieme Verlag, 1988, pp 149–153. 48. Jackson CG, Glasscock ME, Harris PF: Glomus tumors: Diagnosis, classification, and management of large lesions. Arch Otolaryngol 108:401–406, 1982. 49. Shambaugh GE: Surgical approach for so called glomus jugulare tumors of the middle ear. Laryngoscope 65:185–198, 1855. 50. Farrior JB: Glomus tumors: Postauricular hypotympanotomy and hypotympanotomy. Arch Otolaryngol 86:367–373, 1967. 51. Farrior JB: Transcanal hypogympanotomy: Management of glomus tumors or the middle ear and hypotympanum. Oper Tech Otolaryngol Head Neck Surg 7:113–117, 1996. 52. Gardner G, Cocke EW, Robertson JH, et al: Combined approach surgery for removal of glomus jugulare tumors. Laryngoscope 87:665–688, 1977.

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53. Gardner G, Cocke EW, Robertson JH, et al: Skull base surgery for glomus jugulare tumors. Am J Otol 6:126–134, 1985. 54. Fisch U: Infratemporal fossa approach for glomus tumors of the temporal bone. Ann Otol Rhinol Laryngol 91:474–479, 1982. 55. Mann WJ, Amadee RG, Gilsbach J, et al: Transsigmoid approach for tumors of the jugular foramen. Skull Base Surg 1:137–141, 1991. 56. Sasaki T, Kintomo T: Twelve cases of jugular foramen neurinoma. Skull Base Surg 1:153–160, 1991. 57. Kamitani H, Masuzawa H, Kanazawa I, et al: A combined extradural-posterior petrous and suboccipitial approach to the jugular foramen tumours. Act Neurochir 126:179–184. 58. Samii M, Babu RP, Tatugiba M, et al: Surgical treatment of jugular foramen schwannomas. J Neurosurg 82:924–932, 1995. 59. Horn KL, Hankinson HL: Transsigmoid and extreme lateral approaches for removal of jugular foramen tumors. Oper Tech Otolaryngol Head Neck Surg 7:129–135, 1996. 60. Pellet W, Cannoni M, Pech A: The widened transcochlear approach to jugular foramen tumors. J Neurosurg 69:887–894, 1988. 61. Horn KL, Hankinson HL, Erasmus MD, et al: The modified transcochlear approach to the cerebellopontine angle. Otolaryngol Head Neck Surg 104:37–41, 1991. 62. Pellet W, Malca S, Roche PH: The widened transcochlear approach. Oper Tech Otolaryngol Head Neck Surg 7:136–150, 1996. 63. Jackson CG, Haynes DS, Walker PA, et al: Hearing conservation in surgery for glomus jugulare tumors. Am J Otol 17:425–437, 1996. 64. Brackmann DE, House WF, Terry R, et al: Glomus jugulare tumors: Effect of irradiation. Trans Am Acad Ophthamol Otolaryngol 76:1423–1431, 1972. 65. Foote RL, Coffey RJ, Gorman DA: Stereotactic radiosurgery for glomus jugulare tumors: A preliminary report. Int J Radiation Oncology Biol Phys 38:491–495, 1996. 66. Liscak R, Vladyka V, Simonova G, et al: Leksell gamma knife radiosurgery of the tumor glomus jugulare and tympanicum. Stereotact Funct Neurosurg 11:152–160, 1998. 67. Eustacchio S, Leber K, Trummer M, et al: Gamma knife radiosurgery for glomus jugulare tumours. Acta Neurochir 141:811–818, 1999. 68. Liscak R, Vladyka V, Wowra B, et al: Gamma knife radiosurgery of the glomus jugulare tumour—Early multicentre experience. Acta Neurochir 141:1141–1146, 1999. 69. Jordan JA, Roland PS, McManus C, et al: Stereotactic radiosurgery for glomus jugulare tumors. Laryngoscope 110:35–38, 2000. 70. Lustig LR, Jackler RK, Lanser MJ: Radiation-induced tumors of the temporal bone. Am J Otol 18:230–235, 1997. 71. Rubinstein L (ed.): Tumors of the cranial and spinal nerve root. In Atlas of Tumor Pathology, second series, fascicle 6: Tumors of the Central Nervous System. Washington, DC, Armed Forces Institute of Pathology, 1972, pp 205–214. 72. Russell DS, Rubenstein LJ: Pathology of Tumours of the Nervous System, 5th ed. Baltimore, Williams & Wilkins, 1989, p 537. 73. Tan LC, Bordi L, Symon L: Jugular foramen neuromas. Surg Neurol 34:205–211, 1990. 74. Graham MD, LaRouere MJ, Kartush JM: Jugular foramen schwannomas: Diagnosis and suggestions for surgical management. Skull Base Surg 1:34–38, 1991. 75. Horn KL, House WF, Hitselberger WE: Schwannomas of the jugular foramen. Laryngoscope 95:761–765, 1985. 76. Eldevik PO, Gabrielsen TO, Jacobsen EA: Imaging findings of schwannomas of the jugular foramen. Am J Neuroradiol 21:1139–1144, 2000. 77. Brackmann DE, Gherini SG: Differential diagnosis of skull base neoplasms involving the posterior fossa. In Cummings CW, Fredrickson JM, Harker LA, et al (eds.): Otolaryngology—Head and Neck Surgery. St. Louis, CV Mosby, 1985, pp 3421–3436.

78. Kaye AH, Hahn JF, Kinney SE, et al: Jugular foramen schwannomas. J Neurosurg 60:1045–1053, 1984. 79. Sasaki T, Takakura K: Twelve cases of jugular foramen neurinoma. Skull Base Surg 1:152–160, 1991. 80. Samii M, Babu R, Tatagiba M, et al: Surgical treatment of jugular foramen schwannomas. J Neurosurg 82:924–932, 1995. 81. Al-Rodhan NRF, Laws ER: Meningioma: A historical study of the tumor and its surgical management. Neurosurgery 26:832–847, 1990. 82. Yasargil MG, Mortara RW, Curcic M: Meningiomas of basal posterior cranial fossa. In Krayenbuhl H, Brihaye J, Loew F, et al (eds.): Advances and Technical Standards in Neurosurgery, 7th ed. New York, Springer-Verlag, 1980, pp 1–115. 83. Roberti F, Sekhar LN, Kalavakonda C: Posterior fossa meningiomas: Surgical experience with 161 cases. Surg Neurol 56:8–21, 2001. 84. Saleh J, Silberstein HJ, Salner AL, et al: Meningioma: The role of foreign body and irradiation in tumor formation. Neurosurgery 29:113–119, 1991. 85. Sridhar K, Ramamurthi B: Intracranial meningioma subsequent to irradiation for a pituitary tumor: Case report. Neurosurgery 25:643–645, 1989. 86. Rubinstein LJ (ed.): Tumors of the meninges and their derivatives, meningiomas. In Atlas of Tumor Pathology, second series, fascicle 6: Tumors of the Central Nervous System. Washington, DC, Armed Forces Institute of Pathology, 1972, pp 169–189. 87. Goldsher D, Litt AW, Pinto RS, et al: Dural “tail” associated with meningiomas on Gd-DTPA-enhanced MR images: Characteristics, differential diagnostic value, and possible implications for treatment. Radiology 176:447–450, 1990. 88. Tokumaru A, O’uchi T, Eguchi T, et al: Prominent meningeal enhancement adjacent to meningioma on enhanced MR images: Histopathologic correlation. Radiology 175:431–433, 1990. 89. Molony TB, Brackmann DE, Lo WWM: Meningiomas of the jugular foramen. Otolaryngol Head Neck Surg 106:128–136, 1992. 90. Nager GT, Heroy J, Hoeplinger M: Meningiomas invading the temporal bone with extension to the neck. Am J Otolaryngol 4:297–324, 1983. 91. Friedman CD, Fischer A, Peters R, et al: Growth rate of incidental meningiomas of the head and neck. Laryngoscope 100:41–48, 1990. 92. Lalwani A, Jackler RK: Preoperative differentiation between meningioma of the cerebellopontine angle and acoustic neuroma using MRI. Otol Head Neck Surg 109:88–95, 1993. 93. Teasdale E, Patterson J, McLellan D, et al: Subselective pre-operative embolization for meningiomas: A radiologic and pathological assessment. J Neurosurg 60:506–511, 1984. 94. Firsching RP, Fischer A, Peters R, et al: Growth rate of incidental meningiomas. J Neurosurg 73:545–547, 1990. 95. Spetzler RF, Daspit P, Pappas CT: The combined supra- and infratentorial approach for lesions of petrous and clival regions: Experience with 46 cases. J Neurosurg 76:588–599, 1992. 96. Kawahara N, Sasaki T, Sugasawa M, et al: Dumbell type jugular foramen meningioma extending both into the posterior cranial fossa and into the parapharyngeal space: Report of 2 cases with vascular reconstruction. Acta Neurochir 140:323–331, 1998. 97. Al-Mefty O, Fox JL, Smith RR: Petrosal approach for petroclival meningiomas. Neurosurgery 22:510–517, 1988. 98. Fisch U, Pillsbury HC: Infratemporal fossa approach to lesions of the temporal bone and base of the skull. Arch Otolaryngol Head Neck Surg 105:99–107, 1979. 99. Sekhar LN, Schramm VL, Jones NF: Subtemporal-preauricular infratemporal fossa approach to large lateral and posterior cranial base neoplasms. J Neurosurg 67:488–499, 1987. 100. Kondziolka D, Lunsford LD, Coffey RJ, et al: Stereotactic radiosurgery of meningiomas. J Neurosurg 74:552–559, 1991.

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Outline Pathology Chordoma Meningioma Neuroma and Neurilemmoma Craniopharyngioma Radiation Therapy for Parasellar and Clival Neoplasms Interventional Radiology Surgical Anatomy Operative Approaches Tumors of the Clivus: Midline Approaches Transoral-Transpalatal

N

Chapter

Management of Clivus and Parasellar Space Neoplasms

Transpalatal Le Fort I Osteotomy Tumors of the Clivus: Lateral Approaches Infratemporal Fossa, Type B Approach TranscervicalRetropharyngeal Parasellar Tumors Frontal-Temporal/Lateral Facial Approach Infratemporal Fossa, Type C Approach Summary

eoplasms of the mid–skull base present some of the most challenging problems for the skull base surgeon. Management of tumors in this anatomic region are particularly difficult for several reasons: (1) the compact anatomy contains vital neurovascular structures, and the adjacent brainstem and pharynx limit surgical access; (2) radical surgical excision of tumors is limited by vital structures; (3) most neoplasms in this area are benign, slow growing, asymptomatic tumors that are very large before they are detected; (4) even though the metastatic rate of even the “benign” tumors in this region is low,1–4 they can be considered malignant because their local invasiveness leads to the demise of patients; (5) many of these tumors are resistant to conventional radiotherapy; and (6) tumors of the clivus and parasellar region frequently involve both the middle and posterior fossa, requiring combined approaches. Although tumors of the clivus and parasellar region represent only a small percentage of intracranial neoplasms, a substantial body of recent literature focuses on different surgical approaches for treatment of petroclival tumors.3–20 Much thought and considerable energy by many surgeons has been devoted to improving access to this area of the skull base. Any route the surgeon chooses to expose this region is narrow and deep; and it involves retraction or interruption of significant structures. Improved imaging techniques and proper approach planning,21–23 interventional radiology,24 radiation therapy,5,25,26 advancements in microsurgical techniques including image-guided surgery,27 intensive perioperative monitoring, and team-oriented treatment approaches28,29 have enabled surgeons and other specialists to be more successful at removing and treating

Bruce J. Gantz, MD, MS Ted A. Meyer, MD, PhD Miriam I. Redleaf, MD Arnold H. Menezes, MD

tumors of the clivus and parasellar area in a relatively safe manner. Perioperative mortality has decreased substantially, total or near-total tumor removal is common, and new methods of highly focused radiation therapy have allowed patients to live longer lives with significantly less morbidity and higher local tumor control rates.26,30–32 Better understanding of the biology and histology of the different tumors33–35 and the relations between predictive factors such as age, sex, tumor size, and presence of mitotic figures and various tumor markers36 should lead to further improvements in treating patients with these difficult lesions. This chapter reviews the most common neoplasms arising in the base of skull including chordoma, craniopharyngioma, meningioma, and neuroma. The biological behavior of each is described along with management strategies. A variety of surgical strategies have been developed to access the mid–skull base. Approaches that we have found useful are discussed. Primary treatment of tumors and treatment of residual disease with new forms of radiation therapy are also presented.

PATHOLOGY The differential diagnosis of neoplasms of the parasellar and clival regions is lengthy. The most common neoplasms of the sella are primary pituitary adenomas.37,38 Primary lesions of the cavernous sinus include meningiomas, neuromas, and craniopharyngiomas.39,40 Tumors that advance into the cavernous sinus region from adjacent areas are primarily meningiomas, neuromas, chondromas, chondrosarcomas, 1047

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chordomas, and pituitary adenomas.39,41 Pineal tumors, epidermoid tumors, optic gliomas, and optic chiasm germinomas can also encroach on the parasellar space from anterior and superior to the sella.37,38,41,42 Invasion from below can occur with nasopharyngeal carcinomas, esthesioneuroblastomas, nasal gliomas, rhabdomyosarcomas, rhabdomyomas, hemangiopericytomas, nasopharyngeal angiofibromas, synovial carcinomas, and adenocarcinomas.37,43,44 Primary carcinomas elsewhere in the body can metastasize to the skull base, the most common being from the breast and kidney.37,44–46 Non-neoplastic lesions of the parasellar region include aneurysms and cavernous carotid arteriovenous fistulae. Midline tumors of the clivus include chordomas, chondrosarcomas, mucinous adenocarcinomas, neuromas, and primary brainstem neoplasms. Degenerative demyelinating or inflammatory lesions of the brainstem or cerebellum can mimic neoplasm. Infection of the subarachnoid space, petrous apicitis, cavernous sinus thrombosis, or skull base osteomyelitis must also be ruled out.44,47–49 A description of the more common lesions found in the mid-base of the skull follows.

CHORDOMA Chordoma represents 5.2% of primary bone tumors. The peak onset of spheno-occipital (clivus) and cervical chordomas is in the third through fifth decades of life. There is an equal male-female incidence; however, there is a marked male predominance in childhood chordoma of the clivus.50–52 The incidence of spheno-occipital chordoma has been reported as high as 30% of all chordomas in some series, and cervical chordoma varies from 8% to 15%.41,53–57 The location of chordomas is the result of embryologic development. Ectodermal elements form the notochord, which later becomes closely related to the skull base of the embryo’s cranium. The notochord then degenerates, leaving remnants only as the nucleus pulposus of the intervertebral discs. Other remnants of the notochord can be left in the midline of the skull base, particularly in the clivus and the posterior sella, where they later develop into chordomas.37,58–60 Others have suggested that chordomas originate from embryonic rests that were never part of the original notochord.54 Grossly, chordomas are bulky, grey, soft, friable, pseudoencapsulated masses. Microscopic examination of “typical” chordomas reveals fibrous strands separating the tumor into lobules. The lobules are composed of sheets of cells, which are stellate or polygonal. Among these cells is the characteristic physaliferous cell, which contains a frothy vacuolated cytoplasm that appears to contain mucin (Fig. 62-1). The stellate cells appear to be the proliferating element, differentiating into the selfdestructing physaliferous cell. A second type of chordoma has been characterized as a chondroid chordoma. These tumors contain hyaline cartilage with neoplastic cells in the lacunae. It can be difficult to differentiate chondroid chordoma from chondrosarcoma,61 mucinous carcinoma, or ependymoma by light microscopy. Special stains for epithelial markers can differentiate these entities. With chondroid chordoma it is important to obtain cartilage and epithelial elements in the biopsy.53–56,62–66

Figure 62-1. Chordoma with typical physaliferous cells with vacuolated cytoplasm (hematoxylin and eosin).

The diagnosis of skull base chordoma cannot be made on clinical grounds since the presentation is identical to other space-occupying lesions of the intracranial vault. The symptoms of chordoma depend on location and extension of the mass. It is not uncommon for chordoma to be quite extensive, sometimes extending circumferentially around the brainstem. Superior extension can cause endocrine dysfunction, and lateral extension can disrupt the function of cranial nerves II through VI, producing diplopia, optic atrophy, visual field defects, ptosis, and sudden blindness. Posterior or posterolateral expansion can produce dysphagia, hoarseness, facial paralysis, dysequilibrium, hearing loss, and torticollis in children from compression of cranial nerves VII through XII. Intracranial extension can cause ataxia and headache with nausea and vomiting.37,41,52,55,57,58,67–72 In one series, 92% of sphenooccipital chordomas presented with a nasopharyngeal mass and nasal obstruction.52 The most common symptoms of spheno-occipital chordoma are headache, visual changes, and nasopharyngeal obstruction.52,73 Chordoma is a histologically benign-appearing neoplasm with infrequent mitoses and little pleomorphism; however, its characteristic growth is one of relentless extension and recurrence. The high rate of recurrence cited by authors is most likely secondary to incomplete extirpation. The absence of a well-developed capsule, the gelatinous quality of the tumor, and possible seeding of the surgical bed contribute to the difficulty of complete surgical removal. The 5-year survival rate with chordoma is approximately 60% and the 10-year survival is 25%.54,59,74,75 Despite the dismal prognosis, very long-term survival has been reported. The chondroid variant has a better prognosis with only recent reports of metastasis.4,70 Metastases to lung, bone, and lymph node have been reported with typical chordoma.37,41,50,55,71 Imaging modalities have improved substantially in the past decade. Computed tomography (CT) in combination with magnetic resonance imaging (MRI) have replaced skull films, angiography, and pneumoencephalography as imaging studies of choice for delineating most skull base neoplasms. On MRI, 75% of chordomas are isointense and 25% hypointense on T1-weighted images (Fig. 62-2). All are hyperintense on T2. Chondroid chordomas are less

Management of Clivus and Parasellar Space Neoplasms

Figure 62-2. T1-weighted MRI image of clivus chordoma (arrows).

intense on T2. These tumors enhance with gadolinium (Gd) (Fig. 62-3). The multiplanar imaging capacity of the MRI is highly advantageous for lesions that expand in an irregular multidimensional manner. Chordoma extension into the nasopharynx can also be distinguished from nasopharyngeal mucosa on MRI since chordoma is hypointense to mucosa on T1 and hyperintense to mucosa on T2.71,76,77 High-resolution CT scans are necessary to demonstrate the extent of bone destruction and involvement of skull base foramina. Both modalities are essential to develop the most efficient surgical approach to the skull base lesion. MRI alone is the imaging technique of choice for postoperative surveillance scanning.

Figure 62-3. T1-weighted and gadolinium MRI image of clivus chordoma (arrows). Compare with Figure 62-2.

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Surgical extirpation of clivus chordomas is limited by the difficult access and the proximity of vital structures. Complete excision is difficult but provides the best longterm survival with the lowest recurrence and is the treatment of choice.78,79 Every effort should be made to complete a total excision at the initial surgical procedure because scarring, postradiation changes, and distorted anatomy dramatically increase complications and most likely further spread of the tumor. Adjunctive standard fractionated radiotherapy provides little assistance in the management of chordoma. Chordomas are known to be radioresistant.79,80 However, there are a few reports of chordomas demonstrating a radioresponsiveness, including tumor regression and longer quiescent periods before relapse.26,29,35,41,68,81 High-dose radiation must be used to affect tumor growth.51,82 New methods of delivering radiation (stereotactic, gamma, combined proton and photon) to these tumors have met with success. Many authors feel that treatment should be total or subtotal resection followed by highly focused radiation to the small field.2,25,29,83,84 In general, radiotherapy should be considered palliative; however, our limited experience suggests that proton-beam radiation therapy following surgical excision may assist in long-term survival with this disease. Standard radiotherapy can result in life-threatening sequela if re-excision is required. Postoperative radionecrosis increases the risk of cerebral spinal fluid leak and internal carotid artery rupture, especially if oral cavity contamination occurs.

MENINGIOMA Meningiomas are benign neoplasms originating from the dura. Mid–skull base meningiomas can develop in the intrasellar and parasellar regions, medial sphenoid bone, cavernous sinus, clivus, and petrous apex. Of the parasellar group, approximately one half originate from the medial sphenoid wings, one fourth develop from the sphenopyramidal (posterior clinoid, petrous apex, lateral cavernous sinus) region, and one fourth are suprasellar.84 Upper clivus meningiomas are thought to arise from the spheno-occipital synchondrosis; therefore, these lesions are always lateral on the clivus.85 Middle cranial fossa (parasellar) meningiomas demonstrate a female predominance of approximately four to one. Posterior cranial fossa (clival/petrous apex) meningiomas also have a female predominance of about two to one.86,87 Grossly, meningiomas are firm, broad-based, and adherent to the dura from which they originated. On histologic examination, oval and fusiform cells with scant cytoplasm are observed. The cells are arranged in tight interlacing bundles and whorls. Within the tumor mass are laminated, calcified structures termed psammoma bodies (Fig. 62-4). Angioblastic vessel formation within the neoplasm can resemble hemangioma. Both the primary tumor and adjacent hemangiomatous structures are thought to arise from the same mesenchymal origin.43,85,88–91 The location and direction that the tumor expands determines the array of symptoms produced. Common to all mid–skull base meningiomas is the characteristically long interval from onset of symptoms to diagnosis, typically ranging from 2 to 8 years.

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Figure 62-4. Microscopic view of meningioma with oval and fusiform cells with scant cytoplasm. In the tumor mass are laminated calcified structures called psammoma bodies (inset).

The symptoms of clivus and petrous apex meningiomas are caused mainly by compression of the adjacent pons and medulla as well as by extension into the cerebellar pontine angle. The symptoms include the nonspecific effects of increased intracranial pressure (headache, nausea, and vomiting). The most common symptoms are those that result in direct compression of cranial nerves V, VII, and VIII, and include facial dysesthesia, hearing loss, vertigo, and facial paralysis. Dysphagia, hoarseness, and hypoglossal paralysis can also be seen. Compression of cerebellum and cortical spinal tracts result in ataxia. Therefore, gait disturbances are another common symptom.47,86,87,89,92,93 Middle and anterior cranial fossa meningiomas characteristically present as a slowly progressing deficit in either vision or extraocular motility. Evidence of a mass lesion can be appreciated by the presence of periorbital discomfort and exophthalmos.32,88,94–96 On MRI, meningiomas are isodense with brain, and they enhance brightly with Gd (Fig. 62-5). Gadolinium enhancement also helps to distinguish meningioma from adjacent arteries, and assists with the diagnosis of carotid and basilar artery encasement.94 High-resolution CT scanning provides a better view of skull base foramina involvement and the extent of internal carotid canal erosion. Meningiomas also enhance brightly with iodinated contrast on CT. Angiography should be performed to identify involvement of intracranial vasculature. With large parasellar tumors, reversed blood flow can be seen, indicating compression of the cavernous sinus.97 Angiography can also exclude the possibility of a vascular mass, such as an aneurysm, as the cause of the presenting symptoms.44 Operative approaches are discussed in a later section. However, it is appropriate to mention the special problems with meningioma excision. Meningiomas are firm, broadbased lesions that are closely adherent to dura. They require a broader surgical access than the soft, gelatinous chordoma. Meningioma excision requires dural excision and repair, and the craniotomy must exceed the tumor size. Short-term and long-term results of operative treatment of meningiomas have improved greatly in the past 30 years. Clivus meningiomas were considered inoperable in the early 1970s.98 Postoperative morbidity increases with the

Figure 62-5. T1-weighted and gadolinium MRI image of petroclival meningioma. Note the characteristic broad base at the dural margin.

size and location. Removal of lesions from the cavernous sinus can result in diabetes insipidus; loss of olfaction; internal carotid artery injury; and lesions of cranial nerves III, IV, and VI. Clivus and petrous apex lesion excision can result in new or worse dysfunction of cranial nerves V, VII, and VIII; ataxia; and mental status changes.39,40,87 Reports that address improved surgical techniques including acute reconstruction of cranial nerve deficits document relief and control of preoperative symptoms including headache. There has also been a dramatic drop in operative mortality.39,87,95,99 Meningioma does not appear to respond to radiation therapy.40,87 However, stereotactic gamma rays have been used to treat both primary and residual tumors. Over an average 37-month period, tumor volumes were shown to decrease in 23% of patients, remain stable in 68% of patients, and increase in 8% of patients.100 Further studies with longer follow-up will provide more information about the efficacy of stereotactic gamma ray therapy in treating petroclival meningiomas.

NEUROMA AND NEURILEMMOMA Neuroma and neurilemmoma are considered together because they manifest with similar clinical symptoms, are treated similarly, and are distinguished only on histopathology. Intracranial neuromas arise predominantly from the

Management of Clivus and Parasellar Space Neoplasms

vestibular division of cranial nerve VIII in the cerebellar pontine angle and internal auditory canal. However, neuromas can arise from the nerve sheath of any nerve root. Neuromas in the cavernous sinus arise from cranial nerves III and IV, and the first and second division of V. These tumors typically arise from Schwann cells. Some researchers suspect that neuromas arise from sensory nerve “twigs” or ectopic Schwann rests since Schwann cells are not usually found in association with the nerves of the cavernous sinus.39,43,65,101–104 Neuromas and neurilemmomas are pathologically benign, encapsulated, soft masses. Early symptoms of cavernous sinus tumors are facial dysesthesia, diplopia, and anisocoria. Increase in tumor size can displace adjacent structures, producing exophthalmos, optic chiasm compression with homonymous hemianopsia, or ocular immobility.102–104 Histologic examination of neuromas shows uniform spindle cells in close array forming palisades (Fig. 62-6). The neoplastic cells stain densely for reticulin fiber and also demonstrate S-100 protein. As with meningioma, hemangiomatous elements can be found within the tumor, presumably from a common mesenchymal origin.90,91 The MRI features of neuromas are similar to meningiomas and are isodense with brain on T1 images, hyperintense on T2, and enhance well with Gd (Fig. 62-7). Neuromas are highly vascular lesions and enhance with intravenous contrast on CT scan. Neuromas do not display calcification, which is sometimes seen with meningiomas and chordomas. They also lack a broad-based attachment to the dura or dural tails that enhance with gadolinium-like meningiomas.

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Figure 62-6. Histologic picture of typical neuroma with palisading arrays of uniform spindle cells (hematoxylin and eosin).

CRANIOPHARYNGIOMA Craniopharyngiomas are benign congenital neoplasms that most likely arise from remnants of Rathke’s pouch. Thirty to forty percent of craniopharyngiomas are found in patients younger than 15 years; they constitute 28% of parasellar tumors in children. Although some series cite a slight male predominance, most find an equal male-to-female ratio in both children and adults. There is a bimodal incidence of occurrence of this entity between 6 and 10 years and in the fifth and sixth decades.38,84,105–109 During development, the stomodeum is in contact with the infundibulum. Portions of the stomodeum contribute

Figure 62-7. T1-weighted and gadolinium MRI image of a trigeminal neuroma involving foramen ovale and cavernous sinus.

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Figure 62-8. Microscopic characteristics of a craniopharyngioma include palisading cells around a central aggregate of transparent cells with and without foreign body reaction (hematoxylin and eosin).

oral endoderm, which becomes the pars distalis of the pituitary. As this stomodeum recedes from the pituitary, a trail of endodermic rests can be left. Craniopharyngioma is thought to develop from these rests, and it can be found anywhere along this tract, developing intracranially in the sellar region, basisphenoid, and pharynx.60,85 Histologic examination of craniopharyngioma reveals palisading epithelium, which resembles embryonic dental tissue. Characteristic features are peripherally palisading cells around a central aggregate of transparent cells with and without foreign body reactions (Fig. 62-8). At the margin of these aggregates are columnar epithelial cells, radially aligned. Adult and pediatric craniopharyngiomas may differ histologically. One half of the adult tumors demonstrate nonpalisading squamous epithelium. Calcium is seen in many of the adult tumors, but it is more common pediatric cases.85,109,110 The symptoms of craniopharyngiomas are similar to those of other space-occupying lesions in the sella and parasellar region. These tumors expand differently in children and adults. In adults, they tend to grow posteriorly into the interpeduncular space and in children they expand superiorly toward the third ventricle and can block the foramen of Munro. The most common symptoms are those of increased intracranial pressure in both groups. Sixty to eighty-five percent of children present with headache, nausea, and vomiting. Twenty to thirty percent of adult cases are also associated with disorientation, dementia, or mental status changes. Both children and adults experience visual disturbances; however, children are more inclined to accommodate visual changes and may not alert their parents until vision is severely impaired. Fifty-five percent of children have papilledema. Children may experience endocrine dysfunction including growth disturbance, diabetes insipidus, hypothyroidism, and impaired sexual development. Adult pathology includes gonadal dysfunction and diabetes insipidus.38,85,105–107,109–111 Ataxia, hearing loss, spontaneous nystagmus, and facial weakness have also been reported with extension into the prepontine and cerebellar pontine angle regions.112,109 The characteristic appearance of craniopharyngiomas on CT scan contributes to the diagnosis. They are cystic

lesions with parasellar hypodense regions that are broadly calcified. The rim of pericystic tissue enhances brightly with contrast material. Often hydrocephalus is apparent.70,112,113 An important function of the CT is to identify the solid-to-cyst ratio of the neoplasm, which has implications for therapeutic management. MRI provides a better identification of the tumor-brain interphase and minute neuroanatomic details of the distorted brainstem and parasellar structures. These tumors are hyperintense on T2 images and hypointense on T1.114 Total excision of a craniopharyngioma provides the best chance of long-term control. Up to 75% of both adult and pediatric cases are reported cured by attempted total excision.115,116 The introduction of replacement corticosteroids has prevented fatal postoperative adrenal collapse commonly associated with resection.84,111,116 These “cure rates” represent results for “solid” tumors removed by experienced surgeons. Cystic tumors, on the other hand, are usually larger and involve more adjacent vital anatomy, and only subtotal resection is possible. The addition of postoperative radiation therapy in these cases has dramatically improved long-term control rates with up to 70% reported.115 Even with meticulous surgical technique, recurrences of craniopharyngioma have been reported over 10 years following “total resection.” Thus, long-term imaging and endocrine follow-up is imperative.84,112,115

RADIATION THERAPY FOR PARASELLAR AND CLIVAL NEOPLASMS The tumor types just discussed are usually benign histologically but malignant by virtue of their location. The tumors are not prone to metastasize, but their locally aggressive and destructive behavior eventually leads to the patient’s demise unless the tumors can be removed completely or radiated to stop them from growing. Access and total extirpation is sometimes limited by their proximity to vital structures. Therefore, although total extirpation is a treatment of choice with these neoplasms, often the surgeon performs a subtotal resection, either unknowingly or by necessity. In these situations, the benefits and disadvantages of adjuvant radiotherapy becomes an issue. In the past, nonconformal external beam radiation therapy was not deemed very useful in the treatment of any of these histologically benign lesions. More recently, improvements in the delivery systems (conformal therapy) and the advent of different types of radiation therapy (gamma rays, protons) have led to a virtual explosion in the number of centers treating benign intracranial lesions with radiation therapy. Terms such as gamma knife, stereotactic radiosurgery, and noninvasive surgery are commonplace in the literature and in medical advertising. Radiation therapy is touted as safe and cost-effective when compared to surgical removal of these lesions. Stereotactic fractionated radiation therapy has been shown to shrink some tumors and improve local control with chordomas, chondrosarcomas, and meningiomas in the petroclival region.83,117 Gamma rays have also been used to treat small clival chordomas and chondrosarcomas, with approximately one third of tumors decreasing in size. 26,81

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High-dose fractionated proton beam radiotherapy has recently emerged as a therapy for skull base chordomas and chondrosarcomas.84 Local control rate was approximately 83% over a mean follow-up period of 33 months, with all tumors of volume less than 25 cc demonstrating local control. A larger study found that 30% of their patients had a local relapse after surgery followed by highdose proton/photon radiation therapy. Most of these patients received salvage surgery, but the 5-year survival rate in this group was only 6%.2 Radiation therapy has other risks such as rapid tumor growth,118 potential transformation of a benign tumor into a malignancy,119–121 and resultant secondary malignancies.122 If surgery is needed after radiation therapy, the tumor is often very fibrotic and adherent to the surrounding tissues, making tumor removal and preservation of nearby vital structures even more difficult. Long-term follow-up of patients who receive radiation for benign intracranial tumors is essential to evaluate changes over time. The brainstem’s tolerance to radiation can be altered with the extent of surgery, and nonconformal fractionated radiotherapy is not recommended.123 The temporal lobe and other nearby structures can also be damaged with radiation therapy.124,125 The use of radiation therapy in chordoma is controversial. The tumor is relatively radioresistant, and high doses of external beam therapy are necessary for local control even when only microscopic disease remains after resection.1,84 However, there are reports of curing primary chordoma by treating with radiation alone.126 Some have suggested that attempts at total extirpation be foregone altogether and that operative management be directed solely toward obtaining a biopsy or subtotal resection with subsequent radiotherapy as the primary treatment.127 The morbidity from high-dose radiotherapy has been reduced by altering the fractionation intervals and by implanting Iodine 125 brachytherapy seeds into the region to treat residual disease at the time of operation.79,128,129 However, many complications of radiotherapy for chordoma have been reported. These include significant defects in memory and speech production; endocrine deficiencies; parenchymal necrosis; and less serious but problematic mucositis, dry mouth, and reduced taste.126,127 Some series have also suggested that radiotherapy may induce chordomas to undergo dedifferentiation and predisposes them to metastases.50 Finally, postoperative surveillance of the tumor site becomes more difficult following radiation therapy because the irradiated brain parenchyma becomes conspicuously hyperintense on T1 and T2 images, thereby reducing the effectiveness of MRI.76 Our experience with standard radiation therapy in chordoma has been a negative one. We find that irradiation does not significantly alter the course of incompletely excised disease, thereby providing no benefit to the patient. However, the radiation effects on the local tissues make subsequent reexcision significantly more difficult. The tissue planes become obscured, the tumor becomes more adherent to local structures, and, more significant, postoperative wound healing is delayed. Therefore, in our management of chordoma, radiation therapy is reserved for palliation. As mentioned in the section on chordoma, our limited experience with proton beam radiation suggests that this modality may control residual disease.

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Radiation therapy for skull base meningiomas also is controversial, with reports and results similar to those for chordoma.130 Newer gamma ray radiotherapy has been used as both primary and adjunctive therapy for petroclival meningiomas with some tumors demonstrating regression in size.100,131–133 The use of radiotherapy in craniopharyngioma appears to be of benefit, as previously described. Several series describe increased survival and reduced recurrence with combined surgery and radiation therapy.115,134–137 However, many complications of radiation have been reported with craniopharyngioma including radiation-induced vasculopathy, optic neuritis, and induction of malignancies.115,138–140 Radiation therapy has a role in the management of benign but positionally malignant neoplasms of the skull base. The morbidity of radiotherapy; its ability to obscure clinical signs, symptoms, and surveillance; and the alteration of wound healing must be weighed against its potential benefits.

INTERVENTIONAL RADIOLOGY In evaluating neoplasms of the mid-intracranial skull base, selective catheterization and injection of the internal and external carotid and vertebral systems is essential. Angiography will demonstrate displacement of the carotid and vertebral basilar systems as well as vascularity of the tumor. Encasement and narrowing of vessels is best determined by this technique. In addition, catheters have been developed that can cannulate small vessels and selectively deliver occlusive material for embolization of arterial feeders to neoplasms.114,141–147 Superselective embolization has greatly reduced intraoperative bleeding in tumors such as meningioma, glomus jugularae, and angiofibroma.114,148 Complications seen with selective embolization range from transient cranial nerve paralysis to transient aphasia. Our protocol involves embolization the day before the procedure. Lengthy delays between embolization and surgery increases interstitial fibrosis and difficulty identifying tissue planes.

SURGICAL ANATOMY The important anatomical landmarks of the midline and parasellar skull base are seen in Figures 62-9 and 62-10. Tumors in this region are intimately associated with the complicated anatomy of the sphenoid, petrous apex, and occipital bones and their adjacent neurovascular structures. Frequently these neoplasms involve both middle fossa and posterior fossa anatomy. The clivus is a specific term designating the dorsal slanting surface of the sphenoid and basilar occipital bones from the dorsum sellae to the foramen magnum. Surgeons often incorrectly label the entire midline bone the “clivus.” The ventral surface includes the anterior wall of the sphenoid sinus and the basisphenoid and basilar portion of the occipital bone. Near the foramen magnum laterally, the hypoglossal nerve exits the skull through the hypoglossal canal. Lateral and inferior to the canal are the occipital condyles, which articulate with the atlas. The periosteum of the clivus is closely adherent to

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Figure 62-9. Intracranial anatomy of skull base.

Figure 62-10. Extracranial anatomy of skull base.

the ventral dura, forming a dense layer anterior to the medulla and pons. This dura is continuous with the anterior spinal dura inferior to the foramen magnum. The rich basilar plexus of veins is found between the layers of the ventral dura. Many midline skull base tumors extend into the craniovertebral junction. A brief anatomic overview of this complex region is helpful in understanding transoraltranspalatal approaches (Fig. 62-11). The occipito-atlantoaxial joints are approximated by multiple ligamentous structures that are responsible for its multiple movements and stability. The ventral ligaments include the anterior atlanto-occipital membrane (which is the rostral extension of the anterior longitudinal ligament) and its insertions on the anterior clivus. The principal stabilizer of the atlantoaxial joint, the transverse ligament, approximates the dens to the atlas and inserts on the mesial aspect of each atlas lateral mass. The atlas is connected to the occiput by the apical dens ligament, the cruciate ligament, the tectorial membrane, and the oblique alar ligaments. The tectorial membrane is continuous with posterior longitudinal ligament within the spinal canal, attaching the basilar occiput of the clivus to the spinal column. It is fixed below, to the posterior surface of the body of the axis, and expands as it ascends in front of the foramen magnum, where it blends with the cranial dura. Its anterior surface is in relation with the transverse ligament of the odontoid process. The posterior stabilizing tissues include the ligamentum flavum, ligamentum nuchae, the posterior atlanto-occipital membrane, the supraspinous ligaments, and the paracervical musculature. It is important to realize that the posterior pharyngeal musculature is devoid over the basiocciput, and the mucosa is very thin in this location. The circular sinus, part of the basilar sinus, circumscribes the foramen

magnum and is the first structure encountered posterior to the clivus at the foramen magnum. The cavernous sinus is composed of multiple walled venous cavities. Fortunately for the surgeon, it is not a single large cavity like the sigmoid and transverse sinuses. It lies lateral to the sella from the anterior clinoid and superior orbital fissure posterior to the posterior clinoid and petrous apex (Fig. 62-12). The cavernous sinus connects

Figure 62-11. Midline sagittal view of cranial-vertebral junction.

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Figure 62-12. Anatomy of parasellar and cavernous sinus region.

with both the superior and inferior petrosal sinuses to drain into the sigmoid sinus and jugular bulb, respectively. The internal carotid artery lies on the medial wall of the cavernous sinus. The abducens nerve is lateral and slightly inferior to the carotid, and the oculomotor and trochlear nerves are on the superior lateral wall of the sinus. The ophthalmic and maxillary divisions of the trigeminal nerve are on the lateral inferior aspect of the sinus. Lateral to the cavernous sinus the foramen ovale and foramen spinosum with the mandibular division of the trigeminal nerve and middle meningeal artery pass through the greater wing of the sphenoid bone. The foramen lacerum is immediately

TABLE 62-1. Surgical Approaches for Clival and Parasellar Tumors Location of Tumor

Surgical Approach

Clivus Midline (medial to hypoglossal canals) –Upper half clivus –Lower clivus C2-C3 Bilateral extension into pterygoid spaces Lateral to hypoglossal canal –Upper clivus and petrous apex –Lower clivus and C1, C2, C3

Transpalatal Transpalatal/transoral Le Fort I osteotomy

OPERATIVE APPROACHES The literature is filled with articles advocating specific surgical routes for the removal of midline skull base and parasellar tumors. Most are combinations or minor modifications of anterior-midline, lateral, or posterolateral approaches. The specific surgical route selected should provide sufficient access to accomplish total or near-total tumor excision while inducing the least amount of additional morbidity. Our skull base team maintains a flexible attitude and uses a variety of combinations depending on the position and size of the neoplasm as well as the concerns and expectations of the patient. This philosophy, specific procedures, and indications for use in our hands are listed in Table 62-1.

Infratemporal fossa, type B Transcervical/retropharyngeal

TUMORS OF THE CLIVUS: MIDLINE APPROACHES

Preauricular/ frontotemporal/lateral facial Infratemporal fossa, type C

Midline approaches to the middle third of the skull base include the transnasal,149–152 trans-septal–transsphenoidal,153,154 transpalatal-transoral,46,73,153–158 transnasal–transantral,153,159–162 and Le Fort I osteotomy

Parasellar Space (cavernous sinus) No involvement of petrous carotid artery Involvement of petrous carotid and eustachian tube

posterior at the confluence of the sphenoid, petrous apex, and occipital bones. It contains the internal carotid artery and cartilage. Immediately posterior and lateral to the cavernous sinus, the gasserian ganglion of the trigeminal nerve is in a depression of the petrous apex. The dural pocket that surrounds the ganglion is termed Meckel’s cave.

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approaches.163–165 The transseptal–trans-sphenoidal provides the narrowest exposure of this group. This approach provides access to small tumors of the upper clivus and the sella. It is useful for biopsy and can be used for decompression of small craniopharyngiomas. Lateral access is severely limited in this approach and is of little use in chordoma, meningioma, or neuroma. Modifications of the transnasal procedure include widening of the piriform aperture for improved access to the sphenoid rostrum through a sublabial incision. The transantral-transnasal route involves an internasal dissection through a sublabial incision. Sufficient lateral exposure is obtained to remove bone of the anterior face of the maxilla and lateral nasal wall. The mucosa of the floor in the ipsilateral nose is raised and the septum is dislocated from the maxillary crest into the contralateral nares. Mucoperiosteal flaps are raised over the bony septum and the bony septum is removed to gain access to the sphenoid and basisphenoid. A wider lateral exposure on one side is achieved extending from the cribriform plate to midclivus. This approach can be extended by performing a subtotal maxillectomy, including partial resection of the palate.159 The coronoid process and pterygoid plates are removed. A midface degloving procedure in which the soft tissues of the lip and nose are elevated from the bony nasal pyramid and the face of the maxilla enables adequate exposure for the lateral osteotomies.153,159 This approach is, in effect, a radical pterygomaxillotomy. It allows wider lateral access from midline to the carotid artery and inferior access down to the C5 vertebra. Disadvantages include cosmesis with the need for a prosthodontic appliance for palatal reconstruction, and, in all transantral-transnasal approaches, isolation of the dura or CSF from the oral cavity is problematic. The risk of intracranial contamination rises dramatically if the patient has been previously treated with radiation therapy.

Figure 62-14. Lateral view of midline clivus chordoma (MRI with gadolinium), removed through transoral-transpalatal approach.

craniovertebral junction to C3 (Fig. 62-13). Figures 62-14 and 62-15 demonstrate preoperative MRI of clivus chordoma excised using this approach. This is the procedure we prefer for midline lesions that do not extend lateral to the hypoglossal canal or occipital condyles.166 Three days before the procedure, nasopharyngeal cultures are

TRANSORAL-TRANSPALATAL A transoral-transpalatal approach provides good access to midline lesions extending from mid-clivus through the

Figure 62-13. Transoral-transpalatal approach for midline lesions of the clivus. Removing a portion of the hard palate and vomer (dashed lines) allows exposure from the sphenoid sinus to vertebra C3.

Figure 62-15. Axial view of the midline clivus chordoma (arrows) shown in Figure 62-14. (MRI with gadolinium.)

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Figure 62-16. Transoral-transpalatal exposure of basiocciput (clivus) and vertebrae C1 and C2.

obtained. If no pathogens are identified, preoperative antibiotics are started 3 hours prior to beginning the procedure. Antibiotics are continued during the procedure and for 36 hours postoperatively. During the procedure, the patient is ventilated through a tracheotomy tube. Mouth guards made from the patient’s preoperative dental impressions are fitted over the maxillary and mandibular dentition, and a Dingman self-retaining mouth retractor is placed. A midline incision from the anterior hard palate and through the soft palate to one side of the uvula is developed (Fig. 62-16). The mucoperiosteum of the hard palate is elevated laterally to the alveolar ridge, with care not to injure the greater palatine vascular supply at the greater palatine canal. At the posterior margin of the soft palate the nasal mucoperiosteum is elevated and preserved for nasal cavity closure. Retraction sutures are placed in the soft-palate and hard-palate flaps and attached to the Dingman retractor. A Kerrison rongeur is used to remove the bone of the hard palate lateral to the midline. Subperiosteal flaps are then elevated from the nasal septum bilaterally to expose the bony septum and vomer. This bone is then removed with a rongeur, exposing the basisphenoid and anterior wall of the sphenoid sinus (Fig. 62-17). The posterior pharyngeal mucosa is then infiltrated with 0.5% lidocaine solution with 1:200,000 epinephrine.

A midline incision in the posterior pharyngeal median raphe is carried through the mucosa, the constrictor muscles, and the buccopharyngeal fascia. The prevertebral fascia and flaps are elevated laterally and retracted with stay sutures. The longus colli muscles are separated from their ligamentous osseous attachment to expose the caudal half of the basiocciput (clivus), the atlanto-occipital membrane, atlas, and axis as far laterally as the eustachian tubes. The anterior longitudinal ligament and the occipital ligaments are cauterized and sharply dissected free of the caudal clivus, exposing the anterior arch of the atlas and the ventral aspects of the axis body. Inferior exposure to vertebrae C4 and C5 depends on the extent of the tumor. The operating microscope facilitates visualization at this point. If tumor has not extended through the bone, a high-speed drill and diamond burr are used to gain exposure. Bone removal can include the anterior arch of the atlas and odontoid process. The transverse dimension of exposure is 3 to 3.5 cm. Following removal of the tectorial membrane, pulsatile dura becomes apparent. If the tumor extends intradurally, a previously placed lumbar subarachnoid drain is opened. This relieves the turgidity of the ventral dura and allows intradural exposure. A cruciate incision is made in the dura caudal to the foramen magnum and extended cephalad (Fig. 62-18).

Figure 62-17. Exposure of basisphenoid (*) after removal of part of the hard palate and posterior nasal septum. Sutures are retracting soft-palate and hard-palate mucoperiosteum. The tongue is retracted by the blade of a Dingman retractor (T).

Figure 62-18. Exposure of basilar artery (B) following removal of intradural extension of clivus chordoma through transoral-transpalatal approach. Dural margin (arrow).

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Hemostatic clips and bipolar electrocautery control bleeding from the marginal sinuses. Meticulous attention to detail must be maintained during closure to prevent CSF leak and meningitis. Dural closure is accomplished with 4–0 polyglactin sutures. The ideal closure is accomplished by placing fascia (rectus abdominis) and fat adjacent to the dural incision. The longus colli muscles, pharyngeal musculature, and mucosa are approximated in layers with interrupted 3–0 polyglactin sutures. A long nasal speculum is introduced through each nostril to approximate the mucoperiosteum of the nasal septum, and both sides of the nose are packed with half-inch iodoform gauze impregnated with bacitracin ointment. The mucoperiosteal flaps of the hard palate are closed with horizontal mattress stitches and it is tacked to the nasal septum flaps in the midline. The soft palate is closed in three layers (nasal mucosa, muscle, and oral mucosa). Intravenous antibiotics (cefotaxime, Flagyl, and methicillin) are continued for 7 to 10 days. Oral feeding is prohibited for 4 to 5 days and the tracheostomy tube is corked on postoperative day 5 to 7 and then removed as tolerated.

Figure 62-20. Lateral view of a high clivus lesion (see Fig. 62-19) with minimal compression of the pons (arrows).

TRANSPALATAL Isolated high midline lesions located in the posterior sphenoid sinus wall and basiocciput (Figs. 62-19 and 62-20) can be approached through a horseshoe-shaped incision of the hard palate (Fig. 62-21). Exposure is obtained through the transpalatal approach, as shown in Figure 62-22. The bony septum is removed as described for the transpalatal-transoral approach (Fig. 62-23). A Hardy speculum can be introduced transpalatal to gain sufficient exposure of the basiocciput (Fig. 62-24). We have used this approach in children because it does not interfere with the cartilaginous growth centers of the septum. The advantage of transoraltranspalatal approaches is the elimination of facial incisions while providing sufficient access.

LE FORT I OSTEOTOMY

Figure 62-21. U-shaped palatal flap for transpalatal approach for upper clivus lesions. The hard palate was removed with rongeur (P). Nasal mucosa (N) and periosteum of the nasal septum (arrow) are elevated laterally to allow removal of the posterior nasal septum.

Tumors that extend laterally to the occipital condyles and anterior into the pterygoid fossa behind the maxillary sinus

Figure 62-19. Axial MRI and gadolinium of a midline clivus chordoma posterior to the sphenoid sinus.

Figure 62-22. Exposure of high clivus through the transpalatal approach. The hatched lines show the extent of hard palate removal.

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Figure 62-23. Transpalatal exposure prior to removal of the posterior nasal septum (S). Posteriorly based palatal flap (P), nasal palatal mucosa (N), mouth guard protecting teeth (G).

are approached through a Le Fort I osteotomy (Fig. 62-25). The inferior limit of this route is approximately C1 since the hard palate is depressed in a caudal direction. Excellent access of the entire clivus with lateral extension to the ramus of the mandible on both sides can be achieved. A tracheotomy is essential to achieve maximal depression of the palate. A sublabial incision from one maxillary tuberosity to the other is created. A mucoperiosteal flap is elevated to expose the piriform aperture centrally and the infraorbital nerves laterally. Mucoperiosteal tunnels are elevated in the floor of the nose and nasal septum bilaterally to keep the nasal mucosa intact. A nasal chisel is then used to separate the nasal septum from the maxillary crest of the palate. The Le Fort I osteotomy incisions are marked on the maxilla from the lateroinferior piriform aperture to each maxillary tuberosity above the roots of the teeth (Fig. 62-26). Miniplates are placed at the medial and lateral buttresses and removed prior to creating the osteotomy with an oscillating saw (Fig. 62-27). The palate is down-fractured using Roe disimpaction forceps placed in each piriform aperture, exposing the maxillary sinuses and pterygoid plates (Fig. 62-28). The bony septum can be removed to expose the anterior wall of the sphenoid sinus. The tongue blade of the Dingman mouth gag is used to maintain downward retraction of the palate, providing a wide access to the clivus (Fig. 62-29). The blood supply to

Figure 62-24. Hardy speculum introduced through transpalatal exposure for lateral retraction of nasal mucoperiosteum flaps to expose the basiocciput.

Figure 62-25. Axial high-resolution CT scan of a large clivus chordoma that extends laterally to the pterygoid plates bilaterally. Le Fort I osteotomy approach provides the exposure necessary for total removal.

the upper maxilla is abundant; however, when possible, the maxilla is left adherent on the side contralateral to the main tumor mass.163,165 Closure involves reattachment of the lower maxilla with the previously placed miniplates followed by nasal packing to stabilize the nasal mucosa and septum. Morbidity from this approach is very low. Numbness of the maxillary teeth is a disadvantage. Occlusal

Figure 62-26. Midface degloving for Le Fort I osteotomy approach. The pyriform aperture is exposed (thin arrows). Mark for osteotomy (thick arrow).

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Figure 62-27. Placement of miniplates before completing osteotomy.

Figure 62-29. Dingman mouth gag depressing palate for exposure.

problems are rare, cosmesis is excellent, and the patients experience little postoperative discomfort. Oral intake of liquids can begin on the first postoperative day and patients can advance to a soft diet over a few days. The nasal packs are maintained for 7 to 10 days. The tracheotomy tube can be corked after 3 to 5 days and removed when the patient is ready. A disadvantage of all midline approaches is the relative inability to recruit vascularized muscle flaps (i.e., temporalis, sternocleidomastoid, and trapezius) to assist in closure of the surgical defect. This is critical in an individual who has previously undergone surgical excision and received radiation therapy to the region.

clivus that extend below the foramen magnum are removed through a transcervical retropharyngeal route. This approach involves dissection of the neck, with control of the great vessels and exposure of the retropharyngeal region. Extensive exposure from the mid-clivus to the lower cervical spine can be achieved. An added benefit of the transcervical route is that it can be accomplished without oral cavity contamination in the operative field. Both of these approaches allow rotation of vascularized muscle flaps during closure.

TUMORS OF THE CLIVUS: LATERAL APPROACHES Lateral approaches to the midline skull base are useful for masses that are predominantly to one side and do not extend beyond the contralateral hypoglossal canal and occipital condyle. Lesions involving the upper clivus and extending laterally along the petrous apex and the greater wing of the sphenoid and that obstruct the eustachian tube are best approached by a type B lateral infratemporal approach popularized by Fisch.167 Lateral tumors of the

Figure 62-28. Roe forceps placed in each pyriform aperture to disimpact the palate following osteotomies.

INFRATEMPORAL FOSSA, TYPE B APPROACH Tumors that extend laterally from the upper clivus and encroach on the petrous portion of the internal carotid artery and eustachian tube require additional exposure for adequate control of potential hemorrhage. In these cases, exposure of the petrous internal carotid artery destroys eustachian tube function. In our experience, sacrifice of the middle ear and conductive hearing reduces postoperative chronic otitis media and other complications, especially if radiation therapy is a consideration. An anterior extension of this approach (type C infratemporal fossa approach) is used for tumors of the cavernous sinus and parasellar region when the internal carotid artery and petrous apex are involved. We have combined types B and C exposures with a retrosigmoid craniotomy for removal of large petroclival meningiomas (Fig. 62-30). The type B infratemporal fossa approach does not involve anteriorly rerouting of the facial nerve since exposure of the jugular foramen is not necessary in most tumors of the clivus. The upper limb of the C-shaped skin incision is carried more anteriorly to the level of the lateral orbital rim (Fig. 62-31). The skin flap is elevated at the level of the temporalis fascia. Care must be taken to identify the temporal and zygomatic branches of the facial nerve with a nerve stimulator. They are found on the temporalis fascia as they pass over the anterior one half of the zygomatic arch. Preservation of these nerves is ensured by including the temporalis fascia with the skin flap at the anterior half of the zygoma. The skin and fascia are elevated superiorly to identify the lateral orbital rim and

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Figure 62-32. Infratemporal fossa type B exposure. Zygomatic arch removed and retracted inferiorly. The arrow points to the anterior zygoma. A laminectomy retractor is displacing the condyle (C) and ramus of mandible anteriorly. The temporalis muscle (T) is retracted anteriorly.

Figure 62-30. MRI with gadolinium of a large petroclival meningioma requiring combination of infratemporal fossa approaches type B and C with the addition of a retrosigmoid craniotomy.

zygoma. The ear canal skin is circumferentially elevated 2 to 3 mm medial to the bony-cartilaginous junction and transected. The external canal skin is everted and closed with 3–0 polyglactin sutures. A second layer of mastoid cortex pericranium is sutured over the closed canal to prevent CSF leakage.168 Inferiorly, the incision is carried into a neck crease if control of the great vessels in the neck is necessary. After plating, the zygomatic arch is transected at its anterior and posterior roots and reflected inferiorly attached to the masseter fascia. The temporal muscle is freed of its attachments in the temporal fossa and also elevated inferiorly. A Scoville laminectomy retractor is used to depress the mandibular condyle, allowing access to the middle cranial fossa skull base (Fig. 62-32). Infrequently the condyle is resected. The external auditory canal wall skin, tympanic membrane, malleus, and incus are removed. Care must be taken to remove all skin to prevent the formation of a cholesteatoma. A large diamond

Figure 62-31. Incision for infratemporal approach type B or C (black arrows). Lateral orbital wall (white triangle), anterior extent of incision (white arrow).

burr and high-speed drill are used to identify the internal carotid artery at the medial wall of the eustachian tube. Bone removal continues anteriorly, exposing the petrous carotid artery, foramen spinosum, and foramen ovale of the greater wing of the sphenoid. The middle meningeal artery is cauterized with bipolar electrocautery and transected. The mandibular division of the trigeminal nerve is also transected. The carotid is exposed anteriorly to the foramen lacerum (Fig. 62-33). Inferior and anterior the nasopharynx can be entered to expose the sphenoid sinus, basisphenoid, and basiocciput for tumor removal. A middle fossa and retrosigmoid craniotomy provides the additional exposure sometimes necessary with petroclival meningioma (Fig. 62-34). Closure involves creating anchor holes in the remaining bone of the clivus to secure the rotated temporalis muscle flap (Fig. 62-35). Abdominal fat is harvested to fill the remaining defect. The zygomatic arch is plated in place to ensure cosmesis. Suction drains may be placed if there is no intradural extension, and the skin incision is closed in layers.

Figure 62-33. Infratemporal fossa type B exposure with retrosigmoid craniotomy. PF indicates the posterior fossa dura. The external ear canal and middle ear are removed to expose the internal carotid artery in the petrous apex (star). The fallopian canal and facial nerve have been preserved in normal position (black arrow). Cephalad (C), anterior (A).

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TRANSCERVICAL-RETROPHARYNGEAL

Figure 62-34. Infratemporal fossa types B and C with addition of middle fossa (MF) craniotomy and retrosigmoid craniotomy. (S indicates the sigmoid sinus.) The mandible and condyle (C) are retracted anterior. The fallopian canal (F), facial nerve, and inner ear are preserved.

This approach allows exposure to the entire infratemporal fossa, pterygo-maxillary space, and clivus to the level of the contralateral hypoglossal canal and eustachian tube. The disadvantages of the infratemporal fossa approach include a conductive hearing loss and anesthesia of the mandibular division of the trigeminal nerve.

The transcervical-retropharyngeal approach was originally described by Stevenson.169 Several authors have added a mandibular splitting procedure for added exposure.170,171 In our experience, the additional exposure was not needed and contributed oral cavity contamination. This approach provides anterolateral access to the lower clivus, craniovertebral junction, and cervical spine. Figures 62-36 and 62-37 demonstrate a large chordoma involving the lower clivus to the craniovertebral junction C3 with lateral extension (Fig. 62-36). A transcervical-retropharyngeal approach was used to expose this tumor. Anesthesia is delivered through a nasotracheal tube or tracheotomy, depending on the size and location of the tumor. The oral cavity is kept free of tubes to allow displacement of the mandible. A preauricular skin incision, similar to a modified Blair incision used for a parotidectomy, is carried into a neck crease at mid-thyroid level (Fig. 62-38). The main trunk of the facial nerve and inferior division are identified. The neck is dissected, isolating the internal carotid artery and ligating branches of the external carotid as necessary. The posterior belly of the digastric muscle is transected along with the styloid process and muscles at the skull base. Cranial nerves VII, IX, X, XI, and XII are now visible (Fig. 62-39). The aerodigestive tract and carotid artery are retracted anteriorly, allowing access to the retropharyngeal space (Fig. 62-40). The prevertebral fascia is incised in a vertical fashion to expose the longus colli muscles. These are detached from their medial origin to expose the anterior arch of the atlas. Care must be taken to prevent injury to the hypoglossal nerve as it exits the hypoglossal canal. The osseous ligamentous structures are swept away to visualize the caudal clivus and the upper cervical vertebrae. A high-speed drill and diamond burr are used to remove bone to expose the tumor. If extensive bone removal of the foramen magnum and occipital condyle is necessary and the spine is unstable, a cervical fusion procedure must be planned.

A

B Figure 62-35. A, B, To ensure closure of any dural defect, the nasopharynx is isolated, and to eliminate dead space, a temporalis muscle flap (T in Fig. 62-35A) is rotated into the infratemporal pterygoid fossa (T in Fig. 62-35B). Anchor holes are drilled in the clivus to suture muscle deep in the wound.

Figure 62-36. Coronal MRI view of a clivus chordoma (stars) with inferior and lateral extension. Lateral displacement of the carotid artery (arrow). Transcervical-retropharyngeal exposure is indicated.

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Figure 62-40. Transcervical retropharyngeal approach. A retractor is elevating the carotid artery and pharynx to expose the retropharyngeal space and prevertebral muscles. Tumor exposure (arrow). Figure 62-37. Lateral MRI view of a clivus chordoma (arrows) in the same patient as shown in Figure 62-36. The tumor extends from mid-clivus to inferior C2.

In these instances skeletal traction and a secondary posterior fusion is performed. Opening the neck provides a number of options for rotational muscle flap coverage of the deep wound. A superiorly based sternocleidomastoid muscle or trapezius muscle flap are easily available. Anchoring sutures to the contralateral bone margins helps to maintain the muscle flap in position. If the nasopharynx has been entered, a muscle flap is essential to prevent contamination from oral cavity secretions.

PARASELLAR TUMORS

Figure 62-38. Preauricular incision similar to a modified Blair incision for a parotidectomy is used to expose the transcervical-retropharyngeal route. The inferior limb of the incision is carried anterior to the level of thyroid cartilage (arrow). Sternocleidomastoid muscle (SCM), external ear canal (triangle).

The parasellar region can be exposed using a superior frontal-temporal osteotomy,39,40,172,173 lateral facial,174,175 craniofacial disassembly,176–179 and lateral infratemporal type C approaches.167 We use the frontal-temporal/lateral facial route for parasellar exposure if the petrous carotid artery and eustachian tube are not involved with the disease process. The frontal-temporal osteotomy involves a larger middle cranial fossa craniotomy and is useful for petroclival meningiomas that involve the tentorium. A retrosigmoid approach is added in these cases. The lateral facial exposure provides adequate exposure of cavernous sinus neuromas and small intracavernous lesions. The lateral infratemporal fossa type C is used if eustachian tube function is compromised preoperatively and the petrous carotid artery must be controlled.

FRONTAL-TEMPORAL/LATERAL FACIAL APPROACH

Figure 62-39. Transcervical-retropharyngeal exposure of cranial nerves VII (arrow), X, XI, XII. Posterior belly of the digastric muscle, styloid process, and stylohyoid muscles have been detached and reflected inferiorly. The anterior blade of the retractor on an angle of the mandible. IC, internal carotid artery.

A lateral preauricular approach provides wide access to the cavernous sinus, greater wing of the sphenoid, and supraorbital fissure (Fig. 62-41). The petrous internal carotid artery can also be exposed through this route; however, when eustachian tube function must be sacrificed, the infratemporal fossa type C approach is used. The skin is incised in the preauricular crease, extending cephalad and curving anteriorly at the superior margin of the temporal fossa to the level of the lateral orbital rim (Fig. 62-42).

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A

B

Figure 62-42. Incision for a preauricular frontal-temporal/lateral-facial approach. The anterior extent of the incision (arrow) is at the level of the lateral orbital rim. The anterior superior limb of the incision can be carried to midline if a tumor involves the lesser wing of sphenoid and orbit for frontal craniotomy.

is through the middle cranial fossa floor (squamosa of temporal bone and greater wing of sphenoid); therefore, minimal elevation of the temporal lobe is required for exposure. If the tumor extends into the orbital apex from the cavernous sinus, a portion of the superior orbital rim, lateral orbital rim, and zygomatic arch can be removed en bloc. Before the osteotomies, miniplates are placed and removed, similarly to a Le Fort I procedure. A frontallateral craniotomy exposes the roof of the orbit and lesser wing of the sphenoid for medial osteotomies with a rotating diamond burr (Fig. 62-44). The bone segment is removed along with greater the sphenoid wing to expose the orbital apex and cavernous sinus (Fig. 62-45). A temporalis muscle flap is sutured medially to close the dura (Fig. 62-46). The bone segment is plated in place prior to closure (Fig. 62-47). A high-speed drill and diamond burr are used to remove the greater wing of the sphenoid.

Figure 62-41. A, Coronal view of MRI with gadolinium of clivus chordoma cavernous sinus (large arrows). The internal carotid artery has been displaced inferior and lateral (small arrow). B, Axial view of the same tumor, showing the displaced internal carotid artery (small arrow). The petrous carotid artery and eustachian tube are not involved. A preauricular frontal temporal/lateral facial approach is indicated.

If the tumor involves the lesser wing of the sphenoid and orbital apex, the anterior superior limb is carried to the midline. The skin flap is elevated at the level of the temporalis fascia posteriorly, but it includes the temporalis fascia at the mid-portion of the zygoma to prevent injury to the temporal and zygomatic branches of the facial nerve. The zygomatic arch is divided and temporalis muscle is elevated and retracted inferiorly, similarly to the infratemporal fossa type B approach described previously. A Scoville laminectomy self-retaining retractor is used to depress the mandibular condyle and facilitates exposure of the skull base (Fig. 62-43). The size of the middle fossa craniotomy is dictated by the position and size of the neoplasm. An advantage of this approach is that the access

Figure 62-43. Preauricular frontal-temporal/lateral-facial exposure. A laminectomy retractor is depressing the temporal mandibular joint (thick arrow). The greater wing of sphenoid and the inferior portion of squamosa of temporal bone (smaller arrows) are retracted to expose infratemporal fossa and cavernous sinus. The temporalis muscle is retracted anterior (TM). The zygomatic arch has been retracted inferiorly and attached to the masseter muscle.

Management of Clivus and Parasellar Space Neoplasms

Figure 62-44. En bloc removal of zygomatic arch (Z). The lateral orbital rim and part of the superior orbital rim (O) are visible. Frontal lobe dura exposed (F). Temporalis muscle (T) cuts are made at the posterior root of zygoma (open arrow). Body of zygoma (closed arrow), superior orbital rim (O), and roof and wing of sphenoid are retracted to free the segment.

A

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Figure 62-46. Temporalis muscle sutured medial to close sphenoid sinus, cavernous sinus, and orbital apex (O). Temporalis muscle flap (T), frontal lobe dura (F).

The middle meningeal artery and mandibular division of the trigeminal nerve are divided, exposing the lateral wall of the cavernous sinus. The lateral wall of the sinus is composed of two layers of dura with cranial nerves III, IV, V1, and V2 passing between the layers. Cranial nerve VI and the internal carotid artery are within the sinus.180 If the dissection is caudal and lateral to V1, the remainder of the cranial nerves can be spared, preventing ophthalmoplegia. Electrical stimulation with observation of the orbit is helpful in identifying the motor nerves. Bleeding in the sinus is controlled with Oxycel/Surgicel cellulose (Ethicon) and gentle pressure. This exposure has been sufficient to perform an internal carotid artery saphenous vein graft.39 If the internal carotid artery is involved with the tumor, preoperative balloon test occlusion and possible permanent balloon occlusion proximal to the ophthalmic artery is performed 4 to 6 weeks before the procedure. A vascularized temporalis muscle flap is rotated deep into the wound, isolating the intracranial contents from the infratemporal fossa during closure (see Fig. 62-46). The zygomatic arch is fixed into position anteriorly. If a large dural defect has been created, a previously placed

B Figure 62-45. A, Zygomatic block has been removed, exposing infratemporal fossa (IT) and orbital contents (O). The temporalis muscle (T) is reflected inferior. Zygomatic root (Z), condyle (arrow). B, Exposure of the cavernous sinus that contains the meningioma (C). The greater wing of sphenoid has been removed, exposing mandibular division of trigeminal nerve (V3), second division of trigeminal nerve (V2). Orbit (O).

Figure 62-47. Zygomatic complex (Z) plated (arrows) into position prior to closure. The temporalis muscle flap is visible (T). The craniotomy bone flap has been replaced (C).

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lumbar drain is maintained, and passive Penrose drains are placed deep in the wound.

INFRATEMPORAL FOSSA, TYPE C APPROACH Tumors that involve the cavernous sinus and petrous bone are exposed by extending the infratemporal fossa type B exposure (previously described) anteriorly. An advantage of this approach is the exposure of the internal carotid artery from the carotid bulb in the neck to the anterior margin of the cavernous sinus. Removing the internal carotid artery from the confines of the carotid canal of the temporal bone enables the surgeon to rotate the artery laterally and inferiorly, providing additional exposure.

SUMMARY Midline skull base neoplasms are not confined to specific anatomic regions. Frequently, a combination of the procedures described here must be devised. A skull base team consisting of neurotologic, neurosurgical, and head and neck reconstructive surgeons, along with interventional radiologists, is essential for the management of neoplasms of the clivus and parasellar regions. A meeting of the entire team is convened prior to making final management decisions. The team must be flexible and willing to combine a number of approaches to provide the best possible exposure with the least amount of additional morbidity. The procedures and indications described here are frequently modified to meet the needs of the individual patient. Many institutions are employing multidisciplinary team approaches for surgical planning (interventional radiology, neurotology, neurosurgery), to assess the need for and timing of radiation,181 and to coordinate other treatments or services (e.g., ophthalmology, audiology, speech pathology, rehabilitation therapy) deemed necessary for their patients with clival and parasellar neoplasms. These tumors continue to be of great interest to physicians in many different fields. Ongoing research into the genetic makeup and biological behavior of these lesions as well as progress in the various surgical approaches and radiation therapies will lead to less mortality and improved quality of life for patients with clival and parasellar neoplasms.

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91. Kasantikul V, Netsky MG: Combined neurilemmoma and angioma. J Neurosurg 50:81–87, 1979. 92. Fazi S, Barthelemy M: Petroclival meningioma mimicking the presentation of a transient ischemic attack. Acta Neurol Scand 89:75–76, 1994. 93. Grand W, Bakay L: Posterior fossa meningiomas. Acta Neurochir 32:219–233, 1975. 94. Bradac GB, et al: Cavernous sinus meningiomas: An MRI study. Neuroradiology 29:578–581, 1987. 95. Hannerz J: A case of parasellar meningioma mimicking cluster headache. Cephalgia 9:265–269, 1987. 96. Trobe JD, Glaser JS, Post JD: Meningiomas and aneurysms of the cavernous sinus. Arch Ophthalmol 96:457–467, 1978. 97. Servo A, Jaeaeskinen J: The superior ophthalmic vein and tumours of the sella area. Acta Neurochir 68:195–202, 1983. 98. Olivecrona H: Meningiomas of the clivus. In Olivecrona H, Toennis W (eds.): Handbook of Neurosurgery. Berlin, SpringerVerlag, 1967, pp 185–187. 99. Sekhar LN, et al: Reconstruction of the third through sixth cranial nerves during cavernous sinus surgery. J Neurosurg 76:935–943, 1992. 100. Subach BR, et al: Management of petroclival meningiomas by stereotactic radiosurgery. Neurosurgery 42:437–445, 1998. 101. Goebel HH, et al: Schwannoma of the sellar region. Acta Neurochir 48:191–197, 1979. 102. Kasantikul V, Brown WJ, Netsky MG: Mesenchymal differentiation in trigeminal neurilemmoma. Cancer 50:1568–1571, 1982. 103. Levinthal R, Bentson JR: Detection of small trigeminal neuromas. J Neurosurg 45:568–575, 1976. 104. Schubiger O, et al: Neuroma of the cavernous sinus. Surg Neurol 13:313–316, 1980. 105. Bartlett JR: Craniopharyngiomas: A summary of 85 cases. J Neurol Neurosurg Psychiat 34:37–41, 1971. 106. Hoff JT, Patterson RH: Craniopharyngiomas in children and adults. J Neurosurg 36:299–302, 1972. 107. Hoffman HJ, et al: Management of craniopharyngioma in children. J Neurosurg 47:218–227, 1977. 108. Moore KL: The nervous system. In Moore KL (ed.): The Developing Human. Philadelphia, WB Saunders, 1988, pp 364–401. 109. Sung DI, et al: Treatment results of craniopharyngiomas. Cancer 47:847–852, 1981. 110. Kahn EA, et al: Forty-five years’ experience with the craniopharyngiomas. Surg Neurol 1:5–12, 1973. 111. Matson DD, Crigler JF Jr: Management of craniopharyngioma in childhood. J Neurosurg 30:377–390, 1969. 112. Mokrush T, Schramm J, Fahlbusch R: Repeatedly reversible alteration of acoustic-evoked brainstem responses with a cystic craniopharyngioma. Surg Neurol 24:571–577, 1985. 113. Ammirati M, Samii M, Sephernia A: Surgery of large retrochiasmatic craniopharyngiomas in children. Child’s Nerv Syst 6:13–17, 1990. 114. Berenstein A, Kricheff II: Catheter and material selection for transarterial embolization. Radiology 132:619–630, 1979. 115. Amacher AL: Craniopharyngioma: The controversy regarding radiotherapy. Child’s Brain 6:57–64, 1980. 116. Katz EL: Late results of radical excision of craniopharyngiomas in children. J Neurosurg 42:86–90, 1975. 117. Debus J, Wuendrich M, et al: High efficacy of fractionated stereotactic radiotherapy of large base-of-skull meningiomas: Long-term results. J Clin Oncol 19:3547–3553, 2001. 118. Ho SY, Kveton JF: Rapid growth of acoustic neuromas after stereotactic radiotherapy in type 2 neurofibromatosis. ENT J 81:831–833, 2002. 119. Bari ME, et al: Malignancy in a vestibular schwannoma: Report of a case with central neurofibromatosis, treated by both stereotactic radiosurgery and surgical excision, with a review of the literature. Br J Neurosurg 16:284–289, 2002. 120. Hanabusa K, et al: Acoustic neuroma with malignant transformation: Case report. J Neurosurg 95:518–521, 2001.

121. Shin M, et al: Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. Lancet 360:309–310, 2002. 122. Lustig LR, Jackler RK, Lanser MJ: Radiation-induced tumors of the temporal bone. Am J Otol 18:230–235, 1997. 123. Debus J, Hug EB, et al: Brainstem tolerance to conformal radiotherapy of skull base tumors. Int J Radiat Oncol Biol Phys 39:967–975, 1997. 124. Flickinger JC, Kondziolka D, Lundsford LD: Dose and diameter relationships for facial, trigeminal, and acoustic neuropathies following acoustic neuroma radiosurgery. Radiother Oncol 41: 215–219, 1996. 125. Santoni R, et al: Temporal lobe (TL) damage following surgery and high-dose photon and proton irradiation in 96 patients affected by chordomas and chondrosarcomas of the base of the skull. Int J Radiat Oncol Biol Phys 41:59–68, 1998. 126. Suit HD, et al: Definitive radiation therapy for chordoma and chondrosarcoma of base of skull and cervical spine. J Neurosurg 56:377–385, 1982. 127. Slater JD, Austin-Seymour M, et al: Endocrine function following high dose proton therapy for tumors of the upper clivus. Int J Radiation Oncology Biol Phys 15:607–611, 1988. 128. Kumar PP, et al: Local control of recurrent clival and sacral chordoma after interstitial irradiation with iodine-125. Neurosurgery 22:479–483, 1988. 130. Petty AM, Kun LE, Meyer GA: Radiation therapy for incompletely resected meningiomas. J Neurosurg 62:502–507, 1985. 131. Iwai Y, Yamanaka K, Nakajima H: Two-staged gamma knife radiosurgery for the treatment of large petroclival and cavernous sinus meningiomas. Surg Neurol 56:308–314, 2001. 132. Nicolato A, Foroni R, Pellegrino M, et al: Gamma knife radiosurgery in meningiomas of the posterior fossa. Experience with 62 treated lesions. Minim Invasive Neurosurg 44:211–217, 2001. 133. Nicolato A, Foroni R, Alessandrini F, et al: Radiosurgical treatment of cavernous sinus meningiomas: Experience with 122 treated patients. Neurosurg 51:1153–1159, 2002. 134. Calvo FA, et al: Radiation therapy in craniopharyngiomas. Int J Radiat Oncol Biol Phys 9:493–496, 1983. 135. Hoogenhout J, et al: Surgery and radiation therapy in the management of craniopharyngiomas. J Radiat Oncol Biol Phys 10: 2293–2297, 1984. 136. Lichter AS, et al: The treatment of craniopharyngiomas. Int J Radiat Oncol Biol Phys 2:675–683, 1977. 137. Thompson IL, et al: Craniopharyngioma: The role of radiation therapy. Int J Radiat Oncol Biol Phys 4:1059–1063, 1978. 138. Harris JR, Levene MB: Visual complications following irradiation for pituitary adenomas and craniopharyngiomas. Radiology 120:167–171, 1976. 139. Thomsett MJ, et al: Endocrine and neurologic outcome in childhood craniopharyngioma. J Pediatr 97:728–735, 1980. 140. Waga S, Honda H: Radiation-induced meningioma. Surg Neurol 5:215–219, 1976. 141. Berenstein A, Russell E: Gelatin sponge in therapeutic neuroradiology. Radiology 141:105–112, 1981. 142. Berenstein A, Graeb DA: Convenient preparation of ready-to-use particles in polyvinyl alcohol foam suspension for embolization. Radiology 145:846, 1982. 143. Berenstein A, Kricheff II: Catheter and material selection for transarterial embolization: Technical considerations. Radiology 132:631–639, 1979. 144. Debrun G, et al: Experimental approach to the treatment of carotid cavernous fistulas with an inflatable and isolated balloon. Neuroradiology 9:9–12, 1975. 145. Kerber C: Balloon catheter with a calibrated leak. Radiology 120:547–550, 1976. 146. Pevsner PH: Micro-balloon catheter for superselective angiography and therapeutic occlusion. Am J Roentgenol 128:225–230, 1977. 147. Serbinenko FA: Balloon catheterization and occlusion of major cerebral vessels. J Neurosurg 41:125–145, 1974.

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148. Jungreis CA: Skull-base tumors: Ethanol embolization of the cavernous carotid artery. Radiology 181:741–743, 1991. 149. Beahm EK, Becker SP, Cerullo LJ: The transnasal approach to advanced lesions of the sphenoid sinus and pituitary. Otolaryngol Clin North Am 24:1535–1557, 1991. 150. Laws ER, Jr: Transsphenoidal surgery for tumors of the clivus. Otolaryngol Head Neck Surg 92:100–101, 1984. 151. Papel ID, Kennedy DW, Cohn E: Sublabial transseptal transsphenoidal approach to the skull base. ENT J 65:20–33, 1986. 152. Sofferman RA: The septal translocation procedure. Otolaryngol Head Neck Surg 98:18–25, 1988. 153. Crumley RL, Gutin PH: Surgical access for clivus chordoma. Arch Otolaryngol Head Neck Surg 115:295–230, 1989. 154. Derome PJ: Surgical management of tumours invading the skull base. Can J Neurol Sci 12:345–347, 1985. 155. Kennedy DW, Papel ID, Holliday M: Transpalatal approach to the skull base. ENT J 65:48–60, 1986. 156. Latchaw RE: Imaging of tumor at the base of skull. In Sekhar LN, Schramm VL Jr (eds.): Tumors of the cranial base. Mount Kisco, NY, Future Publishing, 1987. 157. Pásztor E, et al: Transoral surgery for craniocervical space-occupying processes. J Neurosurg 60:276–281, 1984. 158. Seifert V, Laszig R: Transoral transpalatal removal of a giant premesencephalic clivus chordoma. Acta Neurochir (Wein) 112: 141–146, 1991. 159. Cocke EW, Jr, et al: The extended maxillary and subtotal maxillectomy for excision of skull base tumors. Arch Otolaryngol Head Neck Surg 116:92–104, 1990. 160. Miller RH, Woodson GE, Murphy EC: A surgical approach to chordomas at the base of the skull. Otolaryngol Head Neck Surg 90:251–255, 1982. 161. Price JL: The midface degloving approach to the central skull base. ENT J 65:46–53, 1986. 162. Rabadan A, Conesa H: Transmaxillary-transnasal approach to the anterior clivus: A microsurgical anatomical model. Neurosurgery 30:473–482, 1992. 163. Archer DJ, Young S, Uttley D: Basilar aneurysm. J Neurosurg 67:54–58, 1987. 164. Maloney F, Worthington P: The origin of Le Fort I maxillary osteotomy: Cheever’s operation. J Oral Surg 39:731–734, 1981.

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165. Sasaki CT, et al: Le Fort I osteotomy approach to the skull base. Laryngoscope 100:1073–1076, 1990. 166. Menezes AH: Transoral approach to the clivus and upper cervical spine. In Wilkins RH and Rengachary SS (eds.): Neurosurgery Update. New York, McGraw-Hill, 1990, pp 306–313. 167. Fisch U, Pillsbury HC: Infratemporal fossa approach to lesions of the temporal bone and skull. Arch Otolaryngol 105:99–107, 1979. 168. Gantz BJ, Frisch U: Modified transotic approach to the cerebellopontine angle. 109:252–256, 1983. 169. Stevenson GC, et al: A transcervical transclival approach to the ventral surface of the brainstem for removal of a clivus chordoma. J Neurosurg 24:544–551, 1966. 170. Biller HF, Lawson W: Anterior mandibular-splitting approach to the skull base. ENT J 65:61–70, 1986. 171. Krespi YP, Sisson GA: Transmandibular exposure of the skull base. Am J Surg 148:534–538, 1984. 172. Kawase T, Shiobara R, Toya S: Anterior transpetrosal-transtentorial approach for sphenopetroclival meningioma. Neurosurg 28: 869–876, 1991. 173. Yasargil MG, Mortara RW, Curcic M: Meningiomas of basal posterior cranial fossa. In Krayenbuehl H, Brihaye J, Loew F, et al (eds.): Advances and Technical Standards in Neurosurgery, Wein. New York, Springer-Verlag, 1980, 7:4–115. 174. Gates GA: The lateral facial approach to the nasopharynx and infratemporal fossa. Otolaryngol Head Neck Surg 99:321–325, 1988. 175. Holliday MJ: Lateral transtemporal-sphenoid approach to the skull base. ENT J 65:9–26, 1986. 176. Arriaga MA, Janecka IP: Facial translocation approach to the cranial base: The anatomic basis. Skull Base Surg 1:26–33, 1991. 177. Jackson IT, et al: Craniofacial osteotomies to facilitate skull base tumour resection. Br J Plast Surg 39:153–60, 1986. 178. Janecka IP, et al: Facial translocation: A new approach to the cranial base. Otolaryngol Head Neck Surg 103:413–419, 1990. 179. Johns ME, Kaplan MJ: Surgical approach to the anterior skull base. ENT J 65:34–47, 1986. 180. Umansky F, Nathan H: The lateral wall of the cavernous sinus. J Neurosurg 56:228–234, 1982. 181. Zentner J, et al: Petroclival meningiomas: Is radical resection always the best option? J Neurol Neurosurg Psych 62:341–345, 1997.

Chapter

63 John H. Greinwald, Jr, MD Kevin E. Kelly, MD Thomas A. Tami, MD

H

Temporal Bone and Skull Base Trauma Outline Anatomy, Histology, and Classification Longitudinal Fractures Transverse Fractures Mixed and Oblique Fractures Otic Capsule–Sparing and Otic Capsule–Disrupting Fractures Penetrating and Blunt Trauma Temporal Bone Trauma Histology Pediatric Temporal Bone Trauma Clivus Fractures Patient Evaluation in Temporal Bone Trauma Temporal Bone Imaging Computed Tomography Magnetic Resonance Imaging

ead injury is a prevalent problem in our modern society as a result of frequent automobile travel, workplace hazards, and recreational hobbies that pose an everincreasing risk of severe injury and death from head trauma. The long-term economic and personal toll is particularly high since most victims of this disease are young adults entering what should be their most productive years. Although the risk of head trauma and concomitant temporal bone fractures has been reduced by automobile safety belts and air bags, motorcycle helmets, and industrial safety programs, such fractures nevertheless comprise approximately 14% to 22% of all skull fractures and occur in approximately 4% of patients with closed-head trauma.1–3 These fractures have a 3:1 male predominance, which can likely be attributed to higher-risk behavior patterns in males. Motor vehicle accidents account for approximately 50% of temporal bone fractures.4,5 Falls, bicycle accidents, firearms, and physical assaults are other causes. Although blunt trauma is involved in the vast majority of temporal bone fractures, penetrating trauma is increasing at an alarming rate. Because patients with temporal bone trauma frequently suffer from multiple organ trauma, their care is often complicated. A team approach is required to manage the associated multisystem injuries in these patients, but the otologist is best qualified to manage all aspects of the temporal bone trauma. Facial nerve injury, hearing loss, tinnitus, vertigo, and cerebrospinal fluid (CSF) leaks 1070

Complications of Temporal Bone Trauma Facial Nerve Injury Pathology of Traumatic Facial Nerve Paralysis Criteria for Surgical Intervention Immediate versus Delayed Paralysis Topographic Testing Electrical Testing Radiologic Imaging Surgical Management of Facial Nerve Paralysis Experimental Models Results of Surgical Management

Cerebrospinal Fluid Leakage and Meningitis Cholesteatoma Hearing Loss Natural History of Traumatic Hearing Loss Conductive Hearing Loss Incudostapedial Joint Separation Massive Dislocation of the Incus Fracture of the Stapes Fracture of the Malleus Epitympanic Fixation Ossicular Reconstruction Sensorineural Hearing Loss Vertigo

should all be carefully evaluated and treated by the otologist. Advances in temporal bone imaging, facial nerve management, intensive care therapy, and otologic reconstruction have all led to improvement in the care of patients with temporal bone trauma. This chapter presents a comprehensive review of the contemporary evaluation and management of these patients.

ANATOMY, HISTOLOGY, AND CLASSIFICATION Temporal bone trauma includes blunt trauma without fracture, blunt trauma with fracture, and penetrating trauma. Blunt trauma is responsible for more than 90% of temporal bone injuries. A large force is required to produce a temporal bone fracture. Using fresh cadaver skulls, Travis and colleagues6 estimated that 1875 pounds of laterally placed force is required to cause a longitudinal temporal bone fracture. If the force is not sufficient to cause such a fracture, significant concussive injury to the membranous labyrinth can cause hearing loss, vertigo, and tinnitus. Conductive hearing loss can occur from ossicular dislocation or tympanic membrane perforation. Facial nerve edema may cause a neuropraxia and temporary dysfunction. When the force is sufficient to fracture the temporal bone, the fractures tend to follow lines that connect points of weakness in the temporal bone. These locations include

Temporal Bone and Skull Base Trauma

the natural foramina and perforations of the temporal bone, such as the internal and external auditory canals, jugular and carotid canals, the middle ear, and the eustachian tube. Historically, temporal bone fractures were classified by the direction of the fracture to the long axis of the petrous pyramid, and they included longitudinal, transverse, mixed, and oblique.

Longitudinal Fractures Longitudinal fractures follow the long axis of the petrous bone (Fig. 63-1). Clinically, they are reported to be the most common, comprising 70% to 90% of temporal bone fractures.4,5 The mechanism of fracture starts with a blow to the lateral (temporoparietal) skull. The fracture line begins in the squamosal portion of the temporal bone and extends anteromedially to involve the superior aspect of the external auditory canal (EAC) and then passes into the middle ear. When it reaches the hard otic capsule bone, the fracture usually deflects anteriorly toward the foramen lacerum, eustachian tube, and/or foramen ovale. The fracture line may then terminate in the middle cranial fossa,

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extend to involve the sphenoid bone, or cross the midline and involve the contralateral petrous bone. Between 14% and 30% of longitudinal fractures are bilateral (Fig. 63-2).7,8 The classic triad of physical findings in longitudinal temporal bone fractures is bloody otorrhea, EAC bony step-off, and tympanic membrane disruption that is often associated with a conductive hearing loss. Other longitudinal fractures begin more posteriorly and course through the mastoid air cells. These patients exhibit a hemotympanum behind an intact tympanic membrane.

Transverse Fractures Transverse fractures cross the perpendicular axis of the petrous pyramid and reportedly comprise 10% to 30% of temporal bone fractures.4,5 Figure 63-3 demonstrates a typical transverse fracture with the fracture line coursing through the inner ear labyrinth. These fractures usually begin at the foramen magnum from a blow to the occiput. They traverse the otic capsule and because of the excessive force of the trauma, the otic capsule is violated. The fracture line may extend anteromedially to involve the internal

A

Figure 63-1. A, Diagrammatic representation of a longitudinal temporal bone fracture coursing parallel to the axis of the petrous bone. B, Axial CT demonstrating a longitudinal (otic capsule–sparing) temporal bone fracture. Note the ossicular discontinuity (arrow) and partial mastoid opacification due to blood (arrowheads).

B

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A

Figure 63-2. Bilateral longitudinal (otic capsule–sparing) temporal bone fracture.

auditory canal (IAC), cochlea, and geniculate ganglion or it may extend posterolaterally and violate the vestibule and cochlea, as well as the horizontal segment of the facial nerve. The middle ear, EAC, and tympanic membrane are usually lateral to the fracture site and are traditionally spared in this injury. Transverse fractures show fewer external signs (i.e., otorrhea) but are associated with a higher rate of facial nerve paralysis, vertigo, and sensorineural hearing loss (SNHL).

Mixed and Oblique Fractures Mixed temporal bone fractures have features of both longitudinal and transverse fractures. Because their anatomic features are mixed, so are the physical findings that accompany these fractures. Mixed fractures were initially reported as accounting for only a small percentage of temporal bone fractures; however, improved imaging techniques show a greater prevalence. Aguilar and colleagues9 reported that 68% of temporal bone fractures in their series were mixed. Travis and colleagues6 reported on temporal bone fractures made in fresh cadavers, which produced a 50% rate of mixed fractures. Dahiya and colleagues1 reported on 82 subjects with presumed temporal bone fractures and found that 62% of the fractures were reclassified from longitudinal to mixed. They found no true transverse fractures in their series. Ghorayeb and Yeakley7 retrospectively reviewed 150 temporal bone fractures and found transverse fractures in 12%, pure longitudinal fractures in 2.7%, mixed fractures in 9.3%, fractures involving only the petrous apex in 1.3%, but the majority of fractures (74.7%) were classified as oblique. They defined oblique fractures by the orientation of the external component of the fracture in a horizontal plane. Most of the fractures were at a 20- to 30-degree angle of the horizontal plane sloping upward from lateral to medial. This was in contrast to the classical longitudinal fracture with a vertically oriented fracture plane. Both longitudinal and oblique fractures had similar fracture patterns in their medial extension in the middle fossa.

B Figure 63-3. A, Diagrammatic representation of a transverse (otic capsule–disrupting) temporal bone fracture. B, Axial CT with the fracture line involving the vestibule (arrowheads).

Otic Capsule–Sparing and Otic Capsule–Disrupting Fractures Advances in high-resolution computed tomography (CT) scanning rendered the traditional classification system inadequate. New technology demonstrated that most fractures did not fit the classical fracture pattern description. Kelley and Tami10 thus describe temporal bone fractures as otic capsule–sparing or otic capsule–disrupting, based on whether the fracture line entered any part of the inner ear labyrinth (cochlea, vestibule, endolymphatic sac, or semicircular canals). Dahiya and colleagues1 reported on this classification system in 90 subjects with temporal bone fractures. They found only 5.6% of cases with otic capsule– disrupting fractures. Compared to otic capsule–sparing fractures, otic capsule–disrupting fractures had a twofold risk of facial nerve paralysis, a fourfold risk of CSF leak, a sevenfold increase in the likelihood for profound hearing loss, and nearly a twofold increase in intracranial complications such as epidural hematoma and subarachnoid hemorrhage. Since most decisions concerning surgical approaches for complications of temporal bone fractures are based on

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the status of hearing, they proposed that this classification system was simpler and more useful for both prognosis and treatment. In light of this, we use this classification of temporal bone fractures for the remainder of the chapter.

Penetrating and Blunt Trauma Published reports often include penetrating injury of the temporal bone together with blunt trauma. However, penetrating trauma differs significantly from blunt trauma in its mechanism of injury and the complications encountered. Its management must thus reflect these differences. Temporal bone–penetrating trauma is almost always associated with gunshot wounds. Knife injuries are exceedingly rare. Historically, experience from temporal bone–penetrating trauma has derived from military casualties.11 Hooper and colleagues12 described the first series of civilian gunshot injuries to the temporal bone in 1972. Several publications have discussed penetrating trauma to the temporal bone.1,13–15 Cannon and Jahrsdoerfer4 reported that 6% of temporal bone fractures in their series resulted from penetrating trauma. This increase has paralleled the overall increase in civilian gunshot injuries. When a bullet strikes the temporal bone, its kinetic energy is imparted and dissipated throughout the temporal bone and adjacent structures, causing damage to these structures. Because kinetic energy is proportional to the square of the bullet’s velocity, projectile velocity is the most important determinant of tissue destruction. Ninety percent of civilian gunshot injuries are from low-velocity projectiles (slower than 600 meters per second). Highvelocity projectiles (faster than 1200 meters per second), fired from hunting rifles and military assault rifles, have a much greater destructive potential. Figure 63-4 illustrates severe temporal bone trauma from a high-velocity projectile. Fractures from gunshots are almost always of the mixed type because of the variability in projectile type, entry, and path of fragmentation. Destruction from penetrating injuries tends to be more severe than that from blunt injury. Duncan and colleagues16

Figure 63-4. High-velocity projectile injury of the temporal bone. Massive destruction of the temporal bone has occurred.

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reviewed 22 temporal bone gunshot injuries over 10 years. They found that 36% of patients had significant central nervous system (CNS) injury. Emergency craniotomy was necessary in 23% of all patients; significant vascular injury, including injury to the internal carotid artery, internal jugular vein, sigmoid sinus, and carotid-cavernous fistula occurred in 32% of patients. The facial nerve was injured in 50% of cases. Immediate onset of paralysis was present in each instance with one exception of a delayed-onset paralysis. Injury to the middle or inner ear was present in 86% of patients and one-third of patients presented with anacusis. In sum, penetrating injury differs significantly from blunt trauma in its mechanism and pattern of injury. In particular, there is a major risk of intracranial and vascular injury from penetrating temporal bone trauma. Additionally, the incidence of otologic and facial nerve injury is higher in penetrating trauma than in blunt trauma. The neurootologist should consult with a radiologist before obtaining magnetic resonance imaging (MRI) because of intracranial metallic foreign bodies.

Temporal Bone Trauma Histology To understand the pathophysiology of temporal bone trauma, a clear understanding of the histology of the healing of temporal bone fractures is necessary. The special conditions prevailing in the temporal bone prevent a direct extrapolation to the bone repair physiology of long bones. Four distinct types of bone are present in the labyrinthine capsule: (1) the outer periosteal layer, (2) the endochondral layer, (3) islands of calcified cartilage, and (4) the innermost endosteal layer adjacent to the labyrinthine spaces. In marked contrast to other bones, the labyrinthine capsule attains its maximum size and complete ossification before birth. Because of this early mature development, the labyrinthine capsule does not remodel or grow like long bones. Teleologically, endochondral and endosteal layers have very little histologic evidence of osteoblastic activity. Perlman17 studied the histology of healing labyrinthine fractures in dogs and rabbits and found that immediately after the injury, the fracture is filled with fibrin clot. Between 1 and 5 days, marked thickening and fibroblastic proliferation of the periosteum occurred. Fibroblasts had migrated into the fracture and the fracture was filled with fibrous tissue. In contrast to this marked activity of the periosteal layer, the endochondral and endosteal layers showed no reaction. Beginning at 7 days, new periosteal bone was laid at the periosteal margin to form a tightly fitting bony plug by 2 to 3 weeks. Except for a delicate fibrous layer laid down by the endosteum, there was no evidence of osteoblastic activity in the endosteal or endochondral layers. This incomplete healing of the labyrinthine capsule is also seen in human temporal bone studies. Fredrickson and colleagues18 and Ward19 reported cases of incomplete union of labyrinthine fractures, which allowed ingrowth of respiratory mucosa into the fracture and established a CSF fistula. Figure 63-5 shows the histology of the labyrinthine capsule fracture with nonunion. Fracture healing in the temporal bone other than the labyrinthine capsule is more analogous to long bones. Because the temporal bone grows and remodels, it is composed of metabolically active periosteal bone. Complete healing via periosteal callus formation usually occurs unless

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Figure 63-5. Incomplete union of a labyrinthine fracture. There is ingrowth of respiratory mucosa (arrows) from the middle ear cavity (MEC) resulting in a CSF fistula. TM, tympanic membrane; RW, round window. (From Fredickson JM, Griffith AW, Lindsay JR: Transverse fracture of the temporal bone. Arch Otolaryngol 78:770–784,1963. Copyright © 1963, American Medical Association. Reproduced with permission.)

the fracture is severely comminuted or displaced. Fredrickson and colleagues18 noted that longitudinal fractures, which spare the labyrinthine capsule, usually heal by bony union. In Perlman’s study,17 extensive osteogenic activity was present in the bulla. This characteristic healing of the temporal bone may account for a lower incidence of CSF fistulae and late meningitis in longitudinal fractures.

Pediatric Temporal Bone Trauma Many clinicians assert that temporal bone trauma is rare in children due to the flexibility of the child’s skull and the underdevelopment of temporal bone pneumatization. However, these assertions are probably the result of underreporting of temporal bone fractures in children. LiuShindo and Hawkins20 reported that otolaryngology consultation was obtained for fewer than half of pediatric patients with temporal bone fractures. Current data support that although temporal bone fractures in children may not be common, they may occur at a rate similar to that of adult head trauma. Overall, 9% to 22% of temporal bone

fractures occur in patients younger than 18 years of age.4,21 As in adult patients, there is a male predominance of 2:1.22 There is, however, a bimodal age distribution in pediatric temporal bone trauma, with peaks at 3 to 4 years of age and again at 12 to 13 years of age.22,23 Lee and colleagues23 reported that motor vehicle/pedestrian accidents and falls each account for approximately 45% of pediatric temporal bone fractures, with biking accidents and blows to the head accounting for the remainder in cases of blunt trauma. Liu-Shindo and Hawkins20 found that 65% of the patients in their series had trauma associated with motor vehicles. They found that most children younger than 6 years were involved in pedestrian accidents, and most children older than 13 years were inside the vehicle during their accidents. The common presenting signs and symptoms in children are similar to those in adults. They include hemotympanum (58% to 81%), unconsciousness (56% to 65%), bloody otorrhea (47% to 58%), hearing loss (34% to 82%), intracranial injury (58%), and facial nerve palsy (3% to 13%).20,22,23 Otic capsule–disrupting fractures occur in 5% to 13% of pediatric temporal bone fractures.22–24 More recent reports have averaged a 5.5% rate of otic capsule–disrupting fractures, which is similar to that of adults. This decrease may be due to the mandatory use of child restraints and seatbelts and education programs emphasizing home safety.23,24 Overall, long-term complication rates for temporal bone fractures are lower in children than in adults. Shapiro22 reported that facial palsy occurred in only 6% of all cases. Otic capsule–sparing fractures caused paralysis in only 2.4% of cases, and otic capsule–disrupting fractures caused paralysis in 33% of patients. Lee and colleagues23 reported only a 3% overall facial paralysis rate. Although CSF leak rates may be high in children (22% to 27%), they resolve spontaneously in the first week after injury. Similarly, persistent vertigo beyond the first week after injury is rare. Although initially the rate of hearing loss may be similar to the rate in adults, spontaneous improvement of conductive hearing loss and high-frequency SNHL associated with otic capsule–sparing injuries can occur in more than 80% of children.25 Additionally, intracranial injuries are reported to be high (28% to 56%) in children with temporal bone fractures. In sum, pediatric temporal bone fractures are not as similar to adult fractures as was once thought. Most head injuries in children are preventable. Parental awareness and safety education makes up the cornerstone of prevention for these injuries. An interdisciplinary team approach should be used in the diagnosis and management of children with head trauma. The neurotologist should collaborate with pediatricians, intensivists, and neurosurgeons. Since many of the initial complications of temporal bone fractures improve spontaneously, children often do not require surgical intervention.

Clivus Fractures The clivus is anatomically defined as the entire thickness of the basioccipital bone, extending from the tuberculum sella to the foramen magnum. The clivus lies deep in the cranium, protected from direct injury by the facial and frontal bones anteriorly, the temporal bones and petrous pyramids laterally, and the occiput posteriorly.

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information includes a description of the weapon, the trajectory, and the range of the gunshot. 2. Timing of facial paralysis: Whether facial paralysis was immediate or delayed is of critical prognostic importance. 3. Inquiry into head and neck symptoms such as hearing loss, tinnitus, vertigo, hoarseness, diplopia, and numbness. 4. Presence of any preexisting neurotologic disease or symptoms.

Figure 63-6. Axial CT illustrates a transverse clivus fracture (arrows).

Historically, fractures of the clivus were considered exceedingly rare. However, high-resolution CT imaging has permitted increased diagnosis and understanding of these fractures. Figure 63-6 illustrates a transverse clivus fracture. Corradino and colleagues26 reported on 17 clivus fractures evaluated during 30 months. Clivus fractures were classified into longitudinal, transverse, and oblique to the long axis of the clivus. Longitudinal clivus fractures comprised 37.5% (6 of 17) of the group, and their associated mortality was 67% (4 of 6). Mortality was caused by brainstem infarction from basilar artery occlusion. Transverse and oblique clivus fractures accounted for 37.5% (6 of 17) and 29.4% (5 of 17), respectively. These fractures are clinically similar. Unlike longitudinal clivus fractures, most patients with transverse and oblique fractures had associated temporal bone fractures. Mortality in this group was 45% and most survivors had multiple cranial nerve deficits.

Patient Evaluation in Temporal Bone Trauma Evaluation of the patient with a suspected temporal bone injury occurs in three phases: (1) an immediate, comprehensive, multisystem examination to exclude life-threatening traumatic injury, (2) early neurotologic examination, and (3) late neurotologic examination. It is first essential to establish an airway, respiration, circulation, control of hemorrhage, and restoration of intravascular volume. The possibility of life-threatening neurologic, neurovascular, and cervical spine injuries must be excluded. Radiographic studies commonly employed in this initial evaluation include a chest x-ray, cervical spine series, cerebral arteriography, and CT of the brain. Optimal imaging of the temporal bone is typically obtained in a subsequent scan after the patient has been stabilized. Early neurotologic evaluation begins with a complete history and physical examination. Key elements of the history include the following: 1. The mechanism of injury: If the mechanism of injury is a motor vehicle collision, what was the speed of impact? Were safety belts worn? What part of the head was struck? Was there a loss of consciousness? If a penetrating injury was sustained, necessary

Every effort should be made to yield a complete history. Witnesses, emergency medical personnel, and police can supply valuable information, especially when the patient is unconscious. Physical examination should include a complete head and neck examination. Particular attention should be directed toward the following: 1. The external auditory canal and the tympanic membrane: Bleeding from the ear canal, a palpable fracture step-off, and tympanic membrane disruption are common signs of temporal bone fracture. Hemotympanum behind an intact eardrum may also indicate temporal bone fracture, particularly an otic capsule–disrupting fracture. Clotted blood obstructing the ear canal should be removed by means of a sterile technique to facilitate a complete examination and to check for CSF otorrhea. The ear canal should not be packed except in the rare event of life-threatening hemorrhage. 2. The mastoid process: Disruption of the mastoid emissary veins causes ecchymosis over the mastoid process, clinically known as Battle’s sign. 3. The eyes: The eyes should be examined for nystagmus or conjugate deviation. 4. Hearing: Each ear should be tested using live voice and tuning forks. 5. Facial nerve function: An early baseline of facial nerve function is essential. If the patient is cooperative, facial nerve function should be graded according to the House-Brackmann (HB) scale.27 If the patient is comatose, facial nerve function can be confirmed by employing a painful stimulus to elicit a facial grimace. 6. Complete cranial nerve examination: This should include an indirect laryngoscopy. Ancillary tests, including audiograms and high-resolution temporal bone CT are usually an integral part of neurotologic evaluation. MRI is indicated when intracranial injury is suspected. Occasionally, a patient comes to the neurotologist several weeks to months after temporal bone trauma. A persistent complication such as facial nerve paralysis, hearing loss, or vertigo usually causes a person to seek medical treatment. The neurotologic evaluation in this late period is similar to the early evaluation.

TEMPORAL BONE IMAGING Definitive diagnosis of temporal bone fracture and management of complications require radiographic evaluation.

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Although plain x-rays and multidirectional tomography are now of historic interest only, several decades ago they were the only modalities available for temporal bone imaging. Resolution was rather poor with these modalities and radiographic visualization of the temporal bone fracture was present in only 50% to 80% of cases.5,28,29 When the fracture was visualized, its full extent was usually underestimated. Imaging the site of facial nerve injury and ossicular integrity was usually not possible. The introduction of CT in the early 1980s revolutionized temporal bone imaging. MRI has since been added to the temporal bone imaging armamentarium.

Computed Tomography Computed tomography is the study of choice for imaging intratemporal structures and pathology in traumatic injuries. Optimal temporal bone imaging includes 1.0- or 1.5-mm sections in the axial and direct coronal planes that use bone window algorithms. This is known as highresolution CT. Severely injured patients may not be able to tolerate the neck extension necessary for direct coronal scans. For these cases, reconstructed coronal images may be substituted, although the resolution of reconstructed images is less precise than direct coronal images. Standard 10-mm-thick CT scans are not sufficiently sensitive for temporal bone fractures. Holland and Brant-Zawadzki30 compared CT findings in 13 patients with temporal bone fractures who had both 10-mm- and 1.5-mm-thick axial sections. The 10-mm scans missed 9 of 18 temporal bone fractures detected in the thin cut scans. High-resolution CT can accurately determine the fracture extent, ossicular continuity, and integrity of the fallopian canal. It is essentially 100% sensitive in detecting temporal bone fractures and in indicating the extent of these fractures.20,31,32 High-resolution CT can visualize the entire course of the fallopian canal when multiplanar images are obtained. Injury to the facial nerve is represented as disruption of the fallopian canal by the fracture or bony fragments impinging on the facial nerve. Figure 63-7 demonstrates a fracture involving the perigeniculate ganglion region. Johnson and colleagues32 reported 100% correlation between CT imaging of facial nerve site of lesion and findings during facial nerve decompression. The same report also describes CT diagnosis of ossicular pathology in 100% (7 of 7) of patients with conductive hearing loss. The ossicular pathology included incudostapedial disruption, dislocation of incus, and fracture of the malleus. Figure 63-1B is an example of CT imaging of ossicular discontinuity.

Magnetic Resonance Imaging MRI has been used for imaging the traumatized temporal bone. Zimmerman and colleagues25 compared CT with MRI findings in seven patients with temporal bone fractures. T1- and T2-weighted images in axial, coronal, and sagittal planes were performed with a 1.5-Tesla magnet without gadolinium-DPTA contrast. Although intact cortical bone appears as a signal void, MRI identified all or portions of six of eight fractures in seven patients. The key MRI finding that indicated fracture was the presence of blood in

Figure 63-7. Coronal CT demonstrates an otic capsule–disrupting fracture involving the perigeniculate region (arrowheads). The patient had facial paralysis.

the fracture line. Four of these patients were also studied with high-resolution CT sections in axial and coronal planes. In comparison to high-resolution CT, MRI underestimated the full extent of the fracture. The ability of MRI to evaluate the ossicular chain was limited because of the admixture of air, fluid, and blood in the middle ear. Air could simulate portions of the ossicular chain. Because MRI’s soft tissue imaging capability is superior to that of CT, it is superior in evaluating the intracranial complications associated with temporal bone trauma. Zimmerman and colleagues25 reported that MRI discovered five subdural hematomas, two epidural hematomas, and two hemorrhagic contusions that were missed with CT. This finding is consistent with MRI being superior to CT in detecting intracranial complications of otitis media.33 In contrast, MRI of the facial nerve in temporal bone fractures is less promising. Haberkamp and colleagues34 reported on the use of gadolinium-enhanced MRI in determining the site of lesion in 20 patients with traumatic facial paralysis from a variety of causes. Three patients had sustained facial paralysis from temporal bone fracture. In each of these patients, imaging of the facial nerve was obscured by increased signal intensity from the mastoid, usually from blood. This made localization of the facial nerve injury impossible. To summarize, CT and MRI have complementary roles in the imaging of temporal bone trauma. This is analogous to their roles in imaging complicated otitis media and skull base lesions. High-resolution CT is superior for imaging the temporal bone. Its ability to image fine bony detail allows accurate determination of fracture extent, ossicular continuity, and site of lesion when facial paralysis is present. When there is temporal bone trauma, MRI plays a role in the diagnosis of concomitant injury to the CNS.

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COMPLICATIONS OF TEMPORAL BONE TRAUMA

TABLE 63-1. Facial Nerve Pathology Discovered during Surgical Exploration

Facial Nerve Injury Facial nerve paralysis has been a controversial topic, with nearly 4000 articles discussing this problem having been published during the past 25 years. Most of the controversy concerning facial nerve paralysis is centered on surgical intervention. Management of immediate versus delayed paralysis, prognostic testing, timing of surgical intervention, appropriate surgical approach to the injured segments, and results of surgical intervention remain quite controversial. This debate has further been fueled by lack of controlled studies, the relatively small numbers in most reports, and until the introduction of the HB scale27 in 1985, no uniform system for reporting results. Although all of these publications have engendered lively debate, considerable confusion has also been generated because of contradictory reports. The purpose of this section is to present pertinent reports from surgeons who have had the most experience with traumatic facial nerve paralysis. From these data, the neurotologist can develop a rationale for managing this complication. For this discussion, we will consider facial nerve paralysis as a complete paralysis. Partial facial paralysis or paresis rarely needs treatment because it nearly always completely recovers spontaneously. Furthermore, although only intratemporal injury to the facial nerve is considered in this chapter, the neurotologist must be cognizant of the possibility of concomitant extracranial injury when facial laceration is present.

Pathology of Traumatic Facial Nerve Paralysis The neurotologist must have an understanding of the facial nerve pathology common to each type of temporal bone fracture. This knowledge allows for anticipation of likely scenarios during facial nerve exploration. Facial nerve paralysis complicates 7% to 18% of otic capsule–sparing fractures.21,35 Because otic capsule–sparing fractures comprise the overwhelming majority of temporal bone fractures, the neurotologist is most likely to encounter facial paralysis associated with these fractures. Large series by Fisch,36 Coker and colleagues,37 and Lambert and Brackmann29 reported on surgical findings encountered during facial nerve exploration on otic capsule–sparing fractures. In each of these series, the most common site of facial nerve injury was the perigeniculate ganglion region, particularly the distal labyrinthine segment. This location included 80% to 93% of injuries. The next most common site was just distal to the pyramidal eminence. The specific pathologic lesions per fracture type discovered are tabulated in Table 63-1 and include intraneural edema and/or hemorrhage, impingement by bony spicule, and total nerve transection. A mechanism of facial nerve injury can be constructed from these data. Head trauma is a deceleration injury and structures that are tethered are most likely to be injured from sudden deceleration. The facial nerve is tethered in the perigeniculate ganglion region by the greater superficial petrosal nerve. This tethering and sudden deceleration

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Facial Nerve Pathology Total nerve transection Bony spicule impingement Nerve edema and/or hematoma No pathology

Frequency (%) Facial Paralysis in OCSF*

Frequency (%) Facial Paralysis in OCDF*

15 30 43 0

92 8 0 0

*OCSF, otic capsule–sparing fracture; OCDF, otic capsule–disrupting fracture. Data from Chang CY, Cass SP: Management of facial nerve injury due to temporal bone trauma. Am J Otol 20:96–114, 1999.

creates a shearing force on the facial nerve. This force results in intraneural contusion, edema, and hemorrhage. If the shearing force is great enough, then nerve transection will result. The labyrinthine segment is the narrowest part of the fallopian canal; therefore, nerve impingement and ischemia are most likely to occur in this segment. The second most common site of injury is at another tethering point, distal to the pyramidal eminence. Otic capsule–disrupting fractures are complicated by facial paralysis in 38% to 50% of these fractures.35 Fisch36 reported that of 10 patients explored for facial paralysis with otic capsule–disrupting fractures, all had transection of the facial nerve in the distal labyrinthine segment. Because much greater force is required to cause otic capsule– disrupting fractures than to cause otic capsule–sparing fractures, more severe facial nerve injury is expected in the former. Gunshot blasts cause the most severe temporal injuries, with facial paralysis in 45% to 50% of patients with penetrating trauma.14,16 The mechanism of facial nerve injury in these patients is completely different from blunt trauma. Projectiles usually enter the temporal bone from its lateral or inferior aspects. The kinetic energy of the projectile is dissipated as heat and tissue destruction. Therefore, portions of the facial nerve closest to the entry site and course of the bullet sustain the most damage. Coker and colleagues37 reported the extratemporal facial nerve, stylomastoid foramen, and vertical segment of the nerve to be most frequently injured. Most facial nerves were transected, severely crushed, or contused. Interposition grafts or rerouting were required in nearly all instances.

Criteria for Surgical Intervention Surgical intervention for traumatic facial paralysis is fraught with controversy. Ideally, the neurotologist should surgically explore the facial nerve either when reversible facial nerve damage requires repair or when entrapment neuropathy or transection impairs facial nerve regeneration. The point at which paralysis occurs, topographic testing, and electrical testing have all been used as criteria for surgical intervention. Immediate versus Delayed Paralysis Understanding the natural history of traumatic facial nerve paralysis is critical to deciding on treatment options. In 1944, Turner38 reported the largest and earliest series of untreated

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facial nerve injuries. He reported on 30 patients with facial paralysis with various degrees of severity and found that 63% of the patients experienced full recovery. Eighty-two percent of the patients with delayed onset paralysis had full recovery, while an estimated 53% of patients with immediate paralysis had complete recovery. McKennan and Chole39 reported on 3 patients with immediate facial nerve paralysis and 19 patients with delayed paralysis who were not treated with surgical decompression. In the former group, 2 had an HB 3 and 1 had an HB 5. Similar to Turner’s findings,38 they reported that 95% of the delayed paralysis group had recovery to HB 1 or 2. Brodie and Thompson21 reported on 699 patients with temporal bone fractures. All 41 patients with either an incomplete paralysis (8 immediate and 27 delayed) or a delayed complete paralysis had resolution of their paralysis to an HB 1 or 2. Of the three patients with an immediate and complete paralysis, one of the two patients available for follow-up recovered to an HB 1 or 2. Overall, the range in latency to recovery of facial function was 1 day to 1 year. Fifty-nine percent of patients with either complete or incomplete facial paralysis had recovery by 1 month post injury and 88% recovered by 3 months post injury.40 Traditional teaching states that immediate paralysis has a much worse prognosis than delayed paralysis. Immediate paralysis is widely believed to be caused by nerve transection or other severe nerve trauma. Delayed paralysis is believed to be a result of nerve edema and thus has a better prognosis. Some authors advocate routine exploration of immediate facial nerve paralysis because of presumed poor prognosis.41,42 Other authors believe that immediate versus delayed paralysis has little prognostic value.29,36,37 However, Turner’s38 report on the natural history of immediate and delayed traumatic facial paralysis supports observation for most patients (Table 63-2), although it is difficult to ascertain the presence of an immediate versus delayed paralysis in unconscious or comatose patients. May43 stated that several unconscious patients with presumed delayed paralysis had transected facial nerves at exploration. In summary, immediate paralysis should suggest to the neurotologist that severe injury to the facial nerve might have occurred. Immediate paralysis carries a worse prognosis than does delayed paralysis. However, this finding alone should not be an absolute indication for surgical intervention. Topographic Testing Topographic testing of the facial nerve attempts to identify the site of lesion in the nerve. This includes Schirmer’s test, submandibular salivary flow, stapedial reflex, and electrogustometry. Topographic testing has been superseded by electrical testing for determining recovery prognosis, and high-resolution CT better delineates site of injury.

Electrical Testing Electrical testing of the facial nerve is widely used for determining prognosis for recovery from facial nerve paralysis. Excellent and detailed descriptions of electrical testing are included in other chapters in this text. This section focuses on electrical testing as a criterion for surgical exploration of traumatic facial nerve paralysis. The most common electrical tests are the maximal stimulation test (MST) and electroneuronography (ENOG). MST measures the strength of contraction of facial muscles to a 5-mA current or the greatest current the patient can tolerate. A Hilger nerve stimulator is used. The strength of facial contraction elicited by electrical stimulation on the paralyzed side is compared to stimulation on the normal side and is rated as normal, decreased, or no contraction. ENOG is similar to MST, but it produces a quantitative record of the evoked facial muscle contraction. Electrodes are placed on the skin at the stylomastoid foramen, and supramaximal stimulation is applied. Recording electrodes are placed on the skin at the nasolabial fold and the amplitude of the evoked myographic response is recorded on an oscilloscope. Amplitudes on the normal and paralyzed sides are compared. The amplitude loss on the paralyzed side is directly proportional to the percentage of axonal degeneration and denervation. MST and ENOG are similar in theory and in application. Both tests apply a supramaximal electrical stimulus to the facial nerve distal to the site of injury. The strength of evoked muscle contraction is compared to the normal side and the decrement is proportional to the degree of denervation. The degree of denervation can be used as a prognosticator for facial nerve recovery. If complete or severe denervation occurs, then a poor recovery with aberrant reinnervation and synkinesis can be expected. Electrical testing can monitor the degree of denervation and when a threshold of denervation is passed, surgical intervention can be planned. The old maxim, “the sun never sets on a complete facial nerve paralysis,” is strictly applied to electrical testing. The patient is tested daily until either recovery begins or surgical intervention is necessary. MST has the advantage of simplicity, requiring only a Hilger nerve stimulator. Although ENOG requires a somewhat more complicated system, its advantage is that it provides a quantitative measure of nerve denervation. Much of our current understanding of facial nerve recovery is based on acute facial paralysis (Bell’s palsy). May and colleagues44 reported that 88% of patients with a normal response to MST had a complete return of facial nerve function, 73% with reduced response had complete return, and only 27% with no MST response had a complete return of facial nerve function. Fisch45 states that 90% degeneration recorded on ENOG within 3 weeks from onset of complete paralysis is associated with poor recovery in 70% of patients.

TABLE 63-2. Natural History of Traumatic Facial Nerve Paralysis Paralysis

N

Immediate Delayed

19 11

“Good” Recovery 10 (53%) 9 (82%)

Data from Turner JW: Facial palsy in closed head injuries. Lancet 246:756–757, 1944.

Partial Recovery with Synkinesis 6 (32%) 1 (9%)

No Recovery 3 (16%) 1 (9%)

Temporal Bone and Skull Base Trauma

Good recovery can be expected in more than 80% of patients when degeneration is less than 90%. Based on these data, many clinicians use the criteria of no MST response or 90% degeneration by ENOG as a threshold for surgical intervention. Esslen46 found that patients with degeneration on ENOG of 90% to 95% had a 72% chance of recovery, and those with an ENOG with 96% to 98% degeneration had a 54% chance of recovery. Only degeneration greater than 98% was associated with a poor prognosis (30% recovery). He suggested that ENOGs showing greater than 95% degeneration be used at the criteria for surgical decompression. In a comprehensive review, Chang and Cass40 proposed that if greater than 95% degeneration is found in the first 6 days post injury, surgical exploration should be performed. If the degeneration occurs after 14 days, the patients should be considered to have a good prognosis for natural recovery. Surgical repair for degeneration in the period of 6 to 14 days post injury is of questionable benefit. Despite their usefulness, electrical tests do have several disadvantages. They are of no value for approximately 72 hours after onset of complete paralysis. Wallerian degeneration of the distal nerve does not occur until 72 hours after injury. Until wallerian degeneration occurs, normal responses are recorded. Furthermore, although electrical tests measure the percentage of degenerated motor axons, they yield no information on either the location or severity of the nerve injury. The integrity of the endoneurium, perineurium, and epineurium is more important than the degree of axonal degeneration in predicting recovery. Sunderland47 class II nerve injury, axonotmesis, has good recovery because although the axons have degenerated, the endoneurial tubes are intact. Class III–V nerve injury, neurotmesis, has a much worse prognosis. Disruption of the endoneurial tubes allows aberrant reinnervation and synkinesis. Electrical tests cannot discriminate between axonotmesis and neurotmesis and therefore cannot directly assess the degree of damage to the facial nerve. The percentage of axonal degeneration is used as an indirect measure of the status of the supporting neural structures. Nevertheless, the maintenance of electrical stimulation during facial paralysis is an excellent prognostic signal for complete recovery. No surgical intervention should be considered for these patients.

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excellent access to the entire intratemporal length of facial nerve. If the patient has hearing, then most surgeons use a combined transmastoid-middle fossa craniotomy exploration.29,35–37,43 The transmastoid approach permits access to the vertical and horizontal portions of the facial nerve. Exposure to the geniculate ganglion and labyrinthine segments is gained through the middle fossa craniotomy (Fig. 63-8). Yanagihara48 described a transmastoidsupralabyrinthine approach to the geniculate ganglion and the labyrinthine segment. The incus is disarticulated and access to the perigeniculate area is provided by drilling the supralabyrinthine air cells. Although this approach is advantageous because the entire facial nerve can be exposed through a single surgical approach, some authors37 assert that the access to the perigeniculate ganglion is not sufficient. Another disadvantage of the transmastoidsupralabyrinthine approach is a conductive hearing loss that must be repaired. The timing of facial nerve exploration is also a subject of debate. Most surgeons prefer to explore the facial nerve as

A

Radiologic Imaging High-resolution CT is the imaging study of choice for evaluating intratemporal facial nerve injury. Axial and direct coronal sections are necessary to visualize the entire fallopian canal. The patient with complete facial palsy requires this examination for evaluation of site of injury.

Surgical Management of Facial Nerve Paralysis Surgical exploration of the traumatized facial nerve requires opening of the entire length of the fallopian canal. Although most facial nerve injuries occur in the perigeniculate ganglion region, unsuspected injury can occur anywhere along the course of the facial nerve. The key determinant for deciding which surgical approach to use is the patient’s hearing status. If the patient has anacusis, then the translabyrinthine approach is used. This approach allows

B Figure 63-8. A, Diagram shows the middle fossa craniotomy approach to the perigeniculate and labyrinthine segments to the facial nerve. B, Diagram demonstrates repair of the facial nerve in the perigeniculate region by release of the facial nerve from the greater superficial petrosal nerve and either (A) primary anastomosis or (B) cable graft repair.

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soon as the patient’s condition permits. Haker and McCabe35 recommended waiting 21 days after the onset of paralysis. Their reasoning was that the neuron’s metabolism is maximized at that time for axonal regeneration. However, not all reports support this hypothesis of waiting 21 days after injury.49 These data are discussed in detail in the next section. Considerable controversy exists over bony decompression of the facial nerve as compared to incising the epineurial sheath. Some authors advocate routine epineurial sheath slitting.50,51 Their observations indicate that damaged segments of the facial nerve are edematous and contain intraneural hematoma. Slitting the epineurial sheath allows for maximal decompression of the nerve and nerve fascicles are frequently observed to bulge out of the slit as the intraneural pressure is relieved. Other surgeons do not advocate epineurial slitting.52 These authors assert that the barrier to decompression is the bony fallopian canal, not the epineurial slitting. These authors assert that the barrier to decompression is the bony fallopian canal, not the epineurial sheath. In peripheral neuropathy, such as carpal tunnel syndrome, the median nerve responds well to release of its ligamentous tunnel without epineurial slitting. Furthermore, the epineurial sheath serves as a protective barrier and should be left intact. Experimental evidence indicates no benefit to slitting the epineurial sheath over bony decompression alone. These studies are discussed in the next section. Management of the facial nerve injury itself depends on the pathology encountered. We prefer to be as conservative as possible. Neural edema is managed with bony decompression alone. The nerve sheath is slit only if there is a large intraneural hematoma. Any bony spicules are removed. If the nerve is transected or severely injured, which necessitates excision, then primary anastomosis is preferable over cable grafting. With perigeniculate ganglion injuries, additional length of the facial nerve can be gained by rerouting the nerve around the geniculate ganglion. We use an epineurial neurorrhaphy because it is less cumbersome than a fascicular repair. Nerve grafting with the greater auricular or sural nerve is necessary only if tensionfree primary anastomosis cannot be achieved.53 This circumstance is very unusual and occurs only in very severe injuries, such as gunshot wounds. May and Klein54 reported complications associated with facial nerve exploration in 139 patients. These complications are summarized in Table 63-3.The most common complications are associated with hearing loss; however, any structure within or adjacent to the temporal bone can be injured. The authors included reports of injury to the facial nerve itself, the chorda tympani nerve, the vestibular labyrinth, the cochlea, the sigmoid sinus, the superior petrosal vein, the middle meningeal artery, the dura, and the brain. Experimental Models The surgical management of traumatic facial paralysis is quite controversial. Issues debated by neurotologists include (1) the possible benefit of early facial nerve decompression to prevent irreversible facial nerve degeneration, (2) whether to slit the epineurial sheath during decompression, and (3) the timing of facial nerve grafting.

TABLE 63-3. Common Complications of Facial Nerve Exploration Complication High-frequency sensorineural hearing loss Conductive hearing loss Tinnitus Loss of speech discrimination >15% Hearing loss requiring a hearing aid

Incidence (%) 51 14 12 7 5

Data from May M, Klein SR: Facial nerve decompression complications. Laryngoscope 93:299–305, 1983.

Several experimental models of facial nerve paralysis have sought to provide evidence that clarifies these issues. Binns55 created traumatic intratemporal facial nerve lesions in cats. His method consisted of exposing the second genu and lifting the nerve with a hook to stretch the nerve. This method produced facial paralysis with electrical degeneration in 83% (10 of 12) of animals. Immediate facial nerve decompression at the time of injury prevented facial paralysis and electrical degeneration in 100% (12 of 12) of animals. Whether the epineurial sheath was slit was not specified. They concluded that facial nerve decompression for traumatic lesions is of definite value if undertaken within 48 hours of injury and earlier decompression resulted in an improved outcome. Boyle56,57 produced traumatic facial nerve lesions in monkeys by ultrasonic irradiation of the vertical segment. This produced facial paralysis in 83% of nerves (20 of 24). Histologically, this trauma produced breakdown of myelin and intraneural hemorrhage but no axonal degeneration. This lesion is therefore a Sunderland class I injury. Control animals (irradiated but receiving no surgical intervention) had complete recovery within 6 to 8 weeks. Decompression performed 48 hours after injury relieved intraneural pressure with the nerve trunk bulging out of the slit sheath. However, nerves that had been decompressed had no better recovery than the controls. This result is not surprising given the mild nature of the traumatic lesion (neuropraxia). The author also studied the effect of epineurial decompression on normal nerves. Slitting of the epineurial sheath produced no clinical paralysis or electrical degeneration. When decompression was delayed 72 hours, there was no benefit compared to controls. Histologic examination revealed demyelinization in decompressed areas. This suggests that even with careful facial nerve decompression, subclinical neural damage can occur. Greer and colleagues58 studied traumatic facial paralysis in cats. Their method produced a crush injury at the second genu. Control animals had crush injury but no decompression performed. This injury produced facial paralysis with elevation of the nerve excitability threshold (NET) to greater than 5 mA but the nerve was still electrically excitable. Histologically, the nerves showed demyelinization with moderate nerve fiber degeneration (Sunderland II–III). Clinical recovery began at approximately 31 days, with complete recovery by day 43. Immediate bony decompression without sheath slitting resulted in earlier onset of clinical recovery and earlier complete recovery than contralateral control ears. No difference in NET

Temporal Bone and Skull Base Trauma

recovery was noted. However, immediate sheath slitting resulted in a delayed onset and complete recovery. No difference in NET recovery was noted between the groups. Furthermore, NET testing was worse for the sheath-slit nerves. Delayed decompression, either bony or sheath slitting, at 7 days or longer showed no change in clinical recovery nor electrical testing. The authors also compared the histologic and NET findings for normal facial nerves that underwent either bony or sheath decompression. Although either decompression could cause a transient facial paresis, the histology and NET of decompressed nerves were indistinguishable from normal nerves regardless of whether the sheath was slit. Barrs49 investigated the optimal timing of facial nerve repair in young pigs. The vertical segment of the facial nerve was transected and cable grafting was performed immediately and 5, 21, 60, and 90 days after transection. The animals were followed for 3 months after repair. Electrical stimulation across the graft was present in all repaired nerves and no significant difference existed between operative groups and NET values. No animal had clinical recovery. However, axonal counts demonstrated a trend toward a lower regeneration rate in more delayed grafts. Proliferation of fibrous tissue in delayed cases made nerve stump location more difficult, required more nerve stump resection to “refresh” the stumps for grafting, and made facial nerve mobilization technically more difficult. Grafting at 21 days, the peak of neuronal cell body metabolic activity, did not produce better results. Although the best results may be obtained with earlier grafting, nerve repair several months after trauma can be successful. Yamamoto and Fisch59 used polyethylene tubes to produce compression injuries in cats. They found a significant benefit if the compression was relieved within 12 days of the injury. Partial recovery was noted if the decompression was performed between days 14 and 21 and little benefit of decompression was realized after 21 days of compression. Interestingly, the authors incised all nerve sheaths after decompression and did not find decreased improvement with this technique. In summary, experimental models of traumatic facial paralysis support the following conclusions: 1. Decompression of the facial nerve appears to improve recovery if performed within 48 hours of injury. Decompression after this time does not

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improve axonal degeneration. Decompression performed within 2 weeks may assist the regeneration of the facial nerve. 2. Slitting the epineural sheath has no advantage over bony decompression. Some studies indicate that epineural slitting causes further neural damage and may worsen recovery. 3. Results of facial nerve grafting appear to favor early repair over delayed grafting. There is no support for waiting 21 days when neuron metabolic activity is at its peak. Results of Surgical Management As mentioned earlier, comparison of results of surgical exploration of the facial nerve among published reports is difficult because of the lack of controls and, before the House-Brackmann scale, the lack of a uniform reporting system for facial nerve function.60 Table 63-4 summarizes the results obtained in five series of facial nerve explorations following temporal bone trauma. Patient follow-up was at least 6 months in all series. Electrical testing criteria for exploration was either no response to MST or greater than 90% degeneration on ENOG. Table 63-4 also stratifies results into decompression only and nerve anastomosis because of facial nerve transection. Approximately 50% of patients who required decompression had a good outcome, defined as HB 1 or 2. One is tempted to draw the conclusion that early decompression improved the facial nerve recovery in these patients because electrical criteria indicated a poor prognosis for complete recovery. However, Turner’s data38 on the natural history of immediate, complete traumatic facial nerve paralysis showed that 53% of those patients had good recovery without surgical intervention (see Table 63-2). Comparing the results in Table 63-4 with historical controls in Turner’s series, early decompression of the facial nerve does not appear to improve recovery from traumatic facial nerve paralysis. However, this result is not surprising. Experimental data indicate that facial nerve decompression is of value in preventing axonal degeneration only within 48 hours of injury. Because electrical tests do not show evidence of axonal degeneration until approximately 72 hours after injury, “early” facial nerve decompression is employed long after irreversible nerve injury has occurred. Therefore, the goal of surgical intervention

TABLE 63-4. Results from Facial Nerve Exploration following Temporal Bone Trauma Decompression Only Study Lambert and Brackman Kamerer Coker et al. Green et al. Brodie and Thompson Totals

N

H-B 1-2

N

15 42 9 8 7 81

10 (66.7%) 18 (42.8%) 5 (55.5%) 3 (37.5%) 4 (57.1%) 40 (49.4%)

0 20 2 12 0 34

Nerve Anastomosis H-B 1-2

H-B 3-4

0 0 0

15 (75%) 2 (100%) 12 (100%)

0

29 (85.3)

Data from Brodie HA, Thompson TC: Management of complications of 820 temporal bone fractures. Am J Otol 18:188–197, 1997; Coker JN, Kendall DA, Jenkins HA, Alford BR: Traumatic intratemporal facial nerve injury: Management rationale for preservation of function. Otolaryngol Head Neck Surg 97:262–269, 1987; Green JD, Shelton C, Brackmann DE: Surgical management of iatrogenic facial nerve injuries. Otolaryngol Head Neck Surg 111:606–610, 1994; Kamerer DB: Intratemporal facial nerve injuries. Otolaryngol Head Neck Surg 90:612–615, 1982; and Lambert PR, Brackmann DE: Facial paralysis in longitudinal temporal bone fractures: A review of 26 cases. Laryngoscope 94:1022–1026, 1984.

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should be to provide the most favorable environment for axonal regeneration. This includes repair of facial nerve transections and removal of anatomic barriers to regeneration, such as bony spicules. The role of facial nerve decompression to assist axonal regeneration is currently unknown. The role of delayed exploration of the facial nerve also remains controversial. Quaranta and colleagues61 recently reported on nine patients with perigeniculate temporal bone fractures and immediate facial paralysis who underwent decompression surgery 27 to 90 days after injury. All patients had greater than 90% degeneration on ENOG within 6 days of injury and greater than 95% degeneration at the time of surgery. The perigeniculate region and either tympanic or mastoid segments were involved in all cases, with one case involving the labyrinthine segment. A transmastoid-supralabyrinthine approach was used for the decompression with edema found in eight cases and bony impingement in five cases. Seventy-eight percent (7 of 9) had a postoperative HB 1 or 2. The remaining two cases recovered to an HB 3. The authors conclude that delayed repair can be successful if electrical tests show signs of poor prognosis (greater than 95% degeneration). In summary, management of facial nerve paralysis following temporal bone trauma remains controversial. Ideally, surgical intervention takes place when a reversible facial nerve injury threatens to become irreversible because of continued pressure ischemia or other causes. This corresponds histopathologically to the change from axonotmesis to neurotmesis. Unfortunately, the present technology of electrical tests cannot make this discrimination in time for decompression to prevent irreversible neural injury. The goal of surgical intervention should be to provide the most favorable environment for nerve regeneration. Neurotologists need to rely on their surgical judgment, knowledge of temporal bone trauma, and the type of facial nerve pathology likely to be associated with each fracture type. We recommend the following rationale for management of traumatic facial nerve paralysis: 1. Otic capsule disrupting fractures: Facial paralysis in these fractures is likely to be caused by nerve transection. When electrical tests indicate poor prognosis (greater than 95% degeneration on ENOG recorded within 14 days of injury), the facial nerve should be explored via the translabyrinthine approach as soon as the patient’s condition permits. Nerve anastomosis or cable grafting will likely be required. Return of function to an HB 1 or 2 can be expected in approximately 50% of cases. When transection has occurred and either cable grafting or primary anastomosis is performed, there is an 80% chance of obtaining an HB 3 or 4 result. 2. Gunshot injury: Facial paralysis in these fractures is likely to be caused by nerve transection. When electrical tests indicate poor prognosis, the facial nerve should be explored via the translabyrinthine or transmastoidsubtemporal approach depending on the patient’s hearing and the surgeon’s judgment. Exploration should commence as soon as the patient’s condition permits. Cable grafting will likely be required.

3. Otic capsule–sparing fractures: Facial paralysis in these fractures is likely to be caused by intraneural edema or hematoma. When electrical tests indicate poor prognosis, irreversible pressure necrosis has probably occurred. If CT demonstrates bony fragment impingement or fracture disruption of the fallopian canal, exploration is recommended because of probable anatomic barriers to nerve regeneration. If this evidence is lacking, neurotologists must evaluate for each patient whether exploration is warranted. We would consider offering facial nerve decompression via a transmastoid-subtemporal approach based on the criteria for otic capsule–disrupting fractures noted earlier. Patients should be made aware that the clinical and experimental data are indeterminate in showing a clear benefit of decompression. For all three categories, consideration should be made for delayed (longer than 30 days) facial nerve exploration if electrical tests (i.e., ENOG, electromyography [EMG]) indicate a poor prognosis.

Cerebrospinal Fluid Leakage and Meningitis Complication of temporal bone fractures because of CSF leakage is common. Reported rates4,19,23,62 of CSF leakage with temporal bone fracture range from 11% to 27%. CSF leakage is difficult to ascertain immediately after the traumatic event because of the masking effect of associated bleeding. CSF leakage can be detected in this early stage by placing a drop of otorrhea on filter paper of linen. The halo sign, named for the clear halo created by CSF around the centrally pigmented bloodstain, indicates CSF admixed with blood. However, even if the halo sign is absent, a strong suspicion for CSF leakage must exist. The ear canal should be inspected daily for leakage of CSF. As bleeding subsides, detection of CSF leakage becomes easier. β-2-transferrin is a CSF, perilymph, and aqueous humor– specific protein involved in iron transport. It can be assayed to indirectly confirm the presence of CSF in either nasal or ear secretions.63 This testing is thought to be highly specific and sensitive, but laboratory turnaround time can hamper the usefulness of the test. Laboratory evaluation of suspected CSF fluid is generally not useful because of the contamination of native fluids (i.e., nasal secretions). The placement of intrathecal material followed by diagnostic evaluation such as CT cisternography, nuclear medicine, or fluorescein study all represent highly sensitive tests for active CSF leaks. CSF leakage can be clinically evident as otorrhea, rhinorrhea, or both. They are caused by a fistulous connection between the subarachnoid space and the pneumatized spaces of the temporal bone via a dural tear. Otic capsule– sparing fractures usually show CSF otorrhea because of the drainage from pneumatized spaces through a tympanic membrane tear or a fracture of the tympanic bone. Because the tympanic bone and membrane are usually spared in otic capsule–disrupting fractures, CSF egress from the pneumatized spaces is through the eustachian tube and into the nasopharynx. CSF rhinorrhea is more

Temporal Bone and Skull Base Trauma

difficult to diagnose than otorrhea because of the lack of objective findings. However, patients might complain of a salty taste in their nose or mouth or watery rhinorrhea. Most CSF leaks cease within a few days and the conservative management of CSF leakage includes bedrest with the head elevated at least 30 degrees, fluid restriction, and oral acetazolamide. If leakage persists after 5 to 7 days of conservative management, then continuous lumbar subarachnoid drainage is initiated. The drainage is maintained for 5 days and then discontinued. If the patient still has persistent leakage, then surgical closure of the fistula can be planned. Fortunately, operative intervention is rarely necessary. Brawley and Kelly62 reviewed the management of CSF fistulae in more than 300 skull base fractures over a 5-year period. All 35 documented fistulae closed within 2 weeks with conservative management. Otic capsule– sparing fractures usually have a CSF fistula from the middle fossa. An extradural, middle fossa craniotomy with repair of the dura with fascia lata is the usual approach for surgical closure in these cases. Otic capsule–disrupting fractures leak through a labyrinthine fracture. Labyrinthectomy with obliteration of the mastoid is indicated for otic capsule– disrupting fractures. Meningitis complicating traumatic CSF fistulae is a topic of considerable debate. The reported incidence of meningitis following traumatic CSF fistula varies from 3% to 50%.64 However, a compilation of more than 400 cases of traumatic fistulae from the literature revealed a 12.4% rate of meningitis.64 Rhinorrhea was four times more likely to be complicated by meningitis than otorrhea. Prophylactic antibiotic therapy is controversial. Although some authors routinely administer prophylactic antibiotics,62,65 randomized studies have shown no significant benefit.5,64,66 Pneumococcus is the most common infecting organism, followed by Staphylococcus, Streptococcus, and Haemophilus influenza. Late meningitis following temporal bone fracture is distinct from the complication of early meningitis. It may occur years after the trauma and the patient may not even remember the traumatic event. Because of the duration between trauma and late meningitis, the incidence of this entity is not known. Histologic studies reveal that the CSF leak is from incomplete healing of labyrinthine fractures and possible ingrowth of respiratory mucosa, which establishes a microscopic fistula.18,19 A recurrent meningitis may have a traumatic etiology. A diligent search for a CSF fistula includes the use of high-resolution CT, CT with intrathecal contrast, and/or intrathecal injection of radioactive indium. If a labyrinthine fracture is the cause of recurrent meningitis, then a labyrinthectomy with obliteration of the pneumatized spaces and the eustachian tube is necessary.

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These fractures allow squamous entrapment from the EAC through fracture lines in the tympanic bone. Tears of the tympanic membrane also permit implantation of squamous epithelium into the middle ear. The CT in Figure 63-9 shows a large, post-traumatic cholesteatoma. Conversely, otic capsule–disrupting fractures usually spare areas that contain squamous epithelium. Cholesteatoma is a markedly delayed complication of temporal bone fracture. Symptoms usually do not become evident until years after the traumatic event. Therefore, long-term follow-up of patients with temporal bone fractures is essential. Unfortunately, since many patients who sustain temporal bone fractures are noncompliant in their follow-up, post-traumatic cholesteatomas are usually quite advanced. The neurotologist must have a high degree of suspicion for this complication. The presentation of these cholesteatomas is usually atypical. McKennan and Chole39 reported three post-traumatic cholesteatomas. Two occurred behind intact tympanic membranes, presumably from squamous implantation into the middle ear. In one patient, the cholesteatoma was initially diagnosed as an external otitis. Subsequently, a hole in the posterior canal wall with keratin debris was discovered. A temporal bone CT is the imaging study of choice. Characteristically, post-traumatic cholesteatomas occur in well-pneumatized temporal bones. This necessitates an extensive mastoidectomy. Care must be taken while elevating tympanotomy flaps or cholesteatoma matrix in these patients. Dura may be adherent to skin through fracture lines and dural laceration and CSF leaks can easily occur.

Cholesteatoma Healing of temporal bone fractures occurs by callus formation and fibrous or bony union. Mature callus formation produces a barrier to ingrowth of squamous epithelium. However, entrapment of squamous epithelium prior to callus formation can result in cholesteatoma formation. Cholesteatoma following temporal bone fracture has been described as a complication exclusively of otic capsule– sparing fractures.67

Figure 63-9. Axial CT shows a large post-traumatic cholesteatoma. The lesion was caused by squamous ingrowth through a fracture in the bony external canal wall (arrows).

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HEARING LOSS Hearing loss following temporal bone trauma may be caused by injury to any level of the auditory system. The hearing loss (HL) can be sensorineural, conductive, or mixed. Evaluation of hearing should begin as soon as possible. A complete physical examination should note injuries to the ear canal, tympanic membrane, and hemotympanum. The ability to hear a whisper or softly spoken voice in the affected ear with masking of the contralateral ear should be recorded. The critical issue in the initial evaluation is whether severe sensorineural injury has occurred. If anacusis is present, then the translabyrinthine approach can be used if facial nerve exploration is necessary. A baseline audiogram should be obtained as soon as the patient’s overall condition allows. Long-term follow-up and repeat audiograms are necessary.

Natural History of Traumatic Hearing Loss Tos68 reported the audiologic data of 222 patients with temporal bone fractures. All patients with transverse fractures presented with anacusis and had no recovery of hearing. Sixty-seven percent of patients with longitudinal temporal bone fracture had hearing loss greater than 20 dB within 1 week of the trauma. In 88% of these patients, the hearing loss was conductive. Follow-up audiology 3 to 6 months later revealed that only 37% had hearing loss greater than 20 dB. Long-term follow-up from 6 months to 7 years disclosed that 80% had hearing within 29 dB. Ossicular discontinuity was present in 13% of patients and moderate to severe sensorineural hearing loss in 4%. “Mild” high-frequency SNHL was reported for 20% of patients.

Conductive Hearing Loss A degree of conductive hearing loss is nearly always present immediately following temporal bone trauma because of the presence of blood in the ear canal or middle ear or from a tympanic membrane perforation. Uncomplicated hemotympanum resolves over several weeks with lysis of blood clot. Nearly all traumatic tympanic membrane perforations heal spontaneously within 3 months if secondary infection does not occur.69 Therefore, prevention of secondary infection by preventing entry of water into the ear canal is essential during this early healing phase. If conductive hearing loss remains after approximately 3 to 6 months, then surgical intervention can be planned. Persistent conductive hearing loss may be caused by tympanic membrane perforation; blood, brain, cholesteatoma, or CSF in the middle ear; and/or ossicular disruption. Otoscopic examination of these patients may be misleading. With the exception of tympanic membrane perforations, a healed drum and fracture step-off may be the only finding on otoscopic examination. The true condition is often hidden behind the tympanic membrane. Therefore, a high-resolution temporal bone CT should be part of the preoperative evaluation of these patients. This section focuses on ossicular pathology.

TABLE 63-5. Middle Ear Pathology Found in Temporal Bone Trauma Injury Incudostapedial joint separation Massive dislocation of the incus Fracture of the stapedial arch Epitympanic fixation of the ossicles Fracture of the malleus

Incidence (%) 82.3 54.1 30.0 25.0 11.0

Data from Hough JVD, Stuart WD: Middle ear injuries in skull trauma. Laryngoscope 78:899–937, 1968.

Ossicular pathology caused by temporal bone trauma can be divided into five categories: (1) incudostapedial (IS) joint separation, (2) massive dislocation of the incus, (3) fracture of the stapedial arch, (4) fracture of the malleus, and (5) epitympanic fixation of the ossicular chain. Table 63-5 summarizes the frequency of these ossicular conditions as reported by Hough and Stuart.70 Incudostapedial Joint Separation Separation of the incudostapedial joint is the most common ossicular injury encountered in temporal bone trauma. Mechanisms to account for this vulnerability were articulated by Hough and Stuart.70 The axes of the long process of the incus and of the stapes are perpendicular. When the middle ear is subjected to severe stress, the incus and stapes rotate around their separate axes. This produces a large torsion strain on the small surface area of the IS and dislodgment results. The incudomalleal (IM) joint is much less vulnerable. The short process of the incus and the head of the malleus are subject to much larger surface area to disperse the strain. Tetanic contraction of the tympanic muscles, particularly the stapedius, adds to the strain on the IS. Hough and Stuart70 reported a case in which the stapedius muscle avulsed the stapes capitulum from the crural arch. Repair of the IS joint depends on the degree of pathology. Simple anatomic realignment suffices if minimal separation is present. Interposition of cartilage helps to reinforce the joint. When larger separation is present, we commonly use a hydroxylapatite IS joint or titanium prosthesis for reconstruction. Massive Dislocation of the Incus Massive dislocation of the incus is a more severe injury caused by the same mechanisms that produce IS separation. The malleus and stapes are anchored to the tympanic membrane and labyrinthine capsule, respectively, whereas the incus is suspended by relatively weak ligamentous attachments and the IS and IM joints. Massive dislocation of the incus represents much more severe trauma than IS separation because all moorings of the incus are disrupted. Incus location after massive dislocation is variable, and reports have described bizarre locations. It can be subluxed into the middle ear, rotated 180 degrees in the epitympanum, thrown through the fracture line and extruded into the EAC, or missing entirely.71 Various successful reconstruction options are available. Options include repositioned sculpted incus autograft and several commercial incus replacement

Temporal Bone and Skull Base Trauma

prostheses constructed from homograft bone, titanium, or hydroxylapatite. Fracture of the Stapes The twisting torsion of the incus can damage the stapedial arch. The incus tends to torque the stapes superstructure perpendicular to the axis of the crural arch. The superstructure will fracture at it weakest point, its attachment to the footplate. This force is analogous to fracturing the stapes superstructure during a stapedectomy. If the footplate is fixed, a stapedectomy can reconstruct the defect. For a mobile footplate, a total ossicular replacement prosthesis is required. Various designs and materials are available. Fracture of the Malleus Malleal fracture or dislocation is relatively uncommon. The malleus is secured in place by attachments to the tympanic membrane, tensor tympani muscle, epitympanic ligaments, and the IM joint. These attachments make the malleus relatively resistant to traumatic injury. Very powerful forces are required to fracture or dislocate the malleus. Such powerful forces are usually sufficient to cause damage to the other ossicles. Therefore, it is relatively common to have total destruction of the ossicular chain associated with fracture dislocation of the malleus. These injuries are usually quite extensive and challenging to reconstruct. If the stapes superstructure is intact, a partial ossicular replacement prosthesis can successfully reconstruct the ossicular chain. Total ossicular prosthetic replacement is necessary if only the footplate is present. This situation is more difficult to reconstruct because the total ossicular prosthesis is prone to slippage at both the footplate and the tympanic membrane. Epitympanic Fixation Otic capsule–sparing fracture of the temporal bone usually causes a break in the roof of the epitympanum. Subsequently, the ossicular heads can become fixed in the epitympanum from a variety of pathologies. This includes hyperostotic bone, tympanosclerosis, post-traumatic epitympanic fibrosis, and collapse of the epitympanic roof or brain prolapse onto the ossicular heads. Surgical correction of these defects must be individualized for the specific condition. Herniation of brain or meningeal tissue usually requires combined middle fossa and tympanomastoid exposure for repair of the middle fossa floor. Epitympanic fibrosis and tympanosclerosis can be removed with a laser to free the ossicular heads if minimal fixation is present; however, refixation is common with extensive fibrosis or tympanosclerosis. Similarly, if minimal bony epitympanic fixation is present, the bony fixation can be removed with a rotating burr. For most cases of epitympanic fixation, we prefer to remove the incus, remove the malleus head, and reconstruct ossicular continuity with an incus replacement prosthesis. Ossicular Reconstruction Hough and Stuart70 explored 31 ears with traumatic ossicular discontinuity. Seventy-eight percent had closure

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of the preoperative air-bone gap to within 10 dB. Forty-five percent had total closure of the preoperative air-bone gap. One patient had a hearing loss greater than 10 dB. As expected, more severe ossicular pathology had less satisfying outcomes. Brodie and Thompson21 reported on 699 temporal bone fractures and only 5 patients received surgical treatment for conductive hearing loss. The average postoperative air-bone gap was 17.5 dB, although no details of the type of prosthesis were provided. With careful planning, successful reconstruction of conductive hearing loss after temporal bone fracture is very likely.

Sensorineural Hearing Loss Sensorineural hearing loss from temporal bone trauma can be caused by five separate mechanisms: (1) the disruption of the bony and membranous labyrinths from a fracture of the labyrinthine capsule, (2) a concussion injury to the inner ear occurring without evidence of labyrinthine fracture, (3) a blast with noise-induced hearing loss, (4) a perilymph fistula, and (5) injury to the auditory CNS. Otic capsule–disrupting fractures usually break through the anterior portion of the vestibule and the basal turn of the cochlea. Therefore, these fractures usually result in sudden, total hearing loss. They do not commonly cause fracture of the labyrinthine capsule. SNHL in otic capsule– sparing fractures is usually attributed to inner ear concussion. The neurotologist must note that both ears, not just the ear on the fractured side, are usually affected by inner ear concussion. Significant inner ear concussive injury can also occur in the absence of a fracture. Schuknecht72 reported audiologic findings of patients following head trauma. For patients who sustained hearing loss with evidence of temporal bone fracture, he noted the audiologic findings were very similar to noise-induced hearing loss. A high-frequency SNHL centered at 4000 Hz was frequently seen. In severe injury, all frequencies may be involved, with the greatest loss for the high frequencies. Schuknecht conjectured that a traveling pressure wave injured the cochlea. In a subsequent study, Schuknecht and colleagues73 studied the audiologic and histologic findings in cats subjected to head trauma. Similar to results in human audiograms, high-frequency SNHL was centered at 3000 Hz to 8000 Hz. Typically 15 dB to 40 dB of recovery occurred during the first 2 weeks following the trauma. Histology revealed damage to the outer hair cells in the basal cochlea for cats with the least severe injury. More severe injury resulted in damage to larger segments of the cochlea, disappearance of the organ of Corti, and secondary degeneration of the spiral ganglion cells and nerve fibers. Clinical, experimental, and histologic findings conclude that concussive cochlear damage is virtually identical to noise-induced cochlear injury. Hearing loss from peripheral auditory damage has been well documented. However, traumatic central auditory system injury is not well understood. Head trauma can cause edema, hemorrhage, or contusion of the brainstem and cerebrum and it is conceivable that derangement of the auditory CNS occurs. Unfortunately, most patients with severe CNS injury usually expire shortly after injury. Makishima and colleagues74 reported traumatic hearing loss in guinea pigs that had normal electrocochleography

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but elevated evoked responses from the inferior colliculus. Histology revealed degenerative changes in the cochlear nuclei and hemorrhage and laceration of the eighth nerve but preservation of the cochlea and organ of Corti. Clinically, central auditory hearing loss probably occurs, but its incidence is unknown. It is probably much less frequent than peripheral SNHL. Nonetheless, the headinjured patient who has an atypical or progressive SNHL may have a central auditory lesion. The neurotologist must be aware of this possibility. MRI will exclude a correctable structural lesion. For patients who have no residual serviceable hearing after temporal bone fractures, cochlear implantation offers an excellent rehabilitation option. In general, post–lingually deafened adults are traditionally ideal candidates for successful cochlear implantation. Their ability to perform well on standard postimplant test batteries75,76 and, more important, to integrate into the hearing world is well documented. In patients with temporal bone fracture, there are concerns of postfracture ganglion cell survival77 and a lack of patency of the scala tympani due to scarring and ossification.78 Camilleri and colleagues79 reported on successful implantation in six of seven patients with temporal bone fracture, with only one patient having ossification that required a drill-out procedure and precluded a full insertion. Of the six patients with full insertions, all had good hearing results. Cochlear implantation is a rehabilitative option for patients deafened by temporal bone fractures. High-resolution CT scans or MRI of the temporal bones should be performed to evaluate the patency of the cochlea.

VERTIGO Most patients experience some degree of balance disturbance after sustaining temporal bone trauma. Nonspecific dizziness is a core component of postconcussion syndrome. The symptoms of the postconcussive syndrome, which include headache, inability to concentrate, fatigue, and nonspecific dizziness, are usually quite bothersome to the patient and can persist for several months after the trauma. After excluding more serious neurotologic injury, treatment should be conservative and consist of nonsteroidal analgesics, gradual resumption of physical activity, and reassurance to the patient that no permanent neurologic injury is present. True vertigo, defined as an abnormal sense of motion or rotation, is caused by injury to the central or peripheral vestibular system. Establishing the presence of vertigo requires a complete evaluation and examination by the neurotologist. Electronystagmography (ENG) is useful in quantifying the vestibular deficit and may discriminate between central and peripheral vestibulopathy. Newer tests of vestibular function, such as vestibular autorotation tests and dynamic posturography, provide information similar to those obtained from ENG. CT and MRI aid in localizing the site of vestibulopathy. Evaluation of the vertiginous patient is a challenge to the neurotologist and treatment must be individualized rather than categorized into standard regimens. However, several patterns of posttraumatic vertigo exist. Recognition of these patterns and an understanding of their pathophysiology provide the

neurotologist with guidelines for evaluation and treatment of these patients. The most common presentation of post-traumatic vertigo is from concussive injury to the membranous labyrinth. This concussive injury to the membranous labyrinth is a completely separate clinical entity from postconcussive syndrome. Patients with postconcussive syndrome have nonspecific dizziness caused by a global CNS insult rather than a vestibular injury. Patients with membranous labyrinthine injury have true vertiginous symptoms resulting from a specific vestibular injury. Griffiths31 reported this vestibulopathy in 24% of patients with closed-head injury without temporal bone fracture. Typically, patients complain of vertigo with rapid head movement. CT will reveal an intact labyrinthine capsule. ENG is frequently normal. Fortunately, concussive vertigo is nearly always a self-limited problem. Only one patient had residual vertigo after 6 months in Griffiths’ series.31 Cupulolithiasis, as described by Schuknecht,80 is a more severe form of membranous labyrinthine injury. Degeneration of the utricle releases otoconia into the endolymph, which settle onto the most dependent part of the vestibular labyrinth, the posterior semicircular canal ampulla. The displaced otoconia add mass to the cupula, resulting in exaggerated momentum in response to motion. The symptoms of benign paroxysmal vertigo may not begin until months or years after the traumatic event. ENG classically shows a positive Dix-Hallpike provocative test with nystagmus showing delayed onset, limited duration, and fatigability. Treatment with particle-repositioning maneuvers is usually successful with this disease.81 Massive injury to the vestibular labyrinth, such as an otic capsule–disrupting fracture, causes a sudden, complete vestibular deficit. The patient has severe, debilitating vertigo, nausea, and emesis. Physical examination shows vigorous horizontal nystagmus with the fast component beating away from the affected ear. ENG documents the nystagmus and absent calorics from the injured ear. CT often demonstrates a fracture of the bony labyrinth. Treatment of these patients begins with vestibular suppressants (usually diazepam) and antiemetics during the acute vestibular denervation phase. The severe vertigo usually subsides over several days as central compensation commences. Patients are weaned from vestibular suppressants as they gradually increase physical activity. Physical therapy is usually necessary to assist the patient. Fortunately, most trauma patients are young and otherwise healthy, so compensation is usually complete without residual deficit. Complete compensation may take weeks or months. Elderly patients, who have less CNS adaptability, or patients with visual or proprioceptive loss may have lasting imbalance problems. Bilateral otic capsule–disrupting fractures can cause complete loss of vestibular function and the subsequent oscillopsia and disability. Long-term vestibular rehabilitation is required in these patients. Traumatic perilymph fistula (PLF) can complicate temporal bone trauma. Two mechanisms can cause a PLF: explosive and implosive. Explosive fistulae are caused by increased CSF pressure transmitted to the perilymph through the cochlear aqueduct, causing rupture of the round window membrane or, less common, the oval window. Implosive forces are caused by a sudden pressure wave

Temporal Bone and Skull Base Trauma

transmitted through the tympanic membrane. This could result in inward rupture of the round window membrane or inward subluxation of the stapedial footplate into the vestibule. The symptoms of PLF are classically described as fluctuating or progressive SNHL and vertigo. Patients may note worsening symptoms during physical exercise or while straining. A fistula test may be positive. However, symptoms of PLF are quite variable and PLF may even be asymptomatic. Emmet and Shea82 reported discovering 9 unsuspected, massive PLFs in 14 patients undergoing elective tympanoplasty following trauma. No patient in this series had an audiometric abnormality or vertiginous symptoms suggestive of PLF. The neurotologist must have a high degree of suspicion for PLF. Most patients with suspected PLF should be placed on bedrest and managed expectantly. If symptoms persist in spite of conservative therapy, exploratory tympanotomy should be considered. Defects of the oval window are the most common finding and patching with fascia will relieve the vestibular symptoms but rarely improve SNHL. Trauma-induced endolymphatic hydrops has been reported as a cause of post-traumatic vertigo.83 The onset of symptoms is usually delayed after the traumatic event for months or years. Symptoms usually include episodes of vertigo lasting for hours associated with fluctuant hearing loss, tinnitus, and aural fullness. The pathogenesis and incidence of post-traumatic endolymphatic hydrops are not well understood. It is, however, believed to comprise only about 1% of all patients with endolymphatic hydrops.83 Before diagnosis of post-traumatic endolymphatic hydrops, a physician must consider the possibility of PLF. The symptoms of these two diseases may be indistinguishable. Treatment of post-traumatic endolymphatic hydrops includes salt restriction, diuretics, and vestibular suppressants. Difficult cases may require endolymphatic sac surgery. Post-traumatic vertigo usually spontaneously resolves. Rarely, a patient may continue to have disabling vertigo in spite of all nonsurgical therapy. Such a patient may be a candidate for surgical intervention. If no hearing is present, then a labyrinthectomy can be performed. If hearing conservation is a goal, then a vestibular nerve section is the procedure of choice.

REFERENCES 1. Dahiya R, Keller JD, Litofsky NS, et al: Temporal bone fractures: Otic capsule sparing versus otic capsule violating clinical and radiographic considerations. J Trauma 47:1079–1083, 1999. 2. Nageris B, et al: Temporal bone fractures. Am J Emerg Med 12:211–214, 1995. 3. Virapongse C, Bhimani S, Sarwar M: Radiology of the abnormal ear. In Taveras JM, Ferrucci (eds.): Radiology: Diagnosis, Imaging, Intervention. Philadelphia, Lippincott, 1987. 4. Cannon CR, Jahrsdoerfer RA: Temporal bone fractures: Review of 90 cases. Arch Otolaryngol 109:285–288, 1983. 5. Tos M: Course of and sequelae to 248 petrosal fractures. Acta Otolaryngol 75:253–254, 1973. 6. Travis LW, Stalnaker RL, Melvin JW: Impact trauma of the human temporal bone. J Trauma 17:761–766, 1977. 7. Ghorayeb BY, Yeakley JW: Temporal bone fractures: Longitudinal or oblique? The case for oblique temporal bone fractures. Laryngoscope 102:129–134, 1992.

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8. Griffin JE, Altenau MM, Schaefer SD: Bilateral longitudinal temporal bone fractures: A retrospective review of seventeen cases. Laryngoscope 89:1432–1435, 1979. 9. Aguilar EA, et al: High-resolution CT scan of temporal bone fractures: Association of facial nerve paralysis with temporal bone fractures. Head Neck Surg 9:162–166, 1987. 10. Kelly KE, Tami TA: Temporal bone and skull base trauma. In Jackler RK, Brackmann DE (eds.): Neurotology. St. Louis, Mosby, 1994, pp 1127–1147. 11. Lathrop FD: Facial nerve surgery in the European theater of operations. Laryngoscope 56:665–676, 1946. 12. Hooper RE, Rubin RJ, Mahmood K: Gunshot injuries of the temporal bone. Arch Otolaryngol 96:433–440, 1972. 13. Byrnes DP, Crockhard HA, Gordon DS, Gleadhill CA: Penetrating craniocerebral missile injuries in the civil disturbances in Northern Ireland. Br J Surg 61:169–176, 1974. 14. Hagan WE, Tabb HG, Cox RH, Travis LW: Gunshot injury to the temporal bone: An analysis of thirty-five cases. Laryngoscope 89:1258–1272, 1979. 15. Holt GR, Kostohryz G: Wound ballistics of gun shot injuries to the head and neck. Arch Otolaryngol 109:313–318, 1983. 16. Duncan NO, Coker JN, Jenkins HA, Canalis RF: Gunshot of the temporal bone. Otolaryngol Head Neck Surg 94:47–55, 1986. 17. Perlman HB: Process of healing in injuries to the capsule of the labyrinth. Arch Otolaryngol 29:287–305, 1939. 18. Fredrickson JM, Griffith AW, Lindsay JR: Transverse fractures of the temporal bone. Arch Otolaryngol 78:770–784, 1963. 19. Ward OG: The histopathology of auditory and vestibular disorders in head trauma. Ann Otol Rhinol Laryngol 78:227–238, 1969. 20. Liu-Shindo M, Hawkins DB: Basilar skull fractures in children. Int J Pediatr Otolaryngol 17:109–117, 1989. 21. Brodie HA, Thompson TC: Management of complications of 820 temporal bone fractures. Amer J Otol 18:188–197, 1997. 22. Schapiro RS: Temporal bone fractures in children. Otolaryngol Head Neck Surg 87:323–329, 1979. 23. Lee D, Honrado C, Har-El G, Goldsmith A: Pediatric temporal bone fractures. Laryngoscope 108:816–821, 1998. 24. Williams WT, Ghorayeb B, Yeakley JW: Pediatric temporal bone fractures. Laryngoscope 102:600–603, 1992. 25. Zimmerman RA, et al: Magnetic resonance imaging in temporal bone fracture. Neuroradiol 29:246–251, 1987. 26. Corradino G, Wolf AL, Mirvis S, Joslyn J: Fractures of the clivus: Classification and clinical features. Neurosurgery 27:592–596, 1990. 27. House JW, Brackmann DE: Facial nerve grading system. Otolaryngol Head Neck Surg 93:146–147, 1985. 28. Grove WE: Skull fractures involving the ear. Laryngoscope 49:678–707, 1939. 29. Lambert PR, Brackmann DE: Facial paralysis in longitudinal temporal bone fractures: A review of 26 cases. Laryngoscope 94: 1022–1026, 1984. 30. Holland BA, Brant-Zawadzki M: High-resolution CT of temporal bone trauma. Am J Neuroradiol 5:291–295, 1984. 31. Griffiths MV: The incidence of auditory and vestibular concussion following minor head injury. J Laryngol Otol 93:253–265, 1979. 32. Johnson DW, et al: Temporal bone trauma: High-resolution computed tomographic evaluation. Radiology 151:411–415, 1984. 33. Kelly KE, Jackler RK, Killion WP: Diagnosis of septic sigmoid sinus thrombosis with magnetic resonance imaging. Otolaryngol Head Neck Surg 105:617–624, 1991. 34. Haberkamp TJ, Harvey SA, Daniels DL: The use of gadoliniumenhanced magnetic resonance imaging to determine lesion site in traumatic facial paralysis. Laryngoscope 100:1294–1300, 1990. 35. Haker LA, McCabe BF: Temporal bone fractures and facial nerve injury. Otolaryngol Clin North Am 7:425–431, 1974. 36. Fisch U: Facial paralysis in fractures of the petrous bone. Laryngoscope 84:2154–2154, 1974.

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37. Coker JN, Kendall DA, Jenkins HA, Alford BR: Traumatic intratemporal facial nerve injury: Management rationale for preservation of function. Otolaryngol Head Neck Surg 97:262–269, 1987. 38. Turner JWA: Facial palsy in closed head injuries. Lancet 246: 756–757, 1944. 39. McKennan KX, Chole RA: Post-traumatic cholesteatoma. Laryngoscope 99:779–782, 1989. 40. Chang CYJ, Cass SP: Management of facial injury due to temporal bone trauma. Amer J Otol 20:96–114, 1999. 41. Hough JVD, McGee M: Otologic trauma. In Paparella MM, Shumrick DA, Gluckman JL, Meyerhoff WL (eds.): Otolaryngology, 3rd ed. Philadelphia, WB Saunders, 1991, pp 1137–1160. 42. Kettel K: Peripheral facial palsy in fractures of temporal bone. Arch Otolaryngol 51:25–41, 1950. 43. May M: Trauma to the facial nerve. Otolaryngol Clin North Am 16:661–670, 1983. 44. May M, Hardin WB, Sullivan J, Wette R: Natural history of Bell’s palsy: The salivary flow test and other prognostic indicators. Laryngoscope 86:704–712, 1976. 45. Fisch U: Prognostic value of electrical tests in acute facial paralysis. Amer J Otol 5:494–498, 1984. 46. Essen E: The acute facial palsies. Berlin, Springer-Verlag, 1977, pp 41–87. 47. Sunderland S: Nerves and nerve injuries. London, Churchill Livingstone, 1978, pp 133–141. 48. Yanagihara Y: Transmastoid decompression of the facial nerve in temporal bone fracture. Otolaryngol Head Neck Surg 90:616–621, 1982. 49. Barrs DM: Facial nerve trauma: Optimal timing for repair. Laryngoscope 101:835–848, 1991. 50. Alford BR: Indications for surgical decompression of the facial nerve. Laryngoscope 81:620–635, 1971. 51. Jongkees LBW: On peripheral facial nerve paralysis. Arch Otolaryngol 95:317–323, 1972. 52. Adour KK, Boyajian JA, Kahn ZM, Schneider GS: Surgical and nonsurgical management of facial paralysis following closed head injury. Laryngoscope 87:380–390, 1977. 53. Fisch U, Lanser MJ: Facial nerve grafting. Otolaryngol Clin North Am 24:691–708, 1991. 54. May M, Klein SR: Facial nerve decompression complications. Laryngoscope 93:229–305, 1983. 55. Binns PM: Experimental studies of the facial nerve. Trans Am Acad Ophthalmol Otolaryngol 71:665–672, 1967. 56. Boyle WF: Experimental facial nerve paralysis decompression in experimental facial nerve paralysis in monkeys. Laryngoscope 77:1168–1178, 1967. 57. Boyle WF: Experimental facial nerve paralysis: An evaluation of surgical and medical therapy. Arch Otolaryngol 95:313–316, 1972. 58. Greer JA, Lambert EH, Cody DTR, Weiland LH: Experimental facial nerve paralysis: Influence of decompression. Ann Otol Rhinol Laryngol 83:582–595, 1974. 59. Yamamoto E, Fisch U: Experimentally induced facial nerve compression in cats. Acta Otolaryngol 79:390–395, 1975. 60. Mainan DJ, Kusik JF, Anderson AJ, Larson SJ: Non-operative management of traumatic facial paralysis following closed head injury. J Trauma 25:644–648, 1985. 61. Quaranta A, Campobasso G, Piazza F, Quaranta N, Salonna I: Facial nerve paralysis in temporal bone fractures: Outcomes

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after late decompression surgery. Acta Otolaryngol 121:652–655, 2001. Brawley BW, Kelly WA: Treatment of basilar skull fractures with and without cerebrospinal fluid fistulae. J Neurosurg 26:56–61, 1967. Nandapalan V, Watson ID, Swift AC: Beta-2-transferrin and cerebrospinal fluid rhinorrhea. Clin Otolaryngol 21:259–264, 1996. MacGee EE, Cauthen JC, Brackett CE: Meningitis following acute traumatic cerebrospinal fluid fistula. J Neurosurg 33:312–316, 1970. Pearson BW, Fredrickson JM: Trauma to the temporal bone. In English GM (ed.): Otolaryngology, 2nd ed. Philadelphia, JB Lippincott, 4(13):1–23. Klastersky J, Sadeghi M, Brihaye J: Antimicrobial prophylaxis in patients with rhinorrhea or otorrhea: A double blind study. Surg Neurol 6:111–114, 1976. Freeman J: Temporal bone fractures and cholesteatoma. Ann Otol Rhinol Laryngol 92:558–560, 1983. Tos M: Prognosis of hearing loss in temporal bone fractures. J Laryngol Otol 85:1147–1159, 1971. Griffin WL: A retrospective study of traumatic tympanic membrane perforations in a clinical practice. Laryngoscope 89:261–282, 1979. Hough JVD, Stuart WD: Middle ear injuries in skull trauma. Laryngoscope 78:899–937, 1968. Hough JVD: Restoration of hearing loss after head trauma. Ann Otol Rhinol Laryngol 78:210–226, 1969. Schuknecht HF: A clinical study of auditory damage following blows to the head. Ann Otol Rhinol Laryngol 59:331–358, 1950. Schuknecht HF, Neff WD, Perlman HB: An experimental study of auditory damage following blows to the head. Ann Otol Rhinol Laryngol 60:273–289, 1951. Makishima K, Sobel SG, Snow JB: Histopathologic correlates of otoneurologic manifestations following head trauma. Laryngoscope 86:1303–1314, 1976. Waltzman SB, Cohen NL, Shapiro WH: Use of multichannel cochlear implants in the congenitally and prelingually deaf population. Laryngoscope 102:395–399, 1992. Weston SC, Waltzman SB: Performance as a function of time: A study of three cochlear implant devices. Ann Otol Rhinol Laryngol (Suppl) 165:19–24, 1995. Nadol JB, Young YS, Glynn RJ: Survival of ganglion cells in profound sensorineural hearing loss: Implications for cochlear implantation. Ann Otol Rhinol Laryngol 98:411–416, 1989. Green JD, Shelton C, Brackmann DE: Surgical management of iatrogenic facial nerve injuries. Otolaryngol Head Neck Surg 111:606–610, 1994. Camilleri AE, Toner JG, Howarth KL, Hampton S, Ramsden RT: Cochlear implantation following temporal bone fracture. J Laryngol Otol 113:454–457, 1999. Schuknecht HF: Cupulolithiasis. Arch Otolaryngol 90:113–778, 1969. Parnes LS, Price-Jones RG: Particle repositioning maneuver for benign paroxysmal positional vertigo. Ann Otol Rhinol Laryngol 102:325–331, 1993. Emmet JR, Shea JJ: Traumatic perilymph fistula. Laryngoscope 90:1513–1520, 1980. Clark SK, Rees TS: Posttraumatic endolymphatic hydrops. Arch Otolaryngol 103:725–726, 1977.

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Outline Pathogenesis Clinical Presentation

A

Chapter

Temporal Bone Encephalocele

Radiology Surgical Treatment

n encephalocele is the presence of cranial contents beyond the normal confines of the skull.1,2 The term broadly includes meningocele (herniation of meninges and cerebrospinal fluid [CSF]), encephalomeningocele (herniation of brain and meninges), and hydroencephalomeningocele (herniation of cranial ventricles, brain, and meninges). It has also been called dural herniation, brain hernia, cerebral hernia, and brain prolapse. The incidence of encephalocele has been estimated to be 1 per 3000 to 10,000 live births. Cranial encephaloceles most commonly arise in the occipital region due to a defect in membranous ossification, with a 2.3 to 1 predilection for females. However, regional differences occur in the predominant site of the encephalocele. Occipital encephaloceles account for 80% to 90% of all encephaloceles in the Western Hemisphere, but occipital and frontobasal locations are equally common in the Eastern Hemisphere, including in Southeast Asia and Africa. The cranial base is an uncommon location for encephaloceles with only 5% of the lesions occurring at this site; in this category, the middle fossa is the most common location.3 Temporal bone encephaloceles are uncommon. Fewer than 150 cases have been reported in the last 40 years.4–10 They are characterized by herniation of meningeal or brain tissue into the cavities of the temporal bone. Also known as an endaural encephalocele, the aberrant tissue usually arises from the middle cranial fossa and, rarely, from the posterior cranial fossa.11,12 In 1902 Caboche13 described the first case of temporal bone encephalocele in the French literature. In the early part of the 20th century, transmastoid surgery for otogenic cerebral or cerebellar abscess and lateral sinus thrombosis accounted for the majority of the cases of brain hernia into the temporal bone. More recently, brain herniation into the tympanic cavity occurs mostly as a complication of mastoid surgery for infection. Other causes include congenital cranial base defects, spontaneous hernias, chronic ear infections, and trauma.14 Iurato and colleagues7 in 1989 reviewed 139 cases of mastoid and middle ear encephaloceles and found that 59% occurred as a complication of mastoid surgery; an additional 21% were spontaneous or idiopathic; 9% were a complication of chronic otitis media or chronic mastoiditis; and 9% followed trauma.

Anil K. Lalwani, MD

PATHOGENESIS Spontaneous temporal bone encephaloceles can be divided into two categories: congenital or idiopathic. Knowledge of the embryology of the temporal bone is necessary to understand how a congenital encephalocele may arise. The squamous portion of the temporal bone arises from the membranous bone of the root of the zygomatic process and begins intramembranous ossification from one ossification center around the eighth week of fetal life. The tympanic part of the temporal bone is derived from membranous bone and begins ossification at about the 9th to 10th week of fetal development; at birth it is an incomplete ring that is open superiorly. The petrous portion of the temporal bone, first preformed in cartilage, begins ossification from front to back around the sixth month of fetal life at 14 separate ossification centers. The mastoid portion of the temporal bone arises from the dorsal aspect of the petrous bone and does not begin ossification until 25 to 30 weeks’ gestation.15 Analogous to the occipital encephaloceles mentioned earlier, disturbance in the normal ossification of the temporal bone, especially the squamous and petrous portion, may lead to the formation of an encephalocele. The roof of the middle ear and mastoid is formed by the joining of the superior surface of the petrous bone with the medial extension of the caudal squamous portion of the temporal bone.16 The petrosquamous suture is formed by the dehiscence between the squamous and petrous bone prior to their fusion and is usually obliterated by 1 year of age, but fusion can be delayed. Persistence of the dehiscence due to growth abnormalities, radiation therapy, or chemotherapy may serve as a route for transmission of an encephalocele.17 Nontraumatic or spontaneous brain hernias that present later in life, without a prior history of surgery, trauma, or chronic ear infection, occur frequently. Age at presentation ranges from 6 to 72 years with a mean age of 50.45 years with a 12:15 male-to-female ratio.6 Multiple theories regarding the cause of spontaneous encephalocele have been promulgated. The presence of multiple tegmental defects along the floor of the middle fossa have been reported by several authors and is a plausible explanation for the origin of spontaneous temporal bone encephaloceles. Ahern and Thuleni18 noted a 6% incidence of multiple large defects 1089

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and a 21% incidence of small dehiscences; when present, the bone defects were bilaterally symmetrical. Kapur and Bangash19 reported a 34% incidence of bony defects in their sample of 50 temporal bones with 20% of the specimens having bilateral defects. None of their defects was associated with dural dehiscences. Lang20 found tegmental defects in 20% of 70 adult temporal bones examined. Ferguson and coworkers,21 in examining 27 preserved, dried temporal bones from India, discovered a 22% incidence of tegmen defects, with the majority having 4 to 10 defects per bone. Consistent with the finding of multiple bony defects within the same temporal bone, about 33% of the cases of spontaneous encephalocele have multiple sites of brain herniation.6 Bilateral spontaneous temporal bone encephalocele, as would be expected based on the temporal bone findings already mentioned, has also recently been reported.6 In these temporal bone studies, it was difficult to ascertain whether the defects were congenital or acquired through bone resorption or remodeling throughout the patient’s life. The skull base is normally pneumatized, and numerous areas of the temporal floor are critically thin. It is postulated that over time the trauma from pulsatile CSF pressure leads to bony defects and subsequent herniation of dural or cortical tissue. However, the incidence of spontaneous encephalocele is far less than the reported occurrence of tegmental bony defects. This discrepancy reinforces the observation that tegmental defect is necessary but not sufficient to cause brain/dural herniation without an associated dural deficiency. Others have suggested that increased intracranial pressure, aging, and low-grade inflammation may also contribute to bony and dural dehiscence.3,21 Aberrant arachnoid granulations of the temporal bone may be yet another causal factor in the formation of encephalocele and CSF fistula. Normally the arachnoid granulations protrude into the lumen of venous structures and are involved in resorption of CSF. In the anterior, middle, and posterior fossa dura, they are found within the periosteal bony plate associated with the paranasal sinuses and the mastoid air cells. Their incidence in the temporal bone has been estimated to be 22% in the floor of the middle fossa and 9% in the surface of the posterior fossa.22 They increase in size and complexity with age and physical activity due to direct transmission of CSF pressure through the arachnoid granulations. When not associated with venous structures and surrounded by bone, the arachnoid granulations enlarge by erosion and resorption of the adjacent bone. The presence or absence of bone erosion is directly correlated to the size of the arachnoid granulation. Gacek23 demonstrated in a temporal bone study that arachnoid granulations smaller than 3 mm2 (37% of the lesions) do not cause bone erosion, whereas osseous erosion and communication with the mastoid air cell system was common with arachnoid granulations larger than 3 mm2 (63% of the lesions). Radiologically, these lesions appear as small, rounded defects in the bony middle or posterior fossa plate. Possibly, the bony defects documented in earlier temporal bone studies represent bone erosion due to large arachnoid granulations. Iatrogenic complications of mastoid surgery for chronic ear infection is the most common cause of temporal bone encephalocele. Their incidence has increased in recent times due to the increased frequency of revision mastoid

surgery.24 The pathogenesis of iatrogenic encephalocele following mastoid surgery is well delineated. Dural exposure in isolation due to tegmental dehiscence at the time of mastoid surgery is insufficient to cause brain herniation; the dura is able to support the brain over large bony defects. This observation is confirmed by the frequent finding of exposed dura at the time of revision mastoid surgery without associated cerebral or meningeal hernia. Dural tear at the site of bony defect is a prerequisite for herniation of intracranial tissue.25 Dedo and Sooy26 noted that brain herniation may occur through a dural defect as small as 2 mm. Not infrequently, the dural tear and the associated CSF leak are unrecognized at the time of surgery. The encephalocele may develop within weeks or after many years following surgery. Largely a preventable complication, it behooves the otologic surgeon to avoid dural injury at sites of tegmental dehiscence and to practice caution during revision mastoid surgery. At the time of surgery, areas of exposed dura should be examined for breaks in integrity, and repair should be performed to prevent the complication of CSF otorrhea and brain herniation. Temporal bone encephalocele attributed to chronic otitis media with or without cholesteatoma likely arises as a result of bone resorption and dural injury due to chronic inflammation and enzymatic degradation. Cholesteatomas frequently erode the tegmen to expose dura; the exposed dura is often weak and granular in appearance because of infection. Pathogenesis of encephalocele due to trauma is well understood. The dura is tightly adherant at the skull base, especially in the young and the elderly, and fracture of the temporal bone is frequently associated with dural tear. The initial CSF otorhinorrhea usually resolves within 2 weeks, but the bony dehiscence at the fracture site may persist and enlarge. Simultaneous osseous and dural injury lead to either immediate or delayed temporal bone encephalocele.

CLINICAL PRESENTATION Clinical findings include intermittent or continuous CSF otorrhea or rhinorrhea, CSF masquerading as serous otitis media, conductive hearing loss, recurrent meningitis, headache, and, rarely, a mass behind the tympanic membrane (Fig. 64-1).27,28 Unusual presentations include expressive aphasia, temporal lobe seizures, and facial nerve weakness.29–31 Previous history of ear surgery, chronic otitis media, cholesteatoma, and trauma should be elicited. Serous-appearing middle ear effusion on otoscopy or clear otorrhea following myringotomy is the most common clinical finding at presentation. CSF otorhinorrhea associated with temporal bone encephalocele may be intermittent or continuous. Lesions of the temporal floor are usually associated with recurrent or transient leaks. The CSF fistula opens with a rise in the intracranial pressure and is closed by the weight of the overlying temporal lobe plugging the leak. Unlike the middle fossa floor, CSF drainage into the mastoid from posterior fossa plate defects is often continuous and profuse because they lack gravitational sealing of the fistula by intracranial contents. When a CSF leak is present, the flow may be increased by various maneuvers, including compression of the internal

Temporal Bone Encephalocele

Figure 64-1. Photomicrograph of the right tympanic membrane in a patient with temporal bone encephalocele. It demonstrates a posterior mesotympanic mass with radial blood vessels and appearance consistent with brain. The anterior tympanic membrane was normal in appearance. (Reprinted, with permission, from Lalwani AK, Jackler RK: Endaural encephalocele. Otolaryngol Head Neck Surg 106:309–310, 1992.)

jugular vein, the Valsalva maneuver, and placement of the patient in the supine position. Leaning forward may elicit CSF rhinorrhea when the tympanic membrane is intact. In patients with suspected CSF otorrhea or rhinorrhea, evaluation of the fluid for glucose, protein, and chloride is useful in confirming the diagnosis of CSF leak. A CSF glucose level of 60% of serum value, a protein concentration of less than 200 mg/dL, and a chloride greater than the serum concentration (normal serum value 99 to 107 mol/L) are indicative of CSF leak. Contemporary evaluation of suspected CSF otorhinorrhea includes identification of the protein β2-transferrin in the fluid.32 β2-Transferrin, produced by the neuraminidase activity in the brain, is found only in CSF and can be detected in quantities as small as 1 μL. Therefore, a definitive diagnosis of CSF otorhinorrhea can be made even in the presence of contaminating nasal mucous, saliva, or blood. Rauch has shown that electrophoretic assay of ironloaded transferrin can detect as little as 250 pg of protein and can identify heterogeneity in serum, CSF, and perilymph.33 Recent large studies have corroborated the initial enthusiasm regarding the diagnostic role of β2-transferrin analysis of fluid suggestive of CSF leak.34,35 In a retrospective review of 52 surgical cases of CSF leak, Zapalac and colleagues35 found 98% sensitivity for the transferrin assay. β2-Transferrin combined with radiologic imaging is a powerful tool for the diagnosis and localization of CSF otorrhea.35 A bluish gray mass in the external auditory canal, mastoid cavity, or behind an intact tympanic membrane may be seen on otoscopic examination28,36,37 The mass is soft to the touch, pedunculated or sessile, and characteristically pulsatile. The mass increases in size and is less pulsatile following maneuvers that raise intracranial pressure. Audiologic evaluation usually reveals a conductive hearing loss most likely caused by CSF in the middle ear or the mass effect of the herniated temporal lobe on the ossicles. The abnormal communication between the tympanic cleft and the cranial cavity serves as a route for retrograde spread of infection from the ear, which results in meningitis

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or brain abscess. Ferguson and coworkers21 reported that 36% of the 33 patients in their series with tegmen or posterior fossa defects developed meningitis; it was the presenting symptom in 24% of their patients. Tension pneumocephalus is an unusual presentation of temporal bone encephalocele.38 Air enters the cranial cavity via the bony or dural defect when the extracranial pressure exceeds the intracranial pressure and is unable to escape due to the one-way valve effect of the herniating tissue. As a result, a patient may present with focal neurologic signs, seizures, and progressive neurologic deterioration. Isolated case reports of iatrogenic tension pneumocephalus have been reported following insuffulation of air in the external auditory canal in patients with bony defects in the temporal bone.39,40 Histologically, the herniated brain tissue demonstrates cortical neural tissue with extensive gliosis, degenerative changes, and chronic inflammation. Macrophages are the predominant inflammatory cells. The surface of the encephalocele may be covered either with middle ear mucosa or modified glial cells.6,17 Occasionally, the pathologist may return with the diagnosis of neuroglial heterotopia of the middle ear or mastoid, suggesting an ectopic presence of brain tissue. Neuroglial heterotopia most likely represents acquired encephalocele.41,42 Radiographic or operative finding of continuity of the glial tissue with CNS will confirm this diagnosis because histology alone cannot distinguish encephalocele from a true (and rare) neuroglial heterotopia.

RADIOLOGY Plain film radiography and polytomography have been replaced by computerized tomography (CT) and magnetic resonance imaging (MRI). High-resolution CT scans in the coronal and axial planes are needed to define defects in the tegmen tympani or mastoideum and to identify soft tissue and fluid in the tympanic and mastoid cavities (Fig. 64-2). A CT scan is ideally suited for the study of the

Figure 64-2. Preoperative coronal CT image demonstrating soft tissue in mastoid cavities bilaterally (arrowheads) and dehiscence of temporal floor consistent with temporal bone encephalocele. The patient, a 21-year-old male with a history of cranial irradiation for childhood acute lymphocytic leukemia, presented with vague “echo” in the right ear with the finding of a middle ear mass; the patient was asymptomatic in the contralateral ear with normal otoscopic exam. (Reprinted, with permission, from Lalwani AK, Jackler RK, Harsh GR IV, Butt FYS: Bilateral temporal bone encephaloceles following cranial irradiation. J Neurosurg 79:596–599, 1993.)

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bony anatomy of the temporal bone; however, it is limited in its ability to distinguish between the variety of soft tissues. Three-dimensional CT of the temporal bone while providing better visual anatomy of the underlying pathology does not provide sufficient additional information to justify its additional cost.43 CT with intrathecal administration of Omnipaque, a low-osmolarity, nonionic, water-soluble contrast agent, is useful in opacifying the CSF and identifying the fistulous tract responsible for the CSF leak. MRI is far superior in delineating the nature of soft tissue and is required to differentiate herniated brain from fluid, cholesteatoma, cholesterol granuloma, and other lesions (Fig. 64-3).44 In addition, the availability of images in multiple planes with MRI is of significant value in precise

characterization of the anatomic defect. When CT scans suggest a tegmen defect, high-resolution MRI with 3-mm sections should be performed. MRI is ideal for determining the integrity of the overlying dura. Distortion of the gyri resulting from herniating temporal lobe into the temporal bone (“tear-drop” sign) on coronal CT or MRI scans strongly suggests an encephalocele.17 Shetty and colleagues has prospectively studied the sensitivity and specificity of high-resolution CT scanning and MRI/MRI cisternography in localizing defects in patients with suspected CSF rhinorrhea.45 Both modalities were extremely accurate in localizing the site of CSF leak and demonstrated a sensitivity and specificity of approximately 90%. Likewise, Zaplac and coworkers35 found that CT and MRI were highly effective (≈80% to 85%) in localizing sites of CSF leak.35 They recommended β2-transferrin assay for confirming CSF leak and radiologic imaging for localization of the site of leak.

SURGICAL TREATMENT

A

B Figure 64-3. A, Preoperative coronal T1-weighted MRI with gadolinium enhancement of patient presented in Figure 64-2 shows soft tissue herniating into the right mastoid cavity (arrowheads) from the middle fossa consistent with an encephalocele. B, Preoperative coronal T1-weighted MRI with gadolinium enhancement shows soft tissue that is contiguous with the temporal lobe herniating into the left mastoid cavity (arrowheads) as well. There is distortion of the temporal lobe and its gyri (tear-drop sign) that is highly suggestive of temporal lobe encephalocele. (Reprinted, with permission, from Lalwani AK, Jackler RK, Harsh GR IV, Butt FYS: Bilateral temporal bone encephaloceles following cranial irradiation. J Neurosurg 79:596–599, 1993.)

The temporal bone encephalocele can be repaired via a transmastoid approach (from below), via a middle fossa craniotomy (from above), or by a combined transmastoid/ middle fossa approach (Fig. 64-4). The transmastoid approach is ideal for small lesions involving the tegmen tympani, tegmen mastoideum, and posterior fossa defects.11,24,26,36,46–48 In the transmastoid approach, the herniated glial tissue is amputated with bipolar cautery, and the tegmen defect is repaired with bone or a composite cartilage-perichondrium graft. The use of synthetic material has largely been abandoned in repair of bony or dural defect. The mastoid cavity is obliterated with temporalis muscle or the Palva flap to reinforce the closure and to separate it from the mucosal envelope. The mastoid approach allows visualization of the middle and posterior fossa plates as well as the middle ear and the tympanic cavity. An added advantage is the avoidance of direct contact and injury to intracranial structures. The disadvantages of the mastoid approach include possible hearing loss from ossicular injury and limited anteromedial exposure to the petrous apex. Depending on the presence or absence of sensorineural hearing loss, lesions of the petrous apex may be reached via the subcochlear or transcochlear approach, respectively. The middle fossa approach is ideal for larger encephaloceles without ossicular involvement and provides excellent exposure of the tegmen plate. The middle fossa approach is also preferred for anteromedial defects, such as those toward the petrous apex that are difficult to approach via the mastoid. The repair of the dural defect can be performed either extradurally or intransdurally, or both ways. Dura should be reconstituted with a thick connective tissue graft, such as temporalis fascia, pericranium, and fascialata. Because soft tissue repairs alone may not prove durable, the tegmen defect is best repaired with a bone or cartilage graft. The bone graft may be obtained by harvesting the inner table of the middle fossa craniotomy bone flap. The superior portion of the temporalis muscle should be rotated to provide vascular covering for this free bone graft and to provide an additional tissue layer between the

Temporal Bone Encephalocele

A

B

C Figure 64-4. A, The temporal bone encephalocele with ossicular involvement and the recommended middle fossa craniotomy (dashed lines in the temporal squamosa) are illustrated. B, A three-layer repair of the temporal bone encephalocele, with a free temporalis fascia graft placed intradurally, the inner table of the middle fossa craniotomy bone flap placed extradurally along the middle fossa floor, and an inferiorly based temporalis muscle flap placed between the dura and the bone graft, is shown. C, The temporal bone flap is replaced and secured with a wire. (Reprinted, with permission, from Lalwani AK, Jackler RK, Harsh GR IV, Butt FYS: Bilateral temporal bone encephaloceles following cranial irradiation. J Neurosurg 79:596–599, 1993.)

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cranium and the mastoid cavity. Thus, there is a threelayer repair of the tegmen defect with a free temporalis fascia graft placed intradurally, the inner table of the middle fossa craniotomy bone flap placed extradurally along the middle fossa floor, and an inferiorly based temporalis muscle flap placed between the dura and the bone graft. This technique is uniformly efficacious in the treatment of temporal bone encephalocele. The disadvantages of the middle fossa approach are directly related to the craniotomy and the necessary manipulation of cortical (temporal lobe) and vascular (i.e., vein of Labbé) tissue. For large encephaloceles that impinge on the ossicles, the combined transmastoid/middle fossa approach is indicated to preserve the conductive mechanism of the middle ear (see Fig. 64-4).25,37,49–52 The combined approach provides the additional exposure needed to permit nontraumatic dissection of the ptotic brain tissue from the ossicular chain.17 The combined transmastoid/middle fossa approach provides excellent exposure from above and below, is highly reliable, and is associated with low risk of recurrence (Fig. 64-5). It is the method of choice of many surgeons for repair temporal bone encephalocele. More recently, endoscopic techniques have been introduced in skull base surgery to minimize trauma, increase exposure, and reduce morbidity. The use of the endoscope in pituitary surgery, repair of anterior cranial base lesions including CSF leaks, and posterior fossa arachnoid cysts have already been reported.53–58 Similarly, the primary or adjunctive use of the endoscope may be of

Chapter

65 Barry E. Hirsch, MD, FACS

Otogenic Skull Base Osteomyelitis Outline Introduction Nomenclature Etiology Diagnosis Adults Children Staging Imaging Technetium Gallium

INTRODUCTION Osteomyelitis of the skull base remains one of the more devastating infections encountered today. The potential morbidity and mortality of this aggressive infection warrants the clinician to have a high index of suspicion when formulating a differential diagnosis for otologic and skull base diseases. Malignant external otitis (MEO), a more localized form of skull base osteomyelitis (SBO), is often the source of this progressive infection. Otogenic skull base osteomyelitis typically begins with an invasive infection of the external auditory canal, which spreads to the periauricular soft tissue, cartilage, and bone. If left untreated, this infection could extend throughout the skull base, infratemporal fossa, parapharyngeal space, and nasopharynx and intracranially. It is necessary to exclude other pathologies in this area with similar symptoms or signs such as Wegener’s granulomatosis, carcinoma of the temporal bone and nasopharynx, metastatic lesions to the clivus, Paget’s disease, fibrous dysplasia, and basilar skull fractures.1 This chapter reviews the nomenclature, etiology, diagnosis, imaging, staging, complications, and treatment of MEO and SBO.

NOMENCLATURE The osseous skull base comprises the tympanic ring, mastoid, petrous, maxillary, sphenoid, and occipital bones. Osteomyelitis of the skull base describes an infection in the diploic cancellous bone; the outer or inner, or both, cortical tables and periosteum; the dura; the surrounding soft tissues, the major vessels, and the cranial nerves of the skull base. The infection usually originates in the external auditory canal. The original report by Meltzer and Kelemen in 1959 describes a case of pyocutaneous osteomyelitis of 1096

Computed Tomography Magnetic Resonance Imaging Complications Treatment Surgery Antibiotics Hyperbaric Oxygen Therapy Treatment Termination Summary

the temporal bone due to Bacillus pyocyaneus, known today as Pseudomonas aeruginosa.2 Chandler, in 1968, is credited with coining the term malignant external otitis (MEO), which has remained in the literature for three decades.3 The term malignant, used to emphasize the serious nature of this infection, generated some confusion regarding the presence of neoplastic cells. However, Chandler’s intentions have been conveyed throughout the literature and acknowledge the fact that neoplastic cells are not present. The reluctance to describe an infectious process as malignant has resulted in alternative terms such as progressive, fulminant, invasive, and necrotizing external otitis. In a paper titled “Malignant external otitis: A dangerous misnomer?” the authors express concern that the term does not convey the extent and import of the disease.4 Despite these misgivings, physicians in many subspecialties in medicine, such as otolaryngology, neurosurgery, infectious disease, radiology, internal and nuclear medicine, and family practice are familiar with the term and concept. The problem is recognizing the disease when present, prompting the appropriate evaluation and management. Necrotizing otitis externa (NOE) has been offered as an alternative term for malignant external otitis. However, NOE represents a more limited form of the infection, isolated to the skin and cartilage of the external auditory canal. Although this may manifest as a recalcitrant invasive infection, bone destruction does not necessarily exist. In addition, the organism recovered on culture is not routinely P. aeruginosa. Such cases can be caused by both Staphylococcus epidermidis and S. aureus.5 Osteomyelitis of the skull base, on the other hand, is too encompassing a term to describe the localized form of malignant otitis externa, limited to the auditory canal and infra-auricular soft tissue. Whether this infectious process should be called malignant otitis externa (MOE) or malignant external otitis (MEO) is a moot point. This term is well understood and until a better term is proposed,

Otogenic Skull Base Osteomyelitis

malignant external otitis will likely remain the descriptive phrase for this invasive infection.

ETIOLOGY In a comprehensive review of osteomyelitis, Waldvogel and colleagues note three fundamental factors relevant to the pathogenesis of osteomyelitis: a contiguous focus of infection, hematogenous seeding, and microvascular disease.6 Such is the situation with MEO. Chandler’s initial series in 1968 described 13 patients with this infection, identifying as the at-risk patient the elderly diabetic with known microvascular disease in poor glucose control. He proposed that the known microangiopathy of diabetics compromises the blood supply to affected areas, limiting effective immunologic responses and host resistance.3 Failure to eradicate the local soft tissue and osseous infection of the persistent organism provides continued bacterial seeding. In the microaerobic environment of the infra-auricular area, infratemporal fossa, and parapharyngeal space, soft tissue infection progresses to incorporate the periosteum and cortical bone of the skull base. The diploic cancellous space becomes involved both by direct extension of the cortical infection and by hematogenous spread. The invasion of an opportunistic organism into previously devitalized hypovascular tissue of the cartilaginous portion of the external auditory canal was proposed to be the basic pathogenic mechanism of MEO.7 However, a study by Bernheim and Sade refutes this conclusion.8 They found the major inflammatory process to be in the dermis that overlies the osseous portion of the canal. They feel this more medial location distinguishes MEO from routine otitis externa, which occurs in the cartilaginous portion of the canal. The most common factor identified in the majority of patients with MEO is the existence of diabetes mellitus. Ninety percent of the patients with MEO are diabetic and a majority are 60 years or older.9 Predisposing factors other than age and diabetes mellitus that have been identified include the patient’s use of a hearing aid, a history of chronic otitis media, leukemia, alcoholism, kernicterus, tuberculosis, and otitis related to swimming.10 In addition, the pathogenesis of MEO might occasionally be iatrogenic. In a retrospective study by Rubin, it was determined that 61.5% (8/13) of patients with MEO had unsterile tap water irrigation of their ears by a physician within 2 weeks of the onset of their symptoms. It was hypothesized that P. aeruginosa was forcibly introduced into the ear canal of a susceptible host (the elderly diabetic).11 The potential detrimental effects of aural irrigation contributing to the pathogenesis of MEO have been noted by other authors.12,13 Zikk and colleagues13 went so far as to suggest that cerumen not be removed by irrigation in diabetic or immunocompromised patients. P. aeruginosa is the organism characteristically associated with MEO and SBO in both adults and children. Other organisms have been identified as causative for osteomyelitis of the skull base. In these cases, the patient is often immunocompromised beyond that which is considered to exist with diabetes mellitus. Other organisms responsible for skull base osteomyelitis include Escherichia coli,14 Salmonella,15 Mycobacterium tuberculosis,16 Actinomyces,17 Aspergillus flavus,18

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Aspergillus fumigatus,19 Aspergillus niger,20 Scedosporium apiospermum,21 Malassezia sympodialis,22 Staphylococcus aureus,23 and Staphylococcus epidermidis.5 The patients in whom these organisms were recovered were compromised by diseases such as acute myelogenous leukemia and diabetes mellitus, or they were taking large doses of steroids and cytoxan for pemphigus vulgaris. Of interest, A. fumigatus causing malignant otitis externa has been reported in both immunocompetent and immunocompromised patients.19,24 Similarly, A. niger has caused skull base fungal osteomyelitis in an immunocompetent patient.20 Although P. aeruginosa has been identified in 99.2% of cases of MEO, it is still imperative to obtain a culture to satisfy diagnostic criteria, identify the organism, and determine sensitivities for appropriate treatment.25 The pathogenesis of skull base osteomyelitis classically has its origin from otitis externa. As outlined by Nadol,26 the infection begins in the epithelium of the external auditory canal and extends into the retromandibular fossa through the fissures of Santorini, into the parotid space, or through the tympanomastoid suture. The soft tissue infection at the skull base may involve the facial nerve, typically at the stylomastoid foramen. Once otogenic skull base osteomyelitis exists, it may spread in a variety of directions. The infection incorporates the mastoid tip and area around the jugular foramen with potential thrombosis of the sigmoid sinus and lower cranial nerve paresis. Transvenous sepsis and thrombosis may affect the lateral venous sinus and superior and inferior petrosal sinuses, with progressive osteomyelitis advancing into the petrous apex, middle fossa, base of the sphenoid, and clivus of the posterior fossa. Inadequate recognition and treatment permits continued extension to the contralateral temporal bone and skull base. Posterior spread into the occipital bone elicits nuchal pain and potential compromise of the contents of the posterior fossa. Disease can also extend anteriorly into the infratemporal fossa and facial bones. Malignant otitis externa can also occur following mastoidectomy. Patel and colleagues reported a 63-year-old non-insulin-dependent diabetic male who developed progressive otalgia 5 weeks after a canal wall-up mastoidectomy; there was also CT evidence of soft tissue inflammation across the skull base; weakness of cranial nerves VII, IX, X, and XII; erosion of the temporomandibular joint and temporal bone; and jugular thrombosis. The sedimentation rate was elevated to 90 mm/hr and Pseudomonas was cultured from the ear. He was successfully treated with 6 weeks of intravenous antibiotics and oral ciprofloxacin for an additional 3 months.27 Infections originating in anatomic sites other than the external auditory canal (e.g., the orbit, nasopharynx, and paranasal sinuses) are also responsible for the development of osteomyelitis of the skull base.15,28 The organisms responsible for skull base osteomyelitis of sinonasal origin include Pseudomonas, Aspergillus, Salmonella, Staphylococcus, and mucormycosis.29 These reports document the normal findings in the ear canal and temporal bone. Osteomyelitis of the skull base can originate from the temporomandibular joint (TMJ). The inflammatory reaction within and surrounding the TMJ can extend into the externa and middle ear and spread along the petrous and sphenoid bones in the infratemporal fossa.

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DIAGNOSIS Adults With infection of the external auditory canal being the most common source of skull base osteomyelitis, signs and symptoms usually originate from this area. Differentiating routine severe otitis externa (swimmer’s ear) from necrotizing otitis externa and malignant otitis externa can be difficult based on physical examination alone. The necessary critical information includes the age of the patient; possible precipitating factors; an otologic history; the presence, character, and temporal pattern of pain; the work-up to date (audiometry, culture, biopsy, blood tests, nucleotide and radiologic imaging); the type and duration of treatment to date; and whether a history of diabetes mellitus, a metabolic, hematologic, neoplastic, debilitating, or other immunocompromising disease exists. A comprehensive publication on otitis externa, differentiating MEO from other infections of the external ear is available for review.30 The diagnosis of malignant otitis externa is based on clinical and laboratory evidence along with heightened physician suspicion. Unfortunately, there are no absolute diagnostic criteria for establishing the diagnosis. The typical patient is an elderly diabetic who has not responded to usual local therapy and is complaining of persistent aural pain and discharge. The pain may be severe to excruciating, especially at night, and often awakens the patient from sleep.31 Changes in systemic symptoms and signs such as lethargy, emesis, blurred vision, altered mental status, aphasia, and mental confusion likely herald impending intracranial involvement.32 The physical examination shows evidence of otitis externa characterized by narrowing of the external auditory meatus with inflammation of the skin and often the tympanic membrane with granulation tissue epicentered at the osteocartilaginous junction. The tympanic membrane may be normal or manifest reduced mobility secondary to fluid in the middle ear.33 Cohen and Friedman state that the successful treatment of MEO is facilitated when the diagnosis is made early in its presentation.22 They propose diagnostic criteria for MEO by developing obligatory and occasional categories. The major obligatory criteria found in 100% of 107 cases reviewed in the English literature include pain, exudate, edema, granulation tissue, the presence of microabscesses when surgery was performed, a positive technetium-99m scan or the failure of local treatment after more than 1 week and, in 98% of the cases, the presence of P. aeruginosa. Minor occasional signs (those that appear only in some or most of the cases) are a positive CT scan or tomogram, older age (older than 55 years), cranial nerve involvement, diabetes mellitus, or other debilitating condition. Similarly, in a review of 50 patients with MEO, Bernheim and Sade summarize their definition of the disease: “A clinically severe external otitis which does not improve after 8 days of conservative treatment; pain, especially at night, which progresses; the mandatory presence of granulation tissue, usually over the base of the external auditory canal; a culture of Pseudomonas pyocyanea (aeruginosa); a positive temporal bone scan; and, frequently, the presence of diabetes mellitus.”8 Osteomyelitis of the skull base should be suspected in patients experiencing severe, unrelenting otalgia and

otorrhea despite treatment with topical and oral antibiotics. As mentioned, the infection typically is caused by Pseudomonas in an immunocompromised patient. The disease can also occur in an immunocompetent patient and from a fungal organism. Fungal infection more often is associated with neutropenia and alteration of the normal bacterial flora as a result of prolonged use of antibiotics. The diagnostic criteria of otomycotic skull base osteomyelitis should include not only a positive culture of the causative fungal organism but histopathologic evidence of invasive infection. Physical examination may include a perforation in the tympanic membrane, which appears pale and necrotic. Along with fungal hyphae identified in a biopsy or inflammatory debris, the presence of calcium oxalate birefringent crystals has been frequently noted with A. niger infection.20 Calcium oxalate production has been noted in invasive fungal infections in other areas, such as the lung.34 Aspergillus species accounts for the most common organism encountered with fungal malignant otitis externa. Fungal MEO is most common in patients with end-stage AIDS and hematologic malignancies. Granulation tissue is not as prevalent as in bacterial infections. Furthermore, the infectious process often starts in the middle ear and mastoid air cells, as opposed to the external auditory canal.21 The facial nerve is often the first cranial nerve to become involved by this infection. The site of the lesion is typically the soft tissue of the infra-aurical space surrounding the stylomastoid foramen. The other potential site of pathologic evidence is along the fallopian canal. Nadol identified a normal horizontal portion of the facial nerve with degeneration occurring in the descending portion in an area of active osteomyelitis of the mastoid tip.26 It has also been shown that round cell infiltration of the facial nerve can spread from the middle ear to the fundus of the internal auditory canal.35 A review of four patients infected with Aspergillus MEO revealed that all developed facial paralysis during the course of their disease.36 Whether this reflects the delay in identifying the organism or a truly more virulent infection is unclear. The concern for facial nerve involvement is not just the functional and psychological effects patients experience, but the implication that advanced infection exists. Chandler originally pointed out the significant mortality associated with facial nerve paralysis.37 The inner ear appears to be relatively resistant to gross extension of infection from the middle ear. Signs and symptoms of high-frequency hearing loss and dizziness can be elicited from patients with MEO. Reactive inflammation may be the source of homogeneous eosinophilic material found in the perilymphatic space, causing such finding and complaints.35 However, Nadol showed the otic capsule and membranous labyrinth to be quite resistant to the suppurative process, noting absence of a purulent exudate despite the presence of extensive temporal bone osteomyelitis and petrous apicitis.26 Culture and sensitivities for aerobic and fungal organisms and Mycobacterium tuberculosis is necessary. When involved, a biopsy of the external auditory meatus is performed both to rule out malignancy and to confirm that the histopathology is that of acute and chronic inflammation. The pathologist should also be alerted to examine the specimen for invasive hyphae. Finding a malignant lesion does not rule out MEO in that both processes can coexist. It can be argued that

Otogenic Skull Base Osteomyelitis

superinfection can be present in the face of malignant and necrotic tissue. However, it has been shown that considerable subjective and objective improvement can be achieved in patients with otologic cancer who are diagnosed with, and treated for, MEO. Resolution of pain and clinical findings with lowering of the sedimentation rate has occurred when both diagnoses exist following MEO treatment despite progression of their malignant lesion.38 In the absence of otologic complaints and findings, osteomyelitis of the skull base can be difficult to diagnose. Isolated case reports have been published that review patients diagnosed with skull base osteomyelitis without a history of infection in the ear and with normal findings on otologic examination and imaging.1,39 Consistent with their presenting history is the complaint of deep pain and headaches. The clinician must also be aware of any history of MEO, despite its having been “successfully” treated. The classic presentation of osteomyelitis of the skull base is a patient who has presumably been treated for MEO or acute otitis media with mastoiditis and leaves the hospital completely asymptomatic only to return 4 to 7 weeks later with the onset of low-grade fever, malaise, and a unilateral unremitting headache requiring narcotic analgesics. In addition, it has been reported that skull base osteomyelitis has developed nearly 1 year after resolution of MEO.28

Children Malignant external otitis is not unique to elderly diabetic patients. Though not common, a few cases have been reported in the pediatric population.40 The first cases of MEO in children were published in 1976 by Joachims.41 Both a 2-year-old with various medical problems and a 7-month-old with recurrent bronchopneumonia had cultures of P. aeruginosa obtained from the ear and developed facial paralysis early in their course. However, similar to adults, the causative agent of MEO in children is not always P. aeruginosa. Coser identified Proteus mirabilis in one of the two infants in a study.42 These 5- and 6-monthold infants were in poor health, undernourished, and anemic. In contrast to adults, most children with MEO do not have diabetes mellitus but they are immunocompromised in some fashion in order for this opportunistic infection to take hold. Disorders other than diabetes that have been associated with MEO in children include anemia, leukemia, malnutrition, solid tumors, Stevens-Johnson syndrome, immune globulin deficiency, and genetic agranulocytosis.40,43,44 In the adolescent age group, a pattern similar to that of adults is seen. They are usually healthy children with type 1 diabetes. In contrast to adults, complete facial paralysis is an early presenting sign in adolescents with MEO and often it is permanent.44 Malignant external otitis in children usually involves the tympanic membrane, middle ear, and mastoid. It was proposed that the more medial location of the bony cartilaginous junction in the infant and child accounts for earlier compromise of the facial nerve and mastoiditis.44 The limited development of the mastoid and tympanic ring in the child makes radiographic diagnosis in children more difficult. The CT scan may not be helpful in identifying bone destruction. Thus, modalities other than CT scan are necessary to confirm the diagnosis of MEO.

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The presentation of children with skull base osteomyelitis, in contrast to adults, is often more rapid with early appearance of constitutional symptoms of severe illness, fever, and leukocytosis. Adults present with a more insidious course of progressive, unrelenting pain, otorrhea, and inflammatory changes in the external auditory canal when of otogenic origin.45

STAGING Having a staging system for osteomyelitis of the skull base would alert the clinician that certain diagnostic tests are necessary to determine the presence and extent of disease. As mentioned, a swab and/or tissue culture with the patient who is not receiving topical and systemic antibiotics will identify the causative organism and its sensitivities. Baseline computed tomography and radionuclide scans might help to differentiate NOE from MEO and SBO. Gallium scanning identifies inflammation if immunocompetent white cells are present and functioning. The technetium bone scan reflects increased osteoclastic activity, which indicate osteitis and osteomyelitis. A three-level staging was proposed by Benecke.46 Stage I, or necrotizing otitis externa, has disease limited to the soft tissue and does not involve bone. Stage II disease describes MEO where disease is limited to the mastoid and is the earliest form of SBO. Both gallium and technetium scans are positive. Stage III disease is extensive SBO with markedly positive gallium and technetium scans. This extensive infection could involve the occiput, infratemporal fossa, sphenoid bone, and clivus across the skull base with extension to the contralateral temporal bone.47 Another staging system, proposed by Davis and colleagues, also categorizes patients into three stages but based on clinical manifestations and prognosis.9 Stage I describes infection of the ear and contiguous soft tissue with deep pain with or without facial paralysis. Since contemporary antipseudomonal drugs are efficacious when given early and for the appropriate length of time, these investigators feel that facial paralysis, without other cranial nerve deficits, does not worsen prognosis. Stage II is defined as extension of the infection to include osteitis of the skull base or multiple cranial neuropathies. Stage III entails intracranial involvement including meningitis, epidural empyema, subdural empyema, or brain abscess. Kraus and colleagues propose a third staging system. They suggest clinical staging to include three categories: (I) MEO limited to the external auditory canal and mastoid air cells, (II) skull base osteomyelitis with cranial nerve involvement, and (III) extension to the brain or meninges.48

IMAGING Radiographic and radionuclide imaging play an important role in evaluating, staging, and managing MEO and SBO. Sequential imaging is critical in establishing the diagnosis, determining the extent of disease, monitoring the efficacy of treatment, and determining the duration and end point of therapy. Each method has distinct advantages and limitations that should be understood by the treating physician.

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These imaging modalities include technetium (Tc-99m), gallium (Ga 67), indium (In-111), computed tomography (CT), and magnetic resonance imaging (MRI).

Technetium The technetium scan provides a sensitive method of identifying osteoblastic activity in osteomyelitis. The bone scan response in osteomyelitis can be positive as early as 24 hours following disease onset. Though the technetium scan can be most helpful in identifying osteomyelitis, its utility to determine the efficacy and duration of therapy is limited. Osteoneogenesis is a continuing process, reflected by ongoing osteoblastic activity. Despite resolution of both the symptoms and clinical findings of MEO, the technetium bone scan can remain positive indefinitely.49 In addition, just as with many of the other imaging modalities, a positive technetium scan is not specific for osteomyelitis. Pathologic processes such as malignancy, temporomandibular joint disorders, bone dysplasia, and bone fractures could also depict osteoblastic activity.49 In fact, positive results of technetium scans have been demonstrated in 9 of 12 diabetic and nondiabetic patients diagnosed with severe otitis externa, treated with topical antibiotic drops alone.50 Thus, this method of imaging is sensitive for identifying processes incorporating bone turnover but fails in its lack of specificity for diagnosing MEO. Knowing that a positive scan can be demonstrated in severe otitis externa may impede the physician’s determination of which patient likely has MEO and should receive aggressive and prolonged medical therapy. An advocated application of the technetium scan assisting in the diagnosis of osteomyelitis is blood pool scintigraphy. Following intravenous administration of technetium Tc-99m methylene diphosphonate (99m Tc-MDP), immediate scanning may demonstrate areas of hyperemia. Blood pool scintigraphy has been promoted to have specifically positive results in cases of osteomyelitis or infection of the surrounding soft tissue. For example, results of this method of imaging would be positive in cases of cellulitis, however, the routine bone scan obtained 2 hours after intravenous infusion would not have positive results unless osteoblastic activity is present, indicating a process beyond soft tissue inflammation. In addition, the authors suggest that a positive result of a blood pool scan would assist in distinguishing MEO from malignancy.51 The pool phase image continues to remain positive as long as there is a significant hyperemia of repair as well.52 Technetium scanning recorded within 4 hours after administration of 99mTcMDP will likely demonstrate both soft tissue and bone uptake. Scan acquisition 20 to 24 hours after the tracer is infused reflects bone involvement and identifies osteomyelitis. Another shortcoming of the technetium scan is the fact that it is anatomically imprecise. Increased uptake can be shown to enhance the general area of the temporal bone and skull base involved with osteomyelitis; however, specific sites are not defined as they are with bone and soft tissue algorithms available with computed tomography. Unlike the CT scan, radionuclide imaging cannot show subtle changes in the progression or resolution of disease.53

Despite these limitations, technetium scanning does provide early recognition of skull base osteomyelitis. In order for computed tomography to demonstrate osseous changes, it has been estimated that 30% to 50% demineralization must be present to exhibit lytic lesions.52 However, once abnormalities are detected, the CT scan, unlike the technetium scan, provides a means of monitoring soft tissue inflammation and subtle changes in bone density.54

Gallium Gallium 67 citrate is a radionuclide that is bound by granulocytes and accumulates in areas where the inflammatory process is active. Gallium binds to other rapidly dividing cells including malignant and osteoblastic cells.49 Similar to the technetium scan, this method of imaging is sensitive for identifying infection and inflammation, but like technetium, it has relatively poor anatomic resolution. Differentiating local ear canal and mastoid disease from central skull base and nasopharyngeal disease may be impossible.55 Another radionuclide is indium-111, which is mixed with the patient’s extracted blood and reinfused. The In111-labeled white blood cells are thought to be more specific in identifying inflammation by a factor of two. However, the additional specificity with this method of imaging does not outweigh the heightened sensitivity of gallium in detecting osteomyelitis. Though both the gallium and technetium scans are very sensitive in detecting inflammation and osteomyelitis, the results of the latter test are available much more rapidly. The protocol often employed in technetium bone imaging has scintigraphy recordings taken 2 to 4 hours after injection. This is in contrast to gallium scintigraphy, which is imaged at 24 and 48 hours following the injection.56 Quantitative technetium bone scan and gallium scintigraphy can differentiate malignant otitis externa from severe external otitis. A ratio is calculated comparing the counts from the involved side to those from the normal side. Criteria have been proposed for delineating the parameters for these ratios. Uri and colleagues report that the lesion-to-nonlesion ratios of greater than 1.5 on bone scintigraphy and 1.3 on gallium scintigraphy are indicative of MEO.57 These authors encourage the use of quantitative bone scintigraphy to establish the diagnosis of MEO since it was quicker to perform. A newer technique for identifying concurrent inflammation and osteomyelitis uses a multidetector single-photonemission computed tomography (SPECT) system that allows simultaneous acquisition of dual radiotracers. It can incorporate detection of low-photon emission properties of In-111 WBC scintigraphy along with the higher energy of 99mTc-MDP bone SPECT. It is more difficult with SPECT to identify, interpret, and follow skull base osteomyelitis that occurs postoperatively because of the iatrogenic soft tissue and bony changes. Using the combination In-111 and Tc-99m SPECT scanning method provides an effective way to evaluate and manage cranial osteomyelitis in this setting.58 The limitation of In-111 white blood cell scintigraphy is the relatively high false-negative results obtained after treatment is under way. This method of monitoring may not be reliable for determining termination of treatment.59

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Despite the seemingly prevalent recommendation that a normal gallium scan be the end-point determination for duration of therapy, clinicians should be aware of numerous reports documenting recurrent or persistent disease in the face of a normal gallium study.48,60,61

Computed Tomography Opacification of the mastoid air cells defines radiologic mastoiditis though not necessarily clinical mastoiditis. This finding on plane films or computed tomography does not serve as diagnostic fulfillment for MEO. It has been shown that routine otitis externa (canal infection with P. aeruginosa resolving within 2 weeks of topical treatment) may exhibit clouding of the mastoid.62 The high resolution of the CT scan permits early detection of subtle central skull base erosion. Involvement of the parapharyngeal, infratemporal, and subtemporal spaces and nasopharynx can also be accurately demonstrated. This is illustrated by the images obtained from a 66-year-old nondiabetic male with right chronic otitis media and facial paresis. He underwent a radical mastoidectomy, facial nerve decompression, and transcochlear partial petrous apicectomy for symptoms of a draining ear, deep retroorbital pain, and facial paresis (similar to Gradenigo’s syndrome except there was no lateral rectus palsy). Despite intravenous antibiotics, symptoms persisted. Figure 65-1 shows the bone algorithm image demonstrating the surgical defect and cortical erosion of the inner table of the clivus. Dural thickening at the site of bone erosion is shown in Figure 65-2. The three-dimensional reconstructed image demonstrating the infectious bony process in the petrous apex and midclivus is revealed in Figure 65-3. Rubin and colleagues evaluated the utility of CT imaging in patients with MEO and found that nonspecific findings such as external auditory canal soft tissue density and

Figure 65-1. CT scan, bone window algorithm, demonstrating right petrous apex and clivus SBO. The arrow identifies inner table cortical erosion at the clivus.

Figure 65-2. CT scan, soft tissue algorithm, demonstrating inflammatory process with dural thickening at petrous apex and clivus (arrow).

fluid in the middle ear and mastoid were routinely present. More specific findings including bone erosion, obliteration of fat planes beneath the temporal bone, parapharyngeal space involvement, disease in the masticator space, mass effect in the nasopharynx, clivus erosion, and intracranial extension were more ominous.63 They note that resolution of infra- and subtemporal soft tissue abnormalities disappears or substantially improves within several months following antibiotic therapy. Using the CT scan to determine when therapy can be terminated is limited because of the persistence of residual bony radiographic abnormalities. Despite complete clinical resolution, CT can demonstrate

Figure 65-3. Three-dimensional reconstruction of another patient showing area of left skull base involved with osteomyelitis (arrow).

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persistent abnormal findings for 1 to 10 years in follow-up.55 However, having a repeat CT scan at the conclusion of antibiotic therapy provides an objective baseline image on which to base comparison should symptoms recur. The physician can use CT to make the diagnosis, determine the extent of the infection, exclude progression, and identify resolution of soft tissue changes in the inflammatory process.63

Magnetic Resonance Imaging The strengths of magnetic resonance imaging are the sensitivity in detecting changes in the mucosa of the middle ear and mastoid air cells and the status of the soft tissue of the ear canal and skull base. Involvement of the dura can readily be demonstrated using contrast-enhanced imaging. In areas containing bone or fatty marrow within the calvaria and skull base, MRI is very useful in detecting evidence of inflammation. A bright signal on T1 imaging exists when fat or marrow is present. An enhanced scan with fat saturation sequencing is necessary to eliminate the signal from fat and show evidence of increased contrast uptake within the bone. Unlike CT scanning, MRI cannot identify bone erosion. CT imaging can accurately demonstrate soft tissue inflammatory changes in the external auditory canal, bone changes to the tympanic ring, and extension into the middle ear space and mastoid air cells. In patients who have not undergone surgery, MRI and technetium bone SPECT are the most sensitive techniques for the detection of skull base osteomyelitis, especially when bone marrow is present.58 In summary, various imaging modalities are available to both assist in establishing the diagnosis of MEO and SBO and monitor therapy so as to help determine when treatment may be discontinued. The technetium, CT, and MRI scans are initially useful in identifying soft tissue inflammation and bone involvement. CT scanning readily demonstrates bone erosion and significant demineralization and is the only method to provide accurate detail of the bony anatomy. In order for an MRI to provide useful information regarding bone involvement, the cancellous or medullary bone needs to contain fat or marrow, which harbors the inflammatory process. The CT and MRI remain valuable in monitoring resolution of soft tissue changes. Unfortunately, the technetium scan continues to manifest persistent uptake since bone remodeling is a long-term ongoing process. The gallium 67 citrate scan, though also nonspecific, usually reverts to normal when the inflammation has ceased.64 MRI and gallium scans, and to a lesser degree CT scans, are the imaging modalities useful in monitoring the progression and resolution of the infection.

COMPLICATIONS Cranial nerve neuropathy is the most common noniatrogenic complication with MEO and SBO. P. aeruginosa produces destructive enzymes and exotoxins, promoting tissue necrosis and reversible neurotoxicity.9 Besides the extensive infection that exists with MEO and skull base osteomyelitis, complications other than paralysis of the facial nerve can occur. The jugular foramen (Vernet’s) syndrome, which affects cranial nerves IX, X, and XI,

compromises phonation, swallowing, and protection of the tracheobronchial tree, predisposing to further morbidity from aspiration pneumonia and inanition. Other complications that have been identified include paralysis of cranial nerves III, V, and VI, cerebral abscesses, lateral sinus thrombosis, and death.42 The high mortality historically associated with MEO is exemplified in the original report by Chandler, where 7 of the 13 patients died.3 However, the mortality rate remained high in patients with multiple cranial neuropathies despite optimal antimicrobial therapy. More recent reports with appropriate antibiotic therapy show cure rates to be 80% to 100%.65 Adjuvant treatment with hyperbaric oxygen, reviewed later in the chapter, has further reduced the mortality rate. In untreated or advanced cases of SBO, death is usually caused by meningitis, cerebritis, inanition, pulmonary aspiration, vascular thrombosis or bleed (CVA), or subarachnoid bleed.9,44,65 In addition, medical therapy with prolonged ototoxic and nephrotoxic medications can significantly contribute to patient morbidity and mortality.66

TREATMENT The complete management of MEO and skull base osteomyelitis consists of establishing the diagnosis, determining the extent of involvement, operating when indicated, and providing antibiotic therapy along with adjuvant therapy for the appropriate length of time based on resolution of the infectious process. It is also critical to correct any metabolic abnormalities that coexist. Tighter glucose regulation is usually achieved as the infection is brought under control.

Surgery The role of surgery in management of MEO and SBO is not well defined. Beyond a biopsy, as previously mentioned, there is controversy as to whether surgical intervention is warranted and efficacious. Chandler originally reported on 13 patients, who all had surgical procedures. Based on the methods of treatment and imaging techniques available at that time, he concluded that surgical intervention was necessary in all cases of MEO.3 Davis and colleagues indicated that local debridement of necrotic tissue and drainage of abscesses are an integral part of the standard treatment of MEO.9 Nine of 16 reported cases had surgical debridement or formal tympanomastoid procedures. Farrior proposed planned surgical debridement for persistent pain or failure of the granulation tissue to heal after 2 weeks of intravenous antibiotics.67 The types of procedures he reported in 8 of 10 patients surgically treated included ear canal debridement, postauricular hypotympanotomy with removal of the floor of the ear canal, modified radical mastoidectomy, radical mastoidectomy with partial petrous apicectomy, and embolectomy for jugular vein thrombosis. Raines and Schindler directly addressed the surgical management of recalcitrant malignant external otitis.68 They advocated radical surgery if after 2 weeks of treatment there was persistence of granulation tissue in the external auditory canal, new onset of cranial neuropathies, or other signs or symptoms of active infection. The existence of any one of

Otogenic Skull Base Osteomyelitis

these findings justified surgical intervention. They contended that a subtemporal abscess likely existed and should aggressively be drained. It is agreed that drainage of an abscess is appropriate; however, these recommendations have been tempered over time. Concern exists that surgery may enhance MEO and SBO by opening up fascial spaces and new tissue planes for the infection to spread. Currently, imaging techniques are available that provide the physician with more accurate methods of monitoring the status of the infection, obviating the need for empiric surgical therapy. Operative intervention is usually limited to surgical debridement of persistent granulation tissue, bony sequestra, abscesses, and necrotic cartilage.69

Antibiotics Since the original series report by Chandler in 1968,3 prolonged antibiotic therapy has been the principal means of therapy. At that time, gentamicin was advocated as the treatment of choice. Carbenicillin became available in 1969, providing the ability to treat with synergistic antibiotics. Chandler subsequently agreed that combination therapy would likely prevent the development of Pseudomonas resistance to a single drug.37 The combination of an aminoglycoside (gentamicin, tobramycin, amikacin) and a semisynthetic penicillin (carbenicillin, piperacillin, ticarcillin, and azlocillin) became the standard against which subsequent treatment protocols were compared. Over the past few years, newer antibiotics effective against Pseudomonas have become available. In particular, third-generation cephalosporins have successfully been used as single-agent therapy. Ceftazidime (Fortaz, Tazicef, Tazidime), moxalactam (Moxam), and cefsulodin have been advocated as an alternative method of treatment by various investigators.65,70–72 Moxalactam is no longer approved due to induced bleeding dyscrasias. The use of cefsulodin was reported in 1987; however, this formulation is not FDA approved.71 Ceftazidime, which is available, is effective against Pseudomonas. Successful treatment with ceftazidime was achieved in 11 of 12 patients reported by Johnson and Ramphal.65 Kimmelman and Lucente contend ceftazidime has distinct advantages over the aminoglycoside/semisynthetic penicillin combination in that the efficacy is the same if not better, there is less toxicity, and it has a simpler administration schedule.70 Despite admonition against single-drug therapy,48 these authors have reported successful series of patients treated with ceftazidime alone. A new fourth generation of cephalosporins has been developed since the first edition of this textbook. Cefepime provides effective bactericidal activity against Pseudomonas. This medication, given intravenously twice daily, is an excellent alternative to the aminoglycosides or quinolones, especially when antimicrobial resistance is present or develops. Another antibiotic designated as a carbapenem, that cannot be classified with the previously described formulations, is imipenem. Aztreonam can also be prescribed to treat difficult gram-negative infections, such as Pseudomonas, when there is resistance to more conventional antimicrobials. The decision regarding antibiotic therapy is further confounded by how the medication should be delivered (i.e., parenteral or oral), for what duration, and the method of monitoring used to determine when curative therapy

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has been achieved. It is generally agreed that 4 weeks of antibiotic treatment is the minimum duration of therapy effective in eradicating MEO, especially when the infection is limited to the soft tissue of the external ear and periosteum.73 Skull base osteomyelitis with infection in the soft tissues of the infratemporal fossa or intracranial extension requires more intensive and prolonged antibiotic therapy up to 17 weeks.46 This incurs numerous consequences and risks secondary to the need for prolonged venous access with frequent dosing and careful monitoring of drug levels, hearing thresholds, and renal function. The availability of oral agents effective against P. aeruginosa has significantly altered the method of treatment and, likely, the incidence of MEO. The conventional management of MEO consisted of 4 to 12 weeks of combination intravenous antibiotic therapy with an antipseudomonal beta-lactam agent and an aminoglycoside. Prolonged intravenous administration incurs potential complications and morbidity related to the venous access site, nephro- and ototoxicity, cost of hospitalization, and possible treatment failure. Unfortunately, oral carbenicillin is ineffective in achieving adequate antibiotic tissue levels for antipseudomonal coverage. Management of MEO and SBO significantly changed in October 1987 with the availability of oral fluoroquinolones.74 Although not approved for use in children because of concern for premature epiphyseal closure, ciprofloxacin and ofloxacin are effective against Pseudomonas and well tolerated by patients. In a report by Rubin and colleagues, 10 of 11 patients were cured of MEO using the combination of oral ciprofloxacin and rifampin for 6 to 12 weeks (mean, 8 weeks).75 Oral ciprofloxacin, 750 mg bid, alone effectively cured 21 of 23 patients treated by Lang and colleagues.76 In addition, ciprofloxacin, given orally for 6 weeks to 6 months (mean of 10 weeks), successfully treated patients with MEO whom conventional combination intravenous therapy had failed.77 Similar efficacy with ofloxacin (200 mg bid) given to 17 patients with MEO achieved subjective improvement in all patients within 6 days and objective improvement within 12 days of treatment. Zikk and colleagues78 divided patients with MEO into those with disease limited to the soft tissue of the external auditory canal and those with radiologically confirmed temporal bone involvement. Giving oral ofloxacin 400 mg bid, treatment was necessary for a mean of 30 days in the group with limited disease and a mean of 58 days for those with more extensive involvement. Two patients had a relapse of their disease and required a second course of ofloxacin. Three of the 24 patients (12.5%) failed this oral single-agent therapy due to emergence of P. aeruginosa strains resistant to ofloxacin after 60 days of treatment.75 In cases of severe SBO, combination intravenous antibiotic therapy would be initially indicated, using an oral agent for long-term management. Morrison and Bailey treated two patients with extensive bilateral SBO with oral ciprofloxacin for 6 months following a 6-week course of parenteral treatment with gentamicin and azlocillin.79 There is growing concern regarding the emergence of strains of Pseudomonas resistant to ciprofloxacin. One center reported culture susceptibilities revealing that 25% of cases of malignant otitis externa demonstrated

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ciprofloxacin- resistant Pseudomonas. If this pattern continues, systemic treatment will require prolonged intravenous management of either inpatients or outpatients.80 Fortunately, some resistant strains remain sensitive to levofloxacin.81 When complete resistance to the quinolones is identified, numerous other antibiotics are available, including semi-synthetic penicillins (ticarcillin, piperacillin); third- and fourth-generation cephalosporins (ceftazidime, cefepime); carbapenems (imipenem); aztreonam; and aminoglycosides. Unfortunately, none of these medications can be taken orally. A long intravenous line is then needed for prolonged systemic administration. Treatment of MEO in children is similar to that in adults. Effective anti-Pseudomonas treatment with intravenous combination therapy is necessary. As mentioned, no effective oral antibiotics are FDA approved for use in children. In addition, controversy exists over the duration of therapy. Treatment of adults usually lasts 4 to 6 weeks. In children, it appears that if a clinical response is evident early, a 2- to 3-week course of antimicrobial therapy may suffice.82 However, the subsequent healing of the external auditory canal despite successful treatment of MEO often entails cartilaginous deformities and cicatricial stenosis of the external meatus.42 Despite these problems of wound healing and facial paralysis, the mortality of MEO in children compared with adults is relatively low.40

Hyperbaric Oxygen Therapy Despite the reported efficacy of prolonged systemic antibiotic therapy, treatments do fail. Management consists of extending the duration of treatment or, in the case of relapsing symptoms, multiple courses of antibiotics. Recalcitrant and extensive infection is likely present in the face of multiple cranial neuropathies. Skull base osteomyelitis or intracranial extension defines advanced infection with tissue hypoperfusion and hypoxia. The management plan should incorporate the potential need for treatment beyond the usual 6-week course with consideration for adjuvant therapy. Hyperbaric oxygen (HBO) temporarily increases wound PO2 levels, enhancing the phagocytic oxidative killing of aerobic microorganisms. Hyperbaric oxygen is effective in promoting wound healing, angioneogenesis, and osteoneogenesis and in restoring aminoglycoside antibacterial activity that occurs with reduced oxygen tension.9,66 Adjuvant hyperbaric oxygen therapy has proved efficacious in such cases of recalcitrant, advanced, or recurrent MEO. Mader and Love published one of the earliest reports advocating the use of adjuvant hyperbaric oxygen; they studied a 55-year-old diabetic who was not responding to prolonged high-dose intravenous moxalactam therapy. Treatment consisted of 100% oxygen given for 90 minutes at 21/2 atm absolute pressure, 5 days a week, for 4 weeks (twenty HBO treatments).83 Davis and colleagues9 reported 16 patients with MEO treated with 4 to 6 weeks of parenteral antipseudomonal antibiotics and daily adjuvant hyperbaric oxygen therapy. Using their staging criteria (see the section “Staging”), eight patients were stage I (localized MEO) and eight had stage II or III (multiple cranial neuropathies, skull base osteitis, or intracranial extension). The method of oxygen delivery was in a hyperbaric chamber with each dive lasting approximately

90 minutes. Three 30-minute periods of breathing 100% oxygen from a head tent at 2.4 atm absolute were separated by 10 minutes of breathing room air. Treatments were scheduled once or twice a day for the duration of their parenteral antibiotic therapy, achieving an average arterial PO2 of 1300 mm Hg while in the chamber. All patients were successfully treated despite presenting with a history of repeated treatment failures or severe osteomyelitis, multiple cranial nerve neuropathies, epidural abscesses, or meningitis. Treatment success was defined as 90% or greater return of cranial nerve function and freedom from symptoms and signs of infection for at least 1 year. Davis and colleagues advocated that adjuvant HBO therapy be given in patients with MEO in advanced stages (II and III), with recurrent cases, and when the infection and process become refractory to appropriate antibiotic treatment.

Treatment Termination Various parameters have been proposed to help determine when treatment can be concluded. In cases of MEO, the ear canal should return to its normal state without evidence of drainage, granulation tissue, or inflammation. The patient should also be free of pain. It has also been suggested that three consecutive sterile ear canal cultures be obtained to confirm absence of pathogenic bacteria.78 Another sensitive laboratory marker for monitoring MEO and SBO is the erythrocyte sedimentation rate (ESR). At the onset of therapy, the ESR is usually markedly elevated, although it typically drops within 2 weeks of treatment. A review of 25 patients diagnosed with MEO confirmed all to elevated ESRs.25 Initial mean ESR levels of 81 mm/h (range 41 to 138 mm/h) and 88 mm/h have been reported.65,75 The ESR provides not only a means of monitoring therapy but also an additional method of determining when treatment can be discontinued. Should pain resume after completion of therapy, return of an elevated ESR may be the first objective indication of recurrent disease.25 Several scanning techniques assist in monitoring therapy and determining when treatment may be concluded. The CT scan can demonstrate resolution of soft tissue inflammation but is limited in documenting eradication of bone involvement. MRI is more sensitive in demonstrating the inflammatory changes in the surrounding soft tissue. Obtaining an end-treatment negative result of a gallium scan, having had a positive one at onset of treatment, provides a means of judging when therapy can be terminated. Despite reports of false-negative scan results (normal gallium scan in the face of MEO), the gallium scan is one of the more useful indicators of adequate treatment.48,66 Despite the limitation of taking 48 hours to complete, a normal gallium scan is considered a primary objective measure of disease resolution.45,84,85 Calculating the lesion-to-nonlesion ratio provides a more accurate assessment of the infectious process and when to terminate therapy.57,86

SUMMARY Skull base osteomyelitis is an indolent, invasive, aggres-sive infection with potentially significant morbidity and mortality. The etiology is usually otogenic (MEO),

Otogenic Skull Base Osteomyelitis

although infection can occur from other neurosurgical or cranial base sources and procedures. The most common form of SBO is malignant external otitis, which is typically seen in elderly diabetic patients. The diagnosis is based on obtaining a detailed history of symptoms and signs, baseline data including culture, biopsy, hematologic parameters (glucose levels, ESR, etc.), and imaging studies. Management of MEO entails correcting metabolic abnormalities and preliminarily initiating intravenous antipseudomonal antibiotic therapy until the physician feels comfortable that progression of the infectious process has been controlled. SBO implies more extensive involvement than MEO and warrants more aggressive treatment. Surgical debridement of granulation tissue, bony sequestrations, and devitalization of tissue from the external auditory canal is recommended in cases of MEO. CT imaging should provide accurate information regarding the presence of abscesses, indicating whether formal surgical intervention is warranted. Treatment for recalcitrant infections can be supplemented with adjuvant hyperbaric oxygen therapy. The duration of therapy is determined by numerous factors including the patient’s symptomatic and clinical response and demonstrated resolution of inflammation by monitoring treatment with sequential gallium scans and ESRs. The treatment ranges vary from as short as 2 to 3 weeks for MEO in children to 6 months for SBO in adults. The oral fluoroquinolones (ciprofloxacin) eliminate the potential metabolic, ototoxic, and venous access complications that exist with combination parenteral antimicrobial therapy. Hyperbaric oxygen therapy provides an additional means of increasing tissue oxygenation to promote infection control and healing. In the 30 years since MEO was first described, the morbidity and mortality significantly declined with current methods of diagnosis and treatment.

REFERENCES 1. Sie KC, Glenn MG, Hillel AH, Cummings CW: Osteomyelitis of the skull base, etiology unknown. Otolaryngol Head Neck Surg 104:252–256, 1991. 2. Meltzer PE, Keleman G: Pyocyaneous osteomyelitis of the temporal bone, mandible and zygoma. Laryngoscope 69:1300–1316, 1959. 3. Chandler JR: Malignant external otitis. Laryngoscope 78: 1257–1294, 1968. 4. Lucente FE, Parisier SC, Som PM, Arnold LM: Malignant external otitis: A dangerous misnomer? Otolaryngol Head Neck Surg 90: 266–269, 1982. 5. Barrow HN, Levenson MJ: Necrotizing “malignant” external otitis caused by Staphylococcus epidermidis. Arch Otolaryngol Head Neck Surg 118:94–96, 1992. 6. Waldvogel FA, Medoff G, Swartz MN: Osteomyelitis: A review of clinical features, therapeutic considerations and unusual aspects. 3. Osteomyelitis associated with vascular insufficiency. N Engl J Med 282:316–322, 1970. 7. Ostfeld E, Segal M, Czernobilsky B: Malignant external otitis: Early histopathologic changes and pathogenic mechanism. Laryngoscope 91:965–970, 1981. 8. Bernheim J, Sade J: Histopathology of the soft parts in 50 patients with malignant external otitis. J Laryngol Otol 103:366–368, 1989. 9. Davis JC, Gates GA, Lerner C, et al: Adjuvant hyperbaric oxygen in malignant external otitis. Arch Otolaryngol Head Neck Surg 118: 89–93, 1992.

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10. Corey JP, Levandowski RA, Panwalker AP: Prognostic implications of therapy for necrotizing external otitis. Am J Otol 6:353–358, 1985. 11. Rubin J, Yu VL, Kamerer DB, Wagener M: Aural irrigation with water: A potential pathogenic mechanism for inducing malignant external otitis? Ann Otol Rhinol Laryngol 99:117–119, 1990. 12. Ford GR, Courteney-Harris RG: Another hazard of ear syringing: Malignant external otitis. J Laryngol Otol 104:709–710, 1990. 13. Zikk D, Rapoport Y, Himelfarb MZ: Invasive external otitis after removal of impacted cerumen by irrigation. N Engl J Med 325:969–970, 1991. 14. Genden EM, Goebel JA: Escherichia coli osteomyelitis of the skull base. Otolaryngol Head Neck Surg 118:853–855, 1998. 15. Senegor M, Lewis HP: Salmonella osteomyelitis of the skull base. Surg Neurol 36:37–39, 1991. 16. Kearns DB, Coker NJ, Pitcock JK, Jenkins HA: Tuberculous petrous apicitis. Arch Otolaryngol 111:406–408, 1985. 17. Vannier JP, Schaison G, George B, Casin I: Actinomycotic osteomyelitis of the skull and atlas with late dissemination: A case of transient neurosurgical syndrome. Eur J Pediatr 145:316–318, 1986. 18. Menachof MR, Jackler RK: Otogenic skull base osteomyelitis caused by invasive fungal infection. Otolaryngol Head Neck Surg 102:285–289, 1990. 19. Cunningham M, Yu VL, Turner J, Curtin H: Necrotizing otitis externa due to Aspergillus in an immunocompetent patient. Arch Otolaryngol Head Neck Surg 114:554–556, 1988. 20. Shelton JC, Antonelli PJ, Hackett R: Skull base fungal osteomyelitis in an immunocompetent host. Otolaryngol Head Neck Surg 126: 76–78, 2002. 21. Yao M, Messner AH: Fungal malignant otitis externa due to Scedosporium apiospermum. Ann Otol Rhinol Laryngol 110:377–380, 2001. 22. Cohen D, Friedman P: The diagnostic criteria of malignant external otitis. J Laryngol Otol 101:216–221, 1987. 23. Keay DG, Murray JA: Malignant otitis externa due to Staphylococcus infection. J Laryngol Otol 102:926–927, 1988. 24. Petrak R, Pottage J: Invasive external otitis caused by Aspergillus fumigatus in an immunocompromised patient. J Infect Dis 151:196, 1985. 25. Rubin J, Yu VL: Malignant external otitis: Insights into pathogenesis, clinical manifestations, diagnosis, and therapy. Am J Med 85: 391–398, 1988. 26. Nadol JB Jr: Histopathology of Pseudomonas osteomyelitis of the temporal bone starting as malignant external otitis. Am J Otolaryngol 1:359–371, 1980. 27. Patel SK, McPartlin DW, Philpott JM, Abramovich S: A case of malignant otitis externa following mastoidectomy. J Laryngol Otol 113:1095–1097, 1999. 28. Amedee R, Mann W: Osteomyelitis of the skull base—an unusual manifestation. Am J Otol 10:402–404, 1989. 29. Chan LL, Singh S, Jones D, et al: Imaging of mucormycosis skull base osteomyelitis. AJNR 21:828–831, 2000. 30. Hirsch BE: Infections of the external ear. Am J Otolaryngol 13:145–155, 1992. 31. Chandler JR: Malignant external otitis and facial paralysis. Otolaryngol Clin North Am 7:375–383, 1974. 32. Schweitzer VG: Hyperbaric oxygen management of chronic staphylococcal osteomyelitis of the temporal bone. Am J Otol 11:347–353, 1990. 33. Chandler JR: Malignant external otitis and osteomyelitis of the base of the skull. Am J Otol 10:108–110, 1989. 34. Farley ML, Mabry L, Munoz LA, Diserens HW: Crystals occurring in pulmonary cytology specimens: Association with Aspergillus infection. Acta Cytol 29:737–744, 1985. 35. Sando I, Harada T, Okano Y, et al: Temporal bone histopathology of necrotizing external otitis: A case report. Ann Otol Rhinol Laryngol 90:109–115, 1981.

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36. Phillips P, Bryce G, Shepherd J, Mintz D: Invasive external otitis caused by Aspergillus. Rev Infect Dis 12:277–281, 1990. 37. Chandler JR: Malignant external otitis: Further considerations. Ann Otol Rhinol Laryngol 86:417–428, 1977. 38. Grandis JR, Hirsch BE, Yu VL: Simultaneous presentation of malignant external otitis and temporal bone cancer. Arch Otolaryngol Head Neck Surg 119:687–689, 1993. 39. Grobman LR, Ganz W, Casiano R, Goldberg S: Atypical osteomyelitis of the skull base. Laryngoscope 99:671–676, 1989. 40. Nir D, Nir T, Danino J, Joachims HZ: Malignant external otitis in an infant. J Laryngol Otol 104:488–490, 1990. 41. Joachims HZ: Malignant external otitis in children. Arch Otolaryngol 102:236–237, 1976. 42. Coser PL, Stamm AE, Lobo RC, Pinto JA: Malignant external otitis in infants. Laryngoscope 90:312–316, 1980. 43. Castro R, Robinson N, Klein J, Geimeier W: Malignant external otitis and mastoiditis associated with an IgG4 subclass deficiency in a child. Del Med J 62:1417–1421, 1990. 44. Horn KL, Gherini S: Malignant external otitis of childhood. Am J Otol 2:402–404, 1981. 45. Slattery WH 3rd, Brackmann DE: Skull base osteomyelitis. Malignant external otitis. Otolaryngol Clin North Am 29:795–806, 1996. 46. Benecke JE Jr: Management of osteomyelitis of the skull base. Laryngoscope 99:1220–1223, 1989. 47. Murray ME, Britton J: Osteomyelitis of the skull base: The role of high resolution CT in diagnosis. Clin Radiol 49:408–411, 1994. 48. Kraus DH, Rehm SJ, Kinney SE: The evolving treatment of necrotizing external otitis. Laryngoscope 98:934–939, 1988. 49. Parisier SC, Lucente FE, Som PM, et al: Nuclear scanning in necrotizing progressive “malignant” external otitis. Laryngoscope 92:1016–1019, 1982. 50. Levin WJ, Shary JH, 3rd, Nichols LT, Lucente FE: Bone scanning in severe external otitis. Laryngoscope 96:1193–1195, 1986. 51. Garty I, Rosen G, Holdstein Y: The radionuclide diagnosis, evaluation and follow-up of malignant external otitis (MEO). The value of immediate blood pool scanning. J Laryngol Otol 99:109–115, 1985. 52. Noyek AM: Bone scanning in otolaryngology. Laryngoscope 89:1–87, 1979. 53. Gold S, Som PM, Lucente FE, et al: Radiographic findings in progressive necrotizing “malignant” external otitis. Laryngoscope 94:363–366, 1984. 54. Lee JKT, Sagel SS, Stanley RJ: Computed Body Tomograph. Musculoskeletal System. New York, Raven Press, 1983. 55. Mendelson DS, Som PM, Mendelson MH, Parisier SC: Malignant external otitis: The role of computed tomography and radionuclides in evaluation. Radiology 149:745–749, 1983. 56. Strashun AM, Nejatheim M, Goldsmith SJ: Malignant external otitis: Early scintigraphic detection. Radiology 150:541–545, 1984. 57. Uri N, Gips S, Front A, et al: Quantitative bone and 67Ga scintigraphy in the differentiation of necrotizing external otitis from severe external otitis. Arch Otolaryngol Head Neck Surg 117:623–626, 1991. 58. Seabold JE, Simonson TM, Weber PC, et al: Cranial osteomyelitis: Diagnosis and follow-up with In-111 white blood cell and Tc-99m methylene diphosphonate bone SPECT, CT, and MR imaging. Radiology 196:779–788, 1995. 59. Redleaf MI, Angeli SI, McCabe BF: Indium 111-labeled white blood cell scintigraphy as an unreliable indicator of malignant external otitis resolution. Ann Otol Rhinol Laryngol 103:444–448, 1994. 60. Mendelson MH, Meyers BR, Hirschman SZ, et al: Treatment of invasive external otitis with cefsulodin. Rev Infect Dis 6(Suppl 3): S698–704, 1984. 61. Gherini SG, Brackmann DE, Bradley WG: Magnetic resonance imaging and computerized tomography in malignant external otitis. Laryngoscope 96:542–548, 1986.

62. Laurikainen E, Puhakka H, Rikalainen H: Coincidental radiographic findings in severe external otitis in nonimmunocompromised patients. ORL J Otorhinolaryngol Relat Spec 52:391–394, 1990. 63. Rubin J, Curtin HD, Yu VL, Kamerer DB: Malignant external otitis: Utility of CT in diagnosis and follow-up. Radiology 174: 391–394, 1990. 64. McShane D, Chapnik JS, Noyek AM, Vellend H: Malignant external otitis. J Otolaryngol 15:108–111, 1990. 65. Johnson MP, Ramphal R: Malignant external otitis: Report on therapy with ceftazidime and review of therapy and prognosis. Rev Infect Dis 12:173–180, 1990. 66. Shupak A, Greenberg E, Hardoff R, et al: Hyperbaric oxygenation for necrotizing (malignant) otitis externa. Arch Otolaryngol Head Neck Surg 115:1470–1475, 1989. 67. Farrior J: Osteomyelitis of the skull base. South Med J 82:719–722, 1989. 68. Raines JM, Schindler RA: The surgical management of recalcitrant malignant external otitis. Laryngoscope 90:369–378, 1980. 69. Babiatzki A, Sade J: Malignant external otitis. J Laryngol Otol 101:205–210, 1987. 70. Kimmelman CP, Lucente FE: Use of ceftazidime for malignant external otitis. Ann Otol Rhinol Laryngol 98:721–725, 1989. 71. Meyers BR, Mendelson MH, Parisier SC, Hirschman SZ: Malignant external otitis: Comparison of monotherapy vs combination therapy. Arch Otolaryngol Head Neck Surg 113:974–978, 1987. 72. Haverkos HW, Caparosa R, Yu VL, Kamerer D: Moxalactam therapy: Its use in chronic suppurative otitis media and malignant external otitis. Arch Otolaryngol 108:329–333, 1982. 73. Levy R, Shpitzer T, Shvero J, Pitlik SD: Oral ofloxacin as treatment of malignant external otitis: A study of 17 cases. Laryngoscope 100:548–551, 1990. 74. Strauss M: Current therapy of malignant external otitis. Otolaryngol Head Neck Surg 102:174–176, 1990. 75. Rubin J, Stoehr G, Yu VL, et al: Efficacy of oral ciprofloxacin plus rifampin for treatment of malignant external otitis. Arch Otolaryngol Head Neck Surg 115:1063–1069, 1989. 76. Lang R, Goshen S, Kitzes-Cohen R, Sade J: Successful treatment of malignant external otitis with oral ciprofloxacin: Report of experience with 23 patients. J Infect Dis 161:537–540, 1990. 77. Levenson MJ, Parisier SC, Dolitsky J, Bindra G: Ciprofloxacin: Drug of choice in the treatment of malignant external otitis (MEO). Laryngoscope 101:821–824, 1991. 78. Zikk D, Rapoport Y, Redianu C, et al: Oral ofloxacin therapy for invasive external otitis. Ann Otol Rhinol Laryngol 100:632–637, 1991. 79. Morrison GA, Bailey CM: Relapsing malignant otitis externa successfully treated with ciprofloxacin. J Laryngol Otol 102:872–876, 1988. 80. Berenholz L, Katzenell U, Harell M: Evolving resistant pseudomonas to ciprofloxacin in malignant otitis externa. Laryngoscope 112:1619–1622, 2002. 81. Segatore B, Setacci D, Perilli M, et al: Italian survey on comparative levofloxacin susceptibility in 334 clinical isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 43:428–431, 1999. 82. Rubin J, Yu VL, Stool SE: Malignant external otitis in children. J Pediatr 113:965–970, 1988. 83. Mader JT, Love JT: Malignant external otitis: Cure with adjunctive hyperbaric oxygen therapy. Arch Otolaryngol 108:38–40, 1982. 84. Stokkel MP, Boot CN, van Eck-Smit BL: SPECT gallium scintigraphy in malignant external otitis: Initial staging and follow-up. Case reports. Laryngoscope 106:338–340, 1996. 85. el-Silimy O, Sharnuby M: Malignant external otitis: Management policy. J Laryngol Otol 106:5–6, 1992. 86. Stokkel MP, Takes RP, van Eck-Smit BL, Baatenburg de Jong RJ: The value of quantitative gallium-67 single-photon emission tomography in the clinical management of malignant external otitis. Eur J Nucl Med 24:1429–1432, 1997.

66

Outline Introduction History Anatomy Epidemiology and Symptoms Diagnosis Surgical Approaches Cystic Lesions Cholesterol Granuloma Cholesteatoma Mucocele Cephalocele Infectious

Chapter

Lesions of the Petrous Apex

Petrous Apicitis Skull Base Osteomyelitis Neoplastic Chondrosarcoma Chordoma Meningioma Neurogenic Tumors Metastatic Lesions Other Neoplasms Intrapetrous Carotid Aneurysm Osteodystrophy

INTRODUCTION The petrous apex represents one of the most surgically inaccessible areas of the skull base. The diagnosis and management of lesions in this area present a particular challenge. A thorough understanding of the intricate anatomy of the petrous apex and its surroundings is essential to understanding disease in this region, the expected clinical manifestations of disorders, and their optimal management. Lesions of the petrous apex represent a broad spectrum of abnormalities including congenital, neoplastic, inflammatory, and infectious processes. Once identified, these lesions can be surgical and require medical therapy, or be incidental and require no additional intervention. Particular care must be given to radiologic and clinical clues to differentiate these types of lesion.

HISTORY Historically, lesions of the petrous apex have been difficult to diagnose. Plane films of the skull, tomograms, angiograms, and pneumoencephalograms have all been used with little accuracy for the diagnosis of lesions in this area. Lesions of the petrous apex were therefore identified late, usually only after they had progressed to the point of causing significant symptoms. Petrous apex lesions were often suspected only with the onset of hydrocephalus and multiple cranial neuropathies, and were confirmed only on autopsy. In the early 1900s, surgery of the petrous apex was largely for the drainage of suppurative disease. A middle fossa craniotomy was occasionally used for this, as were transmastoid approaches including radical mastoidectomy

Nikolas H. Blevins, MD Carl B. Heilman, MD

and translabyrinthine procedures.1 In the 1930s, less invasive procedures were developed to follow the pathway of purulence around the otic capsule, thereby possibly sparing the inner ear. All air cell tracts were explored to optimize drainage. Since the advent of antibiotics, however, the incidence and presentation of infectious disorders of the petrous apex has changed considerably. Nevertheless, many of the general principles developed before this time are still applicable today in the surgical management of abscesses in this area. The management of neoplastic disease of the petrous apex has been revolutionized by modern imaging and surgical techniques. Historically, such lesions were unresectable as a rule. Even relatively recently, surgeons advocated surgical approaches intended to marsupialize benign tumors and even slow-growing malignancies for ongoing palliative debulking.2,3 As tumors are detected earlier through advances in noninvasive imaging techniques and as surgical approaches and radiation therapy are refined, more tumors may be approached with the intention for cure.

ANATOMY The petrous apex is a pyramidal projection of bone that comprises the most medial portion of the temporal bone1 (Fig. 66-1). The lateral base of this pyramid is defined by the inner ear, eustachian tube, and intratemporal carotid artery. Its apex lies adjacent to the clivus. The petrous apex may be thought of as composed of three sides, with anterior, posterior, and inferior surfaces. The anterior surface forms the posterior portion of the floor of the middle fossa, abutting the greater wing of the sphenoid bone. The posterior 1107

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Figure 66-1. The petrous apex seen from above. The petrous apex is a pyramid that projects anterior and medial to the inner ear. It can be subdivided into the anterior petrous apex (APA), medial to the cochlea, and the posterior petrous apex (PPA) medial to the semicircular canals.1 Both spaces can contain variable amounts of bone marrow (M) and pneumatization. The carotid artery (CA) is shown in the middle fossa and the jugular foramen (JF) is shown in the posterior fossa. (Adapted from Jackler RK, Cho M. A new theory to explain the genesis of petrous apex cholesterol granuloma. Otology and Neurotology 24(1): 96–106, 2003.)

surface of the petrous apex marks the anterolateral extent of the posterior fossa. The junction of the anterior and posterior surfaces of the petrous apex forms the petrous ridge. Medially, the posterior surface ends at the petroclival and petro-occipital synchondroses, where it abuts the clivus. The inferior surface of the petrous pyramid faces externally as the floor of the lateral skull base. A number of cranial nerves are intimately associated with the petrous pyramid. The trigeminal (fifth) nerve travels over the apex, forming an impression on the anterolateral surface. This trigeminal impression forms the posteromedial wall of Meckel’s cave, where the gasserian ganglion lies. The abducens (sixth) nerve courses along the ventral surface of the pons and then passes over the superomedial aspect of the petrous apex. Here, the sixth nerve enters Dorello’s canal, a space defined by the petroclinoid ligament, before it enters the cavernous sinus. The facial (seventh) and vestibulocochlear (eighth) nerves pass through the petrous apex as they traverse the internal auditory canal (IAC). The porus acousticus, or meatus of the IAC, lies within the posterior face of the petrous apex, and the fundus of the IAC marks the lateral extent of the apex as it terminates at the inner ear. The jugular foramen lies between the junction of the posterior and inferior surfaces of the petrous apex and the occipital bone. The glossopharyngeal (ninth), vagus (tenth), and spinal accessory (eleventh) cranial nerves all exit the skull base though the jugular foramen. Therefore, all of these cranial nerves are susceptible to injury from disease and disorders that affect the petrous apex.

The intratemporal carotid artery defines the anterolateral extent of the petrous apex. It courses along the foramen lacerum, which is a gap between the apex and the greater wing of the sphenoid bone. The petrosal sinuses course along the edges of the petrous apex as they travel posteriorly from the cavernous sinus. The superior petrosal sinus lies within the dura at the petrous ridge, where the dura of the middle fossa, posterior fossa, and tentorium converge. The inferior petrosal sinus courses along petroclival suture line to terminate at the jugular bulb in the jugular foramen. For clinical assessment and treatment planning, it is useful to consider the petrous apex as being divided into two major parts separated by the internal auditory canal.1 The larger anterior compartment is defined medially by the cochlea, and it contains the intrapetrous internal carotid artery, bone marrow, fibrocartilage of the foramen lacerum, and a variable degree of pneumatization. The smaller posterior portion is defined medially by the semicircular canals, and it contains marrow and air cells. The petrous apex is pneumatized to variable degrees. Approximately one third of individuals have a pneumatized petrous apex, with the posterior portion of the petrous apex more likely to contain air spaces than the anterior.4,5 There is often considerable asymmetry in the degree of pneumatization between the two sides. Almost all petrous apices contain some bone marrow.

EPIDEMIOLOGY AND SYMPTOMS Overall, symptomatic lesions of the petrous apex are quite rare, although their incidence is difficult to determine. In a review of 66 patients with petrous apex lesions (excluding petroclival meningioma), 60% were cholesterol granulomas and 9% were cholesteatomas.6 There does not appear to be any overriding sex predilection for petrous apex lesions, and patients of any age can be affected.6 Symptoms are often present for an extended time before the establishment of a diagnosis. It is not uncommon to find in retrospect that symptoms have been present for months or even years. This may be partially due to the relatively nonspecific nature of the majority of symptoms and to the slowly progressive nature of many of the lesions that affect this area. Specific symptoms from petrous apex lesions are related to their involvement of adjacent anatomy. In one review of patients with petrous apex lesions, the most common symptoms were hearing loss (64%), vestibular dysfunction (49%), headache (43%), tinnitus (40%), facial twitching (14%), diplopia (7%), facial paralysis (5%), and otorrhea (6%).6 However, the likelihood of a given symptom is highly dependent on the specific disease. In some disease processes, timely surgical intervention can result in marked improvement of symptoms, with resolution of cranial neuropathy and the potential for hearing improvement.6,7

DIAGNOSIS The diagnosis of petrous apex disease depends on the clinician’s maintaining a level of suspicion for these rare lesions. Otherwise, unexplained cranial neuropathy, otalgia,

Lesions of the Petrous Apex

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TABLE 66-1. Imaging Characteristics of Common Lesions of the Petrous Apex MRI

CT

T1

T2

Gad

CT

+C

Other

Cholesterol granuloma Cholesteatoma Mucocele Cephalocele Petrous apicitis Malignancy* Neurogenic tumors Meningioma Carotid aneurysm Marrow asymmetry

hyper hypo iso hypo hypo hypo iso iso/hyper hypo hyper

hyper hyper hyper hyper hyper hyper hyper iso/hyper mixed hypo

− − − − rim + + + rim −

smooth erosion smooth or scalloped erosion smooth erosion smooth erosion irregular erosion invasion/erosion smooth erosion erosion/hyperostosis erosion of carotid canal none

− − − − rim + + + + −

often highly pneumatized contralateral apex CT may show evidence of chronic otitis media

Apex effusion

hypo

hyper

−

none

−

centered extrinsic to petrous apex pneumatized contralateral apex +/− intralesion calcification +/− cystic changes dural tail enhancement, heterogeneous “onion skin” appearance central flow void preservation of trabeculae

Gad = gadolinium intravenous contrast; +C = intravenous contrast. *Malignancy includes chondrosarcoma, chordoma, metastatic lesions. Adapted from Jackler RK, Parker DA: Radiographic differential diagnosis of petrous apex lesions. Am J Otol 13:561–574, 1992; Muckle RP, De la Cruz A, Lo WM: Petrous apex lesions. Am J Otol 19:219–225, 1998; Chang P, Fagan PA, Atlas MD, Roche J: Imaging destructive lesions of the petrous apex. Laryngoscope 108:599–604, 1998; and Moore KR, Harnsberger R, Shelton C, Davidson C: “Leave me alone” lesions of the petrous apex. Am J Neuroradiol 19:733–738, 1998.

or other neurotologic symptoms must raise the question of a lesion in the petrous apex. Appropriate imaging should be obtained and diligently reviewed in order to establish a timely diagnosis. Petrous apex lesions can often be identified as incidental findings on imaging studies.8 Some of these asymptomatic lesions require treatment, and others are better observed over time. Modern radiologic techniques remain a cornerstone in the accurate diagnosis of petrous apex lesions.4,9,10 The combined use of high-resolution multiplanar magnetic resonance imaging (MRI) and computed tomography (CT) has become the standard for noninvasive diagnosis. The administration of intravenous contrast often helps to make the diagnosis. Specific pathology can often be identified through distinct patterns of appearance from different imaging modalities. An overview of the appearance of common lesions of the petrous apex appears in Table 66-1. Considerable normal variability exists in the amount of pneumatization and bone marrow in the petrous apex. Asymmetric pneumatization or an effusion of the petrous

apex can often be misdiagnosed as a pathologic process.11,12 Marrow in a hypopneumatized petrous apex is bright on T1-weighted MRI because of its high fat content (Fig. 66-2). An effusion in the petrous apex shows low signal intensity on T1-weighted MRI and is bright on T2-weighted images (Fig. 66-3). Both of these can produce a striking asymmetry on imaging, especially if the contralateral side is pneumatized. By obtaining a CT scan in such instances, such benign findings can often be differentiated from pathologic processes that require intervention.11 On CT scans, neither asymmetric pneumatization nor an effusion demonstrates erosion or expansion of surrounding bone. Angiography can be useful in evaluating the internal carotid artery in lesions of the petrous apex. Either magnetic resonance angiography (MRA) or conventional angiography could prove valuable in establishing the diagnosis and thereby influence the approach to treatment. Conventional angiography, although more invasive, remains the best means of vascular imaging. It also provides the added potential for embolization of vascular lesions,

Figure 66-2. Asymmetric pneumatization of the petrous apex. A, Axial CT image showing a unilateral well-pneumatized petrous apex with air cells (AC). Bone marrow (BM) is filling the apex. B, Axial T1-weighted MRI of the same patient showing unilateral bright signal of the bone marrow. Such asymmetry can be mistaken for a pathologic lesion. (From Jackler RK, Parker DA: Radiographic differential diagnosis of petrous apex lesions. Am J Otol 13:561–574, 1992.)

A

B

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A

B

C

Figure 66-3. Effusion of the petrous apex (arrows) identified incidentally on a scan performed for migraine headaches. A, Coronal CT shows opacification of a pneumatized petrous apex with preservation of the surrounding thin bony trabeculae. B, On coronal T1-weighted MRI, the effusion is hypointense compared with adjacent brain. C, On T2-weighted imaging, the effusion is hyperintense. A repeat CT scan in 1 year showed the effusion had cleared completely.

such as glomus tumors, as well as the potential to perform test occlusion of the internal carotid artery should sacrifice of this vessel be contemplated. Routine auditory testing of patients with petrous apex lesions often aids in assessing the degree to which the inner ear and eighth cranial nerve are affected by the lesion. Auditory brainstem response testing may also help to establish the site of the lesion and establish the potential for intraoperative hearing monitoring in selected cases. The surgical approach selected in an individual is usually highly dependent on whether useful hearing is present preoperatively, and careful audiometric testing is central to this decision-making process.

SURGICAL APPROACHES Modern imaging and surgical techniques have significantly improved the management of petrous apex lesions. The combined use of high-resolution multiplanar CT and MRI has granted the skull base surgeon the ability not only to predict the nature of a petrous apex lesion but also to plan a surgical approach suitable to the underlying pathology. With adequate preoperative imaging, the approach can be tailored to an individual’s anatomy to optimize access while minimizing the possibility of injury to vital neurovascular structures. Minimally invasive approaches afforded by use of microsurgical techniques can often avoid the significant surgical morbidity historically associated with surgery in this relatively inaccessible area. Surgical approaches to the petrous apex can be categorized broadly as transmastoid,1,13 transtympanic,14 middle fossa,15 or a combination of these. Occasionally, more frontolateral approaches are employed (either transsphenoidal or frontotemporal transsylvian). The goal of surgical approaches to the petrous apex may be classified broadly as either lesion drainage or excision. Lesions amenable to drainage often require a significantly less invasive procedure than those that require complete excision. Overall, the selection of a surgical approach depends on the presumed nature of the lesion, its anatomic location, the patient’s general suitability to undergo surgery, and the presence of

neurologic deficits. In particular, the presence or absence of useful hearing is critical because the majority of drainage procedures are selected in an attempt to avoid injury to a functioning inner ear. Transmastoid approaches intended for drainage of petrous apex lesions can make use of a number of air cell tracts and possible spaces within the temporal bone. Access to the posterior petrous apex can be particularly amenable to transmastoid approaches. Drainage of lesions situated in this region might be gained while leaving the canal wall intact. The bone comprising the sinodural angle may offer one such pathway for drainage, if bone along the tegmen is removed medially along the petrous ridge posterior to the otic capsule. The infralabyrinthine approach takes advantage of the potential space inferior to the posterior semicircular canal and superior to the jugular bulb. In cases with a low-lying jugular bulb, access to the anterior petrous apex may also be gained via this approach.16 A subarcuate air cell tract, passing through the superior semicircular canal, may also be used to access the posterior petrous apex.17 In selected cases, the petrous apex can be opened via a supracochlear approach, by removing bone from the medial surface of the epitympanum, superior to the tympanic facial nerve.18 Hearing-sparing approaches for drainage of the anterior petrous apex can be quite difficult via the transmastoid route. If the canal wall is removed, air cell tracts passing into the petrous apex along the eustachian tube and internal carotid artery may be followed anterior to the otic capsule.13,19 Alternatively, a transcanal infracochlear approach may be effective with selective lesions.14,16 This approach takes advantage of the possible space inferior to the otic capsule, anterior to the jugular bulb, and posterior to the intratemporal genu of the internal carotid artery. This has been widely used as a minimally invasive means for drainage of petrous apex cholesterol granulomas. For the complete excision of petrous apex lesions, the most direct route involves the resection of part or all of the inner ear. Such transotic approaches can gain excellent exposure to the petrous apex, but they carry the disadvantage of loss of inner ear function and potential facial paralysis if the facial nerve is rerouted. The middle fossa approach15,20 can

Lesions of the Petrous Apex

afford access to lesions of the petrous apex, although the inferior aspects of the petrous apex may remain inaccessible behind the carotid artery. By combining a middle cranial fossa craniotomy with an anterior or posterior petrosectomy, exposure can be augmented. These approaches are collectively known as “petrosal approaches.”21 In favorable anatomic configurations, access to petrous apex lesions for drainage or biopsy can be gained via an anterior transsphenoidal approach. Such an approach may be sufficient for therapeutic drainage of cystic lesions or it may provide a minimally invasive means of confirming a nonsurgical diagnosis. It must be remembered, however, that the course of the internal carotid artery may be immediately in the path of such an approach, which might render such attempts ill advised. The advent of new intraoperative guidance and navigation systems will make this technique safer in the future.22

CYSTIC LESIONS Cholesterol Granuloma Cholesterol granuloma is the most common lesion intrinsic to the petrous apex. Cholesterol granulomas that affect various anatomic regions have been described for many years. In the 1980s, such lesions affecting the petrous apex were defined as distinct clinical entities.23 Although they have historically been called “epidermoid cysts,” “giant cholesterol cysts,” or “mucosal cysts,” they are not true cysts because they are not lined by epithelium. Instead, cholesterol granulomas are fluid-filled expansile lesions with a fibrous capsule. They are the result of a foreign body inflammatory reaction to cholesterol crystals and they contain abundant chronic inflammatory cells including multinucleated giant cells. Cholesterol granulomas appear to evolve as the result of bleeding within petrous apex air cells. The anaerobic metabolism of the free hemoglobin in the pneumatized spaces produces cholesterol crystals, and these crystals subsequently incite a giant-cell foreign body reaction. Ongoing inflammation and gradual expansion causes erosion of surrounding bone and ultimately results in a cholesterol granuloma. Although it is widely accepted that bleeding is an essential element in inciting this chain of events, the factors that predispose an individual to the initial hemorrhage remain controversial. The classic hypothesis of cholesterol granuloma formation suggests that initial hemorrhage into the petrous apex air cells is the result of obstruction of aeration pathways.24 This theory suggests that initial mucosal edema in the tympanomastoid system results in a closed space within the petrous apex. Subsequent gas resorption produces a negative pressure, which in turn predisposes to edema and hemorrhage into the obstructed spaces. There are, however, a number of apparent inconsistencies when considering the classic hypothesis for formation of petrous apex cholesterol granuloma.4 For example, petrous apex cholesterol granulomas are quite rare despite the common occurrence of eustachian tube dysfunction and resultant transient negative pressure in the air cell system. Even with known anatomic closure of the eustachian

1111

tube, granuloma formation is exceedingly rare. The pressure gradient from gas resorption alone does not appear sufficient to incite the hemorrhage required in the vast majority of cases. In addition, once fluid fills an obstructed air cell, the pressure gradient is removed, extinguishing the driving force for additional accumulation of blood products and granuloma formation. Another inconsistency is that cholesterol granulomas form preferentially within highly pneumatized petrous apices. Such pneumatization usually occurs in ears free from significant obstruction. These inconsistencies have led to the proposition of an alternative theory of petrous apex cholesterol granuloma formation by Jackler and Parker, suggesting that initial hemorrhage may result from the exposure of apex marrow to air cell spaces.4 In such circumstances, hemorrhage may result directly from the exposed marrow, thereby inciting the inflammatory response known to underlie granulomar development. A study was undertaken to compare CT data from 13 patients with petrous apex cholesterol granulomas to a group of equally pneumatized controls. The findings suggest that patients with petrous apex cholesterol granulomas have incomplete bony septations between the apex marrow and the air cell system. The need for such a rare predisposing anatomic factor can explain the relative scarcity of petrous apex cholesterol granulomas. Under this theory, as a lesion enlarges, additional bone marrow may be exposed, thereby providing the additional source of hemorrhage to fuel the inflammatory process and further granuloma formation. In addition, the exposed marrow theory accounts for the tendency for cholesterol granulomas to develop in highly pneumatized petrous apices, since these temporal bones seem more likely to bring marrow directly into contact with air cells. Cholesterol granulomas can form in any pneumatized portion of the temporal bone. Small lesions are commonly encountered in the mastoid air cell system during surgery for chronic otitis media. It is important to distinguish tympanomastoid cholesterol granulomas from those in the petrous apex because their pathogenesis and clinical course appear to be quite distinct.4 In contrast to their petrous apex counterparts, tympanomastoid cholesterol granulomas often occur in hypopneumatized air cell systems and are likely the result of bleeding from granulation tissue or chronic inflammation. When occurring in the middle ear cleft itself, cholesterol granulomas have been termed idiopathic hemotympanum or blue eardrum because of their dark color seen at otoscopy.25 However, when a cholesterol granuloma grows within the petrous apex, few symptoms or signs may be evident until it has become relatively large. Grossly, cholesterol granulomas contain a dark brown or yellow fluid with shining cholesterol crystals visible under the operating microscope. Intraoperative cultures are usually sterile.26 Petrous apex cholesterol granulomas usually develop in the absence of other identifiable middle ear disease.27 However, at least one review suggests that as many as half of affected patients had a history of chronic otitis or previous otologic procedure.28 Another study found chronic ear disease to coexist in 20% of patients (5 of 25).29 The great majority are unilateral, although bilateral lesions have been reported.27,28 The peak incidence appears to be in the third to sixth decade.26,28,29

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Retrospective reviews suggest that cholesterol granulomas usually produce the same constellation of symptoms as all expansile lesions in this region. 26,28–30 Complaints of an ipsilateral headache are common, often characterized by retro-orbital pain. Involvement of the sixth cranial nerve can produce diplopia. Symptoms more common to intrinsic ear disease are also seen frequently, including otalgia, aural fullness, vertigo, and hearing loss. Hearing loss has been suggested to be the most prevalent symptom and is the symptom most likely to precipitate evaluation, being present in more than 50% of patients.29 The hearing loss may be sensorineural from impingement on the cochlea or eighth cranial nerve, or it may be conductive in lesions extending to involve the middle ear. Both slowly progressive hearing loss over years as well as rapidly progressive deficits are possible.26 Facial and trigeminal nerve dysfunction are also seen. The radiographic appearance of petrous apex cholesterol granulomas is usually sufficient to make the diagnosis. The lesions have a distinct signal characteristic on MRI, being bright on both T1- and T2-weighted images (Fig. 66-4). Since such a signal pattern is not seen in other common lesions of the petrous apex; its presence is highly suggestive of a cholesterol granuloma.31 These signal characteristics may be secondary to the presence of free methemoglobin within the lesion. Despite this, there can be considerable variability of signal within the lesions. Heterogeneity may be the result of fibrosis or the aggregation of cholesterol crystals in the cavity or of hemosiderin.4,10 In addition, the signal characteristics may vary with the maturity of the granuloma. Early in its evolution, a cholesterol granuloma may exhibit a low signal on T1-weighted imaging.30 The administration of gadolinium may enhance the capsule, but there is no enhancement of the central portion of the lesion.

B

A

C

The additional bone detail provided by CT imaging helps to confirm the diagnosis and defines the relationship of the lesion to surrounding structures better.9 On CT, the cholesterol granuloma is isodense with brain, appearing as an expansile mass with sharp, smooth margins. The contralateral petrous apex is often well pneumatized.27 The loss of normal bony trabeculae within the petrous apex air cells can help to differentiate an expanding cholesterol granuloma from an incidental petrous apex effusion. It should be noted, however, that in early symptomatic cholesterol granulomas, bone erosion, and expansion may be minimal or absent10 (Fig. 66-5). There is no uptake of contrast material, although many show some enhancement at the margin of the lesion. The additional bony detail that CT provides can show encroachment of the lesion onto the posterolateral wall of the sphenoid sinus and the otic capsule, the relation to the intratemporal carotid artery, and the potential inferior extension into the jugular foramen. CT also helps to define any concomitant middle ear or mastoid disease that may have precipitated the formation of the granuloma in the petrous apex. The relationship of the lesion to the mastoid air cell tracts can be studied, and it may prove invaluable in planning a surgical approach. Sagittal reconstructions of CT data may be useful in evaluating access to the lesion via an infracochlear approach (Fig. 66-6). The management of petrous apex cholesterol granuloma is complicated by the relative inaccessibility of the region and the uncertain clinical course of these lesions. It is widely believed that the complete resection of these lesions will be curative. However, the benefits of such an approach need to be weighed against the potential surgical morbidity. Lesions identified incidentally can be managed expectantly with regular follow-up and serial imaging. Many lesions can be

Figure 66-4. Petrous apex cholesterol granuloma (arrows). A and B, The lesion is bright on both T1- and T2-weighted axial MRI images. C, On axial CT, the cholesterol granuloma is isodense with brain and demonstrates smooth bony erosion with sharp smooth margins.

Lesions of the Petrous Apex

A

C

B

D

Figure 66-5. Imaging of a developing cholesterol granuloma in a patient presenting with aural fullness and sensorineural hearing loss. There are abnormal findings in both the anterior petrous apex (arrowheads) and the posterior petrous apex (arrow). A, Axial CT image demonstrates fluid in the petrous apex. There is some thickening and demineralization of the bony trabeculae not normally present with an effusion. Note the well-pneumatized contralateral petrous apex. B, Axial T2-weighted MRI demonstrates bright signal in both the anterior and posterior petrous apex. C, On axial T1-weighted MRI, the lesion is isodense to brain. D, With the administration of gadolinium, there is evidence of mucosal enhancement in the posterior petrous apex. On infracochlear drainage, the lesion was found to contain amber fluid.

followed for years without radiographic evidence of progression.28,30 Such a conservative approach might also be advocated for patients whose symptoms have stabilized or improved.26 Surgery is indicated in medically suitable patients with progressive symptoms or with radiologic evidence of growth. Two main philosophies exist as to the optimal

1113

objective of surgery: drainage or excision. Since the lesions are not neoplastic and contain no epithelium, some surgeons advocate surgical drainage with the establishment of an aeration pathway.14,26,29,32,33 In contrast, some surgeons advocate the complete excision of these lesions to reduce the risk of recurrence.20,30,34–37 Depending on the size and location of the tumor, complete surgical excision can be attempted through a middle fossa approach.20,30,37 If needed, exposure can be improved by a petrosal approach, combining the temporal craniotomy with a transmastoid approach. Such approaches often allow resection of the bone of the anterior petrous apex to expose the granuloma while maintaining the integrity of the inner ear. Because it is difficult to establish a permanent path for drainage and aeration in these cases, an attempt at complete tumor resection is advocated to reduce the risk of recurrence. Obliteration of the cavity with a muscle flap has been suggested.30 If the patient lacks useful hearing preoperatively, a translabyrinthine or transcochlear approach may be used to gain additional access to the petrous apex. In any case the integrity of the dura should be maintained to prevent the granuloma contents from contaminating the subarachnoid space, and thus possibly provoking chemical meningitis. Given our understanding of the pathogenesis of cholesterol granulomas, it stands to reason that if the lesion is adequately drained and aerated, no further progression should occur. Such an argument has been used to advocate for minimally invasive drainage procedures, forgoing attempts at complete resection of the capsule.2,14,26,28,29,32,33 The optimal pathway for such drainage depends on the size and location of the lesion and the particular anatomic configuration of the affected temporal bone.16 The diligent use of preoperative imaging, especially multiplanar high-resolution CT images, is needed to assess access to the lesion. Both the transcanal-infracochlear approach and the transmastoid-infralabyrinthine approaches have been used for this purpose. In properly selected patients, both approaches have the ability to establish drainage with minimal morbidity and preservation of inner ear function. In unusual cases where the lesion abuts the sphenoid sinus, a transnasal–trans-sphenoidal approach might be used to drain the lesion into the nasal cavity. The middle fossa approach can also be used for drainage, but the establishment of a permanent drainage pathway is difficult.29 The transcanal-infracochlear approach provides access to the petrous apex through the hypotympanum, making use of the triangular space beneath the basal turn of the cochlea, posterior to the genu of the carotid artery, and anterior to the jugular bulb. This approach was popularized by Brackmann and Giddings in 1991 and has been used Figure 66-6. Cholesterol granuloma (G) in a sagittal reconstruction of a high-resolution CT scan. The expansile lesion is located between the carotid artery (C) anteriorly and the jugular bulb (J) posteriorly. This image is just medial to the basal turn of the cochlea. This reconstruction helped to assess the space available to drain the lesion via an infracochlear approach.

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with considerable success.6,14,29 A postauricular incision is used, and a superiorly based tympanomeatal flap is elevated. Drilling of the inferior canal provides access to the hypotympanum. Care must be taken to avoid inadvertent injury to the facial nerve in its descending portion as it curves anteriorly into the stylomastoid foramen. Additional careful bone removal is performed to identify the inferior margin of the otic capsule beneath the round window, the carotid artery, and the jugular bulb. The cholesterol granuloma is then entered through this space, and an aeration pathway is established. A Silastic stent can be used in an attempt to maintain patency. The transmastoid-infralabyrinthine approach takes advantage of the potential space inferior to the posterior semicircular canal, superior to the jugular bulb, and posterior to the descending facial nerve. Bone removal through the retrofacial air cells affords entrance to the cystic lesion from posterior. In favorable anatomy, a thin rim of bone can be maintained in this area to prevent the posterior fossa dura from prolapsing into the space and obstructing the aeration pathway. The success of this approach depends on the presence of a relatively low jugular bulb so there is room to work between it and the otic capsule.16 Surgical treatment of petrous apex cholesterol granulomas usually improves symptoms of balance disturbance and tinnitus.26 In a retrospective review of 11 patients treated with surgical drainage, 8 of 9 (88%) patients experiencing vertigo reported improvement postoperatively. Similarly, in the same group, 8 of 11 (73%) felt their tinnitus improved.26 Neuropathies of nerves other than cranial nerve VIII may also improve following surgical management. A review of 7 patients with cranial nerve deficits prior to complete surgical resection of a petrous apex cholesterol granuloma showed that at a mean followup of almost 4 years, 5 had recovered completely and 2 had improved.30 In another study of 12 patients with preoperative cranial neuropathies, 10 resolved postoperatively.29 Many patients can become completely asymptomatic.29,30 Hearing results postoperatively vary, with the majority of patients seeming to stabilize at their preoperative level or to continue to deteriorate. In a study of 11 patients with surgically treated cholesterol granulomas, 6 of 11 (55%) continued to have deterioration in their hearing with an average follow-up of 2 years. Only 1 of these patients had improvement in hearing.26 Recurrence is a risk regardless of the surgical approach. Recurrence is usually heralded by the recurrence of preoperative symptoms. About half of patients who had undergone drainage procedures in some series required some additional intervention for recurrent disease.14,28,34 In another study, only 3 of 25 patients required additional procedures between 1 and 4 years following initial drainage.29 Recurrence usually seems to be precipitated by the closure of the drainage pathway either with soft tissue or bone. Often a limited procedure to clear fibrotic tissue from the stent was all that was needed to restore patency.29 Patients treated with incomplete resection without the establishment of a long-term aeration pathway are at greatest risk.34 Complete resection appears to have a lower incidence of recurrence, with one study finding no recurrence in 10 patients followed for a mean of longer than 3 years30 and another study showing no recurrence in

8 patients followed between 2 and 8 years.20 Therefore, the additional morbidity associated with a larger initial procedure needs to be weighed against the potential for lower overall rate of recurrence. Postoperative imaging can be beneficial in long-term follow-up. Care must be taken in assessing the persistence of a bony cavity. Following drainage procedures, the cavity often remains fluid-filled and can look indistinguishable from preoperative studies on CT. The fluid usually present following adequate drainage usually displays low signal intensity on T1- and T2-weighted MRI imaging.26 Therefore, postoperative findings may often be distinguished from recurrence, which will again show bright signal on both T1 and T2 images. In one study with follow-up imaging performed after drainage procedures (average of longer than 3 years postoperatively), 15 of 18 cavities appeared to be reduced, and they were stable in size in 3 patients. Of the same 18 lesions, 5 were aerated on follow-up imaging.29

Cholesteatoma Epithelial inclusion cysts can develop within the petrous apex. The majority of cholesteatomas involving the petrous apex are the result of direct extension from the middle ear. However, the possibility of a primary developmental lesion (epidermoid) involving the petrous apex should also be considered. The exfoliated keratin debris that characterizes cholesteatomas produces a slowly expanding lesion that progressively erodes the bone of the petrous apex. Congenital cholesteatomas are sterile as a rule unless contaminated by surgery or by erosion into a contaminated space. However, acquired cholesteatomas, arising secondary to chronic otitis media, are much more likely to be complicated by infection. Cholesteatomas spread preferentially through preexisting air cell tracts. Patients with chronic otitis media often have poorly pneumatized, sclerotic temporal bones, with few air cells. Such temporal bones may thereby have more natural barriers preventing cholesteatoma extension to the petrous apex than do normally pneumatized bones. Despite this, growth of cholesteatomas into the petrous apex can occur through perilabyrinthine routes or via an eroded inner ear.38,39 In contrast, congenital cholesteatomas usually occur in otherwise normal, well-pneumatized temporal bones. In these cases, cholesteatoma may spread relatively unimpeded to the petrous apex through air cell tracts. Patients who present with petrous apex cholesteatoma often have a history of chronic middle ear disease or have had surgery. The diagnosis is often supported by findings characteristic of active cholesteatoma on otoscopy. Recurrent disease can present in the petrous apex with minimal or no evidence of recurrence in the middle ear. Cholesteatomas in the petrous apex therefore often present with much more advanced symptoms than do their mastoid counterparts, causing facial paralysis in approximately 50% and hearing loss in about 80%, and commonly causing vertigo, tinnitus, and headache.39,40 In patients suspected of having a petrous apex cholesteatoma, CT imaging provides the most detail about the degree of petrous apex involvement, as well as the status of the middle ear and mastoid (Fig. 66-7). On CT, cholesteatomas show a lesion isointense to spinal fluid

Lesions of the Petrous Apex

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gain adequate access for dissection while preserving inner ear integrity. A translabyrinthine approach may be successfully employed if hearing preservation is not a concern.39 The frequent coexistence of infection with cholesteatoma may increase risk of meningitis if the dura is transgressed. Careful long-term follow-up is needed for patients with petrous apex cholesteatoma. Regular examination and radiologic imaging may provide early indication of recurrence and thereby facilitate timely management.

Mucocele A

B

C Figure 66-7. Petrous apex cholesteatoma (arrows). A, Axial T1-weighted MRI shows a hypointense petrous apex compared to the marrow in the contralateral apex. B, On T2-weighted imaging, the cholesteatoma is hyperintense to brain. C, An axial CT image demonstrates bone erosion of the petrous apex with scalloped margins. There is also evidence of a previously performed canal wall-down mastoidectomy, further supporting the diagnosis of cholesteatoma.

with either smooth or scalloped margins. Cholesteatomas do not enhance with the administration of intravenous contrast, although adjacent inflammation or granulation tissue may show some uptake. Radiologic evidence of middle ear or mastoid disease may be central to establishing the presence of cholesteatoma in the petrous apex. On MRI, cholesteatomas are hypointense on T1-weighted signal and hyperintense on T2-weighted signal.4,41 There is no uptake of intravenous gadolinium. MRI with contrast may also augment CT imaging in the detection of additional intracranial complications from advanced chronic otitis media and cholesteatoma. It should be noted that occasionally cholesteatoma demonstrates MRI signal characteristics similar to those of a cholesterol granuloma.4,10 In contrast to cholesterol granuloma, cholesteatoma is a true epithelium-lined cyst. Therefore, drainage procedures alone usually do not offer the potential for longterm control. As is the case for middle ear cholesteatomas, cholesteatoma involving the petrous apex should be either exteriorized or resected for cure. Adequate exteriorization of disease within the petrous apex is rarely possible given anatomic limitations and the ongoing risks of dural and carotid injury. Complete resection is preferred if possible.42 A number of approaches are available for this depending on the status of hearing and the location of the lesion. Transmastoid and middle fossa approaches may

Mucoceles represent slowly expanding cystic lesions that may evolve from any pneumatized region of the skull base. Mucoceles appear to result from obstruction of a mucuslined space that contains secretory glandular tissue.43,44 They are most common in the paranasal sinuses but can also involve a pneumatized petrous apex. Such lesions are quite rare and present with symptoms common to other slowly expanding lesions of the petrous apex. On CT, mucoceles of the petrous apex appear as sharply defined expansile lesions isodense to spinal fluid. Unlike with the incidental finding of an effusion, bony septations are lost. Absent the presence of infection, they do not enhance, although the rim may enhance somewhat secondary to mucosal inflammation. On MRI, mucoceles are of intermediate signal on T1-weighted images and are bright on T2-weighted signals. There is no central enhancement with gadolinium.45 The management of petrous apex mucoceles is similar to that of cholesterol granuloma just described. Small asymptomatic lesions may be followed clinically and with serial imaging studies. Expanding lesions with progressive symptoms should be considered for surgical management. Craniotomy for resection may be undertaken, but intradural contamination with mucocele contents may produce a significant risk of postoperative meningitis.46 Drainage procedures and the reestablishment of an aeration tract, as done for cholesterol granuloma, should be considered.

Cephalocele On rare occasion, a protrusion of the meninges extends into the petrous apex.47–49 Such lesions may either be a meningocele, containing all of the layers of the meninges including the dura, or an arachnoid cyst extending through a dural defect. Therefore, as a group they may best be referred to as petrous apex cephaloceles.49 The cephaloceles extend from the posterolateral aspect of Meckel’s cave into the petrous apex, and they can either be congenital or acquired, although the pathophysiology remains uncertain. They are usually unilateral but may be bilateral in as many as 30% of patients.49 On CT imaging, cephaloceles have sharp bony edges and a homogeneous low-attenuation center. They extend into the petrous apex from the posterolateral margin of Meckel’s cave and show erosion of the trigeminal impression. On MRI, cephaloceles show signal intensity patterns similar to that of spinal fluid. They display low signal on T1-weighted images and may have mild rim enhancement with the administration of gadolinium. On T2-weighted

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B

Figure 66-8. Imaging studies from a child with a congenital petrous apex arachnoid cyst and CSF leak. A, Axial T2-weighted MRI shows the lesion to have high signal intensity, similar to that of adjacent CSF. B, A coronal CT image was obtained following the administration of intrathecal metrizamide. The metrizamide shows free flow into the petrous apex, thereby confirming the diagnosis of an arachnoid cyst.

A images, the lesions are homogeneously bright. That these lesions are centered extrinsic to the petrous apex and are in continuity with Meckel’s cave are important characteristics in establishing the diagnosis. The differentiation of a cyst containing spinal fluid (meningocele or arachnoid cyst) from one containing keratin (epidermoid or cholesteatoma) can present a challenge.10 They have similar signal intensity on T1- and T2-weighted MRI images. Historically, a CT scan with intrathecal contrast would often be helpful (Fig. 66-8). If the contrast flowed freely into the lesion in question, the presence of CSF could be reasonably assumed. However, with the advent of newer MRI techniques, less invasive means are available to establish the diagnosis. Keratin tends to be slightly hyperintense to CSF on proton-weighted imaging in the great majority of cases; it is only rarely isointense to CSF on all MRI sequences.50 There is also greater heterogeneity in a keratin-filled cyst than in one containing CSF. In addition, fluid-attenuated inversion recovery (FLAIR) sequences tend to leave CSF black, while keratin will remain bright, thereby helping to make the diagnosis.10,51 The degree to which petrous apex cephaloceles cause symptoms is unclear. They may frequently be asymptomatic, being discovered only incidentally on radiologic studies. One series found that 6 out of 10 patients with radiographic evidence of a petrous apex cephalocele had either contralateral or nonspecific symptoms as indications for the imaging study.49 Surgery may be indicated in patients who present with trigeminal nerve dysfunction or spinal fluid leak or other ipsilateral cranial neuropathy. In such cases, the goal of surgery should be resection and plugging of the dural defect.

INFECTIOUS Petrous Apicitis Suppurative infections of the petrous apex have historically had a high associated morbidity; such infections were often fatal in the pre-antibiotic era.1 With the availability of

antibiotics and surgical management of chronic otitis media, petrous apicitis has become increasingly rare.52 The clinician must be aware of this entity, however, because its early clinical and radiologic diagnosis and prompt therapy can avert significant morbidity. The bacteriology of petrous apicitis is similar to that of coalescent mastoiditis. Commonly, Pneumococcus, Haemophilus influenzae, and β-hemolytic streptococcus are seen. Staphylococcus species can be causative in cases associated with skull base osteomyelitis, and Pseudomonas species are common in petrous apicitis associated with chronic otitis media. Petrous apicitis may be classified as either acute or chronic.53 Acute petrositis usually develops from the relatively unimpeded spread of infection in a pneumatized apex. In contrast, chronic petrositis is a more slowly evolving variant, usually seen in temporal bones of patients with a history of chronic otitis media and limited air cell development. Clinically, petrous apicitis is characterized by pain, which may be temporal, occipital, or retro-orbital. Facial pain can occur as the result of fifth nerve involvement. Symptoms suggestive of concurrent otitis media, including hearing loss and purulent otorrhea, are also characteristic. When an abscess develops, the sixth cranial nerve is susceptible to injury as it courses through Dorello’s canal, resulting in an ipsilateral abducens palsy.7 The triad of concurrent diplopia, otorrhea, and retro-orbital pain constitute Gradenigo’s syndrome, which has historically been a hallmark for the diagnosis of petrous apicitis.54 Complications of petrous apicitis may result from the spread of infection to adjacent structures. Intracranial spread may result in brain abscess, subdural empyema, meningitis, or dural sinus thrombosis, including cavernous sinus thrombosis. Intratemporal extension can result in labyrinthitis or facial paralysis. Spread may also extend into the deep neck spaces, producing abscesses in the lateral pharyngeal or retropharyngeal spaces. CT scans of patients with acute petrous apicitis show an expansile lesion with dissolution of normal bony trabeculations (Fig. 66-9). In acute petrous apicitis, the contralateral petrous apex is often well pneumatized. In chronic petrous apicitis, CT reveals a destructive lesion in the petrous apex

Lesions of the Petrous Apex

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Skull Base Osteomyelitis

A

B Figure 66-9. Acute petrous apicitis with abscess formation (arrows). A, On T1-weighted MRI with gadolinium, an abscess of the petrous apex has low signal strength centrally with marked rim enhancement. B, On axial CT imaging, there is evidence of irregular bone erosion. Note the pneumatization of the contralateral petrous apex. It is likely that a similar cell on the infected side gave rise to the abscess. (Jackler RK, Parker DA: Radiographic differential diagnosis of petrous apex lesions. Am J Otol 13:561–574, 1992.)

Skull base osteomyelitis is usually the result of extension of bacterial infection from otitis externa to involve both the cortical and marrow spaces of the skull base. Such “malignant otitis externa” is usually seen in diabetic or otherwise immunocompromised or debilitated patients. It is clinically characterized by unremitting deep pain and the presence of refractory otitis externa. Often, as the disease progresses, cranial neuropathies develop. Care must be taken to exclude malignancy; the clinical picture may be similar. Biopsy of the external ear canal should be considered early. The most common etiologic pathogen is Pseudomonas. The petrous apex is often involved by this invasive infectious process. CT and MR imaging is often nonspecific, especially in the early stages of the disease. With disease progression, bone demineralization and sequestration can be seen on CT. Nuclear medicine studies are more helpful in the diagnosis of skull base osteomyelitis. A technetium-99 scan is quite sensitive to detect osteomyelitis, but it is rather nonspecific. The addition of gallium increases the specificity and helps establish the diagnosis. The resolution of a positive gallium scan can also be used as an indication for the success of systemic antibiotic administration.55 The technetium scan will remain positive indefinitely. The treatment of choice is the prolonged administration of pathogen-specific systemic antibiotics. Surgical management is reserved for cases that show evidence of abscess formation, bony sequestra, or necrotic tissue.

NEOPLASTIC and concurrent evidence of chronic otitis media within the remainder of the temporal bone. With administration of contrast, a rim of inflammatory tissue may enhance, while the center of the lesion usually remains unenhanced. On MR imaging, the lesions demonstrate low signal strength on T1-weighted images and high signal on T2 images. Enhancement of the rim (of the lesion) often occurs with gadolinium administration. The cornerstone of management of petrous apicitis remains the prompt administration of appropriate intravenous antibiotics.7 In the case of clinical progression despite medical management, or the development of suppurative complications, surgical drainage should be considered. As is the case for other lesions of the petrous apex, the selection of a surgical approach depends on the location of the lesion, the surrounding anatomy, and the presence of coexisting deficits. In a nonhearing ear, a translabyrinthine approach remains the most direct. However, in ears with functional hearing, a number of approaches might be used for adequate drainage. Often, the surgeon can follow the natural air cell tracts that initially allowed the spread of infection from the middle ear to the petrous apex. Approaches can pass anterior, superior, or inferior to the inner ear.1,18,19 Subarcuate drainage, passing through the arch of the superior semicircular canal, has also been described.17 Additional treatment of any concurrent middle ear or mastoid disease needs to be undertaken to ensure pronged drainage and prevent recurrence.

Chondrosarcoma Chondrosarcoma is a rare primary malignancy of bone, potentially arising from any bone developing from endochondral ossification, accounting for approximately one third of all primary malignancies of bone. Intracranial chondrosarcomas account for less than 0.2% of all intracranial tumors.56 The cell of origin for chondrosarcomas has yet to be definitively proved. It has long been suggested that chondrosarcomas arise from persistent chondrocytes present at the convergence of the petrosphenoid, petro-occipital, and spheno-occipital sutures.57 The development of chondrosarcoma from these embryologic rests of cartilage helps to explain the characteristic origin of skull base chondrosarcoma at the foramen lacerum or petroclival suture line. This characteristic site of origin off of the midline is in contrast to skull base chordomas, which can otherwise be quite similar in appearance. Other theories suggest that chondrosarcomas originate from metaplasia of fibroblasts or from multipotential cells within the dura or temporal bone itself.58 Chondrosarcomas can be divided into five histologic subtypes: conventional, myxoid, mesenchymal, clear cell, and dedifferentiated, any of which can appear in the petrous apex.59 The expected natural history of a chondrosarcoma is correlated with its histologic grade. Well-differentiated chondrosarcomas with fewer mitoses have significantly better overall prognoses than poorly differentiated,

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histologically aggressive lesions.60 Immunohistochemistry can help to differentiate chondrosarcoma from chordomas. Both tumors express S100 markers and give positive results of vimentin staining. However, chordomas test positive for cytokeratin and epithelial membrane antigen, while chondrosarcomas are not.61 Grossly, chondrosarcomas tend to be gray, avascular, and gelatinous. The tumors can be quite slow growing and are often diagnosed years after the onset of symptoms, with a mean length of approximately 2 years.62 They have no sex predilection and usually occur in the fourth and fifth decades of life.62,63 The most common initial symptoms include headache, hearing loss, diplopia, and lower cranial neuropathy.58,62,63 The overall incidence of metastasis is approximately 15%, with the rate increasing to 70% for poorly differentiated (grade III) tumors.60 On CT, chondrosarcomas appear as infiltrative lesions and enhance with intravenous contrast (Fig. 66-10). Given their infiltrative growth pattern, chondrosarcomas often contain remnants of eroded bone, which appear as specks of calcification on CT images. On MRI, chondrosarcomas are usually homogeneous on T1-weighted images, with low to intermediate signal intensity. They are usually quite bright on T2 images and may be heterogeneous. Areas of calcification can often be seen as a signal void. Chondrosarcomas usually enhance brightly with the administration of gadolinium. They often enhance more with contrast than do chordomas, which may help differentiate these lesions.64 Once identified, surgical excision remains a cornerstone of treatment. Minimally invasive approaches such as through the infracochlear route may be sufficient to establish a diagnosis, but they are unlikely to afford complete tumor resection. A variety of skull base approaches can be used to gain further access to the petrous apex for tumor resection, depending on the size of the lesion, its location, and the existence of preexisting cranial nerve deficits.65 Complete resection can be hindered by tumor involvement of vital neurovascular structures, including the internal carotid artery and brainstem. However, the soft nature of these tumors often facilitates dissection. The role of radiotherapy in the management of chondrosarcoma remains to be fully defined, but it appears to be beneficial in many cases.66 When surgical resection is not possible, stereotactic radiation has been advocated as the sole treatment in patients with small tumors.67 Given the rarity of these lesions, the efficacy of such treatment remains to be

fully defined. The overall expected 5-year control rate with multimodality therapy is approximately 95%.66

Chordoma Chordomas are rare, locally aggressive, primary bone lesions that can affect the petrous apex. Chordomas arise from embryologic remnants of the notochord. They usually originate in the clivus, with most skull base chordomas originating at the spheno-occipital synchondrosis. They often spread laterally to infiltrate the petrous apex and adjacent structures. Primary chordoma of the petrous apex can be seen, however, and are likely the result of embryologic notochord remnants in the petrous apex bone itself.68 When they involve the petrous apex, chordomas can be very similar to chondrosarcomas in their clinical presentation.62,69 They also occur most commonly in the fourth and fifth decades of life and may produce symptoms for years before definitive identification. Their symptoms are similar to other lesions of the petrous apex, with headache and diplopia being most common. On CT imaging, chordomas are usually centered within the clivus in the midline and are lobulated and locally destructive (Fig. 66-11). They may contain retained calcifications from eroded bone, and they enhance with administration of intravenous contrast. On MRI, the signal characteristics of chordoma are similar to those associated with chondrosarcoma, as previously stated. However, chordomas tend to enhance less intensely with administration of gadolinium. This and their midline location can help differentiate chordoma from chondrosarcoma. Like chondrosarcomas, chordomas are grossly gelatinous, gray, and relatively avascular. Often chordomas are differentiated from chondrosarcomas only through histologic analysis. Histologically, chordomas are characterized by vacuolated physaliphorous cells within a myxoid matrix.70 The tumors tend to be arranged in a lobulated pattern, with cells growing in cords or pseudoacini. Chondroid chordoma is a histologic subtype, which comprises about 35% of skull base chordomas.62 Such lesions contain differentiated cartilage tissue, further blurring the distinction from chondrosarcoma. The natural history of chordoma is characterized by frequent local recurrence, even many years after treatment. Distant metastases are infrequent. Histologic evidence of

Figure 66-10. Chondrosarcoma (arrows) involving the petrous apex. A, On an axial T1-weighted MRI with intravenous gadolinium, the chondrosarcoma is seen arising from the petroclival suture line, which is the usual site of origin for these tumors. The lesion is hypointense but enhances with the administration of contrast. B, On a T2-weighted image, the chondrosarcoma is quite bright. C, An axial CT image shows an infiltrative pattern of tumor growth, with indistinct bony margins and intralesional calcifications.

A

B

C

Lesions of the Petrous Apex

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However, the addition of radiosurgery or proton radiation may increase disease-control rates.75

Meningioma

Figure 66-11. Axial CT image of a chordoma involving the petrous apex. The lesion likely arose from within the clivus in the midline (arrow) and grew laterally to erode the bone of the petrous apex (*). Note the indistinct bony margins and the remnants of calcification in the lesion. These findings are characteristic of the growth of both chordoma and chondrosarcoma.

mitoses and poor differentiation portend unfavorable prognoses. The chondroid chordoma subtype was previously thought to have more favorable outcomes than the classic chordoma,69 although more recent reviews suggest this is not the case.71 Overall gross total excision offers the best prognosis, with recurrence-free 5-year survival rates in the 80% range.72,73 However, despite this, 10-year disease-free survival figures continue to drop to below 50%, regardless of treatment.73 The addition of conventional radiation to surgical resection seems to add little to overall prognosis.74

Meningiomas are common intracranial neoplasms that arise from the arachnoid villi of the meninges. They account for between 10% and 20% of all intracranial tumors.76,77 Petroclival meningiomas arise from the dura in the region of the petroclival synchondrosis, cephalad to the jugular tubercle, medial to the trigeminal nerve, and anterior to the porus acousticus.21 These tumors tend to grow very slowly but may adhere to adjacent vital neurovascular structures. On CT imaging, meningiomas are either isodense or hyperdense compared with surrounding brain and are usually homogeneously enhanced by the administration of intravenous contrast. Calcification in a meningioma is often seen, occasionally with almost complete ossification. Hyperostosis of the adjacent calvarium is a classic sign of meningioma and is often identified on CT images (Fig. 66-12). This also can occur in the adjacent petrous apex or clival bone. Occasionally, meningiomas invade the petrous apex. CT is the modality of choice in defining such a process affecting bone. On MRI, meningiomas are usually found to have broadbased dural attachments. If the tumor is small, there may be a thin line of signal void separating the lesion from the adjacent cortex. They can be heterogeneous on both T1- and T2-weighted images if intratumoral calcification or cystic degeneration is present. Most petroclival meningiomas are either isointense or hyperintense to brain on T1- and T2-weighted images.78 They enhance with the administration of gadolinium and often show enhancement of adjacent dura likely from hypervascularity (“meningeal sign” or “dural tail”)79,80 (see Fig. 66-12). A number of microsurgical approaches to petroclival meningiomas have been described.21,81 The most commonly employed are the petrosal approaches, which combine a temporal craniotomy with partial temporal bone resection to improve exposure while minimizing brain retraction. Anterior petrosal approaches combine

Figure 66-12. Petroclival meningioma. A, On T1-weighted MRI with gadolinium, tumor (*) is seen in both the middle and posterior fossae, extending over the petrous pyramid. The meningioma enhances with contrast and is heterogenous in signal strength. There is also enhancement of the adjacent dura (arrow) extending posteriorly into the internal auditory canal (“dural tail”). Areas of hyperostosis are evident (arrowheads) and the bright signal seen from normal marrow within the clivus and petrous apex is lost. B, On an axial CT image at the same level, the hyperostosis can be seen better (arrowheads). There is also an effusion in the mastoid air cells, secondary to tumor obstructing the eustachian tube.

A

B

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Figure 66-13. A, Recurrent vestibular schwannoma affecting the petrous apex (arrows). On T1-weighted MRI, the schwannoma enhances with the administration of gadolinium. On CT imaging, there is evidence of expansile growth eroding the bone of the petrous apex, leaving smooth margins. There is evidence of the initial retrosigmoid attempt at tumor resection undertaken many years before the patient’s presentation with this recurrence.

A

B

a temporal craniotomy with resection of the anterior petrous apex. Posterior petrosal approaches combine a temporal craniotomy with either a retrolabyrinthine, translabyrinthine, or transcochlear posterior fossa craniotomy. A number of variations exist, and the approach and amount of temporal bone resection needs to be tailored to the patient’s individual tumor anatomy and the presence of preoperative neural deficits. Petroclival meningiomas are among the most challenging skull base lesions to treat.76 Attempts at complete resection have historically been hindered by significant surgical morbidity. While morbidity and mortality have decreased with the advent of modern surgical techniques, aggressive attempts at complete resection continue to be fraught with considerable risks. Safe and complete resection is seldom possible. Devascularized residual tumor may display limited growth even with prolonged follow-up.82 Postoperative radiation therapy using stereotactic techniques can effectively control tumor growth in patients with known residual tumor.21,83

Neurogenic Tumors Schwannomas or neuromas arising from adjacent cranial nerves may grow to involve the petrous apex. The fifth cranial nerve may be the origin anteriorly and superiorly. The seventh and eighth nerves may give rise to schwannomas affecting the petrous apex posteriorly and medially. The lower cranial nerves (IX through XII) may be the site of origin for neurogenic tumors affecting the petrous apex from inferiorly. In addition, neurogenic tumors rarely appear to arise primarily within the petrous bone.84–86 Such tumors may arise from the greater superficial petrosal nerve, the deep petrosal nerve, or other small unnamed autonomic fibers. Recurrent vestibular schwannomas are more likely to infiltrate the petrous apex than the primary tumors. On CT, schwannomas usually show smooth, expansile bone erosion (Fig. 66-13). They enhance with administration of intravenous contrast. On T1-weighted MRI, schwannomas can be variable in signal intensity, with the majority displaying low or isointense signal to brain. On T2-weighted imaging, the majority of schwannomas are bright. They show enhancement with administration of gadolinium. Some heterogeneity of signal is often seen, secondary to cystic degeneration or intratumor hemorrhage. Surgical resection remains the treatment of choice if possible. The role of stereotactic radiosurgery in the

management of primary skull base schwannomas remains controversial. Although initial results are promising, longterm control rates with current dosing methods have yet to be established.

Metastatic Lesions Metastatic lesions that involve the petrous apex have long been recognized.87 The most common metastatic lesions in the petrous apex are breast, lung, prostate, melanoma, and kidney.88–91 There appears to be a tendency for hematogenous spread of malignancy to the petrous apex because of the filtering effect of its bone marrow.87 Presumably, slow blood flow through the vascular channels within the marrow facilitate deposition of tumor cells. All ages can be affected by the spread of malignancy to the petrous apex, with the peak incidence coinciding with the greatest risk of development of the primary tumor (usually between age 50 and 70 years).88,91 A review of 212 patients with a history of nondisseminated malignancy who underwent autopsy was performed at a single center.91 The temporal bones were studied histologically, and 47 (22%) had evidence of malignancy from a total of 20 tumor types. The petrous apex was involved in 83% of affected temporal bones, the great majority presumably affected through hematogenous spread. Of note, no patients who had died despite local control of their primary tumor showed evidence of temporal bone malignancy and all of those with hematologic spread had additional metastatic foci elsewhere. These findings suggest that petrous apex involvement is relatively frequent in the final stages of uncontrolled malignancy. Imaging of metastatic lesions of the petrous apex varies depending on the histology of the primary tumor. Breast and prostate carcinoma can incite an osteoblastic reaction. Bone erosion is the rule, and lesions usually enhance with the administration of intravenous contrast (Fig. 66-14).

Other Neoplasms Other solid tumors occasionally present in the petrous apex. Such tumors include nasopharyngeal carcinoma extending through the petro-occipital fissure. Xanthomas may appear in the petrous apex.6 Osteogenic sarcoma and chondromyxoid fibroma are other tumors of bone origin that may present similarly to chordoma or chondrosarcoma.92 Often these rare tumors are identified only

Lesions of the Petrous Apex

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Figure 66-14. Axial CT image of a patient with breast carcinoma metastatic to the petrous apex (arrows). The lesion shows irregular bone destruction suggestive of tumor infiltration. (From Jackler RK, Parker DA: Radiographic differential diagnosis of petrous apex lesions. Am J Otol 13:561–574, 1992.)

Intrapetrous carotid artery aneurysm is a rare entity that may present with symptoms similar to other space-occupying lesions in this area.94,95 Such aneurysms may be congenital or may be acquired as the result of traumatic, mycotic, or inflammatory injury. Bilateral aneurysms can also be seen. CT scans usually show smooth widening of the intrapetrous carotid canal, with contrast enhancement often being heterogeneous as a result of the accumulation of intralesional thrombus (Fig. 66-15). MRI often shows a central flow void if the artery remains patent. With the maturation of old thrombus and the addition of new thrombus, intrapetrous aneurysms often show a characteristic “onion skin” appearance, with heterogeneous layers of signal intensity ringing the lesion. New thrombus tends to demonstrate low signal on T1-weighted images and high signal on T2-weighted images. Over weeks, the T1 signal becomes brighter, and eventually both T1 and T2 signals are of intermediate strength. Once an aneurysm is suspected, angiography is essential to confirm the diagnosis. MR angiography may help to confirm the diagnosis (Fig. 66-16), but standard endovascular studies provide the potential for test occlusion and the possibility for endovascular treatment.

OSTEODYSTROPHY after careful histologic analysis. Endolymphatic sac tumors are papillary adenomatous neoplasms arising from the endolymphatic sac.93 These tend to be locally aggressive. They are often identified by their site of origin, which is along the posterior petrous face, where the sac is normally found. Hematologic systemic malignancy may also appear as a lesion in the petrous apex, owing largely to the presence of marrow in this structure. These neoplasms include eosinophilic granuloma, multiple myeloma, lymphoma, and leukemic infiltration.

Rarely the petrous apex is the center of primary osseous lesion such as fibrous dysplasia, Paget’s disease, or osteopetrosis. Usually the appearance of these lesions on CT imaging and the presence of additional bony abnormalities aids in the diagnosis. Fibrous dysplasia involving the petrous bone can occasionally result in hearing loss secondary to stenosis of the internal auditory canal. Surgical decompression of such lesions can potentially improve hearing.96 The temporal bone may be the only site affected in the monostotic variant of fibrous dysplasia.97,98

Figure 66-15. A, Imaging studies of a large intrapetrous carotid artery aneurysm (arrows). CT scan shows smooth bone erosion consistent with an expansile lesion. Contrast can be seen where flow remains within the arterial lumen (F). B, An axial T1-weighted MR image demonstrates the characteristic laminated appearance of alternating high and low signal regions. This is the result of thrombus of varying degrees of maturation. A flow void (F) is evidence of persistent blood flow within the arterial lumen. (From Jackler RK, Parker DA: Radiographic differential diagnosis of petrous apex lesions. Am J Otol 13:561–574, 1992.)

A

B

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Figure 66-16. Magnetic resonance angiography (MRA) demonstrating bilateral aneurysms of the carotid arteries (arrows). Although MRA can be quite helpful in making the diagnosis, conventional angiography provides confirmation and the potential for endovascular management.

ACKNOWLEDGEMENTS The authors would like to thank Robert Jackler, MD, and Barbara Carter, MD, for their assistance in compiling the radiologic images used in this chapter.

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15. House WF: Middle cranial fossa approach to the petrous pyramid. Arch Otolaryngol 78:460–467, 1963. 16. Haberkamp TJ: Surgical anatomy of the transtemporal approaches to the petrous apex. Am J Otol 18:501–506, 1997. 17. Frechner P: Some remarks on the treatment of apicitis (petrositis) with or without Gradenigo’s syndrome. Acta Otolaryngol (Stockh) 17:97–120, 1932. 18. Telischi FF, Luntz M, Whiteman ML: Supracochlear approach to the petrous apex: Case report and anatomic study. Am J Otol 20: 500–504, 1999. 19. Sperling NM, Bhaya MH: The precochlear approach to the anterior petrous apex: An anatomic study. Skull Base Surg 8:23–27, 1998. 20. Cristante L, Puchner MAJ: A keyhole middle fossa approach to large cholesterol granulomas of the petrous apex. Surg Neurol 53: 64–71, 2000. 21. Aziz A, Sanan A, van Loveren HR, et al: Petroclival meningiomas: Predictive parameters for transpetrosal approaches. Neurosurgery 47:139–150, 2000. 22. Bootz F, Keiner S, Schultz T, et al: Magnetic resonance imaging– guided biopsies of the petrous apex and petroclival region. Otol Neurotol 22:383–388, 2001. 23. Graham MD, Kemink JL, Latack JT, Kartush JM: The giant cholesterol cyst of the petrous apex: A distinct clinical entity. Laryngoscope 95:1401–1406, 1985. 24. Nager GT, Vanderveen TS: Cholesterol granuloma involving the temporal bone. Ann Otol Rhinol Laryngol 85:204–209, 1976. 25. Farrior B, Kampsen E, Farrior JB: The positive pressure of cholesterol granuloma idiopathic blue ear drum: Differential diagnosis. Laryngoscope 91:1286–1297, 1981. 26. Brodkey JA, Robertson JH, Shea JJ, Gardner G: Cholesterol granulomas of the petrous apex: Combined neurosurgical and otological management. J Neurosurg 85:625–633, 1996. 27. Jackler RK, Cho M: A new theory to explain the genesis of petrous apex cholesterol granuloma. Otol Neurotol 24(1):96–106, 2003. 28. Thedinger BA, Nadol JB, Montgomery WW, et al: Radiographic diagnosis, surgical treatment, and long-term follow-up of cholesterol granuloma of the petrous apex. Laryngoscope 99:896–907, 1989. 29. Fong BP, Brackmann DE, Teishi FF: The long-term follow-up of drainage procedures for petrous apex cholesterol granulomas. Arch Otolaryngol Head Neck Surg 1121:426–430, 1995. 30. Eisenberg MB, Haddad G, Al-Mefty O: Petrous apex cholesterol granulomas: Evolution and management. J Neurosurg 86:822–829, 1997. 31. Greenberg JJ, et al: Cholesterol granuloma of the petrous apex: MR and CT evaluation. Am J Neuroradiol 9:1205–1214, 1988. 32. Amedee RG, Marks HW, Lyons GD: Cholesterol granuloma of the petrous apex. Am J Otol 8:48–55, 1987. 33. Gherini SG, Brackmann DE, Lo WW, et al: Cholesterol granuloma of the petrous apex. Laryngoscope 95:659–664, 1985. 34. Altschuler EM, Jungreis CA, Sekhar LN, et al: Operative treatment of intracranial epidermoid cysts and cholesterol granulomas: Report of 21 cases. Neurosurgery 26:606–614, 1990. 35. Sabin HI, Bordi LT, Symon L: Epidermoid cysts and cholesterol granulomas centered on the posterior fossa: Twenty years of diagnosis and management. Neurosurgery 21:798–803, 1987. 36. Wyler AR, Leech RW, Reynolds AF, et al: Cholesterol granuloma of the petrous apex: Case report. J Neurosurg 41:765–768, 1974. 37. Gleason MJ, Fisch U, Makek M, Valvanis A: Mucosal cysts of the petrous apex. In Fisch U, Valvanis A, Yasargil MG (eds.): Neurological surgery of the ear and skull base. Berkeley, Kugler and Ghedini, 1989, pp 3–10. 38. Bartels LJ: Facial nerve and medially invasive petrous bone cholesteatoma. Ann Otol Rhinol Laryngol 100:308–316, 1991. 39. Atlas MD, Moffat DA, Hardy DG: Petrous apex cholesteatoma: Diagnostic and treatment dilemmas. Laryngoscope 102:1363–1368, 1992.

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40. Pyle GM, Weit RJ: Petrous apex cholesteatoma: Exteriorization vs. subtotal petrosectomy with obliteration. Skull Base Surg 1:97–104, 1991. 41. Smith PG, Leonetti JP, Klezker GR: Differential clinical and radiographic features of cholesterol granulomas and cholesteatomas of the petrous apex. Ann Otol Rhinol Laryngol 97:599–604, 1988. 42. Samii M, Tataagiba M, Piquer J, et al: Surgical treatment of epidermoid cysts of the cerebellopontine angle. J Neurosurg 84:14–19, 1996. 43. Evans C: Aetiology and treatment of fronto-ethmoidal mucocele. J Laryngol Otol 95:361–375, 1981. 44 Close LG, O’Connor WE: Sphenoethmoidal mucoceles with intracranial extension. Otolaryngol Head Neck Surg 91:350–357, 1983. 45. Larson TL, Wong ML: Primary mucocele of the petrous apex: MR appearance. Am J Neuroradiol 13:203–204, 1992. 46. Nugent GR, Sprinkle P, Bloor BM: Sphenoid sinus mucoceles. J Neurosurg 32:443–451, 1970. 47. Cheung SW, Broberg TG, Jackler RK: Petrous apex arachnoid cyst: Radiographic confusion with primary cholesteatoma. Am J Otol 16:690–694, 1995. 48. Mulcahy MM, McMenomey SO, Talbot JM, Deleshaw JB: Congenital encephaloceles of the medial skull base. Laryngoscope 107:910–914, 1997. 49. Moore KR, Fishbein NJ, Harnsberger HR, et al: Petrous apex cephaloceles. Am J Neuroradiol 22:1867–1871, 2001. 50. Kallmes DF, Provenzale JM, Cloft HJ, McClendon RE: Typical and atypical MR imaging features of intracranial epidermoid tumors. Am J Neuroradiol 169:883–887, 1997. 51. Kuzma B, Goodman JM: Epidermoid or arachnoid cyst. Surg Neurol 47:395–396, 1997. 52. Glasscock ME II: Chronic petrositis. Diagnosis and treatment. Ann Otol Rhinol Laryngol 81:677–685, 1972. 53. Allam AF, Schuknecht HF: Pathology of petrositis. Laryngoscope 78:1813–1832, 1968. 54. Gradenego G: Ueber die paralyse des nervus abducens bei otitis. Arch Ohrenheilkunde 74:149–187, 1907. 55. Levenson MJ, Parisier SC, Dolitsky J, Bindra G: Ciprofloxacin: Drug of choice in the treatment of malignant otitis externa (MEO). Laryngoscope 101:821–824, 1991. 56. Berkmen YM, Blatt ES: Cranial and intracranial cartilaginous tumors. Clin Radiol 19:327–333, 1968. 57. Jaffe H: Tumors and tumorous conditions of the bone and joints. Philadelphia, Lea and Febiger, 1958. 58. Lau DP, Wharton SB, Antoun NM, et al: Chondrosarcoma of the petrous apex: Dilemmas in diagnosis and treatment. J Laryngol Otol 111:368–371, 1997. 59. Barnes L, Kapadia SB: The biology and pathology of selected skull base tumors. J Neurooncol 20:213–240, 1994. 60. Evans H, Ayala A, Romsdahl M: Prognostic factors in chondrosarcoma of bone: A clinicopathologic analysis with emphasis on histologic grading. Cancer 40:818–831, 1977. 61. Wojno KJ, Hruban RH, Garin-Chesa P, Huvos AG: Chondroid chordomas and low grade chondrosarcomas of the craniospinal axis: An immunohistochemical analysis of 17 cases. Am J Surg Pathol 16:1144–1152, 1992. 62. Volpe NJ, Liebsch NJ, Munzenrider JE, et al: Neuro-ophthalmologic findings in chordoma and chondrosarcoma of the skull base. Am J Opthalmol 115:97–104, 1993. 63. Coltera MD, Googe PB, Harrist TJ, et al: Chondrosarcoma of the temporal bone: Diagnosis and treatment of 13 cases and review of the literature. Cancer 58:2689–2696, 1986. 64. Ikushima I, Korogi T, Hirai T, et al: Chordomas of the skull base: Dynamic MRI. J Comput Assist Tomogr 20:547–550, 1996. 65. Blevins NH, Jackler RK: Combined transpetrosal/middle fossa craniotomy for clival tumors with extension into the posterior fossa. Laryngoscope 105(9 pt 1):975–982, 1995. 66. Castro JR, Linstadt DE, Behary JP, et al: Experience in charged particle irradiation of tumors of the skull base: 1977–1992. Int J Radiat Oncol Biol Phys 29:647–655, 1994.

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67. Muthukumar N, Kondziolka D, Lundsford LD, et al: Stereotactic radiosurgery for chordoma and chondrosarcoma of the cranial base. Neurosurgery 29:38–45, 1998. 68. Brown RV, Sage MR, Brophy BP: CT and MR findings in patients with chordomas of the petrous apex. Am J Neuroradiol 11:121–124, 1990. 69. Heffelfinger MJ, Dahlin DC, Macarty CS, et al: Chordomas and cartilaginous tumors at the skull base. Cancer 32:410–420, 1973. 70. Batsakis J, Solomon A, Rice D: The pathology of head and neck tumors: Neoplasms of cartilage, bone, and the notochord, part 7. Head Neck Surg 3:43–57, 1980. 71. Jeffrey PB, Biava CG, Davis RL: Chondroid chordoma: A hyalinized chordoma without cartilaginous differentiation. Am J Clin Pathol 103:271–279, 1995. 72. Krespi YP, Levine TM, Oppenheimer R: Skull base chordomas. Otolaryngol Clin North Am 19:797–804, 1986. 73. Al-Mefty O, Borba LA: Skull base chordomas: A management challenge. J Neurosurg 86:182–189, 1997. 73. Watkins L, Khudados ES, Kaleoglu M, et al: Skull base chordomas: A review of 38 patients, 1958–88. Br J Neurosurg 7:241–248, 1993. 74. Keisch ME, Garcia DM, Shibuya RB: Retrospective long-term follow-up analysis in 21 patients with chordomas of various sites treated at a single institution. J Neurosurg 75:374–377, 1991. 75. Munzenrider J, Hug E, McManus P, et al: Skull base chordomas: Treatment outcome and prognostic factors in adult patients following conformal treatment with 3D planning and high dose fractionated combined proton and photon radiation therapy. Int J Radiat Oncol Biol Phys 32:27–32, 1995. 76. Cushing H, Eisenhardt L: Meningiomas: Their classification, regional behavior, life history, and surgical end results. Springfield, Ill: Charles C Thomas, 1938. 77. Nager GT, Masica DN: Meningiomas of the cerebellopontine angle and their relation to the temporal bone. Laryngoscope 80:863–895, 1970. 78. Zimmerman RD: MRI of intracranial meningioma. In Al-Mefty O (ed): Meningioma. New York, Raven, 1991, pp 209–223. 79. Goldsher D, et al: Dural “tail” associated with meningiomas on GdDTPA-enhanced images: Characteristics, differential diagnostic value, and possible implications for treatment. Radiology 176: 447–450, 1990. 80. Tokumaru A, Ouchi T, Eguchi T, et al: Prominent meningeal enhancement adjacent to meningioma of Gd-DTPA-enhanced MR images: Histopathologic correlation. Radiology 175:431–433, 1990. 81. Miller CG, van Loveren HR, Keller TJ, et al: Transpetrosal approach: Surgical anatomy and technique. Neurosurgery 33: 461–469, 1993. 82. Samii M, Ammirati M, Mahran A, et al: Surgery of petroclival meningiomas: Report of 24 cases. Neurosurgery 24:12–17, 1989. 83. Subach BR, Lunsford D, Kondziolka D, et al: Management of petroclival meningiomas by stereotactic radiosurgery. Neurosurgery 42:437–443, 1998. 84. Solodnik P, Som PM, Shugar JM: Intraosseous petrous apex neuroma: CT findings. J Comput Assist Tomogr 10:1927–1929, 1986. 85. Kumon Y, Sakaki S, Ohta S, et al: Greater superficial petrosal nerve neurinoma: Case report. J Neurosurg 91:691–696, 1999. 86. Kinouchi H, Mikawa S, Suzuki A, et al: Extradural neuromas at the petrous apex: Report of two cases. Neurosurgery 49:999–1004, 2001. 87. Proctor B, Lindsay JR: Tumors involving the petrous pyramid of the temporal bone. Arch Otolaryngol 46:180–194, 1947. 88. Maddox HE: Metastatic tumors of the temporal bone. Ann Otol Rhinol Laryngol 76:149–165, 1967. 89. Belal A: Metastatic tumors of the temporal bone: A histopathological report. J Laryngol Otol 99:839–846, 1985. 90. Nelson EG, Hinojosa R: Histopathology of metastatic temporal bone tumors. Arch Otolaryngol Head Neck Surg 117:189–193, 1991. 91. Gloria-Cruz TI, Schachern PA, Paparella MM, et al: Metastases to temporal bones from primary nonsystemic malignant neoplasms. Arch Otolaryngol Head Neck Surg 126:209–214, 2000. 92. Keel SB, Bhan AK, Liebsch NJ, et al: Chondromyxoid fibroma of the skull base: A tumor which may be confused with chordoma or

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chondrosarcoma—a report of three cases and review of the literature. Am J Surg Pathol 21:577–582, 1997. 93. Magerian CA, McKenna MJ, Nuss RC, et al: Endolymphatic sac tumors: Histopathologic confirmation, clinical characterization, and implication in von Hippel-Lindau disease. Laryngoscope 105: 801–808, 1995. 94. Halbach VV, et al: Aneurisms of the petrous portion of the internal carotid artery: Results of treatment with endovascular or surgical occlusion. Am J Neuroradiol 11:253–257, 1990. 95. d’Archambeau O, et al: CT diagnosis and differential diagnosis of otodystrophic lesions of the temporal bone. Eur J Radiol 11:22–30, 1990.

96. Morrissey DD, Talbot JM, Schleuning AJ: Fibrous dysplasia of the temporal bone: Reversal of sensorineural hearing loss after decompression of the internal auditory canal. Laryngoscope 107:1336–1340, 1997. 97. Megerian CA, Sofferman RA, McKenna MJ, et al: Fibrous dysplasia of the temporal bone: Ten new cases demonstrating the spectrum of otologic sequelae. Am J Otol 16(4)408–419, 1995. 98. Lustig LR, Holliday MJ, McCarthy EF, Nager G: Fibrous dysplasia involving the skull base and temporal bone. Arch Otolaryngol Head Neck Surg 127:1239–1247, 2001.

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Outline Introduction Fibrous Dysplasia Osteopetroses

Chapter

Diffuse Osseous Lesions of the Temporal Bone

Paget’s Disease Osteogenesis Imperfecta Summary

INTRODUCTION Diffuse osseous lesions of the temporal bone are a heterogeneous group of disorders that represent either focal manifestation of a systemic bone disorder or primary local disease. These bony dysplasias present to the otologist with clinical symptoms of hearing loss, progressive stenosis of the external auditory canal, and cranial nerve dysfunction resulting from foraminal narrowing and changes in the contour of the lateral skull surface. Although these lesions are histologically distinct, clinical presentation and conventional radiography often fail to differentiate among them. However, the employment of modern high-resolution computed tomography (HRCT) imaging with attention to the internal and external auditory canals, middle ear space, otic capsule, and facial nerve canal has enhanced our diagnostic acumen. The HRCT findings, when combined with clinical information, can often secure a definitive diagnosis. This chapter will focus on the clinical, histologic, and radiographic features of fibrous dysplasia, Paget’s disease, the osteopetroses, and osteogenesis imperfecta. General principles of management are outlined.

FIBROUS DYSPLASIA Fibrous dysplasia is a fairly common slowly progressive, locally expansive, benign fibroosseous disorder, which generally becomes quiescent after puberty. This disorder is thought to result from a somatic activating mutation of the alpha subunit in the Gs protein, causing up-regulation of cyclic adenosine monophosphate (cAMP). Through increased intracellular concentrations of cAMP, mesenchymal cells in bone are stimulated to increase the synthesis of interleukin-6 (IL-6). IL-6 is a cytokine that activates osteoclastic cells, resulting in overrepresentation of osteoclastic activity in bone homeostasis.1 Fibrous dysplasia encompasses 7% of all benign bone tumors.2 Lichenstein and Jaffe3,4 identified fibrous dysplasia as a distinct fibroosseous entity based on clinical and histologic features. Three major types have been classified: monostotic, polyostotic, and the McCune-Albright syndrome.5,6 In the monostotic variety,

Steven W. Cheung, MD Karsten Munck, MD Robert K. Jackler, MD

which accounts for 70% of all cases, a solitary bony lesion is identified.7 Although craniofacial involvement is found in only 10% of these cases, temporal bone fibrous dysplasia is commonly monostotic.8 Polyostotic disease represents multifocal bony involvement and accounts for 30% of all cases. The distribution may be monomelic, unilateral, or bilateral. Craniofacial involvement rises to 50% to 100% in the polyostotic form, depending on the extent of disease.9 The McCune-Albright syndrome5,6 is characterized by polyostotic fibrous dysplasia with endocrinopathy and cutaneous hyperpigmentation. This is an uncommon variety and seems to affect primarily females. Overall, temporal bone involvement is seen in 18% of fibrous dysplasia cases affecting the skull.8 A hallmark of fibrous dysplasia is the erosion of cortical bone from within. Normal bone is replaced by abnormal proliferative fibroosseous tissue in the medullary cavity that eventually erodes the cortex into a thin shell. The remodeled bone is immature and structurally weak. The primitive fibrous tissue is gritty in texture, nonencapsulated, vascular, and compressible. Histologically, fibrous dysplasia is heterogeneous, with interspersed regions of predominantly soft tissue or bone. Soft areas are abundant in collagen, mostly acellular, and occasionally contain cysts. Areas of intermediate consistency are populated by fibroblasts, which are often arranged in a whorl pattern. The bony areas have irregularly shaped immature trabeculae that appear to be coarse-fibered woven rather than lamellar bone.8,10–13 The absence of osteoblastic rimming is an important distinguishing feature.14 Common clinical manifestations of temporal bone fibrous dysplasia include external auditory canal stenosis, progressive hearing loss, and increased temporal bone size presenting as postauricular swelling. External auditory canal occlusion occurs in 22% to 42% of the patients.8,10 A complication from entrapment of squamous debris within the obstructed meatus is the formation of cholesteatoma. The entrapped cholesteatoma has been reported to cause chronic infection with otorrhea, ossicular chain fixation and destruction, and fallopian canal erosion.7,10–12,15–16 The otic capsule is spared by the primary disease process, although it may become secondarily involved with cholesteatoma. Hearing loss is seen in 30% to 57% of the patients with 1125

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temporal bone fibrous dysplasia.8,10 The vast majority is conductive in nature. Sensorineural hearing loss (SNHL) is rare and may be secondary to labyrinthine fistula with cholesteatoma or internal auditory canal (IAC) stenosis. Postauricular swelling is a clinical feature that is seen in 30% to 51% of the patients.8,10 Facial nerve paralysis is uncommon but has been reported by Nager and colleagues8 and Cohen and Rosenwasser.17 Facial nerve dysfunction in these cases occurred secondary to either infected cholesteatoma or fallopian canal stenosis. In a study of 39 patients with biopsy proven fibrous dysplasia, Fries18 described three patterns seen on plain radiography. In the sclerotic variety, homogeneous radiodensity is present and associated with bony expansion. A “ground glass” mass replaces normal bone. The borders tend to blend in with adjacent bone.13 In the pagetoid type, areas of radiolucency are evident with subjacent irregular sclerosis. Finally, in the cystic pattern, an ovoid radiolucency with a sclerotic border is observed. Contemporary imaging with HRCT is excellent at evaluating for external auditory canal stenosis and cholesteatoma due to entrapped canal skin.12 Furthermore, the middle ear cleft may be constricted by bony overgrowth, and the ossicular chain can be thickened by the fibroosseous process.8 The external auditory canal may be substantially lengthened, making transcanal procedures technically difficult.11 The otic capsule is usually normal, and IAC stenosis is rare.10,16 The radiographic diagnosis of fibrous dysplasia of the temporal bone is readily achieved in the polyostotic form, due to associated findings of recurrent spontaneous extremity fractures and pathognomonic “shepherd’s-crook” deformity of the upper femur.8 In the monostotic form, definitive diagnosis is often possible because of the predominance of the sclerotic pattern seen on computed tomography (CT) (Fig. 67-1).12 A problematic lesion is the cystic or radiolucent form. In this variant, malignancy cannot be excluded, so biopsy by mastoidectomy is recommended (Figs. 67-2 and 67-3).

No specific medical therapy exists for fibrous dysplasia. However, regular clinical monitoring is essential to assess for progressive external auditory meatal stenosis and cranial neuropathy. HRCT imaging is helpful in delineating middle ear and IAC involvement. Although not reported in the temporal bone, sarcomatous degeneration of fibrous dysplasia has been estimated to be 0.4% in monostotic and polyostotic disease and increased to 4% in the McCuneAlbright syndrome.14 Yabut and colleagues,19 in a review of 83 cases of malignancy arising from fibrous dysplasia, found that the most common transformed malignancy was osteosarcoma, followed by fibrosarcoma, chondrosarcoma, and giant-cell tumors. The craniofacial region was a common site of involvement. The distribution of cases was slightly increased in the monostotic variety. Pulmonary metastases were common. The prognosis was poor, with a mean survival period of 3.4 years. Radiation therapy should

Figure 67-1. Monostotic fibrous dysplasia. Axial CT scan shows replacement of the entire petrous, mastoid, and squamous portions of the temporal bone by an expansile “ground glass” sclerotic fibroosseous lesion. The middle ear space, internal and external auditory canals are narrowed.

Figure 67-3. Malignant fibrohistiocytoma. Axial CT scan shows an erosive lesion of the mastoid air cell system with apparent disruption of the posterior fossa plate. Note the similarity in appearance to the radiolucent variant of fibrous dysplasia. Biopsy, however, demonstrated malignant fibrohistiocytoma.

Figure 67-2. Atypical fibrous dysplasia. Axial CT scan shows an erosive lesion that extends from the mastoid to the region adjacent to the foramen magnum and jugular bulb. This is an atypical radiolucent variant of fibrous dysplasia. Diagnosis confirmed by biopsy.

Diffuse Osseous Lesions of the Temporal Bone

Figure 67-4. Fibrous dysplasia with entrapped cholesteatoma. Axial CT scan shows an expansile, sclerotic fibroosseous lesion and entrapped cholesteatoma within the external auditory canal.

be avoided because of reported increased risk for malignant transformation.19–21 Clinical features that suggest sarcomatous degeneration include pain, swelling, and radiographic evidence of bony destruction and disruption of cortical bone.8 Surgical treatment of temporal bone fibrous dysplasia is largely aimed at the maintenance of a patent external auditory canal to stabilize hearing and prevent complications arising from entrapped cholesteatoma (Fig. 67-4). Radical resection is not warranted for this benign disease. External auditory canal recontouring is plagued by restenosis. Revisions are not uncommon because the fibrodysplastic process may recur. A generous canal lined by splitthickness skin graft bolstered by silastic sheeting is recommended for difficult cases.8,12,16,22 The benefit from decompression of symptomatic internal auditory and fallopian canal stenosis remains investigational. Surgery of dysplastic temporal bone can be hazardous because landmarks may be obliterated and annoying bleeding is often encountered.

OSTEOPETROSES The osteopetroses are a group of inheritable metabolic bone disorders characterized by diffuse, dense sclerosis and faulty bony remodeling. Classically, two types have been identified. The congenita, or lethal, form is autosomalrecessive and result from a mutation in the gene that codes carbonic anhydrase II, causing renal tubular acidosis and cerebral calcifications during infancy.23 Medullary bony overgrowth results in obliteration of the marrow cavity,

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extramedullary hematopoiesis, and progressive pancytopenia. Death often occurs in infancy or childhood secondary to hemorrhage, anemia, or overwhelming infection. Few patients survive to adulthood.24,25 The tarda, or adult, form occurs as two types of autosomal-dominant variants. Type II, also known as Albers-Schönberg disease, is the most common, resulting from a genetic mutation in a chloride channel gene26 located on chromosome 16p13.3.27 This chloride channel gene is highly expressed in osteoclasts and serves to acidify the extracellular environment required for bone breakdown.26 The adult form tends to be benign and has a variable clinical course. Johnston and coworkers28 reported that 40% of the patients in this group are asymptomatic. The diagnosis is commonly made radiographically. Often included in the adult form are a number of craniotubular dysplasias and hyperostoses. These related entities present with similar otolaryngologic features arising from bony overgrowth and foraminal stenosis. However, they are clinically distinct and have been reviewed in detail by Beighton and colleagues.29 The pathogenesis of the osteopetroses is incompletely understood. Pathologically, in both the lethal and adult forms, a defect occurs in bone remodeling. Experimental studies support the hypothesis of a primary defect in osteoclast function.30–33 In regions of endochondral ossification, histopathologic examination reveals abnormal persistence of calcified cartilage.34 The osteopetrotic bone is immature, thick, dense, and brittle. This appearance gives rise to the names chalk, or marble bone, disease. Neurotologic features of the osteopetroses are related to progressive stenosis of neural canals and foramina and hearing loss. In osteopetrosis congenita, Johnston and coworkers28 reviewed 50 reported cases, and their findings are notable for significant optic atrophy (78%), hearing loss (22%), and facial palsy (10%). Facial paresis has been reported to be as high as 50% in Wong’s series of six patients.35 Ophthalmic compromise is felt to be a complication of foraminal stenosis due to bony overgrowth.36 Hawke and colleagues37 studied the temporal bone histology of a 17-year-old boy with osteogenesis congenita who had normal facial nerve function and pure conductive hearing loss documented prior to autopsy. The findings were notable for ossicular infiltration by osteopetrotic bone, primitive stapes, mastoid obliteration, and normal middle ear cleft and otic capsule. In another histologic study, Suga and Lindsay38 found exostoses from the epitympanum constricting the middle ear cleft and an enormously thickened periosteal layer of the otic capsule. The superstructure of the stapes was deeply embedded in the dehiscent facial nerve, and the mastoid antrum was poorly pneumatized. Myers and Stool39 reported a poorly pneumatized mastoid with a fetaltype stapes and persistent stapedial artery. In adult-type osteopetrosis Johnston and coworkers28 reviewed 133 reported cases. Nerve palsies involving cranial nerves II, III, and VII were found in 16% of the patients. Other cranial neuropathies affecting cranial nerves I and V have been documented.40 Hearing loss was not detailed in the Johnston and coworkers’ review.28 The nature of hearing loss was investigated by Bollerslev and colleagues.41 They performed otoneurologic testing on 14 patients with autosomal-dominant osteopetrosis. Hearing impairment was found in nine patients (five mixed, four conductive), and

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“light” facial palsy occurred in one patient. Facial nerve paralysis can be recurrent and has been documented to occur secondary to narrowing of the IAC, as well as the labyrinthine and vertical segments.37,42–44 Milroy and Michaels34 presented the temporal bone histopathology of a 62-year-old patient who died from complications of osteopetrosis tarda. The middle ear cleft was constricted, and the ossicles were abnormally thickened and distorted. The stapes anterior crus was ankylosed to the promontory, and a thickened posterior crus was apposed to the fallopian canal. The eustachian tube was narrowed, mastoid air cells were obliterated, otic capsule was expanded in all three layers, and IAC was markedly stenotic. The temporal bone pathologic findings of the osteopetroses manifest as space encroachment and bony replacement by the dysplastic process. The clinical findings result from complications of progressive faulty remodeling that narrow spaces, canals and foramina either through direct bony replacement or obstruction. Osteopetrosis congenita temporal bone HRCT findings have recently been reported by Bartynski and coworkers45 In summary, HRCT imaging demonstrated a small middle ear cavity with normal ossicles and obliteration of the mastoid antrum. The otic capsule appeared normal. Prominent subarcuate fossae and trumpet-shaped IACs were noted. The radiographic features were consistent with the histologic findings reported by Hawke and colleagues.37 Radiography of osteopetrosis tarda by conventional plain films of the skull will generally demonstrate diffuse chalky sclerosis and thickening of the cranial vault. Bollerslev and coworkers41,46 have classified the skull film findings into types I and II. In type I, sclerosis of the entire

Figure 67-5. Engleman’s disease. Axial CT scan shows chalky sclerosis and diffuse thickening of the entire skull. The internal and external auditory canals are narrowed. The mastoid antrum is obliterated. The ossicles are normal and the epitympanum is patent. The otic capsule is not expanded.

cranial vault is pronounced. In type II, the cranial base is extensively sclerotic and associated with endplate thickening of the spine. Type I has a high incidence of cranial nerve V dysfunction and conductive hearing loss. External and IAC stenoses are seen in association with type I. In type II, all patients exhibit facial nerve dysfunction, manifested by stapedial reflex abnormality, reduced tearing, or dysguesia. By far, temporal bone HRCT imaging can more accurately assess stenosis of neural canals and foramina, encroachment of pneumatic spaces, infiltration of the ossicles and size of the otic capsule (Figs. 67-5 and 67-6). The HRCT findings in ostopetrosis tarda generally reflect a more severely affected temporal bone by the osteopetrotic process. Despite a large number of distinct entities that fall into the general grouping of the osteopetroses, these radiographically dense, chalky sclerotic lesions are readily identifiable. HRCT imaging of the temporal bone is an important diagnostic tool for the otologist to correlate clinical symptoms of hearing loss and cranial neuropathy with status of the skull base. No effective medical therapy exists for the osteopetroses, so intervention is largely surgical. Hearing loss in the osteopetroses is largely conductive. Ossicular chain mechanics in the osteopetroses are dampened either by direct bony infiltration or epitympanic fixation. Furthermore, the stapes may be malformed and the footplate obliterated.39,44,47 External auditory canal stenosis and round window obliteration can be contributory features.48 Improvement of conductive hearing loss by ossiculoplasty may be technically difficult, due to dense middle ear bony disease and footplate abnormalities. As such, nonsurgical therapy by amplification should be considered.49 Recontouring of the external auditory canal may be necessary to facilitate fitting of hearing devices. Surgical decompression of the acoustic nerve for stabilization of SNHL in the osteopetroses remains investigational.

Figure 67-6. Osteopetrosis tarda. Axial CT scan shows narrowing of the internal and external auditory canals. The mastoid antrum is preserved. The ossicles are expanded and the epitympanum is collapsed. The otic capsule is expanded, and loss of distinction is evident between it and the surrounding petrous bone.

Diffuse Osseous Lesions of the Temporal Bone

Facial nerve dysfunction generally presents with acute and recurrent episodes of facial palsy that result in decremental return of function with each successive attack. The expected progressive facial palsy due to gradual fallopian canal stenosis is rare.50 Children with osteopetrosis may present with recurrent facial nerve palsy, which should be evaluated radiographically. Surgical therapy for facial paralysis in the osteopetroses appears to be beneficial. A number of reports support the role of transmastoid-subtemporal total facial nerve decompression.24,25,42,43 The combined approach will ensure complete decompression of all possible skip segments of stenosis along the entire fallopian canal.

PAGET’S DISEASE Paget’s disease, or osteitis deformans, is an incompletely understood disorder but probably involves up-regulation of the nuclear factor beta ligand (RANK) pathway, which is a tumor necrosis factor family receptor.51 Stimulation of the RANK receptor begins the maturation process for immature circulating mononuclear cells into mature osteoclastic cells with increased sensitivity to IL-6, which is know to stimulate osteoclastic actvity.52 The consequence of the increased osteoclastic activity is excessive remodeling of bone that principally affects the axial skeleton.53 The onset of clinical disease is uncommon prior to age 40 years. The overall incidence is 3%, but this figure steadily rises to 10% by the eighth decade.54 Of patients with Paget’s disease, 20% are asymptomatic.55 The diagnosis is commonly made during work-up for skeletal pain or as an incidental radiographic finding. The distribution of cases in Paget’s disease is mostly sporadic, yet in 15% of the cases, an autosomal-dominant inheritance pattern is evident.56 Recent investigation by cell culture techniques has implicated an immunoregulatory defect on chromosome 6. This finding, along with the identification of nuclear viral inclusions in osteoclasts is suggestive of a viral cause in Paget’s disease.57,58 However, no definitive virus has yet been identified. Histologically, alternating waves of osteoclastic and osteoblastic activity result in haphazard bony resorption followed by deposition of structurally weakened, demineralized cancellous bone. Bone resorption dominates in the early phase and can be seen as a lytic lesion. The marrow space is then filled with fibrovascular tissue, which later becomes sclerotic. The sclerosis is marked by a mosaic pattern of coarse fibers composed of irregularly oriented units of several generations of bone.53,59,60 Primary monostotic Paget’s disease of the temporal bone is rare.61 The skull is involved in 65% to 70% of advanced polyostotic cases.62 Bilateral temporal bone involvement is common.52 Tinnitus and vertigo are seen in 20% of these patients.63,64 Hearing impairment is found in 30% to 50% of the patients with skull involvement.53,54 Baraka65 found that the average rate of hearing loss in Paget’s disease as compared with a matched group was at 2 dB per annum, higher than the expected 0.5 dB per annum, although the actual rate varied by frequency. The pattern of hearing loss is predominantly mixed.59,66 The conductive component is most marked in the lower frequencies, whereas the sensorineural component is most pronounced

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in the higher frequencies.54,59 Other clinical manifestations observed are hemifacial spasm (7%), trigeminal neuralgia (6%), and optic atrophy.67 The cause is likely to be secondary to neural foraminal encroachment. Spinal cord lesions with vertebral involvement occurs secondary to fracture, extramedullary hematopoiesis with nerve compression, or vascular steal syndromes. In brainstem and cerebellar compression from basilar impression, ataxia, quadriparesis, hydrocephalus, and lower cranial nerve palsies can ensue.64,67 Basilar invagination is manifested by upward elevation and outward rotation of the petrous apices. The acousticofacial bundle may be attenuated by elongation, resulting in neural hearing loss and hemifacial spasm. The cause of hearing loss in Paget’s disease remains unclear. A large number of pathologic findings has been reported in the literature for both conductive and SNHL caused by Paget’s disease. These findings, reviewed in detail by Khertarpal and Schuknect,68 included external auditory canal stenosis, tympanic membrane abnormalities, tympanic cavity fibrosis and ossification, incus or malleus fixation, stapes fixation, and round window niche obliteration as causal factors in conductive hearing loss. In SNHL, hair cell depopulation, arteriovenous vascular shunts, otic capsule microfractures, IAC narrowing, microneuromata, and acousticofacial bundle elongation were implicated. To address the problem of the cause of hearing loss in Paget’s disease, Khertarpal and Schuknect68 studied the histologic features of 26 temporal bones of 16 patients with audiometrically documented conductive and sensorineural hearing losses. They failed to find consistent histologic changes for these patients and concluded that the pathologic basis of hearing loss was caused by changes in the biomaterial of the pagetoid bone. The investigators postulate that the dysplastic bone serves to dampen motion of mechanical elements in the middle and inner ears. In essence, the audiologic bone line does not necessarily reflect true inner ear reserve in pagetoid bone due to changes in compressive conduction. Other temporal bone findings in Paget’s disease are notable for tortuous external auditory canal, middle ear cleft constriction secondary to remodeling, pagetoid changes of the ossicular chain with increased mass loading, and otic capsule demineralization.54,69,70 Otic capsule invasion occurs in a peripheral-to-central fashion. The periosteal layer is eroded initially. As the disease advances, all layers of the otic capsule are replaced.70,71 When the final endosteal layer is penetrated, the membranous labyrinth may become obliterated.71,72 This pattern of otic capsule demineralization is in distinct contrast to the endochondral erosion of the bony labyrinth with residual cochlear capsule seen in retrofenestral otosclerosis. Pagetoid involvement of the otic capsule is associated with significant SNHL.72,73 A concomitant finding with otic capsule involvement is the demineralization of the petrous pyramid.54 IAC narrowing can cause neural degeneration.74 Facial nerve dysfunction has not been an outstanding feature in the reported literature. Conventional radiography of the skull demonstrates the classic “cotton wool” appearance due to the coexistence of osteolysis and sclerosis. In 10% of the cases, the disease presents in the form of osteoporosis circumscripta cranii, a sharply delineated osteolytic lesion of the skull.75 HRCT

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Figure 67-7. Paget’s disease. This patient has sensorineural hearing loss and hemifacial spasm with weakness. Axial CT scan shows extensive mottled radiolucent changes of the skull base, with a coarse trabecular pattern and areas of sclerosis. This mosaic radiographic pattern reflects the coexistence of osteolysis and sclerosis seen in Paget’s disease. The external auditory canal, middle ear space, and otic capsule are normal bilaterally. The internal auditory canal is, however, stenotic on the side with acousticofacial neural dysfunction.

appearance of the temporal bone depends on the underlying remodeling activity. The radiographic patterns, reflecting the phase of disease, may be broadly categorized into mosaic and translucent.59,60 In the mosaic pattern, diffuse areas of radiolucency are adjacent to foci of irregular sclerosis (Fig. 67-7). A solitary cystic lucency may be the presenting radiographic feature in the early phase of an evolving mosaic pattern. In the translucent variant, the appearance is homogeneous, washed-out, and blurred. HRCT appearance of the otic capsule is unsharp and irregular with pagetoid invasion. This is likely to be accompanied by diffuse demineralization of the petrous pyramid (Figs. 67-8 and 67-9). The internal and external auditory canals and middle ear cleft may be stenotic, due to pagetoid bony encroachment.

Figure 67-8. Advanced Paget’s disease. Coronal CT scan through the otic capsule illustrates the translucent variant of Paget’s disease. The appearance is homogeneous and fuzzy. The otic capsule is eroded in a peripheral to central fashion. A shell of endosteal bone is preserved. Note the concomitant diffuse demineralization of the petrous pyramid.

Figure 67-9. Cochlear otosclerosis. Axial CT scan shows pericochlear lucency. This results from endochondral erosion of the bony labyrinth. A thin residual cochlear capsule remains. Note that this is in distinct contrast to the peripheral to central erosion seen in Paget’s disease.

Monostotic Paget’s disease of the temporal bone is uncommon. Typically, axial skeletal involvement with radiographic features of a mixed pattern of sclerosis and lucency or a flame-shaped resorption front can provide an accurate diagnosis in the vast majority of cases.76 Temporal bone disease of the mosaic pattern may be indistinguishable from fibrous dysplasia. The isolated lucent variant is a diagnostic challenge, and definitive diagnosis should be confirmed by biopsy. The lucent appearance is also seen in atypical fibrous dysplasia, eosinophilic granuloma, infection, metastatic disease, and malignant degeneration.8,76,77 The frequency of sarcomatous degeneration is believed to be approximately 1%.76–78 The degeneration usually occurs in polyostotic disease and has a poor prognosis. Osteosarcoma is the most common transformed malignancy, followed by fibrosarcoma and giant-cell tumors.77 Magnetic resonance imaging is helpful in delineating soft tissue abnormalities seen in sarcomatous degeneration.78 The treatment of symptomatic Paget’s disease is almost exclusively chemotherapy. Paget’s disease causes bone pain, neurologic dysfunction, and cardiovascular stress.53 Calcitonin,79,80 sodium etidronate,81,82 and mithramycin (plicamycin)83,84 have been shown to induce biochemical and clinical improvement. Serum alkaline phosphatase and urinary hydroxyproline, indicators of bone turnover activity, decrease in response to treatment and serve as useful therapeutic response indices.54 Radiographic healing with medical therapy has been documented in a number of reports.85–87 Calcitonin acts by inactivating osteoclasts, thereby arresting bone resorption.88,89 Calcitonin has generally been delivered subcutaneously, but recent experience

Diffuse Osseous Lesions of the Temporal Bone

with intranasal aerosol delivery has been promising.90,91 In neurologic complications of Paget’s disease, calcitonin therapy appears to be beneficial.92,93 This is particularly pronounced in the treatment of brainstem or spinal cord compression.94 Calcitonin therapy for hearing loss in Paget’s disease has had variable success in the past.95–98 But recent reports by El Sammaa and colleagues99 and Lando and coworkers61 have been more encouraging. Sodium etidronate and other diphosphonates are oral agents that are selectively concentrated in bone.100 These compounds inhibit calcium deposition and appear to have selective cytotoxicity for osteoclasts.101,102 The treatment of osteolytic lesions in Paget’s disease by diphosphonates is controversial. Some investigators report healing of the lytic lesions,103,104 but others105,106 report excess fractures. Combined calcitonin/sodium etidronate therapy has been demonstrated to stabilize and even reverse hearing loss in two patients with Paget’s disease.61 Mithramycin, an inhibitor of DNAregulated RNA synthesis, is delivered intravenously. This therapy is associated with nephrotoxicity, thrombocytopenia, and hepatoxiticity and is reserved for patients who fail to respond to calcitonin and diphosphonate treatments.51 Overall, the treatment of cranial neuropathy and hearing loss by calcitonin remains unproven. However, combined calcitonin/sodium etidronate is a promising modality and deserves further investigation.107,108 Surgical therapy for hearing loss and cranial neuropathy in Paget’s disease should be entertained only after a full course chemotherapeutic trial. Davies64 reviewed stapes surgery outcome in the management of apparent conductive hearing loss in Paget’s disease and found that stapedectomy resulted in variable patient benefit and disappointing persistent air-bone gaps. The pathophysiology underlying conductive hearing loss in Paget’s disease is quite variable, so preconceived notions for ossiculoplasty and stapedectomy may be misguided. Modern hearing devices are excellent alternatives to middle ear exploration and should be encouraged. Persistent symptomatic IAC stenosis with SNHL and facial nerve dysfunction following chemotherapy may be an indication for surgical decompression. The pagetoid bone is quite vascular and landmarks can be distorted by the dysplastic process. Surgery is hazardous and should be attempted only by experienced neurotologists.

OSTEOGENESIS IMPERFECTA Osteogenesis imperfecta represents a group of six different types of connective tissue disorders that predisposes the affected individual to recurrent fractures in response to trivial trauma. The vast majority of patients with type I–IV disease have some type of mutation in the COL1A/ COL1A2 genes which code for type I collagen.109 Over the past decade, substantial interest has arisen in the elucidation of molecular mechanisms to explain the clinical behavior of this disease.110 Osteogenesis imperfecta has been commonly classified into congenita and tarda. In the congenita form, the newborn is severely compromised by in utero and peripartum fractures and typically dies shortly after birth. The clinical course of the tarda form is quite variable. Sillence and colleagues111 introduced a classification scheme based on genetic and clinical criteria. Type I, an

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autosomal-dominant form, is mild and manifested by blue sclerae and early hearing loss. The triad of fragile bones, blue sclerae, and hearing loss was described by Van der Hoeve and de Kleyn in 1918. Type II, which is autosomaldominant or -recessive, is uniformly lethal. Type III, which is autosomal-recessive, is marked by progressive skeletal deformities with extreme fragility of bones and very short stature. Type IV, another autosomal-dominant form, is an intermediate between types I and III and exhibits skeletal fragility with moderately short stature. A pathologic hallmark of osteogenesis imperfecta is the deposition of osteogenic immature bony tissue that is weak or fragile. Microfractures can be found. Histologically, an increased number of osteocytes occur in both woven and lamellar bone, and a relative reduction occurs in matrix substance.112–114 The bone turnover rate is high.115 Conflicting theories have been espoused to explain the pathogenesis of this disease. In light of the observed large number of osteoblasts and reduced matrix volume, several investigators116–119 have proposed that the defect is due to osteoblast dysfunction, resulting in inadequate bony matrix. Parodoxically, ample new bony tissue was found by Villanueva and Frost.120 These investigators hypothesize increased osteoclast activity as the cause. Further understanding lies in unraveling the puzzle of how defective collagen alters bone cell metabolism and bone matrix interactions.104 Osteogenesis imperfecta tarda has multiorgan system manifestations. In addition to fragile bones and hearing loss, patients may exhibit features such as dentinogenesis imperfecta, blue sclerae, loose joints, mitral valve prolapse, easy bruising, and growth deficiency.109,111 Hearing loss in osteogenesis imperfecta tarda has been estimated to be 25% to 60%.112,121,122 Pedersen123 reviewed 201 Danish patients with osteogenesis imperfecta and found hearing loss in 50% of the group. Of the patients with hearing loss, 24% were purely conductive, 54% were mixed, 16% were sensorineural, and 6% were anacoustic. The majority of patients (69%) had their onset of hearing loss between the second and third decades. Hearing loss in osteogenesis imperfecta tarda can be audiometrically indistinguishable from otosclerosis. However, the earlier onset of hearing impairment and higher incidence of a sensorineural component are clinical features that distinguish osteogenesis imperfecta from otosclerosis.113 Footplate fixation in osteogenesis imperfecta tarda can arise either from an otospongiosis-like focus as seen in early otosclerosis or diffuse structural changes.123 Despite histologic similarities between osteogenesis imperfecta and otosclerosis, biochemical analyses of stapes sulfhydryl groups and various enzymes have clearly demonstrated differential concentrations in the two diseases.124–128 A common genetic origin for osteogenesis imperfecta and otosclerosis is therefore unlikely. Moreover, surgical problems encountered during stapedectomy common to osteogenesis imperfecta but unusual for otosclerosis include thin canal wall skin, brittle scutum, stapedial crural fractures, easy mobilization of the footplate, and excessive bleeding.108 The incus long process may be fragile and prone to fracture during crimping. The pathophysiology of SNHL in osteogenesis imperfecta is not well understood. Microfractures of the otic capsule and encroachment of the bony labyrinth by dysplastic bone have been postulated as possible mechanisms.111,129

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Figure 67-10. Osteogenesis imperfecta. Coronal CT scan through the otic capsule shows proliferation of undermineralized dysplastic bone that has expanded the cochlea and semicircular canals. The dysplastic bone involves the tympanic segment of the fallopian canal. (Courtesy of Barry E. Hirsch, MD.)

Temporal bone histology in osteogenesis imperfecta congenita has been reported by Bergstrom.112 Four cases were studied, and the following observations were made. The tympanic membrane was normal. The ossicles were lightly ossified, and the continuity of the stapes was disrupted or nearly disrupted. The otic capsule layers were thin and poorly formed. No otic capsule fractures were observed. The mastoid was poorly pneumatized and filled with hematopoietic tissue. Facial nerve dysfunction is a rare complication of osteogenesis imperfecta. Tabor and colleagues129 recently described a case of bilateral facial nerve paresis in a 19-year-old woman with osteogenesis imperfecta tarda. The weaker facial nerve was explored and found to be completely encased by dysplastic bone in the labyrinthine and tympanic segments. Pathologic examination of the excised segment revealed marked perineural and endoneural fibrosis. The facial nerve was reconstructed with a cable graft. Temporal bone HRCT findings in osteogenesis imperfecta may be nearly identical to those found in otosclerosis.130–132 In otosclerosis, HRCT may demonstrate fenestral involvement by showing an excrescent promontory mass protruding from the region of the oval window.132–134 Otic capsule, or retrofenestral, involvement manifests as cochlear lucency with or without sclerosis. The typical hypodense band around the cochlea is known as the “double ring” sign. Extensive endochondral demineralization of the otic capsule may occur in severe cases of cochlear otosclerosis. However, diffuse resorptive changes in

Figure 67-11. Osteogenesis imperfecta. Axial CT scan demonstrates lateral extension of the proliferative dysplastic process to abut the ossicles. The dysplastic bone blocks the right aditus ad antrum and causes mastoid obstruction. (Courtesy of Barry E. Hirsch, MD.)

vast areas of the otic capsule are more often seen in osteogenesis imperfecta.131 Other temporal bone HRCT findings in two patients with advanced osteogenesis imperfecta tarda were reported by Tabor and coworkers.129 In summary, the middle ear cleft was narrowed by proliferative bone, and the oval and round windows were obliterated by the dysplastic process. Extensive proliferation of undermineralized bone occurred involving all or part of the otic capsule. The dysplastic bone involved the cochlea, facial nerve, and semicircular canals (Figs. 67-10 and 67-11). These reported cases represent advanced osteogenesis imperfecta of the temporal bone. The findings of extensive facial nerve canal involvement and severe proliferative otic capsule dysplasia are clear distinguishing features of osteogenesis imperfecta tarda and are not seen in cochlear otosclerosis. Medical therapy for osteogenesis imperfecta remains elusive. A number of agents including calcitonin, sodium fluoride, and vitamin D have been employed. No convincing evidence supports their efficacy in the treatment of this disease.109 The primary otologic feature in osteogenesis imperfecta is conductive hearing loss that occurs between the second and third decades. Stapedectomy in osteogenesis imperfecta tarda is technically more demanding than in otosclerosis because of the tendency for bleeding and fragile footplate that may “float” during moblilization. Despite these features, a number of reports135–138 have supported stapes surgery with favorable short- and long-term results. As such, stapedectomy in osteogenesis imperfecta is recommended.

TABLE 67-1. Clinical Manifestations of Temporal Bone Osseous Dysplasias

Fibrous dysplasia Osteopetroses Paget’s disease Osteogenesis imperfecta Cochlear otosclerosis

Conductive Hearing Loss

Cochlear Hearing Loss

Neural Hearing Loss

Facial Nerve Dysfunction

Very common 30–57% Very common Very common 30–50% Very common 20–50% Very common

Rare Uncommon Common Uncommon Very common

Rare Common Uncommon None None

Uncommon Common Uncommon 7% Rare None

Diffuse Osseous Lesions of the Temporal Bone

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TABLE 67-2. Radiologic Findings in the Temporal Bone Osseous Dysplasias EAC Stenosis

Middle Ear Involvement

Otic Capsule

IAC Stenosis

Pattern

Fibrous dysplasia

Common 22–42%

Uncommon

Uninvolved

Rare

Osteopetroses

Common

Common

Common

Paget’s disease

Uncommon

Uncommon

Osteogenesis imperfecta

None

Uncommon

Cochlear otosclerosis

None

Rare

Expanded when advanced Uncommon peripheral to central demineralization Demineralization seen when advanced Demineralization seen

1. Pagetoid 2. “Ground glass” sclerosis 3. Cystic lucency Chalky sclerosis

Although facial nerve dysfunction in osteogenesis imperfecta is an unusual occurrence, HRCT imaging is recommended preoperatively to help delineate the extent of the dysplastic process and guide exposure and decompression. The neurotologist should be prepared for facial nerve reconstruction with an interposition graft because dysplastic changes within the fallopian canal can irreversibly damage segments of the facial nerve.

SUMMARY Diffuse osseous lesions of the temporal bone are an intriguing group of heterogenous disorders that present to the otologist with symptoms of external auditory canal occlusion, hearing loss, and cranial neuropathy. HRCT imaging of the temporal bone is an important diagnostic tool in differentiating among several otodystrophies. The radiographic patterns, in conjunction with clinical data, can often secure a definitive diagnosis. The uncommon isolated lucent lesion is an exception to this rule and mandates open biopsy to rule out malignancy. Tables 67-1 and 67-2 summarize key features of several osseous dysplasias. Appropriate therapy, medical or surgical, can then be initiated.

REFERENCES 1. Schoenau A, Rauch E: Fibrous dysplasia. Horm Res 57:79–82, 2002. 2. Coley BL: Fibrous dysplasia of the bone: Review of 24 cases. Am J Med 44:421–429, 1968. 3. Lichtenstein L: Polyostotic fibrous dysplasia. Arch Surg 36: 874–898, 1938. 4. Lichtenstein L, Jaffe HL: Fibrous dysplasia of bone. Arch Pathol 33:777–816, 1942. 5. McCune DJ, Bruch H: Osteodystrophia fibrosa: Report of a case in which the condition was combined with precocious puberty, pathologic pigmentation of the skin and hyperthyroidism, with review of the literature. Am J Dis Child 54:806–848, 1937. 6. Albright F, Butler MA, Hampton AO, et al: Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction with precocious puberty in females. N Engl J Med 216:727–746, 1937. 7. Van Tilburg W: Fibrous dysplasia. In Vinken PJ, Bruyn GW (eds.): Handbook of Clinical Neurology, vol 14. Amsterdam, North Holland, 1972, pp 163–212.

Uncommon None None

1. Lucency with irregular sclerosis 2. Washed-out translucency More extensive pericochlear lucency Pericochlear lucency

8. Nager GT, Kennedy DW, Kopstein E: Fibrous dysplasia: A review of the disease and its manifestations in the temporal bone. Ann Otol Rhinol Laryngol 91(Suppl 91):1–52, 1982. 9. Windolz F: Cranial manifestations of fibrous dysplasia of bone. Am J Roentgenol 58:51–63, 1947. 10. Barrionuevo CE, Marcallo FA, Coelho A, et al: Fibrous dysplasia and the temporal bone. Arch Otolaryngol 106:298–301, 1980. 11. Sataloff RT, Graham MD, Roberts BR: Middle ear surgery in fibrous dysplasia of the temporal bone. Am J Otol 6(2):153–156, 1985. 12. Lambert PR, Brackmann DE: Fibrous dysplasia of the temporal bone: The use of computerized tomography. Otolaryngol Head Neck Surg 92(4):461–467, 1984. 13. Pecaro BC: Fibro-osseous lesions of the head and neck. Otolaryngol Clin North Am 19(3):489–496, 1986. 14 Levine PA, Wiggins R, Archibald RWR, et al: Ossifying fibroma of the head and neck: Involvement of the temporal bone—An unusual and challenging site. Laryngoscope 91:721–725, 1981. 15. Pouwels ABPM, Cremers CWRJ: Fibrous dysplasia of the temporal bone. J Laryngol Otol 102:171–172, 1988. 16. Smouha EE, Edelstein DR, Parisier SC: Fibrous dysplasia involving the temporal bone: Report of three new cases. Am J Otol 8(2):103–107, 1987. 17. Cohen A, Rosenwasser H: Fibrous dysplasia of the temporal bone. Arch Otolaryngol 89:31–43, 1969. 18. Fries JW: The roentgen features of fibrous dysplasia of the skull and facial bones: A critical analysis. Am J Roentgenol Radiat Ther 77:71–88, 1957. 19. Yabut SM Jr, Kenan S, Sissons HA, et al: Malignant transformation of fibrous dysplasia. A case report and review of the literature. Clin Orthop 204:281–289, 1988. 20. Schwartz DT, Alpert M: The malignant transformation of fibrous dysplasia. Am J Med Sci 247:1–20, 1964. 21. Huvos AG, Higinbotham NL, Miller TR: Bone sarcomas arising in fibrous dysplasia. J Bone Joint Surg 54A:1047–1056, 1972. 22. Nager GT, Holliday MJ: Fibrous dysplasia of the temporal bone update with case reports. Ann Otol Rhinol Laryngol 93:630–633, 1984. 23. Hul EV, Gram J, Hul WV, et al: Localization of the Gene Causing Autosomal Dominant Osteopetrosis Type 1 to chromosome 11q12-13. J Bone Miner Res 17:1111–1117, 2002 24. Hamersma H: Osteopetrosis (marble bone disease) of the temporal bone. Laryngoscope 80:1518–1539, 1970. 25. Miyamoto RT, House WF, Brackmann DE: Neurotologic manifestations of the osteopetroses. Arch Otolaryngol 106:210–214, 1980. 26. Cleiren E, Benichou O, Hul WV, et al: Albers-Schönberg disease results from mutation in the CICN7 chloride channel gene. Hum Mol Genet 10:2861–2867, 2001. 27. Benichou O, Cleiren E, Hul WV, et al: Mapping of autosomal dominant osteoptetrosis type II to chromosome 16p13.3. Am J Hum Genet 69:647–654, 2001.

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28. Johnston CC, Lavy N, Lord T, et al: Osteopetrosis—A clinical, genetic, metabolic, and morphologic study of the dominantly inherited, benign form. Medicine 47(2):149–167, 1968. 29. Beighton P, Horan F, Hamersma H: A review of the osteopetroses. Postgrad Med J 53:507–515, 1977. 30. Walker DG: Osteopetrosis cured by temporary parabiosis. Science 180:875, 1973. 31. Walker DG: Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells. Science 190:784–785, 1975. 32. Walker DG: Control of bone resorption by hematopoietic tissue: The induction and reversal of congenital osteopetrosis in mice through use of bone marrow and splenic transplants. J Exp Med 142:651–653, 1975. 33. Marks SC Jr: Morphological evidence of reduced bone resorption in osteopetrotic mice. Am J Anat 163:157–167, 1982. 34. Milroy CM, Michaels L: Temporal bone pathology of adult-type osteopetrosis. Arch Otolaryngol 116:79–84, 1990. 35. Wong ML, Balkany TJ, Reeves J, et al: Head and neck manifestations of malignant osteopetrosis. Otolaryngol Head Neck Surg 86:584–594, 1978. 36. Lehman RAW, Reeves JD, Wilson WB, et al: Neurological complications of infantile osteopetrosis. Ann Neurol 2:378–384, 1977. 37. Hawke M, Jahn AF, Bailey D: Osteopetrosis of the temporal bone. Arch Otolaryngol 107:278–282, 1981. 38. Suga F, Lindsay JR: Temporal bone histopathology of osteopetrosis. Ann Otol Rhinol Laryngol 85:15–24, 1976. 39. Myers EN, Stool S: The temporal bone in osteopetrosis. Arch Otolaryngol 89:460–469, 1969. 40. Kintworth GK: The neurologic manifestations of osteopetrosis (Albers-Schönberg’s disease). Neurology 13:512–519, 1963. 41. Bollerslev J, Grontved A, Andersen PE Jr: Autosomal dominant osteopetrosis: An otoneurological investigation of the two radiological types. Laryngoscope 98:411–413, 1988. 42. Dort JC, Pollak A, Fisch U: The fallopian canal and facial nerve in sclerosteosis of the temporal bone: A histopathologic study. Am J Otol 11(5):320–325, 1990. 43. Yarington CT, Sprinkle PM: Facial palsy in osteopetrosis. Relief by endotemporal decompression. JAMA 202:549, 1967. 44. Kiettzler G, Paparella M: Otolaryngological disorders in craniometaphyseal dysplasia. Laryngoscope 79:921–941, 1969. 45. Bartynski WS, Barnes PD, Wallman JK: Cranial CT of autosomal recessive osteopetrosis. Am J Neuroradiol 10:543–550, 1989. 46. Bollerslev J, Andersen PE Jr: Radiological, biochemical and hereditary evidence of two types of autosomal dominant osteopetrosis. Bone 9:7–13, 1988. 47. Shea J, Gerbe R, Ayani N: Craniometaphyseal dysplasia: the first successful surgical treatment for associated hearing loss. Laryngoscope 91:1369–1374, 1981. 48. Jones MD, Mulcahy ND: Osteopathia striata, osteopetrosis, and impaired hearing: A case report. Arch Otolaryngol 87:116–118, 1968. 49. Morgan DW, Aldren C, Hoare TJ: Hearing loss due to craniometaphyseal dysplasia. J Laryngol Otol 104:807–808, 1990. 50. Hamersma H, May M: Osteopetrosis and facial palsy. In May M (ed.): The Facial Nerve. New York, Georg Thieme Verlag, 1986, pp 469–476. 51. Laurin N, Brown J, Morissette, Raymond V: Recurrent mutation of the gene encoding seqestosome 1 in Paget’s disease of bone. Am J Hum Genet 70:1582–1588, 2002. 52. Neale SD, Schulze E, Smith R: The influence of serum cytokines and growth factors on osteoclast formation in Paget’s disease. Q J Med 95:233–240, 2002. 53. Nager GT: Paget’s disease of the temporal bone. Ann Otol Rhinol Laryngol 84(Suppl 22):1–32, 1975. 54. Freeman DA: Southwestern internal medicine conference: Paget’s disease of bone. Am J Med Sci 295(2):144–158, 1988. 55. Stein I, Stein R, Beller M: Living Bone in Health and Disease. Lippincott, Philadelphia, 1955.

56. Avioli LV: Paget’s disease: State of the art. Clin Ther 9(6):567–576, 1987. 57. Mills BG, Singer FR: Nuclear inclusions in Paget’s disease of bone. Science 194:201–203, 1976. 58. Mills BG, Singer FR, et al: Evidence for both respiratory syncytial virus and measles virus antigens in the osteoclasts of patients with Paget’s disease of bone. Clin Orthop Relat Res 183:347–355, 1984. 59. Clemis JD, Boyles J, Harford ER, et al: The clinical diagnosis of Paget’s disease of the temporal bone. Ann Otol Rhinol Laryngol 76:611–623, 1967. 60. Juster M, Michel JR, Vignaud J: Paget’s disease. In Vignaud J (ed.): The Ear, Diagnostic Imaging. New York, Masson Publishing USA, 1986, pp 205–209. 61. Lando M, Hoover LA, Finerman G: Stabilization of hearing loss in Paget’s disease with calcitonin and etidronate. Arch Otolaryngol 114:891–894, 1988. 62. Collins DH: Paget’s disease of bone. Incidence and subclinical forms. Lancet 2:51–57, 1956. 63. Gutman AB, Kasabach H: Paget’s disease (osteitis deformans). Analysis of 116 cases. Am J Med Sci 191:361–380, 1936. 64. Davies DG: Paget’s disease of the temporal bone. Acta Otolaryngol (Suppl) 242:1–47, 1968. 65. Baraka ME: Rate of progression of hearing loss in Paget’s disease. J Laryngol Otol 98:573–575, 1984. 66. Lindsay JR, Perlman HB: Paget’s disease and deafness. Arch Otlolaryngol 23:581–587, 1936. 67. Clarke CRA, Harrison MJG: Neurological manifestations of Paget’s disease. J Neurol Sci 38:171–178, 1978. 68. Khetarpal U, Schuknecht HF: In search of pathologic correlates for hearing loss and vertigo in Paget’s disease—A clinical and histopathologic study of 26 temporal bones. Ann Otol Rhinol Laryngol 99(3)(Suppl 145):1–16, 1990. 69. Davies DG: The temporal bone in Paget’s disease. J Laryngol Otol 84:553–560, 1970. 70. Proops D, Bayley D, Hawke M: Paget’s disease and the temporal bone—A clinical and histopathological review of six temporal bones. J Otolarngol 14:20–29, 1985. 71. Lindsay JR, Suga F: Paget’s disease and sensori-neural deafness: Temporal bone histopathology of Paget’s disease. Laryngoscope 86:1029–1042, 1976. 72. Lindsay JR, Lehman RH: Histopathology of the temporal bone in advanced Paget’s disease. Laryngoscope 79:213–227, 1969. 73. Linthicum FH, Filipo R, Brody S: Sensorineural hearing loss due to cochlear otospongiosis. Theoretical consideration of etiology. Ann Otol Rhinol Laryngol 84:544–551, 1975. 74. Applebaum EL, Clemis JD: Temporal bone histopathology of Paget’s disease with sensorineural hearing loss and narrowing of the internal auditory canal. Laryngoscope 87:1753–1759, 1977. 75. Collins DH, Winn JM: Focal Paget’s disease of the skull. (Osteoporosis circumscripta). J Pathol 69:1–9, 1955. 76. Levine RB, Rao VM, Karasick D, et al: Paget disease: Unusual radiographic manifestations. Crit Rev Diag Imag 25(3):209–232, 1986. 77. Seret P, Basle MF, Rebel A, et al: Sarcomatous degeneration in Paget’s bone disease. J Cancer Res Clin Oncol 113:392–399, 1987. 78. Kelly JK, Denier JE, Wilner HI, et al: MR imaging of lytic changes in Paget disease of the calvarium. J Comput Asst Tomogr 13(1):27–29, 1989. 79. Haddad JG, Birge SJ, Avioli LV: Effect of prolonged thyrocalcitonin administration on Paget’s disease of bone. N Engl J Med 285:549–555, 1970. 80. Shai F, Baker RK, Wallach S: The clinical and metabolic effects of porcine calcitonin on Paget’s disease of bone. J Clin Invest 50:1927–1940, 1971. 81. Smith R, Russell RGG, Bishop M: Diphosphonates and Paget’s disease of bone. Lancet 1:945–947, 1971. 82. Altman RD, Johnson CC, Kairi MRA, et al: Influence of disodium etidronate on clinical and laboratory manifestations of Paget’s disease of bone (osteitis deformans). N Engl J Med 289:1379–1384, 1973.

Diffuse Osseous Lesions of the Temporal Bone

83. Ryan WG, Schwartz TB, Fordham EW: Mithramycin and long remission of Paget’s disease of bone. Ann Intern Med 92:129–130, 1980. 84. Elias EG, Evans JT: Mithramycin in the treatment of Paget’s disease of bone. J Bone Joint Surg 54:1730–1736, 1972. 85. Eisman JA, Martin TJ: Osteolytic Paget’s disease. J Bone Joint Surg 68-A(1):112–117, 1986. 86. Dodd GW, Ibbertson HK, Fraser TRC, et al: Radiological assessment of Paget’s disease of bone after treatment with the bisphosphonates EHDP and APD. Br J Radiol 60(717):849–860, 1987. 87. Murphy WA, Whyte MP, Haddad JG: Healing of lytic Paget bone disease with diphosphonate therapy. Radiology 134:635–637, 1980. 88. Chambers TJ: The pathophysiology of the osteoblast. J Clin Pathol 38:241–252, 1985. 89. Nicholson GC, Moseley JM, Sexton PM, et al: Abundant calcitonin receptors in isolated at osteoclasts. J Clin Invest 78:355–360, 1985. 90. Gagel RF, Logan C, Mallette LE: Treatment of Paget’s disease of bone with salmon calcitonin nasal spray. JAGS 36:1011–1014, 1988. 91. Reginster JY, Albert A, Franchimont P: Salmon-calcitonin nasal spray in Paget’s disease of bone: Preliminary results in five patients. Calcif Tissue Int 37:577–580, 1985. 92. De Rose J, Singer FR, Avaranides A: Response of Paget’s disease to porcine and salmon calcitonins. Am J Med 56:858–866, 1974. 93. Frank MS, Brandt LJ, Kaufman DM, et al: Oropharyngeal dysphagia in Paget’s disease on bone (osteitis deformans): Response to calcitonin. Am J Gastroenterol 77:450–453, 1982. 94. Douglas DL, Duckworth T, Kanis JA, et al: Spinal cord dysfunction in Paget’s disease of bone. J Bone Joint Surg 63B:495–503, 1981. 95. Moffatt WH, Morrow JD, Simpson N: Effects of calcitonin therapy in deafness associated with Paget’s disease of bone. Br Med J 4:203, 1974. 96. Menzies MA, Greenberg PB, Joplin GF: Otological studies in patients with deafness due to Paget’s disease before and after treatment with synthetic human calcitonin. Acta Otolaryngol 79:378–382, 1975. 97. Grimaldi PMGB, Mohamedally SM, Woodhouse NYJ: Deafness in Paget’s disease: Effect of salmon calcitonin treatment. Br Med J 2:726, 1975. 98. Solomon LR, Evanson JM, Canty DP, et al: Effect of calcitonin on deafness due to Paget’s disease of bone. Br Med J 2:485–487, 1977. 99. El Sammaa M, Linthicum FH, House HP, et al: Calcitonin as treatment for hearing loss in Paget’s disease. Am J Otolaryngol 7:241–243, 1986. 100. Russell RGG, Fleisch H: Pyrophosphate and diphosphonates in skeletal metabolism. Clin Orthop 108:241–263, 1975. 101. Smith R, Russell RGG, Bishop MC, et al: Paget’s disease of bone: Experience with a diphosphonate (disodium etidronate) in treatment. Q J Med 42:235–256, 1973. 102. Russell RGG, Smith R, Preston C, et al: Diphosphonates in Paget’s disease. Lancet 1:894–898, 1974. 103. Woodhouse NJY, Joplin GR, MacIntyre I, et al: Radiological regression in Paget’s disease treated by human calcitonin. Lancet 2:992–994, 1972. 104. Doyle FH, Greenberg PB, Joplin GF, et al: Radiographical evidence for a dose-related response to long-term treatment of Paget’s disease with human calcitonin. Br J Radiol 47:1–8, 1974. 105. Canfield R, Rosner W, Skinner J, et al: Diphosphonate therapy of Paget’s disease of bone. J Clin Endocrinol Metab 44:96–106, 1977. 106. Kantrowitz FG, Byrne M, Schiller Al, et al: Clinical and biochemical effects of diphosphonates in Paget’s disease of bone. Arthritis Rheum 18:407, 1975. 107. Hosking DJ, Bijuoet OL, van Aken J, et al: Paget’s bone disease treated with diphosphonate and calcitonin. Lancet 1:615–617, 1976. 108. Nagant de Deuxchaisnes C, Rombouts-Lindemans C, Haux JP, et al: Paget’s disease of bone. Br Med J 283:1054–1055, 1981. 109. Ward LM, Lalic L, Roughley PJ, Glorieux FH. Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV. Hum Mutat 17:434, 2001.

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110. Marini JC: Osteogenesis imperfecta: Comprehensive management. Adv Pediatr 35:391–426, 1988. 111. Sillence DO, Senn A, Danks DM: Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 16:101–116, 1979. 112. Bergstrom LV: Osteogenesis imperfecta: Otologic and maxillofacial aspects. Laryngoscope 87(Suppl 6):1–42, 1977. 113. Shapiro JR, Pikus A, Weiss G, et al: Hearing and middle ear function in osteogenesis imperfecta. JAMA 247(15):2120–2126, 1982. 114. Cohen, BJ: Osteogenesis imperfecta and hearing loss. Ear Nose Throat J 63:283–288, 1984. 115. Jett S, Ramser JR, Frost HM, et al: Bone turnover and osteogenesis imperfecta. Arch Pathol 81:112–116, 1966. 116. Bullough PG, Davidson DD, Lorenzo JC: The morbid anatomy of the skeleton in osteogenesis imperfecta. Clin Orthop 159:42–57, 1981. 117. Follis RH: Maldevelopment of the corium in the osteogenesis imperfecta syndrome. Bull Johns Hopkins Hosp 93:225–233, 1953. 118. Canniggia A, Gennari C: Calcitonin treatment in Ekman-Lobstein disease. Calcif Tissue Res 9:243–244, 1972. 119. Teitelbaum SL, Kraft WJ, Lang R, et al: Bone collagen aggregation abnormalities in osteogenesis imperfecta. Calcif Tissue Res 17:75–79, 1974. 120. Villanueva AR, Frost HM: Bone formation in human osteogenesis imperfecta, measured by tetracycline bone labeling. Acta Orthop Scand 41:531–538, 1970. 121. Riedner ED, Levin LS, Holliday MJ: Hearing patterns in dominant osteogenesis imperfecta. Arch Otolaryngol 106:737–740, 1980. 122. Quisling RW, Moore GR, Jahrsdoerfer RA, et al: Osteogenesis imperfecta. A study of 160 family members. Arch Otolaryngol 105:207–211, 1979. 123. Pedersen U: Osteogenesis imperfecta: Clinical features, hearing loss and stapedectomy. Acta Otolaryngol (Suppl 415):1–36, 1985. 124. Arslan M, Ricci V: Histochemical investigation of otosclerosis with special regard to collagen disease. J Laryngol Otol 77:365–373, 1963. 125. Chevance LG: On some histochemical aspects of the otosclerotic focus. State and significance of the sulfhydryl groups. Acta Otolaryngol 58:175–182, 1964. 126. Chevance LG: Compariaison des lesions histogiques de la platine stapedienne au cours de l’osteogenesis imperfecta et de l’otospongiose. Probl Actuels Otorhinolaryngol, 150–158, 1965. 127. Causse JR, Chevance LG, Bretlau P, et al: Enzymatic concept of otospongiosis and cochlear otospongiosis. Clin Otolaryngol 2:23–32, 1977. 128. Holdsworth CE, Endahl GL, Soifer N, et al: Comparative biochemical study of otosclerosis and osteogenesis imperfecta. Arch Otolaryngol 98:336–339, 1973. 129. Tabor EK, Curtin HD, Hirsch BE, et al: Osteogenesis imperfecta tarda: Appearance of the temporal bones at CT. Radiology 175(1):181–183, 1990. 130. Swartz JD: Imaging of the Temporal Bone. New York, Thieme, 1986. 131. Mafee MF, Valvassori GE, Deitch RL, et al: Use of CT in the evaluation of cochlear otosclerosis. Radiology 156(3):703–708, 1985. 132. d’Archambeau O, Parizel PM, Koekelkoren E, et al: CT diagnosis and differential diagnosis of otodystrophic lesions of the temporal bone. Europ J Radiol 11:22–30, 1990. 133. Jackler RK: CT and MRI of the ear and temporal bone: Current state of the art and future prospects. Am J Otol 9(3):232–239, 1988. 134. Mafee MF, Henrikson GC, Deitch RL, et al: Use of CT in stapedial otosclerosis. Radiology 156(3):709–714, 1985. 136. Armstrong BW: Stapes surgery in patients with osteogenesis imperfecta. Ann Otorhinolaryngol 93:634–636, 1984. 137. Garretsen JTM, Cremers WRJ: Ear surgery in osteogenesis imperfecta. Arch Otolaryngol 116:317–323, 1990. 138. Pederson U, Elbrond O: Stapedectomy in osteogenesis imperfecta. Otorhinolaryngol 45:330–337, 1983.

Chapter

68 P. Ashley Wackym, MD David R. Friedland, MD, PhD

A

Abnormalities of the Craniovertebral Junction Outline Surgical Anatomy Osseous Relationships Neural Relationships Vascular Relationships Congenital and Acquired Malformations of the Craniovertebral Junction Neural Malformation Osseous Malformation Basilar Impression Synostoses Atlanto-Axial and Atlanto-Occipital Dislocation Anomalies of the Odontoid Process Rheumatoid Arthritis Signs and Symptoms General Neuro-otologic Symptoms Radiographic Evaluation of Craniovertebral Malformations Management of Craniovertebral Junction Malformations Tumors of the Craniovertebral Junction Frequency and Sites

bnormalities of the craniovertebral junction comprise a variety of congenital malformations, acquired deformities, and neoplastic processes that produce symptoms related to compression of nervous and vascular structures at the cervicomedullary junction. Vertigo, hearing loss, and tinnitus are frequent complaints, and the neurotologist frequently plays an important role in the diagnosis and management of these syndromes. A wide variety of surgical approaches have been designed for management of disease in this region, and a successful outcome depends on a complete understanding of the functional anatomy and pathophysiology of the ongoing process. The purposes of this chapter are to review the most common disease processes affecting the craniovertebral junction and to outline the surgical anatomy and operative approaches to the foramen 1136

Clinical Findings Radiographic Evaluation Plain Roentgenograms Myelography Computed Tomography Magnetic Resonance Imaging Angiography Surgical Therapy Preoperative Considerations Operative Approach Treatment Results Surgical Approaches to the Craniovertebral Junction Anterior Approaches Transoral Approach Subfrontal-Transbasal Approach Transsphenoidal Approach Lateral Approaches Transcervical Approach Infratemporal Fossa Approach Fisch D Infratemporal Fossa Approach Extreme Lateral Approach Posterior Approach Suboccipital Approach Endoscopic Assistance

magnum and anterior brainstem as they relate to treatment of these syndromes.

SURGICAL ANATOMY Osseous Relationships The craniovertebral junction comprises the region of the occipital bone and first two cervical vertebrae (Fig. 68-1). The occipital bone surrounds the foramen magnum, a large oval skull base foramina that transmits the medulla. The squamous part of the occipital bone is located posterior to the foramen magnum, the basal part (clivus) lies anteriorly, and the paired condylar parts are located

Abnormalities of the Craniovertebral Junction

1137

Figure 68-1. Osseous anatomy of the craniovertebral junction. A, Superior and, B, inferior views of occipital bone. Continued

laterally. The condylar parts of the occipital bone articulate inferiorly with the lateral masses of the first cervical vertebra (atlas). The atlas differs from other cervical vertebrae by lacking a vertebral body and a spinous process. The position of the vertebral body of the atlas is occupied by the odontoid process (dens) of the second cervical vertebra (axis). The articulation of the atlas and axis comprises four synovial joints: two median ones on the front and the back of the odontoid process, and paired lateral ones between the articular facets on the lateral masses of the atlas and axis. The atlas and axis are further united by the cruciform ligament, the anterior longitudinal ligament, and the posterior longitudinal ligament. The cruciform ligament has transverse and vertical parts, which cross behind the odontoid process to form the transverse ligament. The transverse ligament is a strong band that separates the anterior odontoid process from the posterior spinal canal. The atlas and the

occipital bone are united by the articular capsules surrounding the atlanto-occipital joints and by the anterior and posterior atlanto-occipital membranes. Four fibrous bands, the tectorial membrane, and paired alar ligaments, and the apical ligament, connect the axis and the occipital bone, completing the complex articular mechanism of the craniovertebral junction (Fig. 68-2).1 Rotation occurs around the odontoid process as an axle, with a telescoping effect that occurs because of the sloping atlanto-occipital joint.2

Neural Relationships The neural structures in the region of the foramen magnum include the caudal part of the brainstem, the cerebellum and fourth ventricle, the rostral part of the spinal cord, the lower cranial nerves, and the upper cervical nerves (Fig. 68-3). The spinal cord blends into the medulla at a

Figure 68-1, cont’d. C, Superior and, D, inferior views of axis. E, Superior and, F, inferior views of atlas. (Published with permission, © 1992 P.A. Wackym.)

1138 SKULL BASE DISEASES

Figure 68-2. Midsagittal section through the head and neck demonstrating the ligamentous anatomy of the occipito-atlanto-axial joint. (Published with permission, © 1992 P.A. Wackym.)

Abnormalities of the Craniovertebral Junction 1139

Figure 68-3. Neuroanatomy of the craniovertebral junction. A, Anterior view of the cervicomedullary junction after removal of the clivus, anterior arch of the atlas, and odontoid process. Continued

1140 SKULL BASE DISEASES

Figure 68-3, cont’d. B, Posterior view of the cervicomedullary junction after suboccipital craniectomy and removal of the posterior arch of the atlas, the lower part of the biventral lobule, and cerebellar tonsils. (Published with permission, © 1992 P.A. Wackym.)

Abnormalities of the Craniovertebral Junction 1141

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surface of the medulla through the foramen magnum. The dura mater around the foramen magnum is supplied by the anterior and posterior meningeal branches of the vertebral arteries, the meningeal branches of the ascending pharyngeal arteries, and branches of the occipital arteries. Venous drainage is provided by an anastomotic network of extradural and intradural veins and the dural venous sinuses.1

level arbitrarily set to be at the rootlets forming the first cervical nerve, and therefore the medulla, not the spinal cord, occupies the foramen magnum. The dentate ligaments form a fibrous sheet extending from the lateral surfaces of the spinal cord to the dura. The most rostral dentate ligament is at the level of the foramen magnum. At this level, the dentate ligaments are intimately associated with the vertebral and posterior spinal arteries and the C1 nerve roots, which makes separation of these structures difficult at this level. The cerebellum and its overlying dura rest on the posterior and lateral edge of the foramen magnum. The lower part of the cerebellar hemispheres, formed by the tonsils and the biventral lobules, and the lower part of the vermis, formed by the nodule, uvula, and pyramid, are related to the foramen magnum. Rootlets forming the hypoglossal nerve arise from the medulla along a line that is continuous inferiorly with the line along which the ventral spinal nerves arise. The hypoglossal rootlets course anterolaterally through the subarachnoid space and pass behind the vetebral artery to reach the hypoglossal canal. Rostral to this level, the rootlets of the glossopharyngeal, vagus, and accessory nerves emerge from the dorsolateral surface of the medulla. Spinal rootlets arising from the upper cervical spine pass through the foramen magnum and join the cranial portion of the spinal accessory nerve in the posterior fossa. The glossopharyngeal nerve exits the calvarium through the pars nervosa of the jugular foramen, and the vagus and spinal accessory nerves exit the skull base via the pars venosa of the jugular foramen. Further rostrally, the pons is demarcated from the medulla by the pontomedullary sulcus. The abducent nerves arise in the medial portion of the pontomedullary sulcus and ascend to depart the region of the craniovertebral junction. The facial and vestibulocochlear nerves arise in the lateral part of the pontomedullary sulcus and pass laterally into the cerebellopontine angle (CPA) to enter the internal auditory canal (IAC).1

Congenital and acquired malformations of the craniovertebral junction have a range of symptoms referable to the brainstem, cerebellum, upper spinal cord, and lower cranial nerves. Impingement on the neuroaxis can be dorsal, ventral, or both, and thus there is variability in clinical presentation. Traumatic, metabolic, and inflammatory processes contribute to the acquired lesions. In addition, multiple concurrent malformations are common.3,4 Several mechanisms have been proposed to describe the pathophysiology of the craniovertebral syndromes. These include mechanisms for direct compression of neural tissue at the foramen magnum. For example, autopsy studies have revealed gliotic changes of the cerebellar tonsils in mild cases and frank medullary necrosis in severe cases of the Chiari malformation.5 Alternatively, symptoms might be related to traction injury to the lower cranial nerves or upper spinal nerves. Angulation or compression of blood vessels at the cervicomedullary junction could account for the variable and intermittent nature of these syndromes.3 Compromise of the anterior inferior cerebellar artery may lead to predominant vestibulocochlear symptoms,6 whereas diffuse vertebrobasilar insufficiency may produce more widespread symptomatology.

Vascular Relationships

Neural Malformation

The major arteries related to the craniovertebral junction are the vertebral and posterior inferior cerebellar arteries, the meningeal and spinal branches of the vertebral arteries, and the external and internal carotid arteries (Fig. 68-4). The paired vertebral arteries ascend through the transverse processes of the upper six cervical vertebra, pass posterior to the lateral masses of the atlas, and enter the dura behind the occipital condyles. The terminal extradural segment of the vertebral artery gives rise to the posterior meningeal artery, the posterior spinal artery, and occasionally the posterior inferior cerebellar artery. The vertebral artery, the posterior spinal artery, and the first cervical nerve pierce the dura through a single dural foramen. Once inside the dura, the paired vertebral arteries ascend along the ventral surface of the medulla and join to form the basilar artery at the pontomedullary junction. Most often, the posterior inferior cerebellar artery arises from the intradural segment of the vertebral artery, passes dorsal to the glossopharyngeal, vagus, and accessory nerves, and supplies the cerebellar vermis and hemispheres. The anterior spinal artery originates from the vertebral artery near the origin of the basilar artery and descends along the anterior

The Chiari malformations constitute a group of posterior fossa congenital herniation syndromes. They are classified into four types of malformation of the hindbrain. In type I, there is downward herniation of long, thin cerebellar tonsils through the foramen magnum (Fig. 68-5). In type II, also referred to as the Arnold-Chiari malformation, the cerebellar vermis extends through the foramen magnum, and there is caudal displacement of the lower pons and medulla, often overlapping the upper portion of the upper cervical spinal cord. A portion of the fourth ventricle extends into the spinal canal, and the upper cervical rami course cephalad before leaving the spinal canal. In type III, the cerebellum herniates through a bony defect in the occipital bone, and type IV has cerebellar hypoplasia.7,8 The type II, III, and IV malformations cause florid symptoms and signs and are likely to be recognized in infancy or childhood. The type II malformation is the most common, and most cases are associated with myelomeningocele, spina bifida, and hydrocephalus. Type III is equivalent to an occipital meningoencephalocele, and type IV is sometimes classified as a variant of the Dandy-Walker syndrome.9 Type I is the least severe manifestation and often presents

CONGENITAL AND ACQUIRED MALFORMATIONS OF THE CRANIOVERTEBRAL JUNCTION

Figure 68-4. Vascular anatomy of the craniovertebral junction. A, Anterior view after removal of the clivus, anterior arches of C1 and C2, and dura. Continued

Abnormalities of the Craniovertebral Junction 1143

Figure 68-4, cont’d. B, Posterior view with the cerebellum and spinal cord exposed and the right cerebellar tonsil removed. Continued

1144 SKULL BASE DISEASES

Figure 68-4, cont’d. C, Posterior view after removal of the cerebellum and the left half of the roof of the fourth ventricle. (Published with permission, © 1992 P.A. Wackym.)

Abnormalities of the Craniovertebral Junction 1145

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Figure 68-5. Sagittal MRI demonstrating the Chiari I malformation with tonsillar herniation. The arrows represent the level of the foramen magnum.

during adult life. In the series from the Mayo Clinic and the Cleveland Clinic,10,11 the average age of presentation was 40 years, and there was a female predominance of approximately 1.5:1. The Chiari malformations are frequently associated with other abnormalities of the craniovertebral junction, including syringomyelia, basilar impression, atlanto-occipital fusion, and the Klippel-Feil deformity.12 The Chiari II, III, and IV malformations, which present in childhood, are most likely developmental abnormalities. Considerable evidence suggests that the Chiari I malformation, which presents in middle age, may be an acquired disorder related to an intracranial-intraspinal cerebrospinal fluid (CSF) pressure gradient across the foramen magnum. Welch and coworkers13 described a series of patients that developed tonsillar herniation, indistinguishable from the Chiari I malformation, after placement of lumboperitoneal shunts. Although most patients with the Chiari malformation do not have indwelling CSF shunts, CSF leakage from spinal meningeal defects has been reported in patients with spontaneous intracranial hypotension. This is a syndrome secondary to low CSF pressure manifested by postural headache frequently associated with auditory and vestibular symptoms. Radionuclide cisternography has suggested the presence of spontaneous CSF leakage as the most common etiology for this syndrome.14 It is possible that chronic intracranial hypotension leads to tonsillar herniation by the same mechanism described by Welch and colleagues.13 Alternatively, an intracranial-intraspinal CSF pressure gradient may develop secondary to subarachnoid adhesions.5 Syringomyelia occurs in approximately 40% of cases of type I Chiari malformation.11 The etiology for syringomyelia remains controversial. The hydrodynamic theory proposed by Gardner and Angel15 holds that CSF pulse waves generated by choroid plexus pulsations pound at the obstructed lower end of the fourth ventricle and are transmitted into the syrinx through a patent central canal, causing dilation of the central canal. Williams16,17 proposed that transient elevations in intrathoracic pressure

during coughing or straining maneuvers causes a transient craniospinal pressure differential. He felt that the high pressure within the cerebral subarachnoid space relative to the pressure within the syrinx forces CSF into the syrinx, which causes enlargement over a period of time. Ball and Dayan18 found prominent small arteries and veins in the wall of syrinxes, with widened perivascular spaces. They proposed that these widened perivascular spaces represented enlarged Virchow-Robin spaces, which could serve as a conduit for CSF to enter the syrinx during coughing or straining. Olivero and Dinh19 feel that the hydromyelic cavities associated with the Chiari I malformation may not be related to fluid being driven into the cord from some external source, but rather that fluid that normally exits the cord cannot escape, perhaps due to abnormal hydrodynamic forces created in the subdural space by dural obstruction at the foramen magnum. Most cases of Chiari malformation are amenable to posterior decompression by suboccipital craniectomy and laminectomy of C1 and C2. In cases of anterior impingement, transoral anterior decompression may be beneficial.12 In cases accompanied by syringomyelia, patients may additionally benefit from a shunting procedure to redirect the flow of CSF away from the syrinx cavity. In their extensive review of the literature, Levy, Mason, and Hahn10 found that 46% of cases improved, 32% remained clinically stable, and 20% worsened after surgical intervention. Syrinx shunting was not clearly superior to decompression in cases with syringomyelia.

Osseous Malformation Basilar Impression In this anomaly, the lips of the foramen magnum are turned up and infolded, and there is rostral migration of the tip of the odontoid process, with impingement on the lower brainstem and upper spinal cord. There are two types of basilar impression. Primary basilar impression is a congenital abnormality often associated with other systemic or vertebral defects, including atlanto-occipital fusion, atlanto-occipital dislocation, hypoplasia and dysplasia of the atlas, odontoid abnormalities, achondroplasia, Down syndrome, the Chiari malformation, and the Klippel-Feil syndrome (Fig. 68-6).4,20–22 Primary basilar impression is an uncommon condition; it is more frequent in males and in some races, such as northern Africans.23 Secondary basilar impression is an acquired process that is due to softening of bone at the skull base. It is frequently seen with osteogenesis imperfecta, osteomalacia, rickets, hyperparathyroidism, Hurler’s syndrome, osteomyelitis, osteoporosis, neurofibromatosis, rheumatoid arthritis, and Paget’s disease.20,23,24 Synostoses Atlanto-occipital fusion has also been referred to as assimilation or occipitalization of the atlas. It results from failure of segmentation between the skull and the first cervical vertebra. The bony fusion can be partial or complete. This is a relatively common anomaly, occurring in 0.25% to 1% of the population. In many cases there are no neurologic

Abnormalities of the Craniovertebral Junction

1147

Figure 68-6. A, Sagittal tomogram with atlanto-occipital fusion, odontoid hypoplasia, and an accessory vertebral ossicle in a patient with Down syndrome. Arrows delineate the tip of the hypoplastic odontoid process, which does not extend rostrally to the level of the arch of C1. Arrowheads demonstrate fusion of the anterior and posterior arches of atlas with occipital bone, and the curved arrow demonstrates the accessory ossicle. B, Sagittal MRI demonstrates cervicomedullary compression (center) in this patient.

symptoms. There is frequent association with fusion of the first three cervical vertebrae (Fig. 68-7). In symptomatic cases, there is gradual posterior luxation of the odontoid process, which impinges on the spinal cord. In addition, there is upward displacement of the odontoid into the foramen magnum. Symptomatic patients typically begin to experience problems in the third or fourth decade.2,20,21,25 The Klippel-Feil syndrome is a congenital process that arises from failure of the mesodermal somites to divide during weeks 3 to 8 of gestation, resulting in congenital cervical fusion. The most common variant involves fusion of one or two cervical interspaces and is associated with hemivertebrae and atlanto-occipital fusion, although more extensive fusions involving the cervical, thoracic, and lumbar vertebrae also occur. The syndrome classically presents with low posterior hairline, short neck, and limitation of neck movement, although this complete triad is present in only 50% of cases. Associated systemic manifestations include cardiovascular, genitourinary, ocular, and facial anomalies. Neurologic sequelae of atlanto-axial instability are common.26,27 Atlanto-Axial and Atlanto-Occipital Dislocation Dislocation of the atlanto-axial joint can be congenital or acquired. Congenital dislocation is associated with

dysplasias of the odontoid process, basilar impression, atlanto-occipital fusion, Down syndrome, Morquio’s syndrome, Hurler’s syndrome, and achondroplasia.3,25 This is a relatively common malformation in India, where it occurs three times more frequently in males than in females.28 Acquired forms of atlanto-axial dislocation include traumatic etiologies, rheumatoid arthritis, and ankylosing spondylitis.25 Nasopharyngeal and neck infections have been implicated as a cause of atlanto-axial subluxation in children.29–31 Dislocation of the atlanto-occipital joint is often traumatic. This injury is caused by excessive hyperflexion of the skull with distraction and is usually fatal.25 Anomalies of the Odontoid Process Malformations of the odontoid process include congenital dysplasias and the os odontoideum deformity. Hypoplasia of the odontoid usually presents as a short, stubby odontoid process projecting just above the C1–C2 facet articulation. Aplasia of the odontoid is very rare and associated with an excavation defect into the body of the axis. The os odontoideum malformation consists of a separate bone located rostral to the axis body. Embryologic, traumatic, and vascular etiologies have been suggested to describe the pathogenesis of os odontoideum. These anomalies are often associated with an incomplete cruciate ligament, and symptomatic individuals present with myelopathy related to atlanto-axial instability.20,25 Rheumatoid Arthritis

Figure 68-7. Lateral cervical spine radiograph demonstrating atlanto-occipital fusion (arrows) associated with fusion of C2 and C3 (open arrowheads).

Crockard2 states that rheumatoid arthritis is the most common cause of craniocervical compression. This is a systemic inflammatory disease that involves small blood vessels, synovium, and connective tissue. The cervical spine is the second most common anatomic site of involvement, superseded only by the metacarpophalangeal joints of the hands. Approximately 90% of patients with rheumatoid arthritis have radiographic evidence of cervical spine involvement.32 The most severe manifestation at the craniovertebral junction is rheumatoid basilar invagination,

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TABLE 68-1. Neurologic Deficits in 219 Patients with Craniovertebral Junction Anomalies Neurological Deficits

Number of Patients

Motor Myelopathy Quadriparesis Paraparesis Upper Lower Hemiparesis Triparesis Monoparesis No myelopathy

148 8 32 4 3 7 17

Sensory and Urinary Abnormality Posterior column Hypalgesia Bladder dysfunction

112 12 137

Brainstem Dysfunction

Figure 68-8. A, Sagittal MRI demonstrating mild C1–C2 subluxation with posterior spinal cord displacement (arrowhead) in a patient with rheumatoid arthritis. B, Sagittal MRI demonstrating severe cervicomedullary compression (arrowhead) secondary to C1–C2 subluxation and pannus formation in a patient with rheumatoid arthritis.

or the so-called cranial settling. This consists of vertical odontoid penetration through the foramen magnum, occipito-atlanto-axial dislocation, lateral atlantal mass erosion, downward telescoping of the anterior arch of C1 on the axis, and rostral rotation of the posterior arch of C1, which produces both dorsal and ventral cervicomedullary compromise.33 Atlanto-axial dislocation was the main cause of death in 8% and contributory in 2% in a consecutive series of 104 autopsies of people who had rheumatoid arthritis (Fig. 68-8).34

Signs and Symptoms General Cervicomedullary disease can present as myelopathy, brainstem dysfunction, cranial or cervical nerve dysfunction, or vascular insufficiency. The neurologic deficits in a series of 219 patients with craniovertebral anomalies from the University of Iowa are summarized in Table 68-1. Motor weakness associated with myelopathy is variable, ranging from mild weakness to quadriplegia. In cases of syringomyelia, there may be a dissociative sensory loss, with loss of pain and temperature sensation and preservation of vibrotactile and position sensation. Sensory and motor deficits are often falsely localizing. Brainstem compression is manifested by respiratory compromise late in the clinical progression. All of the lower cranial nerves may be affected variably, and cervical nerve irritation often produces suboccipital headache. Vascular symptoms include syncope, unsteadiness, altered level of consciousness, and transient visual field loss, attributed to the intermittent compromise of blood flow in the vertebral and anterior spinal arteries.25

Nystagmus Apnea Sleep apnea Ataxia Dysmetria Internuclear ophthalmoplegia Facial diplegia

35 4 9 19 17 9 4

Cranial Nerve Dysfunction Hearing loss Dysphagia Paralysis of soft palate Trapezius weakness Tongue atrophy

52 31 27 22 3

Vascular Symptoms Syncope Dizziness Confusion Transient loss visual fields Intermittent paresis

16 37 5 10 17

Adapted from VanGilder JC, Menezes AH, and Dolan KD: The Craniovertebral Junction and Its Abnormalities, Mount Kisco, NY, Futura, 1987. Published with the permission of Futura Publishing Company, Mount Kisco, NY.

Neurotologic Symptoms Perhaps the most relevant of acquired abnormalities at the craniovertebral junction to both the surgical and medical neurotologist is the Chiari I malformation. Signs and symptoms with Chiari I deformity are also applicable to understanding clinical presentations of other craniovertebral lesions. In a recent review of 77 patients with Chiari I malformation, Kumar and colleagues35 noted a wide range of neurotologic complaints affecting the vestibular system (imbalance: 45%; dizziness: 32%; vertigo: 21%; lightheadedness: 9%); auditory system (hearing loss: 20%; tinnitus: 27%), and generalized sensory systems (occipital headache: 36%; general headache: 29%; neck pain: 27%; vision changes: 25%; peripheral weakness and sensory deficits: 9% to 30%). Similar rates of vestibular symptoms were found by Sperling and coworkers36 but they had much higher incidences of audiologic complaints (tinnitus: 81%; hearing loss: 56%). In a large series of 130 patients with Arnold-Chiari malformation Rydell and Pulec7 found 20% had either auditory or vestibular symptoms. Milhorat and coworkers37 found vestibular disorders to be prevalent

Abnormalities of the Craniovertebral Junction

in more than 60% of 364 patients with Chiari I malformation. Other studies have noted that progressive hearing loss, tinnitus, vertigo, and poor balance are among the most frequent complaints in Chiari malformation.9,37,38 Clinical examination of patients with Chiari I malformation may inform more objective indications for surgical intervention. In the Kumar series, all patients categorized as having severe symptoms had neurologic deficits on evaluation.35 Objectively, 94% of these patients had abnormal findings on extensive caloric testing and 50% of those tested had an abnormal audiogram. In contrast, the moderately symptomatic group had only 82% and 36% abnormal findings on vestibular and audiometric testing, respectively. Other signs include gait disturbances, which are characteristically broadbased with difficulty in tandem walking.39 Documented deficits may facilitate the decision to surgically intervene in this patient population. Improvement was noted in 76% of those patients with severe symptoms and neurologic deficits who chose to undergo craniovertebral decompression.35 Similar neurotologic symptoms are found in other diseases that affect the craniovertebral junction. Van Gilder, Menezes, and Dolan25 noted that the hearing loss, while never the chief complaint, was the most frequent cranial nerve abnormality in patients with craniovertebral junction abnormalities; it occurred in 24% of cases. Up to 75% of patients with basilar impression may suffer from vertigo, hearing loss, and tinnitus. Elies and Plester40 radiographically examined 180 patients with nonspecific dizziness and unilateral sensorineural hearing loss (SNHL) and found basilar impression in 18%. The Klippel-Feil syndrome has a 30% incidence of SNHL, and auricular malformations have been described in this syndrome.27 In cases of sensorineural deafness, temporal bone pathology demonstrates hypoplasia of the bony and membranous labyrinth, cochlea, and auditory nerve.41 Conductive hearing loss with ossicular deformity and stapes fixation has also been described in the Klippel-Feil syndrome.42,43 A common sign for cervicomedullary or cerebellar disorders is downbeat vertical nystagmus.39,44 Patients with this finding should be evaluated with high suspicion of a craniovertebral junction lesion or abnormality. Common etiologies include basilar impression, tumor, demyelinating disorders, vascular disorders, and meningoencephalitis.39,44 It has frequently been reported that Chiari I malformation often presents with vertical downbeat nystagmus,45 but the recent series by Kumar and colleagues found only a 4% incidence.35 They did note, however, that 35% of their patients had horizontal spontaneous nystagmus. Supporting this, Milhorat and coworkers37 found horizontal nystagmus to be almost three times as prevalent as downbeat nystagmus in more than 300 patients with Chiari I malformation. Common ocular findings on electronystagmography include enhancement of spontaneous nystagmus on lateral gaze and after rapid position change in the sagittal plane, impaired smooth pursuit, perverted nystagmus on caloric stimulation, and impairment of fixation suppression.46 In cases of craniovertebral compression, physiologic and ablation studies indicate that nystagmus may result from compromise to the dorsal vermis, fastigial nuclei, and floccular-nodular lobe of the cerebellum.47 This release of cerebellar inhibition of vestibular activity may enhance caloric responses, and hyperactive responses have been reported.35

1149

Radiographic Evaluation of Craniovertebral Malformations The advent of MRI has simplified the process of radiographic evaluation of the craniovertebral junction. The medulla and spinal cord are well visualized with this imaging modality, and the position of the foramen magnum can be discerned by the high signal intensity of marrow within the clivus. Abnormalities in size and position of the cervicomedullary junction, cerebellar tonsil position, and the presence of syringomyelia are accurately demonstrated.25 The main drawback of MRI relates to its inability to provide information concerning the bony anatomy of the craniovertebral junction. Nevertheless, MRI is the current preferred modality for evaluation of the craniovertebral junction as well as tumors that may affect this region. In most instances, adequate information concerning the osseous anatomy of the base of the skull can be discerned by plain radiographs or pluridirectional tomography. Several radiographic reference lines have been described to help define osseous relationships at the craniovertebral junction. Chamberlain’s line is defined by a straight line drawn from the hard palate to the posterior margin of the foramen magnum. No more than one third of the odontoid process should be above this line. Wackenheim’s clivus canal line is drawn along the posterior surface of the clivus on the lateral projection. The odontoid process normally lies anterior and inferior to this line. McRae’s line connects the anterior and posterior margin of the foramen magnum, which has an average sagittal diameter of 35 mm. On the anteroposterior projection, Fishgold’s digastric line extends between the mastoid processes. This line is 11 mm above the atlantooccipital junction and defines the normal upper limit of odontoid process. In the Towne projection, the average transverse diameter of the foramen magnum is also 35 mm.4 Radiographic studies are undertaken to demonstrate not only the anatomic but also the pathophysiologic characteristics of craniovertebral junction anomalies. Flexion and extension lateral tomography and midsagittal magnetic resonance imaging help to demonstrate the dynamics of the craniovertebral compression. Cervical traction is subsequently applied to determine the reducibility of the lesion. Less frequently employed imaging modalities include myelography, computed tomography (CT) scanning, and arteriography.25

Management of Craniovertebral Junction Malformations Treatment of symptomatic craniovertebral junction malformations involves the reduction and stabilization of reducible pathology and decompression of those lesions that cannot be reduced (see Fig. 68-9). When radiographic investigation identifies a reducible process, initial stabilization involves immobilization in a halo vest. Unstable reducible lesions require posterior bony stabilization. Methods for posterior fixation have included autogenous bone grafting from the iliac crest or rib and rigid mechanical fixation with various appliances, including contoured loop fixation, interlaminar or interfacet wiring, and acrylic fixation.2,48 Surgical decompression is undertaken in cases of irreducible craniovertebral malformation. If dynamic radiographic studies demonstrate posterior encroachment,

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Figure 68-9. Management of craniovertebral junction malformations.

dorsal decompression is undertaken by the suboccipital approach. For cases demonstrating ventral compromise, anterior decompression is performed, most often by a transoral approach.4 The majority of patients undergoing anterior decompression exhibit postoperative craniovertebral instability and require immediate or staged fixation by posterior fusion. Children younger than 12 years have the potential for new ventral bone formation while in halo fixation after odontoidectomy if the transverse ligament and dens periosteum are preserved. This may obfuscate the need for posterior fixation after anterior decompression. Similarly, osteoarthritic changes in the lateral atlanto-axial joints are often associated with postoperative stability after anterior decompression. Approximately 75% of patients who undergo anterior decompression require dorsal fixation.48

TUMORS OF THE CRANIOVERTEBRAL JUNCTION Frequency and Site Tumors that occur at the craniocervical junction can be described as either extradural or intradural lesions.

Primary extradural tumors include aneurysmal bone cysts, osteoblastomas, and osteoclastomas.2 Chordomas and metastases comprise the most common extradural lesions.49–51 Intradural tumors in the region of the foramen magnum can be classified further into intramedullary and extramedullary neoplasia. Astrocytomas and ependymomas account for the majority of the intramedullary tumors.52 Occasionally, tumors arising from the lower part of the cerebellar hemisphere or vermis, including ependymomas, medulloblastomas, and choroid plexus papillomas, extend inferiorly into the region of the foramen magnum.51,53 Benign intradural extramedullary tumors account for approximately 30% of the neoplasms at this site.51 These lesions are of particular interest to the skull base surgeon because they are theoretically respectable and may have a good prognosis. Cushing and Eisenhardt54 divided these lesions into a craniospinal group, which originates intracranially and extends down toward the foramen magnum in an anterior or anterolateral position, and a spinocranial group, which arise from below and grow up toward the foramen magnum in a lateral or posterior position.54 Tumors of the foramen magnum are most commonly located in an anterior or anterolateral position, with only 17% occurring in a posterior or posterolateral position (see Table 68-2).55–58

TABLE 68-2. Tumor Location Relative to Foramen Magnum Reference

Number of Patients

Anterior

Anterolateral

Posterior or Posterolateral

Guidetti and Spallone Meyer, Ebersold, and Reese George, Demantens, and Cophignon Stein et al

26 102 15* 25*

8 (31%) 61 (60%) 2 (13%) 1 (4%)

14 (54%) 20 (20%) 12 (80%) 21 (84%)

4 (15%) 21 (20%) 1 (7%) 3 (12%)

TOTAL

168

72 (43%)

67 (40%)

29 (17%)

*Series limited to meningiomas. From Guidetti B, Spallone A: Benign extramedullary tumors of the foramen magnum. Adv Tech Stand Neurosurg 16:84–120, 1988; Meyer F, Ebersold M, Reese D: Benign tumors of the foramen magnum. J Neurosurg 61:136–142, 1984; George B, Dematens C, Cophignon J: Lateral approach to the anterior portion of the foramen magnum. Surg Neurol 29:484–490, 1988; and Stein B, Leeds N, et al: Meningiomas of the foramen magnum. J Neurosurg 20:740–751, 1963.

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TABLE 68-3. Histopathology of Benign Intradural Extramedullary Tumors of the Foramen Magnum References

Number of Patients

Meyer, Ebersold, and Reese Guidetti and Spalone

102 26

George TOTAL

27 155

Histopathology 78 meningiomas (76%) 23 neurinomas (23%) 1 teratoma (1%) 17 meningiomas (65%) 9 neurinomas (35%) 15 meningiomas (56%) 12 neurinomas (44%) 110 meningiomas (71%) 44 neurinomas (28%) 1 teratoma (0.6%)

From Meyer F, Ebersold M, Reese D: Benign tumors of the foramen magnum. J Neurosurg 61:136–142, 1984; Guidetti B, Spallone A: Benign extramedullary tumors of the foramen magnum. Adv Tech Stand Neurosurg 16:84–120, 1988; and George B: Meningiomas of the foramen magnum. In Schmidek H (ed.): Meningiomas and Their Surgical Management. Philadelphia, WB Saunders, 1991, pp 459–470.

Meningioma is the most common disease, accounting for 71% of benign extramedullary tumors of the foramen magnum (see Table 68-3).55–58 These lesions represent 1.8% of all meningiomas, 6% to 7% of posterior fossa meningiomas, and 8% to 9% of spinal cord meningiomas. There is a definite female predominance in most series of craniovertebral meningiomas; the female-to-male ratio ranges from 2:1 to 3.6:1. The majority of these lesions become apparent in the fourth through sixth decades of life.59 These tumors are typically benign meningoepithelial or fibroblastic meningiomas. Macroscopically, most are classified as type I tumors by the mode of dural implantation, arising from a 1.0- to 1.5-cm stalk at the anterior or anterolateral rim of the foramen magnum. A minority of the tumors are type II, or the en plaque type, and have a broad dural attachment that can extend into the petroclival and subtemporal area.60 Neurinomas account for the second most frequent benign intradural extramedullary tumor of the foramen magnum, representing 28% of the neoplasms in this region.55–57,61 The majority arise from the C2 nerve root and are located in an anterior or anterolateral position relative to the spinal cord and medulla. Dermoids, teratomas, lipomas, cavernous hemangiomas, and meningeal melanocytomas infrequently have been reported to occur at the craniovertebral junction.26,61–70

Clinical Findings Craniovertebral tumors often present with ill-defined symptoms, and neurologic exam frequently fails to demonstrate signs that are easily referable to disease at the foramen magnum. In the pre-MRI era, this often led to inaccurate and delayed diagnosis. Frequent mistaken diagnoses have included hydrocephalus, multiple sclerosis, cervical spondylosis, syringomyelia, Arnold-Chiari malformation, basilar impression, amyotrophic lateral sclerosis, intra-axial tumor, vascular disease, and carpal tunnel syndrome. Further confounding the issue, temporary spontaneous remission occurs in 30% to 50% of the cases and may be erroneously attributed to nonspecific medical treatment. An average delay of 14 to 28 months between the onset of symptoms and accurate diagnosis has been reported in some series.56,57

Suboccipital headache and upper cervical pain are the most frequent initial complaint. Characteristically, the pain is aggravated by neck movements, coughing, straining, or a Valsalva maneuver. Hyperesthesia in the C2 distribution may accompany the pain and, when present, is an important finding suggestive of a foramen magnum tumor. Numbness and tingling sensations in the hand and fingers are also a frequent early symptom. Other common sensory disturbances include cold or burning dysesthesias, which also affect the upper extremities more frequently than the lower extremities.53,56,57,61 Subsequently, a progressive quadriparesis develops with foramen magnum tumors. A “typical” progression of weakness has been described, where paresis develops first in the ipsilateral arm, with subsequent spread to the ipsilateral leg, then the contralateral leg, and last the contralateral arm. Although this progression is common, it is by no means universal. Bladder disturbance and respiratory symptoms, including diaphragmatic and vocal cord paralysis, are late findings in the clinical progression.53,56,57,61 Physical examination can be misleading. Initial neurologic examination can be normal in up to 40% of cases, and a significant number of patients (20%) have normal examination at the time of surgery.57 Hyperreflexia and extremity weakness are the most common finding, and the Babinski sign is frequently seen. A dissociated sensory loss occurs in 25% of these patients, with appreciation of pain and temperature being disturbed while tactile sensation is preserved. Astereognosis and hand clumsiness are sometimes found. Atrophy of the intrinsic hand muscles occurs relatively frequently and may suggest a lesion in the low cervical spine, resulting in the erroneous diagnosis of spondylosis. The mechanism of astereognosis remains controversial, but anterior spinal artery compression, hydromyelia, venous obstruction with cord edema, and cord rotation with contralateral traction have been suggested as possible etiologies. Nystagmus, usually of the horizontal type, and ataxia can be found in 25% to 40% of patients. Spinal accessory nerve palsy is the most frequent cranial neuropathy, found in approximately 30% of cases.56,57 Historically, CSF analysis has played a role in the diagnosis of foramen magnum tumors. Lumbar puncture reveals increased protein in 50% to 80% of cases,56,57

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although the white cell count and glucose levels are typically normal.53 When carried out in the face of intracranial hypertension, lumbar puncture carries significant risk for fatal tonsillar herniation, particularly for cases that demonstrate preexisting low-lying cerebellar tonsils.71 The advent of CT and MRI has obviated the need for CSF analysis in most instances of foramen magnum tumors. Imaging studies that demonstrate unequal pressures between intracranial compartments, manifested by lateral shift of midline structures, loss of the suprachiasmatic and basilar cisterns, obliteration of the fourth ventricle, or obliteration of the superior cerebellar and quadrigeminal plate cisterns, identify those patients at greatest risk for herniation following lumbar puncture. Gower and associates72 state that a mass in the posterior fossa constitutes the strongest contraindication to lumbar puncture.

Radiographic Evaluation Plain Roentgenograms Cervical spine x-ray evaluation of the foramen magnum tumor includes anteroposterior, lateral, 35-degree oblique, and Towne basal projections. Enlargement of the intervertebral foramina, pedicle erosion, and increased C1–C2 interlaminar distance is suggestive of cervicospinal neurinoma, and a hyperostotic lesion suggests the presence of a meningioma at the foramen magnum. Plain x-ray studies may reveal such specific findings in 26% of cases.57 However, approximately 50% of plain-film examinations demonstrate spondylosis, and therefore cervical spine films can be misleading.56,57,61 Myelography Contrast myelography has a diagnostic accuracy of 95% when a complete examination is carried out, but failure to examine the patient in both the prone and supine positions increases the frequency of false-negative studies.56,57 The technique for myelographic examination of the foramen

magnum has been well described.73–75 Suggestive findings in cases of foramen magnum tumors include (1) a widening of the interval between the dens and the anterior margin of the cervical subarachnoid space by an anteriorly located tumor, (2) lateral displacement of the contrast column caused by a laterally placed tumor, (3) a dorsal defect in the contrast column by a dorsal or dorsolateral tumor, and (4) a complete block of the column of contrast material.58 This technique has been largely replaced by magnetic resonance imaging. Computed Tomography CT with intravenous contrast enhancement is diagnostic in 75% of foramen magnum tumors56,57and suggestive of disease or malformation in an additional 20% of cases.63 It is particularly helpful to identify calcification within a meningioma (Fig. 68-10A and B) and bone erosion. However, CT is limited by beam-hardening artifact at the base of skull, which limits soft tissue resolution. CT myelography offers excellent tumor delineation but, as with plain-film myelography, MRI is the preferred study; however, it is less frequently employed. Magnetic Resonance Imaging MRI has several distinct advantages over CT and myelography in demonstrating lesions of the craniovertebral junction (Fig. 68-11). MRI has excellent soft tissue resolution and is particularly useful in demonstrating the relationship between the tumor and adjacent structures, particularly the vertebral arteries. It has multiplanar imaging capabilities and can create images in the coronal, axial, and sagittal planes without requiring patient repositioning.76 Contrast enhancement with gadolinium is useful in distinguishing meningiomas from neurinomas on T1-weighted studies.77 The major limitations of MRI appear to arise from its inability to demonstrate calcification with meningiomas (seen in approximately 10% of foramen magnum meningiomas) (see Fig. 68-10C) or skull base tumor invasion.59

Figure 68-10. Axial CT scan with: A, Brain window and, B, Bone window demonstrating a calcified posterior fossa meningioma. C, Axial MRI at same level as in part B. Note that the most densely calcified portion of tumor appears as a signal void because MRI cannot resolve bone density.

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1153

Figure 68-11. A, Sagittal and, B, axial MRI scan demonstrating a clival meningioma (arrowheads) with posterior and lateral displacement of the medulla. C, Digital subtraction angiogram demonstrating a tumor blush (open arrowhead) and feeding vessel (arrow) arising from the ascending pharyngeal artery.

George60 reported an average interval of 9 months from first symptoms to diagnosis in 27 patients with foramen magnum meningiomas and neurinomas, compared to intervals of 14 months and 28 months reported by Guidetti and Spallone56 and Meyer, Ebersold, and Reese,57 respectively. George attributed his relatively short time interval for diagnosis to increased reliance on the use of CT and MRI. Angiography Arteriographic demonstration of both the vertebral and carotid arteries is often carried out in evaluation of foramen magnum tumors. This study has the potential to demonstrate the relative importance of each vertebral artery, and in cases of vessel encasement, preoperative test occlusion can be carried out. Tumor vascularity can be ascertained preoperatively (Fig. 68-11C ), and the feeding vessel originating from the ascending pharyngeal artery or from small branches of the vertebral artery can be embolized in cases of hypervascular tumors. Vertebral artery aneurysms have been misdiagnosed as foramen magnum tumors,78,79 and angiography is the most sensitive method for making this distinction, particularly if there is calcification or partial thrombosis.59

Surgical Therapy Preoperative Considerations Perioperative adrenocorticoid steroids and prophylactic antibiotics are advocated by many authors.59,80,81 Nutritional assessment should be made, and parenteral or enteral supplementation should be considered particularly if a transoral approach is employed, because no oral intake is permitted the first week after operation.82 Assessment of the degree of tolerance to flexion of the head and neck is made because it could result in neurologic impairment during patient positioning. If a semisitting position is chosen for a posterior approach, a right atrial catheter is inserted to monitor for air embolization. Some authors employ a G-suit to further decrease the risk of air embolization.

Common electrophysiologic monitoring techniques include somatosensory and brainstem auditory evoked potentials. For cases of hydrocephalus, placement of a perioperative ventriculostomy should be considered.59 With very large posterior fossa tumors associated with hydrocephalus, ventriculoperitoneal shunting 1 to 2 weeks before tumor resection is recommended. Preoperative decompression allows recovery of mental status and improvement of hydration and nutrition. Furthermore, CSF shunting facilitates intraoperative exposure and reduces the risk of postoperative complications, including cerebellar tonsillar herniation and incisional or eustachian tube CSF leakage.83 In cases for which the high risk of lower cranial nerve or respiratory compromise is likely, tracheotomy should be planned. Tracheotomy also improves intraoperative exposure during the transoral approach and prevents postoperative complications related to upper airway edema.82 Operative Approach The choice of surgical approach is determined by several factors, including tumor location with respect to the bony ring of the foramen magnum, anteroposterior relationship to the spinal cord and medulla, rostral-caudal extent, laterality, and tumor size.59 Although anterior and lateral approaches have been described for resection of foramen magnum tumors, in the past the posterior approach has been the most employed for management of intradural lesions at this site.1,51,53,56,57,59,61,84 The midline suboccipital approach provides excellent exposure of a 120-degree arch of the posterior foramen magnum after suboccipital craniectomy and C1-C2 laminectomy, without requiring transposition of any vital nervous or vascular structures. Posterior intradural tumors can be separated easily from the brain and spinal cord by this approach. Resection or partial resection of one cerebellar tonsil facilitates exposure in cases where there is tumor extension rostrally into the cerebellomedullary fissure. More often, tumors are located in an anterior or anterolateral position, and sectioning of the upper dentate ligaments facilitates

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retraction of the medulla and upper spinal cord. Occasionally, adequate exposure requires division of the ipsilateral upper cervical roots or even some roots of the lower cranial nerves, although morbidity is obviously increased by these maneuvers.1 The extreme lateral approach, which has been referred to as the transcondylar suboccipital or dorsolateral suboccipital approach in the neurosurgical literature, further improves exposure of the lateral and anterior foramen magnum. This technique allows for resection of the lateral mass of the axis, occipital condyle, medial transposition of the vertebral artery, and, if necessary, division of the sigmoid sinus at the jugular bulb.55,60,84,85 Once tumor has been exposed adequately, the tumor capsule is incised and the intracapsular contents are removed. The Cavitron ultrasonic aspirator (CUSA) or CO2 laser are helpful in this task. Finally, the remaining tumor capsule is separated from the surface of the brainstem and nerves and removed. A duraplasty is performed if a defect has been created or if there is any tension on reapproximation of the dural leaves. In cases where swelling compromises the space of the posterior fossa, suboccipital craniectomy with excision of the posterior foramen magnum ring effectively decompresses the operative field and reduces the risk for postoperative cerebellar tonsillar herniation. Tumors located in an extreme anterior position present a technical challenge. Anterior approaches have been used in this situation. The transoral approach has most often been reserved for management of extradural lesions of the ventral craniovertebral junction, because intradural exposure by this approach has a relatively high incidence of CSF fistula and meningitis. However, advantages of this technique arise from the fact that it provides the most direct route to lesions of the anterior foramen magnum, and the cranial nerves and vertebral arteries are not interposed between the surgeon and the lesion. With this approach the lateral exposure is limited to a width of 2 to 3.5 cm by the sixth and twelfth cranial nerves, the internal carotid and vertebral arteries, inferior petrosal sinuses, and the contents of the jugular foramina.80,82 There is an increased incidence of postoperative velopharyngeal incompetence compared to extradural transoral procedures, probably related to the more extensive bone removal required for adequate intradural exposure. Disruption of the anterior bony and ligamentous structures of the craniovertebral junction increases instability of the cervical spine and often requires posterior fusion.

The likelihood of CSF leakage may be diminished by use of autogenous fascial grafts, fat grafts, bone grafts, fibrin adhesive, and prolonged CSF diversion. Neurinomas, which are typically well circumscribed, may be more amenable to complete transoral removal than meningiomas, which may encroach on surrounding nerves and vessels.51,86,87 Treatment Results Treatment results for three series of benign intradural extramedullary tumors of the craniovertebral junction are summarized in Table 68-4. Although there have been reports of remarkable, near-complete recovery in patients with severe neurologic compromise from foramen magnum tumors,88 this analysis stresses the importance of early diagnosis: In general, functional recovery is largely comparable to the preoperative neurologic status.55,57,58 Meyer and associates57 analyzed 102 benign extramedullary intradural tumors at the craniovertebral junction, reporting an operative mortality rate of 5%. An additional 5%, all of whom had incomplete resections, succumbed to recurrent disease within 3 years of surgery. Postoperatively, 12% had mild functional impairment and 13% had marked functional impairment. Guidetti and Spallone56 reported their experience with 26 foramen magnum meningiomas and neurinomas. The operative mortality was 11%, and there were no documented cases of incomplete tumor removal or recurrence. Of the survivors, 15% were noted to have mild weakness, which was present preoperatively, and all survivors were leading “normal lives.” George60 reported an operative mortality rate of 11% and poor outcome in 4% in a series of 27 foramen magnum meningiomas and neuromas. The most common sequela was dysphonia and dysphagia related to unilateral injury to cranial nerves IX and X. There were no recurrences of tumor.

SURGICAL APPROACHES TO THE CRANIOVERTEBRAL JUNCTION The surgical approach to lesions of the craniovertebral junction is determined by the anatomy and pathophysiology of the ongoing process. The principal approaches to pathology in this region are outlined in Table 68-5. These procedures are reviewed briefly in the following section.

TABLE 68-4. Treatment Results of Benign Intradural Extramedullary Tumors of the Foramen Magnum Reference Meyer, Ebersold, and Reese Guidetti and Spallone George TOTAL

Number of Patients

Mortality

Postoperative Functional Impairment

102 26 27 155

10% 11% 11% 10%

25% 15% 4% 20%

From Meyer F, Ebersold M, Reese D: Benign tumors of the foramen magnum. J Neurosurg 61:136–142, 1984; Guidetti B, Spallone A: Benign extramedullary tumors of the foramen magnum. Adv Tech Stand Neurosurg 16:84–120, 1988; and George B: Meningiomas of the foramen magnum. In Schmidek H (ed.): Meningiomas and Their Surgical Management. Philadelphia, WB Saunders, 1991, pp 459–470.

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TABLE 68-5. Surgical Approaches to the Craniovertebral Junction Anterior Approaches Transoral approach Subfrontal-transbasal approach Trans-sphenoidal approach

Lateral Approaches Transcervical approach Infratemporal fossa approach Fisch Type D infratemporal fossa approach Extreme lateral approach

Posterior Approaches Suboccipital approach

Endoscopic Assisted Approaches

Anterior Approaches Transoral Approach The patient is positioned supine with the head in a head holder or in traction using cranial tongs (see Fig. 68-12). After induction of general anesthesia, a tracheotomy may be performed. Procedures at the level of the atlas and axis may not require tracheotomy, but procedures directed toward more rostral regions of the craniovertebral junction usually require tracheotomy for adequate exposure. After placement of a self-retaining oral retractor, the posterior pharyngeal wall is incised in the midline and the mucosa and prevertebral muscles are elevated in a subperiosteal plane. To improve exposure of the clivus, the soft palate can be retracted superiorly into the nasopharynx with a silk suture passed through the nose. This provides exposure of

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the clivus and first three cervical vertebrae over a total length of 2.5 to 3.0 cm. Alternatively, the soft palate can be divided in the midline, laterally based flaps can be raised off the hard palate, and a portion of the hard palate can be removed with rongeurs. Le Forte I osteotomy with maxillary down fracture or lateral rhinotomy provides additional exposure to the area of the sphenoid, sella turcica, and midline anterior skull base. Lateral exposure is limited to a width of 2.0 to 3.5 cm by the sixth and twelfth cranial nerves, the internal carotid arteries, the vertebral arteries, the internal jugular veins, and the inferior petrosal sinuses. Further exposure can be obtained inferiorly by making a midline mandibulotomy and placing downward retraction on the tongue between the mandibular halves. Splitting the tongue and floor of the mouth provides inferior exposure down to the level of the supraglottic larynx. Using the operative microscope for magnification and illumination, the surgeon uses a high-speed drill with a diamond burr to remove the anterior arch of the atlas, the caudal clivus, and then the odontoid process. To provide access to intradural lesions, the transverse ligament is removed and the ventral dura is incised in a cruciate fashion. Bleeding from the circular sinus is controlled with clips, and the dural leaves are retracted with sutures. This provides exposure to the vertebral arteries, the inferior basilar artery, and the ventral brainstem and upper cervical spinal cord. At the conclusion of the procedure, intradural exposure requires placement of a fascial graft taken from the external oblique aponeurosis of the tensor fascia lata, which is then reinforced with fat. The prevertebral muscles and pharyngeal mucosa are then closed in a water-tight fashion. If the incision extends up onto the clivus, this area may be bolstered with a posterior nasal pack. Postoperatively, the patient is maintained with 5 to 7 pounds of skeletal

Figure 68-12. The transoral approach to the craniovertebral junction. A, Incisions through the soft palate and oropharyngeal mucosa are outlined after placement of an oral retractor. B, Lateral reflection of the prevertebral muscles and palatal mucosa exposes the hard palate, clivus, and anterior arches of the atlas and axis. C, A high-speed drill is used to remove the clivus, anterior arch of the atlas, and odontoid process, exposing the dura. D, Dural leaves are opened and retracted laterally, exposing the vertebrobasilar junction and brainstem. (Published with permission, © 1992 P.A. Wackym.)

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Figure 68-13. The subfrontal-transbasal approach to the craniovertebral junction. A, Exposure is provided to the anterior foramen magnum by separation of the subfrontal dura from the orbital roofs and resection of the posterior part of the floor of the anterior cranial fossa. B, Inset demonstrates extent of bifrontal craniotomy. (Published with permission, © 1992 P.A. Wackym.)

traction. If the dura was opened, no oral feedings are allowed for 7 days, and intravenous antibiotics and spinal drainage are continued for 10 days. Evaluation of cervical spine stability is undertaken after 7 days, and posterior spinal fusion is carried out if necessary.1,81,82 Subfrontal-Transbasal Approach A bicoronal scalp incision is carried out behind the hairline and a bifrontal free bone flap is created (Fig. 68-13). The subfrontal dura is then raised off the orbital roofs. The olfactory projections are divided at the cribriform plate, and dural elevation is carried out posteriorly to the lesser wings of the sphenoid bones, the tuberculum sellae, and the base of the anterior clinoid process. Access is gained to the clivus by upward retraction of the frontal lobes and resection of the posterior portion of the floor of the anterior cranial fossa. From this point, the clivus can be resected down to the anterior margin of the foramen magnum. Elevation of the posterior pharyngeal mucosa and muscles provides access to the first three cervical bodies. Upon completion of the procedure, dural defects are closed with autogenous fascial grafts, and the skull base is reconstructed with autogenous bone grafts. Anosmia is a universal postoperative result following completion of this approach.1

mucous membrane is elevated off the right nasal floor. This right inferior tunnel is then connected with the right septal mucoperichondrial flap. An inferior tunnel is created on the left side, and the cartilaginous septum, with attached left mucoperichondrium, is dislocated to the left and elevated in continuity with the mucous membrane of the left nasal floor. The pyriform aperture is then widened with a high-speed drill, but an attempt is made to preserve the anterior nasal spine. The osseous nasal septum is removed in a piecemeal fashion, exposing the sphenoid rostrum. A Lee or Hubbard self-retaining retractor is then placed, and the anterior wall of the sphenoid sinus is removed with Hajek or Kerrison rongeurs. The width of exposure obtained is determined by the distance between the two medial pterygoid plates and is, in most instances, between 2.4 and 2.9 cm. A cross-table x-ray confirms the position of the retractor relative to the sella turcica. To approach the clivus, the floor of the sella turcica is removed and extended downward on the clivus to the inferior margin of the sphenoid sinus. Lesions of the upper third of the clivus can be biopsied or partially removed through this technique.89,90

Lateral Approaches Transcervical Approach

Transsphenoidal Approach After induction of general anesthesia, the surgical field is infiltrated with 1% lidocaine with 1:100,000 epinephrine, and topical vasoconstriction is obtained by means of 4% cocaine or oxymetazoline on cotton applicators (see Fig. 68-14). A nasal septal hemitransfixion incision is made and the right septal mucoperichondrium is elevated. A separate anterior sublabial incision is then made and the

Tracheotomy or nasotracheal intubation is achieved to allow the mouth to be tightly closed (see Fig. 68-15). The patient is positioned in the supine position, with cervical hyperextension and rotation of the neck away from the side of the lesion. A horizontal submandibular incision is made from the mastoid tip to the mandibular symphysis, and a vertical incision is then carried inferiorly from the midpoint of the submandibular incision along the

Abnormalities of the Craniovertebral Junction

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Figure 68-14. The transsphenoidal approach to the clivus. A, The Lee or Hubbard retractor is placed through the pyriform aperture after lateral reflection of the nasal mucosa and cartilaginous nasal septum. B, Exposure of the keel of the sphenoid sinus after removal of the bony nasal septum. C, The keel of the sphenoid sinus is removed to expose the sella turcica and superior portion of the clivus. (Published with permission, © 1992 P.A. Wackym.)

Figure 68-15. The transcervical approach to the craniovertebral junction. A, A submandibular skin incision extends from the mastoid tip to the submeatal region, running two fingerbreadths below the inferior margin of the mandibular body. A vertical component is dropped from the submandibular incision along the sternocleidomastoid muscle. B, This approach provides exposure to the clivus and anterior components of the atlas and axis. C, The prevertebral muscles are exposed through the plane between the carotid sheath structures posteriorly and the hypopharynx anteriorly. D, Midline division of the prevertebral muscles in a subperiosteal plane exposes the clivus and first three cervical vertebrae. Intradural exposure is achieved after removal of the clivus, anterior arch of the atlas, and the odontoid process. (Published with permission, © 1992 P.A. Wackym.)

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sternocleidomastoid muscle. A fascial plane is developed between the prevertebral muscles and the pharynx, retracting the sternocleidomastoid muscle laterally. The carotid sheath structures are retracted laterally or medially. To obtain adequate exposure of the ventral aspect of the clivus, atlas, and axis, it may be necessary to divide the ascending pharyngeal and superior thyroid arteries, the superior laryngeal nerve, the ansa hypoglossi, the lingual artery, the digastric muscle, the stylohyoid ligament, and the stylopharyngeus and styloglossus muscles. Resection of the tip of the styloid process and anterior dislocation of the mandibular condyle may further facilitate exposure. Retraction for exposure of the anterior arch of the axis, the odontoid process, and a 2-cm width of clivus puts the internal carotid artery and ninth through twelfth cranial nerves at some risk. At the conclusion of the procedure, the superior pharyngeal constrictor muscles and the buccopharyngeal fascia are sutured to the prevertebral fascia, and a nasopharyngeal pack is placed to ensure obliteration of the retropharyngeal space.56,91 Infratemporal Fossa Approach A large C-shaped temporal scalp incision is fashioned approximately 6 cm behind the postauricular crease, with the lower limb extending inferiorly two fingerbreadths below the mandible (see Fig. 68-16). The facial nerve is identified at the stylomastoid foramen, and its branches are followed peripherally. The carotid sheath is opened and the external carotid artery is dissected distally. The external auditory canal is divided and the auricle is reflected anteriorly. The skin of the external auditory canal is then removed along with the tympanic membrane and handle of the malleus. A radical mastoidectomy is performed, exposing the facial nerve from the stylomastoid foramen to

the geniculate ganglion. At this point, the facial nerve can be mobilized and transposed anteriorly to the root of the zygoma if additional exposure is required in the region of the jugular foramen. For tumors of the clivus, this is usually unnecessary, and adequate anterior exposure is afforded by resection of the mandibular condyle and reflection of the zygomatic arch. Tumors of the parasellar and parasphenoid regions required inferior reflection of the zygoma with its orbital process and portion of the lateral orbital rim. The tympanic bone and styloid process are resected, following the internal carotid artery superiorly from the bifurcation. For parasellar tumors, the internal carotid artery is followed superiorly to the cavernous sinus, dividing the eustachian tube, middle meningeal artery, and mandibular nerve. The pterygoid plate is drilled away and the internal carotid artery is followed through the foramen lacerum. Division of the maxillary nerve provides rostral exposure to the level of the superior orbital fissure. At the conclusion of the procedure, the zygoma is miniplated back into normal position, the eustachian tube is obliterated, and the temporalis muscle is rotated down to fill the surgical defect. The external auditory canal is closed as a blind sack, and the wound is closed in two layers.92 Fisch D Infratemporal Fossa Approach This approach is an extension of the Fisch C infratemporal fossa dissection but it uses a preauricular incision to avoid disturbing the middle ear and mastoid. It provides access to the middle and upper clivus and petrous apex without the need for mastoidectomy or infratemporal facial nerve rerouting. The incision is similar to the modified Blair incision used for parotidectomy with a superior curvilinear extension to the frontal hairline (Fig. 68-17). Skin and soft tissue are reflected anteriorly, with care being taken to

Figure 68-16. The type C infratemporal fossa approach. A, Postauricular skin incision. B, Exposure of the infratemporal fossa after removal of the zygomatic arch and lateral orbital rim. C, Pterygopalatine fossa exposed after removal of the pterygoid process. (Published with permission, © 1992 P.A. Wackym.)

Abnormalities of the Craniovertebral Junction

A

V2 V1 Foramen ovale

Internal carotid artery

Zygomatic arch

Foramen magnum

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avoid injury to the frontal branch of the facial nerve by dissecting deep to the superficial layer of the temporal fascia. Periosteum overlying the zygomatic arch is likewise elevated to protect the frontal facial nerve branch. A zygomatic osteotomy is performed and the temporalis muscle reflected anteroinferiorly. The extratemporal facial nerve trunk is identified along with its branches within the parotid gland. The mandibular condyle is inferiorly displaced along with the joint capsule to expose the glenoid fossa. A frontotemporal craniotomy in conjunction with a drill-out of the glenoid fossa provides access to the petrous carotid. This requires sacrifice, with bipolar cautery, of the middle meningeal artery and mandibular division of the trigeminal nerve. Subsequent decompression and lateral retraction of the petrous carotid exposes the medial petrous apex. Completion petrosectomy can now be performed to allow access to the posterior fossa for intradural lesions and middle fossa dura for upper clival and cavernous sinus tumors. Closure is directed toward filling the defect to prevent CSF leakage and consists of duraplasty, temporalis muscle rotation flap or tissue transfer such as a latissimus muscle or rectus abdominis free flap. Miniplate fixation of the craniotomy bone flap and of the zygomatic arch completes and secures the reconstruction. Alternatively, a cranioplasty can be performed instead of miniplate fixation of the bone flap, which has the advantage of replacing the skull where the craniectomy has been performed. In addition, the eustachian tube needs to be oversewn and long-term ventilation of the middle ear considered.93 Extreme Lateral Approach

Eustachian tube

B

V2 V1

Clivus

Foramen ovale

Internal carotid artery Foramen magnum

Foramen spinosum

C

Facial nerve

Figure 68-17. The type D infratemporal fossa approach. A, Preauricular skin incision. B, Dissection of the infratemporal fossa after removal of the zygomatic arch, transection of the eustachian tube, and sacrifice of the middle meningeal artery and mandibular nerve. C, The medial petrous apex exposed after decompression and retraction of the horizontal carotid artery. (Published with permission, © 2004 P.A. Wackym.)

A skin incision is made 6 cm caudally from the base of the mastoid process along the lateral aspect of the neck (Fig. 68-18). The sternomastoid muscle is detached superiorly, and the splenius capitis and cervicis muscles are undermined and divided close to their anterior attachments. The vertebral artery is identified and exposed from the transverse foramen of C2 to the zone of dural penetration. A small dorsolateral craniectomy is performed, and dural exposure is continued by performing a hemilaminectomy of C1 and C2. Resection of the lateral mass of C1 is continued to include the transverse process, which allows for medial and caudal transposition of the vertebral artery. Subsequently, the capsule of the atlanto-occipital joint is incised, and the posteromedial portion of the occipital condyle is drilled away. Drilling is carried anteriorly to expose the hypoglossal canal and cranially until the jugular tubercle is resected. This procedure allows visualization of the anterior rim of the foramen magnum. To obtain further anterior exposure, a limited mastoidectomy is carried out to expose the vertical segment of the facial nerve, the jugular bulb, and the sigmoid sinus. The sigmoid sinus is then divided at the jugular bulb.55,84,85

Posterior Approach Suboccipital Approach The patient is positioned in the half-sitting position or the lateral dorsal position (Fig. 68-19). A skin incision is carried from a point 4 cm above the inion to the fifth cervical

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Figure 68-18. The extreme lateral approach to the craniovertebral junction. A, The skin incision is outlined. B, Dorsolateral suboccipital craniectomy and removal of a portion of the occipital condyle and lateral masses of the first two cervical vertebrae exposes the dura and vertebral artery. A limited mastoidectomy exposes the sigmoid sinus anteriorly. C, Dural incision exposes the anterior and lateral cervicomedullary junction. (Published with permission, © 1992 P.A. Wackym.)

Figure 68-19. The suboccipital approach to the craniovertebral junction. A, Skin incision and retraction. Bone removal includes suboccipital craniectomy and C1–C2 laminectomy. B and C, Cruciate dural incision exposes a 120-degree arch of the posterior foramen magnum. (Published with permission, © 1992 P.A. Wackym.)

Abnormalities of the Craniovertebral Junction

vertebra. The skin is retracted and a Y-shaped incision is made in the underlying fascia. The posterior muscles are then elevated in a subperiosteal plane and retracted laterally. The squamous portion of the occipital bone and the spinous processes and laminae of the first two cervical vertebrae are removed after identifying and protecting the vertebral arteries as they pass dorsal to the lateral masses of the atlas. For intradural pathology, a Y-shaped incision is made in the dura, which is retracted laterally with stay sutures. This provides exposure of the posterior one third of the foramen magnum. At the conclusion of the procedure, hemostasis is achieved and the dura is closed with interrupted sutures. If the dura has been resected, then a suitable dural substitute is used for reconstruction.56

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in the far-lateral transcondylar approach97 and with a small incision preauricular infratemporal fossa approach.98 Case reports have also suggested that endoscopic surveillance can ensure completeness of surgical resection and allow for less radical surgical approaches. Endoscopes have been used in subtemporal-infratemporal approaches,99 transmaxillary-transclival approaches,100 and transoraltranspharyngeal approaches.101 An illustrative example of the ability of endoscopes to ensure tumor removal and aid in the identification of neurovascular structures is demonstrated in Figures 68-20 and 68-21. Figure 68-20 demonstrates an anterior extraaxial meningioma at the craniovertebral junction causing significant brainstem compression. Figure 68-21 shows

Endoscopic Assistance The past several years have seen an increase in the number and types of surgeries in which endoscopes have played a primary or adjunctive role.94,95 The high magnification and detailed resolution provided by modern endoscopes often surpasses that afforded by the operating microscope and facilitates the identification and preservation of fine vessels and nerve branches. Current limitations in the use of endoscopy for skull base surgery, however, includes the narrow field of view, potential thermal injury by the endoscope, and the relative lack of specific instrumentation designed for endoneurotologic surgery.96 Nevertheless, reports of endoscopic-assisted surgeries of the craniovertebral junction are increasing. Feasibility studies in cadaveric preparations have demonstrated improved visualization of neural structures

A

B

Figure 68-20. Post-contrast T1-weighted sagittal magnetic resonance image of an extra-axial meningioma at the anterior margin of the foramen magnum. Notice compression of the medulla posterior to the mass. (From Wackym PA, Rice D, and Schaeffer S. Minimally Invasive Surgery of the Head and Neck and Cranial Base. Philadelphia, Lippincott Williams and Wilkins, 2002. Published with permission.)

Figure 68-21. Endoscopy-assisted resection of this caudal meningioma. A, Intraoperative view with a 4-mm, 0° endoscope demonstrates the tumor (T) between the petroclival junction (left) and the ventral brainstem (right). Cranial nerves VII, VIII, IX, X, XI, and XII are seen. The porus acousticus (P) and jugular foramen (JF) are clearly visualized. B, Following complete tumor resection, advancement of the 4-mm, 0° endoscope delineates the trigeminal (V), abducens (VI), facial (VII), vestibulocochlear (VIII), glossopharyngeal (IX), vagus (X), spinal accessory (XI), and hypoglossal (XII) nerves. The basilar artery (B) is seen along the ventral brainstem. (From Wackym PA, Rice D, Schaeffer S. Minimally Invasive Surgery of the Head and Neck and Cranial Base. Philadelphia, Lippincott Williams and Wilkins, 2002. Published with permission.)

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the operative field through a 4-mm, 0° endoscope before and after tumor removal. The endoscope facilitated dissection through the lattice of cranial nerves around the craniovertebral junction and ensured complete tumor removal.

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26. Diekmann-Guiroy B, Huang P: Klippel-Feil syndrome in association with a craniocervical dermoid cyst presenting as aseptic meningitis in an adult case report. Neurosurgery 25:652–655, 1989. 27. Magib M, Maxwell R, Chou S: Klippel-Feil syndrome in children: Clinical features and management. Child’s Nerv Syst 1:255–263, 1985. 28. Sinh G: Congenital atlanto-axial dislocation. Neurosurg Rev 6:211–220, 1983. 29. Hess J, Bronstein I, Abelson S: Atlanto-axial dislocation unassociated with trauma and secondary to inflammatory foci of the neck. Am J Dis Child 49:1137–1147, 1935. 30. Lipmann R: Arthropathy due to adjacent inflammation. J Bone Joint Surg 35:967–979, 1953. 31. Sullivan A: Subluxation of the atlanto-axial joint and sequel to inflammatory process of the neck. J Pediatr 35:451–464, 1949. 32. Bland J: Rheumatoid arthritis of the cervical spine. J Rheumatol 1:319–342, 1974. 33. Menezes A, VanGilder J, Clark O: Odontoid upward migration in rheumatoid arthritis. J Neurosurg 63:500–509, 1985. 34. Mikulowski P, et al: Sudden death in rheumatoid arthritis with atlanto-axial dislocation. Acta Med Scand 198:445–451, 1975. 35. Kumar A, Patni A, Charbel F: The Chiari I malformation and the neurotologist. Otol Neurotol 23:727–735, 2002. 36. Sperling N, Franco R, Milhorat T: Otologic manifestations of Chiari I malformation. Otol Neurotol 22:678–681, 2001. 37. Milhorat T, Chou M, Trinidad E, et al: Chiari I malformation redefined: Clinical and radiographic findings for 364 symptomatic patients. Neurosurgery 44:1005–1017, 1999. 38. Chiat G, Barber H: Arnold-Chiari malformation—some otoneurologic features. J Otolaryngol 8:65–70, 1979. 39. Cogan D: Down-beat nystagmus. Arch Ophthal 80:757–768, 1968. 40. Elies W, Plester D: Basilar impression: A differential diagnosis of Ménière’s disease. Arch Otolaryngol 106:232–233, 1980. 41. McLay K, Maran A: Deafness and the Klippel-Feil syndrome. J Laryngol Otol 83:175–184, 1969. 42. Edwards W: Congenital middle-ear deafness with anomalies of the face. J Laryngol Otol 78:152–170, 1964. 43. Jarvis J, Sellars S: Klippel-Feil deformity associated with congenital conductive deafness. J Laryngol Otol 88:285–289, 1974. 44. Faria M, Spector R, Tindall G: Downbeat nystagmus as the salient manifestation of the Arnold-Chiari malformation. Surg Neurol 13:333–336, 1980. 45. Bronstein A, Miller D, Rudge P, et al: Down beating nystagmus: Magnetic resonance imaging and neuro-otological findings. J Neurol Sci 81:173–184, 1987. 46. Baloh R, Spooner J: Downbeat nystagmus and a type of central vestibular nystagmus. Neurology 31:304–310, 1981. 47. Zee D: New concepts of cerebellar control of eye movements. Otolaryngol Head Neck Surg 92:59–62, 1984. 48. DiLorenzo N: Transoral approach to extradural lesions of the lower clivus and upper cervical spine: An experience of 19 cases. Neurosurgery 24:37–42, 1989. 49. Castellano F, Rugiero G: Meningiomas of the posterior fossa. Acta Radiol 104:xi–177, 1953. 50. Congdon C: Benign and malignant chordomas: A clinicoanatomical study of twenty-two cases. Am J Pathol 28:793–821, 1952. 51. Love J, Thelon E, Dodge H: Tumors of the foramen magnum. J Internat Coll Surg 22:1–17, 1954. 52. Love J, Adson A: Tumors of the foramen magnum. Trans Am Neurol Assn 67:78–81, 1941. 53. Dodge H, Love J, Gottlieb CM: Benign tumors at the foramen magnum: Surgical considerations. J Neurosurg 13:603–617, 1957. 54. Cushing H, Eisenhardt L: Meningiomas. Springfield, Ill, Charles C Thomas, 1938, pp 169–180. 55. George B, Dematens C, Cophignon J: Lateral approach to the anterior portion of the foramen magnum. Surg Neurol 29:484–490, 1988. 56. Guidetti B, Spallone A: Benign extramedullary tumors of the foramen magnum. Adv Tech Stand Neurosurg 16:84–120, 1988.

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57. Meyer F, Ebersold M, Reese D: Benign tumors of the foramen magnum. J Neurosurg 61:136–142, 1984. 58. Stein B, Leeds N, et al: Meningiomas of the foramen magnum. J Neurosurg 20:740–751, 1963. 59. Scott E, Rhoton A. Foramen magnum meningiomas. In Al-Mefty O (ed.): Meningiomas. New York, Raven, 1992, pp 543–568. 60. George B: Meningiomas of the foramen magnum. In H. Schmidek (ed.): Meningiomas and Their Surgical Management. Philadelphia, WB Saunders, 1991, pp 459–470. 61. Yasuoka S, Acazaki H, Daube J: Foramen magnum tumors: Analysis of 57 cases of benign extramedullary tumors. J Neurosurg 49:828–838, 1978. 62. Abrahamson I, Grossman M: Tumors of the upper cervical cord. J Nerve Nerv Ment Dis 57:342–363, 1923. 63. Salas E, Sekhar LN, Ziyal IM, et al: Variations of the extremelateral craniocervical approach: Anatomical study and clinical analysis of 69 patients. J Neurosurg 90(4 Suppl):206–209, 1999. 64. Bucy P, Gustafson W: Intradural lipoma of the spinal cord. Zentralbl Neurochir 3:341–349, 1938. 65. Elsberg C, Strauss I: Tumors of the spinal cord which project into the posterior cranial fossa. Arch Neurol Psychiatry 21:261–273, 1929. 66. Limas C, Tio F: Meningeal melanocytoma (“melanotic meningioma”). Its melanocytic origin as revealed by electron microscopy. Cancer 30:1286–1294, 1972. 67. MacCarty C, Lougheed L, Brown J: Unusual benign tumor at the foramen magnum: A case report. J Neurosurg 16:463–467, 1959. 68. Misch W: Meningeal lipoma in the foramen magnum. J Neurol Psychopathol 16:123–129, 1935. 69. Uematsu Y, et al: Meningeal melanocytoma: Magnetic resonance imaging characteristics and pathological features. J Neurosurg 76:705–709, 1992. 70. Weinstein E, Wechsler I: Dermoid tumor in the foramen magnum with astereognosis and dissociated sensory loss. Arch Neurol Psychiat 44:162–170, 1940. 71. Sullivan H: Fatal tonsillar herniation in pseudotumor cerebri. Neurology 41:1142–1144, 1991. 72. Gower D, Baker A, Bell W: Contraindications to lumbar puncture as defined by computed cranial tomography. J Neurol Neurosurg Psychiatry 50:1071–1074, 1987. 73. Baker H: Myelographic examination of the posterior fossa with positive contrast medium. Radiology 81:791–801, 1963. 74. Malis L: Myelographic examination of the foramen magnum. Radiology 70:196–221, 1958. 75. Margolis M: A simple myelographic maneuver for the detection of mass lesions at the foramen magnum. Radiology 119:482–485, 1976. 76. Wagle V, et al: Diagnostic potential of magnetic resonance in cases of foramen magnum meningiomas. Neurosurgery 21:622–626, 1987. 77. Watabe T, Azuma T: T1 and T2 measurements of meningiomas and neuromas before and after Gd-DTPA. Am J Neuroradiol 10:463–470, 1989. 78. Bull J: Massive aneurysms at the base of brain. Brain 92:535–570, 1969. 79. Michael W: Posterior fossa aneurysms simulating tumors. J Neurol Neurosurg Psychiatry 37:218–223, 1974. 80. Crockard H, Sen C: The transoral approach for the management of intradural lesions at the craniovertebral junction: Review of 7 cases. Neurosurgery 28:88–98, 1991.

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81. Menezes A: Complications of surgery at the craniovertebral junction—avoidance and management. Pediatric Neurosurg 17: 254–266, 1992. 82. Menezes A: Anterior approaches to the craniocervical junction. Clin Neurosurg 37:756–769, 1991. 83. Steenerson R, Payne N: Hydrocephalus in the patient with acoustic neuroma. Otolaryngol Head Neck Surg 107:35–39, 1992. 84. Bertalanffy H, Seeger W: The dorsolateral, suboccipital and transcondylar approach to the lower clivus and anterior portion of the craniocervical junction. Neurosurgery 29:815–821, 1991. 85. Sen C, Sekhar L: An extreme lateral approach to intradural lesions of the cervical spine and foramen magnum. Neurosurgery 27:197–203, 1990. 86. Bonkowski J, Gibson R, Snape L: Foramen magnum meningioma and transoral resection with a bone baffle to prevent CSF leakage. J Neurosurg 72:493–496, 1990. 87. Miller E, Crockard H: Transoral transclival removal of anteriorly placed meningiomas at the foramen magnum. Neurosurgery 20:966–968, 1987. 88. Siqueira E, Kanaan I, Ali M: Large meningioma of the foramen magnum in a 4-year-old child. Surg Neurol 31:409–411, 1989. 89. Kern E, Pearson B, McDonald T: The transseptal approach to lesions of the pituitary and parasellar regions. Laryngoscope 89:1–34, 1979. 90. Lee K, Goodrich I, Pensak M: Pituitary surgery and current status: Including transsphenoidal surgery. Am J Otolaryngol 5:138–150, 1984. 91. Stevenson G, Stoney R, Perkins R: A transcervical transclival approach to the ventral surface of the brainstem for removal of a clivus chordoma. J Neurosurg 24:544–551, 1966. 92. Fisch U, Pillsbury H: Infratemporal fossa approach to lesions in the temporal bone and base of skull. Arch Otolaryngol 105: 99–107, 1979. 93. Sanna M, De Donato G, Taibah A, et al: Infratemporal fossa approaches to the lateral skull base. Keio J Med 48:189–200, 1999. 94. Jho H: The expanding role of endoscopy in skull-base surgery. Indications and instruments. Clin Neurosurg 48:287–305, 2001. 95. Wackym P, Rice D, Schaeffer S: Minimally Invasive Surgery of the Head and Neck and Cranial Base. Philadelphia, Lippincott Williams & Wilkins, 2002. 96. Wackym P, King W, Meyer G, et al: Endoscopy in neuro-otologic surgery. Otolaryngol Clin North Am 35:297–323, 2002. 97. Hayashi N, Cohen A: Endoscope-assisted far-lateral transcondylar approach to the skull base. Minim Invasive Neurosurg 45:132–135, 2002. 98. Hartnick C, Myseros J, Myer CR: Endoscopic access to the infratemporal fossa and skull base: A cadaveric study. Arch Otolaryngol Head Neck Surg 127:1325–1327, 2001. 99. Sarma S, Sekhar L: Brain stem cavernoma excised by subtemporalinfratemporal approach. Br J Neurosurg 16:172–177, 2002. 100. Cha S, Jarrahy R, Yong W, et al: A rare symptomatic presentation of ecchordosis physaliphora and unique endoscope-assisted surgical management. Minim Invasive Neurosurg 45:36–40, 2002. 101. Frempong-Boadu A, Faunce W, Fessler R: Endoscopically assisted transoral-transpharyngeal approach to the craniovertebral junction. Neurosurgery 51:60–66, 2002.

Chapter

69 P. Ashley Wackym, MD Christina L. Runge-Samuelson, PhD

Gamma Knife Radiosurgery and Other Forms of Radiosurgery for Management of Skull Base Tumors Outline Introduction Frame Attachment General Principles Tools and Orientation Localization and Placement Post and Screw Attachment and Measurements Radiation Physics Introduction Basic Concepts Irradiation Technique Quality Assurance Biologic Effects Treatment Planning

INTRODUCTION It was in 1951 that Dr. Lars Leksell first conceived of what is now known as Gamma Knife radiosurgery. As articulated, he envisioned “the delivery of a single, high dose of radiation to a small and critically located intracranial volume through the intact skull.” He first thought that this would be accomplished via a center of arc principle and in fact, the early attempts at accomplishing this utilized a single arc across which radiation was delivered to the intracranial target. The first Gamma Knife unit (Elekta Instrument AB, Stockholm, Sweden) was installed in Stockholm in 1968 and it was not until 1987 that the first Gamma Knife (model U) was installed at the University of Pittsburgh. The Gamma Knife model B was first introduced in 1996 and this is the unit that is most used throughout the United States. The Gamma Knife model C was introduced in 1999 and the biggest change associated with this unit is that there is an automatic positioning system (APS). Other than this, the unit is quite similar to the model B and both contain 201 60Co sources and beam channels. When the collimator helmet is locked into position, the 201 openings of the collimator helmet coincide with these cobalt sources. There is a shielded chamber that contains the 60 Co sources and stainless steel shielding doors that protect the treatment room from the 60Co sources. A treatment couch with an adjustable mattress slides into the Gamma Knife unit together with the collimator helmet and the patient. Figure 69-1 schematically shows the orientation of the components of the Gamma Knife model C and 1164

Placing Shots Wizard Fine-Tuning Plugging Peripheral Isodose Grouping Shots Protocols Export Treatment Procedure Manually Setting Coordinates Automatic Positioning System Applications and Outcomes

Other Radiosurgery Techniques Fractionated Stereotactic Radiosurgery Intensity-Modulated Radiation Therapy CyberKnife® Stereotactic Radiosurgery Overview of Treatment Planning Dose Distribution Localization Treatment Delivery Summary

Figure 69-2 shows the overall appearance of the Gamma Knife model C unit. Stereotactic radiosurgery can be applied to a wide range of skull base diseases, but it is used most frequently to treat acoustic neuromas. This form of treatment, just as is the case with microsurgery, has advantages and disadvantages, which must be thoroughly discussed with the patient. For the patient, it is very attractive to undergo an outpatient procedure rather than the much longer period of care required to undergo microsurgical management of the tumor. As an example, with a typical acoustic neuroma managed via microsurgery, surgery takes place on the day of admission and an overnight stay in the intensive care unit is typical. This is subsequently followed by 5 to 7 days of hospitalization and a post discharge recovery of 2 to 4 weeks. This is in sharp contrast to Gamma Knife radiosurgery, which is performed on an outpatient basis. Clear demonstration of tumor control and, with current methods, low cranial nerve morbidity have been published in our literature. Unfortunately, some advertised claims are very misleading to patients. For example, in Figure 69-3 the magnetic resonance imaging (MRI) images taken 6 months, 1 year, and 3 years after radiosurgery seem to show that the tumor becomes progressively smaller than it was presurgery. This is misleading, however, because the MRIs were photographed at different levels, artificially changing the size of the tumor. This illustrates the critical need for accurate measurement and reporting of tumor volume over time. Although this illustration shows distorted image reporting with the CyberKnife system,

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Figure 69-1. Gamma Knife radiosurgery. Schematic illustration of the Gamma Knife model C, which uses the automatic positioning system. (Reproduced with permission, copyright © 2003, Elekta Instrument AB, Stockholm, Sweden.)

this type of misleading representation has unfortunately been true with other systems. In fact, the MRI images used to illustrate “tumor shrinkage” in the classic New England Journal of Medicine article reporting outcomes of a cohort of patients treated with Gamma Knife radiosurgery suffers from the same problem of comparing different levels.1 Since the introduction of the Leksell Stereotactic System in 1949, preceding Leksell’s adaptation of this technology for stereotactic radiosurgery, the Karolinska Institute in Stockholm has developed clinical collaboration with leading medical institutions around the world. Several of these institutions arrange courses for other centers who have invested in the Leksell Stereotactic System or the Leksell Gamma Knife. During the last 10 years, more than 1000 neurosurgeons, neurotologists, physicists, and radiation oncologists have attended these educational programs. Elekta Instrument AB (Stockholm, Sweden) offers basic training courses as well as advanced technical workshops. The courses consist of didactic lectures, observation of patient treatment, and practical hands-on training. Additionally, all new installations of the Leksell Gamma

Figure 69-2. Gamma Knife model C. (Reproduced with permission, copyright © 2003, Elekta Instrument AB, Stockholm, Sweden.)

Knife are accompanied by a 1-week on-site start-up training, for which the neurotologists, neurosurgeons, radiation oncologists, and physicists constituting the Gamma Knife treatment team are responsible for coordinating with the manufacturer.

Figure 69-3. CyberKnife® radiosurgery treatment of a right acoustic neuroma. This patient was imaged prior to radiosurgery, as well as at 6 months, 1 year, and 3 years post radiosurgery. The gadolinium-enhanced axial MR images of the acoustic neuroma at each post radiosurgery time point appear to demonstrate progressive shrinking of the tumor; however, note that the 6-month follow-up image is positioned higher than the preradiosurgery image. Likewise, the 1-year and 3-year postradiosurgery images are progressively lower and both are at lower levels than the preradiosurgery MRI shown. This presentation of images at different levels falsely suggests that the tumor is decreasing. It should be noted that the Web site does not make this claim; however, this type of imagery is misleading to patients who rely on the Internet to supplement information provided by their physicians. (Adapted with permission, copyright © 2004, CyberKnife® Society Accuray Incorporated, Sunnyvale, Cal.; http://cksociety.org/ PatientInfo/MedicalConditions/ acousticneuroma.asp#treatment.)

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Frame Attachment General Principles The following sections present the procedure typically used to attach the stereotactic head frame. Two procedures must be performed before Gamma Knife radiosurgery. (1) Before attaching the frame to the patient’s head, the target should be centered in the frame, and (2) the frame attachment should be very stable. These steps should be confirmed before the beginning of the frame attachment. In lateral targets, such as acoustic neuromas, there is a risk for collisions between the collimator helmet of the Gamma Knife unit and the opposite lateral side of the frame, the posts, or the fixation screws. Similarly, other targets located in the posterior fossa can result in frame collisions of the anterior post. Because of these factors, the target should be located as close to the center of the frame as possible. Tools and Orientation Absolute stability of the frame is required—avoid screw fixation in bone flaps, cranioplasty materials, burr holes, or skull defects—because treatment accuracy is based on the geometry of the stereotactic frame coordinates. Figure 69-4 shows the usual array of tools used for the frame attachment, namely, a variety of screws from which to choose those ideally suited for the individual location of the post, two pairs of screwdrivers, and generally 20 mL of local anesthesia. The placement of the frame should begin with an accurate location of the target in the patient’s head.

Figure 69-4. Stereotactic head frame at the time of assembly. Pins used for fixation before imaging, treatment planning, and Gamma Knife radiosurgery are seen in the foreground. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

The target should be located in the fiducial range and placed centrally in the frame, thereby avoiding collisions with the collimator helmet and granting sufficient accuracy for the stereotactic target definition. Localization and Placement After the surgeon is oriented regarding the location of the target, the stereotactic frame is preliminarily attached with ear plugs, a Velcro band, or a stereotactic fiducial box. When a fiducial box is used to facilitate frame placement, it is important to use the MRI fiducial box rather than the computed tomography (CT) or angiography fiducial box because it is the smallest of the three Plexiglas fiducial boxes (Fig. 69-5). Complete asymmetric frame placements are possible and do not impair the accuracy of imaging. The frame can be shifted from side to side or can be moved as far as possible to the front or back. When the frame is successfully placed, meaning that the position of the target is as close as possible to the center of the frame, the nurse or assistant holds and stabilizes the stereotactic frame with two hands. The frame is stabilized against the patient, thereby providing a constant position in the optimal localization. The surgeon can now adjust the length of the posts to suit the patient’s head as well as to give stability to the frame while being careful to avoid bone flaps, cranioplasty materials, burr holes, and skull defects. Post and Screw Attachment and Measurements For targets in the posterior fossa, a low position of the anterior posts can sometimes avoid anterior collisions with the collimator helmet, particularly if the patient has

Figure 69-5. Gamma Knife radiosurgery. During placement of the stereotactic head frame, the plastic MRI fiducial box is secured to the frame and used to determine that adequate space remains around the head. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

Gamma Knife Radiosurgery and Other Forms of Radiosurgery for Management of Skull Base Tumors

a large head. After the posts are adjusted and firmly fixed to the frame, local anesthesia is injected by inserting the needles through the holes provided for the screws. The screws can now be inserted. The goal of this step is to attain a preliminary frame fixation in the desired position. Fixation with diagonally opposing screws provides the best stability without changing the desired frame position. If the frame has to be shifted to one side, apply the longest screws first, thereby defining the desired distance of the target to the frame. The frame is now preliminarily stabilized with the screws on the patient’s head. The length of the screws is considered ideal if the tips do not extend more than 8 mm to 10 mm off the posts; however, this surgeon prefers to limit this projection to 4 mm to 6 mm. If the screw extends further, exchange the existing screw with a screw that has the ideal length for the position of the head. The length of the four posts is determined by measuring from the top surface of the frame to the tip of each post. In addition to that, the length of the screws that extend over the posts is measured. These measurements are required for the frame and skull section in Leksell GammaPlan treatment planning software. The stereotactic frame attachment is completed once the volume of the head has been measured using the plastic bubble, simulating the relationship of the frame to the collimator helmet (Fig. 69-6). These measurements are also required for Leksell GammaPlan treatment planning software in the frame and skull section. In critical positions, collisions can sometimes be avoided by using the curved posts in the anterior position in certain posterior fossa tumor cases.

Figure 69-6. Gamma Knife radiosurgery. After placement of the stereotactic head frame, a plastic bubble simulating the collimator helmet is attached. Through defined entrance points, measurements from the bubble to the face and scalp are recorded. Likewise, post height and pin length are recorded. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

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Radiation Physics Introduction Under certain circumstances, small and well-delineated cerebral targets can be treated very selectively by means of narrow, high-energy beams of gamma radiation. The Leksell Gamma Knife emits this radiation by 201 sources containing the radioactive nucleus 60Co. Healthy brain tissue located between skull and target can be spared provided that a suitable irradiation technique has been chosen and the target is small. Consequently, the radiation energy affects only the target cells and can therefore be delivered in a single session through the intact skull. Depending on the histologic type of target and the size, a single maximum dose of 20 gray to 160 gray (Gy) is prescribed (10 Gy to 80 Gy delivered to the 50% isodose line). Currently, for acoustic neuromas, the routine prescription is 12 Gy to 14 Gy delivered to the 50% isodose line. The actual irradiation procedure is carefully planned for each case by means of calculated dose distributions overlaid on images of the brain, cranial nerves, and surrounding structures. The quality of the resultant treatment plan, which is tailored using virtual reality in the Leksell GammaPlan treatment planning software, must then be assessed with tools described later in this chapter. Basic Concepts The quantity absorbed dose, or simply the dose, describes the average energy that is absorbed in a small volume of mass such as tissue, water, and so on. This quantity is used to prescribe radiologic procedures, such as radiosurgery. Absorbed dose has the unit gray (Gy). From a dosimetric perspective, the radiation energy is deposited in tissue or in other matter in discrete events. On the soft cellular level, the energy depositions vary substantially and are scattered randomly among the molecules of the cells. These discrete energy depositions have relevance for the outcome of the treatment. For practical dosimetric reasons, their local average (that is, the absorbed dose) is used. From a clinical perspective, the dose cannot be prescribed to a point because a point by definition has no mass, nor can the dose be prescribed for the entire target because the dose may vary by a factor of 2 or more. Thus, without a meaningful definition of where the dose is prescribed (for instance, to the periphery of the target), the dose information is of limited value. The quantity radioactivity describes the rate at which the unstable atoms of radioactive matter disintegrate. An unstable atom has an excessive energy, which it releases generally by emitting particles with mass or without, in order to reach its stable, nonradioactive level. This transition from an unstable atom to the final stable state can include several transitions. At each step, energy is radiated. The unstable 60Co nuclide, which is used as the radiation-emitting source of the Leksell Gamma Knife, transforms into 60Ni in one transition. Radioactivity is a measure of how many atoms are disintegrating per unit of time, but it says nothing about the energy emitted by this process. When the stable element 59 Co is exposed to neutrons in a reactor, one of these neutrons is absorbed by the nucleus of a 59Co atom and the unstable cobalt nuclide 60Co is created. 60Co has an

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excessive energy, which must be released. The process is as follows. One of the neutrons of 60Co nucleus transforms spontaneously into a proton and an electron. The electron is instantly emitted by the nucleus but never reaches the patient; it is absorbed by matter in the neighborhood of the nucleus. The 60Co nucleus transforms by this process into a new element, 60Ni, the nucleus of which instantly emits two gamma photons with energies of 1.17 and 1.33 mega electron volts, respectively (Fig. 69-7). New sources consist mainly of 60Co. With time, the cobalt is transformed into nickel. The rate at which this transformation takes place is measured in terms of half-life, which is a well-known physical entity used to characterize unstable nuclei. 60Co has a half-life of 5.27 years. In practice, this means that after little more than 5 years, the treatment time for the same dose is doubled. Finally, the treatment time becomes too long and the sources must be replaced. When photons interact with biologic tissue, two major processes compete. The photoelectric effect dominates at low energies and the Compton effect dominates at 100 kilo electron volts and higher. The gamma radiation emitted by 60Co is highly energetic and interacts mainly with tissue via the Compton effect. The gamma photon interacts with one of the outer electrons of an atom with a penetrated soft tissue. The Compton photon and the Compton electron are ejected, sharing the energy and the momentum of the incoming gamma photon. The created Compton photon interacts with the new atom or may be scattered out of the tissue. The energetic Compton electron interacts intensely with molecules and atoms close to its short path through tissue, leaving behind a cloud of ionized molecules. The desired clinical effect is caused by these ionized molecules of the irradiated cells. A dose of 10 Gy to 80 Gy is delivered to the periphery of the radiosurgical lesion in a single session. However, normal tissue located adjacent to the radiosurgical lesion must not be affected by the same radiation. Irradiation technique must therefore be selected with a dose fall-off that is very steep at the border of the target. At the same time, the whole target must be covered.

Figure 69-7. Gamma Knife radiosurgery. The 60Co nucleus transforms spontaneously into a proton and an electron. Through this process it is transformed into a new element, 60Ni, the nucleus of which instantly emits two gamma (γ) photons. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

In other words, the dose distribution must conform to the shape and size of the target and the dose must be delivered selectively. This is one of the strengths of using 60Co as a radiation source. The radiation dose decreases with depth as a result of two phenomena. The number of energytransporting photons decreases with depth as they are absorbed by the water or are scattered out of the beam. There is also so-called inverse square law, which states that when the distance to the radiation source is doubled, the dose is decreased by a factor of 4. This effect dominates in the case of the Leksell Gamma Knife because the distance from source to isocenter is short; however, a single beam delivers most of its radiation dose to the region of its entrance. The following section outlines the strategy developed by the Gamma Knife system to overcome this issue. Irradiation Technique To overcome the problem that single-photon beams deliver most of their energy at the beam entrance, we need to cross fire the target with radiation from many directions. A large number of beams can be directed so that they converge toward one single region where the target resides during treatment. At the beam intersection, energy from all beams is delivered to the cells. Outside that region, the radiation dose decreases rapidly so that tissue between beam entrance and target is not affected by the radiation. There are several technical solutions for achieving a convergent beam irradiation technique. A single radiation source can be moved relative to the patient’s head or vice versa. Naturally, a combination of patient and source movements can also be used. The safest and most reliable converging irradiation technique is the one with irradiation emitting sources and the patient remaining stationary during treatment. This stationary procedure requires that the patient’s head be surrounded by a large number of sources during treatment and all the beams aim at a common region where the radiosurgical target resides; this is the technique used with the Leksell Gamma Knife. Radiophysical and technical tolerances of all components that affect dose delivery are so narrow that all 201 beams of one unit are identical, from a radiophysical perspective. This fact holds true not only for each unit but also for all units of the same design, which facilitates comparison of clinical results published by different Leksell Gamma Knife centers. Because the beam characteristics are identical, they do not need to be measured at each Leksell Gamma Knife installation. They are therefore prestored in the treatment planning software, Leksell Gamma Plan, which greatly simplifies commissioning of a new Leksell Gamma Knife. When treatment is initiated, the treatment couch is automatically moved from its idle position into the treatment unit together with patient and helmet. Once the couch is docked in its treatment position, the helmet collimator and corresponding collimators in the unit form a beam channel, allowing the radiation that is continuously emitted by the sources to reach the patient (see Fig. 69-1). At the end of each irradiation “shot,” the couch is automatically withdrawn, either to its idle position or to a position outside the radiation focus to reposition the patient for the next irradiation shot. There are four interchangeable helmets of which the size of the radiolesion sphere can be changed

Gamma Knife Radiosurgery and Other Forms of Radiosurgery for Management of Skull Base Tumors

to 4 mm, 8 mm, 14 mm, or 18 mm (Fig. 69-8). The combination of four sizes of radiolesion spheres and repositioning the patient in the three-dimensional space defined by the stereotactic head frame is an effective tool to deliver the radiation dose selectively and can conform to radiosurgical targets of any shape (Fig. 69-9). The use of convergent very narrow beams poses some strict technical and radiophysical requirements on the radiation-delivering apparatus. The axis of all beams must intercept at one point and its precise location and space must be known. The radiophysical character of the radiation beams must be well known, be stable in time, and optimize to the sharp beam edges. Figure 69-10 illustrates these basic requirements, which are important for selective and reproducible dose delivery. Five perfect beams intersect the center of a two-dimensional brain. It is important that the beam axes be aligned precisely. Any intersection of the beam axis that deviates from the ideal will affect the dose distribution. Imperfections inherent in all equipment, regardless of manufacturer, must be kept small enough to have no clinical significance during the life of the treatment unit. Because of technical and radiophysical characteristics of the system, there are limits to how small the radiolesion can be in order to ensure safety and reproducibility. Figure 69-11 illustrates the narrow beam of the Leksell Gamma Knife discussed previously on a hypothetical level, with the combined dose distribution of all 201 beams. It also illustrates the beam size effect and the penumbra associated with each of the four collimator helmet sizes. With wider beams, alignment is less critical. On the other hand, their edges begin to overlap farther from the target periphery (see Figs. 69-10 and 69-11). The distance at which the beams begin to overlap depends on beam size for a given irradiation technique, meaning that the dose outside the target periphery depends on the beam size. This means that theoretically a relatively high dose is delivered outside the target to a large volume of normal tissue. At some point we can no longer claim that the treatment is selective and we must then find an alternative irradiation technique.

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Figure 69-9. Gamma Knife radiosurgery. In this example, the tumor target can be filled with five shots using a larger collimator helmet or with 18 shots with a smaller collimator helmet. In contrast to the model U and model B, the model C uses an automatic positioning system (APS) and can therefore complete a large number of shots in a timely manner. (Reproduced with permission, copyright © 2003, Elekta Instrument AB, Stockholm, Sweden.)

The dose absorbed in normal tissue adjacent to the target periphery is the most significant factor that limits the volume that can be treated radiosurgically. The widest beam of the Leksell Gamma Knife is 18 mm in diameter at isocenter, here shown as an off-axis distance (see Fig. 69-11). Quality Assurance When the radiophysical characteristics of a Leksell Gamma Knife are investigated for quality assurance, measured and calculated dose profiles are compared. At present, experimental profiles are obtained by means of chromatographic film dosimetry. The special dose distribution is verified by means of two films. The films are consecutively exposed in Elekta’s spherical head phantom, rotated 90 degrees relative

Figure 69-8. Four sizes of collimator helmets are used in Gamma Knife radiosurgery. The diameter of each (4 mm, 8 mm, 14 mm, or 18 mm) determines the diameter of the sphere of radiation delivered with each shot. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

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film, it is pierced by the needle. The location of the optical density distribution is compared with the location of the narrow hole in the film. The two films are exposed consecutively with their planes rotated 90 degrees. The deviation between the center of the optical density and the needle hole is measured in the direction of the three main axes of the stereotactic coordinate system. The deviation between the mechanically defined isocenter and the location of the radiation focus is measured in this way. Biologic Effects Figure 69-10. Gamma Knife radiosurgery. Four overlapping beams of two different widths demonstrate the difference in additive radiation effects around a central target. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

to each other. The calculated profile is used as a template. Optical density (OD) profiles are measured from the films along the three main axes of the stereotactic coordinate system. The OD profiles are converted into dose profiles by an OD dose calibration procedure. The measured profiles are compared with corresponding profiles calculated with the Leksell Gamma Plan software. The calculations are made with the assumption that the irradiation and the experimental conditions are the same. These hypothetical profiles are used as reference. The distribution of the dose in a volume surrounding the radiation focus is investigated in this way. The stereotactic spherical volume used to expose films for evaluating dose distribution of the Leksell Gamma Knife does not have the narrow geometrical tolerances required to determine the location of the radiation focus in the irradiation unit. For this purpose, an aluminum bar that is machined to very narrow tolerances is used. It has a spring-loaded needle and a space for a small film. When the tool is aligned exactly between the trunnions of the helmet, the sharp tip of the needle is located in the exact mechanical isocenter. Just before exposure of the

Figure 69-11. Gamma Knife radiosurgery. The beam size effect is shown graphically and numerically. The right side of the figure shows the isodose curves for the 4-mm, 8-mm, 14-mm, and 18-mm collimator helmets. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

Radiation dose is the most important factor in determining the outcome of a radiosurgical procedure, but it is far from the only factor. The type of radiation is important. Charged particles, such as powerful particles, are about three times as efficient per unit dose as photons. The clinical result of the treatment may be seen months to years following the irradiation. The time interval between irradiating and observation is therefore important. The irradiated volume is important in two ways. One is the large volume of normal tissue adjacent to large targets that receives a high dose. A second factor is the size of the target volume per se. More cells must be affected by the stochastically distributed energy, meaning that the dose should be increased to keep the number of unaffected cells low. The biologic response to radiation depends on the type of cells that are irradiated. If a single dose is delivered with a low dose rate by photons, the DNA of the cells has a longer time to repair. With the example of benign skull base tumors, such as acoustic neuromas and meningiomas, very few cells are actively dividing at the time of treatment. Therefore, the primary effect is not destruction of these more radiosensitive dividing cells, but rather a longer-term decreasing of the vascular supply to the tumor (Fig. 69-12). As will be discussed later, this was a hard lesson learned in the initial application of Gamma Knife radiosurgery to these types of tumor. The use of radiation doses appropriate for malignancy resulted in excellent tumor control; however, unacceptably high levels of hearing loss, trigeminal nerve

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Figure 69-12. Gadolinium-enhanced T1-weighted axial MRI shows homogeneous appearance of left acoustic neuroma at the time of Gamma Knife radiosurgery. A, Repeat imaging 6 months after Gamma Knife radiosurgery shows reduced gadolinium enhancement in the tumor’s center, suggestive of decreased vascularization (B). (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

dysfunction, and facial nerve dysfunction were seen.1 It has been pointed out by Pitts and Jackler2 that no evidence has been presented of decreased vascularity after Gamma Knife radiosurgery and that in the animal studies performed by Linskey and colleagues,3 there was no reduction of vascularity in xenograft acoustic neuromas after treatment with 10 Gy. Figure 69-12 shows the pretreatment MRI and the typical appearance 6 months after Gamma Knife radiosurgery. This patient received 12 Gy at the 50% isodose line, which means that the maximum tumor dose was 28 Gy focused, no doubt, where the reduced gadolinium enhancement in the center of the tumor can be seen.

Treatment Planning Placing Shots Leksell GammaPlan is the dedicated software treatment planning system for the Leksell Gamma Knife. Dose planning for Gamma Knife surgery means precisely conforming the isodose distribution to the target. The isodose distribution is built up by a number of individual shots or isocenters. The Leksell GammaPlan software is designed to help the operator as much as possible to perform this procedure and is quite straightforward to use (see Fig. 69-9). Dose planning with Leksell GammaPlan involves composing shots to develop a conformal isodose. By definition, this includes the whole target but spares the surrounding healthy tissue. Figure 69-13 shows an acoustic neuroma. The target is well positioned on the screen and magnified for good visibility. When the shot menu is opened, one can select the size of the collimators. Selecting 14 mm would be too large for the target and would not give an effective treatment. The shots are placed sequentially and the size of the collimator is selected based on the tumor shape and

the gaps in coverage of the 50% isodose line displayed over the tumor. Shots are placed to cover the target as effectively as possible. Changing the position of the shots and taking additional shots with low weight quickly lead to a conformal dose plan. The dose plan can be checked using Leksell GammaPlan with the three-dimensional image or the measurement tools, such as dose volume histograms. The subject of conformity index is beyond the scope of this chapter, however, an excellent review of available methods has been published by Paddick.4 Leksell GammaPlan indicates the point in the stereotactic space where a global maximal dose can be found. Leksell GammaPlan also calculates the individual shot times. Once the treatment plan has been determined to be appropriate by the team (surgeon, radiation oncologist, and radiation physicist), the stereotactic coordinates and irradiation times are printed and used during the Gamma Knife treatment. Wizard An automated approach to initial treatment planning has been developed by Elekta Instrument AB. This software “wizard” is an interactive tool that assists the treatment planner in generating a good initial dose plan quickly and it helps the operator develop the dose plan. The operator first selects the shot size and the degree of density with which the wizard should fill the target. A mouse click instructs the wizard to fill the target with shots. If the initial dose distribution is not sufficient, a mouse click on the run button instructs the wizard to optimize the plan by moving and weighting the shots. After a few more changes, a satisfactory dose plan can be created. However, in this surgeon’s experience, manual placement of the shots, particularly for acoustic neuromas, has always resulted in a better treatment plan than those created by the wizard.

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Figure 69-13. Initial treatment planning at the Gamma Knife workstation involves building a three-dimensional model of the tumor. Determination of the conformation of the treatment plan follows placement of the shots and assignment of the radiation dose delivered to the specified isodose line. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

Fine-Tuning Fine-tuning is made by small adjustments toward optimization of the dose plan. Leksell GammaPlan simplifies this. For example, if the three-dimensional image shows a dose missed part or parts of the target, shots can be moved, weighted, or added to produce a more conformal plan. As shown in Figure 69-14, high isodose lines show the dose distribution inside the target, making homogeneity and hot spots easily visible. Low isodose lines show the dose in the surroundings of the target. The purpose of this step is to show the dose distribution to at-risk structures, such as the facial nerve, in order to minimize the risk of complications after treatment. Leksell GammaPlan also allows the creation of different plans for the same target. This allows the operator to follow different strategies and later compare plans and select the best plan for the actual treatment. Treatment plans can use as few as 1 or 2 shots, such as when treating trigeminal neuralgia, or as many as 10 to 12 shots, such as when treating a 2-cm acoustic neuroma (maximum axial dimension within the cerebellopontine angle) plus filling the internal auditory canal. With the enhanced capabilities of Leksell Gamma Knife C, plans with 20 shots or more can easily be implemented in a timely manner because the model C does not require manual adjustments of the X, Y, and Z coordinates by the Gamma Knife treatment team. This allows improved conformity and selectivity of Gamma Knife surgery, possibly reducing complications.

effect on the target peripheral isodose. The beam channels that need to be plugged can be seen in the plug pattern (Fig. 69-15). The plug patterns can be merged for all shots of the same size so that the operator has to plug the helmets for the treatment only once. Peripheral Isodose In the final plan, the peripheral dose is set to a value, which is assessed as optimal for a particular patient. Indication, size, and location of the target are taken into account, as well as clinical experience. The peripheral isodose is usually set to the 50% isodose line. This is exactly half the maximum

Plugging To shape the dose distribution for the low isodose lines in one direction in particular, one or more of the 201 collimators can be replaced with a closed shield, called a plug. One can select spherical areas called shields with different diameters and place them over risk centers in the brain or cranial nerves. Once the shields are in place, within the software, Leksell GammaPlan closes off all beams that would irradiate through the shielded area. The result is a modified dose plan in the low isodose lines with only little

Figure 69-14. Gamma Knife radiosurgery. Selecting the Absolute Dose Level and Display Isodose options allows verification that the maximal radiation dose is not delivered near critical structures, such as the facial nerve. In this example, 14 Gy delivered to the 50% isodose line was prescribed. As shown, the maximum dose (28 Gy) is delivered to the center of the tumor (smallest circle). The largest circle represents the 20% isodose line where 6 Gy of radiation is delivered. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

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Export When the treatment set-up has been completed, the treatment protocol has to be exported to Leksell Gamma Knife. This information is transmitted via a special secured direct serial connection. Leksell GammaPlan accepts only valid and verified treatment plans for export. An added protective design limits transfer of treatment plans to the Leksell Gamma Knife to one patient at a time. Once the data has been transferred to the operator’s console, it is verified and the patient can be treated.

Treatment Procedure Manually Setting Coordinates

Figure 69-15. Gamma Knife radiosurgery. Plugging is another strategy to avoid excessive radiation to critical structures, in this example, the optic chiasm. The treatment planning software determines which paths of the collimator helmet should be replaced with a solid plug to eliminate radiation from passing through the collimator helmet and contributing to the radiation delivered to the critical structure. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

dose in the target, referred to as the hot spot (see Figs. 69-12 and 69-14). Along the 50% line the dose gradient is usually the steepest, which ensures sufficient dose within the target, while the dose level outside falls steeply, which spares the surrounding healthy tissue. Leksell Gamma Plan can also display the absolute dose values if desired. It will show the point in the stereotactic space where the global maximum dose can be found. With acoustic neuromas it is valuable to complete this exercise because the maximal dose at the “hot spot” should be positioned well away from the facial nerve. In addition, plotting the absolute dose lines will help in determining the actual level of radiation delivered to surrounding structures.

Treatment can be performed automatically using the automatic positioning system or manually using trunnions. As described previously, for the model B, manual setting of the X, Y, and Z coordinates, as well as the gamma angle if necessary, is accomplished by the treatment team. The Y and Z coordinates are set with the Y, Z slides on the coordinate frame, whereas the X coordinate and the gamma angle are set with the trunnions. Another check and balance is the visual verification of each coordinate by a different team member. Automatic Positioning System With the automatic positioning system, the treatment is controlled from the operator’s console. Once the treatment starts, the selected run is carried out automatically. Before repositioning, the couch will move out a short distance to bring the patient out of treatment focus. At this point, the APS will move the patient’s head to the next target position. When the first run is completed the remaining runs, with different-sized collimator helmets, are selected and performed in the same manner after manually changing the collimator helmet.

Applications and Outcomes Grouping Shots When the dose planning is completed, Leksell GammaPlan has to check and sort the shots. Assume, for example, that the treatment consists of two shots with 8-mm collimators and 5 shots with 4-mm collimators. Leksell GammaPlan will group all shots and use the same collimators during each series of shots of a given size. For the model C unit, the operator does not need to enter the treatment room during a run. However, with the model B the treatment team reenters the treatment room after each shot is delivered and manually adjusts the X, Y, and Z coordinates, as well as the gamma angle if necessary. With both the models B and C, the team needs to manually change the collimator helmet as dictated by the treatment plan. Protocols Several detailed protocols can be viewed and printed. All relevant data can be documented—details of the treatment plan, targets, dose volume histograms, snap shots, and images.

As is the case with other forms of medical and surgical therapy, the outcomes of Gamma Knife radiosurgery for the treatment of acoustic neuromas and other skull base tumors has evolved and improved over time. This change in methods has been based on patient outcome, as described earlier. Next, we will focus on questions that remain to be answered as well as examples of good and poor outcomes with hearing after Gamma Knife radiosurgery. Comparison to surgical outcomes is beyond the scope of this chapter5,6; however, with this topic is well discussed in the chapter on “Acoustic Neuroma (Vestibular Schwannoma).” Finally, we will discuss issues related to the expansion of the technology in areas that are inappropriate. The first Gamma Knife unit model U was installed at the University of Pittsburgh in 1987. This group has the longest and largest clinical experience in treating acoustic neuromas with Gamma Knife radiosurgery. There have been several reports of this series; however, the Kondziolka and colleagues summarize their experience with 162 acoustic neuromas treated between 1987 and 1992.1 The average dose at the tumor margin was 16 Gy and they reported

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a tumor control rate of 98%. They also reported normal facial nerve function in 79% of patients after 5 years of observation. They likewise reported normal trigeminal nerve function in 73% of these patients; stated conversely, this is an astounding rate of trigeminal nerve dysfunction of 27%. They reported “no change in hearing ability” in 51% of these patients, and this method of reporting auditory performance points to the difficulty in interpreting most studies that report hearing outcome in patients with acoustic neuroma who have been treated with Gamma Knife radiosurgery. Although tumor control of 98% is excellent, the poor facial nerve and trigeminal nerve outcomes reported, combined with the poor hearing ability, led to reduction in the average dose delivered to the tumor margin. In a series of an additional 190 acoustic neuroma patients, Flickinger and colleagues reviewed the University of Pittsburgh experience from 1992 to 1997.7 The average dose to the tumor margin was reduced to 13 Gy and excellent tumor control was still achieved at 97.1%. There was a marked reduction in both facial nerve and trigeminal nerve dysfunction with only 1.1% ± 0.8% facial nerve dysfunction, and reduced trigeminal nerve function was present in only 2.6% ± 1.2% of patients. In this study, issues highlighted earlier with reporting of hearing outcome are equally apparent. They reported “hearing-level preservation” in 71% ± 4.7% of patients. They also reported a “preservation of testable speech discrimination ability” in 91% ± 2.6% of subjects. Obviously, testable speech discrimination ability is far different from useful hearing and it is unfortunate that these authors did not report the actual auditory thresholds or speech discrimination ability. Most important, these results were not reported as a function of time post Gamma Knife radiosurgery. An interesting finding was that facial paresis did not develop in any patient who received a marginal dose of less than 15 Gy (163 patients out of 190 patients). In addition, they reported that “hearing levels improved” in 10 (7%) of 141 patients who exhibited decreased hearing defined as GardnerRobertson8 classes II–V (Table 69-1) before undergoing Gamma Knife radiosurgery. In the Medical College of Wisconsin Acoustic Neuroma and Skull Base Program, we have established a protocol for all of our patients undergoing Gamma Knife radiosurgery for primary or secondary treatment of their tumors. Following completion of their stereotactic radiosurgery, at 6-month intervals, each patient undergoes a gadoliniumenhanced MRI as well as an audiometric test battery and caloric testing to assess peripheral vestibular function. TABLE 69-1. Gardner-Robertson Hearing Classification System Auditory Grade

Hearing Level

Pure Tone Speech Discrimination Average (dB) Score (%)

I II III IV V

Good Serviceable Nonserviceable Poor None

0–30 31–50 50–90 91 max Nontestable

70–100 50–69 5–49 1–4 0

Source: Gardner G, Robertson JH: Hearing preservation in unilateral acoustic neuroma surgery. Ann Otol Rhinol Laryngol 97(1):55–56, 1998.

Pretreatment they undergo a complete electronystagmography test battery, a complete audiometric assessment, and facial nerve electromyography. We have recently analyzed these early outcomes data and have published a summary of these data.9 Figures 69-16 through 69-20 summarize the hearing and vestibular outcomes over time. As shown, these data are presented for individual patients over time, which is unique in the stereotactic radiosurgery literature. Gamma Knife radiosurgery remains an option for patients who are deciding on a treatment modality. As is the case with observation and microsurgery, there are advantages and disadvantages associated with these three treatment modalities. The systematic study of outcomes with each of these methods will ultimately determine which patient cohorts are best suited to each treatment. There are also anecdotal cases worthy of discussion to illustrate a few specific points about stereotactic radiosurgery and the outcomes associated with treatment with fractionated stereotactic radiosurgery or Gamma Knife radiosurgery. First, we have found that a distortion in the MRI data set is produced by the stereotactic head frame used in Gamma Knife radiosurgery. As shown in Figure 69-21, the treatment plan and outline of the tumor, based on MRI treatment planning, is approximately 1 mm more anterior than the position of the internal auditory canal as visualized with CT imaging. We are in the process of systematically evaluating this distortion; however, several Gamma Knife centers use MRI exclusively to build the three-dimensional work space and complete the treatment planning, which raises questions about long-term treatment outcomes if regions of the tumor are undertreated and adjacent structures, such as the facial nerve, are overtreated. An anecdotal case that points out the need to critically assess terms such as tumor control involves a woman who decided to travel to a large fractionated stereotactic radiosurgery center for treatment of a small acoustic neuroma. As seen in Figure 69-22, the patient has had excellent tumor control relative to the medial portion of the tumor. However, it can be seen that she had progressive growth of the tumor laterally until her fundus was completely filled with tumor. Office notes and direct conversations with the treating radiosurgeon indicated that he considered this complete tumor control. Unfortunately, as shown in Figures 69-23 and 69-24, her thresholds and speech recognition continued to worsen until she was ultimately left with no useful hearing on the side of the tumor. At 18 months post fractionated stereotactic radiosurgery, her pure tone average fell from 15 dB to 63 dB, and her speech discrimination fell from 92% to 20%, clearly a poor hearing outcome. Another anecdotal case that illustrates a dilemma when counseling a patient about management options is worthy of brief discussion. A young woman was referred to a neuro-otologist (PAW) for evaluation and discussion of management options for her small acoustic neuroma (Fig. 69-25). She had poor auditory function with a pure tone average of 52 dB and speech discrimination of 60%. The advantages and disadvantages of observation, microsurgery, and Gamma Knife radiosurgery were discussed with her at length during several office visits. Based on her age as well as the position and size of her tumor, I thought she would be best served with observation and ultimately microsurgical removal via a

Figure 69-16. Auditory function over time after Gamma Knife radiosurgery treatment of unilateral acoustic neuromas (Medical College of Wisconsin series). Three-frequency averages of pure tone thresholds (PTA-3) in dB HL at 0.5, 1, and 2 kHz were determined for all patients with measures at the preoperative interval and at least one postoperative interval. The PTA-3 difference was calculated for each time interval relative to the preoperative PTA-3. The differences are plotted as a function of postoperative time interval, with zero representing the preoperative interval. A positive difference value indicates a higher, or poorer, postoperative PTA-3. In general, over time, patients had PTA-3s that were poorer or similar to preoperative PTA-3s, even though a few individuals showed some initial improvement (e.g., s13). (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

Figure 69-17. Auditory function over time after Gamma Knife radiosurgery treatment of unilateral acoustic neuromas (Medical College of Wisconsin series). Four-frequency averages of pure tone thresholds (PTA-4) in dB HL at 0.5, 1, 2, and 4 kHz were determined for all patients with measures at the preoperative interval and at least one postoperative interval. The PTA-4 difference was calculated for each time interval relative to the preoperative PTA-4. The differences are plotted as a function of postoperative time interval, with zero representing the preoperative interval. A positive difference value indicates a higher, or poorer, postoperative PTA-4. In general, over time, patients’ PTA-4s were poorer or similar to preoperative PTA-4s, even though a few individuals showed some initial improvement. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

Figure 69-18. Speech recognition testing was performed using the Northwestern University Auditory Test No. 6, NU-6,10 monosyllabic words (Medical College of Wisconsin series). The stimuli were presented at the 40-dB sensation level (i.e., above speech recognition threshold), or if this was too loud, at the patient’s most comfortable listening level. Speech recognition was scored in percent correct. As with PTA, the differences between preoperative and postoperative speech recognition were calculated and plotted as a function of postoperative time interval. Positive values are consistent with an improvement in speech recognition. Approximately half of the patients showed improvement in speech recognition at 6 months post treatment, while the other half showed a decrease in performance. However, over time the patients generally demonstrate speech recognition performance similar to or poorer than pretreatment performance. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

Figure 69-19. Vestibular paresis was determined by bithermal caloric testing (Medical College of Wisconsin series). A positive difference value indicates greater vestibular paresis post Gamma Knife radiosurgery. Both degradation and improvement in vestibular paresis are observed across patients. Within patients, the postoperative degree of vestibular paresis generally tends to remain stable over time. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

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Figure 69-20. The Gardner-Robertson classification system was used to broadly characterize audiometric outcome after Gamma Knife radiosurgery (Medical College of Wisconsin series). The system includes classification based on three-frequency PTA and speech recognition scores. Classes range from I (best performance) to V (no measurable performance) (see Table 69-I). If PTA and speech recognition fell into two classes, a “half-value” that fell between the classes was assigned. Changes in class from preoperative to post treatment are shown, with positive values indicating changes to a poorer performing class. As indicated with the other measures, there is both improvement and degradation in audiometric measures; post-treatment, several patients remained in their pretreatment class. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

translabyrinthine approach, or alternatively, with microsurgical removal via a translabyrinthine or middle cranial fossa approach as soon as she would want to this. It was anticipated that it would likely take 5 or more years for the tumor to fill the internal auditory canal and then it still would not change the facial nerve outcome during translabyrinthine resection of the tumor. Despite this, she decided to undergo Gamma Knife radiosurgery. As shown in Figure 69-25, the tumor initially increased in size and later was reduced. There was also a surprising

improvement in both her auditory thresholds and speech recognition ability (Figs. 69-26 and 69-27). At 18 months post Gamma Knife radiosurgery, her pure tone average had increased to 33 dB and her speech discrimination had improved to 84%. Longer-term follow-up is certainly necessary and will be completed; however, this outcome was not anticipated and she is extremely pleased with her management decision. One statistic is particularly alarming to patients considering Gamma Knife radiosurgery for the treatment of their

Figure 69-21. Gamma Knife radiosurgery. This example illustrates the distortion introduced by MRI relative to CT during the data acquisition for treatment planning. As shown, the tumor volume and 45% isodose line (second circle) as defined on the MRI data set are approximately 1 mm more anterior than the internal auditory canal seen with CT. This has implications for the delivery of excessive radiation to the facial nerve during treatment. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

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Figure 69-22. Fractionated stereotactic radiosurgery. Example of serial MRI studies of a small right acoustic neuroma. Note excellent tumor control at medial aspect; however, continued growth laterally ultimately fills the fundus entirely. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

Figure 69-23. Fractionated stereotactic radiosurgery. As the tumor shown in Figure 69-22 grew laterally, the auditory performance in that ear progressively worsened. Over an 18-month interval, this patient’s pure tone average (PTA) fell from 15 dB to 63 dB. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

Figure 69-24. Fractionated stereotactic radiosurgery. As the tumor shown in Figure 69-22 grew laterally, the auditory performance in that ear progressively worsened. Over an 18-month interval, this patient’s speech recognition fell from 92% to 20%. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

Gamma Knife Radiosurgery and Other Forms of Radiosurgery for Management of Skull Base Tumors

Figure 69-25. Gamma Knife radiosurgery. Example of serial MRI studies of a small left acoustic neuroma. Note at 6 and 12 months post Gamma Knife radiosurgery the tumor is larger than it was pretreatment. By 18 months the tumor is smaller. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

acoustic neuroma and it is often quoted by individuals who are biased against Gamma Knife radiosurgery: To date, eight cases of malignancy in acoustic neuromas have been reported. These have been summarized by Bari and colleagues in 2002.11 Four of these tumors had been previously treated with radiosurgery and four other cases did not receive radiation. While it remains possible that these four cases developed after the radiation treatment, it is more likely that these malignant tumors were misdiagnosed at the outset of evaluation and treatment. The concept of delayed development of radiation-induced neoplasms was addressed by Pollock and colleagues in 1995.12 They reviewed the 26year experience with radiosurgery in more than 20,000 patients worldwide and they found no increased incidence of new neoplasm development. They defined neoplasm as a new growth of tissue serving no physiologic function and this would include both benign and malignant disease.

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Despite the limitations of the studies just reviewed, it is important to counsel patients about this possibility. It is likewise appropriate to counsel them about the possible etiologies of these malignant schwannomas. Regarding the possibility of radiation-induced malignancies, it is important to consider four major points: (1) The second neoplasm must arise in the irradiated field; (2) a latent period of at least several years must have elapsed between the radiation exposure and the development of the second neoplasm; (3) there must be histologic and radiographic evidence of the preexisting condition, in addition to microscopic proof of a tumor; and (4) the histologic type of the second tumor must be different from that previously irradiated, to eliminate the possibility of recurrence of the original tumor or a missed diagnosis of the original tumor. With these criteria in mind, Lustig and colleagues in 199713 reported the development of a squamous cell carcinoma following radiation treatment of an acoustic neuroma. In addition, Hanabusa and colleagues14 reported the malignant transformation of an acoustic neuroma following Gamma Knife radiosurgery. There was histologic evidence of acoustic neuroma following a retrosigmoid resection of the tumor. Four years after this resection, recidivistic tumor was identified and the patient was subsequently treated with Gamma Knife radiosurgery. Six months post treatment, the tumor had grown and the patient underwent surgical resection via a combined retrosigmoid-translabyrinthine approach. Abnormal mitotic figures were observed on histologic sections and the diagnosis of malignancy was assigned. The patient died 6.5 years after the initial treatment of the malignant disease. A concerning early trend in stereotactic radiosurgery is the concept of “debulking” the tumor and subsequently radiating the tumor for the purpose of “hearing preservation” and “facial nerve preservation.” The biggest variable during this process is the amount of tumor resected prior to radiation. In the absence of applying intraoperative

Figure 69-26. Gamma Knife radiosurgery. Hearing outcome of the tumor shown in Figure 69-25. Over an 18-month interval, this patient’s pure tone average (PTA) improved from 52 dB to 33 dB. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

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Figure 69-27. Gamma Knife radiosurgery. Hearing outcome of the tumor shown in Figure 69-25. Over an 18-month interval, this patient’s speech recognition fell from 60% to 84%. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

MRI to visualize the remaining tumor volume, it is a difficult task to be certain when or if the preoperative goal for debulking has been achieved. This approach is not being used in high-volume acoustic neuroma programs nationally, and the traditional neurotologist/neurosurgeon team is not involved with the “innovative” surgical approach. Figure 69-28 shows a case where a neurosurgeon completed a “debulking procedure” which, as shown in Figure 69-28B (right panel), was essentially a biopsy. Aside from the unnecessary expense of completing both the craniotomy and Gamma Knife radiosurgery, the ethical and moral questions presented by this example are troubling. In light of the current outcomes in microsurgery and stereotactic radiosurgery,5 there is no justification for this type of management algorithm. Figure 69-29 shows the treatment that the patient described earlier received. This is also an excellent example of a poor conformation to the tumor volume. As shown, the brightest line seen outside of the tumor outline (best seen in the axial section) represents the 50% isodose line to which a prescription of 13 Gy was given. It should be noted that a significant amount of radiation was

Figure 69-28. Gamma Knife radiosurgery. An example of an “innovative” combined microsurgery and radiosurgery approach to the management of acoustic neuromas. Advocates of this method anecdotally assert that better hearing preservation and facial nerve outcome can be achieved. With this example, essentially a biopsy of the tumor was performed with subtotal resection, followed by Gamma Knife radiosurgery. Ethical and cost-effectiveness issues are raised. (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

delivered to the brainstem based on this plan. In contrast, Iwai and colleagues15 applied this concept in a more appropriate way. They reported a series of 14 patients managed over a 6-year interval with acoustic neuromas too large (range 3.0 cm to 5.8 cm) to treat primarily with radiosurgery. Subtotal resection was achieved in 13 and partial resection due to hypervascularity was performed in 1 patient. After recovery, radiosurgery was performed to treat the recidivistic tumor. One final issue to consider is tumor growth after radiosurgery. It is important to appreciate that the tumor is larger after radiosurgery. Typically, this post-treatment edema persists for 6 months; however, it can remain up to 1 year. Consequently, pretreatment counseling should include this information. There have been anecdotal cases discussed and occasionally reported that describe increased tumor size early after radiosurgery. The challenge is in making a decision about whether to operate on these tumors and when.2,12,16–19 Pollock and colleagues12 emphasized the need to demonstrate sustained tumor growth by serial MRI before making the decision to operate and also

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Figure 69-29. Gamma Knife radiosurgery. Poor treatment plan including poor conformation of radiation dose to tumor margin (brightest circle represents 13 Gy at the 50% isodose line). Note excessive radiation delivered to brainstem (a portion receives 13 Gy at the 50% isodose line) and inadequate treatment of internal auditory canal portion of tumor (portion outside of the 50% isodose line). (Reproduced with permission, copyright © 2004, PA Wackym, MD.)

to review the case with the surgeon who performed the radiosurgery before a surgical decision is made. The other related controversy is whether the facial nerve dissection and subsequent preservation is more difficult during microsurgical resection after radiosurgery. On one end of the spectrum,12 descriptions of no increased difficulty have been reported, and on the other end of the spectrum,16–19 markedly increased difficulty in separating the tumor from the facial nerve and poorer facial nerve function outcome has been reported. The report of Watanabe and colleagues17 includes a histopathologic analysis of the resected facial nerve. They found microvasculitis of the facial nerve, axonal degeneration/loss of axons, and proliferation of Schwann cells. In light of the mechanism of delayed effects following radiosurgery, these findings are not surprising. Moreover, these findings emphasize the need for the neurotologist to be certain that the treatment plan avoids high radiation adjacent to the facial nerve. Recall that a dose of 12 Gy delivered to the 50% isodose line means that the maximum tumor dose is 24 Gy. If the treatment plan delivers this maximal dose to the area of the facial nerve, greater radiation effects will be observed. For this reason, if the neurotologist and the patient have made a decision to resect a tumor previously treated with radiosurgery, it is important to review the treatment plan to determine the amount of radiation delivered to the facial nerve in order to appropriately counsel the patient preoperatively.

OTHER RADIOSURGERY TECHNIQUES Fractionated Stereotactic Radiosurgery In the preceding sections of this chapter, much attention was focused on Gamma Knife radiosurgery. Many principles of radiation biology and stereotactic surgery hold true for fractionated stereotactic radiosurgery. Historically, the maximum radiation dose that could be given to a tumor site has been restricted by the tolerance and sensitivity of the surrounding nearby healthy tissues. One-session Gamma Knife systems and other one-session LINAC technologies are available. In addition, several manufacturers currently offer conformal radiation treatment systems that can involve multiple fractionated treatments. The most well-recognized systems by trade name at this time are the Peacock (NOMOS Inc., Cranberry Township, Penn.), the SmartBeam IMRT (Varian Medical Systems Inc., Palo Alto, Cal.), The Precise (Elekta, Inc., Stockholm, Sweden),

and the CyberKnife (Accuray, Sunnyvale, Cal.). The CyberKnife is different in that it is an “image-guided” technology. Conformal radiation is different from conventional radiation therapy in that radiation therapy targets a uniform shape to a total area to cover the tumor. Thus, with conventional radiation therapy, some healthy tissue is always irradiated and the entire target area receives a homogeneous or even dose of radiation. Conformal radiation treatments have the ability to deliver a higher dose to the tumor and thus can cause more damage to the tumor without so much damage to the surrounding healthy tissue as conventional external beam radiation treatment does. With the various methods of fractionated stereotactic radiosurgery, the patient is fitted with some type of reusable localization device, which may be a mask or a body frame. This assists in targeting with reproducibility and consequently greater accuracy. Typically, with skull base tumors including acoustic neuromas, the localization device is molded to fit the precise contours of the individual patient. This molded device is placed on the patient each time he or she receives a treatment. Multiple treatments are usually required with conformal radiation, as they are with conventional radiation therapy. These treatments may range from 1 to 28 treatments, fewer than the usual conventional radiation treatments. Treatment time itself for each session is typically longer than with conventional radiation therapy because of the treatment’s complexity. The outcomes after treatment of acoustic neuromas with fractionated stereotactic radiosurgery are being reported; however, fewer patients to date have been treated with these types of modalities than have been treated with Gamma Knife radiosurgery.20-22

Intensity-Modulated Radiation Therapy Intensity-modulated radiation therapy (IMRT) is a powerful, relatively new technology. This therapy can be used to target skull base tumor cells while limiting radiation to important normal tissues such as the eyes, optic nerves, brain, brainstem, adjacent cranial nerves, inner ear, salivary glands, and spinal cord. There are five principle advantages of IMRT compared with traditional radiation therapy: (1) decreased chance of harming normal cells, (2) decreased radiation dosage to sensitive surrounding tissue, (3) delivery of higher radiation dosage to cancer cells, (4) precise radiation distribution, and (5) increased chance of destroying tumor cells.

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A more traditional radiation therapy called threedimensional conformal radiation therapy (3D CRT) uses digital diagnostic imaging, a computer workstation, and specialized software to conform the radiation beam to the shape of the tumor. IMRT is the latest advancement in 3D CRT technology. IMRT not only uses three-dimensional imaging and treatment delivery, but it allows use of varying intensities of radiation to produce dosage distributions that are more conformal to the tumor volume than those possible with 3D CRT. In IMRT, very small beams, sometimes referred to as beamlets, with varying intensities can be aimed at a tumor from many angles. The intensity of each beamlet can be controlled. The radiation dose can be made to bend around important normal tissues in a way that is impossible with traditional radiation techniques. Special high-speed computers, treatment-planning software, multileaf collimators, which control the radiation beams, diagnostic imaging, and patient-positioning devices are used to plan individual treatment and to control the radiation during therapy (Figs. 69-30 and 69-31). IMRT uses an inverse treatment planning in which the computer workstation and associated software is used to determine the ideal beam arrangement and intensity based on the desired dosage. IMRT can improve the effectiveness of radiation therapy by delivering a larger radiation dose to tumor cells while reducing the exposure to surrounding normal cells. The anatomic position of the tumor and surrounding normal tissues must be accurately defined for IMRT to be effective. CT and MRI scans provide the necessary three-dimensional anatomic information that is used in the software platform during the treatment planning. In contrast to Gamma Knife radiosurgery but similar to fractionated stereotactic radiosurgery, a regimen of IMRT treatments is usually given over several weeks. The total dose of radiation and the number of treatments needed

Figure 69-30. Stereotactic radiosurgery using intensity-modulated radiosurgery. The Novalis® Shaped Beam Surgery system is shown. This system is described as a high-resolution IMRT instrument and technique. (Reproduced with permission, copyright © 2003, BrainLAB AG, Munich, Germany.)

Figure 69-31. Multileaf collimator. IMRT systems use multileaf collimators that shape the radiation fields that are delivered to the tumor. The Novalis Beam Shaper uses 3-mm fine leaves for high-resolution intensity-modulated radiosurgery. (Reproduced with permission, copyright © 2003, BrainLAB AG, Munich, Germany.)

depend on the size, location, and type of tumor, the patient’s general health, and other medical therapy the patient is receiving.

CyberKnife® Stereotactic Radiosurgery Overview of Treatment Planning The CyberKnife system’s linear accelerator maneuverability offers the radiosurgery team several treatment options. The treatment planning system is designed to support the radiosurgery team in determining the optimal plan, including beam weight, targeting positions, dose distributions, and other factors for each patient’s treatment. The CyberKnife stereotactic radiosurgery system permits the following planning and delivery options: (1) inverse planning, (2) nonisocentric delivery, and (3) hypofractionation. The system is based on CT scanning. MR images can be fused with the CT to provide optimal information on soft tissue as well as skeletal anatomy. CT angiography can be used when vascular skull base lesions, such as arteriovenous malformations or extensive glomus jugulare tumors, are to be treated with this technique. Additionally, the CyberKnife system provides a range of treatment options, including the ability to use either forward or inverse treatment planning, allowing the radiosurgery team to customize each patient’s treatment plan. With forward treatment planning the radiation oncologist determines what dose to deliver from a particular targeting position. Subsequently, the planning software calculates the total dose within the lesion for the user. With inverse treatment planning, the radiation oncologist specifies total dose to be delivered to the tumor and the surgeon and radiation oncologist set boundaries to protect adjacent critical structures. The software determines targeting positions and doses to be delivered from a particular targeting position. While other stereotactic radiosurgery systems offer the inverse planning option, the number of possible plans is somewhat limited by the constraints of the delivery system. The flexibility of the robotic arm that supports the linear accelerator possibly allows the CyberKnife to implement a wider range

Gamma Knife Radiosurgery and Other Forms of Radiosurgery for Management of Skull Base Tumors

of treatment plans than other systems. Furthermore, because the system does not require the use of a stereotactic head frame temporarily attached to the patient’s head, it allows scanning, treatment planning, and quality assurance to take place at any time before the treatment. Dose Distribution The CyberKnife system offers a choice of a nonisocentric or an isocentric treatment approach. With other stereotactic radiosurgery systems, a fixed calculated isocenter is used. Isocentric treatment, or multi-isocentric treatment, involves filling the lesion with a single or multiple overlapping spherical dose distributions. Isocentric treatment is effective for spherical lesions. However, with irregularly shaped lesions, isocentric delivery can produce significant dose heterogeneity (Fig. 69-32). Clinically, this is not a significant issue, provided that the treatment plan accounts for the relationship of the maximum dose to the critical structure to be considered. For example, if a Gamma Knife radiosurgery treatment plan for an acoustic neuroma uses 12 Gy at the 50% isodose line, the maximal radiation dose at the “hot spot” will be 24 Gy. During the treatment planning, assessment of the plan quality would include visualizing the location of this maximal dose and determination that this maximal dose was adjacent to the facial nerve or brainstem. Similarly, it is important to determine the conformation of the treatment plan to the tumor volume in order to determine regions that might be undertreated by delivery of inadequate doses, resulting in areas that would allow continued tumor growth. Nonisocentric treatment plans are also possible with the CyberKnife system. The delivery of these treatment plans

Figure 69-32. Isocentric treatment planning using the CyberKnife® radiosurgery system. Isocentric treatment, or multi-isocentric treatment, involves filling the lesion with a single or multiple, overlapping spherical dose distributions (ISO-1, ISO-2, ISO-3). Isocentric treatment is effective for spherical lesions; however, with irregularly shaped lesions, isocentric delivery can produce significant dose heterogeneity. Note the radiation overlap with critical structure (e.g., brainstem). (Reproduced with permission, copyright © 2003, Accuray Incorporated, Sunnyvale, Cal.)

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is possible because of the robotic arm that, because of the 6 degrees of freedom (discussed below), enables the delivery of radiation to complex treatment volumes. The beams originate from arbitrary points in the workspace and are delivered into the lesion. The result is a nonisocentric concentration of beams within the lesion (Fig. 69-33). Nonisocentric treatment allows nonsymmetric irradiation. With the CyberKnife system, the treatment plan can use fractionated or hypofractionated approaches. Fractionated treatment is possible because localization of the lesion is achieved using image-guidance technology. Dose delivery in two to five treatment sessions, termed hypofractionation, is another option with the CyberKnife system. Although not directly applicable in managing tumors in the posterior fossa, it has been suggested to be particularly useful in the treatment of large tumors. The argument for fractionation is that lowering the dose for each of a number of treatments, as opposed to a single, larger dose, allows healthy tissue to rejuvenate between treatments. The advantage of fractionated or a single radiation dose remains an active area of investigation and debate. Because of the rigid fixation that occurs with securing the stereotactic head frame in Gamma Knife radiosurgery, fractionated or hypofractionated delivery of radiation is not possible. Furthermore, it remains to be determined if equal accuracy can be achieved with these two systems and whether there is an advantage of fractionation or hypofractionation in the treatment of skull base tumors. Localization The CyberKnife system’s use of stereotactic principles for tumor localization differs from other stereotactic radiosurgery systems in one specific way. It uses an imageguidance technology that depends on the skeletal structure

Figure 69-33. Nonisocentric treatment planning using the CyberKnife® radiosurgery system. Nonisocentric treatment plans are possible because of the robotic arm which, because of the 6 degrees of freedom, enables the delivery of radiation to complex treatment volumes. The beams originate from arbitrary points in the workspace and are delivered into the lesion. The result is a nonisocentric concentration of beams in the lesion, avoiding critical structures such as the brainstem while maintaining tumor conformation. (Reproduced with permission, copyright © 2003, Accuray Incorporated, Sunnyvale, Cal.)

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of the body as a reference frame (Figs. 69-34 and 69-35). In addition, it continually monitors and tracks the patient’s position during treatment. The CyberKnife’s operating system correlates live radiographic images with preoperative CT scans to determine patient and tumor position repeatedly over the course of treatment. The imaging information is transferred from the computer’s operating system to the robot so that it can compensate for changes in the patient’s position by repositioning the linear accelerator (LINAC). Treatment Delivery The CyberKnife stereotactic radiosurgery system uses a compact 6-MV linear accelerator, a computer-controlled robotic arm with 6 degrees of freedom, and an imageguidance technology that does not depend on a rigid stereotactic frame and thereby enables treatment of extracranial sites. Possible benefits of this approach include (1) increased access to and coverage of any target volume including the ability to treat lesions in and around the cranium that are unreachable with other systems, for example, in the lower posterior fossa and foramen magnum; (2) enhanced ability to avoid critical structures; (3) capability to treat lesions in the neck and spine; (4) ability to treat lesions throughout the body; (5) delivery of highly conformal dose distributions; (6) option of fractionating treatment; and (7) potential to target multiple tumors at different locations during a single treatment (e.g., skull base and neck). The CyberKnife system’s computer-controlled robotic arm has 6 degrees of freedom. The robot can position the LINAC to more than 100 specific locations, or nodes. Each node has 12 possible approach angles, translating to more than 1200 possible beam positions. The treatment planning system determines a set sequence of approach angles, beam weights, and dose distributions. The calculated plan can be incrementally improved by the physicist

Figure 69-34. CyberKnife® treatment room layout. Ceiling-mounted diagnostic energy x-ray sources emit low dose x-rays through the patient’s tumor treatment area. Amorphous silicon image detectors capture radiographic images from ceiling-mounted diagnostic energy x-ray sources to produce live radiographs. The operating system (typically located adjacent to the treatment room) correlates patient location detected by image-guidance system with reconstructed CT scan and directs robot to adjust position accordingly. The compact linear accelerator is mounted on a computer-controlled robotic arm, which adjusts position to maintain alignment with target, compensating for any patient movement and uses X-band technology for mobility. (Reproduced with permission, copyright © 2003, Accuray Incorporated, Sunnyvale, Cal.)

and physicians. The actual delivery follows a step-and-shoot sequence. The patient is placed in a position approximating that of the CT scan. Image detectors acquire radiographs of the tumor region. The image-guidance system software then compares the real-time radiographs with the CT information to determine location of the tumor. This information is transmitted to the robot to initialize the pointing of the LINAC beam. The robotic arm then moves the LINAC through the sequence of preset nodes surrounding the patient. At each node, the LINAC stops and a new pair of images is acquired, from which the position is redetermined. Corrected position is transmitted to the robot, which adapts beam pointing to compensate for any movement. LINAC delivers the preplanned dose of radiation for that position. The entire process is repeated at each node. The total time from imaging to robot compensation is about 7 seconds. The total treatment time depends on the complexity of the plan and delivery paths, but it is comparable to standard LINAC treatments. Each treatment session ranges from 30 to 90 minutes. Physicians may elect to treat with a single dose or a hypofractionated dose typically in two to five sessions or a more traditional fractionated regimen. Outcomes following CyberKnife treatment of acoustic neuroma are unknown at this time. A review of the literature revealed that only one publication exists that reports a single child who underwent CyberKnife stereotactic radiosurgery after three subtotal resections of a rapidly growing tumor that was first diagnosed when he was 10 years old. No long-term follow-up data was presented. The CyberKnife® Society Web site (www.cksociety.org/ PatientInfo/MedicalConditions/acousticneuroma.asp) shows an example of a patient with an acoustic neuroma treated with CyberKnife stereotactic radiosurgery imaged preradiotherapy and at 6 months, 1 year, and 3 years post radiotherapy. As shown in Figure 69-3, the maximum axial

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Figure 69-35. CyberKnife® radiosurgery system treatment hardware components. Ceiling-mounted diagnostic x-ray sources (1). The linear accelerator mounted on computer-controlled robotic arm can be seen in relationship to the patient and the silicon image detectors. Inset, control room is located adjacent to the treatment room. (Reproduced with permission, copyright © 2003, Accuray Incorporated, Sunnyvale, Cal.)

tumor size appears progressively smaller; however, the axial images are not at equivalent levels, thereby artificially “showing” a reduction in tumor size. These misleading claims do a disservice to patients who are weighing their options.

SUMMARY There is diversity in the techniques and instrumentation used to perform stereotactic radiosurgery. The field continues to evolve rapidly and advances are being made in improving accuracy, effective radiation dose, and parameters necessary to maximize outcomes. Stereotactic radiosurgery, just like any other treatment modality, has advantages and disadvantages that must be discussed with a patient who has an acoustic neuroma or other skull base tumor. An informed decision to pursue observation, microsurgery, or stereotactic radiosurgery, or a combination of these methods must be made and it remains the responsibility of the surgeon to provide a balanced view of the relative advantages and disadvantages of each method.

REFERENCES 1. Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC: Longterm outcomes after radiosurgery for acoustic neuroma. N Engl J Med 339:1426–1433, 1998. 2. Pitts LA, Jackler RK: Treatment of acoustic neuromas. N Engl J Med 339:1471–1473, 1998. 3. Linskey ME, Martinez AJ, Kondziolka D, et al: The radiobiology of human acoustic schwannoma xenografts after stereotactic radiosurgery evaluated in the subrenal capsule of athymic mice. J Neurosurg 78:645–653, 1993.

4. Paddick I: A simple scoring ration to index the conformity of radiosurgical treatment plans. J Neurosurg 93(Suppl 3):219–222, 2000. 5. Kaylie DM, McMenomey SO: Microsurgery vs gamma knife radiosurgery for the treatment of vestibular schwannomas. Arch Otolaryngol Head Neck Surg 129(8):903–906, 2003. 6. Yamakami I, Uchino Y, Kobayashi E, Yamaura A: Conservative management, gamma-knife radiosurgery, and microsurgery for acoustic neurinomas: A systematic review of outcome and risk of three therapeutic options. Neurol Res 25(7):682–690, 2003. 7. Flickinger JC, Kondziolka D, Niranjan A, Lunsford LD: Results of acoustic neuroma radiosurgery: An analysis of 5 years’ experience using current methods. J Neurosurg 94(1):1–6, 2001. 8. Gardner G, Robertson JH: Hearing preservation in unilateral acoustic neuroma surgery. Ann Otol Rhinol Laryngol 97(1):55–66, 1998. 9. Wackym PA, Runge-Samuelson CL, Poetker DM, et al: Gamma Knife radiosurgery for acoustic neuromas performed by a neuro-otologist: Early experiences and outcomes. Otol Neurotol 25(5), 2004. 10. Tillman TW, Carhart R: An expanded test for speech recognition utilizing CNC monosyllabic words. Northwestern University Auditory Test No. 6. Technical Documentary Report (No. SAM-Tr-66-55). USAF School of Aerospace Medicine Technical Report. Brooks Air Force Base, TX, 1966. 11. Bari ME, Forster DM, Kemeny AA, et al: Malignancy in a vestibular schwannoma. Report of a case with central neurofibromatosis, treated by both stereotactic radiosurgery and surgical excision, with a review of the literature. Br J Neurosurg 16(3):284–289, 2002. 12. Pollock BE, Lunsford LD, Kondziolka D, et al: Vestibular schwannoma management. Part II. Failed radiosurgery and the role of delayed microsurgery. J Neurosurg 89(6):949–955, 1998. 13. Lustig LR, Jackler RK, Lanser MJ: Radiation-induced tumors of the temporal bone. Am J Otol 18(2):230–235, 1997. 14. Hanabusa K, Morikawa A, Murata T, Taki W: Acoustic neuroma with malignant transformation. Case report. J Neurosurg 95(3):518–521, 2001. 15. Iwai Y, Yamanaka K, Ishiguro T: Surgery combined with radiosurgery of large acoustic neuromas. Surg Neurol 59(4):283–289, 2003.

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16. Ho SY, Kveton JF: Rapid growth of acoustic neuromas after stereotactic radiotherapy in type 2 neurofibromatosis. Ear Nose Throat J 81(12):831–833, 2002. 17. Watanabe T, Saito N, Hirato J, et al: Facial neuropathy due to axonal degeneration and microvasculitis following gamma knife surgery for vestibular schwannoma: A histological analysis. J Neurosurg 99(5):916–920, 2003. 18. Lee DJ, Westra WH, Staecker H, et al: Clinical and histopathologic features of recurrent vestibular schwannoma (acoustic neuroma) after stereotactic radiosurgery. Otol Neurol 24(4):650–660, 2003. 19. Personal communication, Rick Friedman, MD, PhD, April 6, 2004.

20. Andrews DW, Suarez O, Goldman HW, et al: Stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of acoustic schwannomas: Comparative observations of 125 patients treated at one institution. Int J Radiat Oncol Biol Phys 50(5): 1265–1278, 2001. 21. Williams JA: Fractionated stereotactic radiotherapy for acoustic neuromas. Int J Radiat Oncol Biol Phys 54(2):500–504, 2002. 22. Perks JR, St George EJ, Hamri K, Blackburn P, Plowman PN: Stereotactic radiosurgery XVI: Isodosimetric comparison of photon stereotactic radiosurgery techniques (gamma knife vs. multileaf collimator linear accelerator) for acoustic neuroma, and potential clinical importance. Int J Radiat Oncol Biol Phys 57(5):1450–1459, 2003.

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Outline Osteoradionecrosis Effects of Radiation on the Soft Tissues of the Ear Effects of Radiation on the Great Vessels Neurologic Complications of Radiation

Chapter

Complications of Therapeutic Radiation to the Cranial Base

Secondary Oncogenesis Complications of Stereotactic Radiotherapy Summary

R

adiation therapy is frequently used to treat malignant and certain benign neoplasms of the head and neck. Radiation can be administered by seed implants (brachytherapy), standard external beams, or by highly targeted stereotactic radiotherapy. Stereotactic radiotherapy is a comparatively new modality for treatment of tumors of the skull base, whose specific risks are discussed briefly here. The lateral skull base is an uncommon target for primary radiation therapy, but it might be involved in radiation of adjacent areas such as the nasopharynx. The dose received by the lateral cranial base depends on the location of the target and the technique of radiation. Despite attempts to limit the field to the specific target, the lateral cranial base often receives substantial doses of radiation. The basic pathology of radiation is a vasculitis of the small and medium blood vessels, causing an obliterative endarteritis, which results in secondary avascular necrosis. The specialized structures of the lateral cranial base, which includes the temporal bone and associated soft tissues, make the complications of radiation unique to this area. In this chapter we discuss the complications of radiation therapy by tissue type.

OSTEORADIONECROSIS Osteoradionecrosis (ORN), which can be induced by any type of radiation, is an avascular necrosis and sequestration of bone that is usually accompanied by an intense reparative fibrosis. At the lateral skull base, necrotic bone is particularly vulnerable to secondary infection because of the potential for contamination via the external auditory canal and the eustachian tube. ORN of the temporal bone therefore carries a high rate of morbidity and mortality and its treatment is consequently quite challenging. The incidence of ORN of the lateral skull base is difficult to determine because the process can be silent, becoming problematic many years after treatment. There are many

Eric E. Smouha, MD, FACS Collin S. Karmody, MD, FRCSE

case reports of this condition.1–8 Bone cells have low rates of mitosis and are traditionally considered relatively resistant to the effects of radiation. Additionally, there seems to be poor correlation among the development of ORN, the dose of radiation, and its mode of delivery.1,5,7–9 The critical factor is the dose received by bone rather than the dose delivered to the tumor.10 Marx and Johnson reported that, in the mandible, the severity of ORN was multifactorial and related to the source, total dose, rate of treatment, concomitant surgery, chemotherapy, and the use of diathermy.11 Schuknecht and Karmody first described the histopathologic features of radiation necrosis of the temporal bone— essentially avascular necrosis and reparative fibrosis.6 The specific histologic picture was empty lacunae (signifying death of osteocytes), osteolysis, connective tissue surrounding sequestrated bone, loss of bone marrow, and lack of osteoneogenesis. These findings may be localized or generalized within the temporal bone (Fig. 70-1). ORN probably begins during or soon after the completion of radiation therapy, but it is slowly progressive. Death of osteocytes, decreased vascularity, and reparative fibrosis increase with time; spontaneous revascularization does not occur.11 The development of ORN in the temporal bone is favored by its superficial location, sparse soft tissue coverage, poor blood supply, and compact (rather than cancellous) structure.5 The time of presentation of ORN, which is usually triggered by infection, varies greatly from 1 year to more than 20 years after treatment, with a mean interval of 7.5 years.5 The temporal bone becomes infected via the eustachian tube or by breakdown of the skin of the external auditory canal. The clinical hallmark of ORN of the temporal bone is persistent otorrhea, sometimes accompanied by pain, and ORN should be suspected in any case of refractory external otitis post radiation of the head and neck. Ramsden and colleagues identified two patterns of ORN of the temporal bone: local and diffuse.5 Diffuse ORN usually results from high-dose irradiation directly to the temporal bone9; local ORN, which usually involves the external 1187

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∗

A

A

B Figure 70-1. Histologic photographs demonstrating findings typical of ORN. A, On lower magnification, islands of avascular necrosis of bone are intermingled with areas of reparative fibrosis. Secondary infection is present. B, On higher magnification, one can appreciate osteolysis with empty lacunae, a general absence of cellularity, and infiltrative connective tissue surrounding areas of dead bone. (A, Illustration from Laryngoscope 76:1416–1428, 1966. Reprinted with the permission of the publisher.)

B canal, is more likely after radiation of adjacent targets such as the nasopharynx or brain and is heralded by mild otalgia and offensive otorrhea.5 The typical finding is exposed dead bone on the floor and anterior wall in the external auditory canal. Necrosis of the ossicles occurs infrequently. Cholesteatoma develops if squamous epithelium invades bony defects in the external canal. Computed tomography (CT) might demonstrate irregularity of the bony external auditory canal, foci of bone loss, and sequestration (Fig. 70-2A). Localized ORN often (but not always) responds to conservative measures such as topical antibiotic preparations. Gentle removal of loose sequestra sometimes leads to complete healing (Fig. 70-2B). When conservative treatment fails to control progression of the process, diffuse ORN should be suspected. Diffuse ORN is asymptomatic until secondary infection causes profuse otorrhea and deep, boring pain. There is bony tenderness. External canal stenosis often limits otoscopy. Complications such as facial paralysis, labyrinthitis, and intracranial infections can occur. CT scanning is helpful

Figure 70-2. A, Coronal CT of left temporal bone showing changes associated with localized ORN. The floor of the bony external canal has a “moth-eaten” appearance (arrow). An epitympanic cholesteatoma (asterisk) has created a “natural atticotomy.” B, Right external auditory canal showing bony sequestrum extruding spontaneously. This is an example of local ORN.

for determining the extent of disease and might demonstrate diffuse osteoporosis, loss of bony architecture, sequestration, and filling of the mastoid cells with fibrous tissue. The radiologic appearance can mimic a neoplastic process (Fig. 70-3). Diffuse ORN with severe secondary infection (often the presenting sign) requires vigorous treatment with intravenous antibiotics guided by culture and sensitivity studies. The dosage and prolonged treatment should be the same as for the management of osteomyelitis. Wide surgical removal of affected bone is indicated if antibiotics fail to control the process or if more serious complications develop, but cure is not always possible. Radical mastoidectomy is usually

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Hyperbaric oxygen (HBO) has been recommended as an adjunctive treatment for ORN, on the theory that elevated serum oxygen tension improves the survival of bone with a marginal blood supply. Experimentally, HBO has been shown to promote fibroplasia and angiogenesis in irradiated bone.11 HBO is now an accepted modality in the treatment of mandibular ORN, where the combination of trauma and exposure to oral flora accelerates bone loss. HBO is typically administered in a regimen of 40 “dives” of 90 minutes’ duration in 100% oxygen at 2.5 atmospheres of pressure; sequestrectomy or wide resection is performed after the 30th dive in patients who have not healed completely.13 Several clinical studies have reported rates of recovery of 70% to 100%,14–18 although one study has doubted its value.19 There are few reports of HBO for ORN of the temporal bone but one study documented good results in 3 cases.15 A major disadvantage of HBO is that it can be expensive and is available at only a few centers. Up to one third of patients may require myringotomies.14 Seizures and other signs of oxygen toxicity are rare.

Figure 70-3. Axial CT of the left temporal bone showing diffuse ORN involving middle ear, mastoid, temporomandibular joint, and petrous apex. There has been extensive destruction of bone, and the bony defect has been replaced with proliferative fibrous tissue. These radiologic findings might be mistaken for a destructive neoplasm.

necessary, with removal of devitalized bone back to a bleeding margin. In some instances, exposure of the dura of the posterior and middle cranial fossae, labyrinthectomy, or subtotal petrosectomy is required. Dura should be preserved unless there is evidence of necrosis of meninges and brain. Because eradication of all diseased bone might not be possible, the rate of failure is rather high. In Ramsden’s series, half of the patients required multiple surgical procedures to control the process.5 Large surgical bony defects should be filled with soft tissue using local or free flaps. This is absolutely necessary if there is suspicion of or the potential for a cerebrospinal fluid leak. Ma and Fagan observed that vascular compromise after radiation may affect the viability of skin flaps and advocate using a preauricular incision to avoid transecting the superficial temporal vessels.4 They and others favor the use of pedicled local muscle flaps, such as temporalis muscle, to provide a new blood supply. Obliteration of the cavities, however, has the potential disadvantage of burying recurrent disease and should be avoided when the status of the remaining bone is not certain. Determining the viability of bone at the surgical margins is difficult but can be helped by radionuclide scanning. Technetium-labeled methylene diphosphonate (Tc-MDP) is incorporated into actively metabolizing bone, with decreased absorption in necrotic areas but increased uptake in osteomyelitis; sites of ORN may therefore be defined by a paradoxically increased uptake of Tc-MDP.12 Because of its low resolution and specificity, bone scanning provides only a rough estimate of involved bone. Tetracycline, which is absorbed by healthy bone and fluoresces under ultraviolet light, can also be used intraoperatively to judge the viability of bone.2,3

EFFECTS OF RADIATION ON THE SOFT TISSUES OF THE EAR The anatomic and physiologic complexities of the external middle and inner ears are reflected in the unique and diverse complications from the effects of radiation. Borsanyi reported a 50% to 60% incidence of ear symptoms in a series of 100 patients after radiation therapy to the head and neck.20,21 Radiation may cause early and late changes in the soft tissues of the ear, which are fundamentally epithelial edema and atrophy, as well as ciliary impairment and proliferation of fibrous tissue. Arteriolar occlusion and neural and neuroepithelial degeneration may also occur with or without ORN. Radiation therapy most frequently affects the external auditory canal and the middle ear. The skin of the external canal is affected in about 10% of patients; other complications include ulceration, epithelial thickening with stenosis, subepithelial fibrosis, atrophy of ceruminous glands, and cholesteatoma.22 Severe stenosis of the canal can result in chronic external otitis, which might conceal the development of chronic otitis media and cholesteatoma. The middle ear is more likely to be affected by direct irradiation to the temporal bone. Radiation otitis media consists of hyperemia of the tympanic membrane, mucosal edema, serous middle ear effusion, and occasionally purulent otitis media.20 The pathogenesis of this condition involves irreversible mucosal hyperplasia, loss of ciliary function, and eustachian tube obstruction. Serous middle ear effusions after radiation may be resistant to even prolonged trials of the usual conservative therapies such as antibiotics, topical and systemic decongestants, and self-insufflation.23 Myringotomy and ventilating tube placement can be performed in refractory cases, but it has a higher-than-usual rate of persistent perforation of the tympanic membrane and chronic otorrhea. The procedure therefore should be avoided if possible because a closed, noninfected ear might be changed into one with chronic suppurative otitis media that is difficult to manage.24 If

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hearing loss is the only complaint, a hearing aid might be a reasonable alternative. The development of cholesteatoma in an irradiated ear is favored by several factors: obstruction of the eustachian tube, adhesive otitis media, external canal stenosis,24 and bony defects which allow invasion of squamous epithelium (see Fig. 70-2A).6 Cholesteatoma should be suspected in chronic otorrhea, when a narrow canal prevents adequate examination. CT should be obtained but might not distinguish cholesteatoma from other soft tissue changes. Surgical therapy is indicated for cholesteatoma, and an open cavity mastoidectomy is preferred to facilitate postoperative care. Although neural tissue is relatively radioresistant, the facial nerve might be vulnerable to injury from higher doses of direct radiation because ischemia and perineural fibrosis renders the nerve more susceptible to middle ear infection and cholesteatoma. Facial nerve paresis in the presence of chronic infection is an indication for immediate surgical exploration and decompression of the nerve. Radiation therapy might lead to conductive or sensorineural hearing loss. Conductive hearing loss can be caused by external canal stenosis, tympanic membrane perforation, serous otitis media, ossicular necrosis, middle ear adhesions, or cholesteatoma.24,25 Sensorineural loss might result from primary radiation toxicity to the cochlea, ischemia, or chronic infection.26,27 The incidence of radiation-induced sensorineural hearing loss varies among studies. Borsanyi observed temporary loss in 6 of 40 patients, which he attributed to radiation vasculitis.21 Leach reported a 36% incidence of sensorineural loss, with early and late sequelae developing in a non-dose-dependent fashion.26 Moretti found sensorineural impairment in 7 of 13 patients, a higher than expected incidence, and emphasized the possibility of delayed loss.27 Johannesen and colleagues found hearing losses after radiation for brain tumors,28 and Ondrey and colleagues observed that the cochlea receives significant radiation during treatment for nasopharyngeal cancer, and they recommended that radiation treatment ports be designed to reduce radiation to hearing structures.29 Radiation-induced histopathologic changes in the cochlea were described by a number of authors. Kelemen observed perilymphatic edema, disintegration of the organ of Corti, and secondary infection in rats at doses above 300 rad (cGy).30 In guinea pigs, Gamble and colleagues found atrophy of the stria vascularis at lower doses and sometimes endolymphatic hydrops; they saw destruction of the organ of Corti only at doses above 3000 rad.31 Schuknecht and Karmody6 and Kovar and Waltner25 observed similar changes in human specimens. Winther found the outer hair cells of guinea pigs to be most susceptible to damage at doses exceeding 6000 rad,32 and Bohne and colleagues noted that, at 2 years follow-up, damage to sensory and neural elements occurred in a dosedependent fashion from 4000 to 9000 rad.33 The neuroepithelium of the vestibular system may also be affected. Experimentally, Winther observed degeneration of vestibular hair cells at doses above 6000 rad, with type II cells being more susceptible.34 In the clinical setting, the incidence of impairment of the vestibular system after radiation therapy is low. Leach reported that 4 of 36 patients developed vertigo after radiation therapy,

1 early and 3 late,26 and Johannesen and colleagues28 found 3 of 33 patients had canal paresis. Vestibular deficits may manifest as gait imbalance, continuous vertigo, episodic vertigo, or paroxysmal positional vertigo, but patients many remain asymptomatic because of ongoing compensation. For most patients, vestibular suppressants and physical therapy provide satisfactory control of symptoms.

EFFECTS OF RADIATION ON THE GREAT VESSELS Radiation therapy may have deleterious effects on the arteries of the head and neck. Experimental studies have demonstrated that relatively low doses of radiation may damage both small vessels and large elastic arteries. Lindsay and colleagues described the process of radiation-induced atherosclerosis in experimental animals,35 and Gold demonstrated that radiation-induced atherogenesis was enhanced by a high-fat diet.36 Fonkalsrud and colleagues described the histologic sequence of damage to the femoral arteries of dogs after 4000 rad.37 Intimal sloughing occurred after 48 hours, with incomplete healing after 3 weeks. There were areas of fibrosis, round-cell infiltration, necrosis of the media, and hemorrhage and inflammation of the adventitia after 1 week. Clinically, carotid occlusive disease may be an early or late sequela. Butler and colleagues described three distinct clinical patterns: early occlusion (within 5 years) from mural thrombus caused by intimal damage; progressive occlusion (within 10 years) caused by mural fibrosis; and late occlusion (after 20+ years) from accelerated atherosclerosis.38 Radiation-induced carotid stenosis occurs in younger patients, has a higher predilection for the common carotids, tends to form longer stenotic segments, and involves only areas within the field of radiation.39–41 Endarterectomy can usually be performed successfully, although planes of dissection may be blurred by periarterial scarring.42 Resection and bypass grafting are preferred by some surgeons.38 Dissecting aneurysms of the carotid artery caused by subintimal hemorrhage are rare clinical occurrences that present with sudden neurologic deficits. A case is presented in Figure 70-4. Rupture of the carotid artery is an infrequent but calamitous event. In the neck, rupture of the carotid mostly occurs after surgery and is usually associated with inadequate soft tissue coverage, local infection, or salivary fistula. At the skull base, rupture of the internal carotid artery, which is heralded by sudden profuse bleeding from the ear or nose, is usually preceded by the development of ORN and the formation of a pseudoaneurysm.43 Histologic studies following carotid rupture show round-cell infiltrates and subintimal edema, premature atherogenesis, disruption of the elastic lamina, and fibrosis of the media and adventitia.44 Rupture of the carotid artery in the neck requires urgent ligation of the vessel; repair of the artery is seldom possible. Rupture of the artery at the skull base is handled by endovascular occlusion. Ligation or occlusion of the internal carotid artery, however, has a high mortality rate because of the possibility of rebleeding and stroke. Lam and colleagues have advocated temporary balloon

Complications of Therapeutic Radiation to the Cranial Base

Figure 70-4. Axial magnetic resonance image (MRI) of the neck showing acute carotid dissection (arrow) secondary to radiation-induced carotid injury. The patient was a 44-year-old woman who had received 6500 rad 6 years earlier for laryngeal cancer, followed by laryngectomy and right neck dissection. She presented with pain and sudden appearance of a lump in her neck, without neurologic symptoms. The lesion was treated conservatively and did not progress.

occlusion followed by extra- to intracranial arterial bypass grafting.43 Excision of tumors at the skull base that abut or involve the carotid artery may require bony decompression, mobilization, or resection with grafting or permanent ligation. Previous irradiation therefore demands increased caution when handling the vessels. Preoperative arteriography is essential for determining the extent of arterial involvement. The safety of sacrificing the carotid artery can sometimes be predicted by temporary balloon occlusion with neurologic and/or encephalographic monitoring,45 or by assessment of cerebral blood flow by xenon-enhanced scanning.46 Surgical management of the internal carotid artery at the skull base is beyond the scope of this chapter, but is reviewed in detail elsewhere.47,48

NEUROLOGIC COMPLICATIONS OF RADIATION Because neurologic complications of radiation therapy may be grossly debilitating or lethal, portals of treatment are usually designed to exclude the brain. Although neural tissue is relatively radioresistant, glial tissue and vascular endothelium are sensitive. Radiation-induced neurologic complications include encephalopathy, which can be acute, subacute, or delayed, and cranial neuropathies. Each type has a unique pathogenesis.49 Acute radiation encephalopathy, which is dose-dependent, occurs within 24 hours of exposure with increasing incidence at doses above 2 Gy (200 rad). Symptoms are probably caused by brain edema and may be global (e.g., dementia, headache, somnolence, nausea) or focal (e.g., exacerbation of preexisting neurologic signs). Treatment with corticosteroids is usually effective.50 Subacute encephalopathy, or early delayed encephalopathy, occurs 2 to 3 months or longer after the completion of therapy and is thought to be caused by radiation-induced demyelination. Symptoms such as ataxia, nystagmus, and

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dysarthria indicate injury to the brainstem and cerebellum. Corticosteroids are sometimes but not always helpful. Delayed encephalopathy is synonymous with cerebral radiation necrosis (CRN). This condition may present from 3 months to 6 years after completion of therapy and is even seen after irradiation of extracranial neoplasms. The pathology of CRN is coagulative necrosis and cavitation of white matter, with areas of astrogliosis caused by ischemia, injury of glial cells, or antigenic sensitization, which elicits an immunologic response.51 Focal CRN involvement of brain can be indistinguishable from other intracranial lesions. CT and magnetic resonance imaging (MRI) usually demonstrate a mass with variable contrast enhancement but cannot differentiate CRN from tumor.52 MR spectroscopy is more specific. In one study, patients with temporal lobe necrosis after treatment for nasopharyngeal cancer all showed decreased N-acetyl aspartate peaks, and most had decreased choline and creatine; however, those with increased choline might be misdiagnosed with neoplasm.53 The initial promise of positron-emission scanning has not been upheld in clinical practice.54 Brain biopsy might therefore be necessary for definitive diagnosis in some cases. The estimated incidence of CRN is about 0.04% but varies in different studies.55,56 The incidence may be rising because of increased recognition and the longer survival of patients. CRN seems to be dose-related. There is a consensus that upper “safe” levels of radiation to brain are 2 Gy per day and 60 Gy total,57 but CRN can occur with lower doses. Male sex, age older than 50 years, large fields of radiation, coexistent diseases, and adjunctive chemotherapy increase the incidence of complications.56 CRN may be treated surgically or medically but excision of the lesion has been classically regarded as the treatment of choice.57 Excision or aspiration may be lifesaving by relieving the mass effect, and symptoms often (but not always) regress. Corticosteroid therapy may also be employed, although its value is inconsistent.57,58 When improvement occurs, long-term steroid therapy is often necessary. The cranial nerves are rarely impaired after radiation therapy, but deficits can occur from 1 to 12 years later that are thought to be fibrous entrapment with direct injury playing a lesser role.59 Therefore, most cranial neuropathies that present after radiation of the head and neck are caused by tumor recurrence or metastasis. Of the cranial nerves, the hypoglossal is the most frequently involved; the reason for this is unknown. The vagus and accessory nerves are the next most frequently involved; glossopharyngeal impairment is rare, although isolated deficits are clinically difficult to detect. Cochleovestibular symptoms are more usually caused by damage to the labyrinth (see above) than to the eighth nerve. Likewise, seventh nerve palsy is more often a result of acquired middle ear disease.

SECONDARY ONCOGENESIS Radiation therapy may lead to the development of both benign and malignant secondary tumors within the original field of treatment. Radiation-induced tumors usually present between 10 and 35 years later. In the head and neck, the thyroid and salivary glands are particularly susceptible.

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The increased incidence of both benign and malignant lesions of the thyroid gland is well established. Shore and colleagues found 24 carcinomas of the thyroid and 52 adenomas in 2650 patients who received thymic irradiation in childhood compared to no cancers and 6 adenomas in 4800 sibling controls.60 There appears to be a linear relationship between dose and the incidence of cancer for doses greater than 1000 rad.61 Several retrospective, case-controlled studies have shown an increased relative risk for tumors of the salivary glands after low- or medium-dose radiotherapy (300 to 2000 rad) given for a variety of benign conditions in childhood.62–65 Most radiation-associated tumors of the salivary glands are benign, mainly pleomorphic adenomas, and the most frequent malignant tumors are mucoepidermoid carcinomas. The parotid gland is affected in 75% of cases with a latency range from 7 to 20+ years. Radiation of the head and neck is believed to significantly increase the risk of developing tumors of the brain and nervous system. In a retrospective study of more than 10,000 subjects who received low-dose radiation for the treatment of tinea capitis in childhood, Ron and colleagues found that meningiomas, gliomas, and nerve-sheath tumors occurred with a seven-fold relative risk compared with matched controls.61 Meningiomas occur in the field of radiation therapy— usually in the cranial convexity, in the falx, or less commonly, along the cranial base. The latent period is long, about 37 years on average. They present with focal deficits, seizures, increased intracranial pressure, or organic brain syndrome. Radiation-associated meningiomas and naturally occurring tumors have different biologic behaviors. Rubinstein and colleagues found that radiation-induced meningiomas were more likely to be associated with seizures, to be multiple (19%), to be malignant (7%), and to recur after surgical excision (26%).66 Gliomas appear to have a slightly increased incidence after radiation therapy and have been reported after doses varying between 150 and 6000 rad and with latencies of 1 to 26 years.67 Nerve-sheath tumors occur with increased frequency after radiation and usually present as painful masses with progressive neurologic deficits. Devinsky reviewed 26 cases of peripheral nerve-sheath tumors derived mainly from two large retrospective studies.67 The tumors occurred from 4 to 25 years after radiation, with a mean latency of 16 years. In the head and neck, lesions involved the brachial plexus, spinal nerve roots, and vagus nerve. Twenty-one patients had malignant lesions; all but one died of local or metastatic disease. Malignant nerve-sheath tumors have a dismal prognosis regardless of treatment. Genetic susceptibility plays an important role; patients with clinical stigmata or a family history of neurofibromatosis type I are at increased risk of developing malignant schwannomas.68,69 It is therefore advisable to avoid radiation therapy whenever possible in patients with neurofibromatosis type I. Sarcomas of the central nervous system are rare tumors that may occur after radiation. Osteogenic sarcomas may arise in the cranial bones and fibrosarcomas may arise in the cranial cavity or the lateral cranial base as late complications of radiotherapy for pituitary adenomas and glomus

jugulare tumors70 (Fig. 70-5). Osteosarcomas are usually treated surgically and fibrosarcomas have been treated by surgery and/or radiation and chemotherapy. Prognosis is generally poor for patients with both tumors. The risk of inducing a secondary malignancy must be given serious weight when considering radiation therapy for benign tumors of the head and neck, particularly in children and young adults, and should be included in the discussion of therapeutic options because, although rare, its occurrence is almost uniformly lethal.

A

∗

B Figure 70-5. Axial CT of a 48-year-old woman with malignant fibrous histiocytoma, developing 20 years after surgery and radiotherapy for mucoepidermoid cancer of the parotid gland. The bone window CT (A) might be mistaken for ORN, but the soft tissue window (B) shows a mass originating from the dura and invading the temporal bone and brain (asterisk).

Complications of Therapeutic Radiation to the Cranial Base

COMPLICATIONS OF STEREOTACTIC RADIOTHERAPY Stereotactic radiotherapy (or “radiosurgery”) is defined as “the delivery, [usually] in a single session, of a high dose of ionizing radiation to a stereotactically localized volume of . . . tissue.”71 Originally developed by Leksell in Sweden, stereotactic radiotherapy has gained increasing acceptance as a therapeutic modality for acoustic neuromas and other intracranial lesions. As its use increases, complications associated with its use may become more prevalent. Stereotactic radiotherapy can be administered by “gamma knife” (a hemispherical array of Cobalt-60 sources),71 linear accelerator (LINAC),72 fractionated radiotherapy using convergent narrow beams,73 or proton beam.74 All these techniques use CT- or MRI-guided stereotaxis to deliver a highly contoured focus of radiation energy to the target while minimizing exposure of surrounding tissues. Stereotactic radiotherapy has been used for the treatment of brain metastases, arteriovenous malformations, pituitary adenomas, meningiomas, and acoustic neuromas. In the treatment of acoustic neuroma, stereotactic radiation was originally reserved for patients with bilateral or residual tumors, tumors in only-hearing ears, and medical illnesses precluding surgery, but it has been increasingly offered to all patients who opt for nonsurgical therapy.75 The early results of gamma-knife therapy of acoustic neuromas from Stockholm between 1969 and 1984 were promising (in 91 patients, 49% had decreased tumor size, 42% showed arrested growth, and 9% continued to grow), although results for bilateral tumors were poorer (33% had continued growth), and some complications were observed.71 Transient facial nerve palsy occurred in 15% of patients, usually between 6 and 12 months after therapy; total hearing loss developed in 25% and gradual hearing decline in about 50%; facial hypesthesia occurred in 4%. Early results from the University of Pittsburgh were similar.75 Since these early reports, smaller radiation doses have been used in an effort to reduce the incidence of hearing loss and facial nerve palsy. At the University of Pittsburgh from 1987 to 1992, the radiation dose was reduced from 18–20 Gy to 14–16 Gy at the tumor margin; 58.8% of tumors decreased in size and 3.1% were larger and required surgery after 3 years; by 5 years 71% were smaller. Facial palsy occurred in 15%, trigeminal palsy in 16%, and “useful” hearing was preserved in 47%.76 Using similar doses (13.3 Gy), similar results were obtained at the University of Virginia (in 153 patients, tumor size decreased in 81% and increased in 6%; 5 patients had trigeminal dysfunction, 3 had facial paresis, 60% had eventual decline in hearing).77 Comparable results have also been reported using LINAC72 and fractionated stereotactic radiation.78 Despite these positive reports, concerns remain about the safety of stereotactic radiation therapy as primary treatment for acoustic neuroma. Radiotherapy does not eliminate the tumor, so radiographic surveillance is required for many years after treatment.79 The results of lower-dose regimens are still uncertain; although doses of 12 to 14 Gy have yielded good 5-year results,80 permanent control of tumor growth remains unproved. Some authors

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have questioned the advantage of radiotherapy over simple observation for intracanalicular tumors because some of these will prove to be nongrowing.81 When needed to treat tumor regrowth, surgical excision may be more complicated after radiotherapy.82 Kaylie and colleagues83 and Brackmann and Kwartler84 have even argued that primary surgery has a lower complication rate than radiotherapy. Secondary oncogenesis remains a very worrisome complication, especially in younger patients; sporadic case reports of induced malignancy have appeared,85,86 but the true incidence will probably not be known until many years of follow-up data are collected. Longer prospective studies are needed to settle some of these uncertainties.

SUMMARY The complex anatomy and physiology of the lateral cranial base makes this area susceptible to a distinct set of complications associated with therapeutic radiation. ORN of the temporal bone usually manifests as protracted otorrhea and pain. Focal involvement may be treated by conservative local measures. Extensive ORN requires radical surgical debridement and may be lethal if infection spreads intracranially. HBO may play an adjunctive role in treatment. Direct and indirect effects of radiation on the ear may result in persistent effusion or chronic suppuration, and conductive and sensorineural hearing losses may appear as early or late sequelae. Vestibular impairment occasionally develops. Radiation produces arterial damage and can cause accelerated atherosclerosis, which may lead to premature stroke. Neurogenic effects of radiation include acute and subacute encephalopathy, delayed cerebral necrosis, and cranial nerve palsies. Radiation may induce secondary tumors. The thyroid and salivary glands are particularly susceptible. Meningiomas, gliomas, nerve-sheath tumors, and sarcomas of the central nervous system occur with varying frequency. It is important for the clinician to recognize these complications of therapeutic radiation because they may present years after the completion of treatment and might be life threatening. Understanding their pathogenesis is necessary for proper diagnosis and management.

REFERENCES 1. Guida RA, et al: Radiation injury to the temporal bone. Am J Otol 11:6–11, 1990. 2. Kveton JF: Surgical management of osteoradionecrosis of the temporal bone. Otolaryngol Head Neck Surg 98:231–234, 1988. 3. Kveton JF, Sotelo-Avila C: Osteoradionecrosis of the ossicular chain. Am J Otol 7:446–448, 1986. 4. Ma KH, Fagan PA: Osteoradionecrosis of the temporal bone: Surgical technique of treatment. Laryngoscope 98:554–556, 1988. 5. Ramsden RT, Bulman CH, Lorigan BP: Osteoradionecrosis of the temporal bone. J Laryngol 8:396–400, 1979. 6. Schuknecht HF, Karmody CS: Radionecrosis of the temporal bone. Laryngoscope 76:1416–1428, 1966. 7. Thornley GD, et al: Osteoradionecrosis of the temporal bone. J Otolaryngol 8:396–400, 1979.

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8. Wurster CE, Krespi Y, Curtis AW: Osteoradionecrosis of the temporal bone. Otolaryngol Head Neck Surg 90:126–129, 1982. 9. Wang CC: Radiation therapy in the management of carcinoma of the external auditory canal, middle ear, or mastoid. Radiology 116:713–715, 1975. 10. Schuknecht HF: Pathology of the ear. Cambridge, Mass, Harvard University Press, 1974, pp 311–315. 11. Marx RE, Johnson RP: Studies in the radiobiology of osteoradionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol 64:379–390, 1987. 12. Hutchison IL. Cullum ID. Langford, et al: The investigation of osteoradionecrosis of the mandible by 99mTc-methylene diphosphonate radionuclide bone scans. Br J Oral Maxillofac Surg 28:143–149, 1990. 13. Marx RE: A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg 41:351–357, 1983. 14. London SD, Park SS, Gampper TJ, Hoard MA: Hyperbaric oxygen for the management of radionecrosis of bone and cartilage. Laryngoscope 108:1291–1296, 1998. 15. Vudiniabola S, Pirone C, Williamson J, Goss AN: Hyperbaric oxygen in the therapeutic management of osteoradionecrosis of the facial bones. Int J Oral Maxillofac Surg 29:435–438, 2000. 16. David LA, Sandor GK, Evans AW, Brown DH: Hyperbaric oxygen therapy and mandibular osteoradionecrosis: A retrospective study and analysis of treatment outcomes. J Can Dent Assoc 67:384, 2001. 17. Hao SP, Chen HC, Wei FC, et al: Systematic management of osteoradionecrosis in the head and neck. Laryngoscope. 109:1324–1327, 1999. 18. Curi MM, Dib LL, Kowalski LP: Management of refractory osteoradionecrosis of the jaws with surgery and adjunctive hyperbaric oxygen therapy. Int J Oral Maxillofac Surg 29:430–434, 2000. 19. Maier A, Gaggi A, Klemen H, et al. Review of severe osteoradionecrosis treated by surgery alone or surgery with postoperative hyperbaric oxygen. Br J Oral Maxillofac Surg 38:173–176, 2000. 20. Borsanyi SJ: The effects of radiation therapy on the ear: With particular reference to radiation otitis media. South Med J 55:740–743, 1962. 21. Borsanyi SJ, Blanchard CL, Thorne B: The effects of ionizing radiation on the ear. Ann Otol Rhinol Laryngol 70:255–262, 1961. 22. Adler M, Hawke M, Berger G, et al: Radiation effects on external auditory canal. J Otolaryngol 14:226–232, 1985. 23. O’Neill JV, Katz AH, Skolnik EM: Otologic complications of radiation therapy. Otolaryngol Head Neck Surg 87:359–363, 1979. 24. Smouha EE, Karmody C. Non-osteitic complications of therapeutic radiation to the temporal bone. Am J Otol 16:1–5, 1995. 25. Kovar M, Waltner JG: Radiation effects on the middle and inner ear. Pract Oto Rhino Laryngol 33:233–242, 1971. 26. Leach W: Irradiation of the ear. J Laryngol Otol 79:870–880, 1965. 27. Moretti JA: Sensorineural hearing loss following radiotherapy to the nasopharynx. Laryngoscope 86:598–602, 1973. 28. Johannesen TB, Rasmussen K, Winther FO, et al: Late radiation effects on hearing, vestibular function, and taste in brain tumor patients. Int J Radiat Oncol Biol Phys 53:86–90, 2002. 29. Ondrey FG, Greig JR, Herscher L: Radiation dose to otologic structures during head and neck cancer radiation therapy. Laryngoscope 110:217–221, 2000. 30. Kelemen G: Radiation and ear. Acta Otolaryngol (Stockh) 184(Suppl):1–48, 1963. 31. Gamble JE, Peterson EA, Chandler JR: Radiation effects on the inner ear. Arch Otolaryngol 88:156–161, 1968. 32. Winther FO: X-ray irradiation of the ear of the guinea pig: An electron microscopic study of the degenerating outer hair cells of the organ of Corti. Acta Otolaryngol (Stockh) 69:61–76, 1970. 33. Bohne BA, Marks JE, Glasgow GP: Delayed effects of ionizing radiation on the ear. Laryngoscope 95:818–828, 1985. 34. Winther FO: X-ray irradiation of the ear of the guinea pig: Early degenerative changes in the vestibular sensory epithelia. Acta Otolaryngol (Stockh) 68:514–525, 1969.

35. Lindsay S, et al: Aortic arteriosclerosis in the dog after localized aortic x-irradiation. Circ Res 10:51–60, 1961. 36. Gold H: Production of arteriosclerosis in the rat: Effect of x-ray and a high-fat diet. Arch Pathol Lab Med 71:268–273, 1961. 37. Fonkalsrud EW, et al: Serial changes in arterial structure following radiation therapy. Surg Gyn Obstet 145:395–402, 1977. 38. Butler MJ, Lane RHS, Webster JHH: Irradiation injury to large arteries. Br J Surg 67:341–343, 1980. 39. Hayward RH: Arteriosclerosis induced by radiation. Surg Clin North Am 52:359–366, 1972. 40. Huvos AG, Leaming RH, Moore OS: Clinipathologic study of the resected carotid artery: Analysis of sixty-four cases. Am J Surg 126: 570–574, 1973. 41. Lopez M, et al: Carotid artery disease in patients with head and neck carcinoma. Am Surg 56:778–781, 1990. 42. Silverberg GD, Britt RH, Goffinet DR: Radiation-induced carotid artery disease. Cancer 41:130–137, 1978. 43. Lam HCK, Abdullah VJ, Wormald PJ, Van Hasselt CA: Internal carotid artery hemorrhage after irradiation and osteoradionecrosis of the skull base. Otolaryngol Head Neck Surg 125:522–527, 2001. 44. Marcial-Rojas RA, Castro JR: Irradiation injury to elastic arteries in the course of treatment for neoplastic disease. Ann Otol Rhinol Laryngol 71:945–958, 1962. 45. Meredith SC, Shores CG, Carrasco VN, Pillsbury HC: Management of the carotid artery at the skull base. Am J Otolaryngol 22: 336–342, 2001. 46. de Vries EJ, et al: A new method to predict safe resection of the internal carotid artery. Laryngoscope 100:85–88, 1990. 47. Andrews JC, Valvanis A, Fisch U: Management of the internal carotid artery in surgery of the skull base. Laryngoscope 99:1224–1229, 1989. 48. Chang CYJ, O’Rourke DK, Cass SP: Update on skull base surgery. Otolaryngol Clin North Am 29:467–500, 1996. 49. Rottenberg DA: Acute and chronic effects of radiation therapy on the nervous system. In Rottenberg DA (ed.): Neurological Complications of Cancer Treatment. Boston, Butterworth-Heinemann, 1991, pp 3–17. 50. Stelzer KJ: Acute and long-term complications of therapeutic radiation for skull base tumors. Neurosurg Clin N Am 11:597–604, 2000. 51. Rottenberg DA, et al: Cerebral necrosis following radiotherapy of extracranial neoplasms. Ann Neurol 1:339–357, 1977. 52. Packer RJ, Zimmerman RA, Bilaniuk LT: Magnetic resonance imaging in the evaluation of treatment-related central nervous system damage. Cancer 58:635–640, 1986. 53. Chong VF, Rampel H, Aw YS, et al: Temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma: 1HMR spectroscopic findings. Int J Radiat Oncol Biol Phys 45:699–705, 1999. 54. Ricci PE, Kars JP, Heiderman JE, et al: Differentiating recurrent tumor from radiation necrosis: Time for re-evaluation of positronemission tomography? Am J Neuroradiol 19:407–413, 1998. 55. Lee AWM, et al: Clinical diagnosis of late temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma. Cancer 61:1535–1542, 1988. 56. Sheline GE, Wara WM, Smith V: Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys 6:1215, 1980, p 1228. 57. Shaw PJ, Bates D: Conservative treatment of delayed cerebral necrosis. J Neurol Neurosurg Psychiatry 47:1338–1341, 1984. 58. Gutin PH: Treatment of radiation necrosis of the brain. In Gutin PH, Leibel SA, Sheline GE (eds.): Radiation Injury to the Nervous System. New York, Raven, 1991, pp 271–282. 59. Johnston EF, Hammond AJ, Cairncross JG: Bilateral hypoglossal palsies: A late complication of curative radiotherapy. Can J Neurol Sci 16:198–199, 1989. 60. Shore RE, et al: Radiation and host factors in human thyroid tumors following thymus irradiation. Health Physics 38:451–465, 1980. 61. Ron E, et al: Tumors of the brain and nervous system after radiotherapy in childhood. N Engl J Med 319:1033–1039, 1988.

Complications of Therapeutic Radiation to the Cranial Base

62. Ju DMC: Salivary gland tumors occurring after radiation of the head and neck area. Am J Surg 116:518–523, 1968. 63. Sogg RL, Nikoskelainen E: Parotid carcinoma and posterior fossa schwannoma following irradiation. JAMA 237:2098–2100, 1977. 64. Maxon HR, et al: Radiation-associated carcinoma of the salivary glands: A controlled study. Ann Otol Rhinol Laryngol 90:107–108, 1981. 65. Modan B, et al: Radiation-induced head and neck tumours. Lancet 1:277–279, 1974. 66. Rubinstein AB, et al: Radiation-induced cerebral meningioma: A recognizable clinical entity. J Neurosurg 61:966–971, 1984. 67. Devinsky O: Radiation-induced tumors of the central and peripheral nervous system. In Rottenberg DA (Ed.): Neurological Complications of Cancer Treatment. Boston, Butterworth-Heinemann, 1991, pp 79–81. 68. Ducatman BS, Scheithauer BW: Postirradiation neurofibrosarcoma. Cancer 51:1028–1033, 1983. 69. Foley KM, et al: Radiation-induced malignant and atypical peripheral nerve sheath tumors. Ann Neurol 7:311–318, 1980. 70. Lalwani AK, Jackler RK, Gutin PH: A lethal fibrosarcoma complicating radiation therapy for a benign glomus jugulare tumor. Am J Otol 14:398–402, 1993. 71. Leksell DG: Stereotactic radiosurgery: Present status and future trends. Neurol Res 9:60–68, 1987. 72. Friedman WA, Foote KD: Linear accelerator radiosurgery for skull base tumors. Neurosurg Clin North Am 11:667–680, 2000. 73. Shirato H, Sakamoto T, Sawamura Y, et al: Comparison between observation policy and fractionated stereotactic radiotherapy (SRT) as an initial management for vestibular schwannoma. Int J Radiat Oncol Biol Phys 44:545–550, 1999. 74. Harsh G, Loeffler JS, Thornton A, et al: Stereotactic proton radiosurgery. Neurosurg Clin North Am 10:243–256, 1999.

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75. Lundsford LD, Flickinger J, Coffey RJ: Stereotactic gamma knife radiosurgery: Initial North American experience in 207 patients. Arch Neurol 47:169–175, 1990. 76. Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC: Long-term outcomes after radiosurgery for acoustic neuromas. N Engl J Med 339:1426–1433, 1998. 77. Prasad D, Steiner M, Steiner L: Gamma surgery for vestibular schwannoma. J Neurosurg 92:745–749, 2000. 78. Sakamoto T, Shirato H, Takeichi N, et al: Annual rate of hearing loss falls after fractionated stereotactic irradiation for vestibular schwannoma. Radiother Oncol 60:45–48, 2001. 79. Pitts LH, Jackler RK: Treatment of acoustic neuromas. [letter; comment]. N Engl J Med 339:1471, 1998. 80. Flickinger JC, Kondziolka D, Niranjan A, Lunsford LD: Results of acoustic neuroma radiosurgery: An analysis of 5 years’ experience using current methods. J Neurosurg 94:1–6, 2001. 81. Charabi S, Thomsen J, Tos M, et al: Management of intrameatal vestibular schwannoma. Acta Otol Laryngol 119:796–800, 1999. 82. Schulder M, Sreepada GS, Kwartler JA, Cho ES: Microsurgical removal of a vestibular schwannoma after stereotactic radiosurgery: Surgical and pathologic findings. Am J Otol 20:364–367, 1999. 83. Kaylie DM, Horgan MJ, Delashaw JB, McMenomey SO: A metaanalysis comparing outcomes of microsurgery and gamma knife radiosurgery. Laryngoscope 110:1850–1856, 2000. 84. Brackmann D, Kwartler JA: Treatment of acoustic tumors with radiotherapy. Arch Otolaryngol Head Neck Surg 116:161–162, 1990. 85. Hanabusa K, Morikawa A, Murata T, Taki W: Acoustic neuroma with malignant transformation. Case report. J Neurosurg 95:518–521, 2001. 86. Shamisa A, Bance M, Nag S, et al: Glioblastoma multiforme occurring in a patient treated with gamma knife surgery. Case report and review of the literature. J Neurosurg 94:816–821, 2001.

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Outline Embryology Anatomy Central Pathways Supranuclear Pathways Facial Nucleus and Brainstem Cerebellopontine Angle Temporal Bone Internal Auditory Canal Fallopian Canal Blood Supply

L

ittle was known about facial nerve anatomy until 1550 when Gabriel Fallopius identified the anatomic course of the facial nerve within the temporal bone and recognized the chorda tympani nerve as a branch of the facial nerve.1 Confusion concerning sensation and motor function of the face continued until 1829 when Charles Bell properly attributed sensory innervation to the fifth cranial nerve and motor innervation to the seventh cranial nerve.2 Today the cornerstone of medical and surgical treatment of disease is a solid understanding of relevant anatomy and physiology. Nowhere is this more true than with the facial nerve. From idiopathic palsy to temporal bone fractures, from chronic otitis media to cerebellopontine angle (CPA) tumors, from cerebrovascular accidents to parotid tumors there are numerous pathologic conditions whose diagnosis and treatment require a clinical understanding of normal anatomy and physiology. This chapter attempts to provide a basis for clinicians on which rational treatments are instituted. It outlines basic embryology, anatomy, and physiology pertaining to the facial nerve.

EMBRYOLOGY Development of the facial nerve and its related musculature is well established by the end of the third month of gestation.3 Near the conclusion of the first month of gestation, the acousticofacial primordium develops rostral to the otic placode, the precursor of the inner ear. The acousticofacial primordium gives rise to both the facial and acoustic nerves.4 Early in the second month of gestation, the acousticofacial primordium begins to elongate and a portion extends to the geniculate ganglion, which arises from a thickening of ectoderm emanating from the second branchial arch.

Chapter

Anatomy and Physiology of the Facial Nerve

Facial Nerve Anomalies Facial Nerve Physiology Motor Nerves Nerve Injury Classification of Nerve Injury and Related Outcomes Degeneration and Regeneration Abnormal Regeneration Neurotrophic Growth Factors and Facial Nerve Regeneration

Michael J. LaRouere, MD Larry B. Lundy, MD

Distal to the developing geniculate ganglion, the primordium differentiates into two branches: caudal and rostral. The caudal trunk progresses into the mesenchyme of the second branchial arch and becomes the main trunk of the facial nerve.5 The rostral branch courses through the mesenchyme of the first arch and develops into the chorda tympani nerve (Fig. 71-1). Critical to the formation of the facial nerve is the separate development of its motor and sensory roots. The geniculate ganglion and nervus intermedius, arising from the second branchial arch, form independently of the motor division of the seventh nerve.6 This becomes important in the evaluation of congenital facial paralysis because the sensory contributions of the facial nerve can function normally in the presence of a complete motor paralysis. During the sixth week of gestation, the motor division of the facial nerve curves to run horizontally (tympanic segment) between the membranous labyrinth (otic placode) and the developing stapes (second arch). The nerve then curves vertically and passes into the mesenchyme of the second arch. The rostral branch, the sensory component of the facial nerve, enters the mesenchyme of the first arch ventral to the first pharyngeal pouch, forming the chorda tympani nerve.7 The chorda tympani nerve then joins the lingual nerve, which is a branch of the trigeminal nerve. Also during this gestational period, the greater superficial petrosal nerve, which carries preganglionic parasympathetic fibers toward the pterygopalatine ganglion, develops.8 Near the end of the second gestational month, the major development of the facial nerve within the temporal bone is complete. The precise length and location of the nerve then depend on the development of the temporal bone itself. The bony covering of the facial nerve begins in the fifth gestational month and is not complete until several 1199

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Figure 71-1. The developing embryo during the second gestational month showing the acousticofacial primordium differentiating into two branches, rostral and caudal trunks supplying the first and second branchial arches, respectively.

years after birth.6 These dehiscent areas may contribute to facial palsy associated with otitis media in childhood. The extratemporal portion of the facial nerve begins development during the sixth gestational week with the more proximal branches forming first. Near the end of the second gestational month, all five divisions of the extratemporal nerve are present. The parotid bud rapidly enlarges and engulfs the facial nerve, forming both superficial and deep lobes by the third month of gestation.9 Facial muscles, derived from the second branchial arch, are formed at 7 to 8 weeks’ gestation and are rapidly innervated by the distal facial nerve branches. Facial muscles differentiate before being innervated by a motor fiber. If a facial muscle is not innervated by a motor nerve, the muscle undergoes fatty degeneration. We do not know how long a facial muscle retains the ability to be innervated. At the conclusion of the third gestational month, all facial muscles can be identified and the majority are functional.10 After birth the facial nerve is located very superficially on the face, just beneath the skin, as it emerges from the temporal bone. During a postauricular incision in young children, the facial nerve is at risk near the mastoid tip. Incisions should thus be based more superiorly and posteriorly. As the mastoid tip forms and elongates, the facial nerve assumes a more medial position. Beginning shortly before birth and continuing until age 3 to 4 years, the individual axons of the facial nerve become myelinated. This is important when electrically testing nerves because conduction velocity, proportional to the myelin content, increases with age.11

ANATOMY The anatomy of the facial nerve can be divided into two distinct pathways: central and peripheral. The central pathways include the supranuclear tracts and the facial

nucleus and brainstem components. The peripheral nerve comprises that in the internal auditory canal and fallopian canal.

Central Pathways Supranuclear Pathways Although the facial nerve is frequently thought of as a collection of axons and dendrites bundled together that exit the brainstem and terminate in the muscles of facial expression, its functional origin begins in the cerebral cortex. The voluntary responses of facial musculature, such as smiling or tightly closing the eyes on command, depend on the function of neurons located in the cerebral cortex. The primary somatomotor cortex, located in the precentral gyrus (corresponding to Brodmann’s areas 4, 6, and 8), provides projection fibers of the facial nerve. Cell bodies in this cortex are primarily pyramidal nerve cells of all sizes, including the giant pyramidal cells of Betz. These motor cortex cells coverage into fascicles of the corticobulbar tract and project through the internal capsule near its bend (Fig. 71-2). The fibers continue their projection through the basal part of the pons within the pyramidal tracts. In the caudal portion of the pons, the majority of nerve fibers decussate to reach the facial nucleus of the opposite side, although some fibers innervate the ipsilateral facial nucleus. Consequently, the facial nuclei receive input from both cerebral cortices.12 There is extrapyramidal cortical input to the facial nucleus from the frontal areas, hypothalamus, and globus pallidus via the reticular formation. These inputs account for emotional control of facial expression. Other brainstem nuclei project to the facial nuclei, especially from sensory centers. Visual system afferents contribute to the blink reflex, afferents from the trigeminal nerve and nuclei provide the basis for the corneal reflex, and those from the acoustic nuclei account for eye closure in response to loud noise.

Anatomy and Physiology of the Facial Nerve

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Figure 71-2. Corticobulbar facial nerve fibers projecting through the internal capsule.

Facial Nucleus and Brainstem The facial motor nucleus contains approximately 7000 neurons13 and lies within the reticular formation of the lower third of the pons beneath the fourth ventricle. It is believed that there is distinctly separate ipsilateral and contralateral cortical input within the facial nucleus.14–17 The superior or ventral portion of the facial nucleus receives bilateral cortical input and provides innervation for the occipitofrontal muscle, the corrugator supercilia muscle, and the upper portion of the orbicularis oculi muscle. The inferior or dorsal portion of the facial nucleus receives only contralateral cortical input and is responsible for innervation of the lower facial musculature. This is the basis for the “forehead sparing” used to help differentiate a unilateral cortical or central lesion and a peripheral lesion. Other factors obviously assist in making this distinction; for instance, central lesions cause spastic paralysis whereas peripheral nerve injury results in flaccid paralysis. Although not clear in humans, animal research has demonstrated several collections of cell bodies in the facial nucleus that provide specific innervation.16–18 Cell bodies providing innervation to the auricular muscles and occipital muscle, via the posterior auricular nerve, originate in the dorsomedial portion of the nucleus. Platysma innervation via the cervical branch arises in the ventromedial area of the nucleus. Intermediate portions of the nucleus provide innervation to the stapedius muscle and facial muscles are innervated by the temporal, orbital, and zygomatic branches. Labial and buccinator muscle innervation originates in the lateral aspect of the facial nucleus. The origin of innervation to the posterior belly of the digastric and stylohyoid muscle is less clear.

Efferent projections from the facial motor nucleus emerge in a dorsomedial direction and form a compact bundle that loops over the caudal end of the abducens nucleus beneath the facial colliculus (internal genu). After leaving the internal genu, the fibers pass between the facial nerve nucleus and the trigeminal spinal nucleus and emerge from the brainstem at the pontomedullary junction (Fig. 71-3). In addition to neurons innervating the muscles of facial expression, sensory fibers are responsible for taste, external ear cutaneous sensation, and proprioception. The facial nerve also contains parasympathetic fibers targeted for the lacrimal gland and submandibular and sublingual salivary glands. This collection of fibers is most easily identified anatomically exiting the brainstem and entering the internal auditory canal (IAC). Known as the nervus intermedius, some older descriptions refer to this nerve bundle as the sensory root of the facial nerve, which is an inaccurate term. The nervus intermedius contains three types of sensory fiber and parasympathetic fiber. General visceral efferent (GVE) fibers are parasympathetic and supply the lacrimal, submandibular, sublingual, and minor salivary glands. The cell bodies of the preganglionic parasympathetic nerves arise in the illdefined superior salivatory nucleus and lie alongside the facial nerve just distal to the internal genu. These fibers join the facial nerve after it has passed the abducens nucleus. At the geniculate ganglion, the parasympathetic fibers form two groups. One group passes to the pterygopalatine ganglion via the greater superficial petrosal nerve, innervating the lacrimal gland, minor salivary glands, and mucosal glands of the palate and nose. The second group of fibers forms part of the chorda tympani nerve and proceeds to the submandibular ganglion and subsequently to the submandibular and sublingual salivary glands.

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Figure 71-3. Facial nerve projections within the pons.

Special visceral afferent (SVA) fibers, which form a portion of the chorda tympani nerve, receive input from the taste buds of the anterior two thirds of the tongue, hard and soft palate. The SVAs for taste have their cell bodies in the geniculate ganglion with central terminations in the nucleus of the solitary tract in the medulla. General sensory afferents (GSAs) convey cutaneous information from the external ear canal and postauricular region. There are also some general visceral afferents (GVAs), which provide proprioceptive input. Centrally, the cutaneous sensory fibers enter the spinal trigeminal tracts. It is interesting to note that there are no synapses in the geniculate ganglion, only cell bodies for taste fibers as well as axons, which course through this region. Cerebellopontine Angle The facial nerve (both the motor root and the nerve of Wrisberg) leave the brainstem at the pontomedullary junction in close opposition to the cochleovestibular nerve complex. In fact, the nervus intermedius usually clings to the cochleovestibular nerve complex rather than the facial nerve, and they begin to pass from the eighth to the seventh nerve as they approach the internal auditory meatus. In one series of 73 dissections, 20% showed that the nervus intermedius was not a separate structure until the meatus was reached.19 The relative position of the facial nerve to the cochleovestibular complex changes as it leaves the brainstem and progresses through the IAC by rotating 90 degrees (Fig. 71-4).20 In the CPA, these nerves are devoid of epineurium, covered with pia matter and bathed in cerebrospinal fluid (CSF).

Temporal Bone Internal Auditory Canal The transverse crest divides the IAC into superior and inferior portions. The superior portion is occupied by the facial nerve anteriorly and the superior vestibular nerve posteriorly—the two are divided by a bony ridge, the vertical crest (Bill’s bar) (Fig. 71-5). The inferior portion of the IAC contains the cochlear nerve anteriorly and the inferior vestibular nerve posteriorly. The facial nerve pierces the arachnoid and dura to enter the fallopian canal and the transition is made from dura to epineurium in this region. Fallopian Canal The facial canal is approximately 30 mm long, beginning at Bill’s bar and ending in the stylomastoid foramen. The three intratemporal regions are (1) labyrinthine, (2) tympanic, and (3) mastoid segments (see Fig. 71-5). The labyrinthine segment, being 3 to 5 mm long, is the shortest portion of the intratemporal facial nerve.21 It lies beneath the middle cranial fossa between the labyrinth and cochlea, beginning at the fundus of the internal auditory canal and extending to the distal portion of the geniculate ganglion. The narrowest portion of the entire fallopian canal is at the junction of the IAC and labyrinthine segment (meatal foramen), where it averages 0.68 mm in diameter.22 More important, at the meatal foramen, the nerve occupies 83% of the available space in the bony canal, as opposed to 23% in the tympanic portion and 64% in the mastoid segment.23 The geniculate ganglion is in a plane more superior to that of the remainder of the labyrinthine

Anatomy and Physiology of the Facial Nerve

Figure 71-4. Relationship of the facial nerve to the cochlear and vestibular nerves from the cerebellopontine angle through the external auditory canal.

Figure 71-5. Intratemporal course of the facial nerve.

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segment. The middle cranial fossa bone is dehiscent over the geniculate ganglion in 7% to 15% of cases.24 The greater superficial petrosal nerve contains taste fibers and preganglionic parasympathetic fibers. Taste fibers of the greater superficial petrosal nerve supply the posterior palate. Parasympathetic fibers supply nasal and palatine mucosal glands as well as the lacrimal gland. The greater superficial petrosal nerve progresses from the geniculate ganglion anteriorly to be joined by a sympathetic contribution from the deep petrosal nerve, forming the nerve of the pterygoid canal. The tympanic, or horizontal, segment begins just distal to the geniculate ganglion, extends to the second genu, and is 8 to 11 mm long. This portion of the nerve actually slopes inferiorly and laterally as it courses posteriorly. From the viewpoint of the middle ear, the geniculate ganglion can be localized superior, medial, and anterior to the cochleariform process (Fig. 71-6). A small vertical bony prominence known as the cog projects inferiorly from the roof of the epitympanum and serves as another landmark for the geniculate ganglion. As the facial nerve tracts posteriorly, it is superior to the tensor tympani muscle for part of its course. It is here, along the medial wall of the epitympanum, where the facial canal and the semicanal of the tensor tympani muscle can be mistaken for each other. As the nerve progresses more posteriorly, it passes above the stapes/oval window and curves anterior to the horizontal semicircular canal, thus forming the second genu (see Fig. 71-6). The portion of the facial nerve, after emerging from the second genu, is known as the vertical, or mastoid,

segment, that is, the segment from the second genu to the stylomastoid foramen. This segment descends inferiorly and becomes more lateral in its descent. There are two branches of the facial nerve in this area—the nerve to the stapedius muscle and the chorda tympani nerve. The branch to the stapedius is very short and deep to the vertical segment. The chorda tympani branch, which carries preganglionic parasympathetic fibers to the submaxillary and sublingual glands and taste fibers to the ipsilateral two-thirds of the tongue, branches in a superior, lateral, and anterior direction. The angle between the chorda tympani nerve and the vertical portion of the facial nerve is approximately 30 degrees. The area between these two nerves is the facial recess. If the bone of the facial recess is removed, access is gained to the posterior tympanum and allows visualization of the stapes, promontory, and round window niche. It is important to note that the chorda tympani nerve and the facial nerve are not in the same vertical plane, but rather the chorda tympani is located anteriorly. As the facial nerve continues its course in the mastoid tip, it becomes encased in the thick fibrous tissue of the cranial base periosteum. Two important landmarks are noted in this area—the digastric ridge and muscle and the sigmoid sinus/jugular bulb. As the sigmoid sinus proceeds inferiorly and medially to become the jugular bulb, it passes deep to the vertical segment of the facial nerve. In the posterior mastoid tip, the compact bone of the digastric ridge, corresponding to the digastric groove if viewed from below, can be identified. The digastric ridge and tendon is posterior, inferior, and superficial to the

Figure 71-6. Axial view of the middle ear and epitympanum showing relationship of tenor tympani muscle, cochleariform process, and facial nerve.

Anatomy and Physiology of the Facial Nerve

facial nerve. Fascia extending from the digastric muscle envelopes the facial nerve at this region. The stylomastoid foramen lies between the mastoid tip and the styloid process. At the stylomastoid foramen, the facial nerve passes into the substance of the parotid gland, usually as a common trunk, which then divides into its temporofacial and cervicofacial branches. This division can occur in the temporal bone. After the facial nerve leaves the stylomastoid foramen, there are three minor branches. One is the posterior auricular nerve, which courses lateral to the mastoid and is joined by a filament of the auricular branch of the vagus nerve. The postauricular nerve subsequently supplies the posterior auricularis muscle and the occipital belly of the occipitofrontalis muscle. There is a small, short branch to the posterior belly of the digastric muscle as well as a stylohyoid muscle branch. In its intraparotid course, further arborization occurs, with frequent anastomoses. Although there are multiple variations, the five classic branches of the intraparotid facial nerve are temporal, zygomatic, buccal, mandibular, and cervical.25 Blood Supply The blood supply to the facial nerve is segmented and derived from three arterial sources, as described by Nager and Nager in 1953.26 The portion of the facial nerve extending from the brainstem to the IAC is supplied by a branch of the anterior inferior cerebellar artery (AICA). The perigeniculate portion of the nerve is supplied by a branch of the middle meningeal artery. Few anastomotic connections exist between the above two arterial systems in the area of the meatal foramen (just proximal to the

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geniculate ganglion). This may be significant in Bell’s palsy because edema in the area can cause ischemic injury to the nerve. The mastoid and tympanic portions of the facial nerve are supplied by the stylomastoid branch of the postauricular artery. This vessel enters the temporal bone through the stylomastoid foramen. An intrinsic, highly anastomotic vascular system exists in the epineurium of the intratemporal facial nerve. This most likely accounts for the survival of the facial nerve following transposition out of the fallopian canal.

FACIAL NERVE ANOMALIES Facial nerve anomalies can occur in any portion of the temporal bone. Abnormalities of the nerve should be expected when anomalies of the ossicles, middle ear cleft, and external ear canal are encountered.27,28 Four general classes of anomalies can be found.29 First, there may be congenital bony dehiscences in the fallopian canal. Second, the facial nerve may take an aberrant course within all or part of the temporal bone. Third, the chorda tympani nerve may follow an anomalous pathway and, fourth, an associated structure, namely a persistent stapedial artery or vein, may accompany the nerve. Baxter30 described the major areas of fallopian canal dehiscences and their incidence in his anatomic study of 535 temporal bones (Fig. 71-7). He found an overall rate of 55%. The majority of the dehiscences were in the tympanic segment (91%) with the remainder (9%) in the mastoid segment. The facial canal is formed by contributions from Reichert’s cartilage of the second arch and

Figure 71-7. Major areas of bony dehiscence of the facial nerve.

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Figure 71-8. Anomalous course of the facial nerve through the crura of the stapes.

the cartilaginous otic capsule. The junction of the two occurs at the tympanic segment where the majority of dehiscences are located. Within the tympanic segment, Baxter30 found that more than 80% of the dehiscences involved the lateral, inferior, or medial portions of the canal adjacent to the oval window. The facial nerve protruded from the canal 26% of the time. This protrusion may cause the nerve to lie over the superior aspect of the oval window, possibly adjacent to the crura of the stapes. Within the mastoid segment, the majority of dehiscences were found anteriorly with exposure of the nerve into the facial recess. Occasionally, the nerve protruded from an area of dehiscence in the mastoid segment (12%). By the end of the first year of life, ossification of the fallopian canal is almost complete throughout all segments of the canal; however, the final stages of ossification can continue during the first few years after birth. An aberrant course of the facial nerve is generally associated with other embryologic abnormalities, most often abnormal development of the stapes.31 Rare abnormalities (bifurcations, anomalous course) have been found in the IAC or labyrinthine segment of the facial canal. The majority of the variations have been found in the tympanic and mastoid segments of the fallopian canal. Nager and Proctor29 have identified several congenital abnormalities of the nerve in the tympanic segment including the facial nerve located superior to the horizontal canal, coursing over the oval window, coursing through the crura of the stapes (Fig. 71-8), coursing between the oval and round windows, or coursing over the promontory. Hypoplasia and bifurcations (Fig. 71-9) of the nerve have been observed.

Within the mastoid segment, the most common abnormality is a posterior lateral displacement of the nerve just under the horizontal semicircular canal (Fig. 71-10).32 Other anomalies include an aberrant course of the nerve within the mastoid cavity. The facial nerve has been found to course more lateral, anterior,33 or posterior31 to its usual location. Bifurcations, trifurcations, and hypoplasia23 of the facial nerve have been found in the mastoid segment. The chorda tympani nerve may either follow an aberrant course or possibly contain motor fibers destined to the facial musculature. Jahrsdoerfer34 feels that the latter does not occur and that a “thick chorda” is in reality a very sharply curving facial nerve. The most common abnormality associated with the chorda tympani nerve is a variation in its origin from the main facial trunk. Origins of the chorda tympani nerve have occurred from the stylomastoid foramen to the geniculate ganglion.31 Another anomaly associated with the facial nerve is a persistent stapedial artery or vein traveling with the facial nerve in its tympanic segment before entering the brain.29 Because its blood supply is generally important to the overlying brain and dura, ligation is not recommended.29

FACIAL NERVE PHYSIOLOGY Motor Nerves A typical motor neuron consists of a cell body, a long fibrous axon covered with myelin, and terminal boutons or axon telodendria (Fig. 71-11). Nodes of Ranvier, spaced approximately 1 mm apart, are periodic absences in the

Anatomy and Physiology of the Facial Nerve

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Figure 71-9. Bifurcation of the facial nerve about the crura of the stapes.

myelin sheath that expose an exquisitely permeable axon membrane. The cell body contains the anatomic and functional integrity of the axon by producing proteins the axon and telodendria need to function. The cell body is instrumental to the degenerating neuron because it manufactures the nutrients necessary for regeneration.

The axonal membrane is polarized at rest (positive outside, negative inside) due to differences in ionic concentrations. The sodium ion is primarily responsible for the concentration gradient resulting in a negative 85-mV resting potential. The polarity is reversed during an action potential (AP). An AP can be initiated by any factor that increases the permeability of the axonal membrane to

Figure 71-10. Posterior lateral displacement of the facial nerve at the second genu.

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Figure 71-11. Schematic drawing of a neuron.

sodium. These include electrical, mechanical, and thermal stimulation.35 Once an action potential is created, saltatory conduction36 occurs in a myelinated axon. Because myelin is an effective insulator, depolarization in myelinated axons jumps from one node of Ranvier to the next36 (Fig. 71-12). This allows myelinated fibers, such as those composing the motor fibers of the facial nerve, to conduct up to 50 times faster than unmyelinated fibers.36 A compound action potential (CAP) is typically a broad multiphasic potential resulting from many axons with varying speeds of conduction according to their myelin content and diameter.36 The morphology and amplitude of the CAP varies depending on the type of fiber stimulated as well as the synchrony of axonal discharge. Large myelinated fibers have the lowest threshold of stimulation and are responsible for much of the recorded CAP. Each nerve fiber is surrounded by a connective tissue layer termed endoneurium, which is closely adherent to the Schwann cell layer of each axon.37 The endoneurium is important in nerve injury and repair because it surrounds the Schwann cells and provides an endoneurial tube through which regenerating axons can travel. The second layer of the nerve sheath, the perineurium,3 has two roles.

Figure 71-12. Myelinated axon demonstrating saltatory conduction.

It provides tensile strength to the nerve and maintains intrafunicular pressure.3 The latter is believed to be important in the pathogenesis and treatment of some forms of facial palsy. The perineurium also represents the primary barrier to the spread of infection. The outer layer, the epineurium,38 contains the vasa nervorum and lymphatic vessels, which are the only providers of nutrients to the nerve fibers27 (Fig. 71-13).

NERVE INJURY Classification of Nerve Injury and Related Outcomes Seddon39 describes various degrees of nerve injury as neuropraxia, axonotmesis, and neurotmesis. Sunderland40 expands on this classification, outlining five degrees of injury that a peripheral nerve can incur (Fig. 71-14). A first-degree injury, neuropraxia (physiologic conduction block) represents a loss of conduction, possibly caused by increased intraneural pressure, at a specific point along the nerve. The axon, Schwann cells, myelin, and endoneurium are in continuity and axoplasmic flow continues. The nerve fiber distal to the site of lesion has normal excitability.41 Complete return of neural function is expected. A second-degree injury (axonotmesis) results in axonal disruption without loss of the endoneurial sheath. Axoplasmic flow is disrupted and wallerian degeneration (distal axon degeneration) occurs. Recovery is generally complete provided the endoneurial tubules are not disrupted. In a third-degree injury, the axons, myelin covering, Schwann cells, and endoneurial sheath are disrupted. Loss of continuity of the endoneurial tubules results in faulty regeneration, which leads to an incomplete recovery with synkinesis. A fourth-degree injury causes disruption of the axons, myelin, Schwann cells, endoneurium, and perineurium. The regenerating fibers can be even further misdirected than with a third-degree injury in that they can enter incorrect tubules and fascicles. A poor recovery is

Anatomy and Physiology of the Facial Nerve

Figure 71-13. Cross-section schematic of nerve demonstrating endoneurium, perineurium, and epineurium.

Figure 71-14. Sunderland’s classification of neural injury.

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expected with increased mass motion. Neurotmesis, a fifth-degree injury, results in total nerve disruption, which includes the epineurium. Little recovery is expected spontaneously.

Degeneration and Regeneration Response to injury occurs throughout the nerve muscle unit. The most complex changes occur in the cell body. Nissel42 described these neural changes termed chromatolysis (degeneration of the Nissel bodies), which begin within hours of injury and represent increased neuronal metabolism. Proximal to the site of injury, the nerve is affected in a retrograde manner to the next functional node of Ranvier. If axoplasmic flow is temporarily disrupted (axonotmesis), mild swelling of the nerve may occur, which begins hours after injury. In association with a more severe injury causing axonal disruption, axonal sprouts are noted to appear on the third postinjury day.43 Axonal diameter and myelin thickness also decrease in the proximal segment, as demonstrated by Kreutzberg and Schubert.37 Distal to the site of injury, the axon degenerates (wallerian degeneration). This process begins 12 to 24 hours following injury and is at a peak within 72 hours. Schwann cells are primarily responsible for myelin destruction.44 These cells also produce collagen,45 which can impede axonal growth during the regenerative period. Concomitant with increased protein synthesis in the cell body is an increased transport of this nutrient material throughout the axon; this occurs within hours of injury.46 Axonal buds begin to sprout at the proximal axon stump (25 to 50 buds) and one fiber courses through, at a rate of 1 mm per day, an endoneurial tube formed by bands of Schwann cells called Bungner bands.44 The endoneurial channels are replaced slowly by connective tissue during a period of 3 to 4 months, thereby diminishing the regenerative capacity of the axon.47 Myelination is complete within 4 to 6 weeks following axonal growth. Internodal distances are decreased and the density of sodium channels is increased prior to the onset of activity.13 In the denervated muscle, the number of motor endplates significantly increases48 and inhibitor substances decrease, thereby allowing reinnervation.49 The period of time muscle tissue is able to accept regenerating axons is said to be 1 year; however, muscle atrophy has been noted to vary and viability has been observed for years following injury.48,50

Abnormal Regeneration Incomplete or abnormal facial nerve regeneration can result in facial paresis, synkinesis, and spasm. Crocodile tearing and Frey’s syndrome are other possible complications of facial nerve injury or excision of the parotid gland. Facial paresis, including loss of tone at rest, results from faulty regeneration of axonal fibers. Tone can be maintained with fewer functional axonal segments than were present prior to injury.51 Full functional facial activity also appears possible with far less than the original number of active axon motor end units.

Crumley52 concluded that forms of hyperkinesis following facial nerve injury may be a result of (1) abnormal synaptic transmission to the cell body, (2) decreased intranodal distances, (3) a reduction in the myelin sheath, and (4) splitting and crossing of axons. Synkinesis, or mass movement of the face, is one result of abnormal facial nerve regeneration. Faulty myelination, coupled with shunting of electrical activity in the regenerated facial nerve, is thought to be responsible for synkinesis. Either faulty myelination or ephaptic transmission53 is thought to be responsible for facial spasm. Ephaptic transmission is a spontaneous discharge, resulting in a CAP, occurring at the site of nerve injury. Crocodile tearing, increased lacrimation associated with eating, is believed to result from misrouting of facial nerve efferent fibers normally targeted to travel with the chorda tympani nerve to the submandibular and sublingual glands. These fibers are misdirected through the greater superficial petrosal nerve to the sphenopalatine ganglion and ultimately innervate the lacrimal gland. Parasympathetic fibers now innervate the lacrimal gland instead of their target salivary glands. Frey’s syndrome, gustatory sweating, may occur after a parotidectomy when postganglionic parasympathetic fibers of the ninth cranial nerve, normally targeted for the parotid gland, innervate sweat glands previously supplied by postganglionic sympathetic fibers.54

Neurotrophic Growth Factors and Facial Nerve Regeneration Motor neurons need neurotrophic growth factors for their development and subsequent maintenance of function. It is further believed that after nerve injury neurotrophic growth factors promote nerve regrowth. Yan and colleagues55 found that glial cell line–derived neurotrophic factor is the most potent motor neuron trophic factor found so far. Application of glial cell line–derived neurotrophic factor (GDNF) to transected facial nerves prevents massive motor neuron cell death and atrophy. Li and colleagues56 found that in partial facial palsy the immunoreactivity of acidic fibroblast growth factor was up-regulated as well. It is hoped that further understanding of neurotropic growth factors for motor neurons will provide a new basis to develop treatments for facial nerve injuries.

REFERENCES 1. Bolz EA, Miglets AW, Paparella MM, Saunders WH: Chronologic outline of the development of otology. In Saunders WH, Paparella MM (eds.): Atlas of Ear Surgery. St. Louis, Mosby, 1986, pp 1–17. 2. Glasscock ME, Shambaugh GE (eds.): Facial nerve surgery. In Surgery of the Ear, 4th ed. Philadelphia, WB Saunders, 1990, pp 435–436. 3. Sunderland S, Bradley KC: Stress-strain phenomena in human peripheral nerve trunks. Brain 84:102, 1962. 4. Vidic B: The anatomy and development of the facial nerve. ENT J 57(6):237–242, 1978. 5. Gasser R, May M: Embryonic development of the facial nerve. In May M (ed.): The Facial Nerve. New York, Thieme Stratton, 1987, pp 3–19.

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6. Gasser RF: The development of the facial nerve in man. Ann Otol Rhinol Laryngol 76:37–57, 1977. 7. Pearson AA: The roots of the facial nerve in human embryos and fetuses. J Comp Neurol 87:139–159, 1947. 8. Vidic B, Wozniak W: The communicating branch of the facial nerve to the lesser petrosal nerve in human fetuses and newborns. Arch Anat Histol Embryol 52:371–378, 1969. 9. Gasser RF: The early development of the parotid gland around the facial nerve and its branches in man. Anat Rec 167:63–78, 1970. 10. Gasser RF: The development of the facial muscles in man. Am J Anat 120:357–376, 1967. 11. Waylonis GW, Johnson EW: Facial nerve conduction delay. Arch Phys Rehab 45:539–547, 1964. 12. Miehlke A: Surgery of the Facial Nerve, 2nd ed. Philadelphia, WB Saunders, 1973, pp 7–21, 147–174. 13. DanBuskrk C: The seventh nerve complex. J Comp Neurol 82:303–333, 1945. 14. Courbille J: The nucleus of the facial nerve. The relation between cellular groups and peripheral branches of the nerve. Brain 1:338–354, 1966. 15. Papez JW: Subdivisions of the facial nucleus. J Comp Neurol 43:159–191, 1927. 16. Radpour S: Organization of the facial nerve nucleus in the cat. In Fisch U (ed.): Facial Nerve Surgery. Birmingham, Ala, Aesculapius, 1977, pp 71–81. 17. Radpour S, Gacek RR: Facial nerve nucleus in the cat. Further study. Laryngoscope 90:685–692, 1982. 18. Carpenter B, Sutin J: Pons in human neural anatomy. Baltimore, Williams & Wilkins, 1983, pp 385–389. 19. Rhoton AL, Kobayashi S, Hollinshead WH: Nervus intermedius. J Neurosurg 29:1968. 20. Silverstein H, Norrell H, Smouha E: Retrosigmoid internal auditory canal approach vs retrolabyrinthine approach for vestibular neurectomy. Otolaryngol Head Neck Surg 97:300–307, 1987. 21. Proctor B (ed.): Canals of the temporal bone. In Surgical Anatomy of the Ear and Temporal Bone. New York, Thieme Stratton, 1989, pp 89–128. 22. Fisch U, Esslen E: Total intratemporal exposure of the facial nerve: Pathologic findings in Bell’s palsy. Arch Otolaryngol 85:335–341, 1977. 23. May M: Anatomy of the facial nerve for the clinician. In May M (ed.): The Facial Nerve. New York, Thieme Stratton, 1986, p 35. 24. Rhoton AL Jr, Hall GM: Absence of bone over the geniculate ganglion. J Neurosurg 28:48–53, 1968. 25. Davis RA, Anson BJ, Puddinger JM, Kurth RE: Surgical anatomy of the facial nerve and parotid gland based upon a study of 350 cervical facial halves. Surg Gynecol Obstet 102:385–412, 1956. 26. Nager GT, Nager N: The arteries of the human middle ear, with particular regard to the blood supply of the auditory ossicles. Ann Otol Rhinol Laryngol 62:923, 1953. 27. Botros G: The facial nerve and the surgery of congenital atresia of the ear. Ann Otol Rhinol Laryngol 66:173–181, 1957. 28. Pou JW: Congenital anomalies of the middle ear. Presentation of two cases. Laryngoscope 81:831–839, 1971. 29. Nager GT, Proctor B: Anatomical variation and anomalies involving the facial canal. Ann Otol Rhinol Laryngol (Suppl 93):45–61, 1982. 30. Baxter A: Dehiscence of the fallopian canal. J Laryngol Otol 85:587–594, 1971. 31. Fowler EP: Variations in the temporal bone course of the facial nerve. Laryngoscope 91:937–944, 1961

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32. Kelhel K: Abnormal course of the facial nerve in the fallopian canal. Arch Otolaryngol 44:406–408, 1946. 33. Bellucci RJ: Congenital aural malformations, diagnosis and treatment. Otolaryngol Clin North Am 95–124, 1981. 34. Jahrsdoerfer RA: Embryology of the facial nerve, Facial nerve manual. Am J Otolaryngol 9(5):423–426, 1988. 35. Kellman RM: Facial nerve manual: Physiology and pathophysiology. Am J Otolaryngol 10(1):62–67, 1989. 36. Ganong W: Physiology of nerve and muscle cells. In Review of Medical Physiology, 9th ed. Los Altos, Calif, Lange Medical Publication, 1979, pp 21–34. 37. Kreutzberg GW, Schubert B: Volume changes in the axon during regeneration. Acta Neuropathol (Berl) 17:220–226, 1971. 38. Sunderland S: The connective tissue of peripheral nerves. Brain 33:841, 1965. 39. Seddon HJ: Three types of nerve injuries. Brain 6:237, 1943. 39. Sunderland S: Nerve and nerve injuries, 2nd ed. Edinburgh, England, Churchill Livingstone, 1978, pp 31–60. 41. Crumley RL: Pathophysiology of facial nerve injury. In Gibb AG, Smith MFW (eds.): Otology. London, Butterworth Scientific, 1982, pp 86–104. 42. Nissel F: Uber die veranderungen der gangliengellen am facialiskern des kaninchen nach ausreissung der nerven. Allg Z Psychiat 48:197–198, 1892. 43. May M: Microanatomy and pathophysiology of the facial nerve. In May M (ed.): The Facial Nerve. New York, Thieme Stratton, 1986, pp 63–64. 44. Nathaneal EJH, Peese DC: Regenerative changes in rat dorsal roots following wallerian degeneration. J Ultrastruct Path 9:533–549, 1963. 45. GE XX, Spector G, Carr C: The pathophysiology of compression injuries of the peripheral facial nerve. Laryngoscope (Suppl 31): 1–15, 1982. 46. Grafstein B: Axonal transport communication between soma and synapse. In Costa E, Greengard P (eds.): Advances in Biochemical Pharmacology, vol 1. New York, Raven Press, 1969. 47. Jurecka W, Ammerer HP, Lassman H: Regeneration of a transected nerve. An autoradiographic and EM study. Acta Neuropathol 32:299–305, 1975. 48. Bowden REM, Gutmann E: Denervation and reinnervation of human voluntary muscles. Brain 67:273–310, 1944. 49. Diamond J, Cooper E, Turner C: Trophic regulation of nerve sprouting. Science 192:371–377, 1976. 50. Carlson BM: Denervation, reinnervation and regeneration of skeletal muscle. Otolaryngol Head Neck Surg 90:192–196, 1981. 51. Esslen E: Electromyography and electroneurography. In Fisch U (eds.): Facial Nerve Surgery. Birmingham, Ala, Aesculapius, 1977, pp 93–100. 52. Crumley RL: Mechanisms of synkinesis. Laryngoscope 90:1947–1954, 1979. 53. Adrian ED: The effect of injury on mammalian nerve fibers. Proc Roy Soc Lond (Biol) 106:596, 1930. 54. Hays LL, Novack HA, Worsham JC: The Frey syndrome: A simple effective treatment. Otolaryngol Head Neck Surg 90:419–425, 1982. 55. Yan Q, Matheson C, Lopez OT: In vivo neurotrophic effects of GDWF and neonatal and adult facial motor neurons. Nature 373(6512):289–290, 1995. 56. Li JM, Brackman DE, Hitselberger WE, et al: Coexpression of neurotrophic growth factors and their receptors in human facial motor neurons. Ann Otol Rhinol Laryngol 108:903–908, 1999.

Chapter

72 John S. Oghalai, MD Robert K. Jackler, MD

Overview of Facial Nerve Surgery Outline Introduction Facial Nerve Monitoring Cerebellopontine Angle, Internal Auditory Canal, and Labyrinthine Segments of the Facial Nerve Translabyrinthine Approach Retrosigmoid Approach Middle Fossa Approach

Horizontal Segment of the Facial Nerve Facial Recess Stylomastoid Foramen and Extratemporal Segment of the Facial Nerve Facial Nerve Rerouting Facial Nerve Grafting

INTRODUCTION Facial nerve surgery may be undertaken to treat pathologic conditions directly involving the nerve, including facial nerve schwannoma,1 inflammation of the nerve associated with Bell’s palsy,2 hemifacial spasm, or for trauma, either iatrogenic3 or after a temporal bone fracture.4 However, more commonly, exposure of the facial nerve is performed during temporal bone surgery for conditions unrelated to the facial nerve. These include tympanomastoidectomy for cholesteatoma or chronic otitis media, stapedectomy for otosclerosis, or skull base surgery for acoustic neuroma, temporal bone malignancies, or jugular foramen tumors. Many different approaches to the facial nerve are possible depending on which segment (cerebellopontine angle [CPA], internal auditory canal [IAC], labyrinthine, horizontal, vertical, or extratemporal segments) of the nerve needs to be exposed. Consideration of the patient’s hearing status is required to determine the best operative approach as well.

FACIAL NERVE MONITORING Intraoperative electromyographic monitoring of the facial nerve is becoming more popular for routine use during all temporal bone surgery. Typical placement of electrodes includes recording electrodes within the orbicularis oculi and orbicularis oris musculature. A ground electrode also needs to be placed away from these recording sites, usually in the shoulder. This passive monitoring setup is based on the premise that physical manipulation of the facial nerve will produce electrical activity that can be noted from the recording electrodes. 1212

Commonly, a stimulator is also used within the surgical field. By passing current out of the tip of the stimulator, the surgeon can often precisely identify the location of the facial nerve, even when it is not obviously visible. A separate ground electrode is required to use this monopolar stimulating probe. Facial nerve monitoring can be invaluable in identifying the facial nerve and following its course, particularly when the facial nerve is obscured by disease, such as acoustic neuroma or cholesteatoma. However, facial nerve monitoring is not particularly useful in preventing facial nerve injury by an inexperienced surgeon. Although a helpful tool, facial nerve monitoring can give false reassurance, and it is not a substitute for detailed anatomic knowledge and meticulous microsurgical technique. The facial nerve can be drilled through or cut under direct visualization with little to no response from the facial nerve monitoring machine. Because of this, the best use of facial nerve monitoring is to aid in the identification of the facial nerve and to aid in meticulous microdissection of diseased tissue off of the facial nerve after the nerve has been identified. Its use should not ease the burden of the attending physician while teaching residents chronic ear surgery. Careful observation and patience are still required.

CEREBELLOPONTINE ANGLE, INTERNAL AUDITORY CANAL, AND LABYRINTHINE SEGMENTS OF THE FACIAL NERVE The facial nerve arises from the lateral pons and courses superiorly through the CPA to enter the IAC, anterior to the eighth cranial nerve. It then turns superiorly, entering the fundus of the IAC in the anterosuperior quadrant

Overview of Facial Nerve Surgery

Translabyrinthine Approach

Superior

7

SV

Anterior

Posterior

C

IV

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Inferior Figure 72-1. Anatomy of the fundus of the internal auditory canal. The facial (7), cochlear (C), superior vestibular (SV ), and inferior vestibular (IV ) nerves are shown. The transverse crest (TC) and vertical crest (VC) separate the fundus into four quadrants.

(Fig. 72-1). The cochlear nerve lays directly below it and the superior and inferior vestibular nerves lay posterior to it. Three different operative approaches can be used to visualize the facial nerve in these medial segments: the translabyrinthine, the retrosigmoid, and the middle fossa approach.

The translabyrinthine approach has the potential to permit direct visualization of the entire proximal course of the facial nerve through one opening (Fig. 72-2). Because it entails removal of a portion of the inner ear, it is chosen when the ear is deaf or when hearing conservation would be impossible. This technique involves a standard cortical mastoidectomy with identification of the semicircular canals. A labyrinthectomy is performed with wide opening of the vestibule. During the labyrinthectomy, the facial nerve can be identified just inferior to the lateral semicircular canal. It can be followed past the second genu inferiorly as it courses vertically through the mastoid. The porus acousticus is identified at the medial boundary of the temporal bone, and the IAC is skeletonized from medial to lateral until it joins with the vestibule. Troughs are drilled on either side of the IAC to permit roughly 270-degree exposure around the canal. To expose the CPA and IAC segments of the facial nerve within, the dura needs to be opened. This is most commonly performed for CPA tumors such as acoustic neuroma, but it also has relevance for proximal facial nerve lesions as well. In the typical patient with an acoustic neuroma, the facial nerve is anterior to the tumor. However, the precise course of the facial nerve can have a great deal of variability along the tumor face. For example, it may run along the inferior aspect of the tumor in a linear fashion, entering the IAC in a near normal position. Alternatively, the facial nerve may exit the brainstem and run directly superior across the top of the tumor. Occasionally, the facial

Geniculate Horizontal

Vertical Stylomastoid foramen

Second genu Labyrinthine

Canalicular

CPA Entry zone

Figure 72-2. The translabyrinthine approach. Cranial nerves are numbered. The entire course of the facial nerve can be visualized (Entry Zone, Cerebellopontine Angle [CPA], Canalicular, Labyrinthine, Geniculate, Horizontal, Second Genu, Vertical, and Stylomastoid Foramen). Other landmarks include the transverse sinus (TS), sigmoid sinus (SS), superior petrosal sinus (SPS), jugular bulb (JB), cochlear aqueduct (Ca), dura (D), choroid plexus (Ch), and flocculus (Fl).

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nerve may kink at the “shoulder” of the tumor at the porus acousticus. This feature often is associated with increased adherence of the tumor to the facial nerve and can make complete tumor removal difficult. Careful use of facial nerve monitoring and the nerve stimulator is indicated to both visually and electrically identify the course of the facial nerve. Additionally, the facial nerve is quite susceptible to becoming dry during this dissection process and thorough irrigation on a periodic basis is required to keep the nerve moist and healthy. Electrical “training” during this dissection process usually indicates a healthy facial nerve. Another measure for assessing the health of the facial nerve can be to identify the threshold of stimulability, that is, the minimum voltage or current required to identify a measurable response from the electromyographic recordings. This may be performed at the conclusion of tumor dissection to predict the patient’s long-term facial nerve function. Additionally, suprathreshold evoked myogenic response potentials have been shown to have positive predicted value in long-term facial nerve outcomes.5 Exposure of the facial nerve within the labyrinthine segment is most commonly performed for treating tumors of the facial nerve or geniculate ganglion, nerve injury due to temporal bone fracture, or nerve decompression in a patient with Bell’s palsy or herpes zoster oticus. Additionally, should the facial nerve be injured within the CPA or IAC during resection of an acoustic neuroma, a reanastomosis may be easily performed by performing facial nerve rerouting (Fig. 72-3). Using the translabyrinthine approach, the facial nerve can be decompressed through the labyrinthine segment, up to the geniculate ganglion, and back through the horizontal segment to the second genu. By carefully

elevating the facial nerve out of the fallopian canal, additional length of the nerve is gained either for direct anastamosis or for rerouting. The greater superficial petrosal nerve needs to be divided for this procedure. When insufficient length can be gained through this maneuver, a nerve graft may be interposed between the two cut edges of the nerve (Fig. 72-4).

Figure 72-3. Facial nerve rerouting and reanastamosis using the translabyrinthine approach. Note the greater superficial petrosal nerve has been cut.

Figure 72-4. Facial nerve jump graft in the cerebellopontine angle and internal auditory canal segments. Multiple sutures are used for the distal anastamosis, whereas only one can be used for the proximal anastamosis.

Retrosigmoid Approach The retrosigmoid approach provides exposure to the proximal segment of the facial nerve without inherently sacrificing hearing. However, when exposure of the lateral portion of the facial nerve is required (in the lateral third of the IAC), the major benefit of the retrosigmoid approach is lost. Drilling the posterior surface of the temporal bone to expose the fundus of the internal auditory canal involves sacrificing the inner ear, causing total hearing loss in that ear. The retrosigmoid approach involves a posterior fossa craniotomy behind the sigmoid sinus. The cerebellum is gently retracted and the brainstem and lower cranial nerves identified. The facial nerve can be localized exiting the brainstem anterior to the eighth cranial nerve. The dura of the posterior face of the temporal bone is divided and then elevated both superiorly and inferiorly. A diamond burr is then used to skeletonize the IAC. The porus acusticus is identified initially, and then the IAC can be followed out laterally. The jugular bulb is the inferior landmark and the superior petrosal sinus is the superior landmark of this dissection process. Care must be taken not to enter the inner ear as the lateral portion of the drilling is performed, if hearing is to be preserved. The trough should be shallower and cannot safely be drilled more than one-half to two-thirds of its length.6 The posterior semicircular canal runs close to the inferior aspect of the IAC. If the posterior semicircular canal is breached to a modest degree, bone wax may be used to plug it in an attempt to reduce the risk of sensorineural hearing loss.

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The retrosigmoid approach provides nearly an identical view of the facial nerve to that from the translabyrinthine approach for the CPA and lateral IAC segments. Again, the facial nerve usually runs anterior to the tumor, and the dura of the IAC needs to be opened to perform the dissection of the tumor off of the nerve within the IAC.

Middle Fossa Approach The middle fossa approach is another technique for identifying the facial nerve within the CPA, IAC, and labyrinthine segments. If further exposure of the distal facial nerve is required, a transmastoid approach may also be used through the same skin incision (Fig. 72-5). However, a separate drilling site is needed within the mastoid cavity (Fig. 72-6). Although bot0h the middle fossa/transmastoid combination and the translabyrinthine approaches provide exposure of the entire length of the facial nerve, only the former permits hearing preservation. The middle fossa approach involves a temporal craniotomy with gentle retraction of the temporal lobe. A middle fossa retractor is used for this retraction process because the blade is stiffer than a malleable retractor. Placing the tip of the middle fossa retractor at the petrous ridge is necessary for complete exposure of the medial segments of the facial nerve. The superior petrosal sinus runs along the petrous ridge and occasionally may be injured by the middle fossa retractor. The bleeding may be controlled with medium Weck clips if needed. Temporal floor landmarks include the greater superficial petrosal nerve and the arcuate eminence (Fig. 72-7). The arcuate eminence represents the bulge of the superior semicircular canal. Drilling to identify the IAC commences at the porus acusticus and then extends laterally (Fig. 72-8). This process needs to be performed very carefully with diamond burrs, because the facial nerve usually runs along the superoanterior portion of the IAC. It is directly underneath the dura and can be quite easily injured. The last remaining fragments of bone

Figure 72-6. The combined middle fossa/transmastoid approach. Two bony openings are required (a middle fossa craniotomy and a mastoidectomy).

overlying the dura should be delicately removed with a small elevator. The dura of the IAC needs to be opened in a site away from the facial nerve.7 The course of the facial nerve under the dura can be identified by careful electrical stimulation. The facial nerve can then be followed out laterally toward the area of the geniculate ganglion, although the geniculate does not always need to be exposed. Surgery for a traumatic injury to the facial nerve after temporal bone fracture often involves exposure of the nerve via the middle fossa approach. The nerve can be followed past the geniculate ganglion and through the horizontal portion as well (Fig. 72-9). This involves opening the bone over the attic region of the middle ear space. Care is needed to minimize manipulation of the ossicles. Repair of traumatic facial nerve injuries in this location can be performed either by mobilization of the facial nerve with division of the greater superficial petrosal nerve (Fig. 72-10A) or by the insertion of a short nerve graft (Fig. 72-10B).

HORIZONTAL SEGMENT OF THE FACIAL NERVE

Figure 72-5. Skin incision for a combined middle fossa/transmastoid exploration of the facial nerve.

The horizontal and vertical segments of the facial nerve are most commonly identified via a tympanomastoid approach. This is the standard approach used for routine chronic ear surgery and permits visualization of the facial nerve from the upper tympanic segment all the way to the stylomastoid foramen. Hearing preservation is possible with this approach (Fig. 72-11). Along its horizontal segment, the facial nerve runs medial to the long processes of the incus and malleus. The ampulla of the posterior semicircular canal is directly medial to the facial nerve in the vertical segment.8 The chorda tympani nerve exits the facial nerve in the distal vertical segment and runs in an

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FACIAL NERVE DISORDERS

Horizontal EAC GG ME

Geniculate

Second genu

GSPN Figure 72-7. The operative view of the middle fossa approach with detail of the structures inside of the temporal bone. These include the greater superficial petrosal nerve (GSPN), external auditory canal (EAC), middle ear (ME), geniculate ganglion (GG), middle meningeal artery (MMA), cochlea (CO), facial nerve (7), superior vestibular nerve (SVN), superior petrosal sinus (SPS), and the superior semicircular canal (SSCC).

SSCC Labyrinthine MMA

SPS

CO Canalicular 7 SVN

Figure 72-8. Exposure of the internal auditory canal via the middle fossa approach. A small acoustic neuroma is evident inferior to the facial and superior vestibular nerves.

Figure 72-9. Exposure of the labyrinthine and horizontal segments of the facial nerve via the middle fossa approach. A temporal bone fracture has caused neural disruption.

Overview of Facial Nerve Surgery

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Figure 72-10. Repair of facial nerve injuries via the middle fossa approach. A, The greater superficial petrosal nerve has been divided, permitting mobilization of the facial nerve and primary reanastamosis. B, A jump graft has been inserted between the two cut ends of the facial nerve.

A

B

anterosuperior direction through the middle ear space, just underneath the tympanic membrane. One of the most important surgical relationships of the facial nerve is that it lies inferior to the lateral semicircular canal and superior to the stapes (Fig. 72-12). Cholesteatomata involving the stapes tend to drape over

both the stapes and the facial nerve (Fig. 72-13).9 Dissection of a cholesteatoma in this region is a delicate procedure because the facial nerve is often dehiscent (Fig. 72-14). Facial nerve monitoring is often quite useful, particularly if one is concerned that inflammatory tissue and cholesteatoma might be scarred to the epineurium. The

Second genu Horizontal GSPN Geniculate

Tensor tympani muscle

Eustachian tube

Vertical

Chorda tympani nerve Stylomastoid foramen

Figure 72-11. The horizontal and vertical portions of the facial nerve via transmastoid approach. The canal wall has been left up. The horizontal segment of the facial nerve lies medial to the malleus and incus. FN, facial nerve; GSPN, greater superficial petrosal nerve; LSCC, lateral semicircular canal; PSCC, posterior semicircular canal.

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FACIAL NERVE DISORDERS

GSPN Cochleariform process Tensor tympani tendon Semicanal Figure 72-12. The horizontal and vertical portions of the facial nerve via transmastoid approach. The canal wall has been taken down. The segments of the facial nerve are labeled. GG, geniculate ganglion; GSPN, greater superficial petrosal nerve; Horiz, horizontal segment; Lab, labyrinth; RW, round window; Vert, vertical segment.

Eustachian tube

Tympanic plexus Chorda tympani nerve

use of the laser in dissecting cholesteatomata off of the stapes can often be beneficial.10 However, it is easy to accidentally point the laser at the adjacent facial nerve. Additionally, heat created during use of the laser can injure the facial nerve. To help draw away the heat, it is important to instill water into the middle ear space periodically while using the laser.

FACIAL RECESS The vertical portion of the facial nerve is a complex area. The chorda tympani and tympanic annulus define the lateral aspect of the facial recess, and the facial nerve defines the

medial aspect (Fig. 72-15). Drilling the facial recess involves identifying all of these landmarks. This exposure begins with a complete mastoidectomy and identification of the antrum, lateral semicircular canal, and sinodural angle. The ear canal is thinned as much as possible. The posterior ear canal curves forward at its medial extent, forming the scutum. By following this curve, one can safely open the facial recess lateral to the facial nerve (Fig. 72-16). As the chorda tympani nerve courses under the tympanic membrane, it is possible to accidentally drill too far anteriorly, entering the external ear canal, rather than the middle ear. For this reason, the chorda tympani is a good landmark for the inferior portion of the facial recess, but the tympanic annulus is a better landmark for the superior portion. If the incus is to be preserved with an intact ossicular chain, the buttress of bone to which the short process of the incus is tethered should be preserved. If the incus is not to be preserved, this bone can be safely removed, after disarticulating the incudostapedial joint, to improve exposure.

STYLOMASTOID FORAMEN AND EXTRATEMPORAL SEGMENT OF THE FACIAL NERVE Figure 72-13. A cholesteatoma draped over the stapes and horizontal segment of the facial nerve. A cross-sectional view (left) and surgical view (right) are shown.

The facial nerve runs lateral to the jugular bulb and exits the temporal bone at the level of the digastric ridge, coursing anteriorly. The mastoid tip can be safely removed without

Overview of Facial Nerve Surgery

A

B

C

D

Facial recess

Chorda tympani

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Figure 72-14. Examples of facial nerve dehiscence in the horizontal segment. Cross-sectional views (left) and surgical views (right) are shown. There may be no dehiscence (A), mild dehiscence (B), moderate dehiscence (C), or severe dehiscence (D). The degree of dehiscence depends on the embryonic development of the fallopian canal as well as the degree of bony resorption secondary to chronic otitis media or cholesteatoma.

Tympanic membrane Tensor tympani m.

Facial n. Stapedius m. in pyramid sinus Sinus tympani

Cochleariform process

A Annulus

Chorda tympani

B Figure 72-15. A, The facial recess and sinus tympani viewed from below. The vertical segment of the facial nerve divides these two spaces. B, The surgical view of facial recess anatomy. The facial nerve forms the medal edge and the chorda tympani nerve and the annulus form the lateral edge of the facial recess (facial recess area is shaded).

Figure 72-16. Surgical exposure of the facial recess. A, A standard canal wall up mastoidectomy has been performed. The short process of the incus and the malleus head are visible in the attic. B, Drilling commences along the lateral surface of the facial recess, following the curve of the ear canal anteriorly. C, The facial recess air cells are opened and the annulus, chorda tympani, and facial nerve identified. D, When first opened, the facial recess permits visualization of the stapedial tendon and the stapes capitulum. E, Further drilling inferiorly is required to see the round window niche. F, The buttress to which the short process of the incus articulates with can be removed if the incus is to be removed.

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FACIAL NERVE DISORDERS

P CA

9 12

TM

10

Figure 72-17. The stylomastoid area and extratemporal facial nerve. The facial nerve (FN) lies directly lateral to the jugular bulb (JB). Other cranial nerves are numbered. Sigmoid sinus (SS), jugular vein (JV), semicircular canals (SCC), tympanic membrane (TM), carotid SCC artery (CA), parotid gland (P).

JV

11

JB

FN SS

concern for injury to the facial nerve as long as the digastric ridge has been thoroughly exposed and respected. The facial nerve then enters into the parotid gland and splits at the pes anserinus. Complete exposure of the facial nerve is the key to surgery of the jugular foramen because the facial nerve lies directly in the path of tumors that arise in this region, most commonly glomus jugulare tumors (Fig. 72-17). Most commonly, the facial nerve can be left within a thin bony canal with a complete removal of the surrounding

bone. This is called the fallopian bridge technique11 (Fig. 72-18). This is begun by performing a canal-wall-down mastoidectomy and lowering the facial ridge. Drilling the retrofacial air cells from the mastoid then leads to the sinus tympani and the jugular bulb in a well-pneumatized temporal bone. Unfortunately, the degree of pneumatization required for this technique is rarely encountered in patients with chronic ear disease, although it can occasionally be used to remove cholesteatomata from the sinus tympani.12 Dividing the skull base periosteum from the infratemporal region with a stout scissors is required to connect the jugular vein (identified in the neck) and the jugular bulb (identified in the temporal bone).

FACIAL NERVE REROUTING The alternative to the fallopian bridge technique is mobilization of the facial nerve with rerouting of the nerve anteriorly.13,14 This technique was designed to increase exposure of tumors medial to the facial nerve. However, depending on the length of facial nerve transposed, the blood supply to the facial nerve may be compromised and diminished facial nerve function may result. Short mobilization, from the second genu to the pes anserinus, has only a slight risk of facial nerve compromise, but unfortunately exposure is only minimally enhanced. Long mobilization, from the first genu to the pes anserinus, has a moderate risk of facial nerve injury. Complete mobilization, from the brainstem to the pes anserinus (including division of the greater superficial petrosal nerve) almost always leads to a House-Brackmann grade 3–4 function (at best).

Figure 72-18. The fallopian bridge technique. The entire course of the sigmoid sinus can be followed as it courses into the jugular vein in the neck. The vertical portion of the facial nerve is skeletonized, “bridging” over the jugular bulb.

FACIAL NERVE GRAFTING The two nerves commonly used for interposition grafting of the facial nerve are the greater auricular nerve and

Overview of Facial Nerve Surgery

Figure 72-19. Exposure of the greater auricular nerve. It runs parallel to the external jugular vein, on the lateral surface of the sternocleidomastoid muscle.

the sural nerve. The greater auricular nerve is usually the easiest nerve to obtain, although its length is limited. In contrast, the sural nerve can provide quite long lengths of nerve. The greater auricular nerve can be harvested by extending a standard postauricular skin incision inferiorly down onto the neck (Fig. 72-19). The greater auricular nerve runs over the lateral surface of the sternocleidomastoid muscle in an anterosuperior fashion, beginning at Erb’s point. Erb’s point delineates the entire plexus of cutaneous

1221

sensory nerves that wrap around the sternocleidomastoid muscle, which originates from cervical nerve roots 2, 3, and 4. Importantly, the spinal accessory nerve exits from under the sternocleidomastoid muscle 1 cm superior to Erb’s point, coursing posterolaterally toward the trapezius muscle. Removal of the greater auricular nerve leads to numbness of the pinna and upper neck region. The sural nerve can be identified along the lateral ankle and lower leg regions (Fig. 72-20). A good way to harvest the sural nerve is to make a vertical incision 1 cm posterior to and 1 cm superior to the lateral mallelus of the ankle. Blunt dissection with a small hemostat aids in the identification of the sural nerve. The small saphenous vein also runs in this area. The incision can be extended superiorly as needed to obtain a quite long length of nerve. Resection of the sural nerve produces numbness of the lateral foot. Standard microscopic nerve grafting techniques should be used. Careful neurorrhaphy technique involving 8–0 or 9–0 monofilament suturing under the microscope should be performed. For neurorrhaphy outside of the CPA, typically a minimum of four epineural sutures are placed (see Fig. 72-4—distal anastamosis). The goal is to keep all of the perineural and endoneural structures in close proximity. The intraneural components should not bulge between the sutures. The concept of a perineural repair has all but been abandoned because of its technical difficulty and the lack of demonstrable improvement in long-term facial nerve outcomes. If extratemporal resection of the facial nerve, including the pes anserinus, has been required, fascicles within the nerve graft can be opened up and grafted to the different divisions of the nerve. Often only the frontal, zygomatic, and marginal mandibular divisions can be identified. For neurorrhaphy within the CPA, placement of more than one stitch is nearly impossible because there is no epineurium. A single stitch placed through the entire nerve is adequate (see Fig. 72-4—proximal anastamosis). A small piece of fascia can be gently wrapped around this repair to help funnel regenerating axons in the proper direction.

REFERENCES

Figure 72-20. The sural nerve. The small saphenous vein runs along with the nerve.

1. O’Donoghue GM, Brackmann DE, House JW, Jackler RK: Neuromas of the facial nerve. Am J Otol 10:49–54, 1989. 2. Gantz BJ, Rubinstein JT, Gidley P, Woodworth GG: Surgical management of Bell’s palsy. Laryngoscope 109:1177–1188, 1999. 3. Green JD Jr, Shelton C, Brackmann DE: Iatrogenic facial nerve injury during otologic surgery. Laryngoscope 104:922–926, 1994. 4. Brodie HA, Thompson TC: Management of complications from 820 temporal bone fractures. Am J Otol 18:188–197, 1997. 5. Mandpe AH, Mikulec A, Jackler RK, et al: Comparison of response amplitude versus stimulation threshold in predicting early postoperative facial nerve function after acoustic neuroma resection. Am J Otol 19:112–117, 1998. 6. Blevins NH, Jackler RK: Exposure of the lateral extremity of the internal auditory canal through the retrosigmoid approach: A radioanatomic study. Otolaryngol Head Neck Surg 111:81–90, 1994. 7. Satar B, Jackler RK, Oghalai J, et al: Risk-benefit analysis of using the middle fossa approach for acoustic neuromas with >10 mm cerebellopontine angle component. Laryngoscope 112:1500–1506, 2002. 8. Oghalai JS, Holt JR, Nakagawa T, et al: Harvesting human hair cells. Ann Otol Rhinol Laryngol 109:9–16, 2000.

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9. Jackler RK: The surgical anatomy of cholesteatoma. Otolaryngol Clin North Am 22:883–896, 1989. 10. Saeed SR, Jackler RK: Lasers in surgery for chronic ear disease. Otolaryngol Clin North Am 29:245–256, 1996. 11. Pensak ML, Jackler RK: Removal of jugular foramen tumors: The fallopian bridge technique. Otolaryngol Head Neck Surg 117:586–591, 1997.

12. Pensak ML, Friedman RA: Fallopian bridge technique in surgery for chronic ear disease. Laryngoscope 107:1451–1456, 1997. 13. Fisch U: Infratemporal fossa approach to tumors of the temporal bone and base of the skull. J Laryngol Otol 92:949–967, 1978. 14. Fisch U, Pillsbury HC: Infratemporal fossa approach to lesions in the temporal bone and base of the skull. Arch Otolaryngol 105:99–107, 1979.

73

Outline Evolution, Purpose, and Methods of Electrodiagnosis Minimal Nerve Excitability Test Maximal Nerve Excitability Test Electroneurography Electromyography Interpretation of Electrical Tests

Chapter

Electrical Testing of the Facial Nerve

Comparison of Electrical Tests Maximal-Nerve-Excitability Test–Based Prognosis in Bell’s Palsy General Considerations in Electrical Testing

E

lectrodiagnostic tests are used to evaluate the extent of physiologic damage to nerves, to predict prognosis, and to determine treatment. Over the years, the reliability of electrodiagnostic tests was challenged, and modifications and interpretations were subsequently suggested. Controversy surrounding electrodiagnosis abounds, and this chapter offers clinicians general and specific guidelines for making appropriate decisions. Before recommendations can be made for selecting and interpreting neurodiagnostic facial nerve tests, however, a discussion of test methodology is necessary.

EVOLUTION, PURPOSE, AND METHODS OF ELECTRODIAGNOSIS Electrodiagnosis originated in the late 1800s, when Duchenne performed electrical facial nerve excitability tests and local stimulation of individual muscles. In discussing “rheumatismal” facial palsy, Duchenne noted that the palsies that persisted had absent muscular contractility on nerve stimulation, whereas those that recovered had diminished muscular contractility on nerve stimulation. Duchenne claimed that these tests could reliably predict prognosis from 1 week after onset of the palsy. Duchenne also observed that lost nerve excitability did not return, even after voluntary movement was regained. Faradic and galvanic stimulation tests were used to determine denervation. Faradic stimulation uses an alternating current of high frequency and short duration. Galvanic stimulation uses direct current with long duration of stimulus. A quantitative difference between these two tests was postulated to indicate a “reaction of degeneration.”1 When this concept was found unreliable, volitional electromyography (EMG)2,3 and percutaneous stimulatory nerve Juan Domingo provided original illustrations. The Medical Editing Department of Kaiser Foundation Hospitals provided editorial assistance.

Kedar K. Adour, MD

excitability tests4–7 were introduced to test facial nerve dysfunction. All facial nerve electrodiagnostic tests attempt to determine quality and degree of axonal degeneration (i.e., denervation).8 In neurologic usage, the term denervation denotes “muscle denervation.” In general usage, denervation indicates that an injured nerve either has decreased or no muscle response to electrical stimuli. When denervation is present, a stronger electrical stimulus is needed to produce muscle contraction, and muscle response to maximal nerve stimulation is weak. If denervation is complete, all reaction to electrical stimulation is lost. Degree of denervation and subsequent prognosis are predicted by three components of stimulatory electrical testing: level of stimulation, magnitude of compound muscle action potential (CMAP), and latency between these two parameters. Currently, the most widely used electrodiagnostic tests are the minimal nerve excitability test (NET),9 the maximal-nerve-excitability test (MST),10 and electroneurography (ENOG).11,12 All are administered percutaneously using nerve simulators that produce a square-wave electric pulse of known duration and delivered at an intensity measured in milliamperes (mA) or volts (V). Because neural degeneration is often progressive, a single examination is not sufficient; reexamination on successive days is necessary for accuracy.

Minimal Nerve Excitability Test The NET consists of percutaneous stimulation of the facial nerve at the angle of the jaw or stylomastoid foramen while intensity of a short-duration current is raised until muscle contraction is observed (threshold stimulation). Pulse duration varying from 0.1 to 1.0 ms4,7,8 is advocated. The most popular stimulator used in the United States is the Hilger Facial Nerve Stimulator (WR Medical Electronics, Stillwater, MN),13 which can generate a 6-pulse/sec stimulus; however, any reliable electrical stimulator can be 1223

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FACIAL NERVE DISORDERS

used. The affected and unaffected sides are stimulated, and the threshold level of stimulation between the two is compared.

Electroneurography

The reliability of NET has been challenged14; consequently, the MST has gained popularity as a modified version of NET.10 The stimulator used for NET may also be used for MST. But regardless of modification, NET and MST both require use of an indifferent (ground) electrode, which can be placed on any part of the patient’s body. We recommend that the electrode be placed on the back of the patient’s hand and held in place by the patient to facilitate testing.13 The observer should be positioned to see both sides of the patient’s face simultaneously. The testing (stimulating) probe is applied to the nerve branch to be tested, and the intensity of current is increased to produce a barely visible muscle twitch. When the first twitching is observed, the area is explored to find the most sensitive location, that is, the place where minimum stimulation elicits muscle response. Current is then increased l or 2 mA above this threshold to obtain maximal nerve excitability stimulation. Test results represent visual comparison of facial muscle movement of the affected and normal sides of the face, recorded as equal or decreased. If muscle response to maximal nerve excitability stimulation is decreased, the observer records this decrease as minimal, moderate, severe, or complete denervation. Although facial nerve excitability testing is a simple procedure, experience is required for determining location of peripheral nerve branches (Fig. 73-1).15 The frontalis muscle branch is usually found about an inch posterior to the outer canthus of the eye. The orbicularis oculi branch is stimulated at the bony orbit lateral border. The orbicularis oris branch is the most variable of all three branches but is usually found at a point slightly anterior to the notch where the facial artery traverses the mandible. Determination of maximal response point may necessitate moving the stimulating probe, because the facial nerve can branch in many directions beyond the stylomastoid foramen.

In ENOG, as in NET, the stimulating electrode is placed over the nerve trunk; but unlike NET (which uses threshold stimulation), ENOG uses supramaximal stimulation. Muscle response can be measured with a needle electrode,8 a procedure which produces a true evoked electromyogram (EEMG), or with a surface electrode. In ENOG, similar bipolar electrodes are used for nerve stimulation and for recording the summation CMAP. The nerve is stimulated with a supramaximal stimulus, and the functional status of the nerve is assessed on the basis of the CMAP recorded amplitude. The time interval between nerve stimulation and initiation of CMAP is represented as the facial nerve latency, which may be considered an acceptable indication of nerve function.16 ENOG may provide objective recorded assessment of facial nerve function, but the technique has not yet been standardized.17,18 Technical variables of ENOG include electrode diameter, intercenter distance between electrodes, placement of and pressure applied to electrodes, and definition of supramaximal stimulation. Intercenter distance between electrodes as well as electrode diameter are related to the type of equipment used. In initial studies, stimulation electrodes 8 mm in diameter were placed 11 mm apart.11,17 Recording electrodes (similar to stimulating electrodes) had a diameter of 10 mm and were placed 20 mm apart. Later studies supported an intercenter distance of 20 mm,19 but another study suggested that unconventionally small recording electrodes (i.e., 3 to 7 mm in diameter) produced less test error.20 Most reports recommend that the stimulating electrode be placed near the stylomastoid foramen and that the recording electrode be placed in the nasolabial crease at a point slightly lateral to the nasal ala (standardized technique) (Fig. 73-2).15 Stimulator placement can be in front of the tragus or in the stylomastoid foramen between the ramus of the mandible and the mastoid process. The standardized placement technique allows the stimulating electrode to be moved for technical reasons, including prevention of unintentional activation of the trigeminal nerve; this activation produces a “trigeminal nerve artifact,” which

Figure 73-1. Schematic drawing depicts the location of the facial nerve branches stimulated when performing maximal stimulation tests (MST). (Reproduced, with permission of the publisher and the illustrator, from Adour KK: Who’s afraid of the facial nerve? In Lucente FE [ed.]: Highlights of the Instructional Courses, vol 8. St. Louis, Mosby-Year Book, 1995, p 258.)

Figure 73-2. Schematic drawing shows standardized lead placement of stimulating and recording electrodes and depicts a compound muscle action potential (CMAP). (Reproduced, with permission of the publisher and the illustrator, from Adour KK: Who’s afraid of the facial nerve? In Lucente FE [ed.]: Highlights of the Instructional Courses, vol 8. St. Louis, Mosby-Year Book, 1995, p 260.)

Maximal Nerve Excitability Test

Electrical Testing of the Facial Nerve

corrupts biphasic CMAP measurement.11,21,22 The recording electrode is maintained in a fixed (“standard”) position in the nasolabial crease. In a variation of this standardized technique, the recording electrode is placed on the nasal ala, and the stimulating electrode is placed under the zygoma23 (Fig. 73-3).24 “Optimized” tests12,25 allow the recording stimulating electrodes to be moved to create a more reliable maximal CMAP measurement (i.e., uncorrupted by trigeminal artifact) (Fig. 73-4).15 Each technique records peak-to-peak amplitude of the CMAP from the maximum positive to minimum negative deflection as measured in microvolts (mV). Measurements in the same patient can fluctuate widely when different techniques are used. This fluctuation is affected by pressure exerted on the recording and stimulating electrodes and by the area under the active electrode (i.e., area covered by conducting paste). This matter is subject to disagreement, and local preference therefore determines whether to affix electrodes to the skin or give them to the patient to hold. The final question for consideration when using ENOG involves “maximum stimulation”26–29 of the nerve. After the stimulating electrode is positioned, the current or voltage is gradually raised until summation CMAP reaches a stable level. The stimulus is then raised by 10%, and the reading is recorded; the result should represent the ideal stimulus. However, before such an ideal situation is reached, pain intolerance and the trigeminal artifact (clicking sound made by the patient’s jaw) may corrupt results of the study. Some authors have suggested that in such cases, the stimulus should be decreased and appropriate corrective measures taken.22 Reaching the ideal stimulus intensity required for obtaining a smooth, maximum biphasic CMAP is not always possible.

Electromyography As distinct from EEMG, EMG refers to volitional electromyography.8 In EMG, needle electrodes are placed into striated muscle, and the resultant electrical activity is monitored visually and audiographically on an oscilloscope.30 Normal muscle shows activity when the needle is inserted

Figure 73-3. Schematic drawing shows ENOG electrode placement devised by May’s group. Recording electrode fixed on nasal ala and stimulating electrode under zygoma. (Reproduced, with permission of the publisher and the illustrator, from Adour KK: Who’s afraid of the facial nerve? In Lucente FE [ed.]: Highlights of the instructional courses, vol. 8. St. Louis, Mosby-Year Book, 1995, p 260.)

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Figure 73-4. Schematic drawing shows optimized lead placement of stimulating and recording electrodes and depicts possible variation in size of compound muscle action potential (CMAP). (Reproduced, with permission of the publisher and the illustrator, from Adour KK: Who’s afraid of the facial nerve? In Lucente FE [ed.]: Highlights of the Instructional Courses, vol 8. St. Louis, Mosby-Year Book, 1995, p 260.)

but shows no electrical activity when at rest. Voluntary facial contraction generates CMAPs, which are graded on a scale ranging from +1 to +4, a score of +4 indicating normal response and a score of +1 to +3 indicating diminished response. True denervation (i.e., muscle denervation) exists if the motor endplate is deprived of its nerve supply. With such denervation of the muscle, the needle electrode can be used to record spontaneous electrical discharge of the motor endplates (termed fibrillation potential or denervation potential) 14 to 21 days after wallerian degeneration occurs. If the nerve does not undergo wallerian degeneration, fibrillation potentials do not occur; and when electrical continuity to the muscles is reestablished, EMG will record normal reinnervation potentials. If degeneration has taken place, reestablishment of the nerve to the motor endplates is recorded as a regeneration potential and is often accompanied by spontaneous fasciculation.

INTERPRETATION OF ELECTRICAL TESTS Because most forms of facial palsy originate deep within the temporal bone, direct evaluation of the injured nerve segment is impossible, and electrodiagnosis can assess only the degree of distal axon degeneration. Electrical tests are often regarded as reliable prognostic indicators,9,13,26,29 although they are only indirect indicators of facial nerve neurophysiology. To select the most appropriate electrical tests, clinicians must understand the underlying physiology of nerve injury and repair. Seddon31 classified nerve injury damage in increasing degrees of severity, that is, as neuropraxia, axonotmesis, and neurotmesis. Sunderland1 refers to five degrees of nerve injury in terms of damage to the endoneurium, perineurium, epineurium, and axon (Table 73-1).24 These classifications represent pathology and not neurophysiology. Nerve action potentials can be propagated only if the nerve is neuropraxic (first-degree injury); because presence of axonotmesis or neurotmesis would preclude response to electrical stimulation, electrical tests cannot differentiate among second-, third-, fourth-, and fifth-degree injury

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FACIAL NERVE DISORDERS

TABLE 73-1. Classification of Types of Nerve Injury Classification Pathology

Sunderland1

Seddon31

Conduction block Transection of the axon with intact endometrium Transection of nerve fiber (axon and sheath) inside intact perineurium Transection of funiculi; nerve trunk continuity maintained by epineural tissue Transection of entire nerve trunk

First degree Second degree

Neuropraxia Axonotmesis

Third degree

Neurotmesis

Fourth degree

Neurotmesis

Fifth degree

Neurotmesis

Adapted and reproduced, with permission of the publisher, from Adour KK: Facial nerve electrical testing. In Jackler RK, Brackmann DE (eds.): Neurotology. St. Louis, Mosby, 1994, p 1286.

(Fig. 73-5).24 This lack of response (recorded as failure of an electrical stimulus to produce a CMAP) is termed total denervation, even though less severe injuries have better prognosis. Sunderland’s classification only applies to traumatic peripheral nerve injury, and the facial nerve is not ever discussed in his classic textbook.1 Pathologic classifications have limited application to inflammatory autoimmune lesions of viral origin (Bell’s palsy),32–35 and these lesions are the most frequent cause of facial paralysis. Although Sunderland’s classification is frequently used,

Figure 73-5. Schematic drawing of five degrees of nerve injury and resultant effect on summation compound muscle action potential (CMAP). (Reproduced, with permission of the publisher, from Adour KK: Facial nerve electrical testing. In Jackler RK, Brackmann DE [eds.]. Neurotology. St. Louis, Mosby, 1994, p 1287.)

Seddon’s classification is sufficiently precise to discuss facial paralysis neurophysiology. In patients who have a severed facial nerve, all stimulatory electrical tests performed distal to the lesion maintain normal latency and normal CMAPs for 48 to 72 hours,36 thus refuting existence of prior injury. EMG would reveal absent volitional CMAPs, but this result would be the same if the nerve were in a neuropraxic state. EMG fibrillation potentials would not appear for 2 to 3 weeks. As these facts emphasize, available electrodiagnostic tests may show abnormal results days to weeks after nerve degeneration has taken place. Today’s widespread interest in electrodiagnostic testing is predicated on the faulty assumption that Bell’s palsy is caused by a lesion compressing the vascular system37–40 and that surgical facial nerve decompression is beneficial.5,6,38,40 Compressive neural lesions represent an “either/or” phenomenon.41,42 The nerve-muscle complex will continue to generate electric activity until the compression exceeds the systolic blood pressure,43 at which point total paralysis will occur; partial facial paralysis cannot exist. The nervemuscle complex will recover if compression is released within 3 hours43 or if the systolic blood pressure increases.44 Because Bell’s palsy most often is noted as partial paralysis progressing to any of various degrees of severity, the vascular-compressive theory of causation is not tenable.3,32

COMPARISON OF ELECTRICAL TESTS Historically, patients with Bell’s palsy were selected for surgery on the basis of NET results. Consensus opinion held that excitability could be considered diminished if test results showed a greater than or equal to 2.5 mA side-to-side difference in threshold level of stimulation.4 A side-to-side difference ranging from 2.5 to 3.5 mA has been suggested to indicate impending or progressive denervation5–7 and was used as a criterion for diagnosing facial nerve decompression.5,7,40 Reliability of NET has limitations: because it is a threshold test, NET may not reflect condition of the whole nerve trunk; and NET has produced intertest error of 7% to 9% and results that varied by more than 2.5 mA.45,46 In addition, the facial nerve trunk is deep in relation to the skin and subcutaneous tissue and therefore requires application of stimulus at levels that often trigger the trigeminal nerve artifact reaction in the masseter muscle. Denervation can compound the problem: As a result of the increased stimulus necessary to elicit a response, the test may become too painful for the patient to tolerate.13,14 Nonetheless, NET results can often be used to predict risk for delayed or incomplete recovery.5–7,9 MST of the peripheral facial nerve branches proved superior to NET when predicting prognosis10,13,47 but gained little favor when selecting patients for surgery. NET and MST both have the disadvantage of relying on observation, whereas ENOG has the advantage of recorded and often reproducible results and has become the standard for selecting patients for surgery.27,48–50 However, both ENOG and NET have the disadvantage of reliance on stimulating the nerve trunk. Moreover, ENOG is interpreted on the

Electrical Testing of the Facial Nerve

basis of muscle reaction in only one part of the face; if the upper division of the facial nerve is cut on one side of the face, the CMAP is equal on both sides of the face. Disadvantages of NET and ENOG are avoided by using MST, which stimulates peripheral nerve branches and records the results.12 Testing the peripheral branches (which are more superficial to the skin and thus require less current to produce maximal muscle response) reduces pain for the patient, thus increasing patient compliance. Use of MST also produces no trigeminal artifact and accurately measures the entire facial nerve. No test can distinguish between axonotmesis and neurotmesis; the electric impulse can stimulate only neuropraxic fibers. The statement “at this time we feel that ENOG is the only sufficiently sensitive test to determine the need for possible surgery in Bell’s palsy”51 needs scrutiny. Results of ENOG are considered objective quantification of facial nerve function and can predict whether to do surgery. Predictive sensitivity and specificity tests for ENOG have never been done.46,48–51 In clinical practice, the CMAP generated by ENOG is measured (in microvolts) on each side of the face. Responses detected on the paralyzed and unaffected sides are compared, and the resultant percentage difference is presumed to reflect the number of degenerated fibers.48,49 Fisch named the test electroneuronography.49 Gavilán and colleagues52 pointed out that normal subjects show a 25% side-to-side difference in recorded CMAP and that normal facial nerves cannot be appropriately concluded to have 25% degenerated nerve fibers. The term electroneurography is well established in conventional usage, but a more appropriate term would be neuromyography (NMG)17 because the test results depend on a chain of events that include (1) electrical resistance between stimulation electrode and nerve, (2) nerve conduction velocity, (3) transmission time at the neuromuscular junction, (4) conduction time in the muscle, (5) degree of synchrony in the muscle fiber action potentials producing the CMAP, and (6) number of nondegenerated fibers in the nerve.17 At present, no published study has documented results of electrical tests and pathologic state of the nerve. Because electrical tests can stimulate only neuropraxic fibers, the CMAP reflects nerve fibers that have not degenerated. Side-to-side and test-retest variability have also been suggested to depend on desynchronization of the motor unit volley, which composes the summation CMAP.25,53 Therefore, recommended procedure is to apply stimulation 20 times before the final CMAP is recorded.49 In actuality, test results have shown no difference between the first 5 and the last 5 measurements of CMAP obtained after 25 successive applications of stimuli.52 These findings indicate that applying 20 or more stimuli before definitively registering CMAP is not justified. In addition, low test-retest variability has been observed22,29 and suggests that computerized averaging of CMAP measurements is not necessary. Even with these deficiencies, electrodiagnosis remains an important prognostic tool for evaluating facial paralysis. Although serial applications of NET and ENOG are excellent predictors of final outcome, rates of recovery achieved by using these tests have not been evaluated.

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Serial application of MST is the only available method of credibly predicting rate and degree of recovery.13

Maximal Nerve Excitability Test–Based Prognosis in Bell’s Palsy The clinical course of Bell’s palsy is characterized as producing complete or incomplete paralysis. Most patients with Bell’s palsy have incomplete paralysis initially. Careful observation of the paralysis progression (or lack of progression) and use of electrodiagnostic tests are the most valuable tools for determining rate and degree of denervation as well as prognosis. As early as possible after onset of paralysis, baseline MST is done to determine prognosis. The patient is seen 1 week after onset of paralysis. If the paralysis remains clinically incomplete, no further testing is indicated. If the paralysis becomes clinically complete, MST is done and is repeated 3 to 5 days later. Because degree of denervation is determined by the tester’s subjective impression of the “quality” and “quantity” of muscle motion, prediction of prognosis is a relative process that does not determine prognosis absolutely. Nonetheless, MST has proved a simple, reproducible, and accurate tool in such evaluation.13 For statistical analysis, we devised a modified method of reporting MST response. This modified method operates similarly to the method of reporting EMG findings and better conveys status of the peripheral branches. Degree of denervation is not always equal in every branch; therefore, by assigning response scores (i.e., 4 = equal response, 3 = minimally decreased response, 2 = moderately decreased response, 1 = severely decreased response, 0 = no response) we can compute an averaged (“global”) MST score for the entire face. An example of such an analysis is shown for a hypothetical patient with a “moderately” denervated facial nerve (Table 73-2).15 This condition would result in delayed recovery as well as eventual midface contracture and synkinesis. A global score of less than or equal to 2.7 has 94% accuracy for predicting incomplete recovery with contracture and synkinesis. If maximal NET results show decreased muscle response on the affected side of the face, complete return of facial function without complication cannot be expected. Some degree of contracture or synkinesis always accompanies denervation, but contracture, synkinesis, and facial spasms do not develop unless regeneration occurs.

TABLE 73-2. Method for Computing Mean MST Score Nerve Branch Tested

Visual Muscle Response

Forehead Eye Mouth Averaged score (3 + 2 + 1 ÷ 3)

Minimal decrease Moderate decrease Severe decrease

Numeric Score 3 2 1

MST, maximal nerve excitability test. Adapted and reproduced, with permission of the publisher, from Adour KK: Who’s afraid of the facial nerve? In Lucente FE (ed.): Highlights of the Instructional Courses, vol 8. St. Louis, Mosby-Year Book, 1995, p 257.

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FACIAL NERVE DISORDERS

TABLE 73-3. Recovery Predicted on Basis of Mean MST Score Mean MST Score 4 3–3.9 2–2.9 1–1.9 0–0.9

% Recovery 100 75–100 75 50–75 <50

Recovery Time (weeks) 3–6 4–8 6–12 8–12 12+

Sequelae (severity*) None Minimal Moderate Moderate/severe Severe

*Contracture with synkinesis. MST, maximal nerve excitability test. Adapted and reproduced, with permission of the publisher, from Adour KK: Who’s afraid of the facial nerve? In Lucente FE (ed.): Highlights of the Instructional Courses, vol 8. St. Louis, Mosby-Year Book, 1995, p 258.

Degree of contracture and synkinesis can be predicted by degree of denervation. In patients with only minimal or moderate denervation of the facial muscles, 75% to 100% of facial function can return with mild-to-moderate contracture and synkinesis apparent to a trained observer only. These patients can expect return of volitional facial muscle motion beginning 4 weeks after onset of paralysis and can expect excellent function 8 weeks after onset of paralysis. In patients with severe denervation, percentage of recovered volitional facial function is decreased; contracture, synkinesis, and facial spasms are usually severe; and 6 to 12 weeks is needed for adequate return of facial function. When MST yields no response (i.e., the patient has complete facial denervation), initial recovery of facial motion cannot be expected before 12 weeks; functional return of facial motion is limited to 50% to 75% compared with the opposite side of the face; and more severe contracture and synkinesis occurs (Table 73-3).15 Because degree of regeneration is related to both degree and rate of denervation, serial tests are done. Patients whose paralysis progresses from minimal to severe denervation in 7 to 10 days have better outcome than patients in whom minimal paralysis progresses to severe denervation in 3 to 4 days. In patients with Bell’s palsy, prognosis can be predicted by MST 10 days after onset of paralysis. However, in herpes zoster facial paralysis—a more severe form of Bell’s palsy—denervation can and does occur beyond 14 days after onset of paralysis. Patients with herpes zoster facial paralysis have poor prognosis and a similar degree of contracture and synkinesis as in patients who have rapid denervation. Recovery predicted on the basis of global (averaged) MST scores is listed in Table 73-3.15

GENERAL CONSIDERATIONS IN ELECTRICAL TESTING Electrical recovery does not accompany volitional muscle recovery. Therefore, stimulatory electrical tests are no longer useful for monitoring patients after facial nerve denervation. Because results of stimulatory electrical tests remain abnormal even when volitional facial muscle action has returned, EMG may be of prognostic value early in the regenerative period; however, this result occurs late in the course of the disease. Late in the period of reinnervation

Figure 73-6. Schematic drawing of ENOG using needle electrodes as devised by Kobayashi and colleagues. (Reproduced, with permission of the publisher and the illustrator, from Adour KK: Who’s afraid of the facial nerve? In Lucente FE [ed.]: Highlights of the Instructional Courses, vol 8. St. Louis, Mosby-Year Book, 1995, p 260.)

(i.e., when facial muscle motion is visible), obtaining an electromyogram is superfluous. In general, latency of the CMAP has been studied less than CMAP amplitude. Although latency values increase statistically with higher degrees of degeneration,14,54 latency in individual patients is not a useful measure, even though intersubject variability is low. Effectiveness of latency measurements for evaluating prognosis of facial paralysis remains doubtful.52 Use of electrodiagnosis to determine medical or surgical treatment depends on each practitioner’s training. If the treatment goal is to prevent denervation, use of electrical tests for patient selection may be futile because electrodiagnosis can only detect denervation 3 days after the damaging lesion has appeared. MST has not been used when selecting patients for surgical decompression but is probably the best percutaneous test for predicting prognosis. Patient selection for surgical decompression of the facial nerve is based on ENOG-based comparison of the CMAP on the affected and unaffected sides of the face in each patient: When the CMAP on the affected side is 90% less than on the unaffected side within 2 weeks after onset of Bell’s palsy, decompression is advised.48–51 Half of all affected patients recover without surgery48; percutaneous stimulation tests have inherent faults that produce unreliable measurements of denervation. If surgery is considered on the basis of electrical test results, the technique of Kobayashi and colleagues55 of needle stimulation of the facial nerve should be used (Fig. 73-6)15 to avoid unreliability of surface-stimulating electrodes placed on the skin surface.

REFERENCES 1. Sunderland S: Nerves and Nerve Injuries, 2nd ed. New York, Churchill Livingstone, 1978, p 258. 2. Weddell G, Feinstein B, Pattle RE: The electrical activity of voluntary muscle in man under normal and pathological conditions. Brain 67:178, 1944. 3. Taverner D: Bell’s palsy: A clinical and electromyographic study. Brain 78:209, 1955

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4. Campbell EDR, Hickey RP, Nixon KH, et al: Value of nerveexcitability measurements in prognosis of facial palsy. Br Med J 2:7, 1962. 5. Laumans EP, Jongkees LB: On the prognosis of peripheral facial paralysis of endotemporal origin. Part II. Ann Otol Rhinol Laryngol 72:621, 1963. 6. Laumans EP, Jongkees LB: On the prognosis of peripheral facial paralysis of endotemporal origin. Part III. Ann Otol Rhinol Laryngol 72:894, 1963. 7. Jongkees LBW: Nerve excitability test. In Fisch U (ed.): Facial Nerve Surgery: Proceedings of the Third International Symposium on Facial Nerve Surgery, 9-12 August 1976, Zurich, Switzerland. Birmingham, AL, Aesculapius, 1977, p 83. 8. Yanagihara N, Kishimoto M: Electrodiagnosis in facial palsy. Arch Otolaryngol 95:376, 1972. 9. Alford BR, Sessions RB, Weber SC: Indications for surgical decompression of the facial nerve. Laryngoscope 81:620, 1971. 10. May M, Harvey JE, Marovitz WF, et al: The prognostic accuracy of the maximal stimulation test compared with that of the nerve excitability test in Bell’s palsy. Laryngoscope 81:931, 1971. 11. Esslen E: Electrodiagnosis of facial palsy. In Miehlke A (ed.): Surgery of the Facial Nerve. Philadelphia, WB Saunders, 1973, p 45 (Tr. of Die Chirurgie des Nervus Facialis). 12. Esslen E: The Acute Facial Palsies: Investigations on the Localization and Pathogenesis of Meato-labyrinthine Facial Palsies. New York, Springer-Verlag, 1977. 13. Lewis BI, Adour KK, Kahn JM, et al: Hilger facial nerve stimulator: A 25-year update. Laryngoscope 101:71, 1991. 14. May M: Nerve excitability test in facial palsy: Limitations in its use, based on a study of 130 cases. Laryngoscope 82:2122, 1972. 15. Adour KK: Who’s afraid of the facial nerve? In Lucente FE (ed.): Highlights of the Instructional Courses, vol. 8. St Louis, MosbyYear Book, 1995, p 249. 16. Joachims HZ, Bialik V, Eliachar I: Early diagnosis in Bell’s palsy: A nerve conduction study. Laryngoscope 90:1705, 1980. 17. Adour KK, Sheldon MI, Kahn ZM: Maximal nerve excitability testing versus neuromyography: Prognostic value in patients with facial paralysis. Laryngoscope 90:1540, 1980. 18. Sittel C, Guntinas-Lichius O, Streppel M, et al: Variability of repeated facial nerve electroneurography in healthy subjects. Laryngoscope 108:1177, 1998. 19. Smith IM, Murray JAM, Prescott RJ, et al: Facial electroneurography. Standardization of electrode position. Arch Otolaryngol Head Neck Surg 114:322, 1988. 20. Raslan WF, Wiet R, Zealear DL: A statistical study of ENoG test error. Laryngoscope 98:891, 1988. 21. Hughes GB, Josey AF, Glasscock ME III, et al: Clinical electroneurography: Statistical analysis of controlled measurements in twentytwo normal subjects. Laryngoscope 91:1834, 1981. 22. Hughes GB, Nodar RH, Williams GW: Analysis of test-retest variability in facial electroneurography. Otolaryngol Head Neck Surg 91:290, 1983. 23. May M, Klein SR, Blumenthal F: Evoked electromyography and idiopathic facial paralysis. Otolaryngol Head Neck Surg 91:678, 1983. 24. Adour KK: Facial nerve electrical testing. In Jackler KK, Brackmann DE (eds.): Neurotology. St. Louis, Mosby, 1994, p 1283. 25. Kartush JM, Lilly DJ, Kemink JL: Facial electroneurography: Clinical and experimental investigations. Otolaryngol Head Neck Surg 93:516, 1985. 26. Salzer TA, Coker NJ, Wang-Bennett LT: Stimulation variables in electroneurography of the facial nerve. Arch Otolaryngol Head Neck Surg 116:1036, 1990.

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27. Gantz BJ, Gmuer AA, Holliday M, et al: Electroneurographic evaluation of the facial nerve. Method and technical problems. Ann Otol Rhinol Laryngol 93:394, 1984. 28. Podvinec M: Facial nerve disorders: Anatomical, histological and clinical aspects. Adv Otorhinolaryngol 32:124, 1984. 29. Thomander L, Stålberg E: Electroneurography in the prognostication of Bell’s palsy. Acta Otolaryngol 92:221, 1981. 30. Alford BR, Jerger JF, Coats AC, et al: Neurophysiology of facial nerve testing. Arch Otolaryngol 97:214, 1973. 31. Seddon HJ: Three types of nerve injury. Brain 66:238, 1943. 32. Adour KK, Byl FM, Hilsinger RL Jr, et al: The true nature of Bell’s palsy: Analysis of 1000 consecutive patients. Laryngoscope 88:787, 1978. 33. Jonsson L: On the Etiology of Bell’s Palsy: Immunological and Magnetic Resonance Imaging Abnormalities. Uppsala, Sweden, Faculty of Medicine, University of Uppsala, 1987. 34. Hanner P: Evidence of CNS Impairment in Bell’s Palsy. Göteborg, Sweden, University of Göteborg, 1986. 35. Nakamura K, Yanagihara N: Neutralization antibody to herpes simplex virus type 1 in Bell’s palsy. Ann Otol Rhinol Laryngol 97:18, 1988. 36. Gilliatt RW, Taylor JC: Electrical changes following section of the facial nerve. Proc R Soc Med 52:1080, 1959. 37. Hilger JA: The nature of Bell’s palsy. Laryngoscope 59:228, 1949. 38. Jongkees LB: Bell’s palsy: A surgical emergency? Arch Otolaryngol 81:497, 1965. 39. Blunt MJ: The possible role of vascular changes in the aetiology of Bell’s palsy. J Laryngol Otol 70:701, 1956. 40. Kettel K: Bell’s palsy: Pathology and surgery: A report concerning fifty patients who were operated on after the method of Ballance and Duel. Arch Otolaryngol 46:427, 1947. 41. Denny-Brown D, Brenner C: Lesion in peripheral nerve resulting from compression by spring clip. Arch Neurol Psychiatr 52:1, 1944. 42. Denny-Brown D, Brenner C: Paralysis of nerve induced by direct pressure and by tourniquet. Arch Neurol Psychiatr 51:1, 1944. 43. Devriese PPEOM: Experiments on the facial nerve: A study of nerve action potentials in the cat. Amsterdam, North-Holland, 1972. 44. Roffman GD, Babin RW, Ryu JH: The effect of blood pressure on compression-induced facial nerve neuropraxia in the cat. Otolaryngol Head Neck Surg 89:629, 1981. 45. Adour KK, Swanson PJ Jr: Facial paralysis in 403 consecutive patients: Emphasis on treatment response in patients with Bell’s palsy. Trans Am Acad Ophthalmol Otolaryngol 75:1284, 1971. 46. Kraus P: Reliability of the nerve excitability test in Bell’s palsy. J Laryngol Otol 84:719, 1970. 47. Kerbavaz RJ, Hilsinger RL Jr, Adour KK: The facial paralysis prognostic index. Otolaryngol Head Neck Surg 91:284, 1983. 48. Fisch U: Maximal nerve excitability testing vs electroneuronography. Arch Otolaryngol 106:352, 1980. 49. Fisch U: Surgery for Bell’s palsy. Arch Otolarygol 107:1, 1981. 50. Marsh MA, Coker NJ: Surgical decompresssion of idiopathic facial palsy. Otolaryngol Clin North Am 24:675, 1991. 51. Hughes GB: Prognostic tests in acute facial palsy. Am J Otol 10:304, 1989. 52. Gavilán J, Gavilán C, Sarriá MJ: Facial electroneurography: Results on normal humans. J Laryngol Otol 99:1085, 1985. 53. Cramer HB, Kartush JM: Testing facial nerve function. Otolaryngol Clin North Am 24:555, 1991. 54. Rogers RL: Nerve conduction time in Bell’s palsy. Laryngoscope 88(2 Pt 1):314, 1978. 55. Kobayashi T, Kudo Y, Chow MJ: Nerve excitability test using fine needle electrodes. Acta Otolaryngol (Suppl) 446:64, 1988.

Chapter

74 Charles J. Limb, MD John K. Niparko, MD

The Acute Facial Palsies Outline Introduction Definition of Disorders Bell’s Palsy Herpes Zoster Oticus Incidence and Risk Factors Pathophysiology Clinical Observations Anatomic and Physiologic Studies Histopathologic Studies Etiology Viral Infection Bell’s Palsy Herpes Zoster Oticus Immunologic Injury Ischemia Summary: Pathophysiology and Etiology

Clinical Evaluation Differential Diagnosis Neoplasm Melkersson-Rosenthal Syndrome Lyme Disease Acute Otitis Media/Mastoiditis Chronic Otitis Media Necrotizing (Malignant) Otitis Externa Childhood Facial Palsy Radiologic Evaluation Prognostication with Facial Nerve Testing Sequelae and Natural History Facial Nerve Testing Topognostic Testing Electrophysiologic Testing

Nerve Excitability Testing Maximal Stimulation Test Electromyography Electroneuronography and Evoked Electromyography Transtympanic Stimulation Facial Nerve Assessment with Central Activation Treatment Glucocorticoids Pharmacology Steroid Treatment of Bell’s Palsy and Herpes Zoster Oticus Antiviral Therapy Nerve Decompression Nerve Grafting Conclusion

INTRODUCTION The patient with acute facial palsy suffers not only the functional consequences of impaired facial motion, but also the psychological impact of a skewed facial appearance. In fact, a 1991 poll revealed that the level of discomfort Americans felt upon meeting those with facial abnormalities was second only to that associated with interacting with the mentally ill, and it far exceeded anxiety about encountering the senile, mentally retarded, deaf, blind, and those confined to a wheelchair.1 Centuries of investigation of the facial nerve and its disorders have generated controversy, often lively, and not infrequently acrimonious. Although the work of Sir Charles Bell in the 1800s (Fig. 74-1) resolved many questions about patterns of facial innervation,2 Bell’s palsy, the disorder named for him, continues to generate substantial debate and study. Although recent studies have clarified our understanding of the etiology and pathogenesis of many facial nerve disorders, no clear consensus has yet emerged on many aspects of their evaluation and management. This chapter summarizes investigations of the acute facial palsies that provide the basis for our current understanding of these disorders. It also discusses newer data that have increased our insight into facial paralysis and have improved treatments for patients with acute facial 1230

Figure 74-1. Drawing by Charles Bell (1829) depicting distinct sources of facial motor and facial sensory innervation.

The Acute Facial Palsies

palsies. In particular, it addresses some of the controversies surrounding two common disorders of acute facial palsy— Bell’s palsy and herpes zoster oticus—that serve as models for understanding the acute facial neuropathies.

DEFINITION OF DISORDERS Table 74-1 lists the numerous disorders associated with unilateral facial palsies. Table 74-2 lists disorders associated

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with bilateral facial palsies. Bilateral facial palsy occurs in less than 2% of patients who present with acute facial nerve dysfunction3 and typically reflects a systemic disorder with multiple manifestations. Further information on the evaluation and management of these disorders is provided in comprehensive reports by Miehlke,4 Graham and House,5 Hughes,6 May and Schaitkin,7 Jackson,8 and Mattox.9 Facial movement is a dynamic, complex process with multiple components. Impairment of such motion has been very difficult to describe in a widely agreed-upon manner.

TABLE 74-1. Differential Diagnoses of Unilateral Facial Palsy Birth Molding Forceps delivery Myotonic dystrophy Moebius syndrome (facial diplegia associated with other cranial nerve deficits)

Trauma Cortical injuries Basilar skull fractures Brainstem injuries Penetrating injury to middle ear Facial injuries Altitude paralysis (barotrauma) Scuba diving (barotrauma)

Neurologic Opercular syndrome (cortical lesion in facial motor area) Millard-Gubler syndrome (abducens palsy with contralateral hemiplegia due to lesion in base of pons involving corticospinal tract)

Infection Malignant otitis externa Acute or chronic otitis media Cholesteatoma—acquired and congenital Mastoiditis Meningitis Parotitis Chickenpox Herpes zoster oticus (Ramsay Hunt syndrome) Encephalitis Poliomyelitis (type I) Mumps Mononucleosis Leprosy Human immunodeficiency virus and acquired immunodeficiency syndrome Influenza Coxsackie virus Malaria Syphilis Scleroma Tuberculosis Botulism Mucormycosis Lyme disease

Genetic and Metabolic Diabetes mellitus Hyperthyroidism Pregnancy Hypertension Alcoholic neuropathy Bulbopontine paralysis Oculopharyngeal muscular dystrophy

Vascular Anomalous sigmoid sinus Benign intracranial hypertension

Intratemporal aneurysm of internal carotid artery Embolization for epistaxis (external carotid artery branches)

Neoplastic Acoustic neuroma Glomus jugulare tumor Leukemia Meningioma Hemangioblastoma Hemangioma Pontine glioma Sarcoma Hydradenoma (external canal) Facial nerve neuroma Teratoma Fibrous dysplasia von Recklinghausen’s disease Carcinomatous encephalitis (Bannworth’s syndrome) Cholesterol granuloma Carcinoma (invasive or metastatic, from breast, kidney, lung, stomach, larynx, prostate, thyroid)

Toxic Thalidoide (Miehlke syndrome: cranial nerves VI and VII with atretic external ears) Tetanus Diphtheria Carbon monoxide Lead intoxication

Iatrogenic Mandibular block anesthesia Antitetanus serum Vaccine treatment for rabies Otologic, neurotologic, skull base, and parotid surgery Iontophoresis (local anesthesia) Embolization

Idiopathic Familial Bell’s palsy Melkersson-Rosenthal syndrome (recurrent facial palsy, furrowed tongue, faciolabial edema) Hereditary hypertrophic neuropathy (Charcot-Marie-Tooth disease, Dejerine-Sottas disease) Autoimmune syndromes of temporal arteritis, periarteritis nodosa, and other vasculitides Thrombotic thrombocytopenic purpura Landry-Guillain-Barré syndrome (ascending paralysis) Multiple sclerosis Myasthenia gravis Sarcoidosis (Heerfordt’s syndrome, uveoparotid fever) Wegener’s granulomatosis Eosinophilic granuloma Amyloidosis Hyperostoses (Paget’s disease, osteopetrosis, etc.) Kawasaki’s disease (infantile acute febrile mucocutaneous lymph node syndrome)

After May M: Differential diagnosis by history, physical findings and laboratory results. In May M (Ed.): The Facial Nerve. New York, Thieme-Stratton, 1986.

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TABLE 74-2. Etiologies Associated with Bilateral Facial Palsies (may be concurrent or delayed) Bell’s palsy Diabetes mellitus Sarcoidosis (Heerfordt’s syndrome) Periarteritis nodosa Guillian-Barré syndrome Myasthenia gravis Basilar skull fracture Bulbar palsies Porphyias Leukemia Myotonic dystrophia Meningitis Mobius syndrome Botulism Infectious mononucleosis Leprosy Malaria Poliomyelitis Lyme disease Syphilis Postvaccination neuropathy Isoniazid Osteopetrosis

House,10 May,11 Burres and Fisch,12 Yanagihara,13 and Smith and colleagues14 have provided insights into classification schemes to describe facial movement. The difficulty lies in translating facial impairment into a classification that is continuous and thereby facilitates precise assessment and comparison of functional recovery. Intermediate levels of recovery are particularly difficult to classify with consistent agreement among observers. Although simplicity in the classification enhances acceptance, subtle differences in the quality of the outcome are less likely to be differentiated. Presently, the grading system proposed by House and Brackmann15 has been adopted by the American Academy of Otolaryngology-Head and Neck Surgery and continues to find the greatest acceptance among American otolaryngologists (Table 74-3). One of the important features of the House-Brackmann grading scale is its use of eye closure as an indicator of severity. In cases of facial palsy that hinder complete eye closure via motor impairment or

diminish lacrimation via autonomic disruption, the eye is at risk for exposure keratitis. Injury to the eye can range from mild dryness, which responds to topical lubricant (Fig. 74-2A and B), to exposure keratitis, which can eventually lead to corneal opacification, if left untreated (Fig. 74-3). The risk of exposure keratitis is greater if deficits occur in any or all of cranial nerves III through VI ipsilateral to the facial palsy. Cases of incomplete eye closure should be treated with a moisture chamber, which seals the eye, and topical lubricating ointments. If prolonged impairment is expected, gold weight placement in the upper eyelid should be considered, with or without a lid procedure (tarsal strip or tarsorrhaphy).

Bell’s Palsy No cause can be found for approximately 60% to 75% of acute facial palsies.16,17 The clinical diagnosis of Bell’s palsy is appropriately applied to such cases. Bell’s palsy is an acute, unilateral paresis or paralysis of the face, in a pattern consistent with peripheral nerve dysfunction. Typically, its onset and evolution are rapid (<48 hours) and may associated with acute neuropathies affecting other cranial nerves.18 Pain or numbness affecting the ear, mid-face, and tongue, as well as taste disturbances are common. Recurrence of Bell’s palsy occurs in 7.1%19 to 12%16 of patients. Pitts and colleagues19 found ipsilateral recurrences to be as common as contralateral involvement. Recurrences were more likely in patients with a family history of Bell’s palsy. The incidence of diabetes mellitus in recurrent Bell’s palsy patients was 2.5-fold higher than that noted in nonrecurrent cases. Progressive dysfunction was not seen in this series but has been suggested in others.20–22

Herpes Zoster Oticus Herpes zoster oticus is a syndrome of acute otalgia with varicelliform lesions.23 When the facial nerve is involved, the constellation of findings is referred to as Ramsay-Hunt syndrome.24 Ramsay-Hunt syndrome accounts for approximately 10% to 15% of acute facial palsy cases. The lesions may involve the external ear, the ear canal, or the soft palate

TABLE 74-3. House-Brackmann System of Grading Facial Nerve Recovery GRADE I: GRADE II:

GRADE III:

GRADE IV: GRADE V: GRADE VI:

NORMAL Normal facial function in all areas. MILD DYSFUNCTION Gross: Slight weakness noticeable on close inspection. May have slight synkinesis. At rest, normal symmetry and tone. Motion: Forehead, moderate-to-good function. Eye, complete closure with minimal effort. Mouth, slight asymmetry. MODERATE DYSFUNCTION Gross: Obvious but not disfiguring difference between two sides. Noticeable but not severe synkinesis, contracture or hemifacial spasm, or both. At rest, normal symmetry and tone. Motion: Forehead, slight-to-moderate movement. Eye, complete closure with effort. Mouth, slightly weak with maximum effort. MODERATELY SEVERE DYSFUNCTION Gross: Obvious weakness or disfiguring asymmetry, or both. At rest, normal symmetry and tone. Motion: Forehead, none. Eye, incomplete closure. Mouth, asymmetric with maximum effort. SEVERE DYSFUNCTION Gross: Barely perceptible motion. At rest, asymmetry. Motion: Forehead, none. Eye, incomplete closure. Mouth, slight movement. TOTAL PARALYSIS No movement.

From House JW, Brackmann DE: Facial nerve grading system. Otolaryngol Head Neck Surg 93:146–147, 1985.

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A

Figure 74-4. Skin lesion of the external meatus in a patient with herpes zoster oticus in crusting phase.

B Figure 74-2. A, Patient with superficial corneal irritation of the right eye following mild facial nerve palsy with decreased lacrimation. B, Same patient with healed, nonirritated right cornea after topical lubricant therapy.

and are necessary to establish the diagnosis (Fig. 74-4). Hearing loss, dysacusis, and vertigo reflect extension of the infection to involve the eighth nerve. Cranial nerves (V, IX, and X) and cervical branches (C2, C3, and C4) that have anastomotic communications with the facial nerve may be involved as well. Ramsay-Hunt syndrome is therefore differentiated from Bell’s palsy by the characteristic cutaneous changes and a higher incidence of cochleosaccular dysfunction.25–27

INCIDENCE AND RISK FACTORS

Figure 74-3. Exposure keratitis and corneal opacification (leukomalformation) resulting from long-standing corneal exposure due to facial palsy.

Assessment of the true incidence of Bell’s palsy is complicated by the wide distribution of specialties involved in its management. Nonetheless, this disorder is recognized as a very common neuropathy and appears to be universal in its occurrence. Surveys by Hauser and colleagues,28 Peitersen,29 and Adour and colleagues30 reveal yearly incidence figures of 15 to 40 per 100,000 individuals in the general population. These studies suggest that age and sex influence the likelihood of contracting Bell’s palsy. Bell’s palsy is infrequent in patients younger than 10 years but thereafter increases in incidence with age.30 Females in their teens and twenties carry a predilection for the

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disorder. Among middle-aged adults, there is a nearly equal distribution by sex with a slight male predominance in older age groups. Epidemiologic surveys indicate seasonal variation in incidence in some geographic regions.28,31–33 The risk posed by diabetes mellitus in developing Bell’s palsy remains undetermined, although most studies suggest heightened susceptibility. Korczyn34 reported that 14% of patients with Bell’s palsy were insulin-requiring diabetics. Furthermore, 66% of all patients demonstrated abnormalities in glucose tolerance testing. Alford and Sessions35 noted an association with diabetes mellitus in 21%, and Yasuda and colleagues36 in 38% of Bell’s palsy patients. In contrast, Aminoff and Miller37 and Abraham-Inpijn and Devriese38 found the incidence of abnormal glucose tolerance among Bell’s palsy patients to approximate that of the general population. Yanagihara39 found an 11.2% association rate between diabetes mellitus and Bell’s palsy in patients older than 40 years and that the rate of diabetes in patients with Bell’s palsy was greater than that in the general population. Several authors have demonstrated a correlation between pregnancy and acute facial palsy. Hilsinger and colleagues40 found the incidence of Bell’s palsy in pregnant women to be more than three times greater than in nonpregnant women. These data were confirmed more recently by Cohen and colleagues,41 who found that pregnant women were 3.3 times more likely to have Bell’s Palsy than nonpregnant women. Hilsinger and colleagues,40 Korczyn,34 and Falco and Eriksson42 demonstrated a substantially greater risk of developing Bell’s palsy during the third trimester. Preeclampsia heightens this risk. Preeclampsia was six times more prevalent among women with pregnancyassociated facial palsy than in the general population of gravid woman.42 Recent clinical observations suggest that immunodeficiency confers a risk of acute facial palsy.43,44 Cranial neuropathies, including facial palsy, have been observed in patients infected with human immunodeficiency virus (HIV), often in association with a symmetrical polyneuropathy. Facial nerve dysfunction may reflect direct invasion of the facial nerve as the HIV has demonstrated neurotropism and can be isolated from central and peripheral nerve tissue.45 Facial dysfunction in this setting may also reflect susceptibility to other infectious agents and the development of a lymphoma. Neuropathies may appear at any stage of HIV infection: early after initial infection, as part of the chronic illness characterized by the acquired immunodeficiency syndrome (AIDS), or with AIDS-related meningitis. Facial palsy may occur in a clinical course characteristic of Bell’s palsy43 or herpes zoster oticus.46 Murr and Benecke47 reported a case in which facial paralysis was the initial presenting symptom that eventually led to a diagnosis of HIV positivity. Initial case series suggest that facial palsy in the setting of HIV infection not associated with neoplasm demonstrates patterns of spontaneous recovery that are not unlike those of the general population. Facial palsy associated with the conditions just noted is not necessarily diagnostic of Bell’s palsy.48 These patients should be evaluated as completely as those who do not carry these risk factors.

PATHOPHYSIOLOGY Clinical Observations Theories on the pathophysiology of Bell’s palsy and herpes zoster oticus are based on clinical observations correlated with anatomic and histopathologic findings.49 Dysesthesias in periauricular areas preceding facial motor dysfunction in Bell’s palsy suggest that the pathologic process begins in the sensory component of the facial nerve and then extends to block conduction within the facial motor fibers.50 In support of this pathologic sequence, May found topognostic evidence of an ascending dysfunction of the facial nerve, beginning with involvement of the chorda tympani nerve and the greater superficial petrosal nerve before facial motor impairment. Adour and colleagues30 detected often subtle but frequent dysfunction of cranial nerves V, VIII, IX, and X in association with Bell’s palsy. These observations suggest that an inflammatory process may manifest Bell’s palsy as the facialmotor component of a cranial polyneuropathy. These authors suggest a pathologic sequence induced by viral agents admitted through mucosal membranes.

Anatomic and Physiologic Studies Studies of the intratemporal facial nerve suggest that Bell’s palsy and herpes zoster oticus most commonly result from impaired facial nerve conduction within the temporal bone. The facial nerve enters the temporal bone via the meatal foramen to form the labyrinthine segment of the intratemporal nerve. In the labyrinthine segment the nerve occupies more than 80% of the cross-sectional area of the surrounding facial canal between the meatal foramen and geniculate fossa.51,52 In contrast, the nerve occupies less than 75% of the facial canal lumen as it courses peripherally through the larger tympanic and vertical segments of the canal (Fig. 74-5). The size and configuration of the meatal foramen suggest an explanation for heightened susceptibility to neural injury in this region. The meatal foramen is formed by a confluence of the vertical and horizontal crests of the lateral internal auditory canal with dense periotic bone. Fisch52 determined the mean diameter of the meatal foramen to be 0.68 mm (see Fig. 74-3), substantially narrower than more peripheral segments of the facial canal. Fisch52 and Proctor and Nager53 also demonstrated a circumferential band of periostem that virtually seals the entry site and constricts the nerve at the meatal foramen (Fig. 74-6). The facial nerve is without substantial epineurium in the meatal foramen and is instead ensheathed by this periosteum. Based on its anatomic characteristics, the meatal foramen appears to constitute a pressure transition zone or “physiologic bottleneck” in the presence of neural edema. Eicher and colleagues54 demonstrated that the ratio of the cross-section areas of the nerve to the meatal foramen was significantly smaller in pediatric temporal bones than those in adults. This finding provides a possible explanation for the low frequency of Bell’s palsy in childhood populations. Electrophysiologic evaluation of the facial nerve in Bell’s palsy with intraoperative stimulation was initially provided

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by Fisch and Esslen55 and duplicated in reports by Gantz and colleagues56 and Niparko and colleagues57 (Fig. 74-7). In patients with near-total degeneration who underwent facial nerve decompression for Bell’s paralysis, electrical stimulation demonstrated a transition in responsiveness in the (decompressed) region of the meatal foramen. Sequential stimulation in a distal-to-proximal direction from the second genu to the meatal foramen consistently revealed substantially diminished responses proximal to the meatal foramen. These observations further implicate the meatal foramen as a pathophysiologic transition zone.

Histopathologic Studies

Figure 74-5. Caliber of the (intratemporal) facial canal from meatal foramen to mastoid segment.

In separate reports, Proctor and colleagues58 and McKeever and colleagues59 reported intraneural inflammatory changes in the temporal bone of a Bell’s palsy patient who died 13 days after onset. These changes seemed consistent with viral infection. Substantial leukocytic infiltration and demyelinization of the somatic portion of the facial nerve were evident, most prominently in the proximal, intratemporal segment of the nerve. Although small vessel congestion was present, there was no evidence of arterial thrombosis. In contrast, a histopathologic case study of Bell’s palsy by Fowler60 failed to demonstrate inflammatory changes. Instead, intraneural vascular congestion and hemorrhage in the labyrinthine segment of the nerve were most prominent.

Figure 74-6. Surgical anatomy of the meatal foramen, labyrinthine segment, and geniculate fossa. (After Fisch U: Surgery for Bell’s palsy. Arch Otolaryngol 107:1–11, 1981.)

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a temporal bone specimen from a patient who demonstrated clinical and electrical evidence of severe nerve degeneration subsequent to an acute facial paralysis consistent with herpes zoster oticus. Detailed microscopic evaluation of the meatal foramen demonstrated a sharp line of demarcation between degenerated nerve distal to and normal nerve proximal to the meatal foramen.

ETIOLOGY Although Bell’s palsy has generally been defined clinically as an idiopathic disorder, recent studies have pointed strongly toward a viral etiology. Work by Murakami and colleagues63 and Burgess and colleagues64 have suggested that herpes simplex virus plays a critical role. Immunologic mechanisms and vascular etiologies have also been implicated in the development of Bell’s palsy. Mulkens and colleagues,65 Jackson,8 May,25 and Yanagihara39 have provided noteworthy summaries of the broad spectrum of suspect etiologies underlying the disorder.

Viral Infection A

B Figure 74-7. A and B, Electrically evoked responses obtained after decompression of the meatal foramen in a patient with Bell’s paralysis and greater than 90% reduction on preoperative EEMG. P, pregeniculate (proximal) site of stimulation. D, distal site of stimulation at the tympanic segment of the facial nerve. Responses of reduced amplitude to pregeniculate stimulation suggest the lesion is in the labyrinthine segment of the facial nerve.

Liston and Kleid61 evaluated the histopathology of a case of Bell’s palsy and 18 other reports of postmortem studies of patients with Bell’s palsy, including those cited previously. Although the site(s) and pattern of pathologic changes varied among cases, diffuse involvement of the facial nerve in its intratemporal course was typical. Evidence of an inflammatory neuritis suggesting a viral etiology was most consistently found, though it was not uniformly observed. The authors attributed this disparity to the fact that as a clinical diagnosis, Bell’s palsy does not necessarily describe facial neuropathy from a single cause. Further implicating the meatal foramen as a critical site for nerve injury in herpes zoster oticus are the neuropathologic findings of Jackson and colleagues.62 They obtained

Bell’s Palsy Jackson8 described the resemblance between Bell’s palsy and other neuropathies known to be of viral origin. Poliomyelitis, mumps, Epstein-Barr, and rubella infections can manifest a neuritic component characterized by progressive neural dysfunction, often with subtotal regeneration as seen with Bell’s palsy and herpes zoster oticus. Evidence for a viral etiology in Bell’s palsy is based on clinical observations and experimental models reported over the past 20 years.25,66,67 Kumagami68 found impaired facial nerve conduction and neuropathic change following inoculation of the rabbit nerve trunk with herpes simplex (HS) virus via the stylomastoid foramen. Animal subjects that demonstrated facial motor dysfunction developed paresis that progressed to paralysis within 1 week of inoculation. Circumstantial evidence for an etiologic role played by the herpes simplex virus type 1 has been provided by Djupesland and colleagues,69 who successfully isolated the HS virus from the nasopharynx of two patients during the acute phase of Bell’s palsy. Mulkens and colleagues65 detected HS virus in epineurial biopsies from a patient undergoing facial nerve decompression for Bell’s paralysis. Vhalne and colleagues,70 using complement fixation and immunoassay methods, revealed a higher prevalence of HS viral antibodies in patients with Bell’s palsy than in sex- and age-matched subjects. In a prospective study of 14 patients with Bell’s palsy and 9 patients with Ramsay-Hunt syndrome, Murakami and colleagues63 were able to detect HS virus type I DNA in 79% of patients with Bell’s palsy but in no controls. This study was performed using PCR analysis of facial nerve endoneurial fluid and postauricular muscle. The authors concluded that HS type 1 is the major etiologic agent in Bell’s palsy. HS virus is known to have a predilection for sensory neurons and to exist in a latent phase in sensory cell bodies of the ganglion. Nonspecific factors related to

The Acute Facial Palsies

stress and immunosuppression are thought to reactivate intracellular replication by the virus,71,72 thereby producing a clinical neuritis. The facial nerve contains sensory neurons with cell bodies in the geniculate ganglion. Gussen73 has suggested that infection of the facial nerve as a geniculate ganglionitis underlies Bell’s palsy. Burgess and colleagues64 successfully amplified herpes simplex viral DNA from the geniculate ganglion of a patient who died 6 days after developing Bell’s palsy, lending further support to this notion. Although the data strongly link Bell’s palsy to HS viral infection, causality is much more difficult to establish conclusively. Ultrastructural studies of autopsy material from asymptomatic patients have demonstrated HS viral particles in sensory ganglia of regional cranial nerves, most notably the trigeminal ganglion.74 Thus, although evidence of viral presence in the facial nerve is highly suggestive, it does not conclusively prove that the HS virus plays a causative role. Herpes Zoster Oticus The etiologic role of the varicella-zoster (VZ) virus in herpes zoster oticus is supported by the characteristic varicelliform rash that assumes the dermatomal distribution of afferent fibers of the facial nerve. Serologic confirmation of VZ infection is often but not always possible.75,76 Histologic studies by Atkins and Bruin,77 Tomita and colleagues,78 Findlay,79 and Jackson and colleagues62 indicate facial dysfunction with herpes zoster oticus to be the result of an entrapment neuropathy, with greater degrees of nerve fiber degeneration than that typically found in histopathologic studies of Bell’s palsy. Molecular biological techniques have allowed the establishment of more conclusive evidence supporting the role of VZ in herpes zoster oticus. In an important study by Murakami and colleagues,80 investigators were able to identify VZ viral DNA from auricular lesions, oral lesions, facial nerve sheath, middle ear mucosal, and cerebrospinal fluid of patients with clinical herpes zoster oticus. More recently, Furuta and colleagues81 have quantified the time course of changes VZ copy number in salivary specimens in patients with herpes zoster oticus, noting that the viral load peaks with the appearance of zoster lesions rather than the onset of facial palsy symptoms. The HS and VZ agents are both DNA viruses of the herpesvirus group and have only subtle differences in their ultrastructural features. Despite similarities, these viruses appear to play different etiologic roles in Bell’s palsy and herpes zoster oticus. In the study by Murakami and colleagues63 that confirmed a strong link between HS type I and Bell’s palsy, they also showed that HS type I was not present in patients with herpes zoster oticus. To further complicate the matter, infections from HS and VZ viruses may mimic one another.25 HS, mumps, and cytome-galovirus infections may produce a clinical picture that resembles herpes zoster oticus76 and VZ neuritis may occur in the absence of a rash—zoster sine eruptione82,83 or zoster sine herpete.81 Clinical manifestations of HS and VZ viral infections may evolve in a pattern such that these viruses remain indistinguishable in their clinical presentation.

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Immunologic Injury Several older studies have implicated immunologic injury as a possible cofactor in Bell’s palsy. Neuropathologic findings of segmental demyelinization accompanied by lymphocytic infiltration of the perineurium25 support this etiology. McGovern and colleagues84 found that cromolyn sodium, a mast cell degranulation inhibitor, prevented the neuropathic changes induced by horse serum injection of the perineurial space of the facial nerve. Mast cell degranulation may therefore contribute to the pathologic sequence. Giannoni and Corbacelli,85 using immunoassay methods, detected acute-phase antibodies within the chorda tympani nerve from three of seven patients with Bell’s palsy. Immune complexes found in the chorda tympani nerve fibers were characteristic of viral-antibody (type III) immunologic reaction, suggesting an immune injury triggered by viral antigens. Autoimmune mechanisms of nerve injury have also been suggested. Evidence for humoral86 and cellular87 autoimmunity has been reported. In contrast, Bujia and colleagues88 examined serum levels of soluble interleukin-2 receptors, which reflect T lymphocyte activation, in patients with Bell’s palsy and age- and sex-matched controls, and found no difference in serum levels. They concluded that T-cell activation was not a prominent feature in Bell’s palsy.

Ischemia The most time-honored theory of the genesis of Bell’s palsy holds that impaired neural conduction follows disturbances in microcirculation. The facial nerve derives its extrinsic, circumneural blood supply from three principal sources: the labyrinthine artery proximally, middle meningeal artery centrally, and the stylomastoid artery distally. The circumneural system distributes to an intrinsic vascular supply in the perineurial compartment. The pathologic process is thought to involve primarily the intrinsic system of vessels. Calcaterra and colleagues89 reported two cases of total unilateral facial paralysis that resulted from experimental embolization of the middle meningeal artery. This outcome suggested that ischemia of the horizontal portion of the facial nerve might be responsible for facial paralysis. Sunderland90 suggested that pressure elevations in the intraneural compartments can lead to venous stasis, stagnation of capillary flow and a cycle of further edema, and elevation in intraneural pressure. This pathologic cycle may produce progressive circulatory sludging and ultimately acidosis and anoxia. The mechanism by which the cascade of primary ischemia is initiated remains unclear. Although biochemical (serotonin/tyramine)-vascular interactions are thought to initiate vasoconstriction to produce the class of CNS disorders classified as migraine-related,91 vasospasm resulting in prolonged neuropathy is highly unusual.92,93 In a study of Bell’s palsy complicated by diabetes, facial paralysis was found to have accelerated recovery when treated with lipoprostaglandin E1.94 The effect of this therapy was found to be comparable to that of high-dose steroid therapy. These findings support the idea that impaired microcirculation with resultant ischemia may contribute in an essential manner to the pathophysiology of Bell’s palsy.

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Summary: Pathophysiology and Etiology Postulated mechanisms of nerve injury underlying Bell’s palsy are not necessarily distinct processes. Rather, they may be sequential and synergistic in mediating the pathologic process. Gates and Mikiten,93 Liston and Kleid,61 and Hughes95 have suggested that the disease represents a spectrum of entities with varied pathogeneses. Although inflammation and ischemia (regardless of etiology) appear to dominate the early events in Bell’s palsy, neural blockade and degeneration and subsequent fibroblastic response assume major importance later in the sequence. Given the confinement of the nerve trunk within the meatal foramen, it is likely that compression at this site is a critical event in the genesis of Bell’s palsy and is triggered by one or more of the discussed etiologies. Histopathologic findings suggest that the facial palsy component of herpes zoster oticus is manifest by a similar process of entrapment, with typically greater degeneration of nerve fibers.

CLINICAL EVALUATION Differential Diagnosis

bacterial infection, perinatal factors, and neoplastic involvement of the nerve.16 An acute facial palsy as a result of trauma or infection often presents with characteristic findings that readily point to a diagnosis. In contrast, differentiating neoplastic involvement of the facial nerve from Bell’s palsy frequently poses a dilemma. Several other disorders should be considered in the clinical evaluation of an acute facial palsy. Neoplasm Table 74-1 includes a list of the neoplasms that may produce a facial palsy. Jackson and colleagues96 noted the incidence of sudden facial palsy in 27% of patients who had neoplastic involvement of the nerve—a surprisingly high incidence given the slow growth and encapsulation of most tumors responsible for the palsy. Fisch and Ruttner97 and Neely and Alford98 have reported a similar incidence of acute facial palsy in patients with neoplastic etiologies. Although Bell’s palsy may present with variable symptoms, atypical presentations warrant consideration of other etiologies, particularly neoplasms. A facial palsy produced by a neoplasm may differ only subtly from Bell’s palsy. The following historical and clinical features suggest that a neoplasm is responsible for a facial palsy8,16,99: 1. Progression of a facial palsy over 3 weeks or longer 2. No return of facial function within 3 to 6 months of onset of the paralysis 3. Failure to resolve an incomplete paresis within 2 months 4. Facial hyperkinesia, particularly hemifacial spasm, antecedent to the palsy 5. Associated dysfunction of regional cranial nerves (Fig. 74-8)

The diagnosis of Bell’s palsy is applied to cases of acute peripheral palsy only after the exclusion of traumatic, neoplastic, infectious, metabolic, and congenital etiologies. Strict attention to the evaluation, particularly the history and otoscopic and neurologic findings, may differentiate an acute facial palsy from a true Bell’s palsy. Next to Bell’s palsy, the most common causes of acute, peripheral facial paralysis are trauma, herpes zoster oticus,

A

B

Figure 74-8. Right facial palsy in a neonate with medulloblastoma of caudal brain stem. Note right esotropia indicating right abducens palsy combined with right facial paralysis. A, Face at rest. B, Asymmetric crying facies.

The Acute Facial Palsies

6. Prolonged otalgia or facial pain 7. A mass in the middle ear, external ear canal, digastric region, or parotid gland 8. Recurrent ipsilateral palsy

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parotid pathology. Rhee and colleagues101 reported an interesting case of recurrent facial palsy as a manifestation of leukemic infiltration of the parotid gland. Metastatic disease may also be responsible for facial palsy. Low102 described facial paralysis resulting from metastatic nasopharyngeal carcinoma at three sites: cerebellopontine angle, middle ear, and parotid gland.

Although Bell’s palsy may recur, most authors agree that a recurrent palsy indicates the need for an exhaustive search with radiologic evaluation for tumor. A contrasting perspective was provided by Pitts and colleagues,19 who evaluated 62 patients with recurrent facial palsy and detected no facial nerve neuromas. It should be noted, however, that 62 other patients with recurrence in this study were lost to follow-up or died and magnetic resonance evaluation was not performed. May and colleagues100 surgically demonstrated a neoplasm (most frequently a facial neuroma) in 9% of patients with recurrent facial palsy. As noted by Jackson and colleagues,96 delayed or failed diagnosis of a neoplasm carries potential consequences of extension into the labyrinth and cranial fossae, as well as diminished opportunity for effective reanimation. Facial paralysis may result from neoplastic processes that are not confined to the temporal bone, such as in

Melkersson-Rosenthal Syndrome The Melkersson-Rosenthal syndrome is characterized by unilateral facial motor dysfunction, episodic or progressive facial edema, and lingua plicata (scrotal tongue).103–105 The syndrome is usually sporadic, although familial occurrence has been described. The syndrome is variable in its expression, with many patients showing oligosymptomatic (2 of 3 symptoms) forms of the syndrome.106 Lingua plicata is most likely to occur early in life; facial edema generally occurs after the initial episode of facial weakness. Later, facial dysfunction may be heralded by the onset of a facial swelling, but more typically it precedes the swelling by months or years (Fig. 74-9).

B

A

C Figure 74-9. A, Eight-year-old girl during initial episode of right facial paralysis associated with lower facial and lip swelling. This patient experienced three subsequent episodes of right facial paralysis with swelling on a yearly basis. At age 12, she underwent facial nerve decompression via a middle cranial fossa approach. No subsequent episodes of facial palsy were noted in the ensuing 5 years. B, Patient at age 17, demonstrating full facial movement. C, Patient demonstrates synkinetic eye closure with lip movement.

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The pathophysiologic basis for the Melkersson-Rosenthal syndrome is unknown.104 Granulomatous changes have been evident in biopsies of edematous orofacial tissues. However, such inflammatory changes appear to be present only in long-standing cases and a purely inflammatory basis for the syndrome is doubtful.104 The syndrome is assumed to reflect autonomic dysfunction manifesting vasomotor instability. The association of the Melkersson-Rosenthal syndrome with migraine headaches and megacolon support this pathophysiologic mechanism. Episodes of facial paresis or paralysis typically begin in childhood or adolescence. Swelling of the lips and palatal mucosa assumes a reddish-brown appearance and may be dramatic. Swelling often extends to the cheeks, eyelids, nose, and chin. As facial edema recurs, the course is often that of progressive disfigurement. Facial weakness assumes a peripheral distribution and can be differentiated from Bell’s palsy only when other manifestations of the syndrome are apparent or noted in the history. Although a relapsing course is usual, good to excellent recovery is typical. However, cases of progressive dysfunction have been described.21,107 The treatment of facial palsy associated with the Melkersson-Rosenthal syndrome is empiric. Antiinflammatory (steroid) and antibiotic therapy have been employed.108 Reports of surgical decompression of the meatal and labyrinthine segments21,22,103 suggest benefit in preventing recurrence of the palsy. A case study that suggests benefit with surgery is illustrated in Figure 74-9. Lyme Disease The occurrence of acute facial palsy in association with Lyme disease is now well recognized.109 Lyme disease is a multisystemic illness caused by the tick-borne spirochete Borrelia burgdorferi.110 After a 1- to 4-week incubation period following the tick bite, skin lesions develop in about 50% of infected individuals in association with flulike symptoms. About 38% of infected patients can recall a tick bite. Weeks to months after the initial infection, cardiac and neurologic manifestations, including ipsilateral or bilateral facial palsy, may appear. Arthritic involvement may follow. If Lyme disease is suspected, serologic testing with enzyme-linked immunosorbent assay (ELISA) to detect IgG and IgM antibody to the spirochete is advised. Åsbrink111 and Jonsson and colleagues86 found serologic evidence of Lyme disease in approximately 20% of patients diagnosed with Bell’s palsy. Unilateral or bilateral facial palsy may occur in up to 11% of Lyme disease patients.112 The ratio of unilateral to bilateral involvement is 3:1. Although the majority of patients with Lyme-associated facial palsy note an antecedent rash, the palsy may occasionally be the presenting sign of the illness. The interval between the onset of the rash and facial palsy is less than 2 months. Facial palsy may occur in association with other neurologic deficits produced by meningoencephalitis and radiculoneuritis. In a recent 10- to 20-year follow-up study of patients with Lyme disease, Kalish and colleagues113 noted that patients with facial palsy as a part of their illness often had more widespread involvement of the nervous system, with residual facial paralysis or peripheral nerve deficits. Early antibiotic treatment is thought to enhance symptomatic improvement and prevent long-term sequelae.

A 3-week course of doxycycline (for adults), amoxicillin (for children), or cefuroxime axetil (for penicillin-allergic children)114 is recommended. Tetracycline, penicillin, and erythromycin have been used in the past as effective alternatives. Adequate antibiosis provides high rates of recovery of facial function. Clark and colleagues112 found only a single case of significant residual dysfunction, and mild residual impairment in 13% of patients treated with antibiotics. Residual dysfunction was more likely in patients with bilateral involvement. Kalish and colleagues113 found that patients with long-term neurologic abnormalities or residual facial paralysis had not received antibiotic therapy for Lyme disease. Acute Otitis Media/Mastoiditis Facial palsy due to acute suppurative otitis media (ASOM) is typically seen in children who present with toxicity and otoscopic findings of middle ear empyema. The palsy is often progressive over a 2- to 3-day interval.115 A recent episode of otitis media, in some cases partially treated, may be evident. Radiographic evaluation of the temporal bone may rarely disclose coalescence of infection in the mastoid in cases of prolonged palsy. More typically, ASOMassociated facial palsy is the result of a toxic neuritis and can be adequately treated with wide myringotomy and systemic antibiotics.116,117 Cortical mastoidectomy is required when antibiotics and myringotomy fail to render the patient afebrile after 24 hours or when facial paralysis persists beyond 1 week. Formal nerve decompression is unnecessary except in cases of prolonged dysfunction. In a review of 100 cases of intratemporal complications following ASOM by Goldstein and colleagues,116 82% of patients presenting with facial palsy were treated with antibiotic therapy, and only 18% required mastoidectomy. Chronic Otitis Media Chronic suppurative otitis media (CSOM) can lead to the development of cholesteatoma or severe mucosal inflammation (and resultant granulation tissue), which may produce facial palsy. Facial nerve dysfunction in the setting of CSOM usually reflects a toxic neuritis, external compression, or intraneural compression from edema or abscess. In cases of CSOM-induced facial palsy the middle ear and mastoid should be addressed surgically as soon as possible. Surgical removal of irreversible disease and decompression of the nerve without slitting the sheath is advised. Jackson8 has reviewed the controversies regarding management of the facial nerve in palsy associated with CSOM. Long-standing paralysis (but less than 2 years duration) requires sectioning of attenuated tympanic or mastoid segments of the nerve followed by grafting. Left untreated, CSOM can lead to significant intracranial and extracranial complications, ultimately leading to the development of meningitis and/or brain abscess, which are the most common cause of mortality associated with CSOM.118 Necrotizing (Malignant) Otitis Externa External auditory canal and temporal bone infection with Pseudomonas aeruginosa occurs in patients with diabetes

The Acute Facial Palsies

mellitus or other immunocompromising disorders.119 Necrotizing otitis externa has also been reported with staphylococcal infection, fungal infection, and as a result of immunosuppression following transplantation.120–123 Presenting symptoms typically include progressive otalgia and otorrhea. The pathognomonic sign of this infection is otoscopic evidence of a breach of the external canal skin at the bony-cartilaginous junction that is filled with granulation tissue. Associated facial palsy suggests infralabyrinthine skull base extension along vascular channels and is an ominous sign.124 Treatment requires appropriately directed antibiotics administered urgently and maintained for long durations in conjunction with aggressive debridement of granulation tissue in the ear canal. Operative debridement of the tympanic bone, mastoid, and skull base is necessary when medical treatment fails to produce symptomatic improvement. In the immunocompromised host, more aggressive and earlier surgical treatment is often warranted. Childhood Facial Palsy The onset of facial palsy in childhood is frequently obscured by the excellent tone of aponeurotic tissues and skin in children and the resultant tonic suspension of central and lower portions of the face. Consequently, childhood facial nerve disorders are often referred to as “asymmetric crying facies.” Although Bell’s palsy is the most common etiology for childhood facial palsies, it accounts for a substantially smaller proportion of palsies than in adults.125 A clinically or radiographically identifiable etiology can be found in 20% of adult palsies initially diagnosed as Bell’s palsy,126 whereas this incidence may reach as high as 72% in childhood palsies.127 May and colleagues128 found facial palsies occurring in patients younger than 18 years were most likely due to Bell’s palsy (42%) and trauma (21%), although infection (13%), congenital causes (8%), and neoplasms (2%) accounted for larger proportions than in adults. Therefore, the diagnostic approach to a child with facial palsy should be adjusted accordingly, with a higher suspicion for an identifiable cause. Perinatal Facial Palsy Resulting from Trauma Trauma to the facial nerve may occur in the uterus as a result of compression by the maternal sacrum or in association with prolonged labor, shoulder dystocia, or forceps delivery. A review by Perlow and colleagues129 estimates the incidence of perinatal facial palsy to be 0.6 per 1000 live births. Smith and colleagues14 reviewed the etiologic basis for facial palsy in 95 newborns and found an acquired (traumatic) etiology in 74 (78%). A traumatic etiology is suggested by signs of periauricular injury and findings from electrical (evoked or spontaneous) electromyography. The absence of an overlying mastoid tip in children places the vertical segment of the facial nerve at risk for injury by either mechanism. A traumatic etiology is suggested by hemotympanum, periauricular ecchymosis, and progressive decline of facial nerve responsiveness to an applied stimulus. Temporal bone studies of neonates with facial palsy reveal aberrant facial nerve anatomy in a pattern consistent with trauma-induced necrosis of the nerve.130 Electromyographic evidence of preserved or

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declining neuromuscular activity is most diagnostic.131 In the absence of such activity, muscle biopsy may be required to determine whether a congenital palsy exists. Smith and colleagues14 found excellent recovery in 41 of 45 children with perinatal trauma. One patient had poor recovery, which suggests the need for radiographic and electrodiagnostic evaluation132 to detect an unfavorable prognosis for spontaneous recovery. In such cases, surgical exploration and decompression of the nerve is thought to be critical for effective reanimation. Congenital Facial Palsy Nontraumatic causes account for a smaller proportion of cases of facial palsy in the newborn. Both syndromic and nonsyndromic forms of congenital facial palsy can occur.133 The palsy may be complete or incomplete, unilateral or bilateral, and isolated to particular branches. In a series of 12 children with unilateral congenital facial palsy, Toelle and Boltshauser134 reported a higher incidence (83%) of lower facial involvement. Associated craniofacial malformations, often involving first and second branchial arch derivatives, are common. Microtia and facial clefts were noted most commonly in the series evaluated by Smith and colleagues.14 Palsies isolated to a single branch, particularly the marginal mandibularis, indicate the need for a cardiac evaluation in light of a high rate of concurrent anomalies. Otologic, electrodiagnostic, and radiologic evaluation is performed as needed to rule out treatable and lifethreatening etiologies. A congenital neuromuscular etiology is suggested by concomitant deficit(s) of other cranial nerves and absence of electrical responsiveness to evoked and spontaneous electromyographic evaluation.131 The Möbius syndrome encompasses a wide spectrum of anomalies caused by brainstem maldevelopment with resultant neuromuscular deficits peripherally. Bilateral absence of facial and abducens nerve function, as well as other cranial neuropathies, may occur. Although this disorder is generally considered to affect the brainstem at the nuclear level, Saito and colleagues135 described temporal bone findings in a patient with Möbius syndrome in which the horizontal portion of the facial nerve was absent bilaterally. The auditory brainstem response is often abnormal and is a helpful adjunct in diagnosis.133 In a prospective multidisciplinary study of 25 patients with Möbius syndrome, Stromland and colleagues136 noted that autism and mental retardation in one-third of patients. Congenital facial palsy that was not caused by trauma has a poor prognosis for recovery. Facial recovery better than House-Brackmann grade III dysfunction is unlikely.134 Unfortunately, the prognosis for effective facial animation with congenital facial palsies is also poor, although resting tone may provide adequate eye coverage and oral competence even into adulthood. Long-term follow-up is required to evaluate the need for facial rehabilitative procedures.

Radiologic Evaluation Radiologic assessment of the patient with facial paralysis has become one of the cornerstones of diagnosis. Plain films are no longer used to evaluate the temporal bone. Instead, high-resolution computed tomography (CT) and magnetic resonance imaging (MRI) have become the

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A

Figure 74-11. A male patient who presented with left facial paralysis of unclear etiology.

B Figure 74-10. A, CT scan of temporal bones demonstrating facial nerve neuroma involving tympanic segment in a 42-year-old woman with left facial paralysis. B, CT scan of temporal bones (in the same patient as in A) showing neuroma involving mastoid segment of the left facial nerve.

primary modalities for evaluation of the facial nerve. The goal of imaging is generally to exclude neoplasm and other pathologic processes along the intracranial, intratemporal, and extratemporal portions of the facial nerve. CT scanning of the temporal bone does not require contrast and is excellent at revealing the detailed bony anatomy of the temporal bone137 (Fig. 74-10). Such images permit assessment of the mastoid and middle ear spaces, as well as the course of the facial nerve from the internal auditory canal to the stylomastoid foramen. This is particularly helpful to evaluate possible infectious, neoplastic, or traumatic causes of facial palsy.138 High-resolution, thin-slice CT scanning of the temporal bone10 can reliably detect lesions larger than 5 mm that may involve the intracranial, meatal, labyrinthine, tympanic, and mastoid segments of the facial canal.139,140 Figure 74-11 shows a patient with left-sided facial palsy who was found on CT scanning (Fig. 74-12, arrow) to have a neuroma of the mastoid segment of the facial nerve.

The magnetic resonance (MR) signal is based on a combination of mobile proton density, vascular flow, and the time required for proton reorientation with changes in the magnetic field.141 Although not particularly useful for bony anatomy, MR provides the most sensitive method of imaging the intratemporal segment of the facial nerve and extends the assessment to include the entire intracranial

Figure 74-12. Temporal bone CT image of the patient in Figure 74-11, showing facial neuroma in the mastoid portion of the facial nerve (arrow).

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contrast-enhanced MRI detects neoplasms and other pathologic changes with high sensitivity, its utility in positively diagnosing Bell’s palsy is limited when background enhancement is prominent. The prognostic value of MRI in this setting appears limited. Nonetheless, correct interpretation of MR findings with clinical correlation may enable the clinician to advise and reassure the patient.

PROGNOSTICATION WITH FACIAL NERVE TESTING

Figure 74-13. MRI scan of brain enhanced with gadolinium demonstrating facial neuroma throughout the intratemporal facial canal (same patient as in Figure 74-10).

(pontine, cerebellopontine angle, and intracanalicular) and extratemporal segments of the nerve (Fig. 74-13). Before the availability of MR, the diagnosis of Bell’s palsy was established when the clinical presentation, taken in the context of historical features and physical findings, failed to reveal other pathology. MR-based observations, however, suggest that the diagnosis of Bell’s palsy may be positively established in some cases. Daniels and colleagues,142 Tien and colleagues,143 and Schwaber and colleagues144 detected gadolinium enhancement of the affected facial nerve in cases of Bell’s palsy. Enhancement in these cases is often diffuse, in contrast to the focal enhancement produced by neoplasms. These findings are consistent with the notion that vascular engorgement produced by inflammation and entrapment may underlie Bell’s palsy. Although these observations suggest that gadoliniumenhanced MR may be used to verify a diagnosis of Bell’s palsy, the significance of nonneoplastic enhancement of the facial nerve remains unresolved. Daniels and colleagues,142 Tien and colleagues,143 and Schwaber and colleagues144 noted mild facial nerve enhancement in the absence of facial dysfunction. Gebarski and colleagues145 performed a retrospective imaging review of 46 patients who were without symptoms referable to the brainstem and facial nerve. Focused temporal bone MRI revealed visible enhancement of the intratemporal facial nerve in 83% of cases, with right-to-left asymmetry in 42% of cases. These authors suggested that the pattern of enhancement corresponded with the topographic features of the lush circumneural plexus of vessels normally found in the facial canal. More recently, Kress and colleagues146 studied the intensity of facial nerve enhancement in patients with Bell’s palsy and concluded that degree of enhancement could be used as a predictive measure of facial nerve recovery. These observations indicate the need for further evaluation of the role of MRI in evaluating patients with acute facial palsies. The appearance of the facial nerve on an MRI should be considered on the basis of intensity, homogeneity, and distribution of enhancement and whether the nerve is displaced. Contralateral comparison is required and care should be taken not to mistake enhancing mucosa or fat for the facial nerve.143 Although

The natural history of Bell’s palsy varies along a continuum, from a course of early, complete recovery to a debilitating course of nerve degeneration with permanent motor dysfunction. In the majority of Bell’s palsies, spontaneous, complete recovery occurs. Unfortunately, a significant number of patients suffer from long-term disability. Differentiating between patients who are likely to recover and those who are not therefore remains a major area of concern.

Sequelae and Natural History Residual deficits from an acute facial palsy can be characterized as major and minor (Table 74-4). Suboptimal regeneration of motor nerve fibers can result in mild paresis, which leads to epiphora, nasal obstruction, and oral incompetence. Dysacusis is commonly thought to reflect stapedial muscle paresis, although Citron and Adour147 have questioned whether this symptom is due solely to motor dysfunction. Persistent dysgeusia, ageusia, and dysesthesias may result from involvement of sensory components. Mild synkinesis from aberrant motor reinnervation typically presents as involuntary closure of the eye with lip movement (Figs. 74-9C and 74-14B). Substantial nerve degeneration followed by impaired or aberrant reinnervation can produce profound synkinesis (mass motion), residual weakness, and facial spasm and tics. These sequelae are classified as severe because they frequently produce a skewed facial appearance and substantial functional impairment. The spontaneous course of Bell’s palsy has been characterized by Peitersen,29,148 May and colleagues,149 Adour and colleagues,30 and Taverner and colleagues.150,151 Although these studies vary somewhat in their findings, some patterns were observed across studies (Fig. 74-15): 1. Approximately one-third of Bell’s palsy patients demonstrated varied levels of preserved facial function (paresis or incomplete paralysis). The remaining patients demonstrated complete clinical paralysis.

TABLE 74-4. Major and Minor Sequelae of Facial Paralysis Major

Minor

Paresis Tension Contracture Tics Spasm Synkinesis

Ageusia Dysacusis Epiphora Gustatory lacrimation Nasal obstruction

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A

B Figure 74-14. A, A 44-year-old woman 1 year after recovery from Bell’s paralysis with face at rest. B, Synkinetic closure of the patient’s right eye with lip movement.

2. Patients who did not advance to complete paralysis enjoyed an excellent prognosis for full recovery of facial function; few of these patients demonstrated long-term sequelae, and sequelae that were present were likely to be mild. 3. For patients who developed a complete paralysis, some recovery occurred in all patients, although the extent of the recovery varied. 4. A complete return of function was highly likely for patients who demonstrated signs of recovery within 4 to 6 weeks of onset of the paralysis. This was the course for the majority of patients who developed complete paralysis. 5. The remaining patients with complete paralysis showed some evidence of recovery 2 months or longer after the onset of the paralysis and were likely to develop sequelae of greater severity. These observations suggest that the longer the interval before recovery begins, the greater the likelihood of severe residual deficits. Overall, the spontaneous course of a paralysis produced by Bell’s palsy is associated with inadequate or inappropriate nerve regeneration, producing severe sequelae in 15% to 40% of patients, about half of whom report resultant disability (see Fig. 74-15).

Figure 74-15. Natural history of Bell’s palsy—patterns of recovery. (Data from Peitersen E: n = 1, 101. Hauser WA, Karnes WE, Annis J, et al: Incidence and prognosis of Bell’s palsy in the population of Rochester, Minnesota. Mayo Clinic Proceedings 46:258–164, 1971; n = 121 and Adour KK, Byl FM, Hilsinger RL, et al: The true nature of Bell’s palsy: Analysis of 1000 consecutive patients. Laryngoscope 88:787–811, 1978; n = 1502. Taverner D: n = 100. May M, et al; n = 273.

The prognosis for recovery of facial function with herpes zoster oticus is less favorable than that associated with Bell’s palsy. Devriese27 found that only 16% of cases of herpes zoster oticus recovered function and were free of sequelae. The remaining patients demonstrated incomplete recovery, with major sequelae in about half of these cases. Devriese and Moesker152 reported only a 10% rate of full recovery for those with complete paralysis, and a 66% rate of full recovery after an incomplete paralysis. May25 and Robillard and colleagues26 similarly reported that 40% to 50% of patients afflicted with herpes zoster oticus failed to achieve satisfactory recovery.

Facial Nerve Testing In the evaluation of patients with acute facial paralysis, the initial focus is often directed toward determination of etiology. However, the prognosis for recovery is often the most relevant concern of the patient, and the assessment of prognosis is a crucial part of facial palsy management. Impaired transmission of neural impulses can result from physiologic blockage (in the absence of nerve fiber degeneration) or axonal disruption with subsequent wallerian degeneration. Because the clinical presentation of a facial paralysis does not distinguish between simple conduction block and axonal disruption, investigators have explored an array of testing procedures designed to define the extent of nerve injury. Early determination of the prognosis for recovery may then permit intervention to minimize nerve injury and optimize regeneration. Topognostic Testing Topognostic test batteries were initially intended to determine the level of facial nerve injury.153 Injury to the facial nerve as detected by topognostic testing is suspected at, or proximal to, the level of an impaired branch. If tearing is diminished, the lesion is assumed to be proximal to the

The Acute Facial Palsies

point at which the greater superficial petrosal nerve branches from the geniculate ganglion. Abnormal stapedial muscle function, as revealed by immittance testing, presumably reflects nerve impairment above the stapedial motor branch from the facial nerve trunk distal to the posterior genu.154 Function of the chorda tympani nerve is determined by submandibular gland secretion and taste testing.155,156 Dysgeusia and diminished salivary gland flow presumably reflect nerve impairment above the branch point of the chorda tympani nerve from the vertical segment of the facial nerve. Early observations suggested that more proximal levels of dysfunction correlated with a higher risk of degeneration and incomplete recovery. However, topognostic modalities have often provided unreliable information on the level of neural injury. These tests appear subject to vagaries produced by “skip” lesions of the nerve that differentially affect the motor, sensory, and autonomic portions of the nerve.157–160 For example, Schirmer’s tear test provides a practical guide for assessing tear production and the need for adjunctive eye care. Logically, it would also seem to provide an index of proximal nerve function in establishing a lesion at or above the level of the geniculate ganglion, but Gantz and colleagues56 found an accuracy rate of only 60% using intraoperative electrical stimulation to specify the site of nerve conduction block in Bell’s palsy. Because of the uncertainties inherent in topognostic testing, electrophysiologic responsiveness has emerged as the most reliable means of assessing nerve conductivity and the risk of nerve fiber degeneration. Furthermore, the body of evidence that implicates the meatal foramen as the primary site of nerve injury in Bell’s and herpes zoster palsies (a site that is consistently approached only through the middle cranial fossa) has eliminated the need for topognostic testing in selecting a surgical approach. Electrophysiologic Testing The facial nerve consists of approximately 10,000 nerve fibers, approximately 7000 of which are myelinated, motor fibers. The validity of electrophysiologic testing of an acute facial palsy relies upon two inferences with regard to nerve fiber status: 1. Segmentally demyelinated fibers maintain the capacity to propagate a stimulus albeit at a higher threshold than that of normal fibers.161 Anatomically intact fibers will therefore continue to propagate an applied stimulus, whereas those that are disrupted and have subsequently degenerated will fail to do so. 2. Determination of the proportion of degenerated motor fibers distinguishes palsies that are likely to recover from those that will fail to recover spontaneously and will produce long-term sequelae. What degree of nerve fiber injury produces a conduction block and places the fiber at risk for degeneration? Several models for analyzing this question are available. Seddon162 originally proposed that peripheral nerve injury involves varying degrees of neuropraxia (blockade), axonotmesis (division of individual fibers), and neurotmesis (division of fascicles and epineurium). Sunderland90 and Sunderland and Cosar163 produced a clinical-pathologic classification of nerve injury (Fig. 74-16) that expanded on

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Figure 74-16. Correlation between Seddon’s and Sunderland’s classifications of neural injury. (From Turzis JK, Smith KL: The Peripheral Nerve: Structure, Function and Reconstruction. New York, Raven Press, 1991.)

Seddon’s pathologic scheme. More recently MacKinnon164 has added a sixth category of nerve injury that combines the injury classifications proposed by Sunderland. This addition is based on observed patterns of blunt and penetrating injuries of the nerve. 1. First-degree injury is characterized by blockage of axoplasmic flow within the axon. There is sufficient pressure to restrict its replenishment when metabolic needs dictate. This blockade constitutes a neurapraxic injury according to Seddon’s classification. Although an action potential cannot be propagated across the lesion site, a stimulus applied distal the lesion will conduct normally to produce an evoked response. 2. Second-degree injuries entail axonal and myelin disruption distal to the injury site as a result of progression of a first-degree injury. Such injuries abolish propagation of an externally applied stimulus as wallerian degeneration of the axon ensues. 3. Third-degree injuries involve complete disruption of the axon and its surrounding myelin and endoneurium. 4. Fourth-degree injuries entail complete disruption of the perineurium. 5. Fifth-degree injuries are characterized by disruption of the epineurium. 6. Sixth-degree injuries are characterized by normal function through some fascicles and varying degrees of injury (first through fifth-degree injury) differentially involving fascicles across the nerve trunk.

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Histopathologic studies of Bell’s palsy and herpes zoster oticus25 suggest that nerve injuries as severe as fourth-degree injury may occur in these disorders. Central to Sunderland’s classification is the notion that axonal recovery depends directly on the integrity of connective tissue elements of the nerve trunk. This model predicts good chances for complete recovery when endoneurial tubules remain intact to support reinnervation. In contrast, disruption of the endoneurium— a third-degree injury or worse in Sunderland’s model— presumably increases the likelihood of irreversible axonal injury and aberrant patterns of regeneration. Electrophysiologic testing ideally indicates severity of injury to the nerve as a whole by reflecting the proportion of motor fibers that have progressed beyond a first-degree injury. Correlation of the ultimate level of recovery with early electrophysiologic findings determines the test’s prognostic performance in identifying the subset of patients who will not obtain satisfactory recovery. Common electrophysiologic tests indirectly assess the severity of injury to the intratemporal facial nerve. Given the bony encasement of this segment of the nerve, electrical stimulation proximal to the site of conduction blockade is possible only when the nerve is activated intracranially. For this reason, the ability of a nerve to propagate an impulse is assessed distal to the stylomastoid foramen. Even in the presence of severe neural injury, conduction distal to a lesion will continue until its axoplasm is consumed and wallerian degeneration ensues. This process requires 48 to 72 hours to progress from intratemporal to extratemporal segments, thereby rendering electrical stimulation tests falsely normal during this period. Routine electrophysiologic tests therefore fail to detect nerve conduction as it occurs, thereby delaying differentiation of neuropraxia from degeneration. Nerve Excitability Testing Minimal excitability testing with the Hilger165 nerve stimulator has provided a readily accessible method of facial nerve assessment. The test reflects the elevated thresholds for neuromuscular stimulation produced by axonal disruption and degeneration. The lowest stimulus intensity that consistently excites all branches on the uninvolved side establishes the normal threshold.166 A 2- to 3.5-mA difference between the uninvolved and involved sides is reported to suggest impending denervation. This test offers technical advantages in the portability of the necessary equipment and the use of minimal stimulation that is comfortable for the patient. The test, however, introduces subjectivity in that it relies on visual detection of the response.167 In addition, current levels at threshold for peripheral branches are likely to selectively activate large nerve fibers (with lower thresholds) and those fibers closer to the stimulating electrode,168 thereby excluding some motor fibers from the assessment. Maximal Stimulation Test May and colleagues169 proposed that maximal electrical stimulation could be used to determine whether clinically significant nerve degeneration developed in the course of an acute facial paralysis. This test uses transcutaneous

electrical stimulation designed to saturate the nerve and activate all functioning fibers.170 The response on the involved side is characterized as (1) equal to the contralateral side, (2) minimally diminished, that is, 50% of normal, (3) markedly diminished, that is, less than 25% of normal, or (4) absent. Experience with this test suggested that when the response was markedly diminished or absent within the first 2 weeks of the clinical paralysis, there existed a 75% chance of incomplete facial nerve recovery.169 When the response completely disappeared within the first 10 days, recovery was typically incomplete and significant sequelae ensued. Conversely, if responses were symmetric during the first 10 days of a clinical paralysis, complete return was found in more than 90% of patients tested. The use of supramaximal stimulation early in the course of an acute facial paralysis provides sensitivity and consistency in testing. However, interpretation of the maximal stimulation test can be influenced by subjectivity in visually grading the evoked response. Electromyography The electromyographic (EMG) response reflects postsynaptic membrane potentials that may be (1) initiated at the neuromuscular junction with voluntary activation or (2) spontaneously produced across the muscle membrane. These potentials are recorded easily with either simple bare-tip (monopolar) or concentric (coaxial) needle electrodes.90,171 Granger172 correlated EMG evidence of preserved motor unit potentials with the ultimate level of recovery from paralysis in patients with Bell’s palsy. Motor unit potentials in four of five muscle groups in the first 3 days after onset of an acute facial paralysis was associated with a satisfactory outcome in more than 90% of patients. Motor units in two of three muscle groups predicted a satisfactory outcome in 87% of patients. If motor units were limited to one muscle group or abolished, satisfactory recovery occurred in only 11% of cases. Although these findings suggest a role for early EMG testing in prognosticating functional recovery, Gordon and Friedberg173 and Dumitru and colleagues174 have noted potential pitfalls of early EMG testing. Sparse residual motor units that suggest a favorable outcome may be evident despite severe injury to large portions of fibers that are at risk for degeneration. Clinical evidence of this was provided by May and colleagues,169 who noted unsatisfactory recovery despite voluntary motor potentials in 38% of patients with Bell’s palsy. These observations suggest that EMG assessment should be performed in at least two muscle groups to assess the degree of denervation more accurately. Early in the course of an acute facial paralysis, preserved facial motor activity may escape clinical inspection and yet provide prognostic information when combined with other testing modalities. For example, subclinical motor activity detected by the EMG complements the use of evoked electromyography in the early phase of a clinical paralysis.51,175 EMG monitoring is of limited use in detecting early degeneration since electrical evidence of nerve degeneration is absent in the first 10 days of the paralysis.90 Ten to 14 days following the onset of a clinical paralysis, EMG

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recordings reflect the dynamic resting membrane potentials of postsynaptic elements. In this phase, muscle deprived of “trophic” substances normally transported through the axon undergoes changes that destabilize the resting potential of the muscle membrane. These changes produce spontaneous depolarizations reflected in the EMG as fibrillation potentials and indicate persistent denervation. Substantial axonal loss and impaired reinnervation yield fibrillation potentials as long as postsynaptic membranes remain electrically active.90,174 With persistent denervation, EMG recordings are silent and the short burst of discharges normally found on needle insertion are absent. Conversely, successful reinnervation generates high-frequency polyphasic potentials that increase in amplitude and duration and replace fibrillation potentials. In rare cases of protracted paralysis caused by Bell’s palsy, longitudinal EMG evaluations detect persistent nerve degeneration or reinnervation. Electroneuronography and Evoked Electromyography Similar to the maximal stimulation test, evoked electromyography (EEMG) or electroneuronography (ENOG) assesses the facial motor response to a supramaximal stimulus.176 In contrast to maximal stimulation testing, the EEMG technique records the compound muscle action potential (CMAP) with surface electrodes placed in the nasolabial fold (Fig. 74-17). The CMAP can be displayed graphically for quantitative analysis and printed for the medical record. Waveform responses are analyzed to compare peak-to-peak amplitudes between normal and involved sides. Kartush and colleagues,177 Gutnick and colleagues,178 Coker and Salzer,179 and Coker180 have stressed various technical features of the EEMG that are critical for obtaining reliable results. Esslen51 and Fisch181,182 recognized the importance of correlating EEMG test results with the clinical history and facial motor examination. Patients with incomplete paralysis caused by Bell’s palsy invariably recover function to normal or near-normal levels and do not require EEMG evaluation. The reappearance of facial movement within 3 to 4 weeks after onset also predicts an excellent prognosis for functional recovery. EMG sampling of motor activity to detect visually imperceptible facial function is advised. When EEMG is used in a timely fashion, reductions in response of the affected side are thought to reflect the percentage of motor fibers of the facial nerve that have degenerated.51 Facial EEMG is most reliable during that initial phase of accelerated denervation when reliable results can be obtained, that is, in the first 2 to 3 weeks following onset of a paralysis caused by Bell’s palsy or herpes zoster oticus. When neurapraxic fibers become “deblocked” either in the recovery phase or later on as axons regenerate peripherally, stimulated nerve fibers discharge asynchronously.181 Because regenerated fibers do not discharge in synchrony, the response is disorganized and consequently diminished. This phenomenon imposes a time constraint on the reliability of EEMG testing that must be considered in interpreting test results.181 Clinical trials conducted by Mamoli,183 Thomander and Stalberg,184 May,25 and Sillman and colleagues175 support

Figure 74-17. Placement of recording and stimulating electrodes for facial EEMG recordings. The compound muscle action potential is reflected in biphasic response.

the early findings of Fisch and Esslen,55 Esslen,51 and Fisch182 that EEMG (electroneuronography) provides an accurate prognostic guide early in the course of facial paralysis. In clinical trials based at the University of Zurich, recovery of facial function was graded subjectively by patients and objectively by examiners who were unaware of the corresponding electrical profile. These trials indicated that more than 50% of patients with complete paralysis who exhibited a 90% or greater reduction in CMAP amplitude ultimately had poor spontaneous return of facial function. When results demonstrated less than 90% denervation (>10% in CMAP amplitude relative to the normal side), excellent recovery was uniformly observed. Repeated testing every other day is recommended to detect ongoing degeneration beyond the 90% critical level. The time course of reduced electrical excitability (velocity of denervation as demonstrated by repeated testing) and the degree of degradation of the CMAP response (the nadir of the response) are very useful in predicting the ultimate level of spontaneous recovery.51,181,182,185 The earlier the EEMG response drops to 10% or less than normal, the worse the prognosis. Using a modified recording montage, May and colleagues169 observed that the EEMG response on the day 5 after the onset of paralysis was most predictive of the pattern of return, with little spontaneous recovery and major sequelae predicted by EEMG amplitudes below 10%. Electrophysiologic testing with EEMG is now recognized as the most straightforward and accurate means of

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assessing the degree of facial nerve injury associated with Bell’s and herpes zoster oticus. However, accurate results depend on an evaluation that incorporates historical and physical findings determined before testing, as well as care in administering and interpreting results. For many of these electrophysiologic tests, it has not been possible to establish a clear correspondence between response profiles in the acute phase of paralysis and functional outcome. With EEMG testing, however, it is possible to identify early patients who are at heightened risk for permanently impaired facial function. The utility of these data are to stratify patients into various risk groups. Patients who are at increased risk for permanent dysfunction can then be assessed for possible surgical treatment. Transtympanic Stimulation In cases of facial palsy thought to result from injury distal to the tympanic segment of the facial nerve (e.g., parotid surgery or neck surgery), it is sometimes unclear whether the facial nerve is weak due to neuropraxia or transection. In this setting, transtympanic stimulation of the facial nerve may be useful.186 This technique involves a myringotomy and stimulating the tympanic facial nerve through the myringotomy using a monopolar nerve stimulator. If the nerve is intact but neurapraxic, then it should be responsive to supramaximal stimulation of the proximal segment of the nerve. A positive finding would thereby assist in management of this problem, indicating that transection has not occurred and that a facial nerve exploration is unnecessary. A negative finding, however, is less helpful. This technique has been described only recently, and further studies are needed to assess its utility.

Figure 74-18. Topographic representation of (mean) amplitude and latency of evoked neural potentials from facial genu (A), region dorsal to facial nucleus (B), and nucleus (C). Stimulus intensity = 0.4 mA; duration = 100 μs; N = 100 stimuli for each trial. (Reprinted with permission, Niparko JK, Kartush JM, Bledsoe SC, Graham MD: Antidromically evoked facial nerve response. Am J Otolaryngol 6:353–357, 1985.)

The previously described electrodiagnostic tests indirectly assess the severity of injury to the intratemporal segment of the facial nerve. Investigators have explored alternative testing procedures in which the facial nerve is activated central to the presumed site of involvement within the temporal bone.

demonstrated that the far-field response to antidromic stimulation represented composite activity along the facial pathway and did not appear to reflect stimulation of the facial nerve at a specific site along the intracranial segment. Nakatani and colleagues192 found that patients with Bell’s palsy invariably displayed abnormal waveforms in response to antidromic stimulation, suggesting that this test may be useful in assessing progression of facial nerve injury in Bell’s palsy.

Antidromic Conduction

Magnetic Stimulation

Antidromic conduction testing is an alternative to peripheral electrodiagnostic testing that, at least theoretically, can provide direct and immediate assessment of facial nerve function.187 The F wave represents activity in facial muscles generated by antidromically activated motor neurons and contains no reflex components.188 For electrodiagnostic purposes, F waves evoked by electrical stimulation may be recorded with intramuscular needle electrodes. This response has a long latency and is normally small in amplitude, thereby limiting its dynamic range and prognostic value. In patients with Bell’s palsy, electrical stimulation of the nerve reliably produces F wave responses only after recovery has begun. Antidromic conduction (opposite-to-normal direction) of electrical activity in the facial nerve can be measured with near- and far-field techniques in animals189 (Fig. 74-18) and clinically with middle ear recording electrodes.187,190 Niparko and colleagues189 and Kartush and colleagues191

Transcranial magnetic stimulation employs an electromagnetic coil to produce neural activation.193 This method of neural activation is unique in that the intensity of the stimulus is minimally attenuated by intervening tissue.194 This feature enables central activation via transcranial application of induced current. Animal studies have demonstrated that transcranial magnetic stimulation can be used to activate the facial nerve centrally, although the precise site of stimulation is difficult to determine. Observations suggest that the evoked response is likely caused by excitation of the facial nerve intratemporally195 or intracranially196 rather than via cortical or brainstem excitation. This distinction is crucial to the future use of transcranial magnetic stimulation for facial nerve injury prognostication, and it continues to generate controversy.193,197 Clinical experience with electromagnetic stimulation in pathologic states including Bell’s palsy is in keeping with observations that localize the lesion intratemporally.195

Facial Nerve Assessment with Central Activation

The Acute Facial Palsies

In 11 patients with recent onset of Bell’s palsy, none demonstrated evoked CMAPs with magnetic stimulation. The lack of response is attributed to the elevation in threshold associated with segmental demyelination and the inability of the current generated by the electromagnetic field to reach threshold. In a cat animal model of traumatic facial nerve injury, Har-El and McPhee showed that the severity of facial nerve injury corresponded to the threshold necessary for transcranial magnetic signals to induce facial movement.198 Similar data in humans may ultimately confirm the utility of transcranial magnetic stimulation in producing proximal activation of the facial nerve. Trigeminofacial Reflex Although infrequently used today, electromyographic recording of the trigeminofacial (blink) reflex can provide quantitative assessment of facial nerve conduction via activation of the facial nucleus centrally.168,174,199 This technique records action potentials reflexively generated in the orbicularis oculi muscle in response to an electrical stimulus applied to the supraorbital area (V1 branch). Responses between the affected and normal sides are compared to provide quantitative assessment of the reflex, thereby providing a measure of the functional integrity of the facial nerve. Kimura and colleagues200 evaluated the prognostic value of trigeminofacial reflex. An abolished R1 response was associated with little chance of recovery in the first 2 months following the onset of paralysis. Preserved early R1 responses predicted return within the first month. The performance of this test in selecting patients with absent R1 responses who have a poor long-term prognosis is yet to be evaluated.

TREATMENT Treatment of facial palsy has centered on the timely administration of steroid drugs. Antiviral therapy, in contrast, is a more controversial form of treatment. Recent investigations have also suggested a possible role for surgery.

Glucocorticoids Pharmacology Because the glucocorticoid steroids exert an inhibitory effect on virtually every phase of the inflammatory response, they have assumed an important role in treating a vast range of inflammatory and immune-mediated disorders.201,202 The precise mechanism by which steroids exert their beneficial effect is incompletely defined for many of the conditions for which they are prescribed. In many cases, guidelines and indications for steroid treatment are empiric. Such guidelines apply to the use of steroids in the treatment of Bell’s and other facial palsies where their use is of uncertain benefit. Nonetheless, the pharmacologic effects of steroids make them attractive agents for ameliorating symptoms associated with the acute inflammatory phase of disorders such as Bell’s palsy and herpes zoster oticus and, theoretically, for improving the likelihood of full recovery. The inflammatory response is mediated by numerous chemical intermediaries and cell types. The general

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anti-inflammatory effect of glucocorticoids can be attributed to effects on vascular tone and permeability and to suppression of leukocytes and collagen biosynthesis. Demopoulos and colleagues203 provided evidence that lipid peroxidation induced by oxygen-free radicals forms the molecular basis for post-traumatic neuronal degeneration and that ste-roids might inhibit this degenerative process. Using spinal cord homogenates as a model for neural injury, Hall and Braughler204 observed that large pretreatment doses of methylprednisolone were required to produce this anti-oxidant effect and that pretreatment with lower doses was ineffective. The glucocorticoid steroids are used extensively in treating a wide variety of traumatic and inflammatory CNS and peripheral nerve disorders. Steroids are known to have multiple effects on CNS neuronal and glial metabolism, and their effect on insulted neural tissue may extend beyond limiting edema.205 Although steroids have been shown experimentally to confer tissue protection in CNS trauma, clinical trials have failed to demonstrate effects on mortality convincingly, and effects on the quality of outcome are contradictory.206 Steroid therapy for inflammatory neuropathies such as idiopathic optic neuritis is likewise controversial.207,208 Although glucocorticoids appear to reduce pain and shorten the period of associated blindness, there is little evidence that they positively influence the ultimate level of visual recovery. In addition to their anti-inflammatory properties, the glucocorticoid steroids also exert a facilitatory action on the neuromuscular junction.209 These combined effects may contribute to the recovery of neuromusculature function in disorders such as inflammatory polyradiculoneuropathies (the Landry-Guillain-Barré syndrome), the pathology of which is marked by inflammatory, segmental demyelinization. Steroid Treatment of Bell’s Palsy and Herpes Zoster Oticus Steroid therapy for Bell’s palsy has long been, and continues to be, a controversial subject. Adour,17 Stankiewicz,87,210 and May25 have provided comprehensive reviews of steroid therapy in Bell’s palsy. Most early studies of the value of steroids in treating Bell’s palsy were based on comparisons of treated patients with retrospective controls.150 The doubleblind, randomized, controlled clinical trial performed by Adour and colleagues211 demonstrated a significantly higher rate of complete functional recovery in glucocorticoidtreated patients than in the control group. However, the lack of randomization and concurrent controls and the dose of glucocorticoid have been questioned.6 A follow-up study using appropriately stratified patient groups performed by May and colleagues212 demonstrated that the eventual outcome remained unaffected by steroid therapy. Prospective, randomized trials using larger doses of steroids213 and large doses of glucocorticoids with dextran and pentoxifylline214 demonstrated improved rates of recovery in the treated groups, although the treatment effect did not achieve statistical significance in the former study. Another controlled, double-blind trial similarly demonstrated beneficial effects of glucocorticoid therapy, especially when initiated early in the disease process.215

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A recent meta-analysis of all randomized studies of steroid therapy for Bell’s palsy concluded that steroid therapy did not appear to produce significant benefit in terms of ultimate function or cosmesis.216 This conclusion is also supported by a recent meta-analysis of studies of patients younger than 16 years of age with Bell’s palsy that found no benefit with steroid therapy.217 In contrast, Grogan and Gronseth218 performed an evidence-based review of the literature and concluded that although the data were not overwhelming, steroid therapy was probably beneficial for Bell’s palsy. Ramsey and colleagues219 reviewed 47 trials (27 of which were prospective) of steroid therapy for patients with complete idiopathic facial paralysis only and concluded that steroid therapy did improve recovery for complete paralysis. As evaluated by Stankiewicz,210 steroid therapy in Bell’s palsy: ■ ■ ■ ■ ■

may reduce the risk of denervation if initiated early. may prevent or lessen synkinesis. may prevent progression of incomplete to complete paralysis. may hasten recovery. may prevent autonomic synkinesis (crocodile tearing).

The desired goal of glucocorticoid therapy of acute facial paralysis is to induce effective anti-inflammatory control. To provide such control, the inflammatory process should be countered with consistent, pharmacologic levels of an anti-inflammatory agent beginning as soon as possible.220 Once the inflammatory process is checked and the stimulus for inflammation removed, therapy can be discontinued. However, abrupt withdrawal may be followed by a rebound of disease activity. To prevent reacceleration of the inflammatory process, a tapered withdrawal of the daily glucocorticoid dose over 10 to 14 days is recommended. The optimal glucocorticoid dosage regimen for treating an inflammatory neuritis depends on the time course of the underlying disease process. The duration of accelerated inflammation associated with viral neuropathy is more difficult to estimate. As discussed previously, two viruses frequently associated with facial palsy are the HS and VZ viruses, which have incubation periods of approximately 3 and 14 days, respectively.221 Although the duration of the active phase of these infections is impossible to establish, the typical electrical profiles of progression of the palsy in patients with Bell’s palsy and herpes zoster oticus point to reasonable conclusions. May25 suggested that the acute phase of the infection, as measured by the EEMG response, peaks in 5 to 10 days in Bell’s palsy and 10 to 14 days in herpes zoster oticus. These findings are compatible with those noted by Esslen51 in Bell’s palsy patients stratified with electroneuronography. Because lesions induced by these infections in other organs generally heal in 1 to 2 weeks, it seems that accelerated inflammation of the facial nerve with these viruses would normally be confined to this period. These considerations suggest the following strategy for steroid treatment of Bell’s palsy and herpes zoster oticus: oral prednisone (1 mg/kg/day) divided into 3 doses per day for 7 to 10 days. The daily dose should then be tapered to zero over the following 10 days. Theoretically, this dosing regimen maximizes anti-inflammatory activity

while minimizing side effect and is consistent with antiinflammatory schedules that are effective in controlling acute hypersensitivity, as well as autoimmune and other inflammatory disorders. Side Effects Well-known side effects of steroid treatment are numerous and include hyperglycemia, CNS changes (e.g., psychotic reaction), fluid shifts, electrolyte disturbances, and gastrointestinal irritation.220 Given the reportedly high incidence of glucose intolerance in several series of patients with acute facial palsy, steroids should be initially prescribed with caution, especially in diabetics. Patients who are taking steroids long term should be placed on gastrointestinal prophylaxis with acid-suppression therapy. In addition to electrolyte changes, glucocorticoids elevate the white blood cell count, thereby making the laboratory white count unreliable as an indicator of systemic inflammation or infection. An adverse effect of glucocorticoid administration that deserves special consideration is heightened susceptibility to infection. The effects of glucocorticoids on cellular and humoral components of inflammation may lessen host immunity to bacterial, viral, and fungal infections. Latent infections may reactivate and disseminate. Moreover, suppression of the inflammatory response may conceal symptoms and signs of infection. Although this effect on host resistance has been demonstrated in experimental trials, typical daily doses of glucocorticoids (1 mg/kg/day prednisone or its equivalent) given for 2 weeks or less are rarely associated with an increased susceptibility to infection. The risk of steroid-induced dissemination of viruses presents a particular concern in treating acute facial palsies of viral origin. The risk of virus dissemination is significant with steroid therapy beyond 1 month220 and in immunosuppressed patients.221 Otherwise, clinical experience suggests that the risk of this complication is minimal and that steroids can ameliorate postherpetic neuralgia.222,223

Antiviral Therapy Viral etiologies are suspected to play the major role in most forms of idiopathic facial paralysis. Antiviral chemotherapy has been a controversial subject, and there is a lack of compelling data to justify its use.224 Although other agents such as valacyclovir and famciclovir have emerged, acycloguanosine (Acyclovir) has been the prototype of antiviral medication for facial palsy. Acyclovir is a synthetic purine nucleoside analogue that inhibits herpes simplex types I and II, VZV, Epstein-Barr virus, and cytomegalovirus in cell culture.225 This inhibition is based on a disruption of viral replication, and it is poorly phosphorylated by uninfected cells, lending it a selective antiviral effect. A preliminary report by Dickens and colleagues226 suggested that acyclovir may mitigate neurologic deficits produced by herpes zoster oticus. Intravenous acyclovir (10 mg/kg every 8 hours for 7 days) produced substantially greater functional return in patients treated within the first 72 hours after the onset of paralysis. Moreover, Dickens demonstrated early recovery of facial nerve function and reversal of sensorineural hearing loss associated with herpes zoster oticus in response to the drug early on.

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Since these initial studies, many recent investigations have examined the role of antiviral therapy for facial paralysis. In a meta-analysis, Grogan and Gronseth218 ranked every study of antiviral and steroid therapy according to quality of study. As with steroid therapy, no absolutely conclusive results could be achieved. However, acyclovir in combination with prednisone was found by one large study their meta-analysis to have a significant beneficial effect on outcome for Bell’s palsy, and it was therefore softly recommended by the authors. Morrow227 reviewed treatment agents for facial paralysis and recommended antiviral therapy in conjunction with oral steroids for complete paralysis. Sweeney and Gilden228 have recently supported antiviral therapy for the treatment of Ramsay Hunt syndrome (known to be caused by VZV ) in addition to Bell’s palsy. Most studies of antiviral therapy include steroid treatment as part of the regimen. This fact makes it difficult to assess the efficacy of antiviral therapy as an independent factor. Nevertheless, antiviral therapy is generally well-tolerated, and has a low side effect profile. Therefore, the potential benefits of its use appear to outweigh the drawbacks of lacking prospective, randomized data. Future studies are needed to confirm the utility of antiviral therapy for idiopathic facial paralysis.

Nerve Decompression Reports of surgical decompression of the facial nerve for Bell’s palsy date back to the work of Ballance and Duel in 1932.229 Adour and Diamond,230 May and colleagues,100 Hughes,6 Alford and Sessions,35 Cawthorne and Wilson,231 and Jackson96 have documented the evolution of surgical criteria and preferred surgical approaches to decompression. The role of surgery has evolved in concert with developments in electrophysiologic testing and techniques of enhanced surgical exposure of the facial nerve. Early on, decompression was performed when facial nerve excitability with electrical stimulation was lost.229 Topognostic testing and, subsequently, electrodiagnostic techniques then emerged as tests of choice for selecting patients whose unfavorable prognosis might be improved by surgery.51,132,232,233 The decompression procedure was then extended in parallel with developments in facial nerve testing. Initially, the vertical segment alone was decompressed. Next, decompression of the entire mastoid segment was recommended.234 The preferred procedure was then extended to include the tympanic and mastoid segments235 and most recently, the labyrinthine segment including the meatal foramen (see Figs. 74-7 and 74-8). Huizing and colleagues160 found little if any therapeutic benefit on the ultimate outcome of patients with acute facial paralysis following decompression of the mastoid segment of the facial nerve. Based on these clinical observations and the work of Esslen,51 Fisch,52 and Fisch and Esslen,55 postauricular decompression of the mastoid and tympanic segments alone was abandoned by those reporting results of decompression.95 As anatomic and electrophysiologic evidence of a specific anatomic site of lesion in Bell’s palsy has emerged, procedures for surgical intervention have focused on decompressing the meatal foramen and adjacent labyrinthine segment of the nerve for those cases thought to have a

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poor prognosis for complete recovery with medical treatment alone. Both transmastoid236 and middle fossa55 approaches have been described. The transmastoid approach to the geniculate ganglion and the labyrinthine segment obviates a craniotomy but requires removal of the incus in poorly pneumatized bones to facilitate exposure of the facial nerve proximal to the cochleariform.236 Goin237 performed a temporal bone study to evaluate this approach. The transmastoid approach entirely uncapped the labyrinthine segment in 60% of preparations. In 40% of temporal bones the vestibular labyrinth, particularly the ampullated end of the superior canal, prevented complete exposure of the proximal labyrinthine segment. Using the transmastoid approach for nerve decompression, May236 found that decompression improved recovery in patients whose maximal nerve stimulation responses were reduced by 75% or more. However, long-term follow-up of these patients failed to show significant benefit from this procedure; the rate of satisfactory recovery (85% of 273 patients) did not differ from the spontaneous recovery rate (84%) found by Peitersen.29 The meatal foramen is most easily and uniformly addressed via the middle cranial fossa approach. This approach to the meatal, labyrinthine, and geniculate segments of the nerve as first described by House238 facilitates direct decompression with minimal risk to the labyrinth. The middle cranial fossa approach also permits direct stimulation of the facial nerve proximal to the meatal foramen, enabling verification of the site of impairment if complete loss of response to electrical stimulation has not yet occurred.55–57 Intraoperative stimulus trials typically reveal severely attenuated or no response proximal to the foramen, whereas stimulation distal to the foramen evoked potentials of substantially greater amplitude (see Fig. 74-7). In a prospective study of Bell’s palsy stratified by EEMG, Fisch182 performed decompression via the middle fossa approach when evoked response amplitudes were 10% (or less) that of the normal side. This criterion was based on the observation that approximately one-half of patients that progressed to a nadir of 95% to 100% degeneration within 2 weeks of the onset of the paralysis demonstrated permanent, unsatisfactory recovery of facial function. Furthermore, most patients who reached a 90% level of degeneration progressed beyond 94% degeneration in the EEMG profile. Therefore, the proposal that immediate surgical decompression be performed as soon as the 90% level of degeneration is reached entailed unnecessary surgery in, at most, 10% of patients. All patients who underwent decompression when degeneration reached 90% demonstrated satisfactory return of facial movements. The 90% rate of satisfactory outcome with surgery compared favorably with the 50% chance of satisfactory return noted in patients who had no surgery matched by EEMG profile. Surgery performed on 8 patients in the third week after the onset of the palsy when degeneration exceeded 90% did not significantly improve the return of facial function.182 However, two patients in this group demonstrated exceptional return of facial movement after decompression. This experience suggests that studies of more patients with delayed degeneration are needed before the role of surgical

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decompression can be assessed definitively in this subset of patients. Gantz and colleagues239 described the use of ENOG as a guide to whether aggressive surgical treatment (which consisted of middle fossa decompression of the facial nerve medial to the geniculate ganglion) was warranted. In this multicenter study, poor outcome was defined in accordance with guidelines derived by Fisch and Esslen55 described previously. All patients that did not have 90% degeneration on ENOG within 2 weeks had ultimately good facial function (House-Brackmann grade I or II). Patients with greater than 90% degeneration on ENOG and without voluntary EMG potentials within 2 weeks of onset of facial paralysis were considered to have a poor prognosis. These patients were offered middle cranial fossa decompression of the facial nerve at the tympanic segment, geniculate ganglion, labyrinthine segment, and meatal foramen. Of these patients, those who chose surgical decompression had a 91% rate of recovery to HouseBrackmann grade I or II facial palsy. In comparison, those who refused surgery had a 58% chance of an ultimately poor outcome (House-Brackmann grade III or IV). This difference between surgical and nonsurgical outcomes was highly significant statistically, allowing the authors to draw the conclusion that surgery for Bell’s palsy (if performed within the first 2 weeks) is an appropriate therapeutic measure in carefully selected cases using electroneurographic and electromyographic criteria.

Nerve Grafting Surgical management of facial paralysis is an extensive subject that is beyond the scope of this chapter. Numerous surgical methods have been devised to rehabilitate the paralyzed face, whether due to tumor or parotid, otologic, or cranial base surgery. These methods have ranged from static techniques designed to suspend the facial musculature, such as facial slings, to dynamic techniques aimed at restoring function, such as nerve grafting. One method of nerve grafting that is well described in the literature for facial paralysis is the hypoglossal-facial nerve anastomosis. In this technique, the ipsilateral hypoglossal nerve is transected near the tongue and swung posteriorly to join the facial nerve, which has usually been injured proximally.240,241 Results with these techniques have been mixed, and surgeons have searched for a better way to reinnervate the facial nerve. During skull base surgery, the facial nerve is often injured just after its exit from the brainstem. Such injury may be due to cerebellopontine angle pathology, which may cause neural compression or invasion, or due to iatrogenic trauma following tumor resection. In cases where the continuity of the nerve has been maintained (albeit severely tested), it appears that long-term facial function is best preserved by leaving the integrity of the nerve unviolated.242,243 Facial function often returns to normal in these patients. In cases where the facial nerve must be transected, nerve repair has emerged as a useful means of maximizing outcome. In some cases, the transected ends of the facial nerve are in close proximity and a primary facial reanastomosis can be performed.244,245 When the transected ends are too far from one another, an interposition cable graft (often using the sural or greater auricular nerves) may be

performed.246 Fibrin glue is helpful in such procedures.243 In appropriately selected cases, long-term follow-up after such procedures can reveal excellent results. Reported results in the literature range from fairly good to average. Although the utility of the House-Brackmann grading scale in patients undergoing facial nerve repair has been questioned,247,248 it remains the primary system for reporting results of facial function. In general, one should not expect facial function better than House-Brackmann grade III following nerve grafting.240,243,249 In evaluating these outcomes, clinicians should remember that the preoperative function of these patients (who may have large cerebellopontine angle tumors or facial neuromas) is generally impaired and that nerve grafting may allow patients to maintain their baseline degree of function.

CONCLUSION Acute facial palsy remains a difficult problem to manage, from both diagnostic and therapeutic perspectives. Great advances in our understanding of idiopathic facial palsy have been made, and it appears likely that a viral infection is the etiologic agent in many cases of “idiopathic” acute facial palsy. Electrophysiologic testing has improved our ability to identify patients who are not likely to recover, and hence, those who might benefit from more aggressive therapy. Pharmacologic advances, such as newer antiviral agents, have given us a medical means of targeting the suspected agent in disorders such as Bell’s palsy, and they continue to be promising. Surgical treatment of facial nerve paralysis, ranging from decompression to nerve grafting, continues to evolve. Although the goal of reestablishing normal facial function to all patients continues to be elusive, we are currently able to offer remedies that will provide at least some improvement of a patient’s impaired facial function.

ACKNOWLEDGEMENT The authors thank Anne Barson Niparko, BA, for expertise in preparing this manuscript.

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233. Jongkees L: Bell’s palsy: A surgical emergency? Arch Otolaryngol 81:497–501, 1965. 234. Morris W: Surgical treatment of facial paralysis: Review of 46 cases. Lancet 2:558–561, 1939. 235. Lewis M: A variation in technique of facial nerve decompression. Laryngoscope 66:1451–1463, 1956. 236. May M: Total facial nerve exploration: Transmastoid, extralabyrinthine and subtemporal. Laryngoscope 89:906–917, 1979. 237. Goin DW: Proximal intratemporal facial nerve in Bell’s palsy surgery. Laryngoscope 92:263–272, 1982. 238. House WF: Surgical exposure of the internal canal and its contents through the middle cranial fossa. Laryngoscope 71:1363–1385, 1961. 239. Gantz J, Rubinstein JT, Gidley P, Woodworth GG: Surgical management of Bell’s palsy. Laryngoscope 109(8):1177–1188, 1999. 240. Hammerschlag PE: Facial reanimation with jump interpositional graft hypoglossal facial anastomosis and hypoglossal facial anastomosis: Evolution in management of facial paralysis. Laryngoscope 109(2 Pt 2 Suppl 90):1–23, 1999. 241. Koh KS, Kim JK, Kim CJ, et al: Hypoglossal-facial crossover in facial-nerve palsy: Pure end-to-side anastomosis technique. Br J Plast Surg 55(1):25–31, 2002. 242. Fenton JE, Chin RY, Fagan PA, et al: Predictive factors of longterm facial nerve function after vestibular schwannoma surgery. Otol Neurotol 23(3):388–392, 2002. 243. Sherman JD, Dagnew E, Pensak ML, et al: Facial nerve neuromas: Report of 10 cases and review of the literature. Neurosurgery 50(3):450–456, 2002. 244. Yammine FG, Dufour JJ, Mohr G: Intracranial facial nerve reconstruction. J Otolaryngol 28(3):158–161, 1999. 245. Janecka IP, Sekhar LN, Sen CN: Facial nerve management in cranial base surgery. Laryngoscope 103(3):291–298, 1993. 246. Magliulo G, D’Amico R, Forino M: Results and complications of facial reanimation following cerebellopontine angle surgery. Eur Arch Otorhinolaryngol 258(1):45–48, 2001. 247. King TT, Sparrow OC, Arias JM, O’Connor AF: Repair of facial nerve after removal of cerebellopontine angle tumors: A comparative study. J Neurosurg 78(5):720–725, 1993. 248. Gidley PW, Gantz BJ, Rubinstein JT: Facial nerve grafts: From cerebellopontine angle and beyond. Am J Otol 20(6):781–788, 1999. 249. Green JD Jr, Shelton C, Brackmann DE: Surgical management of iatrogenic facial nerve injuries. Otolaryngol Head Neck Surg 111(5):606–610, 1994.

Chapter

75 Gerard M. O’Donoghue MD, FRCS Thomas Nikolopoulos, MD, DM, PhD

Tumors of the Facial Nerve Outline Histopathology Facial Nerve Schwannoma Gross Pathology Microscopic Appearances Topography of Facial Nerve Schwannomas Effects of Schwannomas on the Facial Nerve Microstructure Traumatic Facial Nerve Neuromas Hemangiomas Granular Cell Tumors Glomus Tumors of the Facial Nerve Primary Malignant Temporal Bone Tumors Parotid Tumors Metastatic Disease Neoplastic Involvement in Childhood

J

ohn Conley,1 the great pioneer of facial nerve surgery, aptly commented that tumors of the facial nerve can tax the abilities of the clinician and exhaust the sophisticated resources of modern technology. In many of these patients, preliminary investigations are negative and they typically have been advised by specialists in diverse disciplines, all of whom shed a different perspective on the problem, often to the patient’s bewilderment. Some patients even have undergone well-intentioned but misdirected surgical interventions before a correct diagnosis was made. The facile label of Bell’s palsy is all too readily applied to these patients and may result in delayed diagnosis and compromised outcome from reconstructive surgery. The possibility of neoplastic involvement of the facial nerve should be considered in every patient with any affection of the facial nerve; as often as not, the possibility is dismissed but at least it should always be entertained. This discussion is confined to neoplastic affections of the facial nerve excluding tumors that affect the facial nucleus and its supranuclear connections.

HISTOPATHOLOGY Tumors that affect the facial nerve may arise either intrinsically from within the facial nerve (schwannoma, 1258

Epidermoids, Meningioma, Vestibular Schwannoma, and Other Petrous Apex Tumors Clinical Presentation Symptoms Facial Nerve Symptoms Otologic Symptoms Parotid Mass Pain Office Examination The Facial Nerve Otologic Assessment Examination of the Neck Neurologic Examination General Physical Examination Investigations Audiologic Testing Stapedial Reflex Measurements

Vestibular Testing Other Topographic Tests Electroneuronographic Testing Radiologic Investigation Treatment Transmastoid Approach Transmastoid-Middle Cranial Fossa Surgery Transdural Middle Fossa Resection TranslabyrinthineTranscochlear Approaches Decompression Surgery Watchful Waiting with Interval Scanning Parotid Surgery Stereotactic Radiosurgery Results Summary

hemangioma, etc.) or may arise from structures adjacent to the nerve (cholesteatoma, meningioma, vestibular schwannoma, etc.) or from infiltrative processes in the leptomeninges (leukemia, meningeal carcinomatosis). Primary tumors can arise from the Schwann cell, the fibroblast support cells of the endoneurium, and the epithelial-like cells of the perineurium. Some neuropathologists use the term peripheral nerve sheath tumors because these tumors often contain more than one of these components. The terms neuroma and neurinoma are nonspecific, relate to no particular histopathologic appearance, and are merely loose descriptive terms for a swelling on a nerve.

Facial Nerve Schwannoma The terms schwannoma and neurilemoma are synonymous and are applied to tumors arising from the Schwann cell. It has been said2 that these tumors usually arise in the facial nerve from sensory nerves but there is no histopathologic or clinical basis to support this suggestion. Histologically, they appear as interlacing bundles of spindle-shaped cells frequently arranged in palisades. Two patterns are typically recognized: Antoni type A, which comprises densely cellular areas with cohesive cells arranged in regular patterns, and Antoni type B with areas of vacuolation between cells due to accumulation of extracellular matrix. Schwann cells can

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undergo cytological changes with nuclear pleomorphism and hyperchromicity, which may simulate aggressivity; there are, however, no mitoses. These changes are referred to as “ancient change.” Verocay bodies may appear and represent a whorl-like arrangement of cells with no particular prognostic significance. From a clinical standpoint, schwannomas arise eccentrically, compressing the adjacent nerve trunk, and can often be surgically removed while leaving the trunk intact. Malignant schwannomas of the facial nerve have occasionally been reported. Neurofibromas arise principally from endoneurial connective tissue; they infrequently arise from the nerve roots of cranial nerves but are more commonly found on peripheral nerves in the subcutaneous tissue. Neurofibromata may be associated with von Recklinghausen’s disease. Neurofibromas arise intrinsically in nerves and their removal usually requires nerve resection. Gross Pathology Facial nerve schwannomas can arise at any point along the course of the facial nerve, from the pontomedullary junction to parotid.3 A surgeon’s ability to distinguish an invasive acoustic neuroma from a true facial schwannoma must be questioned. In a series by Dort and Fisch4 each of the five patients with intracranial facial schwannoma also had eighth nerve involvement that required resection. They conclude that the histogenesis of intracranial tumors may be different from that of schwannomas at other sites and that they are more likely to represent an invasive vestibular schwannoma. Macroscopically, these tumors appear as a diffuse bulging of the facial nerve, sometimes over several segments. At times, the enlargement is like a series of dumb-bells and the surgeon needs to exercise considerable caution in determining the limits of tumor resection (frozen section histology is usually necessary).Tumors can reach a considerable size and take the path of least resistance. Thus, they may present as external or middle ear masses or may extend medially toward the cerebellopontine angle (CPA) or cephalad to present as a middle fossa mass.5 Rarely, bilateral facial schwannomas are a manifestation of neurofibromatosis type 2.6 Microscopic Appearances In a study of 600 temporal bones from the Massachusetts Eye and Ear Infirmary,4 undiagnosed intratemporal facial schwannomas were found; 4 of these patients had normal facial nerve function and 1 had a mild paresis.2 The suggestion that this might represent an incidence in the general adult population of 0.8% is untenable because temporal bone collections are clearly not drawn from a representative section of any population. In a review7 of 1400 temporal bones at the University of Minnesota Medical School, only one facial nerve schwannoma was found in the labyrinthine segment; the patient had had a facial paralysis and had an additional schwannoma of the vestibular nerve. In a temporal bone study by Saito8 a tiny neurilemoma of the horizontal portion was seen, which had decompressed itself by erosion of the facial canal and protruded into the middle ear. Intact nerve fibers can permeate a tumor and thus biopsy of these lesions might precipitate a facial paralysis.9

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The histology of facial nerve schwannomas seems to be consistent throughout the different portions of the facial nerve with the possible exception of those arising intracranially. Unlike acoustic neuroma, facial nerve schwannomas are uniformly slow growing and most have been present for many years. An important feature of facial nerve schwannomas is their apparent multicentricity. What may appear to the naked eye as multiple discrete tumors on a nerve is not borne out by histopathologic studies. Instead, multiple discrete intraneural connections are seen between distant portions of the lesion. Janecka and Conley10 reported on 30 primary facial nerve tumors: 26 (87%) were benign, 4 (13%) were malignant, and 4 were multicentric. It is not sufficiently appreciated that these tumors can erode the adjacent otic capsule bone to produce an asymptomatic fistula of either the cochlea or the labyrinth (usually the anterior end of the lateral semicircular canal or the superior canal). In one large series,3 29% of patients had varying degrees of otic capsule erosion. In patients with good cochlear reserve, the risks to hearing loss from surgical removal of a tumor may be considerable and should be weighed seriously in the balance when planning management. Topography of Facial Nerve Schwannomas There is considerable disparity in the literature on the relative incidence of schwannomas at different sites along the facial nerve (Fig. 75-1). These differences are probably no more than a reflection of differing referral practices at the various institutions that report these results. In a review of 48 patients with facial nerve schwannomas at the Otologic Medical Group in Los Angeles the following segments were found to be involved: intracranial, 14; internal auditory canal, 20; labyrinthine segment, 16; geniculate ganglion, 22; horizontal portion, 21; vertical portion, 21; and the extratemporal portion in 7 patients.3 A further review11 found intratemporal tumors to be the most common and commented on the relative rarity of intracranial facial nerve schwannoma. Advances in diagnostic imaging, especially in magnetic resonance (MR) imaging, have helped to define the true anatomic extent of these lesions and their relationship to adjacent structures.5,11,12 It must be said, however, that in large petrous apex tumors, where the anatomy may be considerably distorted and the facial nerve cannot be identified with certainty, a surgeon may have great difficulty deciding if a tumor represents the common vestibular schwannoma or the rarer facial nerve neuroma. In a review of 30 primary facial nerve tumors, 17 were extracranial (12 in the main trunk, 5 affecting the peripheral branches) and 13 were intratemporal (10 involving the horizontal and vertical segments and 3 at the geniculum).10 As noted earlier, many tumors are apparently multicentric and a precise site of origin may be impossible to determine. Tumors in the temporal bone exhibit a distinct predilection for the area of the geniculate ganglion.3,4 The reasons for this are speculative but may well be related to the major structural reorganization of the nerve that takes place at the geniculate ganglion.13 This ganglion marks the junction between the intracranial portion of the nerve (which is surrounded to a variable degree by cerebrospinal fluid [CSF]) and the true intratemporal nerve with its fascicular

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described by Sunderland.18 Three stages are described as follows: Stage 1: The epineurial veins are compressed and become occluded, resulting in venous congestion in the intrafascicular capillaries with a resultant rise in intrafascicular pressure. The nerve dysfunction is usually reversible. Stage 2: With prolonged compression, endothelial damage occurs with extravasation of protein, causing intrafascicular edema. The impermeability of the perineurium may result in a sustained rise in intrafascicular pressure and axonal transport may be arrested. Uncorrected, this results in ischemia, segmental demyelination, scattered axonal disruption, and degeneration. Stage 3: Arterial flow is compromised and permanent damage becomes inevitable. Fibroblast migration is stimulated, resulting in fibrosis of the nerve trunk. Degenerative changes also occur proximally in the cell body.

Figure 75-1. Typical distribution of a facial nerve neuroma. These neuromas often extend over several segments of the facial nerve; in this case it involves the geniculate ganglion, tympanic, and descending portions of the facial nerve. (Courtesy Dr. Robert Jackler, San Francisco.)

arrangement caused by the in-growth of connective tissue at the ganglion. Facial nerve schwannomas should not be confused with the more recently described Jacobson’s nerve schwannoma, which lies in close approximation to but remains distinctly separable from the tympanic portion of the facial nerve.14 Rarely, a discrete schwannoma affects the nervus intermedius,15 the greater superficial branch,16 or the chorda tympani.17 Effects of Schwannomas on the Facial Nerve Microstructure Because tumors compress nerves it is worth briefly reviewing the pathophysiology of facial nerve compression as

The responsiveness of some neoplastic paralyses to steroids may be a result of their effect on the edema described in stage 2. As will be seen, intratemporal facial nerve schwannomas commonly involve varying degrees of facial paralysis. It is likely that schwannomas arising in the fallopian canal exert a compressive effect on the nerve and that at times the bony confines may expand, resulting in a temporary respite from the paralysis. Such recoveries are usually incomplete and with each successive palsy, fewer intact fibers remain. Indeed, some studies have revealed some regenerative capacity of the facial nerve during prolonged compression.8 The resistance of facial nerve fibers to compression is remarkable. This is witnessed most frequently in acoustic neuromas when the nerve is often considerably thinned without clinical dysfunction. This resistance to compression seems to depend on the integrity of the epineurium. Once this is breached (not often the case in benign tumors), facial function is likely to be impaired. It is noteworthy that as many as 50% of facial nerve fibers may have degenerated before clinical signs of facial nerve dysfunction appear. The narrowest portion of the fallopian canal is the labyrinthine segment and the nerve is therefore more vulnerable to compression at this point; in its descending portion, the canal is more commodious with the nerve occupying only about two-thirds of the diameter of the canal.

Traumatic Facial Nerve Neuromas Traumatic neuromas are nonneoplastic proliferations of peripheral nerves. They are composed of disrupted axons, Schwann cells, and endoneurial and epineurial fibroblastic cells in a dense collagenous matrix. Most traumatic neuromas are attributed to an exuberant reparative response to injury. Traumatic facial nerve neuromas may follow relatively trivial injury to the head or face. In some cases, a chronic inflammatory response juxtaposed to a dehiscent nerve has been thought to result in a proliferation of neural and connective tissue elements.19 Indeed, some schwannomas may simulate granulation tissue on a nerve such that a surgeon may be tempted to excise it.20 An unusual form of neuroma, called inflammatory neuroma, may complicate chronic suppurative otitis media when there is no history of trauma to the temporal bone.21

Tumors of the Facial Nerve

Hemangiomas Hemangiomas are probably not true neoplasms but are more likely to be vascular hamartomas composed of blood vessels and are described according to the predominant type of blood vessel found in them, capillary or cavernous. They are located most frequently at the geniculate ganglion (Fig. 75-2). In an elegant study on cats, a highly vascular geniculate capillary plexus was demonstrated.22 In a further study on human temporal bones, vessel counts were taken along the facial nerve and confirmed a rich vascular plexus at the geniculate ganglion with relatively low vessel counts, especially in the labyrinthine segments.23 It has been postulated that the rich vascular network around Scarpa’s and

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geniculate ganglions accounted for the frequency of vascular tumors at this site.13 An important feature of hemangiomas is their tendency to arise eccentrically from nerve, allowing the separation of these tumors from the nerve trunk without disruption of nerve continuity, provided these lesions are diagnosed at an early age.23,24 Unlike schwannomas, these tumors can produce facial paralysis even when only a few millimeters in diameter. This may suggest a vascular steal phenomenon resulting in ischemia of the nerve trunk because many of these tumors are too small to exert a compressive effect. Once considered to be extremely rare, these are now becoming increasingly recognized and, in some centers, are outstripping the incidence of schwannomas. This probably reflects the greater sophistication in microsurgery of the facial nerve and better imaging rather than a true increase in incidence. In some of these tumors, the hemangiomatous blood vessels are surrounded by newly formed lamellar bone giving rise to the “ossifying hemangioma” with its classic radiologic features.13 Grossly, these tumors have a red sponge-like appearance.24 This ossification may represent dystrophic changes related to the very slow development of these tumors (between 4 and 11 years). It is also possible that the bone spicules may result from bone remodeling in response to the tumor. Intratumoral bone formation may help in the preoperative radiologic diagnosis of these lesions, especially in the CPA.

Granular Cell Tumors Granular cell tumors are derived from Schwann cells, have a predilection for the upper respiratory tract, develop typically in the fourth and fifth decades, and have a higher incidence in women and blacks.25 Granular cell tumors may be completely confined within the nerve sheets, which may serve as a pseudocapsule for the tumor. The tumor consists of sheaths of polyhedral cells with eosinophilic granular cytoplasm; the granules stain intensely with periodic acid-Schiff and the diagnosis can be confirmed immunohistochemically.

Glomus Tumors of the Facial Nerve Most glomus tumors can be classified either as glomus tympanicum or jugulare tumors and they can directly invade the facial nerve. A glomus tumor arising from a glomus body in the facial canal has been reported.26 The tumor involved the nerve just proximal to the stylomastoid foramen and extended for 1 cm extracranially. These tumors typically present as either a facial paralysis or pulsatile tinnitus and a case for conservative management can be made in some patients.27 A fibroangioma of the horizontal portion of the nerve has also been described.28

Figure 75-2. A hemangioma of the facial nerve at its most usual location, the geniculate ganglion. Even if small, these lesions can cause a significant facial weakness and can easily be overlooked if diagnostic imaging is not precisely targeted toward the intratemporal facial nerve. (Courtesy Dr. Robert Jackler, San Francisco.)

Primary Malignant Temporal Bone Tumors Most primary malignant tumors of the temporal bone are squamous carcinomas of the external ear canal, which typically involve the adjacent tympanic and mastoid portions

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of the nerve. Facial paralysis may be caused by infiltration and destruction may also be the result. These tumors invade periosteal bone but enchondral bone is remarkably resistant. A comprehensive review of this subject is provided by Stell.29 Other primary tumors, such as papillary adenocarcinoma,30 primary malignant melanoma of the CPA,31 and primary lymphoma of the internal auditory canal32 are much rarer.

Parotid Tumors The facial nerve is an arbitrary divider of the parotid gland into superficial and deep lobes. Primary or secondary neoplasms may infiltrate the main trunk or its peripheral divisions to produce a facial paralysis. In a review of occult neoplasms and facial paralysis, Conley and Selfe1 found that 80% were malignant tumors in the parotid gland. It is worth noting that not all parotid masses that produce a facial paralysis are malignant.33 Pressure effects, especially from recurrent tumor (the mastoid portion being especially vulnerable), kinking, inflammation, and local toxic factors may all play a part. A decision to sacrifice any facial nerve should be taken only after histologic confirmation of the pathologic process and consultation with the patient.

for the temporal bone but when it does, it can erode the facial canal but rarely causes facial paralysis. Intracranial yolk sac tumors may also present with facial paralysis in childhood and are particularly interesting because the biologic marker, α-fetoprotein, can be used to aid diagnosis and monitor response to treatment.36 Although facial nerve neuromas are rare in children they vary considerably in their behavior; thus, conservative treatment may be useful for slow-growing tumors, but when they develop rapidly, early surgical intervention is needed and outcomes are encouraging.37 Interestingly, a primary meningioma of the facial canal in the fallopian canal was described in a 7-year-old girl.38

Epidermoids, Meningioma, Vestibular Schwannoma, and Other Petrous Apex Tumors It is of the utmost surgical importance to appreciate the different relationship nonacoustic tumors can have with the facial nerve16 since the facial nerve does not typically lie on the anterior surface of these tumors and is thus more prone to surgical injury.39,40 This topic is discussed in detail in other chapters of this textbook.

Metastatic Disease The temporal bone, especially the rich vascular marrow spaces of the petrous apex, is a frequent site of subclinical metastatic deposits. The metastases result from hematogenous spread from primary sites in the breast, kidney, lung, and stomach and occasionally from other sites (skin, prostate, etc.). In a study by Saito and Baxter2 of 26 temporal bones from patients with advanced malignancy, 7 (27%) showed evidence of metastatic disease, a much higher percentage than one might think. It is interesting that in nearly half the patients with metastatic involvement of the facial canal, no facial paralysis had been observed and one specimen actually showed evidence of nerve regeneration. They felt that invasion of the labyrinthine segment was especially likely to result in facial paralysis. The resistance of nerve fibers to invasion was considerable with some intact nerves seen in the substance of some neoplasms. In a study of 14 patients with metastatic tumor to the temporal bone, 6 showed evidence of facial paralysis.7 There was a strong correlation between the presence of paralysis and disruption of the nerve sheath. Furthermore, facial paralysis usually denoted extensive intracranial metastatic disease. In order of frequency, the most common sites for metastatic involvement were the internal auditory canal, the mastoid, and the tympanic and labyrinthine segments. Involvement of the labyrinthine segment increased the risk of facial paralysis.

Neoplastic Involvement in Childhood Neoplastic involvement of the facial nerve in childhood is rare. In a review of 25 consecutive cases, three neoplastic causes were identified: cerebellar astrocytoma, leukemia, and rhabdomyosarcoma.34 Facial paralysis may be the presenting symptom of childhood leukemia.35 Eosinophilic granuloma (Langerhans’ cell histiocytosis) has no special predilection

CLINICAL PRESENTATION The rarity of primary neoplastic affections of the facial nerve is a major obstacle to early diagnosis. It is conceivable that most neurologists and plastic surgeons would never encounter such a case; most otolaryngologists would see no more than one or two patients in a working lifetime. Tunnel vision adds to the difficulty because most specialists view the facial nerve from their own narrow perspective: The neurologist or neurosurgeon will persist with brain scans, the neurophysiologist will rely on electrical tests, the plastic surgeon will respond to the challenge of reconstructive surgery, the otologist will focus on the temporal bone, and infectious disease specialists will indulge in virology studies—the patient is thus at the mercy of the first physician to whom he or she presents. On the other hand, idiopathic facial paralysis is a common entity and the results from masterly inactivity are excellent. Thus, many clinicians are understandably lulled into a sense of security when treating the patient with a paralyzed face. It is incumbent, therefore, on all specialists experienced in facial nerve conditions to educate their colleagues of the importance of carefully assessing every patient with a facial paralysis and to refer onward if any doubt prevails. The medicolegal aspects of failure to diagnose the neoplastic basis of a facial paralysis are worth mentioning. Patients are understandably aggrieved when, after months or years of misdirected treatment, the cause of their paralysis is finally discovered. The fact that the eventual outcome of facial nerve reconstruction is closely related to the duration of the preoperative facial paralysis3,4 is welcome ammunition for the compensation lawyer, highlighting further the need for early diagnosis of these conditions. The importance of careful history-taking and documentation of physical findings cannot be overstressed. There is

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too great a tendency to reach for a request slip for the most expensive imaging technique without having done the essentials of good medical practice. As stated by Conley and Selfe,1 the most important step is the human evaluation carried out by the responsible surgeon. His 14 patients with occult neoplasms affecting the facial nerve had no fewer than 12 operative procedures: mastoid surgery (2), temporal bone exploration of the facial nerve (3), oculoplasties (2), hypoglossal crossover (1), rhytidectomy (3), and fascial slings (1). Of these patients, 80% had malignant parotid tumors and 15% had neurilemomas of the main trunk.

Symptoms Patients with neoplasms of the facial nerve may present in a variety of ways depending on three factors: 1. The response of the nerve to compression or infiltration. 2. The site of the neoplasm and hence its effect on adjacent anatomic structures, most notably the cochlea and the ossicular chain. 3. Histopathology: Small vascular tumors may present with paralyses one might normally see with larger tumors. Facial Nerve Symptoms From the section on histopathology, it is clear that the facial nerve is particularly resistant to compression and that facial paralysis may not be a feature of neoplastic involvement. In one study2 nearly half the patients with histologic evidence of tumor involvement showed no paralysis. In another series of eight neuromas, only two patients actually presented with a facial nerve deficit.41 In the Zurich experience,4 3 out of 16 patients had normal facial nerve function; at the Otologic Medical Group in Los Angeles, 26 patients out of 48 had normal function.3 Janecka and Conley10 found that 84% of patients with intratemporal tumors and 35% with extratemporal tumors had facial paralysis. The most typical presentation of facial nerve tumors is gradually progressive facial paralysis, often accompanied by twitching of the facial musculature. The paralysis may be intermittent and may be labeled “recurrent Bell’s palsy.” In such instances, recovery of facial nerve function is rarely complete during attacks because with each episode, further facial nerve fibers are lost. Sudden complete facial paralysis occurs in about half the patients with Bell’s palsy, but such an onset can occur in more than a third of patients with neoplastic involvement of the facial nerve.42 Most patients with Bell’s palsy begin to show signs of recovery at or before 3 months. The diagnosis of Bell’s palsy should not be accepted if there are no signs of recovery at 6 months, and the search for a tumor should be intensified. Slow progression of a facial paralysis beyond 3 weeks is indicative of a tumor. However, continued progression of a facial palsy up to 10 days from the onset is sometimes seen in Bell’s palsy. A congenital facial paralysis caused by an intratemporal neuroma has been reported.43 The response of a facial paralysis to a trial of steroids is sometimes said to support the diagnosis of idiopathic

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facial paralysis. However, paralysis caused by tumors may also respond to steroids and one cannot therefore attach much diagnostic importance to such a response.1 Portmann,44 who practiced in a major wine-growing part of France, commented that gustatory or lacrimal reasons were never the presenting features of the patients he encountered. His experience was that facial paralysis was well established by the time they presented. A neuroma of the chorda tympani presented with conductive hearing loss.45 Otologic Symptoms Tumors that arise from the intratemporal facial nerve are likely to exhibit a variety of otologic symptoms. Tumors that arise from the labyrinthine portion will most likely develop cochlear or vestibular symptoms (sensorineural hearing loss, tinnitus, or vertigo). In a review of 48 patients at the Otologic Medical Group, the most frequent presenting symptom was hearing loss, occurring in 33 (69%) patients.3 In addition, 29 (60%) patients had tinnitus and 16 (34%) had experienced vertiginous episodes. In other patients, discharge from the ear may be a major feature.46 Lesions that affect the descending portion of the facial nerve may interfere with the ossicular chain, causing a conductive loss. It is perhaps worth drawing attention to the fact, well known to otologists, that hearing loss is not a feature of Bell’s palsy. Therefore, the combination of hearing loss and facial paralysis should heighten the clinical suspicion of a facial nerve schwannoma. Parotid Mass Neoplastic involvement of the extratemporal facial nerve is heralded either by the presence of a parotid mass or by single branch paralysis. Malignant tumors of the parotid account for about 80% of such cases, with 15% being attributable to neurilemomas of the nerve.1 It is important to emphasize that although a facial nerve schwannoma may present as a parotid mass, the neoplastic involvement may extend proximal for several segments. In one 6-month-old child, such a tumor was found to extend to the geniculate ganglion.3 Pain Pain accompanying any disturbance of facial nerve function or a parotid mass always deserves special attention, especially if the pain lasts for weeks or months. Pain may be a feature of Bell’s palsy or of the Ramsay Hunt syndrome but it rarely lasts for more than a few days. Pain is often a major feature of malignant parotid disease, commonly as a result of involvement of the trigeminal nerve (usually the auriculotemporal nerve). Extensive local destruction inevitably involves the dural surfaces of the temporal bone, the eustachian tube, and the lower cranial nerves.

Office Examination The glamour accorded contemporary sophisticated diagnostic techniques has often resulted in physicians according relatively little importance to the clinical examination.

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This is most unfortunate because without the guidance offered by clinical assessment, many of these techniques can be quite useless and may merely delay diagnosis. The office evaluation should encompass five areas: 1. The facial nerve 2. Otologic assessment 3. Examination of the neck and oral cavity (with special reference to the parotid gland) 4. Neurologic examination 5. General physical examination The Facial Nerve Although it is unlikely that even the most cursory examination would miss a total facial paralysis, it is certainly true that subtle degrees of facial weakness can easily be missed. As mentioned earlier, neoplastic involvement of the nerve is likely to induce a partial paralysis or paralysis of a single branch; therefore, the utmost attention to the assessment of facial movement is essential. It may be necessary to ask the patient to make repeated facial movements in quick succession to highlight subtle differences between the two sides of the face. A useful maneuver is to ask the patient to close the eye while the examiner tries to keep the lids apart; a slight loss of power that may not be detectable on observation alone may become apparent. Twitching of the facial musculature should always be looked for because mild twitching may be entirely asymptomatic. Synkinesis, mass movements, and contractures may all occur and are usually quite unmistakable. Although contemporary grading systems of facial paralysis have definite limitations, especially in terms of the wide interobserver variation in partial paralysis, it is still worth recording the grade of paralysis. The House-Brackmann grading system is the most internationally used at present and is recommended for this purpose.47 It is essential to document the paralysis by means of a range of still photographs as the patient attempts a standard range of facial movements. Video documentation can be an even more valuable record. The evaluation of the eye and the assessment of the protection of the cornea are of paramount importance. An eye that is apparently wet, with pooling of tears and epiphora, is as much at risk as a dry eye. The early involvement of a colleague in oculoplastic surgery is indispensable and should always be sought in cases where the cornea is at risk. Urgent ophthalmologic attention should be sought for patients who also have diminished or absent corneal sensation. Otologic Assessment Examination of the ear is mandatory in the evaluation of a patient with facial paralysis. Otoscopic evaluation may reveal a mass behind the tympanic membrane (Fig. 75-3). In one series, a mass was present in 14 (29%) cases; it is noteworthy that the mass had been unwittingly biopsied in 8 cases and usually resulted in a facial paralysis.3 Less frequently, a tumor presents as an aural polyp, especially if it arises in the descending portion of the facial nerve when it

Figure 75-3. A facial nerve neuroma can present as a middle ear mass causing a conductive hearing loss. Biopsy of such a lesion can result in a facial paralysis and should be undertaken only on a fully informed patient. (Courtesy Dr. Robert Jackler, San Francisco.)

may erode the bone and present in the ear canal.20 In these instances, there may be an associated infection or inflammation and the diagnosis of otitis externa or otitis media may be applied until, after some weeks or months, it becomes clear that the situation is more complicated. Tuning fork testing is useful in categorizing the hearing loss into a conductive or sensorineural variety. In one series,3 31 of 48 patients had hearing loss; in 21 it was sensorineural, in 9 it was conductive, and 1 patient had a mixed deficit. Examination of the Neck The parotid gland is so intimately related to the facial nerve that it must be systematically examined in patients with facial paralysis. Large lumps are obvious and usually have come to the notice of the patient. However, small tumors, especially in patients with obese necks, can be extremely difficult to detect on physical examination. Examination of the deep lobe should not be omitted. General examination of the neck, especially to exclude nodal metastases, is essential. Some recommend the use of fine needle aspiration biopsy for preoperative diagnosis.48 Neurologic Examination A comprehensive neurologic examination is mandatory in patients with facial paralysis, with special attention to the trigeminal and lower cranial nerves and to the presence or absence of cerebellar signs. General Physical Examination This general examination, often best done by an internist, may shed light on unsuspected subclinical disease. One should bear in mind the host of medical conditions that

Tumors of the Facial Nerve

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can cause a facial paralysis and that may go undiagnosed if the examination is confined to the head and neck.

gland secretions to estimate chorda tympani function were equally unpleasant and did not gain much popularity.

INVESTIGATIONS

Electroneuronographic Testing

Audiologic Testing

Opinions differ on the usefulness of electroneuronographic (ENOG) testing. Difficulties have arisen because of a lack of standardization among centers and there are many sources of potential error—skin impedance, electrode placement, and artifacts due to stimulation of the masseter muscle. Inter-test variations are frequent and different apparatuses may yield different test results. It is likely, therefore, that these tests will be most useful to clinicians who use them frequently and who are familiar with the limitations of their own test procedures. In one series, preoperative electroneuronography or electromyography was always abnormal; it appears that the electromyographic finding of simultaneous denervation and reinnervation is consistent with compression neuropathy.24 Electrophysiologic tests are useful in evaluating the extent of nerve injury. It is not uncommon to repeat tests to obtain a clear picture of the stimulability of the nerve. These tests may also indicate subclinical dysfunction of an apparently normal nerve and may help differentiate preoperatively between the more common acoustic neuroma and a true facial nerve schwannoma.

A pure tone audiogram is so readily available in clinical practice that it should be obtained in all patients with facial paralysis. An audiogram can detect subtle degrees of hearing impairment that may be unnoticed by the patient. It is worth reiterating that Bell’s palsy does not cause hearing impairment and therefore any abnormality on the pure tone audiogram should mandate further investigation. If surgery is being contemplated, the hearing status of the contralateral ear should be confirmed. Electric response audiometry is a useful office investigation in patients whose paralysis is accompanied by sensorineural hearing impairment, tinnitus, or vertigo. Any indication of retrocochlear pathology on the tracing is highly significant and mandates further investigation.

Stapedial Reflex Measurements Stapedial reflex measurements should be first-line investigations because of their availability and usefulness. The contraction of this muscle in response to pure tones of about 85 dB is bilateral and results in stiffening of the sound-conducting mechanism detectable by an impedance probe in the ear canal. A stapedial reflex in a patient with a dense facial paralysis implies a lesion distal to the branch to the stapedius muscle and should make the clinician look especially carefully at the parotid gland. This test has distinct limitations. If, for instance, there is a conductive loss in the ear being tested, the stapedius muscle contraction will not be observed. Lesions proximal to the branch to the stapedius muscle do not always result in loss of the stapedial reflex because sufficient fibers may remain intact to cause a muscle contraction.

Vestibular Testing Electronystagmographic testing is especially indicated in patients with suspected erosion of the otic capsule or where major temporal bone surgery is contemplated. Other Topographic Tests In the past, formal “site of lesion tests” received considerable attention but the much improved imaging techniques have sounded the death knell for many of these tests. The Schirmer’s test is easy to perform with commercial kits but there are many pitfalls. For instance, if the lower conjunctival fornix is not emptied of pooled secretions before the test, the wetting of the paper strip may appear better than it should be. Also, the secretomotor fibers to the lacrimal gland can be remarkably resistant to pressure so that even in lesions affecting the labyrinthine portion of the nerve, a normal Schirmer’s test may be recorded. Electrogustometry, based on the response of the tongue to electrical stimulation, was unpleasant and entirely based on a patient’s subjective response. Collection of maxillary

Radiologic Investigation The greatest recent advance in the diagnosis and management of facial nerve tumors is the ability to image them with much greater accuracy than previously. However, it must be reemphasized that diagnostic imaging is not a substitute for detailed clinical evaluation. It is unreasonable to expect a neuroradiologist to make the best use of contemporary imaging modalities in the absence of pertinent observations from the referring clinician. The choice of initial investigation often reflects the bias of the referring physician. For instance, a neurologist is likely to request a brain scan and an otolaryngologist is most likely to request mastoid or temporal bone views. The complementary role of high-resolution thin-section computed tomography (CT) with bone algorithms and magnetic resonance imaging (MRI) can be used to good effect when investigating patients with a facial paralysis.11 The high spatial resolution not only in the x- and y-axes but also in the z-axis using multislice spiral CT gives excellent visualization of the bony anatomic detail around a suspected lesion of the facial nerve.11 Multiplanar three-dimensional T2-weighted fast spinecho (FSE) was found to be of value in demonstrating the relationship of the facial nerve to small tumors in the internal auditory canal but was less effective with bulky tumors.12 Undoubtedly, contemporary MRI sequences have enabled much more accurate prediction of the degree of involvement of a facial nerve by a tumor,5 which has helped surgical planning and patient counseling. However, the heightened sensitivity of MRI can be undermined by its relative lack of specificity. The approach to imaging the intratemporal portion of the nerve has to be flexible and the scan planes must be adjusted to take into account the

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tortuous intratemporal course of the nerve. The approach has to be meticulous because it is easy to miss tiny lesions, most notably hemangiomas, which can cause paralysis early in their course and which are eminently resectable when small, often leaving the main trunk of the nerve intact.

TREATMENT The management of facial nerve tumors calls for considerable versatility and expertise on the part of the surgeon. In many cases, no treatment could be the best treatment.49,50 In cases where the diagnosis has been made and diagnostic imaging has been appropriate, the surgeon can have a comprehensive discussion with the patient about the advisability of surgery. In elective surgery of this kind, it is essential that every attempt be made to counsel patients about the risks of operative intervention and to compare them with the risks of the untreated disease. Clearly, the risks of intervention should be less than those of the natural history of the disease itself. It is important therefore that surgeons cite their own results based on their experience in this kind of surgery and not those of the great luminaries in the field. For many surgeons who only occasionally deal with these tumors, the best course of action may be for the surgeon to stay his or her hand and observe the patient’s progress. Certainly, if surgery is indicated, the surgeon should have experience in the full range of temporal bone surgery to deal competently with these challenging lesions. Tumors may be encountered as a surprise during tympanoplasty surgery or for surgery of a parotid mass. This presents the surgeon with a difficult dilemma. To proceed with tumor removal after having gained appropriate exposure would risk having the patient recover from anesthesia to find a paralyzed face. This would be very distressing for the patient and the relationship between surgeon and patient could be irretrievably damaged. To have a biopsy of the tumor and to defer definitive surgery to another occasion is another option, but it is not without the risk of a facial paralysis. Bear in mind that many intact facial nerve fibers may traverse a tumor and their disruption will result in paralysis.51 It therefore seems much more prudent to abandon surgery without interference with the tumor, to explain to the patient the difficulties encountered, to arrange appropriate diagnostic studies, and to plan surgery on another occasion or to manage the condition by interval scanning. Three general factors determine the surgical approach: 1. The site of the lesion 2. The extent of the lesion 3. The hearing status in both ears The surgeon embarking on treating these tumors should be able to expose the facial nerve from “pons to parotid” because the tumors may be more extensive than predicted. Neuromonitoring of the facial nerve can be helpful when preservation of the continuity of the nerve is a realistic possibility.

Transmastoid Approach If the lesion is confined to the transverse or descending portions of the nerve, a transmastoid approach alone should be sufficient. Typically in these situations a conductive loss

exists and reconstruction of the ossicular chain may be attempted immediately or as a secondary procedure. Nerve grafting, from great auricular or lateral sural, is eminently possible and should always be attempted, irrespective of the duration or severity of the facial paralysis. It is eminently feasible to graft the facial nerve at the brainstem and the outcome is remarkably good.3 Partial nerve resection can be treated by inlay techniques, but it can often be difficult to decide when to excise and graft and when to inlay. Lesions in the more proximal portion of the horizontal portion of the nerve can sometimes be difficult. The exposure afforded by the technique described by May52 is worth bearing in mind because it may save some patients the need for middle fossa surgery. Lesions can extend distally into the parotid and the surgeon must be prepared to follow the tumor accordingly. Frozen sections should always be taken to ensure that margins are free because the naked eye appearances are unreliable. This may mean adding a middle fossa procedure to a transmastoid approach in order to gain satisfactory clearance. It is important to bear in mind that facial nerve schwannomas tend to extend like beads along the nerve (from “pons to parotid”) and several segments may be involved despite radiologic appearances of a very discrete lesion. Patients must always be advised about this feature of facial nerve schwannomas. Determining where the tumor-nerve interface lies can be done with reasonable accuracy using appropriate MRI. Frozen section of the tumor itself should be undertaken to confirm the diagnosis. More difficult for the histopathologist to interpret, however, are samples from the nerve itself as hematoxylin and eosin staining shows only gross morphologic change in the nerve trunk. Besides, frozen section samples are notoriously small for correct processing and are plagued by trauma artifact. Thus, samples are best taken and sent for immunohistochemical staining. The addition of the neurofilament and C-IV-22 immunostains to the S-100 protein analysis is particularly useful.53 The S-100 is a calciumbinding protein that is expressed in normal and neoplastic Schwann cells and is a useful marker of Schwann cells in nerves and nerve-derived tumors. Incomplete tumor resection may result in tumor recurrence.54

Transmastoid-Middle Cranial Fossa Surgery The transmastoid-middle cranial fossa approach is the most widely adopted in the surgical management of these tumors. Lesions that involve the genu or the labyrinthine segment of the nerve (and where there is a desire to preserve cochlear function) usually warrant the combined exposure of these approaches. Facial nerve tumors may cause a fistula into the labyrinth and the utmost care must be taken during removal to prevent loss of cochlear and vestibular function. Small hemangiomas of the facial nerve can be removed and leave the main trunk intact, often through a middle fossa procedure alone.24

Transdural-Middle Fossa Resection Transdural resection of these tumors has been advocated10 because of the enhanced visibility but the added morbidity,

Tumors of the Facial Nerve

especially epilepsy and aphasia, of this approach (as distinct from extradural surgery) is a major concern.

Translabyrinthine-Transcochlear Approaches If cochlear function in the tumor ear is poor or absent and if the contralateral ear has normal hearing, a translabyrinthine or transcochlear approach is likely to be the approach of choice. These approaches give full exposure of the intracranial and intratemporal portions of the nerve and allow nerve suturing, rerouting, end-to-end anastomosis, and interposition grafting as appropriate. Formal closure of the defect, usually with abdominal fat, is essential to prevent leakage of CSF.

Decompression Surgery Many patients with normal facial nerve function or with mild paralysis are unwilling to undergo formal excision and grafting of the nerve because of the risk of greater disfigurement. In these patients, wide bony decompression of the nerve may be a compromise, postponing definitive surgery until the paralysis progresses.49 This surgery carries a risk to cochlear function by a number of mechanisms: drilling into the labyrinth, inadvertently uncovering an inner ear fistula, and trauma to the ossicular chain.

Watchful Waiting with Interval Scanning Serious consideration should always be given to nonsurgical management of facial schwannomas. Surgery undoubtedly carries a risk of significant morbidity, especially in terms of deterioration of facial nerve function (most notably in patients with good facial nerve function whose lesions require excision and grafting of the nerve). There is also a risk of sensorineural hearing loss and tinnitus. Most schwannomas are indolent, slow-growing lesions. Patients with normal facial nerve function or those with mild weakness and patients with normal hearing in the tumor ear are naturally often reluctant to undergo major temporal bone surgery. One series that compared patients who underwent surgery for their schwannomas with those whose tumors were managed conservatively found that the facial nerve outcome was much better in those managed conservatively.50 They concluded that delaying surgical resection gave patients the opportunity to enjoy normal facial function, possibly indefinitely. In these patients, serial scanning is a commendable management strategy. The timing of intervention, if it is ever needed, is mandated by the behavior of the tumor. The suggestion55 that upon diagnosis of neoplastic involvement of the nerve, the surgeon should adopt the philosophy of the cancer surgeon, even though most lesions are benign, is now entirely untenable.

Parotid Surgery Extratemporal tumors can be approached in the same way as a standard parotidectomy. However, these lesions have been found to extend into the mastoid bone as far proximally as the internal auditory canal. The surgeon should

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therefore bear this in mind and have the requisite equipment and expertise at the time of surgery to excise the tumor completely and graft the nerve.

Stereotactic Radiosurgery The attraction of stereotactic radiosurgery for patients lies in the avoidance of surgery and the lack of perceived risk. However, the treatment does not remove tumors and simply aims to “control” growth. The treatment is certainly attended by the risk of significant collateral injury to adjacent structures and the possibility of malignant change in benign lesions many years down the line.56 Nonetheless, nonacoustic schwannomas have been subjected to radiosurgery with excellent preliminary tumor control and a favorable toxicity profile.57 However, the incremental benefit of radiosurgery over no treatment remains uncertain.

Results Most series, with some notable exceptions, have reported relatively small numbers of primary facial nerve tumors. The major determinant of facial nerve outcome is the duration of the preoperative facial paralysis. Patients with long-standing complete paralysis tend to do badly, presumably due to irreversible degenerative changes in the axon both proximally and distally and at the motor endplate. In one large series,3 schwannoma removal required resection of the nerve and interposition grafting in 36 (75%) explorations, 7 patients had the nerve rerouted and end-to-end anastomosis performed, and 11 patients had the schwannoma removed but more than 50% of the main trunk was left behind and inlay grafting was used. No distinct advantage emerged for any type of reconstruction. In the Zurich series14 of 26 patients, the nerve had to be sacrificed in all but 1 patient in which the nerve was successfully dissected off the pes anserinus. Nerve grafting (great auricular or sural nerve) was always used irrespective of the duration of preoperative paralysis, patient’s age, or size of nerve defect. Partial nerve resection or inlay grafting was not done. Graft lengths ranged from 1 cm to 10 cm (mean 4.3 cm) and both single and cable grafts were used. It is interesting that the longer grafts yielded slightly better functional results than did short grafts (though not to a statistically significant level). Cable grafts and single grafts had similar average recovery scores. There was no significant difference in recovery scores between patients with and without preoperative facial dysfunction. There was a trend toward poorer recovery in patients with long-standing palsy. Nerve substitution procedures are used with patients in whom the ultimate return of function is poor. Static and dynamic facial reanimation procedures are also important therapeutic options in the rehabilitation of these patients. In all cases of facial paralysis, the early involvement of an oculoplastic surgeon is strongly recommended to ensure that the cornea is protected in a way that causes the patient the least discomfort. A variety of nursing, medical, and surgical techniques are available and the reader is referred to an excellent review of the subject by Seiff and Chang.58 It is interesting that some authors appear to overlook reporting of postoperative hearing results, especially for

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intratemporal lesions. Some patients may find the loss of hearing or the development of tinnitus a high price to pay for removal of a relatively asymptomatic tumor and, therefore, nonoperative treatment should be presented to these patients as an entirely reasonable management approach.

SUMMARY About 5% of peripheral facial paralyses are caused by tumors and as many as 50% of patients with facial nerve tumors do not have facial paralysis when they consult a physician. Gradually progressive or recurrent paralysis or facial twitching suggest neoplastic involvement of the nerve. Schwannomas can involve many contiguous segments of the nerve and they can erode the adjacent otic capsule bone. Hemangiomas can produce facial paralysis even though they may be extremely small. Basic history-taking and examination coupled with a continued awareness of the possibility of a neoplasm are essential for early diagnosis. The judicious use of CT and MRI scanning by an experienced neuroradiologist working in close collaboration with a clinician will invariably confirm the diagnosis. Patients with these neoplasms, especially those with normal facial nerve function and hearing, need detailed preoperative counseling by the surgeon who should cite personal results in this surgery to the patient and not the best reported results in the literature. A compelling case for conservative management can be made and should be presented to patients at the outset. Restoration of nerve continuity should always be undertaken at the primary procedure by either rerouting or grafting, with nerve substitution procedures being reserved for those with poor return of facial nerve function. The most important determinant of outcome in terms of facial nerve function is the duration of the preoperative paralysis.

ACKNOWLEDGMENT The author acknowledges the helpful advice given in the preparation of this chapter by Professor J. Lowe, Department of Neuropathology, University of Nottingham.

REFERENCES 1. Conley J, Selfe RW: Occult neoplasms in facial paralysis. Laryngoscope 91:205–210, 1981. 2. Saito H, Baxter H: Undiagnosed intratemporal facial nerve neurilemmomas. Arch Otolaryngol 95:415–419, 1972. 3. O’Donoghue GM, Brackmann DE, House JW, Jackler RK: Neuromas of the facial nerve. Am J Otol 10:49–54, 1989. 4. Dort JC, Fisch U: Facial nerve schwannomas. Skull Base Surg 1:51–56, 1991. 5. Kertesz TR, Shelton C, Wiggins RH, et al: Intratemporal facial nerve neuroma: Anatomical location and radiological features. Laryngoscope 111:1250–1256, 2001. 6. Fenton JE, Morrin MM, Smail M, Sterkers O, Sterkers JM: Bilateral facial nerve schwannomas. Eur Arch Otorhinolaryngol 256:133–135, 1999. 7. Jung TTK, Jun B, Shea D, Paparella MM: Primary and secondary tumors of the facial nerve. A temporal bone study. Arch Otolaryngol Head Neck Surg 112:1269–1273, 1986.

8. Saito H: Tumor invasion of the facial nerve: A study of eight temporal bones. In Graham MD, House WF (eds.): Disorders of the Facial Nerve. New York, Raven, 1982, pp 225–236. 9. Hajjaj M, Linthicum FH Jr: Facial nerve schwannoma: Nerve fibre dissemination. J Laryngol Otol 110:632–633, 1996. 10. Janecka IP, Conley J: Primary neoplasms of the facial nerve. Plastic Reconstr Surg 79:177–183, 1987. 11. Sartoretti-Schefer S, Kollias S, Valavanis A: Spatial relationship between vestibular schwannoma and facial nerve on threedimensional T2-weighted fast spin-echo MR images. Am J Neuroradiol 21:810–816, 2000. Comment in: Am J Neuroradiol 21:805, 2000. 12. Jager L, Reiser M: CT, MR imaging of the normal and pathologic conditions of the facial nerve. Eur J Radiol 40:133–146, 2001. 13. Fisch U, Ruttner J: Pathology of intratemporal tumors involving the facial nerve. In U Fisch (ed.): Facial Nerve Surgery. Birmingham, Ala, Kugler/Aesculapius, 1977, pp 448–456. 14. Kesser BW, Brackmann DE, Ma Y, Weiss M: Jacobson’s nerve schwannoma: A rare middle ear mass. Ann Otol Rhinol Laryngol 110:1030–1034, 2001. 15. Kudo A, Suzuki M, Kubo N, et al: Schwannoma arising from the intermediate nerve and manifesting as hemifacial spasm. Case report. J Neurosurg 84:277–279, 1996. 16. Michel O, Wagner M, Guntinas-Lichius O: Schwannoma of the greater superficial petrosal nerve. Otolaryngol Head Neck Surg 122:302–303, 2000. 17. Biggs ND, Fagan PA: Schwannoma of the chorda tympani. J Laryngol Otol 115:50–52, 2001. 18. Sunderland S: Some anatomical and pathophysiological data relevant to facial nerve injury and repair. In Fisch U (ed.): Facial Nerve Surgery. Birmingham, Ala, Kugler/Aesculapius, 1977, pp 47–61. 19. Synderman C, May M, Berman MA, Curtin HD: Facial paralysis: Traumatic neuromas vs facial nerve neoplasms. Otolaryngol Head Neck Surg 98:53–59, 1988. 20. Zhang Q, Jessurun J, Schachern PA, Paparella MM, Fulton S: Outgrowing schwannomas arising from tympanic segments of the facial nerve. Am J Otolaryngol 17:311–315, 1996. 21. Telischi FF, Arnold DJ, Sittler S: Inflammatory neuroma of the facial nerve associated with chronic otomastoiditis. Otolaryngol Head Neck Surg 113:319–322, 1995. 22. Balkany TJ: The intrinsic vasculature of the cat facial nerve. Laryngoscope 96:70–77, 1986. 23. Balkany TJ, Fradis M, Jafek BW, Rucker NC: Hemangioma of the facial nerve: Role of the geniculate capillary plexus. Skull Base Surg 1:59–63,1991. 24. Shelton C, Brackmann DE, Lo WMM, Carberry JN: Intratemporal facial nerve hemangiomas. Otolaryngol Head Neck Surg 104:116–121, 1991. 25. May M, Beckford NS, Bedetti CD: Granular cell tumor of facial nerve diagnosed at surgery for idiopathic facial nerve paralysis. Otolaryngol Head Neck Surg 93:122–126, 1985. 26. Dutcher PO, Brackmann DE: Glomus tumor of the facial canal. Arch Otolaryngol Head Neck Surg 112:986–987, 1986. 27. Petrus LV, Lo WM: Primary paraganglioma of the facial nerve canal. Am J Neuroradiol 17:171–174, 1996. 28. Barbary ASE: Fibro-angioma of the facial nerve. J Laryngol Otol 80:1265–1267, 1966. 29. Stell PM: Carcinoma of the external auditory meatus and middle ear. Clin Otolaryngol 9:281–299, 1984. 30. Dadas B, Alkan S, Turgut S, Basak T: Primary papillary adenocarcinoma confined to the middle ear and mastoid. Eur Arch Otorhinolaryngol 258:93–95, 2001. 31. Whinney D, Kitchen N, Revesz T, Brookes G: Primary malignant melanoma of the cerebellopontine angle. Otol Neurotol 22:218–222, 2001. 32. Angeli SI, Brackmann DE, Xenellis JE, et al: Primary lymphoma of the internal auditory canal. Case report and review of the literature. Ann Otol Rhinol Laryngol 107:17–21, 1998.

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33. DeLozier H, Spinella MJ, Johnson GD: Facial nerve paralysis with benign parotid masses. Ann Otol Rhinol Laryngol 98:644–647, 1989. 34. Grundfast KM, Guarisco JL, Thomsen JR, Koch B: Diverse etiologies of facial paralysis in children. Int J Pediatr Otorhinolaryngol 19:223–239, 1990. 35. Zappia JJ, Bunge FA, Koopman CF, McClatchey KD: Facial nerve paresis as a presenting symptom of leukemia. Int J Pediatr Otolaryngol 19:259–264, 1990. 36. Frank TC, Anand VK, Subramony C: Passim yolk sac tumor of the temporal bone: Report of a case. Ear Nose Throat J 79:183, 187–188, 191–192, 2000. 37. Van Den Abbeele T, Viala P, Francois M, Narcy P: Facial neuromas in children: Delayed or immediate surgery? Am J Otol 20:253–256, 1999. 38. Jabor MA, Amedee RG, Gianoli GJ: Primary meningioma of the fallopian canal. South Med J 93:717–720, 2000. 39. Hilton MP, Kaplan DM, Ang L, Chen JM: Facial nerve paralysis and meningioma of the internal auditory canal. J Laryngol Otol 116:132–134, 2002. 40. Mallucci CL, Ward V, Carney AS, O’Donoghue GM, Robertson I: Clinical features and outcomes in patients with non-acoustic cerebellopontine angle tumors. J Neurol Neurosurg Psychiatry 66: 768–771, 1999. 41. Latack JT, Gabrielsen TO, Knake JE: Facial nerve neuromas: Radiologic evaluation. Radiology 149:731–739, 1983. 42. May M: The Facial Nerve. New York, Thieme-Stratton, 1986, pp 365–399. 43. Portmann M, Vazel P, Paiva A: Apropos d’ un cas de neurinome intra-temporal du nerf facial chez une jeune enfant avec paralysie néonatal. Rev Laryng (Bordeaux) 102:439–443, 1981. 44. Portmann M: Clinical features and diagnosis of facial paralysis caused by intratemporal tumors. In Fisch U (ed.): Facial Nerve Surgery. Birmingham, Ala, Kugler/Aesculapius, 1977, pp 457–462. 45. Weit RW, Lotan AN, Monsell EM, Shambaugh GE: Tumor involvement of the facial nerve. Laryngoscope 93:1301–1309, 1983.

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46. Hingorani RK: Neurilemmoma of facial nerve. J Laryngol Otol 84:1275–1280, 1970. 47. House JW: Facial nerve grading system. Laryngoscope 93:1056–1069, 1983. 48. Chong KW, Chung YF, Khoo ML, et al: Management of intraparotid facial nerve schwannomas. Aust N Z J Surg 70:732–734, 2000. 49. Angeli SI, Brackmann DE: Is surgical excision of facial nerve schwannomas always indicated? Otolaryngol Head Neck Surg 117:S144–S147, 1997. 50. Liu R, Fagan P: Facial nerve schwannoma: Surgical excision versus conservative management. Ann Otol Rhinol Laryngol 110: 1025–1029, 2001. 51. Johnsson LG, Kingsley TC: Herniation of the facial nerve in the middle ear. Arch Otolaryngol 91:598–602, 1970. 52. May M: Total facial nerve exploration: Transmastoid, extralabyrinthine, and subtemporal. Results. Laryngoscope 89:906–916, 1979. 53. Chen JM, Moll C, Wichmann W, Kurrer MO, Fisch U: Magnetic resonance imaging and intraoperative frozen sections in intratemporal facial schwannomas. Am J Otol 16:68–74, 1995. 54. Vrabec JT, Guinto F Jr, Nauta HJ: Recurrent facial neuromas. Am J Otol 19:99–103, 1998. 55. Jackson CG, Glasscock ME, Hughes G, Sismanis A: Facial paralysis of neoplastic origin: Diagnosis and management. Laryngoscope 90:1581–1595, 1980. 56. Shamisa A, Bance M, Nag S, et al: Glioblastoma multiforme developing in a patient treated with gamma knife radiosurgery: Case report and review of the literature. J Neurosurg 94:816–821, 2001 57. Mabanta SR, Buatti JM, Friedman WA, et al: Linear accelerator radiosurgery for nonacoustic schwannomas. Int J Radiat Oncol Biol Phys 43:545–48, 1999. 58. Seiff SR, Chang J: Management of ophthalmic complications of facial nerve palsy. In Jackler RK (ed.): Acoustic neuroma II. Otolaryngol Clin North Am 25:669–690, 1992.

Chapter

76 Edwin M. Monsell, MD, PhD, FACS

Iatrogenic Facial Nerve Injury: Prevention and Management Outline General Preventive Measures Surgery of the Middle Ear and Mastoid Normal Anatomy and Variations Mastoidectomy Technique Surgical Technique Diagnosis and Management Acoustic Neuroma Surgery Middle Fossa Surgery

I

njury to the facial nerve is one of the most feared complications of ear surgery. When its occurrence is unexpected, the outcome can be devastating to both the patient and the surgeon. Tort litigation commonly follows. Sometimes injury cannot be prevented, as when a malignant tumor invades the facial nerve or when a large, rapidly growing acoustic neuroma is densely adherent to a markedly splayed, extenuated nerve. When an anatomic anomaly and extensive disease combine to obscure the position of the nerve, injury can occur even in the most experienced hands. Fortunately, injury can be avoided in nearly all cases of middle ear and mastoid surgery. There are many causes of operative injury to the facial nerve. Direct laceration of the nerve by a high-speed drill or microdissecting instrument is probably the most common mechanism of injury. Adequate irrigation removes heat generated by a diamond burr. Heat can denature the macromolecules in nerve axons, causing mild or severe injury. Laser energy and electrical stimulation from electrocautery or stimulating current may have a similar effect. Stretching can break axons and strip myelin sheaths from axons. Mobilization of the tympanic and mastoid segments in surgery for glomus jugulare tumor can deprive the nerve of a portion of its blood supply, making it more susceptible to trauma from dissection. Dissection trauma can cause a hematoma to form within the nerve sheath, causing facial paralysis by entrapment neuropathy. Retrograde edema originating in the chorda tympani nerve is a possible cause of delayed facial paresis.1

GENERAL PREVENTIVE MEASURES Whenever the facial nerve is going to be in the operative field, the surgeon plans a deliberate strategy to identify it by known anatomic landmarks. Wide exposure is very 1270

Surgery of the External Auditory Canal Cochlear Implantation Paraganglioma Congenital Anomalies Children Injury to the Chorda Tympani Nerve Counseling Conclusion

important, especially in mastoid surgery. We identify anatomic landmarks in a systematic fashion proceeding from lateral to medial. The nerve is identified under direct vision by its appearance and by its relationships with neighboring structures. A thin plate of bone is left over the nerve whenever possible. The techniques for identification are mastered by long practice in a temporal bone dissection laboratory. The facial nerve is a friendly landmark that helps to identify other important structures. As Conley2 has indicated, identification of the facial nerve early in a procedure improves the safety, speed, and “rhythm” of the operation and promotes a climate of “responsibility and professionalism.” Once the nerve has been identified, the Halstedian principles of gentle handling of tissues apply. When the nerve is enclosed by its sheath, it is permissible to probe gently the tympanic or mastoid segments of the nerve. The nerve will give slightly and recover quickly. This effect can be used to distinguish the nerve from the mucosa of an air cell in the mastoid. Abrasion, contusion, stretching, and other mechanical insults to the nerve must be avoided. If cholesteatoma or tumor is implanted on the nerve and a plane of dissection cannot be established between the mass and the nerve, a portion of the sheath may be dissected away from the nerve and resected with the mass by precise microdissection. Dehiscence of the facial nerve should be anticipated in surgery for cholesteatoma.3,4 Great care must be used with electrocautery. Only microbipolar cautery should be used near any cranial nerve. Laser energy must be directed in such a way that high-energy direct or reflected light does not strike the nerve. The surgeon must adjust the stimulus current from nerve stimulators to a level near threshold to reduce the chance of injury.5 Of course, any device used in surgery must be used according to manufacturers’ recommendations.

Iatrogenic Facial Nerve Injury: Prevention and Management

Wide experience and preliminary evidence indicate that intraoperative monitoring of the facial nerve may reduce the risk of injury resulting from dissection along the nerve, for example, in acoustic neuroma surgery. Although monitoring is very common in acoustic neuroma surgery, it used much less often in middle ear and mastoid surgery.6 Whether monitoring can make a difference in the outcome of routine middle ear and mastoid surgery, especially in experienced hands, is uncertain. It is not currently the standard of care to monitor the facial nerve during all ear operations. It is unwise to depend completely on monitoring to warn the surgeon about possible facial nerve injury. Any monitoring device can fail, or the patient could receive muscle relaxants without the surgeon’s knowledge. The possibility of a facial nerve anomaly increases in the presence of any congenital anomaly of the ear, including auricular tags or pits, stenosis or atresia of the external auditory canal, congenital sensorineural hearing loss, congenital conductive hearing loss, and hemifacial microsomia. A history of facial paralysis from any cause, even with full recovery, may increase the sensitivity to injury.

SURGERY OF THE MIDDLE EAR AND MASTOID The incidence of facial nerve injury during surgery for chronic otitis media remains low, even in training programs. Palva, Karja, and Palva7 reported a rate of 0.5% for all intraoperative facial nerve injuries during surgery for chronic otitis media. They recorded a rate of 0.05% (1 case in a series of 2192 operations) for total transection of the nerve. Lee and Schuknecht8 reported 2 cases of severe injury in a series of 1074 operations (0.2%). One nerve was crushed in the tympanic segment by a less experienced surgeon. In the second case the nerve was completely transected near the stylomastoid foramen by an experienced surgeon. House9 reported that 7 of 500 fenestration cases (1.4%) developed a temporary, delayed facial paresis, from which all that subsequently recovered. Althaus and House reported a rate of 0.2% of mild, delayed facial paresis following stapedectomy.1

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Figure 76-1. Relationships of the facial nerve in the middle ear and mastoid, right ear from the lateral perspective. FN, facial nerve; GSPN, greater superficial petrosal nerve; HSCC, horizontal (lateral) semicircular canal; PSCC, posterior semicircular canal. (Reprinted with permission. Selesnick S, Jackler R: Facial paralysis in suppurative ear disease. Oper Tech Otolaryngol HNS 3:61–68, 1992.)

dehiscence extensive enough to be seen from the surgical position during stapes surgery.13,14 These larger dehiscences most commonly occur next to the anterior rim of the oval window.15,16 Laser energy from a reflective surface or a curved probe might reach the facial nerve through a dehiscence of any size. Other common areas of dehiscence include the portion of the geniculate ganglion adjacent to the tensor tympani tendon, the facial recess, the medial wall of the anterior epitympanum, and the mastoid segment, where the nerve sheath may be covered only by the mucosa of an air cell.11,15

NORMAL ANATOMY AND VARIATIONS The anatomic relationships of the facial nerve in the temporal bone are described in standard textbooks of surgical anatomy.10,11 In the middle ear, it has important relationships with the medial wall of the anterior epitympanum, the cochleariform process, the tympanic nerve, the oval window, the round window, and the sinus tympani (Figs. 76-1 and 76-2). In the mastoid the facial nerve has important relationships with the incus, the lateral semicircular canal, the facial recess, the posterior semicircular canal, the chorda tympani nerve, the stylomastoid foramen, and the digastric ridge. The fallopian canal is frequently dehiscent, particularly in certain regions (Fig. 76-3, Table 76-1). The most common site in the middle ear or mastoid is the tympanic segment,12 where more than half of histologic specimens show dehiscence of at least 0.4 mm. Twenty-two percent have more than one area of dehiscence.12 Only 5% to 7% of cases have

Figure 76-2. Relationships of the facial nerve in the middle ear and mastoid, right ear from the lateral perspective following removal of the tympanic ring, malleus, and incus. Facial nerve components: labyrinthine segment (lab), geniculate ganglion (GG), greater superficial petrosal nerve (GSPN), horizontal or tympanic segment (Horiz), second genu, and vertical or mastoid segment (Vert). HSCC, horizontal (lateral) semicircular canal; PSCC, posterior semicircular canal. (Reprinted with permission. Selesnick S, Jackler R: Facial paralysis in suppurative ear disease. Oper Tech Otolaryngol HNS 3:61–68, 1992.)

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Figure 76-4. This photograph of a partially dissected temporal bone shows a tumor-like herniation of the facial nerve from the fallopian canal just superior to the oval window. (Figure and caption reprinted with permission. Schuknecht HF, Gulya J: Anatomy of the Temporal Bone with Surgical Implications. Philadelphia, Lea & Febiger, 1986, and Johnson LG, Kinglsey TC: Herniation of the facial nerve in the middle ear. Arch Otolaryngol 91:598–602, 1970.)

Figure 76-3. Common sites of dehiscence in the fallopian canal. (Reprinted with permission. Proctor B: Surgical Anatomy of the Ear and Temporal Bone. New York, Thieme, 1989.)

A “pseudotumor” of the facial nerve consists of an inflammatory swelling of the nerve sheath caused by the trauma of previous surgery and active inflammation.17 A technique has been described for removal of a pseudotumor that includes resecting a segment of the nerve sheath.14 Alternatively, a mass associated with the facial nerve may be a portion of the nerve itself. The facial nerve may herniate through a dehiscence, giving the appearance of tumor or granulation tissue (Figs. 76-4 and 76-5). An attempt to resect such a mass would be expected to result in transection of many axons and facial paralysis. Such a mass may be exposed to any middle ear inflammatory process and be susceptible to the formation of associated granulation tissue. Numerous anatomic variations in the course of the facial nerve have been described (Fig. 76-6). The most common is posterior placement in the mastoid. Bifid and trifid facial nerves have been described.18 In the middle ear, the nerve may take a course that is anterior and inferior to the oval window. Other anatomic variations in the temporal bone,

such as a low tegmen overlying the antrum, may disorient the surgeon, leading to error.

MASTOIDECTOMY TECHNIQUE Injury to the facial nerve occurs most commonly during surgery of the mastoid. A common lament is that the surgeon did not know how the nerve could have been injured because the nerve was not seen during surgery. Injury in such cases probably could have been avoided if the nerve had been systematically identified. A common error is failure to obtain adequate surgical exposure. During mastoid surgery, landmarks are identified in a series of levels proceeding medially from the most lateral level. Surface landmarks are identified first, including the external auditory canal, the spine of Henle, the mastoid tip, the mastoid emissary vein,

TABLE 76-1. Congenital Dehiscence of the Facial Nerve Estimated % of Dehiscence

Minimum Size (mm)

Number of Ears

Type of Observation

Reference

— — — — — 0.4

440 100 52 64 28 535

Surgical* Surgical* Gross** Gross** Histologic Histologic

Derlacki13 Kaplan14 Beddard16 Mollica43 Nagakura44 Baxter12

“Large” ≥ 0.5 >1.5

— 100 400

Surgical* Gross** Histologic

House45 Rhoton46 Saito47

Oval Window 5 7 25 25 25 55

Facial Hiatus over Geniculate Ganglion 5 15 9

*Inspection and palpation under surgical microscope during surgery. **Inspection and palpation under surgical microscope during cadaver dissection.

Iatrogenic Facial Nerve Injury: Prevention and Management

Figure 76-5. Same specimen as Figure 76-4 showing a histologic cross section of the nerve after it has been removed from the facial canal. The entire nerve trunk takes an omega-shaped course out of its canal. (Reprinted with permission. Schuknecht HF, Gulya J: Anatomy of the Temporal Bone with Surgical Implications. Philadelphia, Lea & Febiger, 1986 and Johnson LG, Kinglsey TC: Herniation of the facial nerve in the middle ear. Arch Otolaryngol 91:598–602, 1970.)

the superior temporal line, and the cribrose area of the mastoid surface. As dissection proceeds medially, the tegmen (middle fossa plate), the external auditory canal, and sigmoid sinus are identified. The tegmen is identified as a plane that may curve inferiorly into the mastoid space as dissection proceeds medially. The plane may curve superiorly again as the antrum is approached. A common error is to dissect near the tegmen only at one point out of fear of injuring the middle fossa dura. Failure to expose the entire middle fossa plate in the mastoid as a plane leads to inadequate exposure and a risk of nerve injury. The triangular area posterior to the junction of the external auditory canal and the tegmen is maintained as the deepest part of the dissection medially until the antrum is identified. Care is exercised to thin the bone of the tegmen without exposing dura. The sinodural angle is opened. At the next level, the antrum is identified. The antrum is a small space in the mastoid between the central mastoid cell tract and the fossa incudis. The surgeon has entered the antrum when the short process of the incus and the smooth, curved bone over the lateral semicircular canal are seen. Then the facial nerve itself can be identified. There are four methods to locate the facial nerve in the mastoid: (1) the facial recess method, (2) the digastric ridge method, (3) the retrofacial cell tract method, and (4) the fossa incudis method. These techniques must be mastered in the dissection laboratory under the direction of experienced teachers so that surgeons can identify the facial nerve and other structures of the ear without damaging them. Each method will be described briefly. Additional detail is available in textbooks of temporal bone anatomy and surgery. The facial recess method is preferred under most circumstances because the facial nerve is identified where its

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course is most constant in the mastoid. The landmarks used in this approach include the incus, the lateral semicircular canal, and the oval window. The facial recess is an indentation of the tympanic cavity lateral to the facial nerve. This triangular space is bounded medially by the facial nerve, laterally by the chorda tympani nerve, and superiorly by the crest of bone where the tendon of the short process of the incus is attached, the “incus buttress.” The technique of locating the facial nerve is to proceed as though one were going to open the facial recess from the mastoid into the middle ear. Long strokes are made with the burr parallel to the course of the nerve. Burrs are exchanged for progressively smaller burrs until either the nerve is identified or the facial recess is opened. If the recess is opened first, the bulge of the fallopian canal will be seen next to the oval window. Then the nerve can be followed from that point distally into the mastoid. When the facial nerve cannot be located at the facial recess because it is obscured by disease, the digastric ridge method offers a reasonable alternative. The digastric muscle inserts along a groove on the medial surface of the mastoid tip. The reflection of this groove is a ridge on the inside of the mastoid bone. The facial nerve supplies the digastric muscle with a small branch that leaves the main trunk of the facial nerve just outside the stylomastoid foramen. Thus, the facial nerve and the digastric ridge are adjacent and located at the same depth within the mastoid bone. The technique of locating the facial nerve is first to identify the basic landmarks of the mastoid, as described previously. Then the posterior external auditory canal wall and the bone overlying the sigmoid sinus are thinned. Dissection continues toward the mastoid tip, where a thin white crescent of soft tissue is identified. This is the periosteum of the skull base in the digastric groove. The crescent is followed anteriorly, where the facial nerve is met at the stylomastoid foramen. A common, but less reliable, method to locate the facial nerve in the mastoid is the method of the retrofacial cell tract. This method has the disadvantage that the segment of facial nerve to be located is the segment with the highest rate of anatomic variation. The mastoid segment of the facial nerve lies just anterior to the retrofacial tract of air cells at a point just inferior to the posterior semicircular canal. The technique of locating the facial nerve is first to identify the basic landmarks of the mastoid as previously described. Then the posterior external auditory canal wall is thinned and the lateral and posterior semicircular canals are outlined so that the inferior and posterior boundaries of the posterior semicircular canal are well delineated. The retrofacial cell tract lies anterior to the sigmoid sinus, inferior to the posterior semicircular canal, and medial to the facial nerve. From within the mastoid and somewhat within the retrofacial cell tract (but always dissecting bone that is in full view), the surgeon makes long strokes with the burr parallel to the nerve along its visualized course and gradually advances anteriorly until the nerve is encountered. Another reliable method for locating the facial nerve when the incus is absent or is being removed is the method of the fossa incudis. This may apply in translabyrinthine surgery or some cholesteatoma surgery. The method relies on the fact that the tympanic segment of the facial nerve is one of the most anatomically constant segments of the nerve.

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Figure 76-6. Illustration of common anomalies of the facial nerve in the middle ear and mastoid. A, Normal course. B, Lateral to the lateral (horizontal) semicircular canal; C–F, divided across both sides of the stapes; G, overhanging the stapes footplate. (Reprinted with permission. Proctor B: Surgical Anatomy of the Ear and Temporal Bone. New York, Thieme, 1989.)

The technique of locating the facial nerve is first to identify the basic landmarks of the mastoid as previously described. The incudostapedial joint is divided either through the ear canal or through the facial recess. The malleoincudal articulation is disrupted and the incus is removed through the mastoid. A cylindrical bulge corresponding to the course of the tympanic segment of the nerve lies in the floor of the fossa incudis. This bulge is followed distally into the mastoid.

SURGICAL TECHNIQUE Cholesteatoma and some neoplasms have the capacity to erode bone locally and expose the facial nerve (Fig. 76-7). Granulation tissue and hyperplastic mucosa can obscure

the facial nerve. Because of its location, the tympanic is the segment most commonly affected by these processes. During any surgery for cholesteatoma, it is wisest to assume that disease has exposed the nerve. It is better to remove gross amounts of cholesteatoma matrix by excision with microscissors than to pull it out with microforceps. Once a segment of the facial nerve has been identified, one can usually lift the matrix off the nerve gently with a small dissector under direct vision. Revision surgery presents additional challenges. The facial nerve and other structures may have been exposed by disease or prior surgery and landmarks may be distorted.19 In addition to careful preoperative examination of the ear, the surgeon may wish to consider high-resolution computed tomography and intraoperative facial nerve monitoring in some cases.20–22

Iatrogenic Facial Nerve Injury: Prevention and Management

Figure 76-7. Typical sites of facial nerve erosion by cholesteatoma. The posterior portion of the tympanic segment and second genu (1) are the most common regions of the facial nerve injured by posterior epitympanic cholesteatoma and posterior mesotympanic cholesteatoma. In anterior epitympanic cholesteatoma, the facial nerve is more often involved in the anterior portion of the tympanic segment and the geniculate ganglion (2). (Reprinted with permission. Selesnick S, Jackler R: Facial paralysis in suppurative ear disease. Oper Tech Otolaryngol HNS 3:61–68, 1992.)

DIAGNOSIS AND MANAGEMENT It is important to establish whether an injury’s onset is immediate or delayed because treatment may differ accordingly. It is recommended that all patients be checked in the recovery room after otologic surgery to verify that facial nerve function is completely intact. Flaring of the nostrils on inhalation is one of the earliest signs of spontaneous facial nerve activity during emergence from general anesthesia. Normal nostril flaring does not rule out mild degrees of facial nerve injury. Occasionally the degree of facial nerve injury is clouded by the presence of facial edema. If the patient has a paralyzed face, but the eye closes, the observer may think that only a mild injury has occurred. Despite complete transection of the facial nerve, some patients can close the eye by relaxing the superior levator palpebrae muscle, which has innervation from the trigeminal nerve. Local anesthesia may cause facial paresis, particularly in children. The paralytic effect of lidocaine should have worn off by 2 to 3 hours after injection. If complete facial paralysis is observed immediately after surgery, a severe injury may be expected. Even if the nerve has been completely transected, the distal segment of the nerve may maintain a normal ability to conduct action potentials for 3 days before a rapid decline in nerve conduction occurs. Serial studies of nerve conduction by electrically evoked electromyography of the facial muscles beginning 2 to 3 days after injury will help resolve doubtful cases of severe injury. If electrical activity declines rapidly over the course of just a few days, one may conclude that

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nerves are degenerating rapidly. One may then infer that most or all nerve axons have been transected. If electrical activity remains strong even 2 or 3 weeks after surgery, spontaneous recovery is likely. Facial paralysis with delayed onset usually resolves completely even without further treatment. A permanent paresis is still possible. Consequently, patients with delayed onset of severe postoperative facial paralysis should be followed by serial electrodiagnostic testing. Prompt surgical exploration would be indicated if evidence of degeneration were found. Incomplete facial paralysis of immediate onset is also likely to recover, but sequelae such as synkinesis and increased motor tone may occur months later as damaged motor axons regenerate. Treatment of all degrees of injury with corticosteroids, whether the nerve is operated upon or not, is a common and rational practice, although its efficacy has not been confirmed in clinical trials. If injury is recognized intraoperatively, the surgeon must make a judgment of the degree of injury. If there is a minor contusion, it may be best to leave the nerve alone. If there is a more extensive contusion, it may be advisable to explore a segment of the nerve, remove the overlying bone, and slit open the sheath to allow the nerve to expand to prevent edema from causing an entrapment neuropathy. The long-standing recommendation of prompt exploration of any severe injury to the facial nerve still applies.23 The alternative to immediate exploration is to explore contingent upon the development of nerve degeneration as evidenced by serial electrical studies. The rationale of early exploration is to uncover a possible expanding hematoma within the nerve sheath. As days go by, accumulating granulation tissue at the site of nerve injury makes repair more difficult. As with facial paralysis of any cause, appropriate eye care is essential. When an iatrogenic facial nerve injury occurs, it is important for the operating surgeon and the referral surgeon to communicate regarding the probable site and mechanism of injury. Reports from the operating surgeon may provide information on the severity of the injury. If the facial nerve was not identified at surgery, severe injury is more likely. Referral surgeons should understand that psychologic denial by the referring surgeon is common and that the referring surgeon needs emotional support, as does the patient.

ACOUSTIC NEUROMA SURGERY Even small acoustic tumors can form attachments to the facial nerve. As the tumor grows larger, it causes extension and splaying of nerve fibers. The degree of attachment between the nerve and tumor is variable and cannot be predicted preoperatively. The intracranial and internal auditory segments of the facial nerve lack the perineurial and epineurial connective tissue that helps to protect the more distal segments of the nerve. Even mild stretching may produce some damage to the nerve. The translabyrinthine approach as perfected by William House revolutionized acoustic neuroma surgery. In addition to permitting tumor removal with the least amount of

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brainstem manipulation, it has the advantage of permitting identification of the facial nerve using secure bony anatomic landmarks. The key landmark is the vertical crest of the fundus of the internal auditory canal, a crest of bone that marks the point of separation between the superior vestibular nerve and the labyrinthine segment of the facial nerve. The surgeon identifies the facial nerve where it is not next to the tumor. The point where the nerve joins the tumor establishes the appropriate plane of dissection. The surgeon follows this plane across the entire extent of the tumor–nerve interface. Facial nerve outcomes immediately after surgery and 1 year later have differed in various series. As expected, larger tumors are associated with greater degrees of facial nerve injury. Preoperative facial weakness is rare except in very large tumors. A history of facial paralysis with recovery or of facial twitching may alert the surgeon to the possibility of a primary tumor of the facial nerve or a metastasis implanted on the nerve. Data from one large series have illustrated that even if the facial nerve is anatomically preserved (96.6% of cases), immediate postoperative paresis (54%) and paralysis (13.5%) may still occur.24 House and others have described techniques for identification and dissection of the facial nerve in translabyrinthine surgery.24,25 It is important to avoid burr trauma during dissection of the mastoid and internal auditory canal. The nerve may be densely attached to other structures at the vestibulofacial anastomosis in the fundus of the internal auditory canal and at the porus acousticus where the nerve crosses the point where dura is reflected from the posterior surface of the temporal bone to the internal auditory canal. The nerve is usually somewhat more adherent in the cerebellopontine angle than in the internal auditory canal. Trauma from laser energy and ultrasonic devices should be avoided. The surgeon gently distracts the nerve–tumor interface, avoiding medially directed stretching forces that could damage the delicate structure of the nerve. Sharp dissection is less traumatic than blunt dissection. The motor activity evoked by trauma can be recorded electrically or mechanically. Stimulation with small currents (approximately 0.5 mA) helps to distinguish facial nerve fibers from strands of arachnoid, which may be visually indistinguishable. Routine decompression of the labyrinthine segment has been proposed as a means to reduce the risk of late postoperative entrapment neuropathy secondary to edema induced by dissection trauma, but no such benefit has been demonstrated yet. The electrical threshold for stimulation of the nerve may be roughly predictive of facial nerve outcome.26 An additional advantage of the translabyrinthine approach is that a primary facial nerve anastomosis can often be accomplished if necessary. This is achieved by transecting the greater superficial petrosal nerve anterior to the geniculate ganglion and mobilizing the nerve distally to the stylomastoid foramen. This maneuver develops as much as a centimeter of additional nerve length to reach the proximal stump of the nerve in the cerebellopontine angle. A primary facial nerve anastomosis or cable interposition graft may be necessary in revision surgery, for unusually large tumors, or for a facial nerve neuroma. Delayed facial paralysis may occur in 15% (translabyrinthine and middle fossa approaches) to 25% (suboccipital

approach) of cases.27–29 Nearly all cases recover to their immediate postoperative state. Onset within 48 hours after surgery and milder degrees of paresis indicate a better prognosis for recovery and earlier recovery.27 Injury to the nervus intermedius during acoustic neuroma surgery sometimes results in postoperative dysgeusia. This complication may be unavoidable.

MIDDLE FOSSA SURGERY The frontalis, or temporal, branch of the facial nerve may be cut or contused during exposure of the middle fossa. This branch crosses the upper border of the zygoma near the auriculotemporal hairline. The nerve lies within a fascial plane between the subdermal fat and the temporalis muscle.14,23 This fascia represents a continuation of the superficial musculo-aponeurotic system (SMAS).30 Facial nerve injury may occur during elevation of the dura of the middle cranial fossa due to a dehiscence in the bone overlying the geniculate ganglion (see Table 76-1). The risk of injury may be reduced by elevating the dura from the posterior toward the anterior direction along the superior surface of the temporal bone.

SURGERY OF THE EXTERNAL AUDITORY CANAL The facial nerve sometimes takes an anterior course through its mastoid segment, coming to lie superficially under the bone of the external auditory canal.31 During surgery on the external auditory canal for congenital or acquired atresia, keratosis obturans, exostoses, and other conditions, the nerve cannot be located using the usual anatomic approaches. Great care combined with an awareness of the possibility of injury will prevent catastrophe in most cases. Keratosis obturans is an unusual condition in which layers of squamous debris build up within the external auditory canal. The bone of the canal may be eroded, exposing the mastoid segment of the facial nerve to the squamous epithelium of the ear canal. Debridement of the squamous debris usually restores the epithelium to normal. Facial nerve injury may be avoided by careful intraoperative assessment of the extent of bony erosion, preoperative radiographic studies, and intraoperative monitoring. Exostoses of the external auditory canal occur in individuals who frequently swim in cold water, such as lifeguards at ocean or great lakes beaches. Removal must be conducted with care to avoid facial nerve injury.

COCHLEAR IMPLANTATION The facial nerve is at risk during cochlear implant surgery, though few injuries have been reported. The most likely site of injury is the mastoid segment at the facial recess. A nerve in an anomalous position may be injured near the round window. Such anomalies are more common in cases with congenital deafness. Stimulation of the facial nerve may occur during activation of the implant. Multichannel systems can be adjusted or

Iatrogenic Facial Nerve Injury: Prevention and Management

programmed to eliminate this stimulation in nearly all cases. While this stimulation may be a nuisance to the patient, there are no reported cases of facial nerve damage from this stimulation.32,33

PARAGANGLIOMA Paragangliomas are neoplasms of paraganglia tissue that may occur in the middle ear, jugular bulb, or elsewhere. While these tumors are nearly always biologically benign, they may be locally invasive. Preoperative imaging studies may demonstrate spread from the middle ear into the hypotympanic air cells medial to the facial nerve. Paragangliomas can become implanted on the facial nerve sheath, requiring resection of a portion of the sheath. Rarely, they may invade the substance of the nerve itself. Segmental resection of the nerve is necessary for complete tumor removal in such cases. Glomus jugulare tumors can be removed completely only by temporary or permanent displacement of the facial nerve anteriorly and superiorly away from the region surrounding the jugular bulb.34,35 Intraoperative monitoring with meticulous microsurgical technique may reduce the risk of damage from traumatic dissection during such maneuvers.31

CONGENITAL ANOMALIES Numerous congenital anomalies in the course of the facial nerve have been described in association with congenital atresia and other congenital anomalies of the ear.7,36,37 The most common variation is an acute anterior bend in the nerve just posterior to the oval window. In such cases the nerve crosses the middle ear space. In surgery for congenital atresia it lies inferiorly and posteriorly in the operative field as the surgeon is removing the atretic bone.38 The nerve is also at risk in low-set atretic ears and in cases of canal stenosis with accompanying cholesteatoma.38 Identification of the facial nerve is critical in surgical repair of congenital atresia and ossicular malformation. Often, high-resolution computed tomography will help confirm that at least a portion of the facial nerve lies in a normal anatomic position. Facial nerve monitoring has been advocated in atresia surgery, but not universally deemed necessary or helpful. Identification must still be made by direct vision.

CHILDREN Before the development of the mastoid process, which usually occurs by age 2 years, the facial nerve lies in a superficial position at the stylomastoid foramen, where it is prone to injury. Postauricular incisions in young children should be made away from this area. Iatrogenic facial nerve injuries from whole body casts and orthotics have been reported.39 Forceps injury to the facial nerve at birth is uncommon. Most cases recover spontaneously.40 Usually there is evidence of a soft tissue contusion near the stylomastoid foramen. Congenital facial paresis is more often due to an abnormality of the intrauterine position than to forceps

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injury.41 Distortion in the shape of the face on the same side is a pathognomonic sign of such an injury. Congenital absence of the facial nerve is rare. It is usually bilateral, complete, and associated with other cranial nerve anomalies. Spontaneous recovery has not been reported.40

INJURY TO THE CHORDA TYMPANI NERVE The seventh cranial nerve contains fibers that provide taste sensation to the anterior two-thirds of the tongue. The cell bodies of these neurons lie in the geniculate ganglion and reach the tongue by way of the chorda tympani nerve and the lingual nerve. The sensation is carried by fibers in the nervus intermedius, which lies next to the facial nerve in the cerebellopontine angle, to the nucleus of the tractus solitarius. It has been suggested that stretching the chorda tympani nerve is more likely to produce than deliberately cutting it. After the nerve has been injured, a numb feeling or metallic taste is sometimes perceived. This sensation may persist for weeks or months. It may be very distressing to some patients, but nearly all patients seem to get used to it in time.35 Atrophy of the fungiform papillae of the ipsilateral tongue may indicate a poor prognosis for recovery of normal sensation.42 Dysgeusia is best prevented by knowledge of anatomy and meticulous surgical technique. Injury may occur at any point along the nerve. The nervus intermedius is commonly resected during acoustic neuroma surgery. Damage to the labyrinthine, tympanic, or mastoid segments of the facial nerve can also injure its visceral sensory component. The chorda tympani nerve may be injured as a separate structure in its own mastoid segment during mastoid surgery. It forms the lateral boundary of the facial recess, where it may be injured during posterior tympanotomy. The chorda tympani may need to be manipulated during stapes surgery or resected if it is implanted with cholesteatoma matrix or tumor. It can be injured during removal of the malleus head in its position between the head of the malleus and the point where the tensor tympani tendon attaches to the malleus neck. It may be injured in the anterior epitympanum in its course medial to the anterior malleal ligament and the iter through which it leaves the tympanic cavity. Bilateral injury to the chorda tympani nerves should be avoided. The chorda tympani nerve also carries parasympathetic secretomotor fibers to the submandibular and sublingual salivary glands. Symptomatic dryness of the mouth is not common after ear surgery because salivary flow is not abolished by sectioning only one chorda tympani nerve. Nevertheless, some patients may have increased periodontal disease on the involved side due to a loss of some of the protective effect of saliva.

COUNSELING Several measures can make a bad situation a little better for all concerned. Preoperative counseling, especially in high-risk cases, can help prepare the patient emotionally.

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The operating surgeon can help provide emotional support to the patient by conveying a sense of continuing concern. Patients need to understand what happened and how because conceptualizing the circumstances of the injury helps them to deal with it emotionally. Patients also need to understand how long it will take for facial function to recover and the extent to which recovery is likely.

CONCLUSION Facial paralysis is one of the most feared complications of ear and skull base surgery. As with most surgical complications, it is better to prevent facial paralysis than to deal with it after it occurs. Thorough knowledge of anatomy and gently handling of tissues are the best ways to prevent operative injury.

REFERENCES 1. Althaus SR, House HP: Delayed post-stapedectomy facial paralysis: A report of five cases. Laryngoscope 83(8):1234–1240, 1973. 2. Conley J: Search for and identification of the facial nerve. Laryngoscope 88(1 Pt 1):172–175, 1978. 3. Selesnick S, Jackler R: Facial paralysis in suppurative ear disease. Oper Tech Otolaryngol HNS 3:61–68, 1992. 4. Selesnick S, Lynn-Macrae A: The incidence of facial nerve dehiscence at surgery for cholesteatoma. Otol Neurotol 22:129–132, 2001. 5. Love JT Jr, Marchbanks JR: Injury to the facial nerve associated with the use of a disposable nerve stimulator. Otolaryngology 86(1):767–775, 1978. 6. Dickins J: Facial nerve monitoring: An EAR Foundation alumni study. Am J Otol 17:162–164, 1996. 7. Palva T, Karja J, Palva A: Immediate and short-term complications of chronic ear surgery. Arch Otolaryngol 102(3):137–139, 1976. 8. Lee K, Schuknecht HF: Results of tympanoplasty and mastoidectomy at the Massachusetts Eye and Ear Infirmary. Laryngoscope 81(4):529–543, 1971. 9. House HP: The fenestration operation: A survey of five hundred cases. Ann Otol Rhinol Laryngol 57:41–54, 1948. 10. Donaldson J, Duckert L, Lambert P, Rubel E: Surgical Anatomy of the Temporal Bone, 4th ed. New York, Raven Press, 1992. 11. Schuknecht HF, Gulya J: Anatomy of the Temporal Bone with Surgical Implications. Philadelphia, Lea & Febiger, 1986. 12. Baxter A: Dehiscence of the fallopian canal. An anatomical study. J Laryngol Otol 85(6):587–594, 1971. 13. Derlacki E, Shambaugh G, Harrison W: The evolution of a stapes mobilization technique. Laryngoscope 67:420–447, 1957. 14. Kaplan J: Congenital dehiscence of the fallopian canal in middle ear surgery. Arch Otolaryngol 72:197–200, 1960. 15. Guild S: Natural absence of part of the bony wall of the facial canal. Laryngoscope 59:668–673, 1949. 16. Beddard D, Saunders W: Congenital defects in the fallopian canal. Laryngoscope 72:112–115, 1962. 17. Gacek R: Dissection of the facial nerve in chronic otitis media surgery. Laryngoscope 92:108–109, 1982. 18. Miehlke A: Surgery of the Facial Nerve, 2nd ed. Philadelphia, WB Saunders, 1973. 19. Graham M: Prevention and management of iatrogenic facial palsy. Am J Otol 5:513, 1984. 20. Moller A, Janetta P: Monitoring of facial nerve function during removal of acoustic tumors. Am J Otol (Suppl):27–29, 1985. 21. Prass R, Kinney S, Hardy R, Hahn J: Acoustic (loudspeaker) facial electromyographic monitoring. Part I. Neurosurgery 19:392–400, 1986.

22. Silverstein H, Smouha EE, Jones R: Routine intraoperative facial nerve monitoring during otologic surgery. Am J Otol 9(4):269–275, 1988. 23. Kettel K: Peripheral Facial Palsy. Springfield, Ill, Charles C Thomas, 1959. 24. House W, Luetje C: Evaluation and preservation of facial function. In House W, Luetje C (eds.): Acoustic Tumors. Los Angeles, House Ear Institute, 1985, pp 89–96. 25. Fisch U. Operations on the Facial Nerve in Its Labyrinthine and Meatal Course, 2nd ed. Philadelphia, WB Saunders, 1973. 26. Nissen A, Sikand A, Curto F, et al: Value of intraoperative threshold stimulus in predicting postoperative facial nerve function after acoustic tumor resection. Am J Otol 18:249–251, 1997. 27. Megerian C, McKenna M, Ojemann R: Delayed facial paralysis after acoustic neuroma surgery: Factors influencing recovery. Am J Otol 17:630–633, 1996. 28. Kartush J, Lundy L: Facial nerve outcomes in acoustic neuroma surgery. Otolaryngol Clin North Am 25:623–647, 1992. 29. Arriaga M, Luxford W, Berliner K: Facial nerve function following middle fossa and translabyrinthine acoustic tumor surgery: A comparison. Am J Otol 15:620–624, 1994. 30. Mitz V, Peyronie M: The superficial musculo-aponeurotic system (SMAS) in the parotid and cheek area. Plast Reconstr Surg 58(1):80–88, 1976. 31. Leonetti JP, Brackmann DE, Prass RL: Improved preservation of facial nerve function in the infratemporal approach to the skull base. Otolaryngol Head Neck Surg 101(1):74–78, 1989. 32. Liebman EP, Webster RC, Berger AS, DellaVecchia M: The frontalis nerve in the temporal brow lift. Arch Otolaryngol 108(4):232–235, 1982. 33. Litton WB, Krause CJ, Anson BA, Cohen WN: The relationship of the facial canal to the annular sulcus. Laryngoscope 79(9):1584–1604, 1969. 34. Fisch U: Infratemporal fossa approach for glomus tumors of the temporal bone. Ann Otol Rhinol Laryngol 91(5 Pt 1):474–479, 1982. 35. May M, Klein SR: Facial nerve decompression complications. Laryngoscope 93(3):299–305, 1983. 36. Jahrsdoerfer RA: The facial nerve in congenital middle ear malformations. Laryngoscope 91(8):1217–1225, 1981. 37. Takahashi H, Kawanishi M, Maetani T: Abnormal branching of facial nerve with ossicular anomalies: Report of two cases. Am J Otol 19:850–853, 1998. 38. Jahrsdoerfer R, Lambert P: Facial nerve injury in congenital aural atresia surgery. Am J Otol 19:283–287, 1998. 39. Beddow FH: Facial paralysis complicating splintage for congenital dislocation of the hip in the newborn. J Bone Joint Surg Br 51(4):714–715, 1969. 40. Alberti PW, Biagioni E: Facial paralysis in children. A review of 150 cases. Laryngoscope 82(6):1013–1020, 1972. 41. Hepner WR: Some observations on facial paresis in the newborn infant: Etiology and incidence. Pediatrics (8):494–497, 1951. 42. Cowan PW: Atrophy of fungiform papillae following lingual nerve damage: A suggested mechanism. Br Dent J 168(3):95, 1990. 43. Mollica V: Considerazioni anatomo-cliniche e patogenetiche sulle anamalie del eanale di Faloppio Minerva. Otolaryngologica (12):230–233, 1962. 44. Nagakura M: A histoanatomical study of the facial nerve and facial canal. Nippon Jibiinkoka Gakkai Kaiho 69(9):1629–1648, 1966. 45. House WF, Crabtree JA: Surgical exposure of the petrous portion of the seventh nerve. Arch Otolaryngol (81):506–507, 1965. 46. Rhoton AL Jr, Pulec JL, Hall GM, Boyd AS Jr: Absence of bone over the geniculate ganglion. J Neurosurg 28(1):48–53, 1968. 47. Saito H, Ruby RR, Schuknecht HF: Course of the sensory component of the nervus intermedius in the temporal bone. Ann Otol Rhinol Laryngol 79(5):960–966, 1970.

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Outline Introduction Candidacy for Hearing Aid Use Type of Loss Degree of Loss Audiometric Configuration Speech Discrimination (Word Recognition) Ability Other Factors Style and Type of Hearing Aid Physical Factors Audiologic Factors Number of Hearing Aids Required

Chapter

Hearing Aids and Assistive Listening Devices

The Head Shadow Effect Binaural Summation Squelch Sensory Deprivation History of Hearing Aid Selection Procedures Selective Amplification Comparative Approach Modern Prescriptive Formulas Real Ear (Probe Tube) Measures Earmold Acoustics Technological Advances

Fitting Flexibility Loudness Control Noise Reduction Deciding between Digital and Digitally Programmable Other New Developments Deep Canal Fittings Disposable and Entry-Level Hearing Aids Assistive Listening Devices Conclusions

INTRODUCTION Compared with medicine, the discipline of audiology is a relatively new science. Similar to medicine, however, its philosophies and procedures have evolved rapidly and notions once considered sacrosanct have been revised or even discarded. Historians trace the birth of the audiologic profession to 1945 when Dr. Raymond Carhart opened the first hearing clinic at Deshon Hospital in Butler, Pennsylvania.1 World War II veterans suffering from noise-induced hearing loss needed their hearing status measured and subsequent rehabilitative procedures. In those “pioneering” days, wearable amplification devices were cumbersome, body-borne, vacuum-tube devices with limited versatility and rather poor fidelity. The historical selection of hearing aids was very basic and assumed that the electroacoustic parameters of the hearing aid (mainly frequency response and gain) should be the mirror image of the patient’s audiogram (an error that inevitably resulted in significant overamplification). Furthermore, the delivery system of hearing aids was highly restrictive. A patient went to the physician, had his hearing tested (usually, but not always, by an audiologist), and was then referred to a local commercial hearing aid dealer who often had limited scientific training, albeit considerable experience in sales techniques. In those days, obtaining a hearing aid that fit was mainly a function of the fitter’s artistic and persuasive skills, rather than the fitter’s mastery of scientific concepts. Now, in the beginning of the twenty-first century, the audiologist’s goal is to improve the listening abilities of the patient, and hearing aids and assistive listening devices are often but a means to that end.

Robert W. Sweetow, PhD

The purpose of this chapter is to review some of the significant changes that have taken place in the technology and approaches to fitting amplification devices for the hearing impaired. Specific attention is paid to (1) candidacy for hearing aid use, (2) styles and types of hearing aid, (3) the evolution of fitting strategies and verification procedures, (4) the rationale for binaural amplification, (5) technologic advances in hearing aids, including digital instruments, and (6) assistive listening devices other than hearing aids. Please note that the discussion is limited to instruments producing amplification in the external meatus; middle ear implantable appliances and cochlear implants are considered elsewhere in the book.

CANDIDACY FOR HEARING AID USE Type of Loss Through the mid-1960s, a common belief among audiologists and physicians alike was that hearing aids were beneficial to individuals suffering from conductive hearing losses but were not helpful for listeners with sensorineural impairments. Patients were informed that hearing aids could make sounds louder but would not make sounds clearer. The rationale behind this thinking was that since conductively impaired listeners could process speech “normally” once the decrease in threshold was overcome, hearing aids would provide benefit simply by amplifying incoming sound in a linear manner. In general, this was true. It was erroneously believed, however, that sensorineural impaired listeners could not use hearing aids effectively since increased volume would not necessarily 1281

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overcome the decrease in clarity or diminished speech discrimination ability exhibited by these patients. This attitude was reinforced by reports of unfavorable results from those sensorineural impaired patients who did try hearing aids. Of course, it is now recognized that early attempts at fitting sensorineural impaired listeners with hearing aids were seriously hampered by (1) the limited choice of electroacoustic variations obtainable with wearable amplification systems 30 years ago, (2) the use of fitting strategies that are now recognized to be flawed, (3) limitations in the electronic and acoustic capabilities of the earlier instruments, and (4) a lack of approaches designed to minimize interference from background noise. The fact that medical and surgical advances have rendered the need for fitting most, though not all, patients with otosclerosis and other conductive pathologies obsolete, combined with the reality that more than 95% of the estimated 24 to 28 million hearing-impaired Americans exhibit sensorineural rather than conductive losses, has motivated audiologists and hearing scientists to concentrate efforts on improving amplification for the sensorineural impaired population.

Degree of Loss The prognostic value of amplification cannot be determined simply as a function of the degree of hearing loss. The predictive value of the speech reception threshold (SRT) is highly overestimated. It is important to keep in mind that the SRT is a value that is not designed to represent a comprehensive picture of a patient’s hearing deficit. An example of how the SRT can provide misleading information is shown in Figure 77-1. Note that for this patient, the SRT is 5 dB, well within the range of normal. This value reflects the patient’s normal auditory sensitivity at 500 and 1000 Hz. Yet, inspection of the audiogram depicts a severe hearing loss above 1000 Hz, which results in considerable difficulty for communication skills in many acoustic environments. A more effective, although still flawed, single numerical value predictor for potential hearing aid effectiveness is the average of the pure tone thresholds for 1000, 2000, 3000, and 4000 Hz. These frequencies better

Figure 77-1. The SRT for this patient was 5 dB. However, the patient’s speech discrimination score at a normal conversational level was only 60%.

reflect the information conveyed by the mid- and highfrequency consonants, which happen to carry the vast majority of intelligibility information in the English language. Data collected in the classic French and Steinberg Articulation Index study2 illustrated the relationship between the more intense, low-frequency sounds (usually vowels and nasal phonemes in English) and the weaker, high-frequency sounds (usually consonants) as a function of intelligibility. Consider, for example, that while 95% of the overall speech energy is located below 1000 Hz, only 40% of the contribution to intelligibility is carried by this energy. Conversely, the energy above 1000 Hz contributes only 5% to the overall intensity while allowing for 60% intelligibility. As a counseling technique, one can employ the “count-the-dots” version3 of the Articulation Index to illustrate how intelligibility varies as a function of unaided and aided threshold (Fig. 77-2). To grossly determine the predicted percentage of understandable speech, count the number of dots located below the appropriate threshold curves. For the example shown, there are 20 dots below the unaided threshold curve, as opposed to 80 dots below the aided threshold curve. The implication is that this listener’s reception would improve from 20% to 80% with the use of this particular hearing aid. Even with Articulation Index and similar considerations,4 or the four-frequency pure tone average, determining candidacy for amplification on the basis of degree of hearing loss is at best a questionable practice. If one insists on using it, however, the following broad guidelines may be considered for a motivated user: Mild Loss (20 to 40 dB): Amplification may be useful, depending on the patient’s communicative needs. Some patients may prefer to use amplification only part-time (as needed). Moderate Loss (45 to 65 dB): Amplification is needed and will usually be successful if proper fitting strategies are employed.

Figure 77-2. The count-the-dot audiogram format. There are 20 dots below the unaided curve but 80 dots below the aided threshold curve.

Hearing Aids and Assistive Listening Devices

Severe Loss (70 to 85 dB): Cannot function auditorily without aid. Amplification is necessary if the patient desires to use the auditory channel as the primary receptive mode. Profound Loss (90 dB or more): At the minimum, amplification is useful as a signal warning device; at maximum, it will allow the patient auditory use and will likely enhance speech-reading capabilities. Effectiveness may depend on the age amplification is first employed. Cochlear implantation may also be effective.

Audiometric Configuration Most early hearing aid users had conductive impairments characterized by flat or slightly rising audiometric configurations. Thus, it was long believed that these audiometric configurations were most amenable to hearing aid fittings. Countering this belief, however, were those difficult-to-fit patients suffering from Ménière’s syndrome whose air conduction audiograms were similar to those presented by otosclerotics. It also was believed that high-frequency hearing losses would be the most difficult to fit, and indeed, results often reinforced this belief. A variety of reasons accounted for the large number of fitting failures for this population, however. Among these were central auditory processing problems associated with presbycusis,5 distorted and overamplification of the mid frequencies, underamplification of the higher frequencies due to loss of external ear canal resonance caused by occlusion of the ear canals,6 and unnatural perception of one’s own voice resulting from the occlusion effect. All of these issues are discussed in greater detail later. With the versatility available in modern hearing aids (particularly digital and programmable instruments), audiometric configuration is much less of an issue in determining candidacy.

Speech Discrimination (Word Recognition) Ability Generally, the better the patient’s speech discrimination (more accurately referred to as the word recognition) score, the better will be the performance with a hearing aid. This was one of the reasons that patients with conductive hearing losses responded so well to amplification, whereas there were more failures among sensorineural impaired listeners. It is erroneous to conclude, however, that the sole reason for failure with amplification was reduced word recognition ability. Indeed, any dispenser can recount numerous success stories of patients with poor (under 70%) word recognition scores. Word recognition ability becomes diminished because of four main factors: (1) reduced audibility; (2) cochlear distortions producing reduced frequency and temporal selectivity and resolution; (3) abnormal auditory processing ability, including overly large interference from background noise; and (4) impaired central and cognitive function.7 Clearly, modern technology affords audiologists with the ability to correct for reduced audibility. The other three factors, however, may not be amenable to correction by amplification, so they can, in fact, render a poor prognosis for success with amplification.

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Another important consideration regarding speech discrimination ability appears to be the relative discrimination ability of the two ears. Patients presenting bilaterally asymmetrical word recognition scores often prefer monaural amplification (for the better ear). There are many exceptions, however, so unless there are other contraindications (i.e., no speech discrimination ability, medical contraindications, extremely limited dynamic range, etc.), neither monaural nor binaural low discrimination scores should in and of themselves preclude a trial with amplification.8

Other Factors It is not unusual to find that the most important factors determining success or failure of a fitting are unrelated to audiometric findings. In particular, one must take into consideration all of the following: the age and general physical and mental health of the patient; the patient’s (as opposed to only the family’s) motivation; finances; cosmetic considerations; and communication needs. It is interesting to note that finances and cosmetics were listed by only a very small percentage (5.1% and 3.4%, respectively) of respondents as primary reasons for rejections of amplification; the most cited reasons for patient rejection were (1) difficulty hearing in background noise and (2) discomfort from loud sounds.9 Problems presented by the latter reason should rarely occur if proper, modern-day fitting techniques are followed; however, the magnitude of the first mentioned shortcoming has been reduced but remains a significant problem.

STYLE AND TYPE OF HEARING AID In the early 1950s, listeners were limited to a choice between two styles of hearing instrument: body-borne aids or eyeglass aids. These styles are rarely used today. Hearing aid industry statistics show that as of 2000, 84% of hearing aid sales were of the in-the-ear (ITE) type (including in-thecanal, ITC, and completely in-the canal, CIC, aids), and 16% were behind-the-ear (BTE) models.10 The remainder (less than 1%) were the few body-borne devices still on the market, and bone-conduction hearing aids. The size of BTEs varies and is not correlated with the power or gain of the aid, but the shape of these models has remained relatively consistent (and is likely to remain so barring an evolutionary change in the anatomy of the human skull and pinna). In-the-ear hearing aids, on the other hand, are available in a variety of sizes, shapes, and models. They include the fully occluding custom all-in-the-ear model, the partially occluding half concha, the canal or mini-canal aid, and the tiniest of current styles, the completely in the canal instrument. Within the category of ITEs, custom full concha aids accounted for 35%, ITC and mini-canal aids 27%, and CICs 22% of the 2000 sales market.10 Decisions regarding which of these aids is appropriate for a specific patient are based on physical factors, audiolgic factors, and whether the patient needs one or two hearing aids.

Physical Factors Certain anatomic characteristics can clearly dictate the style of hearing aid chosen. For example, it is obvious that

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certain auricles are not conducive to postauricular wear. In order to be able to wear a canal or CIC type of hearing aid, the meatus must be of sufficient diameter and must have a sharp enough contour to retain the aid, but not so tortuous that it precludes easy insertion and removal. If the diameter of the meatus is insufficient but the patient still insists on a less than full concha fitting, a half concha style may be selected. Manual dexterity is an important, and occasionally overlooked, variable. Not only is the removal and insertion of certain hearing aids difficult for some patients, particularly the elderly, but ability to manipulate the volume control (when present) and battery should be considered and tested before any aids are selected. In addition, patients whose external auditory meatae produce excessive cerumen or require adequate ventilation may be ill-advised to wear CIC, canal, or even certain full concha ITE aids. Draining ears or ears with other medical contraindications for use of an earmold may require bone-conduction systems. Sound transmission through the cranium clearly is not as efficient as air-conduction transmission, and as a result boneconduction hearing aids have traditionally not been entirely satisfactory. In the past 15 years, there have been significant improvements in bone-anchored hearing aids designed to enhance bone-conduction transmission. For a review of these systems, the interested reader should consult Chasin, 2002.11

Audiologic Factors It is highly regrettable that many professionals and patients base decisions regarding hearing aid selection on cosmetic rather than audiologic factors. Unfortunately, there remains an undeniable societal stigma to hearing aid wearers that associates them with being elderly or of less intelligence than their normal-hearing counterparts.12,13 As a result, many manufacturers market and advertise their hearing aid products to maximize “invisibility.” Too frequently, these considerations overshadow audiologic guidelines. For example, individuals with regions of normal hearing, particularly in the low frequencies, may be better suited to systems that do not occlude the ear canal.14 There are a variety of reasons for this: First, many hearing aids produce at least some low-frequency amplification. By not occluding the canal, some of this unwanted amplification is shunted out, allowing the listener to make better use of his normal, natural low-frequency hearing ability. Second, occluding an ear canal inevitably produces an occlusion effect. The perception of an individual’s own voice is altered when the external auditory meatus is obstructed. This can be easily demonstrated by vocalizing an open vowel, such as an “ee” while alternately blocking the ear canal with a plug, or even one’s finger, and then leaving the canal unobstructed. This resultant increase in perceptual loudness and alteration of timbre is referred to as the occlusion effect. It is not a particularly bothersome problem for most people because their open ear canals offer an escape route for the additional low-frequency vibration created by vocalization. However, for hearing-impaired listeners whose ear canals are fully or partially occluded by the presence of an earmold or hearing aid shell, this effect is quite common and annoying. Furthermore, in addition to the perceptual alteration created by the occlusion effect,

A

B Figure 77-3. Illustration of the occlusion effect. A, The net gain in decibels created by insertion of an occluding earmold. The patient’s own voice saying “eee” served as the test signal. B, The relative response gains measured near the tympanic membrane for the occluded ear (lighter curve) and the unoccluded ear (darker curve) for the same sound.

amplification may produce a further acoustic and perceptual modification. The vibration trapped by an earmold obstructing the cartilaginous portion of the external auditory meatus produces this enhanced and unwanted low-frequency perception.15 The resultant effect is an increase in low frequencies, as illustrated by Figure 77-3. Thus, in order to provide a patient with minimal lowfrequency amplification and minimal occlusion, a more open coupled system may be necessary and this may be obtained only with certain BTE aids and open, nonoccluding earmolds. Attempts at adequately venting CIC instruments are restricted by the size of the ear canal. In addition, occluding the ear minimizes or even eliminates the 17 to 20 dB of natural resonance that occurs in the normal adult ear canal at about 2700 Hz. This is discussed in detail later in this chapter, as is the concept of deep canal fittings, an attempt to circumvent some of these problems. Conversely, the significant benefits yielded by certain amplification enhancements such as the use of dual and directional microphones (discussed later) may be significantly diminished by the use of open coupling systems. Preconceptions aside, there is much to be said cosmetically for fitting a patient with a small or mini-BTE aid coupled to the ear with an open earmold. Many, including this author, believe that a mini-BTE aid coupled to the ear with an open earmold is less conspicuous than most ITE, many ITC, and even some CIC aids. Acoustic feedback resulting from leakage of amplified sound from the earmold back into the hearing aid’s microphone has traditionally been an important consideration in

Hearing Aids and Assistive Listening Devices

the selection and fitting of amplification. Generally speaking, the closer the microphone is to the receiver, the greater the likelihood of feedback. Therefore, BTE aids often present an advantage over smaller ITE or ITC aids. Technologic advancements have now rendered this a lesser consideration. In the past, many manufacturers provided “feedback controls,” which were little more than potentiometers that reduced high-frequency amplification. While this did indeed accomplish the desired effect of reducing feedback, it did so at the expense of reducing the audibility of vitally important high-frequency consonants. However, with the increased use of digital hearing aids, phase-shifting techniques greatly minimize feedback problems, often allowing for nonocclusion and full usage of the natural resonance and increasing usable gain by more than 10 dB.16 A critically important advantage of BTE aids and many ITE (though currently not CIC) aids is the inclusion of a telecoil (magnetic induction loop). This feature allows the hearing aid to bypass its microphone and amplify signals presented electromagnetically (by law, nearly all modern public and private telephones produce electromagnetic leakage for this very purpose). In addition, telecoils interface with a variety of assistive listening devices, as discussed later in this chapter. There are certain distinct advantages of ITE aids over BTE aids, as well. Because of the placement of the microphone, ITE aids take advantage of the pinna effect as well as the concha resonance. These effects can enhance the amplified signal entering the canal by as much as 2 to 5 dB compared to a BTE microphone placement.17 As much as a 13-dB high-frequency enhancement has been demonstrated for CIC hearing aids.18

NUMBER OF HEARING AIDS REQUIRED More than 72% of hearing aid fittings in the United States are binaural.10 Often, word recognition scores measured in quiet sound-treated rooms are not sensitive enough to prove or disprove the notion of binaural superiority with regard to hearing aid use.19 Even so, preference investigations and anecdotal reports of enhanced laterality and more comfortable listening through binaural systems abound.20 Laboratory generated psychoacoustic data clearly demonstrate a number of binaural listening advantages. Of these, perhaps the most important advantages are elimination of the head shadow effect, binaural summation, squelch, and minimization of sensory deprivation.

The Head Shadow Effect Sound intensity is decreased by an average of 6.5 dB as it crosses the head (the head shadow). Because of the fluctuating nature of our acoustic environment, however, listeners find themselves in adverse positions (wherein the “good” ear may be closer to the unwanted background noise and the “bad” ear is closer to desired sound source, i.e., speech) nearly 50% of the time. As a result, the difference between monaural direct listening and monaural indirect listening may be as much as 13 dB. Furthermore, the head shadow effect is greatest for the high frequencies, those most responsible for

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speech intelligibility. The use of binaural aids minimizes the probability of being in the adverse monaural indirect location. This is also the principle applied to contralateral routing of sound (CROS) amplification21 as used for patients with only one ear that is amenable to amplification.

Binaural Summation Absolute binaural thresholds are 2 to 3 dB better than monaural thresholds.22 At suprathreshold levels, where listeners receive amplified sound, summation increases by as much as 6 to 10 dB.23 Thus, a hearing aid user can achieve the same loudness perception with binaural hearing aids set at a lower volume control than with a monaural aid. This may greatly reduce feedback problems. In addition, one might reason that if binaural stimulation sounds louder than monaural stimulation, it would be necessary to limit the maximum power of a hearing aid to keep it from exceeding the patient’s loudness discomfort level. Hawkins24 found that when subjects were asked to match the loudness of binaural and monaural stimuli, the summation effect occurred but these same subjects reported no reduction in binaural loudness discomfort versus monaural loudness discomfort. In fact, most indicated that the binaural stimuli could be more intense than the monaural stimuli before it produced discomfort. Thus, it follows that the dynamic range of listening is greater for binaural listening than for monaural listening.

Squelch Forty years ago, Koenig25 described the concept of binaural squelch demonstrating that dichotic listening (receiving two separate and distinct signals in each ear) is more tolerable than either monotic (all signals to one ear only) or diotic (the same signal to each ear). A series of experiments26,27 showed that a significant release from masking could be achieved under certain conditions because of the out-ofphase relations of the signal and noise reaching two ears. The magnitude of this release (termed masking level differences) cannot be achieved through monaural listening.

Sensory Deprivation In a 5-year retrospective study,28 it was found that word recognition scores decreased in the unaided ears of monaurally aided patients but not in the aided ears. In a matched group of binaurally aided patients, however, word recognition scores in both ears remained constant. Similar findings were reported by other researchers;29 however, it remains uncertain whether this is a peripheral or central phenomenon. Thus, the general rule is that unless a significant asymmetry exists between the ears in either sensitivity or word recognition ability, the standard should be trial with binaural amplification. Of course, there are patients for whom one ear is clearly unaidable because of a total lack of auditory sensitivity (i.e., following certain destructive surgeries), extremely poor word recognition ability, vastly reduced loudness tolerance, or medical conditions precluding the insertion of anything into the external auditory meatus. For these patients, CROS aids are available (some in wireless FM form). Also, some hearing instrument specialists have

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reported success using a transcranial CROS approach, in which a powerful hearing aid is placed in or on the dead ear, thus transferring the amplified signal (minus interaural attenuation) across to the better cochlea via bone conduction.30,31 This type of fitting is most effective when the better ear has normal or nearly normal hearing and the poorer ear has no residual hearing that might produce recruitment or other distortion factors.

HISTORY OF HEARING AID SEZLECTION PROCEDURES The evolution of hearing aid selection procedures has progressed in the following manner.

Selective Amplification Prior to the 1940s, fitters looked at audiometric results and attempted to “mirror” the audiogram, that is, gain equal to hearing loss at each frequency.32 Mirroring the audiogram, even with a constant subtracted from each frequency, inevitably led to overamplification in certain frequency regions, however. In 1940, Watson and Knudsen33 suggested establishing a “most comfortable equal-loudness contour” by first finding the most comfortable level at 1000 Hz and then defining the remainder of the contour by matching frequencies to the 1000-Hz level. Amplification was then prescribed as the mirror image of that contour and adjusted by the volume control of the hearing aid. In 1944 Lybarger34 prescribed the “one-half rule” whereby gain was one-half of the threshold level. He based this rule on his empirical observation of where listeners set the volume controls (termed use gain) on their hearing aids. A major study later called “The Harvard Report,”35 indicated that an “optimal” frequency response (rising at 6 dB per octave) would satisfy the needs of most hearing-impaired listeners, regardless of the audiometric configuration.

Comparative Approach Later that year, a comparative approach, known as the Carhart method,36 became the main selection procedure and was used for the next 25 years. Basically, this procedure consisted of comparing several preselected hearing aids set to produce a comfortable listening level for a 40-dB HL speech input, on the following parameters: aided SRT, uncomfortable (or loudness discomfort) level, and measurement of word discrimination for phonetically balanced monosyllabic words in quiet and noise. These tests were rather time consuming and subsequent data37 proved that the resultant measures were not sensitive enough to differentiate among hearing aids, in addition to the fact that they carried questionable face validity. Despite the popularity of the Carhart method, interest in prescriptive fitting techniques continued. A logical, though never widely accepted approach in the United States, called “otometrics” was introduced by Victoreen38 in the early 1960s. In this method, the difference in decibels between the “normal” loudness comfort contour and the hearingimpaired individual’s loudness contour, as obtained using

an ascending presented damped wave-train signal, determined the recommended gain and frequency response.

Modern Prescriptive Formulas Victoreen and Lybarger were ahead of their time. Today, most hearing aid fittings are based on computer-based prescriptive formulas. Perhaps the most common formulas are those proposed by Byrne and Dillon of the National Acoustics Laboratory of Australia39 and the desired sensation level (DSL).40 While based on threshold measures, these formulas also take into account the audiometric slope and average loudness growth, so they are more complex than simple one-half or one-third gain rules. In addition, they incorporate the unique ear canal characteristics of each patient through the use of probe tube measures.

Real Ear (Probe Tube) Measures Although researchers have proposed a variety of formulas to best predict the “ideal” aided response, it was not until the refinement of probe tube, or real ear measures, that prescriptive techniques really became predominant. Probe tube measurements allow noninvasive, rapid measurement of the sound received within approximately 5 mm of the tympanic membrane, and thus take into account the effects of the ear canal. It has long been known that the physical characteristics of the external auditory meatus produce a resonance that may vary from ear to ear. Figure 77-4 depicts an “average” adult real ear unaided response (REUR) of the unoccluded ear, as well as a real ear aided response (REAR) for the same patient. Figure 77-5 shows examples of the variety of ear canal resonances that are common. It is apparent that the response of any given hearing aid will be received at the tympanic membrane differently for any given patient, depending on that patient’s ear canal resonance pattern. Certain anatomic peculiarities that could result from pathologic conditions such as exostoses can significantly alter the REUR. Since the validity of most prescriptive formulas is based on assumptions holding true for the “average” ear, individual variation may result in considerable deviation from that average.41 Modern prescriptive formulas are based on the assumption that a systematic relationship exists between hearing thresholds and judgments of comfort or preference, resulting in specific gain at each frequency. The formula specifies a target as the goal of the real ear insertion response (REIR),

Figure 77-4. A typical real ear unaided response (REUR) and real ear aided response (REAR) for the same patient.

Hearing Aids and Assistive Listening Devices

Figure 77-5. Comparison of an average REUR (heavy curve) with two atypical REURs (dashed curves).

which is simply the difference between the REAR measured at the tympanic membrane and the REUR. Both the REUR and REAR are typically measured with an input of 50, 60, or 70 dB. Figure 77-6 shows a target gain and REIR for a patient for whom a good target match was achieved all the way out to 4500 Hz. Matching the target for higher frequencies is often not possible. Note that the same hearing aid on a patient with a different REUR would produce a different REAR and thus would not match the target gain. The goal of all hearing aid fittings is to package the amplified speech inside the listener’s dynamic range (defined as threshold level to loudness discomfort level).42 In other words, the amplified signal must be audible across the frequency range but must not be uncomfortably loud for the listener at any frequency. Refined computer software packages such as the Desired Sensation Level40 are available to prescribe the amount of desired gain and output in order to allow conversational speech to fall within these limits. These programs map the amplified level of conversational speech in relationship to the listener’s threshold and REAR. Additionally, and of extreme importance, they also map the desired maximum output against the listener’s real ear saturation response (RESR). The RESR is simply the REAR measured with a 90-dB SPL input. This input level is sufficient to drive the hearing aid into saturation so that there is a measure of the maximum amount of amplification provided by the hearing aid regardless of further increases in input. The hard walled coupler equivalent to this procedure formerly was referred to in the literature as the maximum power output and is now commonly referred to as the SSPL 90. It is an essential measure to

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ensure that the individual’s loudness discomfort level is not exceeded for any frequency. It is always ideal to have at least a 10- to 20-dB difference between the REAR and the RESR so that there is adequate “headroom” in the hearing aid to minimize distortion should there be an increase in input.43 Most audiologists now assess the REAR using multiple input levels to approximate the response at soft (45 to 50 dB SPL), conversational (65 to 70 dB SPL), and loud (86 to 90 dB SPL). Despite the proliferation of real ear prescriptive procedures, it is critical that the audiologist view these results merely as “starting off” points. Keep in mind that even though real ear measures are a step in the right direction in tailoring the aid to the individual’s external ear canal characteristics, further individual variations in loudness growth, and so forth, still need to be accounted for. Therefore, additional fine-tuning must be made to suit the individual’s preference and verification procedures using a variety of stimuli including speech. Measures such as the hearing in noise test (HINT)44 and the sentence in noise (SIN) test45 using adaptive procedures to maintain a certain subjective percentage of continuous discourse recognition in the presence of varying degrees of background noise are becoming increasingly popular as a supportive validation technique.

EARMOLD ACOUSTICS Perhaps the most important data provided by real ear measures are those related to the effect of earmold coupling on the hearing aid’s response as received at the tympanic membrane. As already stated, the REUR shows the natural resonance produced by the physical characteristics of the external ear. When an ITE or ITC or BTE aid coupled to an earmold of any style fully or partially occludes the ear, this natural resonance is altered. The amount of occlusion, vent diameter and length, length of the earmold, bore of the earmold, and so on all have measurable effects on the REAR. Generally, for example, the larger the vent, the less the low-frequency gain; the longer the canal length, the greater the overall gain; if the coupler contains a belled bore, the greater the high-frequency gain; and most important, the greater the occlusion (real ear occluded response, or REOR), the more the natural REUR is diminished (Fig. 77-7). Thus, it would be ideal if the hearing aid could be coupled to the ear in a completely nonoccluding manner, thus preserving the REUR. Unfortunately, the sound in the canal, once amplified by more than about 30 dB, escapes the acoustic seal and leaks back into the microphone of the hearing aid, thus producing feedback. This is where technological advances, such as electronic phase shifting to control feedback, become important.

TECHNOLOGICAL ADVANCES

Figure 77-6. Target gain and REIR. The REIR is the difference between the REAR and the REUR. Note that the gain of the hearing aid is typically diminished above 4000 to 6000 Hz.

The last several years have brought about a myriad of dramatic technological advances in hearing aids. These advances have been obtained using three types of signal processing: analogue, hybrid, and digital. Analogue instruments amplify, filter, and limit the maximum power by manipulating parameters via on-instrument

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Fitting Flexibility

A

B Figure 77-7. A, The REUR (heavier curve) and the REOR for an occluding, closed earmold. B, The same two measures for a nonoccluding earmold. Notice the loss of the REUR that occurs by blocking the ear, whereas the REUR is essentially unaltered by the nonoccluding earmold.

potentiometers, switches, or rotary controls. Their efficiency was limited because most of the processing objectives that will be discussed shortly could not be implemented. In the late 1980s, technology took a step forward with the introduction of digitally programmable hearing aids. With these instruments, signals remain processed by analogue components, as in the case with conventional amplification. This type of amplification is considered hybrid (a combination of analogue and digital) because a computer (digital technology) is used to program the hearing aids. In addition to enhancing precision and quality control, hybrid hearing aids allow increased flexibility of the aids, both for the audiologist and the user. In 1996 digital hearing aids were introduced. Digitization means that incoming analogue signals received by the microphone are sent through a preamplifier to an analogue-to-digital (A/D) converter where the signals are converted to a series of binary digits (0s and 1s). These numbers are then manipulated by the digital signalprocessing (DSP) unit according to a set of instructions (algorithms) that are either preset or programmed by the audiologist. A new set of binary digits is formed, which is then reconverted from digital to analogue (D/A) as it exits the hearing aid’s loudspeaker and enters the ear canal. Although DSP in and of itself doesn’t guarantee a “better” instrument, added features and processing schemes are available with digital technology that were not possible before.46 The objectives of these features and processing schemes have been directed primarily to enhance fitting flexibility, loudness control, and noise reduction.

The ability to selectively amplify certain frequency regions in accordance with the wearer’s audiometric characteristics is enhanced by the presence of multiple frequency shaping bands. Analogue hearing aids generally contain variable screw potentiometers that allow the fitter to alter the tilt of the frequency response or the output levels. Hybrid and digital aids typically use multiple channels of compression and frequency shaping (similar to a graphic level equalizer) that allow for enormous flexibility in frequency response for nearly any audiometric configuration. In addition, multiple filtering bands in these hearing aids allow more precise control over gain and frequency response. This is particularly important not only for unusual audiometric configurations but also in light of recent research data. These findings indicate that providing audibility to high-frequency regions where hearing loss is greater than 55dB HL may produce little or no improvement in speech recognition. Indeed, amplifying this region may even produce decreased intelligibility.47 A hearing aid that produces only a single response regardless of the acoustic input is often not adequate for hearing-impaired individuals exposed to a multitude of acoustic environments.48 Thus, manufacturers began introducing a family of automatic signal-processing (ASP) devices that automatically alter the electroacoustic parameters depending on the characteristics of the incoming signal. The automatic actions enacted by the hearing aid initially were relatively elementary but now, because of digital technology, have progressed to the point where there are literally millions of calculations and actions per second. Early ASP strategies were based on the fact that most, though not all, background noises comprise mainly low-frequency energy. Thus, hearing aids were made to automatically reduce the low-frequency gain when the low-frequency input reached a certain level. An example of an automatic low-frequency reduction response is shown in Figure 77-8. These aids were initially referred to as having “automatic noise reduction,” but in reality, both the signal and the noise were reduced by the same amount, thus maintaining an identical physical signal-to-noise level. Subjectively, however, the “perceptual” signal-to-noise level is often enhanced since the low frequencies in noise may be annoying while the low frequencies in speech carry minimal weight in terms of intelligibility. There have been

Figure 77-8. Two gain curves generated by an automatic signal-processing (ASP) hearing aid. Note that the introduction of excessive low-frequency (background) noise produces a decrease in low-frequency gain (dashed curve).

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Loudness Control

Figure 77-9. Four frequency responses produced by a multiprogram hybrid hearing aid.

conflicting reports in the literature as to the benefit of such strategies.49,50 A useful feature in many digital and hybrid hearing aids is the presence of multiple programs so that at the touch of a button on the aid or in a remote control device, the electroacoustic characteristics of the aid can be instantaneously changed to compensate for the particular acoustic environment. In a sense, it is similar to giving people the option to change from prescriptive sunglasses to regular eyeglasses. The number of programs available in a particular aid varies among models and manufacturers, most providing two to four programs. Frequency responses from a hearing aid that contains four programs are depicted in Figure 77-9. The usefulness of multiple programs is not limited to the provision of choices for the experienced user in a variety of acoustic environments. Some audiologists also use it as a means of gradually introducing variations in the amplified sound to the new user. For example, some patients with high-frequency loss initially find that a sharply sloping high-frequency response sounds too tinny. For this listener, program 1 could incorporate a flatter, broader-band frequency response that more closely resembles what the patient is accustomed to hearing. As the wearer becomes more acclimated to amplification, he may then switch to program 2, which has been programmed to filter out the low frequencies and provide a high-frequency emphasis that is believed to be more appropriate for his hearing loss. Additional programs may be entered to provide similar frequency responses but different compression characteristics. Multiple programs also can be set to provide an acoustically acceptable response for telephone use. One of the most common problems for hearing aid users, particularly those wearing ITE aids, is feedback occurring when the telephone receiver is held close to the microphone of the hearing aid. One program can be set to filter out the high frequencies that are responsible for feedback. This will not affect the received, amplified telephone signal because telephone receivers have frequency responses that typically roll off above 3000 Hz. The individual with fluctuating hearing loss, such as the patient with Ménière’s disease, also can benefit from multiple programs. Rather than having to return to the audiologist each time hearing thresholds change, various programs can be set in anticipation of the expected amount of shift.

It is essential to prevent the amplified signal from reaching the loudness discomfort level of the wearer. Early hearing aids used a method of limiting the output referred to as peak clipping (linear amplification). Linear amplification provides a constant gain (output minus input), regardless of input level, until the output (gain plus input level) reaches a certain, predetermined ceiling level. At this point, further increases in input no longer produce an increase in output. Unfortunately, once the aid reaches this saturation point, the energy is redistributed into other frequency regions, thus producing distortion. An alternative output-limiting approach that is useful in minimizing distortion is compression (sometimes referred to as automatic gain control, or AGC). In compression circuits, gain is automatically reduced once a predetermined level (based on either the input or the output level) is presented to the hearing aid microphone (or receiver) in such a way that the hearing aid never reaches the saturation point. An example of compression is shown in Figure 77-10. Although compression is an improvement over peak clipping in terms of minimizing amplitude distortions such as harmonic and intermodulation distortion, there is some degree of temporal distortion introduced during the activation and release of the function that may not be advisable for severely and profoundly impaired listeners.51 Two basic rules must be followed if a hearing aid fitting is to be successful. They are (1) soft sounds must be made audible and (2) loud sounds must not be uncomfortable. Compression is designed to accomplish this effect. However, it can fail to achieve this objective. This is because many early analogue compression instruments use single-band compression. In other words, when compression is activated, amplification of all sounds (low-, medium-, and high-pitched) is reduced. This broad reduction is not good for two reasons. First, hearing-impaired individuals tend to show greater tolerance for sounds at certain frequencies than for others. Second, an invasive noise that may be restricted to certain frequencies (i.e., the low frequencies) would produce a decrease in amplification for all of the frequencies, thus making the weaker high-frequency consonants in speech harder to hear. Thus, the characteristics programmed into the hearing aid needs to differ for the various frequencies. Through the use of multiple bands, a completely unique set of signal-processing instructions can

Figure 77-10. Single-channel compression. These three gain curves were produced with an 80-dB input (lower curve), 70-dB input (middle curve), and 60-dB input (upper curve).

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be provided for different frequencies. This not only helps to maintain comfort throughout the frequency range, but it also ensures that reduction in amplification is limited to frequencies that comprise the offending, loud noises. To combat the single-channel shortcoming, there are now hearing aids that contain multiple compression circuits that act independently in two or more frequency bands.52–54 The pattern of recruitment in any given individual cannot be predicted simply on the basis of a pure tone audiogram. Therefore, it is beneficial to have adjustable characteristics for the various compression parameters such as kneepoint (activation level), compression ratio (how severely the gain is reduced), and release time (how soon the aid returns to a linear mode once the activating signal ceases). In this way, frequency regions that display recruitment (such as the high frequencies for certain patients) can use compression circuitry, while other frequency regions that may not show recruitment (such as the low frequencies for certain patients) can be amplified in a linear manner. Taking this approach in conjunction with the principle of amplitude acoustic transparency, one can, for example, provide an extra boost to soft high-frequency sounds while providing a decrease in the gain of unwanted, loud low-frequency sounds. This is the concept embodied by “full-range dynamic compression” in which very-lowinput sounds are amplified linearly but high-input sounds receive little or no electronic processing.55 All of the digital hearing aids currently on the market contain multiple bands of compression. Presently, the number of bands range from as few as 2 to as many as 20. There are no published data yet that clearly demonstrate an optimal number of bands. It is interesting to note, however, that the increasing number of bands is now approaching the number of critical bands in the normal cochlea. Yet another benefit is realized through the flexibility afforded by multiple bands. If the appropriate electroacoustic parameters have been defined and programmed based on the clinical test battery, the need for frequent (if any) volume control manipulations by the user is greatly minimized. Thus, most digital hearing aids do not contain volume controls.

Noise Reduction Previous attempts at automatic noise reduction were based on the assumption that noise comprises primarily low frequencies. When the low-frequency input to the hearing aid exceeded a certain intensity level, the gain was automatically reduced. The flaw in this strategy is that not all noise is limited to low frequencies. Moreover, the auditory system does not function as a mere spectrum analyzer; rather, it is exquisitely tuned to temporal characteristics. Digital signal processing allows instruments to attempt a differentiation of noise from speech, not only on the basis of spectral composition but also on the basis of temporal characteristics. Noise and speech have quite distinct temporal patterns. For example, speech modulates at a much slower rate than does noise. Thus, digital hearing instruments assess the modulation pattern (rate and depth) of the incoming signal to predict whether that signal is

primarily speech. If it is, full amplification will be provided. If not, gain will be attenuated within that frequency band. While this approach to noise reduction appears to offer subjective improvement, its benefit has not yet been proven objectively. In spite of the new developments in noise-reduction strategies, the fact remains that in all of these approaches, the signal-to-noise ratio in any given band remains constant. In other words, if the gain is reduced in one band, both the signal and the noise in that band are deemphasized by the same amount. So this may assist the patient’s perceived comfort in a noisy or loud environment, but it may have little positive effect on the patient’s ability to understand speech. In reality, the only method of truly enhancing signal-tonoise ratio is through the use of directional or multiple microphones. Improvement in the signal-to-noise ratio can reduce noise and improve comfort in noise. There are several excellent reviews of the entire gamut of available microphone arrays including directional, multiple, and beam-forming technologies.56–59 These approaches allow for communication between microphones that can effectively minimize the gain based on the directional origin of the incoming signal. Thus, sounds originating behind the hearing aid (i.e., with azimuths of 135 to 225 degrees) can be significantly suppressed relative to sounds occurring in front of the hearing aid. Among the improvements in microphone technology available in some digital instruments is a variety of polar patterns (the directional pattern of suppression), including automatically adapting polar patterns, and user-switchable omnidirectional/directional operating modes. Although omnidirectional microphones are often preferred for quiet listening, significant objective and subjective improvement in noise are consistently shown in multiple microphone modes. Figure 77-11 depicts the suppression of sound originating behind the listener versus that in front of the listener. Although the use of multiple microphones does not technically require digital processing, flexibility and future degrees of directionality may be enhanced by digital control. Additionally, it is exciting to note that some of the new digital hearing aids now contain an FM receiver that can be used with a remote microphone for optimal improvement in signal-to-noise ratio. The advantage of FM technology with hearing aids will be explained shortly. Perhaps the greatest current advantage of digital technology is the ability to minimize or suppress acoustic feedback. Digital feedback suppression allows a hearing aid to produce 10- to 15-dB greater gain before producing sustained audible feedback. It does so by measuring and anticipating the feedback escape route and then producing an electronic phase-shifting transfer function.60

Deciding between Digital and Digitally Programmable New developments in hearing aid technology do not necessarily translate into user benefits. Studies have reported findings of subjective preferences for digital hearing aids but have been unsuccessful in verifying objective

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A

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The decision regarding whether digital or hybrid aids should be prescribed should be arrived at following extensive discussion by the audiologist and the patient. The determination should be based largely on the acoustic needs of the patient. A patient who lives alone and who wants to wear amplification for the sole purpose of watching television does not require digital hearing aids. The phrase “you don’t need to drive a Rolls Royce if all you are going to use it for is to drive to the supermarket” is suitable. Furthermore, digital in and of itself may not be a sufficient cause to add to a patient’s expense. If the processing algorithm is not superior to that which can be provided by an analogue system, there may be little justification for using that product.

OTHER NEW DEVELOPMENTS Deep Canal Fittings

B Figure 77-11. A, Aided response measured with the sound source originating at 0 and a 180-degree azimuth for an aid with an omnidirectional microphone (upper panel). For comparison, B shows the same measures for an aid with a directional microphone. Note that the omnidirectional microphone aid provides equal amplification for sounds lower than 2000 Hz regardless of their origination.

superiority from these instruments. In the majority of the studies, objective superiority (in the form of improved word recognition scores) is demonstrated only for low presentation levels. On the other hand, at high levels, and in very adverse noise conditions, no statistical differences have been shown. A variety of factors may explain this apparent discrepancy in findings. It is possible that word recognition scores simply are not sensitive enough to demonstrate differences. It is also possible that sufficient adaptation time and/or auditory training with both sets of devices was not given to maximize performance. Furthermore, it is possible that the old standard of word recognition scores simply does not reflect everyday communication function and those features most coveted by hearing-impaired patients. For example, in nearly all of the studies published in the past few years, subjects report greater listening comfort with digital hearing aids. This perceived benefit is not reflected by word recognition scores. It is also interesting to note that one study reported 75% of the subjects assessing both “high-tech hearing aids” and conventional instruments in a double-blind design indicated a preference for the high-tech instruments. But when informed of the retail cost of both types of device, 33% changed their minds.61 In reality, analogue hearing aids can do all of the things a digital system can do; however, it would require excessive size, power consumption, or both. Therefore, digital is clearly the technology of the future where advanced processing is concerned.

As alluded to previously in this chapter, occluding the ear canal can produce a deleterious effect for the hearing aid wearer for two primary reasons: (1) it alters the natural physiologic resonance peak around 2700 Hz that is present in the normal open ear canal, thus degrading the perception of other voices, and (2) it generates a sound pressure in the canal that results in a low-frequency resonance that is interpreted by the patient as “the barrel effect,” thus degrading the perception of the user’s own voice. Zwislocki62 demonstrated that placement of an earplug in the cartilaginous (outer two-thirds) portion of the ear canal yielded more bone-conducted sound in the canal than if the earplug was inserted deeply into the osseous (inner one-third) portion of the meatus. As a result, there have been recent attempts at placing the earmold (or hearing aid) further into the canal, effectively shortening the tubular chamber between the end of the earmold (or hearing aid) and the tympanic membrane. This “deep ear” concept has been used both for earmold coupling used with BTE aids and for deep fittings with ITC hearing aids.63 Although the deep ear concept does not solve the problem of losing the natural resonance at 2700 Hz, it may minimize the “barrel effect.” It is too early to say whether “deep ear fittings” will become routine. At this time, many audiologists are reluctant to fabricate an earmold impression in such close proximity to the tympanic membrane. Also, the physical presence of a physician is required to ensure a perfectly clear external auditory meatus before the taking of the earmold impression. This is particularly a drawback for audiologists who do not work directly with physicians. There are current plans to produce a deep canal fitting with a material that is comfortable and long-lasting for extended wear.

Disposable and Entry-Level Hearing Aids One manufacturer recently introduced disposable hearing aids. These devices are in-the-canal noncustom (“one size fits all”) devices that contain an irretrievable battery designed to last for 1 month. Patients wear the devices and discard them after 1 month’s use. The major advantage of

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these devices is that they are inexpensive (at least in terms of the initial investment) and not subject to technologic obsolescence. Thus, if after a limited period of time, the user decides that the devices are not meeting his or her needs, they can be discarded and no further money is invested. They also should be subject to fewer mechanical breakdowns because the short life span may not be long enough to acquire cerumen blockage, electrical failure, and so on. Conversely, there is some question about their comfort and serious concerns remain regarding the methods with which they will be dispensed to the public. Certainly, the potential for abuse and misuse exists if these devices are unregulated and sold in drug stores or via the Internet or mail order. 64

ASSISTIVE LISTENING DEVICES One of the major goals of amplification strategies is to enhance the signal-to-noise ratio perceived by the listener. Unfortunately, despite all the new technologic advances discussed so far in this chapter, a basic problem remains for which wearable amplification falls woefully short. That problem relates to the physical distance between the microphone of the hearing aid and the source of the sound desired to be heard. Intensity decreases by 6 dB for every doubling of the distance, according to the inverse square law. Thus, if the intensity of a speaker standing 3 feet from the listener is 60 dB, that intensity will be only 54 dB if the speaker-to-listener distance is 6 feet. Unfortunately, background noise commonly surrounds the listener, so while the intensity of the speech decreases with distance, the intensity of the noise may not. Referring to the example just stated; if the original signal-to-noise ratio was +5 dB (meaning that the speech intensity is 5 dB greater than the noise intensity) at 3 feet, that signal-to-noise ratio could decrease to –1 dB at 6 feet. This is one reason that hearing aids transmit sound so well if the speaker talks directly into the microphone, but at longer, more realistic, distances, reception diminishes. It would be ideal to have the sound produced at the source transferred directly to the listener without losing intensity. It is obviously impractical, however, to ask the speaker to move closer to the listener’s ear. One way of achieving this effect is with direct audio input, in which the speaker holds a microphone that is hard wired to the hearing aid itself near his mouth. Many hearing aid wearers are reluctant to ask the speaker to do this, however. An alternative approach is available through infrared transmission, FM transmission, or inductance loop transmission. These systems are currently used in many theatres, concert halls, houses of worship, and households. One of the best uses is for television listening. The portable transmitter, usually a box smaller than most cable boxes, and microphone are located near the TV loudspeaker. The sound picked up by the microphone is then transmitted to a receiver worn by the listener, without a decrease in intensity. These devices can transmit with minimal distortion over a considerable distance (up to 50 feet). Infrared transmissions are limited in that a direct line of sight is required. FM transmission can actually occur around corners and even into different rooms (although occasionally another FM receiver using a similar frequency

can cause interference). Inductance loop systems often do not require an expensive receiver because they are compatible with the telephone coils found in many BTE and some ITE hearing aids. They are sometimes not as popular as infrared and FM systems because they require that a loop be placed around the circumference of the listening area. Assistive listening devices (ALDs) are becoming increasingly apparent in public places as a result of the legislative enactment of the American with Disabilities Act. 65 Other, nonwearable devices that assist the hearingimpaired listener include telephone amplifiers, vibrating alarm clocks, TV closed-caption decoders, inexpensive personal hand-held or body-borne amplifiers, visual alarm systems, and telephone devices for the deaf (TDDs). A detailed description of ALDs is offered by Compton.66

CONCLUSIONS This chapter began with a statement that audiology and the fitting of hearing aids is still a relatively young discipline. We hope that the reader is impressed with the enormous advancements that have taken place during the last half century. In order to achieve proper and optimal utilization of digital technology, however, appropriate fitting algorithms must be further refined. We also hope that it is clear from this chapter that selection and fitting of hearing aids is based on an almost limitless number of variables that contribute to successfully fitting amplification devices. Significant problems remain, however, for which even advanced electronics and computer technology will not provide the solutions. For example, the population for whom hearing aid use is still most prevalent, the elderly, presents difficulties with auditory processing of a central, in addition to a peripheral, nature that may not be amenable to solutions provided by even the most advanced technology and fitting strategies. Therefore, research must focus not only on technology but also on development of clinical psychoacoustic test batteries that will help define each individual’s needs. Moreover, a major portion of aural rehabilitation is counseling. Expectations associated with market portrayal of digital hearing aids and their increased retail cost lead to higher, often unrealistic expectations. Not only can these unrealistic expectations lead to disappointment when the hearing aids fail to deliver perfection, but patients can become “lazy” in their listening skills because they expect the hearing aids to “listen” for them. Audiologists, otologists, and neuroscientists must combine their efforts to develop methods of teaching a hearingimpaired brain to develop new perceptual learning based on amplification.

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4. Pavlovic C: Speech spectrum considerations and speech intelligibility predictions in hearing aid evaluations. J Speech Hear Disord 54:3–8, 1989. 5. Humes L, Roberts L: Speech recognition difficulties of the hearing impaired elderly: The contributions of audibility. J Speech Lang Hear Res 33:726–735, 1990. 6. Mueller HG, Jons C: Some clinical guidelines for the fitting of certain custom hearing aids. Am Speech Hear Assoc 10:57, 1989. 7. Stach BA, Loiselle LH, Jerger JF: Special hearing aid considerations in elderly patients with auditory disorders. Ear Hear 12:131S–137S, 1991. 8. Berger KW, Hagberg EN: An examination of binaural selection criteria. Hear Instrum 40:44–46, 1989. 9. Madell J, Pfeffer E, Ross M, Chellappa M: Hearing aid returns at a community hearing and speech agency. Hear J l 44:8–23, 1991. 10. Strom K: The HR dispenser survey results. Hear Rev 8(6):43:20–42, 2001. 11. Chasin M: Bone anchored and middle ear implants. Trends Amplification 6(2):3–38, 2002. 12. Surr R, Hawkins DB: New hearing aid users’ perception of the “hearing aid effect.” Ear Hear 9:113–118, 1988. 13. Berger K, Hagberg E: Hearing aid users’ attitudes and hearing aid usage. Monogr Contemp Audiol 3:24, 1982. 14. Sweetow R: The truth behind non-occluding earmolds. Hear Instrum 42:48, 1991. 15. Sweetow R, Valla A: Effect of electroacoustic parameters on ampclusion in CIC hearing instruments. Hear Rev 4(9):8–12, 16–18, 22, 1997. 16. Groth J: Digital signal processing has made active feedback suppression a reality. Hear J 52(5):2–36, 1999. 17. Gartrell E, Church GT: Effect of microphone location in ITE vs. BTE hearing aids. J Am Acad Audiol 1:151–153, 1990. 18. Gudmundsen G: Fitting CIC hearing aids: Some practical pointers. Hear J 47(7):10, 45–48, 1994. 19. Carhart R: The usefulness of binaural hearing aids. J Speech Hear Disord 23:42–51, 1958. 20. Balfour PB, Hawkins DB: A comparison of sound quality judgments for monaural and binaural hearing aid processed stimuli. Ear Hear 13:331–339, 1992. 21. Harford E, Barry J: A rehabilitative approach to the problem of unilateral hearing impairment: The contralateral routing of signals (CROS). J Speech Hear Disord 30:121–138, 1965. 22. Haggard M, Hall J: Forms of binaural summation and the implications of individual variability for binaural hearing aids. Scand Audiol (Suppl 15):47–63, 1982. 23. Reynolds G, Stevens S: Binaural summation of loudness. J Acoust Soc Am 32:1337–1344, 1951. 24. Hawkins DB: Selection of SSPL 90 for binaural hearing aid fittings. Hear J 39:23–24, 1986. 25. Koenig W: Subjective effects in binaural hearing. J Acoust Soc Am 22:61–62, 1950. 26. Licklider JC: Influence of interaural phase relations upon the masking of speech by white noise. J Acoust Soc Am 20:150–159, 1948. 27. Hirsh IJ: The influence of interaural phase on interaural summation and inhibition. J Acoust Soc Am 20:536–544, 1948. 28. Silman S, Gelfand S, Silverman C: Effects of monaural versus binaural hearing aids. J Acoust Soc Am 76:1357–1362, 1984. 29. Silverman C, Silman S: Apparent auditory deprivation from monaural amplification and recovery with binaural amplification: Two case studies. J Am Acad Audiol 1:175–180, 1990. 30. Chartrand MS: Transcranial or internal CROS fittings. Hear J 44:24–29, 1991. 31. Sullivan RF: Transcranial ITE CROS. Hear Instrum 39:11–12, 1988. 32. Knudsen VO, Jones IH: Artificial aids to hearing. Laryngoscope 45:48–69, 1935.

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33. Watson N, Knudsen VO: Selective amplification in hearing aids. J Acoust Soc Am 11:406–419, 1940. 34. Lybarger SF: Selective amplification: A review and evaluation. J Amer Aud Soc 3:258–266, 1978. 35. Davis H, Hudgins VC, Marquis RJ, et al: The selection of hearing aids. Laryngoscope 56:85–115, 135–163, 1946. 36. Carhart R: Tests for the selection of hearing aids. Laryngoscope 56:780–794, 1946. 37. Thornton AR, Raffin MJ: Speech discrimination scores modeled as a binomial variable. J Speech Hear Res 21:507–518, 1978. 38. Victoreen JA: Hearing Enhancement. Springfield, lll, Charles C Thomas, 1960. 39. Byrne D, Dillon H: The National Acoustic Laboratories’ (NAL) new procedure for selecting the gain and frequency response of a hearing aid. Ear and Hear 7:257–265, 1986. 40. Seewald R: The desired SL approach for children: Selection and verification. Hear Instrum 39:18–22, 1988. 41. Hawkins DB: Clinical ear canal probe tube measurements. Ear Hear 8:74S–81S, 1987. 42. Skinner M, Pascoe D, Miller J, Popelka G: Measurements to determine the optimal placement of speech energy within the listeners’ auditory area. In Studebaker G, Bess F (Eds.): The Vanderbilt Report. Monogr Contemp Audiol 161–169, 1982. 43. Preves D: Approaches to noise reduction in analog, digital, and hybrid hearing aids. Semin Hear 11:39–67, 1990. 44. Nillson M, Soli S, Sullivan JA: Development of the Hearing in Noise Test for the measurement of speech reception thresholds in quiet and noise. J Acoust Soc Amer 95(2):1085–1099, 1994. 45. Killion M: The SIN report: Circuits haven’t solved the hearing-innoise problem. Hear J 50(10):8–32, 1997. 46. Sweetow R (Guest Ed.): Special issue on digital signal processing hearing aids. Hear J 51, 1998. 47. Turner CW, Cummings KJ: Speech audibility for listeners with high-frequency hearing loss. Am J Audiol 8:47–56, 1999. 48. Libby E, Sweetow R: Fitting the environment: Some evolutionary approaches. Hear Instrum 38:8–12, 1987. 49. Van Tasell D, Larsen S, Fabry D: Effects of an adaptive filter hearing aid on speech reception in noise by hearing impaired subjects. Ear Hear 9:15–21, 1988. 50. Tyler R, Kuk F: Some effects of “noise suppression” hearing aids on consonant recognition in speech-babble and low frequency noise. Ear Hear 10:243–249, 1989. 51. Boothroyd A, Springer N, Smith L, Schulman J: Amplitude compression and profound hearing loss. J of Speech Hear Res 31:362–376, 1988. 52. Moore B: How much do we gain by gain control in hearing aids? Acta Otolaryngol Suppl 469:250–256, 1990. 53. Villchur E: Signal processing to improve speech intelligibility in perceptive deafness. J Acoust Soc Am 53:1646–1657, 1973. 54. Barfod J: Multi-channel compression hearing aids. Report 11. The Acoustics Laboratory. Copenhagen: Technical University of Denmark, 1976. 55. Pluvinage V, Benson D: New dimensions in diagnostics and hearing aid fittings. Hear Instrum 39:28–30, 1988. 56. Valente M, Sweetow R, May A: Using microphone technology to improve speech recognition. High Performance Hearing Solutions, Suppl Hear Rev 6(1):10–13, 1999. 57. Schuchman G, Valente M, Beck L, Potts L: User satisfaction with an ITE directional hearing instrument. Hear Rev 6:12–22, 1999. 58. Wolf RP, Hohn W, Martin R, Powers TA: Directional microphone hearing instruments: How and why they work. High Performance Hearing Solutions, Suppl Hear Rev 6(1)3:14–25, 1999. 59. Ricketts T, Mueller HG: Making sense of directional microphone hearing aids. Am J Audiol 8:117–127, 1999. 60. Edwards B, Struck C, Dharan P, Hou Z: Signal-processing algorithms for a new software-based, digital hearing device. Hear J 51:38–49, 1998.

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61. Newman C, Sandridge S: Benefit from, satisfaction with, and cost effectiveness of three different hearing aid technologies. Am J Audiol 7:115–128, 1998. 62. Zwislocki J: Acoustic attenuation between the ears. J Acoust Soc Am 25:752–759, 1953. 63. Staab W, Finlay B: A fitting rationale for deep fitting canal hearing instruments. Hear Instrum 42:6–10, 1991.

64. Sweetow R: An analysis of entry-level, disposable, instant-fit, and implantable hearing aids. Hear J 54(2):28–43, 2001. 65. Carey AL: Americans with disabilities act. ASHA 34:5, 1992. 66. Compton CL: Assistive devices. Semin Hear 10, 1989.

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Outline Introduction Overview Specific Devices BAHA Vibrant Soundbridge

Chapter

Implantable Hearing Devices

Direct System Middle Ear Transducer Envoy Summary

INTRODUCTION Implantable hearing devices (IHDs) have emerged as safe and effective therapeutic options to rehabilitate hearing loss. All IHDs activate audition through mechanical stimulation of the cochlea. They are distinct from cochlear implants, which restore hearing through electrical stimulation of the inner ear. Although there is little controversy that conventional acoustic hearing aids are the first line of treatment for patients with various hearing loss profiles, IHDs serve a subset of patients troubled by problems associated with conventional amplification devices. Some common complaints are feedback annoyance, hearing appliance discomfort, chronic infection, stigma of wearing an external device, inadequate rehabilitation, and psychological rejection. Further, IHDs provide auditory rehabilitation to a large, underserved population of hearing-impaired individuals who have not been helped by conventional hearing aids. Overall, approximately 28 million Americans are affected by hearing loss. Approximately 14.4 million American adults have moderate to severe sensorineural hearing loss. It is estimated that only 20% of Americans who may benefit from a hearing aid owns one. Only half of the individuals who own a hearing aid use their devices on a long-term basis.1,2 The remarkable designs of IHDs are a tribute to the ingenuity and perseverance of many professionals, scientists, and engineers. Compared to conventional hearing aids, IHDs endeavor to deliver more natural sound, increase gains across the frequency spectrum, reduce feedback, improve comfort and cosmesis, and eliminate ear canal occlusion.

OVERVIEW An IHD converts acoustic energy to mechanical energy and vibrates the cochlea through bone conduction (via a “bone-anchored hearing device”) or direct ossicular *This work was supported by a Merit Review Grant from Veterans Affairs Medical Research to Steven W. Cheung.

Steven W. Cheung, MD Kenneth C. Y. Yu, MD Haruka Nakahara, MD

stimulation (via an “implantable middle ear hearing device”). The basic components of an IHD are a sensor (receptor) that detects and processes acoustic signals and a driver (effector) that activates the auditory pathway. There are three types of IHD: bone-conduction, semiimplantable middle ear, and totally implantable middle ear. Bone-conduction hearing devices stimulate the cochlea by transmitting vibrations to an implanted bone screw that is osseointegrated to the skull. Transcutaneous and percutaneous systems have been developed. In the transcutaneous design, an external receptor processes incoming auditory signals and transmits the information across a thin skin interface to an internal transducer, which is integral to the bone screw. In the percutaneous design, the external appliance is coupled directly to the bone screw and serves as an integrated receptor and effector unit. Implantable middle ear hearing devices (IMEHDs) are either semi-implantable or totally implantable. SemiIMEHDs have separate receptor and effector limbs. The receptor houses the microphone, speech processor, and power supply. It is external, removable, and readily accessible. The effector is affixed to the ossicular chain and implanted in the temporal bone, and it is relatively inaccessible. Sites of driver action are incus head, lenticular process, and stapes superstructure. A thin scalp interface separates the receptor and effector. A centering magnet binds the two in stable position. Radiofrequency coupling between the external and internal limbs serves as the conduit for acoustic information. Totally IMEHDs also have receptors and effectors; however, both limbs are implanted internally in the skull. Two transducer types, electromagnetic and piezoelectric, drive the ossicular chain for both types of IMEHD. Electromagnetic fields generated by induction coils put magnets attached to the ossicular chain into oscillatory motion, thereby activating the cochlea. Piezoelectric transducers use special ceramic materials that alter their volume in response to applied electrical energy. Vibrations to the cochlea are regulated by changes in electrical potential. Piezoelectric transducers can also be used as receptor systems. A major challenge for totally implantable middle

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ear hearing devices is power supply management, for which transcutaneous recharge of internal batteries and scheduled processor exchange are two common strategies. From a surgical perspective, IHDs, particularly IMEHDs, have a number of operative risks. These include sensorineural hearing loss, unplanned ossicular chain disruption, facial nerve injury, external canal fenestration, and cerebral spinal fluid leak. Beyond immediate surgical considerations, issues surrounding IMEHDs are greater expense than conventional hearing aids, uncertainty about new technologies, incompatibility with magnetic resonance imaging (MRI), and future need for explantation and reimplantation. Acoustic considerations for IMEHDs relate to consequences of hardware implantation—increased stiffness, mass loading of the ossicular chain, and jeopardy to residual cochlear function. Once an IMEHD has been implanted, an open question is the ease of reversibility. That is, in the event of explantation, what are the risks to native middle-ear anatomy and cochlea? Along this vein, what is the ease of “upgrade” from a semi-implantable to a fully implantable model? Certainly, a detachable pin connection between internal implant electronics and the effector limb appears advantageous for replacing older hardware with new technological advances. Finally, can an MRI-compatible IMEHD be engineered? Implantable hearing devices have emerged as an important alternative modality to rehabilitate impaired audition. Biomedical engineering advancements for IHDs have been impressive. The trajectory for innovative technologies has been steep. It is likely that creative solutions will be found for many unresolved questions. Continued improvements in hardware and software will undoubtedly bring about even more impressive devices.

SPECIFIC DEVICES

Compact external processor. The Classic 300 uses a linear amplifier strategy and the more miniaturized Compact model employs a compression algorithm. Anecdotal reports indicate that the sound output of the Classic 300 is louder than that of the Compact model. Patients with a PTA between 45 and 60 dB are fitted with the more powerful body-worn Cordelle II. The additional gain is on the order of 10 to15 dB for lower frequencies (<1 kHz) and 5 to 7 dB for higher frequencies.4 All external BAHA units are composed of an integrated audio processor (microphone, speech signal processing electronics, and battery) and a cochlear stimulator. The integrated sensor-driver assembly is snapped to the osseointegrated titanium skullscrew abutment (Fig. 78-1). The surgical procedure requires slow rotation (<25 revolutions per minute) for tapping the bone threads and installing the titanium screw implant. Typically, a 3- or 4-mm screw is positioned just below the level of Darwin’s tubercle and 50 to 55 mm posterior to the external auditory canal. Subcutaneous tissue surrounding the implant must be thinned and hair follicles removed. Otherwise, infection is more likely and snap coupling between the implanted screw and the external device is more burdensome. For adults without bone irradiation, surgery is a single-stage procedure. The bone screw is percutaneously attached to an external abutment flange at the same setting. Osseointegration failure is estimated to range from 1% to 6%.5,6 The fitting of external cochlear-stimulating devices takes place approximately 10 weeks after surgery. For children, surgery is a two-stage process. The implanted screw is exteriorized and connected to the abutment 3 to 4 months following the initial procedure. Psychoacoustic benefit for adults with the implanted BAHA has been rather positive. Patients with a PTA lower than 45 dB reported greater benefit than did those with a PTA between 45 and 60 dB (89% vs. 61%).7 Survey instruments that assessed general well-being, quality of life, overall satisfaction, long-term device use, and

This chapter highlights one FDA-approved bone-conduction (BAHA), two FDA-approved semi-implantable (Vibrant Soundbridge and Direct System), and two investigational (MET semi-implantable and Envoy totally implantable) devices. This review is necessarily incomplete because a number of intriguing devices are at different stages of development and clinical trial evaluation. Information about investigational devices is limited. Of course, proprietary design and confidential performance data are not available. The IHDs highlighted in this chapter illustrate the range of exciting technologies to treat hearing loss that are being developed and refined.

BAHA The BAHA (Entific Medical Systems, Göteborg, Sweden) is an FDA-approved, bone-anchored hearing system for adults and children older than 5 years. Children with craniofacial abnormalities represent an important group of candidates for bone-conduction–based auditory rehabilitation. Audiometric criteria for implantation are bone-conduction pure tone average (PTA) thresholds lower than 60 dB (0.5, 1, 2, and 3 kHz) and speech discrimination scores greater than 60%. Patients with bone-conduction PTA lower than 45 dB are fitted with the ear level BAHA Classic 300 or

Figure 78-1. The BAHA bone-conduction device. The integrated external audio processor and cochlear stimulator is worn either at ear or body (not shown) level. It is snap coupled to the osseointegrated titanium skull screw via a trumpet-shaped abutment piece. The cochlea is activated by bone conduction. Depilatory and soft tissue reduction procedures are necessary to prepare the implant site for transcutaneous device fitting. (Image courtesy of Entific Medical Systems, Göteborg, Sweden.)

Implantable Hearing Devices

hearing amelioration indicate benefits conferred by BAHA along these dimensions.8-11 Lustig and colleagues12 evaluated acoustic benefit for adults by subtracting the postoperative aided from the best preoperative unaided air conduction threshold. The results indicate that the acoustic benefit falls within 10 dB in 80% (40 subjects in cohort) and 5 dB in 60% of patients. Wazen and colleagues8 found a 25-dB improvement in speech reception thresholds in nine patients. BAHA auditory rehabilitation in children is also successful. However, the osseointegration failure rate is higher and ranges from 6% to 16%.13-15 Psychoacoustic benefit for children with implanted BAHA systems parallels that of adult users.13,14 Papsin and colleagues15 measured audiometric function in 31 children with BAHA implants and found acoustic gain comparable to conventional bone-conduction hearing aids. The most pronounced finding was strong user preference for the BAHA over conventional bone-anchored aids with respect to sound quality, conversation, and music listening.

Vibrant Soundbridge The Vibrant Soundbridge (formerly Symphonix Devices, now MED-EL) is an FDA-approved IMEHD. Candidates for implantation are adults with moderate to severe sensorineural hearing loss and speech discrimination scores higher than 50%. The external component is the Audio Processor (AP), and the internal component is the surgically implanted Vibrating Ossicular Prosthesis (VORP). The VORP (Fig. 78-2) is a single-piece assembly that contains the radiofrequency link, demodulator, and ossicular stimulator or floating mass transducer (FMT), which is attached to the incus lenticular process with a titanium clip. The FMT is an electromagnetic effector that uses a magnet housed in an induction coil to generate vibrations. The surgical procedure consists of a mastoidectomy with opening of the facial recess to clip the FMT onto the lenticular process. After a 2-month period of healing, the device is activated. Internal electronics hardware delivers

Figure 78-2. The Vibrant Soundbridge semi-implantable device. The external audio processor (circular black fixture) receives and processes sounds. Signals are transmitted to the internal single-piece Vibrating Ossicular Prosthesis via radiofrequency coupling. A facial recess approach is necessary to attach the floating Mass Transducer to the incus lenticular process using a titanium clip. (Image courtesy of Symphonix Devices, Inc., San Jose, CA.)

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controlled currents to drive the FMT into vibratory motion. For the Vibrant Soundbridge phase III FDA study,16,17 subjects had used acoustic hearing aids for at least 3 months prior to evaluation. Individuals with unilateral hearing loss, active middle-ear infections, tympanic membrane perforations associated with recurrent middleear infections, skin or scalp condition precluding attachment of the Audio Processor, unrealistic expectations, or conductive, retrocochlear, or central auditory disorders were disqualified from the study. FMT mass loading of the incus did not have a clinically significant effect on hearing.18,19 The majority of patients in the U.S. trial experienced a PTA change of less than 10 dB. However, a small percentage (4%, or 2/53) of patients had a 12- to 18-dB decrease in residual hearing. Data from a European clinical trial with 47 subjects reported frequency-specific elevations (>10 dB) in the implanted ear that were attributed to both conductive and sensorineural losses.20 Other adverse effects have been reported. In the European trial, 15% of patients sustained injury to the chorda tympani nerve. In the U.S. trial, there were six device failures; these subjects underwent successful reimplantation after the manufacturer revised the product. One subject with a successful reimplantation had had a disconnection of the FMT. The phase III trial reported statistically significant improvements in average functional gain of 10 to 15 dB across the frequency spectrum. Aided speech recognition scores with the Vibrant Soundbridge and conventional hearing aids were comparable. Subjects reported more satisfaction and improved performance (e.g., greater ease of communication, reduced reverberation, decreased background noise) with the Vibrant Soundbridge than with a heterogeneous group of conventional hearing aids. Occlusion and feedback effects were virtually eliminated.

Direct System The Direct System (SOUNDTEC, Inc., Oklahoma City) is another FDA-approved IMEHD. Candidates for implantation are adults with moderate to severe sensorineural hearing loss and speech discrimination scores greater than 60%. The Direct System is similar to the Vibrant Soundbridge in only one respect—the effector is an electromagnetic transducer. The system consists of a neodymium-iron-boron (Nd-Fe-Bo) magnet that is implanted at the incudostapedial joint. The surgical approach for magnet implantation is a transcanal procedure similar to that for stapedectomy.21 There is no mastoidectomy. Prior to surgery, a customized acrylic earmold/coil assembly embedded with an electromagnetic coil is fashioned for the ear canal (Fig. 78-3). The FDAapproved behind-the-ear (BTE) external system houses the microphone, sound processor, and battery. Processed signals from the BTE component are delivered to the earmold/coil assembly to produce an electromagnetic field that sets the implanted magnet into motion. An in-the-ear (ITE) external processor is under FDA review. Note that the magnet for the Direct System is outside the center of the induction coil. This design feature makes it substantively different from the Vibrant Soundbridge, which houses the magnet at the center of the coil. The phase II trial for Direct System involved 103 patients at 10 U.S. medical

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Figure 78-3. The SOUNDTEC Direct semi-implantable device. The earmold/coil assembly is attached to a behind-the-ear sound processor (inset, left). Processed acoustic signals are transformed to electromagnetic fields that drive the distant neodymium-iron-boron (NdFeBo) magnet, seated at the incudostapedial joint, into motion (inset, right). Mastoidectomy is not performed. The in-the-ear model processor displayed in this figure is under FDA review. (Images courtesy of SOUNDTEC, Inc., Oklahoma City.)

centers.22 There was no significant change in average residual hearing for the study cohort. The increase in average air conduction was 4 dB and in bone conduction was 1 dB. Subpopulation analyses of audiometric data for the Direct System device have not been published. There were minor complications, which included ear canal and tympanic membrane hematomas. An eardrum perforation that occurred during an implantation procedure was repaired successfully. Overall, no major complications were reported in the phase II trial. The Direct System produced an improvement in average functional gain of 10 to 15 dB for all tested frequencies lower than 6 kHz. Aided work recognition, using the Northwestern University (NU-6) test, demonstrated statistically significant improvement in speech discrimination scores. There was greater ease of communication, reduced reverberation, and decreased background noise with Direct System than with optimally fitted conventional hearing aids. Patient satisfaction was also higher. 23

Middle Ear Transducer The Middle Ear Transducer (MET) Ossicular Stimulator (Otologics LLC, Boulder, CO) is an investigational IMEHD that is substantially different from the Vibrant Soundbridge and Direct System devices. Candidates for the MET clinical trial study were adults with moderate to severe sensorineural hearing loss and speech discrimination scores greater than 20%. The MET external Button Audio Processor is similar to receptors in other devices in this class; however, its electromagnetic effector site of action and interface to implanted hardware are distinctive features (Fig. 78-4). The effector acts on the head of the incus and communicates with implanted electronics via a detachable

Figure 78-4. The MET (Middle Ear Transducer) semi-implantable device. The external Button audio processor (inset, right) transfers processed signals to internal electronics hardware via radiofrequency coupling. The Button is worn at ear level. A circular mounting bracket stabilizes the MET. The facial recess is not opened. A detachable pin connection transfers information from internal electronics to the tip of the MET, which is embedded in the incus head. (Images courtesy of Otologics LLC, Boulder, CO.)

pin connector. The surgical procedure for implantation consists of a limited mastoidectomy to expose the tegmen and the incus and malleus heads. The ossicular stimulator’s tip is precisely aligned with the incus head before a mounting bracket is affixed to the mastoid with several screws. A 0.5-mm diameter by 0.8-mm deep hole is created in the incus head with a laser.24 The driver device tip is lowered to the bottom of the hole and retracted slightly to minimize undesirable mass and stiffness loading. Fibrous adhesion between the effector tip and the incus improves the efficiency of mechanical energy transfer to the cochlea. In contradistinction to the Vibrant Soundbridge and Envoy, implantation of the MET Ossicular Stimulator does not entail the facial recess approach. The FDA phase II clinical trial closed without completion. Otologic favors developing a totally implantable device.

Envoy The Envoy (St. Croix Medical Systems, Minneapolis, MN) is a totally implantable hearing device that uses piezoelectric transducers. The Envoy device completed phase I FDA trial in 2004.25 Candidates for Envoy device implantation were adults with mild to severe sensorineural hearing loss and speech discrimination scores greater than 60% (K. Kroll, personal communication). A major design challenge for totally implantable hearing devices is mechanical and acoustic feedback management. By necessity, receptor (sensor) and effector (driver) limbs of the system are in close proximity. During high output by the effector limb,

Implantable Hearing Devices

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the incus lenticular process with a laser (Fig. 78-5). Bone cement affixes the sensor and driver to the floor of the mastoid and affixes the respective tips to the incus body and stapes capitulum. When incoming sounds vibrate the native drum, the incus head is set in motion. The sensor tip, which is firmly attached to the incus head, deflects the piezoelectric transducer. Electrical signals are generated and transmitted to the speech processor. Outflow signals from the effector limb of the processor guide driver tip movements. Receptor and effector limbs connect with internal electronics hardware via detachable pins. In the event of explantation, a laser can be used to vaporize sensor and driver tips to liberate the ossicles. Ossicular continuity is reestablished with a distal incus replacement prosthesis. Reversibility of the procedure appears to be achievable. More will be known about the Envoy when FDA phase I clinical trial data become available to the public. Figure 78-5. The Envoy totally implantable device. Receptor and effector limbs connect to the main processor with detachable pin connections. Bone cement affixes the sensor (inset, upper right) to the incus body and the driver to the stapes capitulum (inset, lower left). The facial recess is opened to access the incudostapedial joint. Note that the distal incus lenticular process is shortened to segregate sensor and driver vibrations. (Images courtesy of St. Croix Medical Corporation, Minneapolis, MN.)

feedback may occur because the sensor detects the output signal. This results in feedback oscillation. The Envoy system addresses this difficult problem by segregating the receptor and effector limbs through planned ossicular discontinuity. The surgical procedure is a mastoidectomy with a facial recess approach to vaporize the distal 2 to 3 mm of

SUMMARY Implantable hearing devices have emerged as exciting treatment options to rehabilitate patients with hearing loss. These devices perform as well as, and perhaps somewhat better than, conventional hearing aids. The main advantages of IHDs are increased patient acceptance and improved psychoacoustic function. A large population of underserved hearing-impaired patients may benefit from IHD technology. Table 78-1 contrasts and compares the key features of several devices discussed in this chapter. Clinical trial data and specific design features guide the clinician to a particular device for his or her patient.

TABLE 78-1. Implantable Hearing Devices Commercial Product Device Class Manufacturer Web Site

Surgical Approach Transducer Type Ossicular Chain Status

Sensor Position

Driver Position

Driver Connection to Internal Electronics

BAHA Bone-Anchored Entific Medical Systems http://www.entific.com

Titanium screw to skull Electromagnetic Intact

External– percutaneous Ear or body level

Osseointegrated titanium skull screw

Integrated external sensor/stimulator processor

Yes; also for children > 5 yr

Vibrant Soundbridge Semi-IMEHD Symphonix Devices, Inc. http://www.symphonix.com

Transmastoid with facial recess Electromagnetic Intact

External Ear level

FMT clipped onto incus lenticular process

Single-piece construction (VORP)

Yes

Direct System Semi-IMEHD SOUNDTEC, Inc. http://www.soundtecinc.com

Transcanal for magnet placement Electromagnetic Intact

External BTE or ITE†

NdFeBo magnet attached to stapes superstructure

Distant electromagnetic transduction; no physical connection

Yes

MET Ossicular Stimulator Semi-IMEHD Otologics LLC http://www.otologics.com

Transmastoid without facial recess Electromagnetic Intact

External Ear level

MET tip embedded in incus head

Detachable pin connector

No; phase II FDA clinical trial closed without completion

Envoy Totally IMEHD St. Croix Medical Systems http://www.stcroixmedical.com

Transmastoid with facial recess Piezoelectric Distal incus removed

Internal Sensor cemented to malleus head

Internal driver cemented to stapes capitulum

Detachable pin connectors

No; phase I FDA clinical trial completed in 2004

FDA Approval for Adults?

BAHA, bone-anchored hearing aid; BTE, behind-the-ear; FMT, floating mass transducer; IMEHD, implantable middle ear hearing device; ITE, in-the-ear; MET, middle ear transducer; NdFeBo, neodymium-iron-boron; VORP, vibrating ossicular prosthesis.

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REFERENCES 1. Kochkin S: MarkeTrak V. Hear J 53(2):34, 2000. 2. Kochkin S: MarkeTrak V. Customer satisfaction revisited. Hear J 53(1):38, 2000. 3. Ko WH, Zu WL, Kane M, et al: Engineering principles applied to implantable otologic devices. Otolaryngol Clin North Am 34(2):299, 2001. 4. Tjellström A, Håkansson B, Granstrom G: Bone-anchored hearing aids: Current status in adults and children. Otolaryngol Clin North Am 34(2):337, 2001. 5. Tjellström A, Jacobsson M, Norvell B, et al: Patients’ attitudes to the bone-anchored hearing aid. Results of a questionnaire study. Scand Audiol 18(2):119, 1989. 6. Snik AF, Beynon AJ, Mylanus EA, et al: Binaural application of the bone-anchored hearing aid. Ann Otol Rhinol Laryngol 107(3):187, 1998. 7. Håkansson B, Liden G, Tjellström A, et al: Ten years of experience with the Swedish bone-anchored hearing system. Ann Otol Rhinol Laryngol (Suppl) 151:1, 1990. 8. Wazen JJ, Caruso M, Tjellström A: Long-term results with the titanium bone-anchored hearing aid: The U.S. experience. Am J Otol 19(6):737, 1998. 9. Wazen JJ, Spitzer J, Ghossaini SN, et al: Results of the bone-anchored hearing aid in unilateral hearing loss. Laryngoscope 111(6):955, 2001. 10. Arunachalam PS, Kilby D, Meikle D, et al: Bone-anchored hearing aid quality of life assessed by Glasgow Benefit Inventory. Laryngoscope 111(7):1260, 2001. 11. Dutt SN, McDermott AL, Jelbert A, et al: The Glasgow benefit inventory in the evaluation of patient satisfaction with the boneanchored hearing aid: Quality of life issues. J Laryngol Otol Suppl 28:7, 2002. 12. Lustig LR, Arts HA, Brackmann DE, et al: Hearing rehabilitation using the BAHA bone-anchored hearing aid: Results in 40 patients. Otol Neurotol 22(3):328, 2001. 13. Granstrom G, Bergstrom K, Odersjo M, et al: Osseointegrated implants in children: Experience from our first 100 patients. Otolaryngol Head Neck Surg 125(1):85, 2001.

14. Powell RH, Burrell SP, Cooper HR, et al: The Birmingham bone anchored hearing aid programme: Paediatric experience and results. J Laryngol Otol Suppl 21:21, 1996. 15. Papsin BC, Sirimanna TK, Albert DM, et al: Surgical experience with bone-anchored hearing aids in children. Laryngoscope 107(6):801, 1997. 16. FDA/Center for Devices and Radiological Health. Food and Drug Administration Web site. Vibrant Soundbridge P99052. Part 2. Summary of Safety and Effectiveness. Available at http://www.fda. gov/cdrh/pdf/p990052.html. 17. Luetje CM, Brackmann D, Balkany TJ, et al: Phase III clinical trial results with the Vibrant Soundbridge implantable middle ear hearing device: A prospective controlled multicenter study. Otolaryngol Head Neck Surg 126(2):97, 2002. 18. Snik FM, Cremers WR: The effect of the “floating mass transducer” in the middle ear on hearing sensitivity. Am J Otol 21(1):42, 2000. 19. Fraysse B, Lavieille JP, Schmerber S, et al: A multicenter study of the Vibrant Soundbridge middle ear implant: Early clinical results and experience. Otol Neurotol 22(6):952, 2001. 20. Fisch U, Cremers CW, Lenarz T, et al: Clinical experience with the Vibrant Soundbridge implant device. Otol Neurotol 22(6):962, 2001. 21. Hough JV, Dyer RK Jr, Matthews P, et al: Early clinical results: SOUNDTEC implantable hearing device phase II study. Laryngoscope 111(1):1, 2001. 22. FDA/Center for Devices and Radiological Health. Food and Drug Administration Web site. SOUNDTEC Direct System P010023. Part 2. Summary of Safety and Effectiveness. Available at http://www.fda.gov/CDRH/PDF/P010023.html. 23. Roland PS, Shoup AG, Shea MC, et al: Verification of improved patient outcomes with a partially implantable hearing aid: The SOUNDTEC Direct hearing system. Laryngoscope 111(10):1682, 2001. 24. Kasic JF, Fredrickson JM. The Otologics MET Ossicular Stimulator. Otolaryngol Clin N Am 34(2):501, 2001 25. St. Croix Medical Products. Discussion with Douglas Hoag, Vice President Marketing and Sales. Available at http://www.stcroixmedical. com/prod01.htm.

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Outline Introduction Cochlear Implant Technology Basics Microphones Speech Processor and Coding Strategies Electrodes Objective Methods for Programming Cochlear Implants Currently Available Cochlear Implants in the United States Clarion Electrode Receiver-Stimulator Speech Processor

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Speech-Processing Strategies Nucleus Electrode Receiver-Stimulator Speech Processor Speech-Processing Strategies Med-El (Medical Electronics) Electrode Receiver-Stimulator Speech Processor Speech-Processing Strategies The Future

INTRODUCTION Cochlear implants (CIs) are electronic devices designed to restore partial hearing function in individuals with severe to profound hearing loss who obtain insufficient benefit from hearing aids. The implant system is intended to bypass the inner ear hair cell transducer system by converting acoustic energy into electrical signals that directly stimulate surviving neurons in the auditory nerve. Cochlear implants do not restore normal hearing but generally allow recipients to function at a level similar to less hearing-impaired patients who are successful hearing aid users.1,2 In 1957 Djourno and Eyries stimulated a cochlear nerve exposed after removal of a large cholesteatoma. An electrode was placed directly on the nerve and stimulated with a simple electric current, which produced an auditory sensation in the patient.3 This experiment led to the concept of direct stimulation of the auditory nerve, the basis of cochlear implants. Following their report, a flurry of investigations ensued, which led to the development of a speech processor to interface with an electrode implanted in the scala tympani. The House 3M singlechannel cochlear implant was the first to be commercially marketed 1972,4 and the first multichannel device, developed at the University of Melbourne, Australia, entered the market in 1982.5 Since then, several other manufacturers have produced and marketed versions of multichannel cochlear implants. Interactions among manufacturers, researchers, and clinicians worldwide have driven the production of improved cochlear implants. The net result has

Adrien A. Eshraghi, MD, MSc Annelle V. Hodges, PhD Fred F. Telischi, MD, MEE Thomas J. Balkany, MD, FACS

been the evolution of improved electrodes and internal receivers, smaller and more efficient speech processors, and more complex speech-coding strategies. These design changes have been particularly rapid within the past few years.5 Initially, emphasis was placed on the external equipment together with development of improved speech-coding strategies. External equipment has steadily become smaller and more versatile. The capacity to store multiple programs and the availability of more than one speechprocessing strategy has become routine. Most recently, attention has once again turned toward internal electrode design, the goal being development of internal arrays that both lie closer to the modiolus6 and result in less insertion trauma.7 These electrodes will run complex programming strategies with less power, paving the way for fully implantable devices.

COCHLEAR IMPLANT TECHNOLOGY BASICS Certain components are basic to all CI systems (Fig. 79-1). The implant consists of both an external component and a surgically implanted internal component. The external portion of the device includes a microphone, microprocessorbased speech processor, a radiofrequency (RF) transmitting coil, and the power source. The implanted portion houses an RF receiver coil, microprocessor-based stimulator, and multichannel electrode array. 1301

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And previous studies found that the speech reception performance under conditions of reduced signal-to-noise ratios can be improved with the addition of a second microphone.9

Speech Processor and Coding Strategies

Figure 79-1. Common to all CIs in use are an external microphone, wearable processor and transmitter, an implantable receiver-stimulator, and an electrode array.

The first step in cochlear implant function is detection of sound in the listener’s environment by the microphone and transmission of that information to the speech processor (SP). Essentially a minicomputer, the SP processes the incoming sound based on which programming strategies described earlier is stored in memory. Once the signal has been processed and encoded by the speech processor, the information is sent to the transmitting coil. The transmitting coil sends the signal provided by the SP transcutaneously to the receiver-stimulator via an RF signal. On reaching the receiver-stimulator, the signal is transduced into electrical pulses. The pattern of activation of the electrodes is determined in part by the nature of the electrode array and in part by the coding strategy. The electric current sent through the implanted electrodes is directed toward the remaining auditory nerve fibers within the cochlea. The patterns of stimulation are conducted along the auditory nerve to the brain and are there interpreted as meaningful sound. The function of CIs depends on the flow of electric current. The way in which this current is generated, processed, and delivered to the patient is the most basic determinant of device function. A cochlear prosthesis must replace the two basic functions of the cochlea: transduction and encoding. In its simplest form, the CI analyzes incoming acoustic energy, transforms it into an electrical signal, which is processed by a combination of amplification, compression, filtering, or extraction, and then delivers the coded signal to surviving elements of the auditory nerve.

Microphones Microphones perform the function of receiving sound energy and converting it into analogous electronic signals. They are typically housed within a behind-the-ear (BTE) unit or in the speech processor enclosure. Sophisticated microphones used in cochlear implantation are quite small, and may be dual and directional. The directional microphone can help in listening to speech under adverse conditions.8 The selectivity of the directional pattern can be increased substantially with the use of multiple microphones.

The speech processor converts the input from the microphone into a pattern of electrical stimulation. And coding strategies define the way in which sounds are transformed into electrical signals that can be meaningfully interpreted by the brain. The more efficient and effective the coding strategy, the greater the possibility that the brain can derive meaning from the CI input. Without meaning, sound is only unwanted noise. The goal in speech-coding strategy development has been to create a coded signal that faithfully represents the original acoustic message. Two major approaches have been employed to meet this goal. One is based on the spectral information; the other concentrates on the temporal cues contained in the acoustic signal. In both, each electrode along the array is assigned a frequency band, placed in tonotopic order based on the cochlea. The acoustic signal is also divided into frequency bands, which are assigned to the electrode carrying that frequency. Intensity of the acoustic signal is coded by current level, with louder sounds being represented by increased current levels. Major differences between the two include which parts of the acoustic signal are sent to the stimulating electrodes, how many electrodes are stimulated at one time, and how rapidly the stimulation occurs. Programming strategies that emphasize spectral information may also be referred to as feature extraction strategies. In feature extraction strategies, the speech signal is analyzed for specific characteristics such as fundamental frequency, formant information, voicing cues, and additional peaks of acoustic energy. Information not considered to be as useful for understanding is eliminated. Only electrodes assigned to the frequency bands carrying or selected to represent these features are activated. The electrodes are stimulated one after another rather than at the same time. Theoretically a nonfunctioning auditory system will not be as overburdened if the information is “preanalyzed” in this manner. Current implementations of feature extraction strategies may sequentially stimulate anywhere from 3 to 10 electrodes for any given acoustic signal. The SPEAK (spectral peak extraction) coding strategy used by the Nucleus device and the n-of-m (number of maxima) strategy used by the Med-El device are both examples of feature extraction strategies. Unlike spectrally based programs, which extract pieces of information, temporally based programs convey the full spectrum of the auditory waveform. This is accomplished by dividing the acoustic input into frequency bands, with each electrode on the array assigned to one frequency band. These frequency bands are typically wider than those used in feature extraction strategies. Every electrode is stimulated rather than only the ones carrying some piece of extracted information. Stimulation may be either pulsatile or analog. No current implant system uses a true

Cochlear Implant Technology

analog signal. In all cases, some digitization of the signal occurs before it is delivered to the electrode array. Current implementations of temporally based programs may stimulate one electrode at a time in a nonsimultaneous stimulation pattern. Or all electrodes may be stimulated at the same time, in a simultaneous stimulation pattern. Simultaneous stimulation provides the greatest degree of temporal resolution, but may be hampered by current spread and channel interaction. Stimulation rate must be high enough to allow all electrodes to be stimulated within each time frame. In theory, more stimulation presented to the auditory nerve means that more information reaches the brain, suggesting that high-rate simultaneous stimulation should provide better speech perception. Continuous interleaved sampling (CIS) is a sequential pulsatile temporally based programming strategy, a form of which is offered by all current devices. Simultaneous analog sampling (SAS) is the only coding strategy that uses simultaneous stimulation of all active electrodes and is offered by the Advanced Bionics device. Results to date, however, have not shown significant differences in patient performance between temporally or spectrally based coding strategies. Several speech-coding strategies that combine features have also been developed with promising results. In one, advanced combination encoder (ACE), the spectral representation of a feature extraction strategy is combined with the higher rate of a temporally based strategy. In another, multiple pulsatile sampling (MPS), simultaneous and nonsimultaneous stimulation are combined into one strategy. Ongoing development of electrodes that can deliver very high-rate stimulation to extremely small, isolated areas of the cochlea without the effects of channel interaction is aimed at the continued development of better speechcoding strategies. The speech processor is powered with batteries. And advances in battery, integrated circuit, and digital signalprocessing (DSP) chip technologies have made possible a progressively smaller and more capable speech processor and implanted receiver-stimulator. There is now an adequate battery life for the head-level processor, allowing patients to use their devices during the waking hours without the need for replacing or recharging batteries.9

Figure 79-2. In monopolar configuration, the current radiates from an active to an indifferent electrode. This minimizes current density but results in broad areas of stimulation.

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Electrodes Electrodes and the electrode carrier must be biocompatible. Electrodes are covered by hard silastic. Because silastic is vapor-permeable, hermetic isolation of implantable circuits within titanium or ceramic cases is required. In addition, further insulation of electrodes using vapor-impregnable coating materials such as Teflon or Paralene-C may be used. Surgical removal of cochlear implants has been necessary in a limited number of cases for upgrade or device failure.10 However, in none of the cases reported have foreign body giant cells been identified. Electrodes can be stimulated in a monopolar or bipolar configuration. At least two contacts are required to complete an electric circuit. In the monopolar configuration, the active electrode is located close to the nerve, and the return, ground, or indifferent electrode is placed farther away (e.g., below the temporalis muscle) (Fig. 79-2). In bipolar configuration, one intracochlear electrode is stimulated in reference to another (nearby) intracochlear electrode (Fig. 79-3). Monopolar electrodes stimulate a larger population of nerves at lower current levels. Conversely, the energy needed to stimulate small electrode pairs in bipolar configuration is considerably greater, but theoretically this would stimulate discrete populations of ganglion cells. Multichannel electrode arrays have been associated with better user performance than that from the single-electrode implants. Multielectrode systems are placed in biocompatible carriers for positioning into scala tympani. The scala tympani offer an accessible site close to dendrites and ganglion cells. The current generation of CI uses platinumiridium as the stimulating contact. The physical size, geometric area, and surface characteristics of the electrode contacts affect current and charge densities. The most commonly used carrier is a very soft silastic, which contains platinum-iridium electrodes positioned longitudinally in the scala tympani. Radial orientation may be beneficial for achieving channel separation.11 Smaller electrode contacts may reduce the neural population recruited by each electrode contact and improve the specificity of stimulation leading to and possibly enhancing frequency stimulation. More electrode contacts may also offer greater flexibility

Figure 79-3. In bipolar configuration, the electrode contacts are placed. This results in more discrete stimulation.

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for speech-coding strategies. New surface treatment of the electrode rings (iridium coating and surface roughening) are under evaluation; they may reduce the impedance or the physical size of the contact surfaces (or both), leading to improved power efficiency and battery life.12 Histologic evaluations of trauma resulting from the insertion of CI electrodes have demonstrated damage to the basilar membrane, osseous spiral lamina. and other structures.7,13 The impact of localized damage to the spiral ligament during implantation is uncertain, but osteoneogenesis may be stimulated and secondary localized tears of Reissner’s membrane may occur. There is general agreement that damage to the osseous spiral lamina, basilar membrane, and Reissner’s membrane will result in at least localized loss of spiral ganglion cells and that the extent of neural damage may be proportional to the degree of cochlear tissue injury. Because implantation is often performed on very young children and patients with substantial degrees of residual hearing, use of hybrid electric/acoustic devices and bilateral implantation are likely to increase, so preventing damage to cochlear structures during implantation is of increasing importance. More recently the trend has been to design perimodiolar electrodes. Perimodiolar electrodes place stimulating contacts consistently close to the spiral ganglion cells in order to reduce power consumption and increase stimulation selectivity.6 The intracochlear position of these electrodes and the dynamic of trauma resulting from the insertion of the electrode array may be studied in the laboratory by videofluoroscopic imaging and computer morphometrics.

Objective Methods for Programming Cochlear Implants Once the implant is in place and the period of healing complete, the external components must be fitted to the patient. All commercially available devices in the United States offer options from the speech-coding strategies described earlier. The process of selecting a speech-coding strategy and obtaining the psychophysical information necessary to customize the stimulation for an individual patient is commonly called programming. The strategy selected and modified with the patient’s own current requirements and tolerances is referred to as the program or map. There remains no sure way to determine what type of strategy will be better for a patient without going through the process of making various maps and having the user compare them. Manufacturers have made attempts to shorten the process through programming “shortcuts.” At the same time, however, programming options continue to increase, possibly offsetting the shortcuts. Programming a CI involves several steps. First, the listener must confirm an auditory perception. Next, in most cases a minimum current level or threshold must be established for each active electrode. With several newer strategies, the setting of thresholds is considered optional. In all cases, for each electrode, a maximum current level must be determined. Exactly how these levels are defined depends on the device. In some cases threshold is defined as 100% detection, and for others threshold is 50% detection. Maximum current level may be either the maximum acceptable loudness

or the most comfortable loudness level. Finally, it is considered important that loudness be essentially equal across all electrodes.5 Setting the minimum response level may be considered the easier of the tasks required for programming. To obtain the minimum response level, a patient may simply report when the stimulus becomes audible as the current is raised and lowered until a threshold value is obtained. Setting the maximum current level is more complicated and requires that the individual be able to understand and report the concept of loudness scaling rather than simple presence or absence of the stimulus. Loudness balancing is another task that requires sophisticated decision making on the part of the patient. The CI user must listen to two sounds of unequal pitch and judge whether or not the loudness perception is equal. Such a task is virtually impossible with a young, language-limited child and is difficult for most adults. Because these subjective judgments are difficult to obtain, especially from young children, the development of objective methods of setting stimulation levels has received a great deal of attention over the years. Three objective measures that have proven useful in programming implants are the electrically elicited stapedial muscle reflex, the electrically elicited auditory brainstem response, and recording of the compound action potential. Electrically elicited stapedial muscle reflex (ESR). This procedure uses the principle of the acoustic stapedial reflex, which is a neuromuscular response mediated via the brainstem. This reflex is an automated reaction of the nervous system, which results in a contraction of the stapedius muscle in response to intense stimulation of the auditory system. Previous research has shown good correlation between the level of current required to elicit threshold of the ESR and the behaviorally obtained maximum stimulus levels for experienced CI users.14,15 Research also indicates that maximum stimulus levels obtained via electrical reflexes are judged to be of equal loudness across electrodes by experienced CI users.14 Data have shown that when maximum stimulation levels are set using ESR, speech recognition performance is equal to or better than performance with subjectively set levels.14 Electrically elicited auditory brainstem responses (EABRs) can be recorded either intraoperatively or postoperatively in much the same way as the commonly used auditory brainstem response.16 The EABR can be used to confirm auditory stimulation and as a guideline, albeit less accurate than the ESR, for estimating programming levels. A major drawback to using the EABR as a programming tool with children is the need for the subject to remain very quiet so as not to obscure the response. EABR can seldom be measured in an awake child and is likely to require sedation. Recoding of the compound action potential is the most recent addition to objective programming measurement. Tools such as neural response telemetry (NRT) are being designed as integral parts of both the hardware and software of implant systems. Such tools make possible the measurement of the electrically evoked whole-nerve action potential directly through the implanted electrode and have the benefit of requiring no external electrodes. They can be recorded through the implant system even if the patient is moderately active, making the procedure more useful in children.16

Cochlear Implant Technology

CURRENTLY AVAILABLE COCHLEAR IMPLANTS IN THE UNITED STATES The Food and Drug Administration (FDA)-approved CI devices in the United States are currently produced by three manufacturers: Advanced Bionics Corporation, Cochlear Limited, and Medical Electronics (Med-El) Corporation. These devices differ with respect to the types of electronic microphones, sound-processing strategies, packaging, and number and placement of electrodes.

Clarion The Clarion CI is manufactured by Advanced Bionics Corporation, headquartered in Sylmar, California. In 1992, the first Clarion clinical trial began with a device that offered the first reverse telemetry, perimodiolar electrode array, multiprogramming options, and multiple program memories in the speech processor. Electrode The original electrode array was unique in its spiral modiolar hugging design. Also unique was the need to use an insertion tool to straighten the array and allow it to recurl around the modiolus as the array was inserted. Proximity to the modiolus was seen as the primary way to reduce current requirements so as to maximize battery life, considering the high power consumption of Clarion programming strategies. The array carries 16 platinum electrodes that face the modiolus. The electrodes are separated by dielectric partitions, functioning to focus the electric stimulation toward the modiolus as well as reducing electrical interaction between the electrodes. This electrode array went through several minor changes prior to 1998 when the “precurled” spiral array was replaced by a “precurved” design, called the HiFocus. This array was designed to be used in conjunction with a flexible silicone-based polymer electrode-positioning system (EPS) to be inserted alongside the electrode array. Two variations were developed, HiFocus I, in which the positioner is a separate entity and is inserted in a two-stage surgical procedure. In the HiFocus II, the positioner is attached to the electrode array and is inserted simultaneously. The EPS was designed to passively position the electrode array closer to the modiolus, thus reducing current requirements. It was also thought that the EPS directed the electrode deeper into the cochlea and had the additional benefit of preventing scar tissue formation by occupying the space immediately lateral to the electrode array. Recent questions about a possible relationship between the positioner and several cases of meningitis led Advanced Bionics to abandon use of the positioner in 2002. The HiFocus I electrode continues to be used without the positioner. Receiver-Stimulator In 2001, Advanced Bionic introduced the CII, the current version of the implantable cochlear stimulator (ICS). This version has the potential for stimulation speeds faster than any other device on the market. For the first time, all 16 electrodes can be programmed individually. An innovative

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aspect of the CII is that it is designed to internally store program information that normally would be stored in the speech processor. This enables the system to operate more efficiently. The CII also has the electronic capability to use two diagnostic and measurement tools not previously available in the Clarion implant system: electric field imaging (EFI) and high-resolution neural response imaging (HRNRI). The EFI enables measurement of electrode status and current delivered by the electrodes, which may provide information useful for device programming. The HR-NRI will allow measurement of the compound action potential once FDA approval for the system is obtained. Speech Processor The platinum series processor is the most recent release in the Clarion line of body-worn speech processors and is the smallest on the market. It measures 5 cm by 6 cm, including the rechargeable battery pack. The platinum processor has three program memory slots. All generations of the Clarion SP have been housed in a metal casing, which has reduced the danger of damage to the system from electrostatic discharge. The body processor has separate control knobs for program selection, volume, and sensitivity. The controls are quite user-friendly and are probably the easiest to manipulate of all currently available devices, making it a good choice for individuals with dexterity problems. In 2000, Advanced Bionics introduced the platinum series ear level device. The ear level processor will run all three available speech-processing strategies. It is powered only by a proprietary rechargeable battery pack. Battery life has been the primary concern with the Clarion ear level device. Speech-Processing Strategies Three FDA-approved coding strategies, including simultaneous analog stimulation (SAS), continuous interleaved sampling (CIS), and multiple pulsatile sampling (MPS), can be used by the Clarion. The SAS strategy is the only available fully simultaneous stimulation mode in which all functional electrodes are stimulated at the same time. The CIS mode digitizes incoming sound from the microphone and stimulates all active channels in a sequential manner. A unique aspect of the CIS strategy is that the order of stimulation may be varied either base-to-apex, apex-to-base, or nonsequentially. MPS is a hybrid strategy in which simultaneous and sequential stimulation are both used. As of the fall of 2003, the newest version of software that allows for high-resolution programming of the CII remains experimental.

Nucleus In 1982, Cochlear Ltd. of Sydney, Australia, introduced the Nucleus multichannel CI system. The Nucleus system has undergone numerous changes over the years. The current system, the Nucleus 24, was introduced in the United States in 1997. FDA approval in both adults and children was obtained in mid-1998. With the exception of the Nucleus 24 Double Array that remains in clinical trial in the United States, all external and internal components of the Nucleus 24 system are FDA approved.

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Electrode Cochlear Corporation currently offers three electrode array configurations: the straight electrode system, a split-array electrode designed for use in difficult insertions (e.g., ossification), and the perimodiolar Contour electrode array. Introduced in 2000, the Nucleus 24k electrode (N24k) array is the current version of the straight electrode. Similar to the original array, the N24k has 22 platinum electrode bands and 10 stiffening rings. The device also has two remote ground electrodes that are not inserted into the cochlea. One of the extracochlear electrodes is a platinum plate attached to the receiver-stimulator unit, and the other is a ball electrode on the end of an independent lead wire, which is placed under the temporalis muscle during the surgery. The purpose of the two extra cochlear electrodes is to reduce the power consumption of the cochlear implant by serving as ground electrodes. The remote grounds enable the use of more power-efficient monopolar modes of stimulation (MP1, MP2, or MP1+2). The device will support monopolar, bipolar, and commonground modes of stimulation. The straight electrode is directly advanced through the cochleostomy, requiring the use of microinstruments designed for the task. The Nucleus 24 Double Array is a specially designed electrode array for patients who have ossification or other physiologic manifestations contraindicating use of a single long electrode array. The Double Array is split into two shorter arrays, each with 11 electrodes. Implantation requires modification of the traditional surgical approach. Two openings must be drilled, one for each of the electrode arrays, which are placed in the first and second turns of the cochlea. The Contour, which was introduced in 1999, is the most recent version of the Nucleus electrode array. The Contour electrode array is precurved with a tapered apical portion designed to match the curvature and size of the cochlea’s scalae. A stylet is embedded within the array to assist in proper positioning of the array during insertion. After the electrode array of the Contour has been advanced through the cochleostomy in a manner similar to that of the straight electrode design, the stylet is withdrawn, allowing the electrode array to tightly hug the modiolus. In the Contour, the previously full-banded electrodes are instead half-banded, to direct stimulation toward the spiral ganglion fibers. The use and function of the two extracochlear ground electrodes have been carried over from the N24k array.

measures, including impedance and compliance telemetry, as well as neural response telemetry (NRT). The hermetically sealed, silicone-encased titanium housing of the Contour receiver-stimulator remains essentially unchanged from that of the Nucleus 24k. However, the device is smaller, and the receiver-stimulator pedestal has been reshaped into a circle. The magnet remains removable, allowing the device to be MRI-compatible. Speech Processor Both a body-worn (Sprint) and an ear level speech processor (Esprit) are available. The current body-worn speech processor, Sprint, was first marketed in 1997 and is compatible with both the straight and Contour internal electrode arrays. The Sprint processor has a four-program capacity and can implement three different speech-coding strategies (CIS, SPEAK, and ACE). Both volume and microphone sensitivity can be manipulated independently. The Sprint also offers an autosensitivity noise reduction paradigm to assist in background noise reduction as well as a lock feature used primarily to keep the inquisitive fingers of children from altering recommended settings. The case is made of plastic and can be powered by either one or two rechargeable or alkaline AA batteries. The headset has a separate microphone housed behind the ear and a transmitting coil, which contains the magnet. Various accessories, including FM system cables, are available for use with the Sprint processor. In 1998, the Esprit 24 became the first commercially available ear level speech processor in the United States. Like the Sprint processor, it is compatible with both the straight and Contour electrode arrays, but differs in several ways. First, the Esprit can use only the SPEAK coding strategy. Patients preferring CIS or ACE or patients with high stimulation requirements may be unable to wear the ear level processor. Also, the Esprit has the capacity to store only two programs rather than four. A single rotary control is present and may be used as either a volume or sensitivity control, but not as both within the same program. Two high-power 675 batteries power the Esprit. A second generation of the Esprit 24 processor, the Esprit 3G was recently introduced. This updated version allows patients to use any of the available speech-coding strategies. One of the most welcome new features of the 3G is the addition of a built-in telecoil. Cochlear Corporation has also produced an ear level device, the Esprit 22, compatible with the older 22M internal components, which continue to be used by approximately 20,000 individuals.

Receiver-Stimulator The N24k has a receiver-stimulator that is a hybrid integrated circuit contained within a hermetically sealed titanium casing coated in silicone. The silicone encasement also contains a platinum receiver coil and titaniumcoated rare earth magnet. The receiver coil functions as an antenna for the signal received from the externally positioned transmitter. The magnet is removable through a simple surgical procedure to permit the use of magnetic resonance imaging (MRI) when necessary. When connected to the programming interface for the Nucleus implant, the N24k has the capacity to perform three types of telemetry

Speech-Processing Strategies Currently, the Nucleus 24 device is capable of using three FDA-approved coding strategies, including the SPEAK, CIS, and ACE.

Med-El (Medical Electronics) After more than 20 years of use in Europe, the Med-El device was introduced to the U.S. market in 1994. The current version of the internal device, the Combi 40+, entered into clinical trials in the United States in 1997.

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The Combi 40+ internal electrode array has three available configurations: the standard, the compressed, and the split arrays. The standard version is a straight electrode array with 24 electrode contacts designed to operate as 12 pairs. Wider spacing of the electrode contacts is designed to minimize channel interaction. The standard electrode, at 31 mm, has the deepest insertion depth of any Combi 40+ device. The Combi 40+ ground electrode is a cloverleaf. The array is directly advanced into the cochlea via the cochleostomy. The compressed electrode design, like the standard version, has 24 electrode contacts as well as an extracochlear ball electrode. The compressed electrode has a smaller spacing between electrode contacts, resulting in a significantly shorter electrode lead. The compressed electrode design allows the full complement of contacts to be inserted when surgical insertion is partially compromised, as in incomplete ossification. For cases of severe ossification or cochlear malformation, the split-array electrode design is available. In this design, the 24 electrode contacts are divided into two separate electrode arrays, which are implanted independently of each other. Use of the split-electrode requires the drilling of two tunnels into separate turns of the cochlea and is indicated for use when insertion of either the standard or compressed electrode arrays are contraindicated or will result in incomplete insertion.

The Med-El body-worn speech processor (CIS PRO+) offers two speech-processing strategies, CIS and n-of-m. The Med-El variation of CIS is unique in that it sends information in the form of nonoverlapping pulses. New information is presented in each pulse. The n-of-m feature extraction strategy allows the audiologist to choose the number of channels to activate in each stimulation cycle, and so the electrodes carrying the most important speech information are stimulated. In addition, the amount of temporal information on the selected channels is increased. The ear level speech processor (Tempo+) uses the CIS+ coding strategy. CIS+ has additional enhancements compared with the CIS used in the body-worn device. The Hilbert transformation is a mathematical algorithm for envelope detection, which tracks amplitude changes over time more accurately than the method used with traditional CIS. In addition, an extended high-frequency range up to 8500 Hz is available with CIS+.

Receiver-Stimulator The receiver-stimulator of the Combi 40+ is housed in a hermetically sealed ceramic case. The circuitry of the Combi 40+ receiver-stimulator permits device telemetry and measurements of voltage compliance, which assists in determining proper functioning of the internal components of the CI. Restricted use of MRI is currently under investigation in the United States, without removal of the internal magnet. This is the first time that the FDA has allowed an implant manufacturer to use a CI with an MRI scanner. MRIs up to 1.5 T are already used with this device in Europe. Speech Processor Although the Med-El offers both body-worn and ear level speech processors, the majority of Med-El patients use the ear level Tempo+ speech processor. The Tempo+ has a modular design enabling customization of the speech processor based on a patient’s choice. This speech processor has the capacity to store nine programs, a rotary dial for sensitivity level control, an on/off switch, and a three-way switch that can be programmed with three volume levels for each program. It is powered by three high-power 675 batteries in a completely BTE format. An accessory unit is available that allows use of a standard AA battery. The remote battery pack, which is connected to the speech processor via a cable, is worn elsewhere on the body.

THE FUTURE CI technology continues to evolve, resulting in improved hearing and speech discrimination outcomes.1 Several developments are being clinically tested and should come into widespread use within the next few years.17,18 Bilateral cochlear implantation has been used with promising early results consisting of improved quality of hearing, especially functional hearing in the presence of background noise.18 However, in order to achieve true binaural hearing, the percepts from the two sides need to fuse when there is a common source, and not when the sources are separate. For this to occur, the implanted electrode arrays on the two sides need to be aligned precisely in the tonotopic dimension. Presently it is impossible to achieve this surgically. Advances in the speech processor may “fill in” some gaps by communicating information that is missing on one side to the appropriate electrode on the other side.19 Although present-day implants have a justifiable emphasis on speech processing and perception, improvements in the perceptions of nonspeech environmental sounds and music are much needed. This area is likely to enjoy greater research focus in the future. Future improvement in electrode design may consist of electrode configurations for abnormal ears, electroacoustic devices,18 and perimodiolar electrodes.6 New electrode design will deal with dysplastic and ossified cochleae. Short arrays for high-frequency stimulation may also be linked to middle ear implants. This so-called hybrid device will use the same microprocessor for both acoustic and electrical signal processing. And finally, the development of perimodiolar electrodes, implantable microphones, and implantable rechargeable batteries promise fully implanted devices in the future. With the use of less traumatic electrodes and with improved outcomes, patients with more residual hearing will become candidates for surgery. Advances in molecular research suggest incorporating otoprotective agents within the electrodes to promote survival or regeneration of

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neural elements in the cochlea. The survival of cochlear neural elements should lead to conservation of residual hearing as well as enhancement of CI performance. Thus advances in both CI technology and molecular biology promise to provide ever-improving opportunities for individuals with hearing loss.20

REFERENCES 1. Balkany TJ, Hodges A, Eshraghi AA, et al: Cochlear implants in children. A review. Acta Otolaryngol (Stockh) 122:356–362, 2002. 2. Eshraghi AA, Telischi FF, Balkany TJ: Cochlear implantation in adult with hearing loss. Federal Practitioner 24(3):409–417, 2003. 3. Djourno A, Eyries C: Prothese auditive par excitation electrique a distance du nerf sensoriel a l’aide d’un bobinage inclus a demeure. Presse Med 35:14–17, 1957. 4. Niparko JK, Wilson BS: History of cochlear implants. In Niparko JK, Kirk KI, Mellon NK, et al (eds.): Cochlear Implants: Principles & Practices. Philadelphia, Lippincott Williams & Wilkins 2000, pp 103–107. 5. Eshraghi AA, King J, Hodges A, Balkany TJ: Cochlear implants. In Johnson F, Virgo K (eds.): The Bionic Patient: Health Promotion for People with Implanted Prosthetic Devices. Totowa, NJ, Humana Press Inc, in press. 6. Balkany TJ, Eshraghi AA, Yang N: Modiolar proximity of three new perimodiolar cochlear implant electrodes. Acta Otolaryngol (Stockh) 122:363–369, 2002. 7 Eshraghi AA, Yang N, Balkany TJ: Comparative study of cochlear damage with three perimodiolar electrode designs. Laryngoscope 113:415–419, 2003.

8. Feinman G, LeMay M, Staller S, et al: Audallion beam forming clinical trial results. Abstract for the Fifth Cochlear Implant Conference. New York, May 1997, p 116. 9. Wilson BS: Cochlear implant technology. In Waltzman SB, Cohen NL (ed.): Cochlear Implants. New York, Thieme Medical Publishers, 2000, pp 109–118. 10. Balkany TJ, Hodges AV, Gomez-Marin O, et al: Cochlear reimplantation. Laryngoscope 109(3):51–355, 1999. 11. Merzenich MM, White M, Vivion MC: Some considerations of multichannel electrical stimulation of the auditory nerve in the profoundly deaf: Interfacing electrode arrays with its auditory nerve array. Acta Otolaryngol 87:196–203, 1979. 12. Busby P: 2002 cochlear collaborative research report. Cochlear, 2002. 13. Kennedy DW: Multichannel intracochlear electrodes: Mechanism of insertion trauma. Laryngoscope 97:42–49, 1987. 14. Hodges AV, Balkany TJ, Ruth RA, et al: Electrical middle ear muscle reflex: use in cochlear implant programming. Otolaryngology Head and Neck Surgery, 117:255–263, 1997. 15. Hodges A, Butts SL, Dolan-Ash MS, Balkany TJ: Using electrically evoked auditory reflex thresholds to fit the clarion cochlear implant. Ann Otol Rhinol Laryngol 108:64–68, 1999. 16. Shallop JK, Facer GW, Peterson A: Neural response telemetry with the Nucleus CI24M cochlear implant. Laryngoscope 109:1755–1759, 1999. 17. Gantz B, Tyler R, Rubintein JT, et al: Binaural cochlear implants placed during the same operation. Otol Neurotol 23:169–180, 2002. 18. Kiefer J, Tillein J, Ilberg C, et al: Electric-acoustic stimulation of the auditory system. ORL J 61:334–340, 1999. 19. Chatterjee M: Cochlear implants: Bridging auditory neuroscience and technology. Hear Rev 9(4):20–29, 2002. 20. Scarpidis BS, Madnani D, Shoemaker C, et al: Arrest of apoptosis in auditory neurons: Implications for sensorineural preservation in cochlear implantation. Otol Neurotol 24:409–417, 2003.

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Outline Patient Selection Audiologic Criteria Medical Evaluation Radiologic Evaluation Promontory Stimulation Other Considerations

C

Chapter

Cochlear Implantation in Adults

Surgical Considerations Operative Procedure Complications Rehabilitation Results Professional Requirements

ochlear implantation is a standard rehabilitative approach for selected individuals with bilateral severe to profound sensorineural hearing loss (SNHL) who do not benefit significantly from conventional hearing aids. Although a number of different cochlear implant devices are currently in use, none can provide normal hearing. The benefit provided to the implant recipient will vary from patient to patient. Advances in technology in implant external and internal hardware and software components have led to substantial improvement in postimplant performance, evidenced by improved open-set speech understanding in adults. The three devices implanted in the United States include the Clarion device (Advanced Bionics Corporation, Santa Clarita, CA), the Nucleus device (Cochlear Corporation, Englewood, CO), and the COMBI 40 device (MED-EL Corporation, Innsbruck, Austria). Hardware innovations include smaller external processors, more robust internal receivers, and modiolar-hugging electrode arrays. The closer proximity of the electrode arrays to the spiral ganglion cells in the modiolus offers theoretical advantages of improved sound quality, speech recognition, and power efficiency. Software innovations include improved speech coding strategies using higher rates of stimulation and different forms of stimulation to enhance patient performance. Newer technology provides information for trouble-shooting device failures and optimizing parameters for speech processing strategies. Future innovations may lead to a totally implantable cochlear implant. Considerable worldwide experience exists regarding the appropriate selection of candidates, surgical considerations, postoperative fitting and training of patients, and professional training and establishment of facility requirements for a cochlear implant center. We address these issues in the remainder of the chapter.

William M. Luxford, MD Dawna Mills, AuD

PATIENT SELECTION Cochlear implants (CIs) are medical devices and come under the auspices of the federal Food and Drug Administration (FDA). Because of this, strict patient inclusion and exclusion criteria are typically specified by the sponsor (usually the manufacturer) for the period of the investigational study. The product labeling on indications for use is based on results for the type of patients studied. However, rarely is patient selection black and white. A variety of factors, including age at time of deafness, age at implant surgery, duration of deafness, status of the remaining auditory nerve fibers, training, and type of implant, may influence patient performance with the device. Two of the more important factors influencing auditory performance following cochlear implantation include age at onset of deafness and duration of profound hearing loss. The ideal adult candidate has an acquired severe-to-profound SNHL. A period of auditory experience adequate for development of normal speech, speech perception, and language offers a significant advantage in learning to use the implant. These postlingually deafened patients represent the majority of adults undergoing implantation. In these patients, there is a significant correlation between duration of severe-to-profound hearing loss and performance. Those with prolonged auditory deprivation receive similar auditory information as do other implant patients but are not able to use the information as effectively in the recognition of running speech, perhaps due to the loss of central auditory processing ability. A smaller number of adult implant recipients have a congenital or very early onset of hearing loss. These prelingually deafened adults have a long period of auditory deprivation and may have had little experience with sound. Expectations for benefit from a CI must be adjusted accordingly. These 1309

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patients typically have greater difficulty assimilating the new auditory information and, in general, have performed less well than those with some degree of auditory memory. However, advances in implant technology have improved performance in the adult patient, encouraging prelingually deafened adults to seek cochlear implantation. FDA-approved studies are now under way examining potential benefits of bilateral cochlear implantation in adults and the use of a hybrid cochlear implant that combines both electric and acoustic stimulation in adult hearing-impaired patients who have mild-to-moderate hearing loss in the low frequencies with a steep dropoff to severe-to-profound hearing loss in the high frequencies.

Audiologic Criteria An audiologic assessment is the primary means for determining implant candidacy. A component of the audiologic assessment is a minimal adult auditory speech battery. The improvements in patient performance with advances in technology keep the audiologic criteria changing over time. Hearing-impaired patients who were not considered candidates for implantation a few years ago might be candidates for implantation today, and patients who may not be candidates for implantation today may be candidates for implantation in the near future. In general, patients who are considered at this time for cochlear implantation have bilateral SNHL, with a three-frequency pure-tone average (500, 1000, and 2000 Hz) unaided threshold in the better ear of 70 dB or poorer; have less than 20% speech discrimination score on consonant nucleus consonant (CNC) words under headphones bilaterally; and have, for non-Medicare patients, a score poorer than 60% in the nonimplant ear and 50% in the ear to be implanted on hearing in noise sentence testing (HINT) sentences with hearing aids to qualify under the most liberal criteria. Medicare has a stricter criteria for potential implant patients. Medicare patients must score less than 30% on sentence material with hearing aids. Criteria for adult Medicaid patients will vary from state to state. In some states, Medicaid does not approve prelingually deafened adults for cochlear implantation. A full list of test procedures and criteria for patient selection recommended by the device manufacturers and principal investigators are typically specified in the product labeling or in the device training manuals.

Medical Evaluation Medical evaluation includes a complete history and physical examination to detect problems that might interfere with the patient’s ability to complete either the surgical or rehabilitative measures of implantation. Appropriate laboratory studies should be ordered to eliminate any suspected medical disorder. Implantation has been performed in patients with many different causes of deafness, and cause of deafness per se does not seem to be a major factor in implant success. Evidence of purulent drainage within the middle ear space, either as a result of acute otitis media or chronic otitis media would be a contraindication on physical exam for cochlear implantation, postponing the procedure until the middle ear disease process was appropriately treated.

Radiologic Evaluation Preoperative imaging serves to complete the candidacy process and assist in surgical planning. A high-resolution computed tomography (HRCT) scan of the temporal bones using a bone algorithm is the study of choice in most centers. Magnetic resonance imaging is the study of choice in several centers and, with improvements, may replace HRCT as the primary imaging procedure. These images allow the surgeon to identify partial or complete ossification of the scala tympani, soft tissue, obliteration of the scala, congenital malformation of the inner ear, and surgical landmarks. Complete agenesis of the cochlea and an abnormal acoustic nerve, the result of congenital malformation, trauma, or surgery, are contraindications for cochlear implant placement. Ossification or fibrous occlusion of the cochlea or the round window does not exclude a patient from implantation, but it may influence outcome. Patients with occlusion of the cochlea are at higher risk of not responding to electrical stimulation or may require substantially higher power output from the signal processor than patients with little or no bone growth. Promontory Stimulation A few implant teams perform an electrical stimulation test at either the promontory or round window membrane. A positive response is a perception of sound on stimulation. Many do not feel that such testing is critical in the selection of candidates because patients with a negative response, particularly at the promontory, may respond to intracochlear stimulation when implanted.

Other Considerations Although most implant programs no longer require a formal psychological evaluation for adult implant candidates, a number of other factors are considered important in the final decision to implant. Counseling is often provided to families who have misconceptions or unrealistic expectations regarding the benefits and limitations of the CI. Support from family and friends is important in the rehabilitation process. Adults who were deafened prelingually or who have been deaf for many years may have a difficult time learning to use the implant or obtaining a benefit from it. Those who have too recently lost their hearing may not yet have fully adjusted to the realities of deafness and may have difficulty accepting the limitations of present CIs. Secondary gains from deafness or changes in family or social roles as a result of deafness can sometimes lead to family difficulties following implantation. As with any rehabilitative process, the needs of the particular individual and his or her family must be considered.

SURGICAL CONSIDERATIONS A CI should be implanted only by a qualified surgeon specifically trained by the implant manufacturer to perform the procedure.

Cochlear Implantation in Adults

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Operative Procedure Selection of the side for implantation is governed by several factors. The most patent cochlea is typically chosen for implantation. It is generally believed that the ear with the shortest duration of deafness may serve as the best ear for implantation; however, if the patient uses a hearing aid in only one ear (the side that is perceived as the ear with better hearing), implanting the contralateral “worse” ear does not negatively affect performance. When no specific factors lead to the choice of one ear over the other, the ear on the side of the dominant hand is chosen to facilitate device manipulation. The implant is inserted via a transmastoid, facial recess approach to the round window/scala tympani. In patients with mastoid cavities or absent posterior ear canal walls, obliteration of the mastoid cavity with blind sac closure of the external auditory canal is preferably done at the time of disease removal. Cochlear implant placement is then performed at a second stage approximately 4 to 6 months later. Surgery is performed with the patient under general anesthesia with the use of continuous intraoperative facial nerve monitoring. Many different incisions have been designed to allow placement of the internal receiverstimulator. The development of the behind-the-ear signal processors has required the internal receiver-stimulator to be placed more posteriorly than in the past. Many physicians are now using smaller postauricular incisions that are more cosmetically acceptable (require less shaving of hair and create a smaller scar), that maintain vascularity of the wound edges, that promote healing, and that allow for the more posterior placement of the internal receiverstimulator. The more posterior placement of the internal device places it posterior to the temporalis muscle, which minimizes the thickness of the scalp over the internal device. A 5- to 7-mm scalp thickness enhances the magnetic coupling of the internal receiver and the external transmitter and reduces power consumption required to transfer the stimulus from the transmitter transcutaneously to the internal receiver. The depressed seat for the internal receiverstimulator is created in the skull posterosuperior to the pinna, with adequate allowance for placement of a behindthe-ear microphone piece and speech processor. A complete mastoidectomy is performed, preserving a bony overhang along the superior posterior margins of the mastoid cavity, to aid stabilization of the carrier coil within the cavity. The bone removal extends back to the sigmoid, but retraction of the sigmoid is not required unless it is far forward. The posterior bony ear canal is thinned without exposing the overlying vascular strip tissue. Thinning of the bony ear canal is necessary because in viewing the round window area, the direction of vision is parallel to the external auditory canal. The short process of the incus and its buttress are then used as bony landmarks to guide development of the facial recess. The chorda tympani is generally left intact unless a narrow recess limits visualization and access to the round window. Once the facial recess is opened, the lip of the round window niche is usually visible just inferior to the stapedius tendon and oval window (Fig. 80-1). With a small diamond stone and intermittent suctionirrigation, the lip of the niche is removed, and the round window membrane comes into clear view. To avoid

Figure 80-1. Open facial recess showing lip of the round window niche just inferior to the staples. (Courtesy of Cochlear Corporation, Englewood, CO.)

possible damage to the facial nerve, the diamond stone is not rotated when passing it through the facial recess to the round window area. In cases where the round window niche is almost hidden under the pyramidal process, one must drill forward and thin the promontory until the scala tympani is entered. The cochleostomy is made anterior and inferior to the round window membrane, in the basal turn of the cochlea. Either before or after the electrode system has been placed within the scala tympani, the internal receiver-stimulator can be placed in its seat and usually held in place by suture ties. The cochleostomy is then sealed with small plugs of temporalis muscle. Occasionally, the round window niche and membrane are replaced with new bone growth. This condition is more frequent in patients whose deafness is attributable to meningitis rather than to other diseases. In these cases, the surgeon must drill forward along the basal coil for as much as 4 to 5 mm. Usually, the new bone is white and can be demarcated from the surrounding otic capsule. Following this white plug of bone with the drill will usually lead to the patent scala, allowing placement of the electrode array. Occasionally, the surgeon may be required to drill more superiorly to enter the scala vestibuli, allowing placement of the electrode in this area. If new bone growth completely obliterates the scala, the surgeon drills forward 10 or 11 mm into the white new bone for placement of the electrode. A second tunnel can also be created more superiorly and anteriorly beneath the area of the cochlear front process to enter the area of the middle turn. The implant manufacturers have modified the electrode systems to include either compressed or split electrode arrays for use in patients who have ossified cochleas. When drilling the round window niche or attempting to create an opening into the scala tympani through new bone growth, the burr must be directed anteriorly toward the nose. Drilling superiorly may damage the basilar membrane and osseous spiral lamina, which may result in the loss of ganglion cells. If the surgeon directs the burr inferiorly, a hypotympanic air cell may accidentally be entered, and the active electrode will be placed improperly into this area. Postoperatively, these cases may fail to stimulate. Revision surgery with placement of the electrode array into the scala tympani

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will remedy this situation. If the surgeon is uncertain of the placement of the electrode, an intraoperative anteroposterior transorbital plane film can be taken to check the electrode position. It is most important that force not be used when advancing the electrode into the scala tympani. This may lead to insertion trauma to the inner ear structures or may distort the shape of the electrode. Both of these problems can adversely affect the outcome. If electrocautery is used after placement of the internal receiver, bipolar electrocautery is recommended because it minimizes the possibility of passing current through the receiver. The postauricular flap is closed in layers, without drainage. Surgery routinely takes 1.5 to 2.5 hours. Patients are usually discharged the day of or the day following surgery, returning for their first postoperative visit in about 1 week. Approximately 3 to 5 weeks pass, allowing for resolution of the edema in the postauricular flap, before beginning fitting the patient with the signal processor.

Complications The risks of the implant procedure are the same as those for chronic ear surgery: infection, facial paralysis, cerebrospinal fluid (CSF) drainage, meningitis, and the usual risks of anesthesia. All of these risks are remote in chronic ear surgery and have proved to be so in implant surgery as well. Failure of healing of the incision and associated minor infections would seem to be the most common problem associated with implant surgery. In a few patients in whom the internal receiver has been placed too close to the wound’s edge, or in patients in whom the flap over the internal receiver is too thin, the internal receiver extruded. It is important to maintain at least 1 to 2 cm between the incision and the edge of the internal receiver. The ideal thickness for the flap is 6 to 7 mm. Although too thin a flap may become necrotic, too thick a flap may diminish device performance by decreasing the transcutaneous transmission of information. Problems with the facial nerve can occur as a result of both surgery and stimulation. It is important to maintain good surgical landmarks when the facial recess is created. Although the facial nerve is identified, it usually does not have to be uncovered with the facial recess approach. It is important to maintain adequate irrigation at the facial recess to help dissipate the heat generated by the turning shaft of the diamond burr that is being used to create the exposure of the round window and entrance into the scala tympani, especially in drill-out cases. The use of facial nerve monitoring may reduce the risk of injury, although it is no substitute for knowledge of temporal bone anatomy and good surgical technique. CSF drainage has occurred at both the internal receiver site and the cochlea. In some patients, the temporal squama can be quite thin. In these cases, to create an adequate seat for the internal receiver package, the bony dissection must be carried down to the dura. If small dural tears do occur, they should be covered with temporalis fascia, and the fascia should be supported with the internal receiver. After insertion of the intracochlear electrode, the cochleostomy is closed with strips of temporalis fascia to

prevent perilymphatic fistulae. Oozing or gushing of CSF is more likely in patients with congenitally malformed inner ears. When this situation is anticipated preoperatively based on imaging findings, the eustachian tube should be temporarily obliterated with Surgicel before the cochleostomy. Rarely do patients require further management of this complication. Meningitis is a possible complication following cochlear implantation, and bacterial meningitis has occurred recently in a small number of American and European cochlear implant users. Although the risk for contracting meningitis after implantation is low (<1%), cochlear implant patients may be at higher risk than the general public. In July 2002, the FDA issued a public health Web notification to this effect, noting that at least 25 cases of meningitis had been diagnosed worldwide in children and adult CI recipients ranging in age from 21 months to 63 years. Onset of meningitis symptoms ranged from less than 24 hours to greater than 5 years from time of implant. The FDA suggested that CI candidates, as well as those already implanted, may benefit from vaccinations against organisms that commonly cause bacterial meningitis, particularly Streptococcus pneumoniae and Haemophilus influenzae. In the elderly population, the possible effects of cochlear implantation on the vestibular system should be considered. An occasional patient may complain of transient dizziness and imbalance.

REHABILITATION Surgical implantation of the internal receiver-stimulator and electrode(s) of the CI device is only the beginning of the treatment process. Approximately 3 to 5 weeks following surgery the patient must return to the clinic to be fitted with the external portions of the device. All of the various CI devices require device settings to be adjusted to the individual patient. The more complex the device, the more complex the process for determining appropriate settings. In addition, determining the best fit for a particular patient may involve repeated changes in settings over time as the patient becomes experienced with the sound provided. In addition to “setting” the device, it is important to introduce or reintroduce the patient to sound and to do so in a manner that provides a realistic idea of the benefits and the limitations of the device in relation to the patient’s own personal situation. That is, a certain amount of rehabilitation must be provided. Most CI programs include providing information on care and use of the device; simple auditory training; and training of auditory speech perception skills. Time spent counseling the patient and family members may be considerable. The amount of rehabilitation and training provided varies from center to center. Furthermore, the amount of time necessary will vary depending on the particular patient and his or her needs. Each CI manufacturer recommends specific rehabilitation approaches or provides written materials for implant training (or both). The minimum number of patient hours in the clinic following implantation is likely to be no less than 20 hours per year. Regular follow-up visits for the first several years with objective assessment of performance are standard practice.

Cochlear Implantation in Adults

RESULTS Despite differences in device design and function, postimplant performance has not differed significantly among the devices. Virtually all patients receiving multichannel cochlear implant devices experience substantial benefit. Up to two-thirds of adults undergoing implantation obtain open-set speech recognition and comprehend speech to some degree while using the telephone. The mean performance for adult implant patients is between 70% and 80% on sentence material and 35% to 45% on CNC word tests after 6 months of implant use. Even poor performers benefit from the awareness of environmental sounds and enhancements of speech-reading abilities. Quality of life questionnaires given to the postlingually deafened adult patients participating in the Nucleus 24 Cochlear Implant Clinical Trial study revealed that 92% felt that their quality of life was improved with the implant, and 88% indicated they were satisfied with their cochlear implant after 3 months of use. In a general performance questionnaire given to the same group, 69% reported enjoying music and 90% reported an overall improvement in communication ability. In a telephone test of recorded open-set sentences, 91% of postlingually deafened adults demonstrated significant improvement in sentence recognition compared with preoperative scores with hearing aids.1 Adult postlingually deafened subjects participating in the FDA clinical trials for the MED-EL Combi 40 device reported the following benefits from their implants; they are more comfortable attending social events, feel less isolated as a result of their deafness, are less often upset because they are deaf, find it less frustrating to communicate, have more satisfying relationships with friends, more often engage in activities that require more hearing, and 84% report that the implant quite positively or very positively affected their life.2 The largest group of patients with bilateral cochlear implants are using the MED-EL Combi 40/40+ systems. Bilateral implantation provides a significant benefit in speech understanding in both quiet and noise.3 Since 1998, Advanced Bionics Corporation, manufacturer of the Clarion Implant, has made several modifications to their internal device, including the electrode array and electrode positioning system (EPS). Zwolan and colleagues reported on postlingually deafened adults who participated in FDA clinical trials for the HiFocus Electrode with EPS and the precurved electrode with EPS.4 The HiFocus electrode with EPS group had a significantly longer duration of deafness and a higher mean age at implantation compared with the precurved electrode with EPS group. Results were not significantly different at the 1-month and 3-month postoperative test interval on speech perception tests for the two groups. However, significantly better scores were obtained with the HiFocus electrode and EPS group on CNC words at the 6-month test interval. Eighty-five percent of subjects with HiFocus electrode and EPS preferred a fully simultaneous (simultaneous analogue stimulation) or a partially simultaneous strategy (paired pulsatile strategy). The newest generation Clarion device, known as the CII System, is presently undergoing FDA clinical trials. The high resolution strategy, which is unique to the CII

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device is capable of much faster rates of stimulation than the previous generation of cochlear implants. Initial results from the first 51 patients reveal that 90% of subjects prefer the high resolution strategy to their control strategy (personal communication, Henson, Ann Marie, 2002). It is well established that duration of deafness has a significant effect on postoperative performance for adult implant recipients. Geier and coworkers reported on 202 subjects who participated in the Clarion clinical trial study and determined that patients who had been deaf for 60% or more of their life demonstrated a slower rate of improvement on speech recognition tests but continue to improve with increased implant experience.5 A commonly held belief among some professionals is that prelingually deafened adults are poorer candidates for cochlear implantation. This group tends to perform poorer on traditional open-set speech perception testing than the postlingually deafened group. Waltzman and colleagues reported on three prelingually deafened adults who demonstrated improvement in sound awareness but not in their speech perception ability.6 Skinner and coworkers obtained similar results from their study of four prelingually deafened adults.7 Zwolan and colleagues reported on user satisfaction for a group of 12 prelingually deafened adults and found that although the group showed little to no improvement on open-set speech perception measures, they were consistent users of their device.8 In addition, the subjects were satisfied with their implant and felt that it improved their communication ability. This group of subjects may require redundant counseling regarding appropriate expectations and will require more encouragement, particularly during the initial 6 months to 1 year of implant use. Based on the poor results generally obtained on open-set speech perception measures, additional closed-set tests and subjective measures should be used to gauge success.

PROFESSIONAL REQUIREMENTS It is imperative that both physicians and audiologists receive specific training related to each different CI device they wish to provide to patients. Each device manufacturer provides training courses. For the physician, training usually includes information regarding patient selection and surgical training with temporal bone lab practice sessions. Audiologists receive training in patient evaluation and selection, device fitting, and rehabilitation. Device fitting includes use of specialized equipment for making electrical measurements and setting individual device parameters of the speech processor. Each different CI a clinic wishes to use requires its own special equipment for device setting, including computer hardware and software. It is not possible to perform as a center that offers CIs without acquisition of such equipment. In addition, specialized surgical tools, test materials, and rehabilitation materials may be necessary. Implicit in becoming a CI center is having the space available for the necessary equipment and for performing rehabilitation. This typically requires at least one room large enough for the equipment and for the patient, a family member, and the audiologist to work on device setting and

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rehabilitation tasks. This is, of course, in addition to having appropriate audiologic testing facilities and equipment. The amount of both direct service and indirect service (e.g., preparation) time per patient is considerably greater for the CI program than for other procedures typically performed in an otologic or audiologic practice. To perform CI procedures on any regular basis frequently requires that at least one audiologist be dedicated to the implant program. Many patients who are evaluated for an implant are not appropriate candidates. But they are patients with hearing impairment who may need hearing aid services or rehabilitation. The advent of the cochlear implant has made materials available for better assessment, hearing aid fitting, and training of those with losses that are troublesome, but not severe enough to become a cochlear implant recipient. It behooves those with an interest in CIs to think in terms of total hearing health care. Otology and audiology combined now have something to offer for every level of hearing loss.

REFERENCES 1. Cochlear LTD, February 2001, Physician’s Package Insert, Durhaum, NC. 2. MED-EL Corporation Web site: www.medel.com. 3. Muller J, Schon F, Helms J: Speech understanding in quiet and noise in bilateral users of the MED-EL COMBI 40/40+ cochlear implant system. Ear Hear 23:198–206, 2002. 4. Zwolan T, Kileny PR, Smith S, et al: Adult cochlear implant patient performance with evolving electrode technology. Otol Neurotol 22:844–849, 2001. 5. Geier L, Barker M, Fisher L, Opie J: The effect of long-term deafness on speech recognition in postlingually deafened adult CLARION cochlear implant users. Ann Otol Rhinol Laryngol (Suppl) 177: 80–83, 1999. 6. Waltzman SB, Cohen NL, Shapiro WH: Use of a multichannel cochlear implant in the congenitally and prelingually deaf population. Laryngoscope 102:395–399, 1992. 7. Skinner MW, Binzer SM, Fears BT, et al: Study of the performance of four prelinguistically or perilinguistically deaf patients with a multielectrode, intracochlear implant. Laryngoscope 102:797–806, 1992. 8. Zwolan TA, Kileny PR, Telian SA: Self-report of cochlear implant use and satisfaction by prelingually deafened adults. Ear Hear 17:198–210, 1996.

BIBLIOGRAPHY Balkany T, Hodges AV, Luntz M: Update on cochlear implantation. Otolaryngol Clin North Am 29:277–289, 1996. Clark GM: Cochlear implants in the third millennium. Am J Otol 20:4–8, 1999. Kim CS, Chang SO, Lim D (eds.): Updates in cochlear implantation. Adv Otorhinolaryngol 57:1–459, 2000. Lenarz T: Cochlear implants: Selection criteria and shifting borders. Acta Otorhinolaryngol Belg 52:183–199, 1998. NIH consensus conference: Cochlear implants in adults and children. JAMA 274:1955–1961, 1995.

SUGGESTED READINGS Cohen NL, Waltzman SB, Fisher SG: A prospective, randomized study of cochlear implants. The Department of Veterans Affairs Cochlear Implant Study Group. N Engl J Med 328:233–237, 1993. Dobie RA, Jenkins H, Cohen NL: Multicenter comparative study of cochlear implants: surgical results. Ann Otol Rhinol Laryngol Suppl 165:6–8, 1995. Fraysse B, Dillier N, Klenzner T, et al: Cochlear implants for adults obtaining marginal benefit from acoustic amplification: A European study. Am J Otol 19:591–597, 1998. Gantz BJ, Woodworth GG, Knutson JF, et al: Multivariate predictors of audiological success with multichannel cochlear implants. Ann Otol Rhinol Laryngol 102:909–916, 1993. Labadie RF, Carrasco VN, Gilmer CH, Pillsbury HC 3rd: Cochlear implant performance in senior citizens. Otolaryngol Head Neck Surg 123:419–424, 2000. Maillet CJ, Tyler RS, Jordan HN: Change in the quality of life of adult cochlear implant patients. Ann Otol Rhinol Laryngol Suppl 165: 31–48, 1995. Svirsky MA, Silveira A, Suarez H, et al: Auditory learning and adaptation after cochlear implantation: A preliminary study of discrimination and labeling of vowel sounds by cochlear implant users. Acta Otolaryngol 121:262–265, 2001. van Dijk JE, van Olphen AF, Langereis MC, et al: Predictors of cochlear implant performance. Audiology 38:109–116, 1999. Waltzman SB, Fisher SG, Niparko JK, Cohen NL: Predictors of postoperative performance with cochlear implants. Ann Otol Rhinol Laryngol Suppl 165:15–18, 1995.

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Outline Patient Selection Implantation in Very Young Children Implantation in Children with Previous Auditory Experience Implantation in Congenitally or Early Deafened Adolescents Cochlear Implant Systems Nucleus Cochlear Implant Systems Clarion Cochlear Implant System Medical Electronic (Med-El) Cochlear Implant System New Developments in Cochlear Implant Electrode Design

Chapter

Cochlear Implants in Children

Audiologic Assessment Medical Assessment Psychological Assessment Surgical Implantation Unusual Surgical Considerations Cochlear Dysplasia Aberrant Facial Nerve Intracochlear Ossification Complications Clinical Results Speech Intelligibility and Language Outcomes Conclusion

C

ochlear implantation in the pediatric age group is a complex process that incorporates sophisticated methodology related to the assessment, rehabilitation, and education of deaf children. Cochlear implants seek to replace a nonfunctional inner ear hair cell transducer system by converting mechanical sound energy into electrical signals that can be delivered to the cochlear nerve in profoundly deaf patients. In this way, damaged or missing hair cells of the cochlea are bypassed. Electrical stimulation of the auditory system is effective because the vast majority of sensorineural deafness results from receptor cell dysfunction within the cochlea. The first national clinical trial to investigate cochlear implants in children was launched by William F. House in 1980.1 Subsequently, a rigorous clinical trial was initiated to study multichannel cochlear implants in children, which ultimately lead to the Food and Drug Administration’s (FDA) approval of the Nucleus 22-channel cochlear implant for children age 2 to 17 years on June 27, 1990.2 A permanent role for cochlear implants for selected deaf children was thus established. Appropriate extensions of the initial approvals continue to evolve. The widespread application of newborn hearing screening programs has resulted in many more infants with congenital hearing loss being identified within the first few months of life. Early identification must be coupled with an effective early intervention program. The Joint Committee This work was supported in part by NIH NIDCD grants RO1 DC00064, RO1 DC00423, and K23 DC00126 and by Psi Iota Xi.

Richard T. Miyamoto, MD Karen Iler Kirk, PhD

on Infant Hearing Loss has recommended that children with hearing loss be identified by the age of 3 months, and that appropriate intervention should begin by the age of 6 months.3 The benefits of fitting hearing aids before the age of 6 months has been demonstrated by YoshinagaItano.4 For infants whose degree of hearing loss exceeds the limits of conventional amplification cochlear implants are a viable option.

PATIENT SELECTION As a result of a number of clinical trials evaluating safety and efficacy, a trend toward earlier implantation and implantation in children with more residual hearing has emerged. Current FDA guidelines permit implantation in children as young as 12 months of age. (At the time of this writing, the lower age limit for the Nucleus device is 12 months but for the Clarion and Med El devices 18 months.) Candidacy criteria differ according to the age of the patients being considered. The current criteria are listed in Table 81-1.

Implantation in Very Young Children The prevailing emphasis placed on early identification of hearing loss has mandated a reevaluation of the lower age limits appropriate for cochlear implantation. This has occurred in an attempt to ameliorate the devastating effects of early auditory deprivation. Electrical stimulation appears 1315

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TABLE 81-1. Pediatric Candidacy Criteria for Cochlear Implantation

Implantation in Children with Previous Auditory Experience

Children age 12 mo to 24 mo

Children age 25 mo to 17 yr, 11 mo

Bilateral profound hearing loss Lack of auditory skills development and minimal hearing aid benefit (documented by parent questionnaire) No medical contraindications Enrollment in a therapy of education program emphasizing auditory development

Bilateral severe-to-profound hearing loss Lack of auditory skills development and minimal hearing aid benefit (word recognition scores <30% correct)

Children who become deaf at or after age 5 years generally are classified as postlingually deafened. These children have developed many or all aspects of spoken language before the onset of their deafness. However, once they lose access to auditory input and feedback, they frequently demonstrate rapid deterioration in the intelligibility of their speech. Implantation soon after the onset of deafness potentially can reverse this rapid deterioration in speech production and perception abilities. Cochlear implantation may be less successful in postlingually deafened children if a long delay takes place between the onset of deafness and implantation.8 A postlingual onset of deafness is an infrequent occurrence in the pediatric population. If this were to be the only category for which cochlear implants positively affected deaf children, this technology would be of limited applicability in children.

No medical contraindications Enrollment in a therapy of education program emphasizing auditory development

to be capable of preventing at least some of the degenerative changes in the central auditory pathways.5 Furthermore, implantation in very young congenitally or neonatally deafened children may have substantial advantages because the development of speech and language competence normally begins at a very early age. Because cochlear implantation involves an elective surgical procedure performed under a general anesthetic, an appropriated risk-benefit ratio must be established. A small but growing number of infants younger than 12 months of age have received cochlear implants. It is our opinion that in experienced hands, surgical risks down to the age of 6 months are no greater than for 12-month-old children. However, there may be a slightly greater anesthetic risk in children younger than 1 year of age.6 It is obviously imperative that a pediatric anesthesiologist experienced with this age group be an integral part of the surgical team. Early implantation may be particularly important when the cause of deafness is meningitis, because progressive intracochlear ossification can occur and preclude standard electrode insertion. A relatively short interval of time exists during which this advancing process can be circumvented. Thus, infants with deafness secondary to meningitis may receive an implant prior to the age of 1 year if they have completed a brief hearing aid trial with no evident benefit. Although implanting in very young children has become more routine for experienced cochlear implant teams, it remains controversial because the audiologic assessment, surgical intervention, and postimplant management in this population is challenging. Profound deafness must be substantiated and the inability to benefit from conventional hearing aids demonstrated. This can be difficult to determine in young children with limited language abilities. For very young children, parental questionnaires are commonly used to assess the benefit from amplification. When inserting implants in very young children, special consideration must be given to the small dimensions of the temporal bone and to potential problems from postoperative temporal bone growth. Nonetheless, extension of implant candidacy to the 6-to-12 month age group is feasible on an anatomic basis. The cochlea is adult size at birth and by age 1 year, the facial recess and mastoid antrum, which provide access to the middle ear for electrode placement, are adequately developed.7

Implantation of Congenitally or Early Deafened Adolescents Congenitally or early deafened adolescents who wish to pursue a cochlear implant present a special challenge. In the past, this group has not demonstrated high levels of success with electrical stimulation of the auditory system. Adolescents with profound hearing loss who have a history of consistent hearing aid use and who communicate primarily through audition and spoken language are among the best candidates in this age group. Conversely, adolescents with little previous auditory experience or those who rely primarily on sign language for communication may have difficulty learning to use the sound provided by an implant and may find it disruptive. This latter group of adolescents is at risk for nonuse of a cochlear implant. Implantation in both groups can be successful if time is spent counseling about potential outcomes and ensuring that both patients and their families have realistic expectations for postimplant benefit.

COCHLEAR IMPLANT SYSTEMS Despite differences in design, all multichannel cochlear implant systems have several essential components in common. These include: A surgically implanted electrode array that is in the cochlea near the auditory nerve An external microphone, which picks up acoustic information and converts it to electrical signals An externally worn speech processor that processes the signal according to a predefined strategy and produces stimuli for the electrode array A transmission link between the external components and the surgically implanted array The processed speech signal is amplified and compressed to match the narrow electrical dynamic range of the ear. The typical response range of a deaf ear to electrical stimulation is on the order of only 10 to 20 dB, even less in the high frequencies. Transmission of the

Cochlear Implants in Children

electrical signal across the skin from the external unit to the implanted electrode array most commonly is accomplished by the use of electromagnetic induction or radiofrequency transmission. The critical residual neural elements stimulated appear to be the spiral ganglion cells or axons. Multichannel, multielectrode cochlear implant systems are designed to take advantage of the tonotopic organization of the cochlea. The incoming speech signal is filtered into a number of frequency bands, each corresponding to a given electrode in the array. Thus, multichannel cochlear implant systems use place coding to transfer spectral information in the speech signal as well as encoding the durational and intensity cues of speech.

Nucleus Cochlear Implant Systems The Nucleus 22-channel cochlear implant was the first multichannel cochlear implant to receive FDA approval for use in adults and children, and it has been used in more patients than any other cochlear implant system worldwide. The Nucleus CI24M cochlear implant received FDA approval for adults and children in 1998. Early speech processing strategies (F0F2 and F0F1F2) used with the Nucleus 22-channel cochlear implant used feature-extraction strategies that conveyed information about such key aspects of speech as the amplitude and frequency of vowel formants and the fundamental frequency of voiced sounds. The third-generation speech processing strategy, MPEAK, encoded additional highfrequency information by stimulating two of three more basal fixed electrodes; the goal was to provide additional information that would yield improved consonant recognition scores. Three processing strategies are currently available for use with the Nucleus cochlear implants. Two of the strategies use the n-of-m approach in which the speech signal is filtered into m bandpass channels, and the n highest envelope signals are selected for each cycle of stimulation.9 The spectral peak, or SPEAK strategy is the most widely used with the Nucleus 22-channel cochlear implant and is available to users of either the Nucleus 22-channel or the Nucleus CI24M system. This strategy filters the incoming speech signal into 20 frequency bands; on each stimulation cycle an average of six electrodes are stimulated at a rate that varies adaptively between 180 and 300 pulses/sec. An n-of-m strategy using much higher rates of stimulation, known as advanced combined encoder (ACE) strategy can be implemented in the new Nucleus CI24M device. The third processing strategy available with the Nucleus CI24M system is the continuous interleaved sampling, or CIS, strategy.10 The CIS strategy filters the speech signal into a fixed number of bands, obtains the speech envelope, and then compresses the signal for each channel. On each cycle of stimulation, a series of interleaved digital pulses rapidly stimulates consecutive electrodes in the array. The CIS strategy is designed to preserve fine temporal details in the speech signal by using high rate, pulsatile stimuli. Two different speech processors are available for new Nucleus cochlear implant recipients. The body-worn SPRINT processor can implement any of the three current

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speech processing strategies. The ear-level ESPRIT speech processor currently can implement only the SPEAK processing strategy.

Clarion Cochlear Implant System The Clarion multichannel cochlear implant system11,12 is manufactured by the Advanced Bionics Corporation. This device has been approved by the FDA for use in adults (1996) and children (1997). The Clarion multichannel cochlear implant has an eight-channel electrode array. Two processing strategies can be implemented through the processor. The first is CIS, described earlier, which is used to stimulate monopolar electrodes. The second strategy, simultaneous analogue stimulation (SAS) filters and then compresses the incoming speech signal for simultaneous presentation to the corresponding enhanced bipolar electrodes. The relative amplitudes of information in each channel and the temporal details of the waveforms in each channel convey speech information.

Medical Electronic (Med-El) Cochlear Implant System The Combi 40+ cochlear implant system is manufactured by the Med-El Corporation in Innsbruck, Austria. The Med-El cochlear implant has 12 electrode pairs and has the capability of deep electrode insertion into the apical regions of the cochlea.13 This device uses the CIS processing strategy and has the capacity to provide the most rapid stimulation rate of any of the cochlear implant systems currently available. Both a body-worn and an ear-level speech processors (the CIS Pro+ and Tempo+, respectively) are available for this the Med-El cochlear implant.

New Developments in Cochlear Implant Electrode Design New designs of the internal electrode array have recently been introduced for the Nucleus and Clarion cochlear implants. The Nucleus Contour electrode array is a curved electrode that is straightened by a stylet for insertion purposes. After surgical placement into the scala tympani, the stylet is withdrawn. The electrode then assumes its preformed shape, more closely approximating the modiolar wall of the cochlea. The Clarion HiFocus electrode is positioned closer to the modiolar wall by inserting a separate positioner into the scala tympani. However, the positioner has now been removed from the marketplace because of a suspected association with postoperative meningitis. Because the spiral ganglion cells are thought to be the sites stimulated by cochlear implants, directing the electrodes toward the modiolus and further positioning the array may improve spatial specificity of stimulation and reduce the current needed to drive the electrodes.14

AUDIOLOGIC ASSESSMENT The audiologic evaluation is the primary means of determining suitability for cochlear implantation. Audiologic evaluations should be conducted in both an unaided

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condition and with appropriately fitted conventional amplification. Thus, all potential candidates must have completed a period of experience with a properly fitted hearing aid, preferably coupled with training in an appropriate aural rehabilitation program. The audiologic evaluation includes measurement of pure tone thresholds along with word and sentence recognition testing. Aided speech recognition scores are the primary audiologic determinant of cochlear implant candidacy. For very young children or those with limited language abilities, parent questionnaires are used to determine hearing aid benefit.

MEDICAL ASSESSMENT The medical assessment includes the otologic history and physical examination. Radiologic evaluation of the cochlea is performed to determine whether the cochlea is present and patent and to identify any congenital cochlear deformities. High-resolution, thin-section computed tomography (HRCT) scanning of the cochlea remains the imaging technique of choice.15 Intracochlear bone formation resulting from labyrinthitis ossificans usually can be demonstrated by HRCT scanning; however, when soft tissue obliteration occurs following sclerosing labyrinthitis, HRCT may not image the obstruction. In these cases, T2-weighted magnetic resonance imaging (MRI) is an effective adjunctive procedure, providing additional information regarding cochlear patency. The endolymphperilymph signal may be lost in sclerosing labyrinthitis. Intracochlear ossification is not a contraindication to cochlear implantation but can limit the type and insertion depth of the electrode array that can be introduced into the cochlea. Congenital malformations of the cochlea are likewise not contraindications to cochlear implantation. Cochlear dysplasia has been reported to occur in approximately 20% of children with congenital sensorineural hearing loss.16 Several reports of successful implantation in children with inner ear malformations have been published.17–21 A thin cribriform area between the modiolus and a widened internal auditory canal is often observed22 and is believed to be the route of egress of cerebrospinal fluid (CSF) when it occurs during surgery or postoperatively. A CSF gusher was reported in several cases. Temporal bone dysplasia also may be associated with an anomalous facial nerve, which may increase the surgical risk. The precise cause of the deafness cannot always be determined but is identified whenever possible; however, stimulable auditory neural elements are nearly always present regardless of the cause of deafness.23 Two exceptions are the Michel deformity, in which congenital agenesis of the cochlea is present, and the small internal auditory canal syndrome, in which the cochlear nerve may be congenitally absent. Routine otoscopic evaluation of the tympanic membrane is performed. An otologically stable condition should be present prior to considering implantation. The ear proposed for cochlear implantation must be free of infection, and the tympanic membrane should be intact. If these conditions are not met, medical or surgical treatment before implantation is required. The management of middle-ear effusions in children who are under consideration for cochlear implantation or who already have a

cochlear implant deserves special consideration. Conventional antibiotic treatment usually accomplishes this goal, but when it does not, treatment by myringotomy and insertion of tympanostomy tubes may be required. Removal of the tube several weeks before cochlear implantation usually results in a healed, intact tympanic membrane. When an effusion occurs in an ear with a cochlear implant, no treatment is required as long as the effusion remains uninfected. Chronic otitis media, with or without cholesteatoma, must be resolved before implantation; this is accomplished with conventional otologic treatments. Prior ear surgery that has resulted in a mastoid cavity does not contraindicate cochlear implantation, but this situation may require mastoid obliteration with closure of the external auditory canal or reconstruction of the posterior bony ear canal.

PSYCHOLOGICAL ASSESSMENT Psychological testing is performed for exclusionary reasons to identify subjects who have organic brain dysfunction, mental retardation, undetected psychosis, or unrealistic expectations. Valuable information related to the family dynamics and other factors in the patient’s milieu that may affect implant acceptance and performance are assessed.

SURGICAL IMPLANTATION Cochlear implantation in children requires meticulous attention to the delicate tissues and small dimensions. Skin incisions are designed to provide access to the mastoid process and coverage of the external portion of the implant package while preserving the blood supply of the postauricular skin. The incision used at the Indiana University Medical Center has eliminated the need to develop a large postauricular flap. The inferior extent of the incision is made well posterior to the mastoid tip to preserve the branches of the postauricular artery. From here the incision is directed posterosuperiorly. In children, the incision incorporates the temporalis muscle to give added thickness. A subperiosteal pocket is created for positioning the implant induction coil. A bone well tailored to the device being implanted is created, and the induction coil is fixed to the cortex with a fixation suture or periosteal flaps. Following development of the skin incision, a mastoidectomy is performed. In infants, care must be exercised because the mastoid process is short and shallow and the facial nerve may exit the temporal bone superficially. The horizontal semicircular canal is identified in the depths of the mastoid antrum, and the short process of the incus is identified in the fossa incudis. The facial recess is opened using the fossa incudis as an initial landmark. The facial recess is a triangular area bound by (1) the fossa incudis superiorly, (2) the chorda tympani nerve laterally and anteriorly, and (3) the facial nerve medially and posteriorly. The facial nerve usually can be visualized through the bone without exposing it. The round window niche is visualized through the facial recess about 2 mm inferior to the stapes. Occasionally, the round window niche is posteriorly positioned and is not well visualized through the facial recess or is obscured by ossification. Particularly in these

Cochlear Implants in Children

situations, it is important not to be misdirected by hypotympanic air cells. Entry into the scala tympani is accomplished best through a cochleostomy created anterior and inferior to the annulus of the round window membrane. A small fenestra slightly larger than the electrode to be implanted (usually 0.5 mm) is developed. A small diamond burr is used to “blue line” the endosteum of the scala tympani, and the endosteal membrane is removed by using small picks. This approach bypasses the hook area of the scala tympani, allowing direct insertion of the active electrode array. After insertion of the active electrode array, the cochleostomy area is sealed with small pieces of fascia.

Unusual Surgical Considerations Cochlear Dysplasia In cases of cochlear dysplasia, a CSF gusher may be encountered on fenestrating the cochlea while performing the cochleostomy. The flow of CSF has been successfully controlled by entering the cochlea through a small fenestra, allowing the CSF reservoir to drain off, inserting the electrode into the cochleostomy, and tightly packing the electrode at the cochleostomy with fascia. It is postulated that the source of the leak is through the lateral end of the internal auditory canal. Supplementally, a lumbar drain can be placed to reduce the spinal fluid reservoir until a satisfactory tissue seal has occurred. In cases of severe dysplasia with a common cavity deformity, the electrode array may be inserted directly by a transmastoid labyrinthotomy approach. The otic capsule is opened posterosuperior to the second genu of the facial nerve, and the common cavity is entered. Several patients have been treated in this way with no vestibular side effects.24 Aberrant Facial Nerve In patients who have malformations of the labyrinth, and occasionally in patients with otherwise normal anatomy, the facial nerve may follow an aberrant course. Although not all aberrant facial nerves affect cochlear implant surgery, those that do must be recognized and dealt with effectively. Two anomalous courses of the facial nerve that place it at risk are the laterally and anteriorly displaced vertical portion of the facial nerve and a facial nerve that courses over the promontory over or anterior to the round window.25

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of 10 to 12 active electrodes, a process that has yielded very satisfactory results. More recently, a specially designed split electrode developed by the Med-El Corporation has been used wherein one branch of the electrode array is placed in the tunnel described earlier and the second active electrode is inserted into an additional cochleostomy developed just anterior to the oval window. Gantz and his colleagues26 described an extensive drill-out procedure to gain access to the upper basal turn. Steenerson and coworkers27 described insertion of the active electrode into the scala vestibuli in cases of cochlear ossification. Although this procedure has merit, the scala vestibuli is frequently ossified when the scala tympani is completely obliterated.

Complications Complications have been infrequent with cochlear implant surgery and can be largely avoided by careful preoperative planning and meticulous surgical technique. Among the most commonly encountered problems are those associated with the incision and postauricular flap and facial nerve injury.28 Using the incision we describe, we have experienced only one flap breakdown in our pediatric cochlear implant population. (This occurred several years postoperatively after head trauma.) We experienced one transient delayed facial paresis and one CSF gusher in a child with a Mondini deformity.29 Several additional patients with the large vestibular aqueduct syndrome have also had gushers.30 Because children are more susceptible to otitis media than adults, justifiable concern has been expressed that a middle ear infection could cause an implanted device to become an infected foreign body, requiring its removal. Two children in our series experienced a delayed mastoiditis (several years after the implant surgery) resulting in a postauricular abscess. These cases were treated by incision and drainage and intravenous antibiotics without the need to remove the implant. Of even greater concern is that infection might extend along the electrode into the inner ear, resulting in a serious otogenic complication, such as meningitis or further degeneration of the central auditory system. To date, although the incidence of otitis media in children who have received cochlear implants parallels that seen in the general pediatric population, no serious complications related to otitis media have occurred in our patients.

Clinical Results Intracochlear Ossification Ossification at the round window is common in postmeningitic patients and has been encountered in approximately one-half of the children whose cause of deafness was meningitis who have received a cochlear implant at our center. In these patients, a cochleostomy is developed anterior to the round window, and the new bone is drilled until an open scala is entered. A full electrode insertion can then be accomplished. Less frequently, labyrinthitis ossificans with extensive intracochlear bone formation may occur with complete obliteration of the scala tympani. In these cases, our preference has been to drill open the basal turn of the cochlea and create a tunnel approximately 6 mm deep and partially insert a Nucleus electrode. This allows implantation

A number of demographic factors influence performance results in children with cochlear implants. Age at the time of implantation is one factor that influences communication skills development. Although the critical period for implantation of congenitally or prelingually deafened children has not been determined,31 it is now apparent that earlier implantation yields superior cochlear implant performance in children.32–34 In a longitudinal analysis of 73 children who were prelingually deafened and received current implant technology and processing strategies before 5 years of age, we have shown that children who underwent implantation before 3 years of age had significantly faster rates of language development than did children with later implantation.35

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In contemporary practice, the majority of children who receive cochlear implants have congenital or prelingually acquired hearing loss. As opposed to postlingually deafened children who use the information transmitted by a cochlear implant to compare previously stored representations of spoken language, prelingually deafened children must use the sound provided by a cochlear implant to acquire speech perception, speech production, and spoken language skills. Because young deaf children have limited linguistic skills and attention spans, the assessment of performance in this population is challenging. To effectively evaluate the communication benefits of cochlear implant use in children, a battery of developmentally and linguistically appropriate tests should be employed.36,37 The development rate of postimplant auditory skills is increasing as cochlear implant technology improves and as children receive implants at a younger age.38–40 Early reports of children who used the Nucleus cochlear implant with a feature extraction strategy demonstrated significant improvement in closed-set word identification (i.e., the ability to identify words from a limited set of alternatives) but very limited open-set word recognition.41,42 With the introduction of newer processing strategies, greater speech perception benefits were seen. Many children with current cochlear implant devices achieve at least moderate levels of open-set word recognition. For example, Cowan and colleagues43 have reported word recognition scores for a group of 19 children that ranged from 4% to 76% words correct with a mean of 44% words correct. Zwolan and coworkers44 reported average scores of approximately 30% correct on a more difficult measure of isolated word recognition in children with the Clarion cochlear implant. Detailed longitudinal studies are needed as pediatric cochlear implant recipients continue to make communication gains long after they have received their implants. For example, O’Donoghue and his colleagues reported that children who received cochlear implants prior to age 7 years were still demonstrating improvements at 5 years postimplant with no evidence of a plateau.45 Furthermore, comparison studies have shown that the speech perception abilities of pediatric cochlear implant recipients meet or exceed those of their peers with unaided pure tone average thresholds greater than 90 dB hearing loss who use hearing aids.46,47 Postimplant factors also directly influence pediatric outcomes. One such factor is the adequacy of speech processor fitting or “map.” As age at implantation drops, it becomes more difficult to obtain reliable behavioral responses from children during mapping. Recently developed objective measures of auditory responses to electrical stimulation, such as neural response telemetry, or NRT, can aid audiologists in the fitting process.48 A second postimplant factor that has been shown to influence outcome is the rehabilitation program provided to the children. Children who participate in regular therapy sessions typically have a better outcome than those who do not. Children in oral programs typically develop better speech perception abilities than children who are in programs that advocate the combined use of signed and spoken English.49 Finally, it has been reported the children who demonstrate motor or cognitive delays prior to implantation are significantly delayed in developing speech perception abilities following implantation.50

Speech Intelligibility and Language Outcomes Improvements in speech perception are the most direct benefit of cochlear implantation. However, if children with cochlear implants are to succeed in the hearing world, they must also acquire intelligible speech and access their surrounding linguistic system. The speech intelligibility and language abilities of children with cochlear implants improve significantly over time51–54 and, on average, exceed those of their age- and hearing-matched peers with hearing aids.53,54 Speech intelligibility and spoken language acquisition are significantly correlated with the development of auditory skills.55 Although a great deal of variability exists, the best pediatric cochlear implant users demonstrate highly intelligible speech and age-appropriate language skills. These superior performers usually receive their implant at a young age and are educated in an oral/ aural modality.52

CONCLUSION Cochlear implants are an appropriate sensory aid for selected deaf children who receive minimal benefit from conventional amplification. Improvements in technology and refinements in candidacy criteria have secured a permanent role for cochlear implantation. With improved postoperative performance, a clear justification for performing implantation not only in patients with bilateral profound sensorineural hearing but also in patients with severe sensorineural hearing loss has been reached. Patients as young as 12 months of age may receive an implant under current FDA guidelines, and experience with even younger children is accumulating. Wide intersubject performance variability continues to exist. However, most postlingually deafened adults with current cochlear implants achieve auditory-only word recognition and communicate very effectively when auditory cues are combined with lipreading. The best adult recipients can converse fluently without lipreading cues. Children using cochlear implants have acquired speaking and listening skills and have developed a spoken language system that is beyond what previously could be achieved with hearing aids. Children who receive an implant at a young age and use oral communication have the best prognosis for developing intelligible speech and age-appropriate language abilities. Challenges remain in effectively assessing peripheral auditory neuronal survival and matching electrically transmitted signals to the future potential of the central auditory system in the deaf subjects.

REFERENCES 1. Berliner KI, Eisenberg LS: Methods and issues in the cochlear implantation of children: An overview. Ear Hear 6(Suppl):6S, 1985. 2. Clark GM, Tong YC, Dowell RC, et al: A multiple-channel cochlear implant: An evaluation using nonsense syllables. Ann Otol Rhinol Laryngol 90:227–230, 1981. 3. American Academy of Pediatrics Joint Committee on Infant Hearing: Joint Committee on Infant Hearing 1994 Position Statement. Pediatrics 95:152–156, 1995.

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4. Yoshinaga-Itano C, Sedey AL, Coulter DK, Mehl AL: Language of early- and later-identified children with hearing loss. Pediatrics 102:1161–1171, 1998. 5. Matsushima JI, Shepard RK, Seldon HL, et al: Electrical stimulation of the auditory nerve in deaf kittens: Effects on cochlear nucleus morphology. Hear Res 56:133–142, 1991. 6. Young NM: Infant cochlear implantation and anesthetic risk. Ann Otol Rhinol Laryngol 111:49–51, 2002. 7. Lenarz T: Cochlear implantations in children under the age of two years. In Honjo I, Takahashi H (eds.): Otorhinolaryngology. 1997, pp 204–210. 8. Gordon KA, Daya H, Harrison RV, Papsin BC: Factors contributing to limited open-set speech perception in children who use a cochlear implant. Int J Pediatr Otorhinolaryngol 56:101–111, 2000. 9. Wilson BS: Strategies for representing speech information with cochlear implants. In Niparko JK, Kirk KI, et al (eds.): Cochlear Implants: Principles and Practices. Philadelphia, Lippincott Williams & Wilkins, 2000, pp 129–170. 10. Wilson BS, Lawson DT, Finley CC, et al: Coding strategies for multichannel cochlear prostheses. Am J Otol 12(Suppl 1):56–61, 1991. 11. Schindler RA, Kessler DK: Clarion cochlear implant: Phase I investigational results. Am J Otol 14:263–272, 1993. 12. Kessler DK, Schindler RA: Progress with a multistrategy cochlear system. The Clarion. In Hochmair-Desoyer IJ, Hochmair ES (eds.): Advances in Cochlear Implants. Wein, Manz, 1994, pp 354–362. 13. Gstoettner WK, Baumgartner WD, Franz P, et al: Cochlear implant deep insertion surgery. Laryngoscope 107:544–546, 1997. 14. Wilson BS: Cochlear implant technology. In Niparko JK, Kirk KI, Robbins AM, et al (eds): Cochlear Implants: Principles and Practices. Philadelphia, Lippincott Williams & Wilkins, 2000, pp 109–127. 15. Yune HY, Miyamoto RT: Medical imaging in cochlear implant candidates. Am J Otol 12(Suppl):11–17, 1991. 16. Jensen J: Tomography of the inner ear in deaf children. Radiological demonstration of two cases with the Mondini malformation. J Laryngol Otol 81:27–35, 1967. 17. Mangabeira-Albernaz PL: The Mondini dysplasia: From early diagnosis to cochlear implant. Acta Otolaryngol 95:627–631, 1983. 18. Miyamoto RT, McConkey AJ, Myres WA, et al: Cochlear implantation in the Mondini inner ear malformation. Am J Otol 7(4):58–61, 1986. 19. Jackler RK, Luxford WM, House WF: Sound detection with the cochlear implant in five ears of four children with congenital malformations of the cochlea. Laryngoscope 97(Suppl 40):15–17, 1987. 20. Silverstein H, Smouha E, Morgan N: Multichannel cochlear implantation in a patient with bilateral Mondini deformities. Am J Otol 9:451–55, 1988. 21. Tucci DL, Telian SA: Cochlear implantation in patients with cochlear malformations. Arch Otolaryngol Head Neck Surg 121: 833–838, 1995. 22. Schuknecht HF: Mondini dysplasia: A clinical and pathological study. Ann Otol Rhinol Laryngol 89(Suppl 65):1–23, 1980. 23. Hinojosa R, Marion M. Histopathology of profound sensorineural deafness. Ann N Y Acad Sci 405:459–484, 1983. 24. McElveen JT, Carrasco VN, Miyamoto RT, Linthicum, FH Jr: Cochlear implantation in common cavity malformations using a transmastoid labyrinthotomy approach. Laryngoscope 107: 1032–1036, 1997. 25. Miyamoto RT, Kaiser AR: Facial nerve anomalies in cochlear implantation. Adv Otorhinolaryngol 57:131–133, 2000. 26. Gantz BJ, McCabe BF, Tyler RS: Use of multichannel cochlear implants in obstructed and obliterated cochleas. Otolaryngol Head Neck Surg 98:72–81, 1988. 27. Steenerson RL, Gary LB, Wynens MS: Scala vestibuli cochlear implantations for labyrinthine ossification. Am J Otol 11:360–363, 1990. 28. Hoffman RA, Cohen NL: Complications of cochlear implant surgery. Ann Otol Rhinol Laryngol 104(Suppl 166):420–422, 1995.

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29. Miyamoto RT, Young M, Myres WA, et al: Complications of pediatric cochlear implantation. Eur Arch Otorhinolaryngol 253:1–4, 1996. 30. Miyamoto RT, Bichey BG, Wynne MK, Kirk KI: Cochlear implantation with large vestibular aqueduct syndrome. Laryngoscope 112:1178–1182, 2002. 31. Brackett D, Zara CV: Communication outcomes related to early implantation. Am J Otol 19(4):53–59, 1998. 32. Waltzman S, Cohen N, Shapiro W: Effects of cochlear implantation on the young deaf 6 child. Adv Otorhinolaryngol 50:125–128, 1995. 33. Waltzman S, Cohen NL, Gomolin R, et al: Perception and production results in children implanted between two and five years of age. In Hongo I, Takahashi H (eds.): Advances in Otorhinolaryngology. Basel, Karger, 1997, pp 177–180. 34. Waltzman SB, Cohen NL: Cochlear implantation in children younger than 2 years old. Am J Otol 19:158–162, 1998. 35. Kirk KI, Miyamoto RT, Lento CL, et al: Effects of age at implantation in young children. Ann Otol Rhinol Laryngol 111:69–73, 2002. 36. Kirk KI, Diefendorf AO, Pisoni DB, et al: Assessing speech perception in children. In Mendel L, Danhauer J (eds.): Audiological Evaluation and Management and Speech Perception Training. San Diego, Singular Publishing Group, 1997, pp 101–132. 37. Kirk KI: Challenges in the clinical investigation of cochlear implant outcomes. In Niparko JK, Kirk KI, Mellon NK, et al (eds.): Cochlear Implants: Principles and Practices. Philadelphia, Lippincott-Raven Publishers, 2000, pp 225–259. 38. Cohen MH: Early results using the Nucleus C124M in children. Am J Otol 20:198–204, 1999. 39. Osberger MJ, Zimmerman-Phillips S, Geier LL, et al: Clinical trials of the Clarion cochlear implant in children. Ann Otol Rhinol Laryngol 108:88–92, 1999. 40. Young NM, Carrasco VN, Grohne KM, et al: Speech perception of young children using Nucleus 22-channel or Clarion cochlear implants. Ann Otol Rhinol Laryngol 108:99–103, 1999. 41. Miyamoto RT, Osberger MJ, Myers WA, et al: Comparison of sensory aids in deaf children. Ann Otol Rhinol Laryngol 98(Suppl 8 Pt. 2):2–7, 1989. 42. Staller SJ, Beiter AL, Brimacombe J, et al: Pediatric performance with the Nucleus 22-channel cochlear implant system. Am J Otol 12(Suppl):126–136, 1991. 43. Cowan RS, DelDot J, Barker EJ, et al: Speech perception results for children with implants with different levels of preoperative residual hearing. Am J Otol 18(Suppl):125–126, 1997. 44. Zwolan TA, Zimmerman-Phillips S, Ashbaugh CJ, et al. Cochlear implantation of children with minimal open-set speech recognition skills. Ear Hear 18(3):40–51, 1997. 45. O’Donoghue GM, Nikolopoulos TP, Archbold SM, Tait M: Speech perception in children after cochlear implantation. Am J Otol 19:762–767, 1998. 46. Meyer TA, Svirsky MA, Kirk KI, et al: Improvements in speech perception by children with profound prelingual hearing loss: Effects of device, communication mode, and chronological age. J Speech Lang Hear Res 41(4):46–58, 1998. 47. Svirsky MA, Meyer TA: Comparison of speech perception in pediatric Clarion cochlear implant and hearing aid users. Ann Otol Rhinol Laryngol 108(Supp 177):104–109, 1999. 48. Abbas PJ, Brown CJ, Shallop JK, et al: Summary of results using the Nucleus C124M implant to record the electrically evoked compound action potential. Ear Hear 20:45–59, 1999. 49. Hodges AV, Dolan Ash M, Balkany TJ, et al: Speech perception results in children with cochlear implants: Contributing factors. Otolaryngol Head Neck Surg 121:31–34, 1999. 50. Pyman B, Blamey P, Lacey P, et al: The development of speech perception in children using cochlear implants: Effects of etiologic factors and delayed milestones. Am J Otol 21(1):57–61, 2000. 51. Allen MC, Nikolopoulos TP, O’Donoghue GM: Speech intelligibility in children after cochlear implantation. Am J Otol 19: 742–746, 1998.

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52. Moog JS, Geers A: Speech and language acquisition in young children after cochlear implantation. Otolaryngol Clin North Am 32(6):127–141, 1999. 53. Svirsky MA: Speech intelligibility of pediatric cochlear implant users and hearing aid users. In Waltzman SB, Cohen NL (eds.): Cochlear Implants. New York, Thieme, 2000, pp 312–314. 54. Svirsky MA, Robbins AM, Kirk KI, et al: Language development in profoundly deaf children with cochlear implants. Psych Sci 11(2):53–58, 2000.

55. Pisoni DB, Svirsky MA, Kirk KI, et al: Looking at the “Stars”: A First Report on the Intercorrelations Among Measures of Speech Perception, Intelligibility and Language Development in Pediatric Cochlear Implant Users. Bloomington, Indiana University, 1997, pp 51–91.

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Outline Introduction Anatomy Auditory Brainstem Implant Device Surgery Patient Selection Surgical Approach and Implantation Procedure Postoperative Care Electrophysiologic Monitoring Postimplantation Psychophysics

Chapter

Auditory Brainstem Implant

Speech Processor Programming Pitch Assessment Performance Monitoring Auditory Performance Speech Recognition Electrode-Specific Pitch Penetrating Auditory Brainstem Implant Summary

INTRODUCTION Since the first edition of this book, substantial progress has occurred in the treatment of deafness by electrical stimulation of the auditory brainstem, including Food and Drug Adminstration (FDA) approval for a multichannel implant in July 2000. The House Ear Institute (HEI) program has implanted more than 140 recipients with an auditory brainstem implant (ABI), and more than 300 individuals have received the device worldwide. The implant has been upgraded and improved, new speech-processing strategies have been implemented, and steps have been taken to go beyond the surface activation of brainstem neurons with a penetrating microarray. The focus of this chapter is to discuss what we have learned over the past 23 years about treating deafness with the ABI. Although the ABI is similar in some ways to cochlear implantation, we hope that highlighting the relevant differences will help maximize success for new implant centers, as well as more established ones. It can be a more complex process than cochlear implantation on all levels, and one that requires more time and experience.

ANATOMY The auditory brainstem region is complex, having multiple nuclei and fiber tracts that mediate sensory and motor function for several regions of the body. Vestibular The authors would like to thank the House Ear Clinic and their patients for their long-term cooperation and participation in the project, as well as Johannes Kuchta, Butch Welch, and John Galvin for assistance with figure production, and Michael Waring for technical and editorial assistance on electrophysiology.

Steven R. Otto, MA Derald E. Brackmann, MD William E. Hitselberger, MD Robert V. Shannon, PhD Mark J. Syms, MD

schwannomas (VSs) in this region, such as those that occur in neurofibromatosis type 2 (NF-2), can significantly affect these neural centers, causing deafness and other disabilities. Complete surgical removal of the VS often results in sectioning of the auditory nerve and deafness. Because cochlear implants would not be effective in such individuals, the ABI was developed and first used successfully at the House Ear Institute in 1979.1–3 The first implanted patient continues to benefit from her device daily. The site of implantation is over the surface of the cochlear nucleus (CN) complex, composed of the ventral cochlear nucleus (VCN) and the dorsal cochlear nucleus (DCN). These nuclei are located adjacent to the lateral recess of the fourth ventricle and are accessed through the foramen of Luschka. The DCN and VCN serve as termination points for all axons of the cochlear nerve. The frequency specificity of neurons in this region probably contributes to the range of pitch percepts that many ABI patients experience when different electrodes are activated. The cochlear nuclei in humans (shaded area in Fig. 82-1) are primarily internal structures with few visible surface landmarks. Other useful landmarks in the region include the facial nerve, the root entry point of the eighth nerve, the choroid plexus, the taenia, and the ninth nerve. Figure 84-1 illustrates the relative position of these structures and the surgical field of view from the typical translabyrinthine approach. These landmarks can be used effectively by the experienced neurosurgeon to help identify the site of implantation. Landmarks also can be distorted or obscured by large VSs, and intraoperative monitoring of evoked auditory brainstem responses (EABR) is used to assist with the identification of the target CN.4–6 The entry into the lateral recess (foramen of Luschka) is found between the roots of the facial and glossopharyngeal 1323

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Figure 82-1. Schematic illustration of the major structures of the pontomedullary region, with the dashed line outlining the surgical field of view from the translabyrinthine approach. (Reprinted from Brackmann DE, Hitselberger WE, Nelson RA, et al: Auditory brainstem implant. I. Issues in surgical implantation. Otolaryngol Head Neck Surg 108:624–633, 1993.)

nerves and normally is marked by the intact choroid plexus. The taenia obliquely traverses the roof of the lateral recess, marking the surface of the VCN. A concavity sometimes visualized between the eighth and ninth nerves should not be confused with the introitus of the recess. The ABI electrode array is positioned within the confines of the recess and activates neurons in both the VCN and DCN. Placements that are too deep or too shallow can result in an increase in potentially annoying nonauditory sensations that can complicate fitting and use of the device.7 Likewise, poor contact of the electrodes with the surface of the CN can require higher stimulus levels that generate larger electric fields and increase the potential of activating nonauditory structures. For proper function, the ABI electrode array must be properly positioned in several dimensions and remain positionally stable indefinitely. Neurosurgical and monitoring expertise is essential to achieve this, and proper training in the implantation of the device is necessary. Within a few days after placement, ingrowth of fibrous tissue into the array carrier occurs, which fixes it in place. These components, in combination with proper programming of the system, are critical in achieving a successful ABI result. The multiple neural centers in the region of the CN create the potential for mild, but significant nonauditory

(mostly tingling) sensations. The majority of patients experience these sensations on at least a few electrodes, and they probably arise from such structures as the facial nerve, the flocculus of the cerebellum, or the inferior cerebellar peduncle. Intraoperative EABRs can alert the neurosurgeon to this undesirable activation4–6 and allow repositioning of the array. Even so, in a relatively small but significant portion of our patients (8%), such sensations have predominated postoperatively, and the patient has not received auditory benefit. Several of these patients initially received implantation on their first tumor sides, so, when the first-side ABI was unsuccessful, another device was placed during second-side tumor removal and was successful. A successful outcome can be influenced by several factors. For example, in one patient, an attempt was made to reposition an electrode array that appeared to have shifted postoperatively, but this proved difficult because of fibrous tissue adhesion. Scarring from previous operations also can complicate subsequent surgery and ABI implantation. Magnetic resonance imaging (MRI) can be useful in assessing such potential difficulties, including unusual variations in brainstem anatomy or possible damage to the CN from tumors or other sources. Variations in size of the lateral recess also have been observed. Large recesses can increase the difficulty of achieving a stable placement with good contact of electrodes with the brainstem surface. In some cases with a large lateral recess we have observed postoperatively that the electrodes have rotated within the recess or floated off the brainstem surface, leading to an unsuccessful implant. Previously, stereotaxic radiosurgery such as with the gamma knife was believed to be a contraindication to the ABI because of scarring and minimal benefit seen in two early patients. More recently, a few patients who received this treatment required surgery to remove tumors that did not respond to the radiation therapy. The lateral recess in those cases was clearly identified, and scar formation from the previous radiosurgery was minimal, so an ABI was placed. Their implants worked acceptably well, and so we no longer consider prior history of radiosurgery as a strict contraindication. However, these cases might present challenges intraoperatively in identification of landmarks, and for that reason may require special consideration preoperatively, including careful evaluation with highresolution MRI.

AUDITORY BRAINSTEM IMPLANT DEVICE Figure 82-2A and B shows the Nucleus multichannel ABI electrode array and associated Sprint speech processor produced by Cochlear Corporation (Englewood, Col.). The electrode array is composed of a flexible 21-contact silicone and fabric mesh assembly that is 2.5 × 8 mm to match the size of the CN. The platinum-iridium disk electrodes are 0.7 mm in diameter. They are individually attached via a flexible cable assembly to a receiver-stimulator package that is seated postauricularly in a fashion similar to cochlear implants. The receiver-stimulator consists of a proprietary electronics package and antenna assembly that decodes digital pulses from an externally worn transmitter

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sensations and in identifying distinctive “channels” for stimulation. The process of programming the ABI for optimum function requires the assessment of auditory sensations (particularly pitch) as well as mild nonauditory sensations that are commonly experienced on individual electrode pairs.10,11 Flexibility in the programming system allows these sensations to be assessed; modified where appropriate; and used in improving ABI sound quality, usability, and performance.

SURGERY Patient Selection A

B Figure 82-2. A, Nucleus multichannel auditory brainstem implant (ABI24) showing the 21-contact electrode array and remote ground ball electrode connected to the implant receiver-stimulator electronics package and circular receiver coil with central removable magnet (star). B, Nucleus Sprint speech processor with behind-the-ear microphone and transmitter coil used by the ABI24 device recipients. Primary control features include adjusting loudness, microphone sensitivity, and selecting one of four processing programs stored in memory.

coil and sound processor that provide information about the amplitude and frequency components of sound stimuli. The device produces electric charge levels that are within established safe limits for neural stimulation.8 Two sound processors have been used in our patients: the Nucleus Spectra and more recently the Sprint. The Spectral Peak (SPEAK)9 speech-processing strategy used in the Nucleus cochlear implant systems also has worked well with ABIs. Alterations in the programming of ABI devices, dictated by the different foci of stimulation, have been necessary to accommodate the highly individualistic response patterns of ABI recipients. As in cochlear implants, the Nucleus ABI programming system allows assessment of electrical threshold and maximum comfortable loudness levels for several stimulation modes. A number of ground configurations can be used, including monopolar (with a remote reference ground), bipolar (with an adjacent electrode on the array as ground), or variable (with user-selectable grounds on the array). This flexibility can be useful in avoiding nonauditory

The ABI was initially created for individuals effected by NF-2, bilateral VS. It has utility in other disorders that compromise the function of the auditory nerve, such as eighth nerve avulsion and cochlear agenesis. The primary use of the device, however, has been in patients with NF2 deafened after VS removal. Although progress has been made in attempting to preserve hearing in patients with smaller tumors via the middle fossa approach,12 patients often present with tumors that are not amenable to middle fossa removal. Patients with NF-2 often have other CNS tumors that compromise function and quality of life. Several factors including age (both young and old) and visual capability also can affect device benefit, the latter because ABI sound is most beneficial in conjunction with lipreading. Consideration of these factors is important in the overall selection and treatment of such patients. Because ABI performance is poorer than that obtained with cochlear implants, and substantial benefit from the device often is slower to develop, thorough counseling prior to implantation will greatly contribute to a satisfactory outcome. Patient expectations must be reasonable to reduce the unpleasant necessity of coping with unmet expectations while trying to adjust to deafness. Although the initial benefits from the multichannel ABI are often modest, high motivation to make maximal use of the sound and to persist during the early rehabilitation period generally provides patients with substantial long-term communication rewards. It is encouraging to patients that such benefits have continued to develop for up to 10 years postimplantation.

Surgical Approach and Implantation Procedure Patients with NF-2 often present with tumors that are not amenable to hearing preservation using the middle fossa approach. In these patients, a translabyrinthine approach is needed, and implantation proceeds as follows. Tumor dissection is accomplished in the normal fashion via a translabyrinthine craniotomy. The translabyrinthine craniotomy provides the best access for tumor removal and exposure of the lateral recess of the fourth ventricle.13 The lateral recess is identified, and a small cottonoid is placed in the recess. The location of the lateral recess may be confirmed by noting the egress of cerebrospinal fluid (CSF) as the anesthesiologist induces a Valsalva maneuver in the patient. This technique should be reserved as a final check after the opening to the recess has been located using

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standard landmarks because CSF will be drained quickly, and the advantage of this technique is lost with multiple Valsalva’s maneuvers. After complete tumor removal and identification of the lateral recess, the site for the internal receiver posterosuperior to the mastoid cavity is determined, and the temporalis muscle in this area is elevated off the parietal skull and excised. Using a replica of the receiver-stimulator as a guide, a circular area of bony cortex in this area is flattened using cutting burrs, and a trough is created between the implant seat and the mastoid cavity for placement of the electrode wires. Suture tunnel holes are then created on either side of the receiver-stimulator, which is then fixed with silk suture prior to electrode array positioning, so that manipulation of the leads does not alter electrode placement. Once the internal receiver has been implanted, only bipolar electrocautery should be used for hemostasis because current transmission through the implant to the brainstem is a potential hazard with monopolar electrocautery. After removing the cottonoid from the foramen of Luschka, the electrode array, mounted on a Rosen needle, is inserted into the lateral recess with the electrodes oriented superiorly. With experience, we have found that the implant functions better, with fewer nonauditory side effects, when the electrodes are placed fully within the lateral recess.14 After placement, selected electrodes in the array are activated to confirm their position over the CN. They are tested for the presence of EABRs, stimulation of adjacent cranial nerves (seventh and ninth), and changes in vital signs. The position of the electrode array usually needs slight adjustment to maximize auditory stimulation and minimize electromyographic responses from the other nerves. The electrode array is secured using a small piece of Teflon felt packed into the meatus of the lateral recess. Subsequent ingrowth of fibrous tissue eventually stabilizes the array in position. The electrode wiring is positioned within the mastoid cavity and bony trough. The eustachian tube is packed with oxidized cellulose (Surgicel), and then the middle ear is packed with muscle. Abdominal fat is used to obliterate the mastoid defect. The magnet in the receiver-stimulator is removed to allow for future surveillance MRIs, and a titanium blank is inserted in its place. The blank assists in achieving a smooth skin profile over the receiver-stimulator. Because the magnet is typically removed from the receiverstimulator at the time of implantation, it may be difficult to identify the receiver-stimulator’s location at the time of initial stimulation. Improper positioning of the external transmitter coil in such cases may lead to the false impression of device failure or stimulation failure on the part of the patient. To prevent this difficulty, the skin over the center of the receiver-stimulator antenna (essentially where the magnet was removed) is tattooed with India ink at the time of surgery. The incision is closed in three layers without drainage.

Postoperative Care Postoperative care after ABI is similar to that following routine craniotomies for acoustic tumor removal. A large mastoid-type dressing is left in place for a total of 5 days. Careful attention to any moisture on the bandages allows

prompt identification of any CSF leak through the postauricular wound. A thorough physical examination of the surgical site is performed to ensure no accumulation of CSF under the flap. Intravenous antibiotics (e.g., cefuroxime [Zinacef] 3 g, one time on induction of anesthesia) is administered prophylactically. The device may be initially activated 4 to 8 weeks after implantation. This allows resolution of edema in the skin flap overlying the receiver-stimulator, which would otherwise prevent an adequate signal from reaching the implant. In actual use, implant patients must shave this area and apply a thin tape and metal disk (“retainer” disk), to which the magnetic transmitter coil adheres. The patient, or a companion, must be trained to ensure proper and consistent positioning of the transmitter coil over the implant receiver-stimulator. Many complaints about poor signal or deterioration in sound quality can be traced to improper positioning of the retainer disk.

Electrophysiologic Monitoring Monitoring of the EABR assists with confirmation that the electrode array is properly positioned. Slight adjustments of the array may be necessary to minimize responses that suggest activation of nonauditory neural structures. For EABR monitoring, subdermal needle electrodes are inserted at the vertex of the head, over the seventh cervical vertebrae, and at the hairline of the occiput. For electromyographic recording of nonauditory activation, the facial nerve is monitored in the standard fashion, and bipolar electrodes are inserted in the ipsilateral pharyngeal (soft palate) muscles to monitor activity from cranial nerve IX. After the receiver-stimulator has been secured and the array placed, a transmitter coil is placed over the receiver antenna. The ABR obtained with biphasic pulsatile stimulation of the CN differs from responses obtained using acoustic stimulation and from electrical stimulation using cochlear implants.5,6 An experienced electrophysiologist interprets these waveforms intraoperatively and provides feedback to the surgeons regarding placement.

POSTIMPLANTATION PSYCHOPHYSICS Speech Processor Programming The basic programming of ABI systems proceeds, with a few significant exceptions, much like that for cochlear implants and has been discussed in detail elsewhere.10,15 Additional steps primarily involve more extensive assessment and management of any nonauditory sensations and electrode-specific pitch. The general process is as follows: thresholds and comfort levels on each monopolar electrode pair are measured. The device manufacturer recommends that patients be connected to monitoring equipment to detect any changes in vital signs from initial stimulation and that emergency medical treatment should be available. During the testing, patients are encouraged to report both auditory and nonauditory sensations and to describe any pitch sensations. These descriptions are recorded for reference in later programming steps. Nonauditory and auditory sensations vary considerably across patients. These sensations typically are scaled

Auditory Brainstem Implant

according to magnitude. This information is then used to optimize the wearable sound processor, which maps the acoustic input to the electrical responses of the patient. Usually electrodes with mild nonauditory sensations can be used in maps without difficulty. We have also found that electrode-specific pitch information can be used by ABI recipients in a fashion similar to that for cochlear implants, although some ABI patients do not report strong pitch differences across electrodes. This may reflect limitations of the surface array in accessing the tonotopic structure of the CN as well as tumor effects on neural survival. In general, although the nonauditory sensations have not been serious, they are more problematic than in cochlear implants. Fortunately, they can often be reduced or eliminated by increasing the stimulus pulse duration or changing the reference ground electrode. In unusual cases when mild nonauditory sensations remain on most or all electrodes, patients have reported a significant reduction in them after a few days to weeks. However, we have observed that patients who initially report only nonauditory sensations with no sound sensation have not developed auditory sensations at a later date. Somewhat rarely, nonauditory sensations can arise and then disappear. In one case, a young patient had an observable facial twitch suddenly appear, and she was told to discontinue use of her processor. A few days later, she was brought into the clinic to determine if one electrode pair was responsible for this phenomenon. During this testing no side effects were observed on any electrode pairs, and she has continued to use her processor without further incident. We have occasionally encountered patients who have nonauditory sensations on nearly every monopolar electrode pair except one or two. Increasing stimulation pulse duration to the limit has not resolved these sensations. The Nucleus programming software allows the use of multiple electrodes as reference ground for other electrodes on the array, called “variable” stimulation mode. Selection of different combinations of ground electrodes has allowed us to provide additional channels that could be used by the patient. Some degree of trial and error is involved in this process, and the experience of the clinician can contribute considerably to resolution of such difficulties. We have also observed some slight but significant changes in sensitivity to electrical stimulation in some patients after surgery to remove other (nonauditory) brain tumors. Three of four cases showed an increase in threshold and comfortable loudness levels, and the fourth showed a decrease. These patients reported noticeable changes in the sound quality from their implants postoperatively. The cause for these changes is uncertain. Only bipolar cautery is used in such patients to prevent damage to implant electronics. However, subtle effects may arise from surgery that change the response of the CN to electrical stimulation. For example, the removal of a significant mass may result in a reformation of the neural structures around the removed tumor. This reshaping may slightly change the physical relation between the ABI electrode and the CN. Based on these occurrences, ABI recipients undergoing brain surgery for other tumors may benefit from a reprogramming session postoperatively prior to returning home. The changes observed in our experience have been

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easily accommodated without significant degradation in performance or sound quality.

Pitch Assessment An important step in the programming of ABI devices is the assessment of any electrode-specific pitch sensations. The methods of pitch scaling and ranking have been described elsewhere.15 These processes provide useful information for channel selection and the frequency ordering of channels in the sound processor. If a number of presentations of each electrode are given, pitch magnitude scaling on a 1-to-100 (low to high pitch) scale yields information about the overall range of pitch perceived by the patient as well as the standard deviation of the judgments (suggesting the degree of independence of each channel). Exploration of other electrode pairs can sometimes provide intermediate pitch sensations that provide useful cues for speech recognition. Pairwise pitch comparisons between electrodes have been used to exclude electrodes that are not discriminable and so are unlikely to provide salient perceptual cues. Large numbers of electrodes have not been necessary for good ABI performance. Initially, many patients were evaluated with all available electrodes, which in some cases resulted in a decrease in perceived sound quality and usability. In a systematic study of channel number and pitch-ranking effects (Fig. 82-3), the number of electrodes programmed into sound processors was progressively reduced from the maximum available to only one or two. A reduction of electrodes by half frequently did not significantly affect performance; however, sound quality did change. The top-performing ABI recipient described the change in sound quality with fewer electrodes as like going

Figure 82-3. Effects on consonant recognition (sound only) of number of electrodes used in ABI speech processors as well as pitch-rank ordering of those electrodes. Leftmost condition is a processor setting with all available electrodes but assigned to processor frequency bandwidths in a random fashion. Other conditions to the right with two or more electrodes having channels assigned to processor frequency bandwidths following pitch-rank ordering studies conducted with each patient. Solid line is a trendline through the mean scores.

REHABILITATIVE NEUROTOLOGY

from piano music played with chords to music played with single notes. As an experienced patient, she said she preferred the complexity of sound with more electrodes. However, as a new user, she said she would have preferred the simpler quality of sound with fewer electrodes. Our experience has been that comments regarding “noisy” sound quality, particularly in new users, could often be resolved by slightly reducing the number of electrodes. Because the number of electrodes is related to the number of analysis frequency bands in the speech processor, reducing the number of available electrodes may cause an undesirable narrowing of the overall bandwidth transmitted by the speech processor. This could prevent the user from detecting some sounds at extreme frequencies. To prevent this effect and provide an overall analysis bandwidth of at least 200 through 4000 Hz, some electrodes were entered more than once when setting up processor maps, in effect creating what appeared to the programming system to be extra channels. For example, it was possible to enter each of 5 electrodes twice in the mapping software and achieve the same overall analysis bandwidth as a 10-electrode processor. This provided improved detectability of higher and lower frequency sounds in the spectrum even when some electrodes were eliminated.

Performance Monitoring Clearly, the extended time involved in programming ABI devices is important to consider when embarking on a program of ABI implantation. During initial stimulation, it is highly beneficial to schedule testing and programming sessions on at least 2 consecutive days to allow an opportunity for the patient to try the processor overnight and for the clinician to manage any difficulties that arise. Because of physical problems related to NF-2, travel back to the clinic often is not a simple matter for many patients. Even so, periodic reprogramming of patient devices can improve benefit by accommodating slight but significant changes in auditory and nonauditory sensations that can occur during the first year of use. Follow-up at 3-month intervals for the first year has worked well in keeping sound processors optimized for best patient performance. It may be possible to extend this to longer intervals; however, significant changes continue to occur during this period that might affect implant benefit. Patients unable to comply with 3-month followups have often reported a decrease in performance that was promptly resolved by a reprogramming session. Reprogramming annually after the first year has served to maintain function and monitor progress. In some cases we have observed continuing improvement with experience as long as 9 years of regular device use. To monitor performance we have conducted regular speech perception testing at each follow-up. The tests have been chosen to be appropriate for ABI levels of performance and include recorded open-set, closed-set, and laser video disk tests for comparing sound only, lipreading only, and sound plus lipreading performance. Patients are evaluated with the test battery using their everyday processor settings. New processor settings also are typically evaluated with vowel and consonant tests.

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MTS (%)

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60

40

20

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7 years 5 years 6 months 1 year 3 years 6 weeks 4 years 3 months 2 years 8 years 6 years 9 months

Figure 82-4. Box-and-whisker plots showing the Monosyllable Trochee Spondee (MTS) word test scores over time, starting from initial stimulation (about 6 weeks postoperatively) and continuing to 8 years thereafter. Individual box-and-whisker plots show the 95th percentile range of scores and the mean scores (solid line). (Reprinted from figure 9 in Otto SR, Brackmann DE, Hitselberger WE, et al: Multichannel auditory brainstem implant: Update on performance in 61 patients. J Neurosurg 96:1063–1071, 2002.)

New processor settings have not always resulted in immediate performance gains. It is not unusual for ABI recipients to react somewhat negatively at first due to a change in perceived sound quality. However, if vowel and consonant recognition scores are within about 10% of previous results, patients soon acclimate and may progress to even better performance with the new settings. Highly experienced patients who are performing well often are usually given considerable leeway regarding their personal preferences for sound quality because it has been difficult to greatly improve on their performance. Although group performance has shown a tendency to improve over time (Fig. 82-4), individual performance has not always done so. Changes in the patient’s physical or mental status, including simple fatigue, can have a profound influence on use, benefit, and performance with the implant. Clinicians should be alert for such effects because a short break in the testing can be beneficial. Patients receiving an implant on their first-tumor sides with useable hearing remaining on the second side have been less likely to use their implants, and performance has not generally improved greatly until after second-side tumor removal, at which point they become totally reliant on the ABI for hearing. Prior experience with the ABI has been very beneficial to such recipients and has eased their transition to deafness in addition to providing a second implant opportunity in the small percentage of cases when the first-side device did not provide auditory sensations.

AUDITORY PERFORMANCE Speech Recognition Detailed results on speech and environmental sound perception with the ABI have been reported elsewhere.16–19 Level of benefit in everyday communication is suggested

Auditory Brainstem Implant

Figure 82-5. Graph showing the CUNY laser video disk sentence test scores for ABI recipients. Black in the bars indicates the vision-only test condition. The total length of the bars indicates scores in the sound-plus-vision condition. The gray in the bars therefore indicates the enhancement in sentence recognition attributable to ABI sound (mean 26%, range 0–66%).

by City University of New York (CUNY) Sentence Test results (Fig. 82-5) from 61 patients with 3 months to 8 years of use. Sentence recognition combining ABI sound plus lipreading is 26% better on average than lipreading only scores (range = 0 to 66%). Thirty-one percent of patients (17 of 55) scored more than 70% correct in the sound plus lipreading mode. In contrast to cochlear implant performance, only 9 (out of 55) ABI recipients scored significantly (20% or better) on sentence recognition using ABI sound only. A few patients have scored as high as 50% correct on CUNY Sentences, indicating the potential for good open-set speech recognition for some ABI recipients. Few ABI recipients can converse to any degree on the telephone, whereas a majority of cochlear implant patients do this regularly. Failure to experience auditory responses after implantation continues to occur in a relatively small percentage (5 of 61) of our cases. A somewhat higher percentage (18%) was observed in the overall U.S. multisite FDA clinical trials.20 This illustrates the importance of careful preparation of ABI candidates preoperatively and shows the value of firstside tumor implantation in providing a second opportunity for successful outcome at the time of second-side tumor removal.

generally excluded from use. Presumably these electrodes would not provide salient perceptual cues. Figure 84-3 shows that top-performing patients demonstrated substantially better (average of 30%) performance on consonant recognition with pitch-ranked maps compared with maps with random channel ordering. A similar pattern was seen for vowels. Performance with even two or three electrodes that were properly pitch-ranked was better than a full complement of randomly ranked electrodes. Rather than spending time finding more useable electrode channels, it may be more productive to carefully pitch-rank electrodes that are distinctive and can function as independent spectral channels of information. As few as four electrodes in our tested patients provided reasonably good performance, which is consistent with cochlear implant studies showing that the assignment of the frequency space to the electrodes of the implant recipient is more important than the absolute number of electrodes.21–24 It may be possible to expand the range of frequency cues available to patients with ABI by using microprobes to penetrate in depth into the CN. We are on the threshold of implementing a penetrating ABI system in humans, which will contribute to our understanding of electrical stimulation of the brainstem.

PENETRATING AUDITORY BRAINSTEM IMPLANT McCreery and others using microstimulation of the CN in cats25 have demonstrated that such stimulation can activate small groups of neurons in the CN and achieve selective activation of tonotopic regions in higher auditory centers (inferior colliculus). A penetrating auditory brainstem implant (PABI) is shown in Figure 82-6. The figure shows that isofrequency regions run at a shallow angle (almost parallel) to the VCN surface. After 12 years of basic research, placement of the array into the VCN in two patients was done in late 2003. Testing showed that discrete pitch activation was possible, as well as improved speech recognition with the PABI. Clinical trials of this device are continuing.

DCN

stabilizers stimulating electrodes

Electrode-Specific Pitch VCN

cable

2 mm

low

1.5 mm 2.5 mm

3 mm

medium

4 mm

high

4 mm

We have observed patterns of pitch variation across ABI electrodes.18 A primary pattern is for pitch to increase in a lateral-to-medial direction across the array. A smaller group of patients shows a tendency for pitch to decline or remain constant across the array. Even with a surface electrode array, there appears to be at least partial access to the tonotopic gradient within the CN. Significant time was spent in ABI processor programming evaluating and quantifying pitch perceptions to provide place-related spectral cues in a fashion similar to cochlear implants. In patients with such perceptions, electrodes that did not sound distinctly different were

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2 mm

stump of cochlear nerve

electrode array

Figure 82-6. Schematic of penetrating auditory brainstem implant electrode array in place in the matrix of the ventral cochlear nucleus (VCN) showing potential electrode contact with frequency-tuned fiber tracts (high, medium, and low). DCN, dorsal cochlear nucleus.

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An investigational device exemption has been issued for PABI clinical trials by the FDA. A surface electrode will be incorporated into the PABI, which will allow a direct comparison between the two types of arrays. Use of ABI systems is also being evaluated in congenital malformation of inner ear structures, bilateral transverse temporal bone fractures, and also cases of complete cochlear ossification. Such devices as the ABI, neural implants for vision loss, and deep brain stimulators to treat Parkinson’s disease will provide real benefits as well as basic knowledge about the function of the human central nervous system.

SUMMARY Selective electrical stimulation of the human auditory brainstem with a prosthetic device has been shown to be safe and effective in hundreds of patients with NF-2. Experience in the implantation and programming of the device is necessary to maximize the probability of success. Adequate preoperative counseling of patients is necessary to ensure reasonable expectations, to describe the potential effects of secondary factors (such as health and vision), and to properly prepare them for the possible outcomes of implantation. ABI devices and patients require more time to manage effectively than cochlear implants. Nonauditory sensations, when present, can typically be managed. Assessment and proper use of electrode-specific pitch information can contribute to benefit. Speech perception testing is valuable in assessing the effect of programming changes and monitoring performance over time. Improvements in performance, which in most cases compares with that for singlechannel cochlear implants, can continue for many years with regular device use. A few ABI recipients demonstrate cochlear implant-like sound-only speech recognition. New penetrating microelectrode designs and new speech processing strategies hold promise of improved performance and will soon be evaluated in humans. As use of the multichannel ABI expands, it is hoped that the device will continue to be used effectively and appropriately and will become more readily available to those for whom it was developed.

REFERENCES 1. Hitselberger WE, House WF, Edgerton BJ, et al: Cochlear nucleus implant. Otolaryngol Head Neck Surg 92:52, 1984. 2. Edgerton BJ, House WF, Hitselberger WE: Hearing by cochlear nucleus stimulation in humans. Ann Otol Rhinol Laryngol 91(Suppl):117, 1984. 3. Eisenberg LS, Maltan AA, Portillo F, et al: Electrical stimulation of the auditory brain stem structure in deafened adults. J Rehab Res Dev 24:9, 1987. 4. Waring MD: Electrically evoked auditory brainstem response monitoring of auditory brainstem implant integrity during facial nerve tumor surgery. Laryngoscope 102:1293, 1992.

5. Waring MD: Intra-operative electrophysiological monitoring to assist placement of auditory brainstem implant. Annals Otol Rhinol Laryngol 104(9)(Suppl)166:33, 1995. 6. Waring MD: Auditory brainstem responses evoked by electrical stimulation of the cochlear nucleus in human subjects. Electroencephalogr Clin Neurophysiol 96:338, 1995. 7. Brackmann DE, Hitselberger WE, Nelson RA, et al: Auditory brainstem implant I: Issues in surgical implantation. Otolaryngol Head Neck Surg 108:624, 1993. 8. Shannon RV: A model of safe levels for electrical stimulation. IEEE Trans Biomed Engr 39:424, 1992. 9. McDermott HJ, McKay CM, Vandali AE: A new portable sound processor for the University of Melbourne/Nucleus multielectrode cochlear implant. J Acoust Soc Am 91:3367, 1992. 10. Otto SR, Staller S: The multichannel auditory brainstem implant: Case studies comparing fitting strategies and results. Annals Otol Rhinol Laryngol 104(9)(Suppl)166:36, 1995. 11. Otto SR, Ebinger K, Staller SJ: Clinical trials with the auditory brainstem implant. In Waltzman S, Cohen N (eds.): Cochlear Implants. New York, Thieme Medical Publishers, 2000, pp 357–366. 12. Brackmann DE, Fayad JN, Slattery WH 3rd, et al: Early proactive management of vestibular schwannomas in neurofibromatosis type 2. Neurosurgery 49(2):274, 2001. 13. Monsell EM, McElveen JT, Hitselberger WE, et al: Surgical approaches to the human cochlear nuclear complex. Am J Otology 8(5):450, 1987. 14. Shannon RV, Fayad J, Moore J, et al: Auditory brainstem implant: II. Postsurgical issues and performance. Otolaryngol Head Neck Surg 108:634, 1993. 15. Otto SR, Shannon RV, Brackmann DE, et al: The multichannel auditory brainstem implant: Performance in 20 patients. Otolaryngol Head Neck Surg 118:291, 1998. 16. Laszig R, Marangos N, Sollmann WP, et al: Central stimulation of the auditory pathway in neurofibromatosis type 2. Ear Nose Throat J 78:110, 1999. 17. Nevison B, Laszig R, Sollmann WP, et al: Results from a European clinical investigation of the Nucleus multichannel auditory brainstem implant. Ear Hear 23:170, 2002. 18. Otto SR, Brackmann DE, Hitselberger WE, et al: Multichannel auditory brainstem implant: Update on performance in 61 patients. J Neurosurg 96:1063, 2002. 19. Vincent C, Zini C, Gandolfi A, et al: Results of the MXM Digisonic auditory brainstem implant clinical trials in Europe. Otol Neurotol 23:56, 2002. 20. Ebinger K, Otto S, Arcaroli J, et al: Multichannel auditory brainstem implant: US clinical trial results. J Laryngol Otol (Suppl) 27: 50, 2000. 21. Fishman K, Shannon RV, Slattery WH: Speech recognition as a function of the number of electrodes used in the SPEAK cochlear implant speech processor. J Speech Hear Res 40:1201, 1997. 22. Shannon RV, Zeng FG, Wygonski J: Speech recognition with altered spectral distribution of envelope cues. J Acous Soc Am 104:2467, 1998. 23. Fu QJ, Shannon RV: Recognition of spectrally degraded and frequency-shifted vowels in acoustic and electric hearing. J Acous Soc Am 105:1889, 1999. 24. Friesen L, Shannon RV, Baskent D, et al: Speech recognition in noise as a function of the number of spectral channels: Comparison of acoustic hearing and cochlear implants. J Acous Soc Am 110(2): 1150, 2001. 25. McCreery DG, Shannon RV, Moore JK, et al: Accessing the tonotopic organization of the ventral cochlear nucleus by intranuclear microstimulation. IEEE Trans Rehab Eng 6:391, 1998.

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Outline Introduction Physiologic Rationale for Vestibular Rehabilitation Central Nervous System Plasticity Static Compensation for Peripheral Vestibular Lesions Dynamic Compensation and Decompensation Therapeutic Implications Assessment of Vestibular Compensation Role of the Clinical History Role of Vestibular Testing Evaluating Physiologic Compensation Evaluating Functional Compensation Evaluation of Motor Output System Vestibular Rehabilitation: Patient Selection Criteria

Chapter

Vestibular and Balance Rehabilitation

Vestibular Rehabilitation as a Primary Treatment Modality Vestibular Rehabilitation as Adjunctive Modality Vestibular Rehabilitation as Therapeutic Trial Inappropriate Candidates Vestibular Rehabilitation: Common Techniques Adaptation Exercises Habituation of Pathologic Responses Postural Control Exercises Visual-Vestibular Interaction Conditioning Activities Maintenance of Initial Results Role of Therapist in Patient Education Vestibular Rehabilitation: Expected Results Vestibular Rehabilitation: Role of the Neurotologist

INTRODUCTION Most patients who suffer an acute vestibular crisis recover nicely with only supportive care. However, some patients develop ongoing symptoms of positional vertigo, dysequilibrium, or lightheadedness that may become quite disabling. Although the concept of using vestibular exercises to provide relief of persistent symptoms has received some attention for many years, customized vestibular rehabilitation therapy (VRT) programs were not formalized or widely available until the 1990s. This modality has its roots in physical therapy, prospering initially in multidisciplinary settings where therapists collaborated with neurotologists, neurologists, and sophisticated vestibular testing facilities. There are now a sufficient number of prospective controlled studies to demonstrate both the efficacy and cost-effectiveness of vestibular rehabilitation.1 As such, this treatment has become widely available in recent years and is now the primary treatment modality for a large percentage of patients with complaints of imbalance and dizziness.

Steven A. Telian, MD Neil T. Shepard, PhD

PHYSIOLOGIC RATIONALE FOR VESTIBULAR REHABILITATION Central Nervous System Plasticity A unique feature of the central nervous system (CNS) is its ability to adjust to asymmetries in peripheral vestibular afferent activity and, to a somewhat lesser degree, to fixed insults within the central vestibular pathways.2 This adjustment process is referred to as vestibular adaptation and results from a neurologic property known as adaptive plasticity. Such plasticity requires active neuronal changes in the cerebellum and the brainstem nuclei in response to the sensory conflicts produced by central or peripheral vestibular pathology. In most instances, this process will reliably relieve vestibular symptoms, provided that the lesion is either stable or producing only gradual progressive deterioration. This chapter is devoted to the physiologic basis for vestibular compensation and how this remarkable plasticity of the nervous system can be exploited for the benefit of patients suffering from vertigo and disorders of 1331

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equilibrium. The interested reader is also referred to the chapters in this text devoted to vestibular physiology as an aid to understanding this material.

Static Compensation for Peripheral Vestibular Lesions Vertigo of acute onset usually results from pathology associated with the vestibular nerve or the labyrinth. Such vertigo is accompanied by nystagmus and a variety of undesirable neurovegetative symptoms, such as nausea and vomiting. Initially, the vertigo and nystagmus are present despite attempts at visual fixation suppression. Rather than indicating pathology of the central system, this finding simply reflects the dramatic disparity in the afferent activity in the vestibular nerve immediately after an acute lesion. The nystagmus intensity typically increases when visual fixation is removed. As the acute phase of compensation for the peripheral vestibular insult proceeds, the subjective symptoms are greatly reduced and the nystagmus diminishes until it can be observed only when visual fixation is eliminated. This occurs initially by a tonic rebalancing of the resting activity in the vestibular nuclei. The changes produced are designed to minimize side-to-side discrepancies among the tonic firing rates in the second-order neurons originating in the nuclei. The inhibitory activity of the cerebellum was initially shown in animal models to dramatically reduce the output from both nuclei, but subsequent studies have demonstrated that the cerebellum is not essential in the acute phase of compensation.2–6 This apparently intrinsic ability of the vestibular nucleus to rebalance tonic firing rates in the setting of an acute peripheral lesion is known as static compensation and generally provides relief from the most intense symptoms of vertigo and vomiting within 24 to 72 hours. Nevertheless, the patient continues to have considerable dysequilibrium, because the system is unable to respond appropriately to the dynamic aspects of vestibular input produced by normal head motions. Thus, even after the intense vertigo has been controlled, it is common to have continued motion-provoked vertigo until dynamic compensation is achieved.

Dynamic Compensation and Decompensation To eliminate persisting disequilibrium and residual motion-provoked vertigo after a vestibular lesion, the system must adjust to produce accurate responses to head movements. This dynamic compensation phase of vestibular adaptation appears to be accomplished by reorganization of brainstem and cerebellar pathways, without modulating the neural input to the vestibular nuclei from the peripheral system.2 This process is much slower than static compensation and may take up to several weeks to be complete. If the peripheral lesion is extensive, the ipsilateral vestibular nucleus becomes responsive to changes in the contralateral eighth nerve firing rate by activation of commissural pathways. In this instance, the entire central vestibular response is produced from the one functioning labyrinth. This feature of the compensation process is critical to recovery following ablative vestibular surgery, such as labyrinthectomy or vestibular nerve section.

Adaptation is the neurologic mechanism primarily used to facilitate dynamic compensation. The neural signals that induce the adaptation are primarily generated by “retinal slip” of the visual image on the retina. This phenomenon is generated by a disordered VOR response, when a head movement produces a perceived motion of an object that is stable in the visual environment. The resulting error signal can lead to fairly prompt and long-term changes in the vestibulo-ocular reflex.7 Full-field optokinetic stimuli may also assist in this process even without head movement. This process of adaptation produced by retinal slip appears to be context dependent, so that specific adjustments must be made for movements of different frequency, directions of head movement, eye position in the orbit, and distances from the visual target.8,9 This illustrates the complexity of the vestibular adaptation process and why residual symptoms are almost unavoidable even in a fairly well compensated individual. If a peripheral lesion is incomplete, the injured labyrinth may produce disordered responses to movements, requiring adjustments in the central system to properly reinterpret the input from the damaged side. This latter process is known as habituation.10 Habituation is the long-term reduction of a response to a noxious stimulus occurring in response to repeated exposure to the stimulus. This phenomenon appears to be context dependent and does not generalize from one head movement to another. This mechanism is essential for a variety of conditions that can produce sensitivity to head movement or motion in the visual surroundings. Although peripheral asymmetry is one common cause of these symptoms, other common causes are central lesions, anxiety disorders, and migraine.11 Although the adjustments produced by habituation are made fairly quickly and are reasonably accurate, the central system requires consistency in the inputs to properly use them for habituation. For this reason, it is essentially impossible to “compensate” for an unstable vestibular lesion. This explains the lack of utility for vestibular rehabilitation in the setting of active Ménière’s disease or perilymphatic fistula. The primary goals of both adaptation and habituation are to produce gaze stability and postural stability in both static and dynamic situations. The response frequency ranges for gaze and postural stability are very different. To achieve gaze stability, the responsible mechanisms must function properly in a range from static position (no motion) up to movements that correlate with head motions as quick as 10 Hz. Postural stability is predominantly a task that requires responsiveness only below 4 Hz.12,13 In addition to adaptation and habituation, another critical component of dynamic compensation involves sensory substitution. This process requires the adoption of alternative strategies for gaze and postural control to replace the lost or compromised sensory function. For example, the individual with bilateral loss of peripheral vestibular function becomes primarily dependent on visual or proprioceptive inputs to maintain postural stability. Although these mechanisms typically need to be developed by the patient in a therapeutic setting, many patients will have developed some of these via trial and error out of necessity prior to coming for evaluation. Although sensory substitution may be very helpful, it also may be maladaptive in some environmental settings, such as the patient who is overly dependent on vision and cannot use proprioceptive and

Vestibular and Balance Rehabilitation

residual vestibular inputs to successfully navigate in darkness. In addition to the common substitution of visual and proprioceptive inputs, some of the other mechanisms that may be useful in the setting of vestibular loss include (1) activation of the cervical-ocular reflex, which is not particularly active in humans14; (2) use of the smooth pursuit tracking system15; and (3) use of saccades. Patients with both unilateral and bilateral vestibular deficits use corrective saccades to adjust for the reduction of VOR-induced eye movements after head movement. With central preprogramming through exposure to specific eye-head coordinated movements, one can automatically use these eye movements to help maintain gaze stability when the VOR is deficient.16,17 It appears that the initial central compensation process is enhanced by head movement but delayed by inactivity.18–21 It is also hampered by preexisting or concurrent central vestibular dysfunction.22 Medications, such as meclizine, scopolamine, and benzodiazepines, that are typically used for controlling acute symptoms of vertigo all cause sedation and central nervous system depression. Although they may provide satisfactory relief during the initial stages of an acute labyrinthine crisis, they are potentially counterproductive with respect to central vestibular compensation, especially if used for extended periods of time.19,23 In addition, chronic anxiety or other psychiatric disorders may delay or disrupt the compensation process.24,25 Although remarkably reliable, central vestibular compensation appears to be a somewhat fragile, energy-dependent process. Even after it is apparently complete, there may be periods of symptomatic relapse due to decompensation. A period of inactivity, extreme fatigue, change in medications, or an intercurrent illness may trigger these relapses. A relapse of vestibular symptoms in this setting does not necessarily imply ongoing or progressive labyrinthine dysfunction.

Therapeutic Implications The features of central compensation reviewed earlier suggest that avoidance of movements and body positions that provoke vertigo, as well as the traditional practice of prescribing vestibular suppressants for these patients, may be inappropriate. Because the stimulus for recovery seems to be repeated exposure to the sensory conflicts produced by movement, once the severe acute symptoms are resolved, the patient’s medications should be discontinued and an active program toward recovery should be encouraged. For most individuals, recovery will be rapid and nearly complete. For some, the symptoms of vestibular dysfunction may persist. These are the candidates for vestibular rehabilitation programs. These programs are helpful in fostering the mechanisms of vestibular compensation previously discussed, including adaptation, habituation, and sensory substitution.

ASSESSMENT OF VESTIBULAR COMPENSATION Role of the Clinical History A complete neurotologic history is probably the single most important component in the diagnostic evaluation of

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a balance disorder. Balance function study results must be interpreted in light of the presenting symptoms and medical history.26 In general, the information sought should include the onset of symptoms and their characteristics at that time, the progression of symptoms over time, the nature and duration of typical spells, any predisposing factors in the past medical history, and use of medications or other management strategies. Complicating features of anxiety, depression, or excessive dependence on medications should be elucidated and addressed. Some effort should be extended to understand the degree of disability produced by the patient’s vestibular complaints with respect to their professional and social activities. The stability and commitment of their psychological support system should also be addressed. Regarding the patient’s suitability for vestibular rehabilitation, the physician must determine that the symptoms are consistently present and that any intense vertigo is primarily motion provoked, as opposed to spontaneous spells without clear provocative factors. There should be no strong evidence for fluctuating or rapidly progressive labyrinthine dysfunction. Patients who are seeking disability compensation may be disinclined toward faithful participation in vestibular rehabilitation.

Role of Vestibular Testing The purpose of balance function studies encompasses three major goals. The most traditional is site-of-lesion localization addressing sensory input elements, motor output elements, or neural pathways that may be involved in producing the reported symptoms. Second, an assessment of the patient’s functional ability to use the sensory input systems in an integrated fashion is completed. This involves maintenance of stance before and after induced sway, and coordination of head and eye movements during gaze activities. The third assessment goal is to evaluate the current degree of physiologic and functional vestibular compensation, factors that will be critical in determining if the patient is an appropriate candidate for rehabilitation therapy. A wide variety of studies may be used to assess the balance system in the broadest sense. Although expensive vestibular testing technology certainly contributes to a better diagnostic assessment of a balance disorder, the principles of these studies can be applied, at least qualitatively, at the bedside and in laboratories of limited size and technical capability. When the predictive utility of the various vestibular tests are reviewed, no significant correlation is evident with the performance of high-level activities of daily living.2 Tests used to determine the extent and site of vestibular lesions are unable to predict the type of vestibular symptoms, the magnitude of those symptoms, or the level of disability of an individual patient. Thus, a therapist can and must proceed with an evaluation of these factors irrespective of the vestibular test results.

Evaluating Physiologic Compensation Clinically significant spontaneous nystagmus, positional nystagmus, or a directional preponderance on traditional electronystagmography (ENG) provide evidence for failure of physiologic compensation in the vestibulo-ocular reflex. Rotational chair testing stimulates the horizontal semicircular canals and their afferent inputs over a broad

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range of frequencies and accelerations. Although this is a physiologic rather than a functional evaluation, it provides information about the vestibulo-ocular system that is not obtained from the traditional ENG. In general, although abnormalities in the timing (phase lead) or amplitude (gain) of the eye movements produced by the vestibulo-ocular reflex provide evidence for peripheral vestibular dysfunction, they do not address the issue of compensation within the central system.27 On the other hand, persistent asymmetry (bias) in the slow-phase eye velocity responses produced by rightward versus leftward rotation strongly suggests that the peripheral lesion is physiologically uncompensated. The nature of the rotational stimulus also allows for testing of visual-vestibular interactions, such as enhancement or suppression of the VOR, assisting in the evaluation of the status of the central vestibulo-ocular pathways. Abnormalities in these measures may help to explain an observed lack of central compensation.

Evaluation of Motor Output System

Evaluating Functional Compensation

The use of vestibular rehabilitation therapy (VRT) in the treatment of benign paroxysmal positional vertigo (BPPV) is well accepted. The use of noncustomized programs such as Cawthorne exercises has a long and fairly successful history for the management of this problem.18,30,31 For many patients, the commonly prescribed Cawthorne program is too intensive and often provokes intense vestibular symptoms, sometimes accompanied by nausea or vomiting. This discourages the patient from continuing. A preferred noncustomized program for BPPV that addresses the needs of most patients is the Brandt-Daroff program.18 An alternative approach for the treatment of classic BPPV due to otoconia free in one of the semicircular canals (canalithiasis), is to perform an appropriate particlerepositioning maneuver.32 When these techniques are insufficient to bring relief, it is appropriate to refer the patient to a vestibular therapist for a customized program.33 The use of VRT as the primary treatment recommendation is appropriate in any condition characterized by a stable unilateral peripheral vestibular deficit when the patient’s natural compensation process is incomplete. Many times, a patient who has previously suffered an acute peripheral insult such as vestibular neuritis will have continued disability due to incomplete compensation. If the medical evaluation reveals no evidence of a progressive process, it is likely that VRT will produce a satisfactory resolution of symptoms. This intervention is certainly preferable to long-term use of vestibular suppressants. Similarly, a VRT evaluation is also indicated for patients with stable bilateral peripheral dysfunction.34 The final indication for the use of VRT as a primary treatment modality is for disorders characterized by multifactorial balance difficulties, such as those seen in the elderly.35 This becomes especially important when other treatment options are unavailable or have been exhausted. These individuals may benefit greatly from postural control exercises and individualized conditioning programs. Frequently the relationship with the therapist assumes a strong counseling function, and the use of assistive devices for safety in ambulation can be introduced as needed.

Dynamic posturography provides adjunctive information about balance system function that is not available through the other vestibular testing modalities. The sensory organization portion of dynamic posturography is primarily a test of functional capabilities rather than a site-of-lesion evaluation. By measuring the degree of postural sway under several test conditions, this test determines whether the patient is able to make proper use of sensory inputs from the visual, vestibular, and somatosensory systems for maintaining stable stance. It can document pathology in the vestibular system, but does not distinguish between peripheral and central lesions. It may also demonstrate sensory preference abnormalities, in which the incorrect conflicting sensory cues are selected inappropriately. The more common patterns of abnormalities are vestibular dysfunction pattern (abnormal sway when using vestibular input alone); visual and vestibular dysfunction pattern (abnormal sway when using vestibular inputs, even with accurate visual input); visual preference pattern (abnormal sway when presented with visually inaccurate information, despite accurate somatosensory or vestibular input); somatosensory and vestibular dysfunction pattern (abnormal sway when using vestibular input despite accurate foot support surface cues); and severe dysfunction pattern (abnormal sway under almost all test conditions). It is not unusual to observe normal sensory organization findings in patients who report only motion-provoked symptoms and show no signs of pathologic nystagmus or significant asymmetry on rotational chair testing. In contrast, some patients will demonstrate significant abnormalities of postural control, documenting inadequate functional compensation, even when the more physiological measures (ENG and rotational chair) suggest complete compensation. In addition to providing information about the patient’s ability to use the available sensory information, posturography may identify environmental conditions in which the patient is at risk for falling. This information is helpful in patient counseling and design of the rehabilitation program.

The movement coordination battery of dynamic posturography may be used to assess the automatic motor output from the central nervous system in response to perturbations of stance. Abnormalities detected may help to explain findings in the sensory organization test, especially the somatosensory and vestibular dysfunction pattern. It may also provide indications of previously undiagnosed peripheral neuropathy or biomechanical deficits resulting from known musculoskeletal conditions.28,29

VESTIBULAR REHABILITATION: PATIENT SELECTION CRITERIA Vestibular Rehabilitation as a Primary Treatment Modality

Vestibular and Balance Rehabilitation

Vestibular Rehabilitation as Adjunctive Modality Several situations may require the use of VRT interventions as an adjunctive treatment modality. The use of routine or selective VRT is helpful in optimizing the outcome following ablative vestibular surgery, such as labyrinthectomy or vestibular nerve section, and in some instances after intratympanic aminoglycoside administration for Ménière’s disease. When a patient with an unstable vestibular condition undergoes an ablative procedure, a more profound, yet stable, unilateral vestibular lesion is created. The process of acute and chronic compensation must begin anew. It is possible that many of the unsatisfactory outcomes following vestibular surgery can be attributed to incomplete or delayed postoperative compensation. All patients should be instructed regarding the importance of central compensation for the success of any ablative vestibular procedure. It is appropriate for the therapist to offer counseling and general instructions to these patients, as well as those who undergo resection of a vestibular schwannoma or other temporal bone tumors that result in an abrupt unilateral loss of residual vestibular function. Any patients who demonstrate a particularly slow recovery should be referred for customized VRT. Those individuals who are at particular risk for poor recovery because of complicating CNS conditions, sedating medications, or poor motivation for recovery should be encouraged to pursue a customized program of VRT early in their postoperative course. Vestibular rehabilitation may play a role in other conditions that include a component of balance complaints.11,36 Frequently, patients who have suffered head injuries have significant disability from vestibular symptoms. Because their conditions often include cognitive and central vestibular involvement along with the peripheral component, VRT techniques are best used as a supplement to a comprehensive, multidisciplinary head injury program, rather than as the primary rehabilitative measure. Similarly, patients with panic disorder and other anxiety disorders often present seeking management of ill-defined vestibular symptoms. After a suitable evaluation is performed, VRT may be recommended as an adjunctive measure for their condition. If the anxiety is mild, VRT functions as a behavioral intervention similar to exposure therapy for treatment of phobias. If the anxiety component is significant, and particularly if panic attacks are frequent, psychiatric intervention will be required as well. Rarely, patients with Ménière’s disease will complain of positional vertigo or other chronic vestibular complaints between their definitive attacks. Although such patients are candidates for VRT, they must proceed with the understanding that the prognosis for lasting relief of chronic symptoms is reduced if the typical severe attacks of Ménière’s disease occur more than monthly. If the attacks are rare, or the Ménière’s disease is inactive, the prognosis is considerably improved.

Vestibular Rehabilitation as Therapeutic Trial Often the physician is uncertain whether the patient’s complaints are due to stable vestibular disease with inadequate

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central compensation or to unstable labyrinthine function. In this setting, a trial of VRT is appropriate and functions to assist in the diagnosis by clarifying this important distinction. Failure to improve in VRT lends further credibility to the diagnostic impression that the lesion is unstable or progressive. It is then suitable to proceed with appropriate surgical management if the symptoms are severe enough to warrant the procedure. This line of treatment is appropriate prior to considering ablative vestibular surgery. Until the preoperative diagnostic criteria for perilymph fistula become clarified, it is appropriate to defer surgical exploration until after a trial of VRT, unless the hearing is clearly endangered. This course is particularly appropriate prior to considering surgical interventions for more avant garde diagnoses such as spontaneous perilymph fistula.37 It is sometimes difficult to determine if a postoperative relapse of vestibular symptoms represents disease progression or merely central decompensation.38 Decompensation may be observed as a late sequela following initially complete compensation for any peripheral lesion, including vestibular surgery. For example, many surgeons consider transmastoid labyrinthectomy to be a definitive procedure for the control of vertigo of peripheral origin. Thus, one must explain why failures occur. Early failures are best attributed to incorrect diagnosis, incomplete removal of the neuroepithelium at the time of surgery, or inadequate CNS compensation. Late failures have been hypothesized to result from “postlabyrinthectomy neuromas.”39,40 Although there is little reason to expect that such lesions could produce symptoms, some surgeons would advocate a vestibular neurectomy in this setting. An alternative explanation for these recurrent symptoms after a complete labyrinthectomy would be late central decompensation, which should respond quickly to VRT. Instead of proceeding to additional surgery, a therapeutic trial of VRT is suitable whenever the possibility of incomplete compensation or decompensation remains.

Inappropriate Candidates Patients whose symptoms occur strictly in spontaneous, discrete episodes, such as seen with Ménière’s disease, are unlikely to benefit from customized VRT. If no body movements or positions reliably provoke spells, and no postural control abnormalities are noted during the evaluation, the patient is best treated with alternative medical or surgical strategies. Nonetheless, such patients should be encouraged to remain active and optimize their general health through physical activities performed at a level that is appropriate for their age and general health.

VESTIBULAR REHABILITATION: COMMON TECHNIQUES The vestibular rehabilitation therapist employs a variety of techniques when providing a program customized to the needs of the individual patient. For a complete discussion of the diagnostic and therapeutic interventions that may appropriately be performed by the therapist, the interested reader is referred to other resources for further reading.41,42

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This section of the chapter will review several general categories that are addressed in a customized program of VRT.

Adaptation Exercises The principal goal of adaptation exercises is the improvement in the VOR gain and accompanying gaze stability for those who demonstrate a VOR deficit physiologically and who have predictable symptoms provoked by head movements. Evidence of a VOR deficit may include a caloric response asymmetry on ENG or an abnormal time constant on rotary chair testing. The activities primarily involve VOR times 1 and times 2 viewing exercises described elsewhere.11,41

Habituation of Pathologic Responses For most patients with positionally provoked symptoms, the primary goal is to extinguish the pathologic responses that remain due to incomplete or disordered compensation. The therapist identifies the typical movements that produce the most intense symptoms and provides the patient with a list of exercises that reproduce these movements. These are performed twice daily, unless limited by severe nausea or dizziness. The patients are counseled that symptoms typically are aggravated by the exercises at first, but that gradual improvement will follow. Patients are often encouraged by experiencing short-term habituation at the end of an exercise session. If they can persevere with their program, most patients will begin to note dramatic relief of positional vertigo within 4 to 6 weeks. There is obviously significant overlap between these and the adaptation activities. The details of the techniques differ relative to speed, visual target, number of movements, and repetition. The underlying principle of habituation exercises is that of brief repeated exposures. This technique can also be used to reduce sensitivity to visual motion provoked symptoms, although that is a more difficult task.

Postural Control Exercises When abnormalities of postural control are detected in the assessment, these may be specifically addressed in the prescribed exercise program. Programs can be designed to correct weight-bearing asymmetries, limited mobility about the center of gravity, and sensory input selection problems. For example, if the patient is found to depend on somatosensory input despite the availability of accurate visual cues, the program may involve exercises that require balancing on thick foam. This would be performed initially with eyes open and eventually with eyes closed. Although working on static balance is one dimension of therapy, more complex gait activities over a short course (such as a 10- to 20-foot walk) are often prescribed. These may involve specific targeted activities such as stepping over objects or incorporating specific reciprocal head movements. The patient may also be asked to practice walking on different types of surfaces such as a compressible soft carpet or an irregular gravel parking lot. These activities are designed to enhance stability in daily activities. Patients with bilateral loss of vestibular function may be instructed to perform exercises that help with sensory

substitution. These may include having them walk in progressively more challenging lighting situations to facilitate somatosensory substitution or to balance on more challenging support services to facilitate visual substitution.

Visual-Vestibular Interaction For patients with bilateral vestibular paresis or disorders of visual-vestibular interaction, exercises may be required that optimize the use of the visual system inputs for maintaining equilibrium and gaze stability. These may be incorporated with hand-eye coordination exercises when needed.

Conditioning Activities Most patients with vertigo and balance disorders have adopted a sedentary lifestyle to avoid their symptoms. Although such a response is understandable, this decision contributes to their ongoing disability and delays their recovery. Thus, all patients who receive customized VRT programs are also provided with suggestions for a general exercise program that is suited to their age, health, and interests. For most individuals, this would involve at least a graduated walking program. For many, a more strenuous program is suggested that may include jogging, treadmill, aerobics, or bicycling. Activities such as golf, bowling, handball, or racquet sports, which involve coordinated eye, head, and body movements may be appropriate. Swimming is approached cautiously because of the disorientation experienced by many vestibular patients in the relative weightlessness of the aquatic environment.

Maintenance of Initial Results Once the patient has completed the initial period of treatment, progress is assessed and adjustments are made in the program. Exercises that no longer produce symptoms are eliminated and replaced by others that were not originally included because of lower priority. This process is continued until the improvements begin to plateau. When this point is reached, it is important to provide the patient with counseling and a program of maintenance exercises to ensure stability of the initial improvements. The maintenance program typically includes continuing the prescribed conditioning exercises, as well as any unique postural control activities that were required. The patient is instructed to resume the habituation exercises if a relapse of positional symptoms should occur.

Role of Therapist in Patient Education A key role of the therapist in the management of balance disorders is to educate patients about their illness. Considerable misinformation must often be addressed. This supportive function of the therapist is particularly essential for the treatment of patients with a less favorable prognosis. A patient who is well educated regarding the nature of vestibular dysfunction will understand the rationale for vestibular rehabilitation. They will recognize that these measures are simply a management technique instead of a cure for the underlying deficits. This orientation takes the patient from a passive role toward an active role in his or her own recovery.

Vestibular and Balance Rehabilitation

VESTIBULAR REHABILITATION: EXPECTED RESULTS A 2-year prospective clinical trial including all patients undergoing VRT at the University of Michigan suggested that one can expect a reduction of symptoms in approximately 85% of cases. Using a disability rating scale, 80% of patients gave lower disability scores after therapy.43 A subsequent controlled clinical trial provided strong evidence that VRT programs customized to the unique needs of the individual patient provided results that are superior to those obtained by generic programs of therapy.44 Whitney has provided a useful review of multiple published studies of VRT efficacy.1 The literature suggests that VRT is highly beneficial after unilateral surgical ablation of vestibular function. Similar results may be expected when treating fixed unilateral lesions such as vestibular neuritis and labyrinthitis. Treatment of canalithiasis causing classical BPPV using the particle-repositioning maneuver is effective in over 90% of cases, but the condition may recur in up to 30% of patients. Habituation exercises have been reported to yield similar results, but do not offer relief as promptly. Patients with bilateral vestibulopathy treated with VRT show significant improvements in speed of ambulation and stair negotiation, postural stability, and reaching distance compared with control subjects. Balance rehabilitation is of particular importance for the older adult with multiple sensory deficits, especially when other treatment options are not available. Many times the therapist also serves as a counselor and may need to make recommendations for strengthening activities and assistive devices. In general, the patients who have a poorer prognosis for improvement with VRT include those with severe bilateral peripheral lesions, combined central/peripheral vestibular deficits and headache syndromes following head injury, and those with established long-term disability. Although some elderly patients may progress poorly due to irreversible multisensory dysfunction, the overall experience with this group has been favorable. The concurrent use of vestibular suppressant medication or other centrally acting agents has been shown to delay the time course of recovery during VRT. Whenever possible, these medications should be tapered to lower doses or discontinued completely. On the other hand, they may be continued if they are essential for treatment of complicating medical conditions or for relief of symptoms during the VRT program, because their use does not seem to dramatically reduce the chances of a satisfactory ultimate outcome.

VESTIBULAR REHABILITATION: ROLE OF THE NEUROTOLOGIST Most neurotologists now recognize the need to develop a successful program of vestibular rehabilitation to serve their patients. This is best pursued by assembling a qualified team of professionals including the neurotologist, vestibular testing personnel, and physical therapists specifically trained in vestibular assessment and treatment. A working relationship with insightful geriatric, neurologic, and psychiatric consultants is also very helpful. Optimally, the physical therapist will understand something of the

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diagnostic aspects of this discipline, as well as the strengths and limitations of conventional medical and surgical modalities. The neurotologist likewise must appreciate the role that the therapist can hope to play in the treatment of this challenging patient population. A mutually supportive and interactive environment is ideal for responding to the diverse needs encountered in a busy vestibular treatment program. The neurotologist will find that the time investment required for education and team development will pay considerable dividends in terms of treatment outcome and patient satisfaction.

REFERENCES 1. Whitney SL, Rossi MM: Efficacy of vestibular rehabilitation. In Shepard NT, Solomon D (guest eds.): Practical issues in the management of the dizzy and balance disorder patient. Otolaryngol Clin North Am 33(3):659–672, 2000. 2. Zee DS: Vestibular adaptation. In Herdman S (ed.): Vestibular Rehabilitation, 2nd ed. Philadelphia, FA Davis, 2000, pp 77–90. 3. Fetter M, Zee DS, Proctor LR, et al: Effects of lack of vision and of occipital lobectomy upon recovery from unilateral labyrinthectomy in the Rhesus monkey. J Neurophysiol 59:394–407, 1988. 4. Igarashi M: Vestibular compensation: An overview. Acta Otolaryngol (Stockh) 406 (Suppl):78–82, 1984. 5. McCabe BF, Sekitani T: Further experiments on vestibular compensation. Laryngoscope 82:381–396, 1972. 6. Schwarz DWF: Physiology of the vestibular system. In Cummings C, Fredrickson J, Harker L, et al (eds.): Otolaryngology-Head and Neck Surgery, vol. 3 (Chapter 144). St Louis, CV Mosby, 1986. 7. Shelhamer M, Tiliket C, Roberts D, et al: Short-term vestibuleocular reflex adaptation in humans. II. Error signals. Exp Brain Res 100:328–336,1994. 8. Clendaniel RA, Shelhamer M, Roberts T: Context specific adaptation of saccade gain. Soc Neurosci Abstr 25 (Part 1), 658, 1999. 9. Shelhamer M, Robinson,DA, Tan HS: Context-specific adaptation of the gain of the vestibule-ocular reflex in humans. J Vestib Res 2: 89–96, 1992. 10. Kandel ER, Schwartz JH: Principles of Neural Science. North Holland, Elsevier, 1982. 11. Shepard NT, Asher A: Treatment of patients with nonvestibular dizziness and disequilibrium. In Herdman S (ed.): Vestibular Rehabilitation, 2nd ed. Philadelphia, FA Davis, 2000, pp 534–544. 12. Grossman GE, Leigh RJ, Bruce EN, et al: Performance of the human vestibuloocular reflex during locomotion. J Neurophysiol 62:264–272, 1989. 13. Grossman GE, Leigh RJ: Instability of gaze during locomotion in patients with deficient vestibular function. Ann Neurol 27: 528–532, 1990. 14. Kasai T, Zee DS: Eye-head coordination in labyrinthine-defective human beings. Brain Res 144:123–141, 1978. 15. Leigh RJ, Huebner WP, Gordon JL: Supplementation of the human vestibule-ocular reflex by visual fixation and smooth pursuit. J Vest Res 4:347–353, 1994. 16. Branes GR: Visual-vestibular interaction in the control of head and eye movement: The role of visual feedback and predictive mechanisms. Prog Neurobiol 41: 435–472, 1993. 17. Crane BT, Demer JL: Human gaze stabilization during natural activities: Translation, rotation, magnification, and target distance effects. J Neurophysiol 78:2129–2144, 1997. 18. Brandt T, Daroff RB: Physical therapy for benign paroxysmal positional vertigo. Arch Otol Rhinol Laryngol 106:484–485, 1980. 19. Igarashi M, Ishikawa M, Yamane H: Physical exercise and balance compensation after total ablation of vestibular organs. Prog Brain Res 76:395–401, 1988.

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20. Lacour M, Xerri C: Vestibular compensation: New perspectives. In Flohr H, Precht W (eds.): Lesion Induced Neuronal Plasticity in Sensorimotor Systems. New York, Springer-Verlag, 1981. 21. Mathog RH, Peppard SB: Exercise and recovery from vestibular injury. Am J Otolaryngol 1982; 3:397–407. 22. Igarashi M, Levy JK, Reschke M, Kubo T, Watson T: Locomotor dysfunction after surgical lesions in the unilateral vestibular nuclei region in squirrel monkeys. Arch Otorhinolaryngol 221:89–95, 1978. 23. Peppard SB: Effect of drug therapy on compensation from vestibular injury. Laryngoscope 96:878–898, 1986. 24. Staab J: Diagnosis and treatment of psychologic symptoms and psychiatric disorders in patients with dizziness and imbalance. In Shepard NT, Solomon D (guest eds.): Practical issues in the management of the dizzy and balance disorder patient. Otolaryngol Clin North Am 33(3):617–636, 2000. 25. Yardley L: Overview of the psychologic effects of chronic dizziness and balance disorders. In Shepard NT, Solomon D (guest eds.): Practical issues in the management of the dizzy and balance disorder patient. Otolaryngol Clin North Am 33(3):603–616, 2000. 26. Baloh RW, Honrubia V: Clinical Neurophysiology of the Vestibular System, 2nd ed. Philadelphia, FA Davis, 1989. 27. Wall C: The sinusoidal harmonic acceleration rotary chair test theoretical and clinical basis. Neurol Clin 8:269–286, 1990. 28. Voorhees RL: Dynamic posturography findings in central nervous system disorders. Otolaryngol Head Neck Surg 103:96–101, 1990. 29. Voorhees RL: The role of dynamic posturography in neurotologic diagnosis. Laryngoscope 99:940–957, 1989. 30. Cawthorne T: The physiological basis for head exercises. J Chart Soc Physiother 30:106–107, 1944. 31. Cooksey FS: Rehabilitation in vestibular injuries. Proc Royal Soc Med 39:273–278, 1946. 32. Herdman S, Tusa R: Assessment and treatment of patients with benign paroxysmal positional vertigo. In Herdman S (ed.): Vestibular Rehabilitation, 2nd ed. Philadelphia, FA Davis, 2000, pp 451–475.

33. Smith-Wheelock M, Shepard NT, Telian SA: Physical therapy program for vestibular rehabilitation. Am J Otol 12:218–225, 1991. 34. Telian SA, Shepard NT, Smith-Wheelock M, Hoberg M: Bilateral vestibular paresis: Diagnosis and treatment. Otolaryngol Head Neck Surg 104:67–71, 1991. 35. Smith-Wheelock M, Shepard NT, Telian SA, Boismier T: Balance retraining therapy in the elderly. In Kashima H, Goldstein J, Lucente F (eds.): Clinical Geriatric Otolaryngology. Philadelphia, BC Decker, 1992, pp 71–80. 36. Shepard NT, Telian SA, Smith-Wheelock M: Balance disorders in multiple sclerosis: Assessment and rehabilitation. Semin Hear 11: 292–305, 1990. 37. Shepard NT, Telian SA, Niparko JK, et al: Platform pressure test in identification of perilymphatic fistula. Am J Otol 13:49–54, 1992. 38. Monsell EM, Brackmann DE, Linthicum FH: Why do vestibular destructive procedures sometimes fail? Otolaryngol Head Neck Neck Surg 99:472–479, 1988. 39. Linthicum FH, Alonso A, Denia A: Traumatic neuroma: A complication of transcanal labyrinthectomy. Arch Otol Rhinol Laryngol 105:654–655, 1979. 40. Ylikoski J, Belal A: Human vestibular nerve morphology after labyrinthectomy. Otolaryngol Head Neck Surg 99:472–479, 1988. 41. Herdman S (ed.): Vestibular Rehabilitation, 2nd ed. Philadelphia, FA Davis, 2000. 42. Shumway-Cook A, Horak FB: Rehabilitation strategies for patients with vestibular deficits. Neurol Clin 8:441–457, 1990. 43. Shepard NT, Telian SA, Smith-Wheelock M, Raj A: Vestibular and balance rehabilitation therapy. Ann Otol Rhinol Laryngol 102: 198–205, 1993. 44. Shepard NT, Telian SA: Programmatic vestibular rehabilitation. Otolaryngol Head Neck Surg 112:173–182, 1995.

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Outline Reasons for Eye Problems After Facial Paralysis Ocular Functions of the Seventh Nerve Ocular Functions of the Fifth Nerve Sixth Nerve Function Common Ocular Symptoms and Their Causes Seventh Nerve Involvement Symptoms Related to Dryness and Their Causes Why the Symptoms Occur Symptoms Related to Wetness and Their Causes Why the Symptoms of Early Excessive Tearing Occur Why the Symptoms of Late Excessive Tearing Occur Fifth Nerve Involvement Symptoms and Their Causes

Chapter

Ocular Treatment and Rehabilitation of the Patient with Facial Paralysis

Why the Symptoms Occur Sixth Nerve Involvement Eye Care Nonsurgical Care— Patient-Controlled Artificial Tears Eye Ointments Slow Release Ophthalmic Inserts (Lacriserts) Taping Protective Devices Protecting Against Ocular Irritants Being Aware of the Humidity Increasing Blinking Chewing Gum Nonsurgical Eye Care— Physician-Aided Bandage Contact Lens Temporary Lid Closure

Surgical Techniques to Improve Lid Position Canthoplasty Upper Lid Entropion Repair Fascia Lata Support of the Lower Lid Stent Support of the Lower Lid Tarsorrhaphy Surgical Techniques to Animate the Upper Eyelid Palpebral Spring Enhanced Palpebral Spring Silastic Elastic Prosthesis (Arion Cerlage) Gold Weights Surgical Elevation of the Brow Surgical Closure of the Tear Drainage System Summary

S

uccessful ocular management of facial paralysis may mean the difference between having a well-protected eye with good vision and having a permanently damaged eye with diminished vision. Even more, the difference may be between a rehabilitated patient who can get on with life and an ocular cripple who must devote an inordinate amount of energy to eye care. This chapter outlines the pathophysiology that results in the ocular symptoms and signs that require the attention of the physician caring for the facial paralysis patient. The chapter also provides a systematic approach for determining the appropriate modes of treatment.

REASONS FOR EYE PROBLEMS AFTER FACIAL PARALYSIS Cranial nerves V, VI, VII, and VIII all exit the brain in close proximity. Any combination of these nerves may therefore be affected by tumors in the cerebellopontine angle (CPA), such as schwannomas, meningiomas, cholesteatomas, hemangiomas, or metastatic tumors. Since the fifth, sixth, and seventh nerves are all concerned with functions necessary to the eye, it is not surprising that ocular complications are common with such tumors. Even when the lesion affects only the seventh nerve, lid function may be

Robert E. Levine, MD

compromised, resulting in ocular problems. Depending on the location of the lesion, the parasympathetic fibers that accompany the seventh nerve on their way to supply the lacrimal gland may also be involved, resulting in a dry eye.

Ocular Functions of the Seventh Nerve In addition to controlling the muscles used for facial expression and speech, the seventh nerve controls blinking and eyelid closure. The seventh nerve also provides the muscle tone necessary to hold the lower lid in position against the eyeball, and to pump the tears through their outflow system. Consequently, any damage to the seventh nerve will affect these functions. The nerve to the tear gland runs along with the facial nerve.

Ocular Functions of the Fifth Nerve It is well known that the fifth nerve supplies sensation to the face and to the cornea (the clear front surface of the eye). It is much less well appreciated, however, that the trigeminal nerve also has an important trophic function critical to the maintenance of tissue integrity and healing ability. For example, a cornea that has lost its fifth nerve supply may undergo spontaneous breakdown even in the presence of normal lid and tear functions. 1339

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Sixth Nerve Function The sixth nerve controls the lateral rectus muscle, the eye muscle that moves the eye on that side laterally (outward). When the sixth nerve is paretic, the eye may be unable to move from a markedly inturned position. Aside from the considerations of diplopia, the protection of an inturned eye in the presence of facial paralysis may present special problems.

COMMON OCULAR SYMPTOMS AND THEIR CAUSES Seventh Nerve Involvement Despite the importance of appreciating the role of other cranial nerves in causing ocular problems, the primary source of such problems in the facial paralysis patient is clearly a result of an impairment of one or more aspects of seventh nerve function. Symptoms Related to Dryness and Their Causes Dryness, Irritation, or a Mucoid Discharge The eye can feel scratchy, burning, or have the sensation of a foreign body present. It may be particularly sensitive to shampoo or particles of dust and sand. One might be bothered by air conditioning or other draft conditions, dry air, cold temperatures, or smoke. Symptoms can worsen as the day progresses. These symptoms are due to minimal irregularities on the front surface of the cornea, the corneal epithelium. Ocular Redness or Sensitivity to Light Generally these are symptoms of corneal irritation or inflammation of moderate or severe degree. Intermittent or Constant Blurring of Vision This results from significant roughness of the front surface of the cornea. Such roughness may represent epithelial irregularity, epithelial loss (corneal abrasion), or even damage to deeper tissues (corneal ulcer).

water layer, which comes from the tear gland; and the outer oil layer, which helps limit evaporation of tears. The middle tear layer (which makes up most of the volume of the tears) is reduced by damage to the nerve fibers to the tear gland. However, the other tear layers (which are produced by glands in the conjunctiva and eyelids) persist, often leaving the eye with a mucoid discharge. Because tears have antibacterial properties, a dry eye is also at increased risk of infection. Reduced Blinking or Incomplete Upper Lid Closure The movement of the upper lid distributes the tears across the front surface of the eye. If the upper lid does not move well or blink well, tears are poorly distributed. Poor Lower Lid Position If the upper lid is to function well as a windshield wiper to distribute tears, it must be able to pick up tears from the normal tear reservoir (called the tear lacus). This reservoir consists of a pool of tears that accumulates at the margin of the lower lid, where it contacts the eye. If the reduced muscle tone in the lower lid results in that lid’s being too low, or turned away from the eyeball (ectropion), the upper lid cannot pick up the tears to distribute them (whether those tears are normal or artificial tears). Also, a poorly positioned lower lid fails to protect adequately the lower aspect of the cornea. The inner aspect of the lid is lined with a mucous membrane (conjunctiva), which also becomes reddened, thickened, keratinized, and irritated if the lid is turned out. Occasionally, the loss of tone in the lower lid causes the lid margin to rotate inward (entropion), which causes the lashes to rub against the eye. Poor Upper Lid or Brow Position Loss of tone in the upper lid may cause the lid margin to rotate inward so that the lashes rub against the eye. Similarly, loss of tone in the forehead muscles can allow the eyebrow to droop. In some people with deep-set eyes, the hairs of the drooping brow may rub against the eyeball. Increased Evaporation of Tears

Why the Symptoms Occur The hydration or “wetness” of the front surface of the eye must be maintained at a certain critical level for the cornea to be optically clear and for the eye to feel comfortable. If that level is to be maintained, the right amount of tears must be produced, the tears must be distributed (by blinking) across the front surface of the eye, and the evaporation of tears must be limited by lid position and closure. Inadequate Tear Production This problem is usually caused by a deficiency in the water layer of the natural tear film, manufactured by the tear gland. The poor function of the tear gland (which is located under the rim of bone at the upper lateral aspect of the eye) is in turn related to the damage to its nerve supply, which accompanies the seventh nerve. The tear film consists of three layers: the inner mucin layer, which bonds the tears to the eye; the middle

The more area available for evaporation, the more rapidly the tears will evaporate. A wide open eye will therefore dry out more quickly than one less open. The eye may be excessively open because the lower lid is down or because the upper lid is up (higher than normal in the open position). Increased evaporation also occurs when the eye is open when it should be closed (e.g., during sleep). Symptoms Related to Wetness and Their Causes Early Excessive Tearing The eye is excessively wet and tears may drain down the cheek. The symptoms may start immediately after surgery or within the following few weeks. Late Excessive Tearing This can occur while chewing, usually beginning some months after surgery.

Ocular Treatment and Rehabilitation of the Patient with Facial Paralysis

Why the Symptoms of Early Excessive Tearing Occur Response to Corneal Irritation When the cornea is irritated and the tearing mechanism is intact (i.e., the nerve to the tear gland has not been damaged), extra tear production is the body’s normal protective mechanism to compensate for the irritation and to attempt to wash out the irritant. Failure of Lacrimal Drainage Excess tearing may also result from the inability of the eyelids to drain the tears properly. Tears do not just drain into the outflow channels (which are located at the lid margins, near the inner corners of the eyelids). Rather, they are pumped through the lacrimal canaliculi by the muscular contraction of the lids. This muscular mechanism is called the lacrimal pump. If the lid muscles are not working because of a loss of seventh nerve innervation, failure of the lacrimal pump allows the tears to overflow the lids and run down the cheek. Why the Symptoms of Late Excessive Tearing Occur Aberrant Regeneration of Nerve Fibers When the parasympathetic fibers accompanying the seventh nerve are damaged, each of the fibers needs to regrow. Unfortunately, the correct fiber ends do not always connect. If a fiber that is supposed to go to a salivary gland winds up connected to the tear gland, every time the normal reflex mechanism that causes chewing to produce saliva is activated, excess tears result instead of saliva.

Fifth Nerve Involvement Patients with fifth nerve involvement have decreased or totally absent corneal sensation.

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from the cornea to the brain, resulting in the brain’s returning an efferent signal to the eyelid to blink. The signal from the cornea to the brain is sent via the fifth nerve, and the return signal is sent via the seventh nerve. The brain also sends an efferent signal via the parasympathetic fibers that run along with the seventh nerve to the tear gland, telling the gland to produce extra tears to wash out the irritant. A patient with combined fifth and seventh nerve deficits, such as an acoustic neuroma patient, therefore, may have deficits that interfere with both the afferent and efferent aspects of this reflex. Loss of Trophic Function The fifth nerve has a role (referred to as its trophic function) in maintaining tissue integrity. The exact mechanism by which this occurs is poorly understood. It is very likely that the fifth nerve produces some chemical substance that is involved in the healing process and that the chemical substance travels down the nerve antidromically. Not only do corneas without fifth nerve supplies break down easily, they also heal poorly. One can thus readily understand why a patient with combined fifth and seventh nerve deficits must take special precautions to avoid ocular problems.

Sixth Nerve Involvement The sixth nerve controls the eye muscle that moves the eye on that side laterally (outward). Some patients whose facial paralysis is due to a tumor at the CPA have double vision (diplopia) immediately after surgery because sixth (abducent) nerve involvement associated with the tumor limits the normal lateral movements of the eye on the involved side. This problem usually resolves quickly, but improvement occasionally may be delayed. Rarely, the deficit persists for more than a year and requires eye muscle surgery. Fresnel prisms or occlusion of one eye may be required to eliminate diplopia until the sixth nerve recovers.

Symptoms and Their Causes Loss of Reflex Blinking and Tearing

EYE CARE

The patient does not feel when an irritant touches the cornea, and the eye does not attempt to blink or tear in response to the irritant.

Nonsurgical Care—Patient-Controlled

Loss of Pain as a Warning Sign

The simplest means of protecting the cornea is with the use of eyedrops. Some drops contain a single active ingredient such as methylcellulose, carboxymethylcellulose, polymeric agents, or polyvinyl alcohol. Others include a wetting agent to simulate more closely the normal tear film. The wetting agent functions in a manner similar to the mucinous inner tear layer—it helps bond the artificial tear to the cornea. In some cases, the use of a wetting agent as a separate drop in combination with an artificial tear drop may work better than a preparation containing both ingredients. Eyedrops also contain a variety of preservatives, some or all of which may be allergenic. Patients who experience irritation from a particular eyedrop may be comfortable with a similar drop prepared with a different preservative or no preservative. The thickness (viscosity) of an eyedrop may be increased to prolong its effect. More viscous drops, however, may

The patient with a numb cornea will not feel pain when the eye is injured and must be taught to look for other signs (e.g., redness or blurring of vision) that the eye has been injured. Ocular Redness A cornea that lacks fifth nerve supply may break down spontaneously (neurotrophic keratitis or ulceration), causing the eye to become inflamed. Why the Symptoms Occur Loss of Corneal Sensation Blinking is a reflex. Suppose an irritant, such as a foreign body, touches the cornea. An afferent pain signal is sent

Artificial Tears

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cause some blurring of vision and tend to crust on the lid. The patient and the ophthalmologist must work out a regimen of drops that will be best suited to the needs of that particular patient. A chart of common brand eyedrops is shown in Table 84-1.

TABLE 84-1. Artificial Tear Preparations and Eye Ointments Trade Names

Ingredients

Artificial Tears Long acting, high viscosity Celluvisc Murocel Visculose 1% Long acting, medium viscosity Adsorbotear Refresh Plus Medium duration, medium viscosity Isopto Tears Lacril Liquifilm Forte Lubrifair Solution Lyteers Moisture Drops Tearisol Tears Naturale II Tears Naturale Free Visculose 0.5% Short duration, low viscosity AKWA Tears Solution Hypotears Hypotears PF Liquifilm Methulose Ocu-Tears Refresh Tearfair Solution Tears Plus

Carboxymethylcellulose 1%* Methylcellulose 1% Methylcellulose 1% Hydroxyethylcellulose, povidone 1.67% with water soluble polymers Carboxymethylcellulose 0.5%* Hydroxypropyl methylcellulose 0.5% Hydroxypropyl methylcellulose 0.5%, gelatin A 0.01% Polyvinyl alcohol 3% Hydroxypropyl methylcellulose, Dextran 70 Cellulose derivative Hydroxypropyl methylcellulose 0.5%, Dextran 30 Hydroxypropyl methylcellulose 0.5%, boric acid Hydroxypropyl methylcellulose 0.3% in water-soluble polymeric system Hydroxypropyl methylcellulose 0.3% in water-soluble polymeric system* Methylcellulose 0.5% Polyvinyl alcohol Polyvinyl alcohol 1% in Lipiden polymer Polyvinyl alcohol 1% in Lipiden polymer* Polyvinyl alcohol 1.4% Methylcellulose 0.25% Polyvinyl alcohol Polyvinyl alcohol 1.4%, povidone 0.6* Polyvinyl alcohol Polyvinyl alcohol 1.4%, povidone 0.6%

Ocular Lubricants (Ointments) AKWA Tears Ointment Duolube Duratears Naturale Hypotears Ointment Lacri-lube NP Lacri-lube S.O.P. Lubrifair Ocu-Lube Petrolatum Refresh P.M. Tearfair

White petroleum, mineral oil* White petroleum, mineral oil* White petroleum, anhydrous liquid lanolin* White petroleum, light mineral oil* White petroleum, mineral oil* White petroleum, mineral oil White petroleum, mineral oil, liquid lanolin White petroleum White petroleum White petroleum, mineral oil, lanolin* White petroleum, mineral oil, lanolin derivatives

Slow-Release Lubricants (Inserts) Lacrisert *Indicates preservative-free preparation.

Eye Ointments Bland eye ointments consist primarily of sterile petroleum jelly and therefore differ little from each other except that some are free of preservatives and therefore may be less likely to cause an allergic response. Other ointment possibilities include the ointment base found in boric acid ointment or in antimicrobials such as sulfa or bacitracin eye ointment. Because eye ointments cause more blurring of vision than drops, their use is usually limited to bedtime. They offer more protection than drops because ointments stay in the eye longer. In addition, some patients may benefit from the fact that ointment will help to stick the eyelashes shut at bedtime, thus helping to hold the eye closed. Patients with low-grade lid infections may also benefit from the addition of an antimicrobial (e.g., bacitracin or sulfa ointment) to their regimen. The normal tear film has an antimicrobial effect. In the presence of tear deficiency, that antimicrobial effect is also lost. Slow Release Ophthalmic Inserts (Lacriserts) These inserts are little pellets that are tucked under the lid. They melt slowly over a period of hours and lubricate the eye. In general, they cause somewhat more blurring than low-viscosity drops, but less than that caused by ointment. They are especially useful in those patients who need to use drops more often than four times a day. In some patients, it may still be necessary to supplement the use of the Lacrisert with drops. In most patients, it is helpful to add a drop of artificial tears immediately after placing the Lacrisert in the eye in order to start the melting of the insert. Although the manufacturer generally recommends that one Lacrisert be used daily, some patients will benefit from the use of more than one per day. Taping Tape may be used to keep the eye closed during the night. Especially in the presence of decreased corneal sensation, it is much safer to tape an eye shut than to patch it. An eye with an anesthetic cornea may open under a patch and the patch can abrade the cornea without the patient’s knowledge. If the eye is taped, the patient knows when the eye comes open and the stiffness of the tape tends to hold it away from the cornea even when the eye is open. Tape can also be used to support a drooping lower lid (Fig. 84-1) and to limit the opening or to enhance the closure of a paralyzed upper lid. Instruction by the ophthalmologist is required in the proper methods of accomplishing these goals. A clear tape that does not leave an adhesive residue, such as Transpore, seems to work best. Some paper tapes are also useful. Protective Devices

Hydroxypropyl cellulose

Protective glasses such as wraparound sunglasses or goggles may be used to decrease evaporation from the eye. Moisture chambers that function as one-sided goggles are

Ocular Treatment and Rehabilitation of the Patient with Facial Paralysis

A

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Figure 84-2. Patient with moisture chamber held in position by elastic band.

The use of a less irritating shampoo, such as baby shampoo, adds an additional safety factor. The eye can be protected against air conditioning drafts in autos by closing appropriate vents so the draft is not directed toward the eye. In air travel where the vent may not be controllable (or when sitting under a hair dryer), a moisture chamber can be used to protect the eye. Similarly, a moisture chamber or goggles can be used to protect against dust and common aerosols (e.g., hairsprays). Being Aware of the Humidity

B Figure 84-1. A, Patient with marked paralytic lagophthalmos of the lower lid. B, Lower lid supported in normal position with tape.

available. These can be attached to glasses or held in place by an elastic band (Fig. 84-2). Bubbles that adhere to the skin are also available. These may cause a problem with chronic use because of skin irritation. Protecting Against Ocular Irritants Chlorinated pool water, shampoo, dry air currents, dust, and aerosols are potential ocular irritants for a normal eye and can be especially irritating to an eye with decreased tearing and blinking. Commonsense precautions to protect against these irritants can prevent major problems. For example, properly fitted swim goggles can offer protection for swimming and even shampooing. Shampooing is also safer if it is done with the head back and the shampoo draining back into a sink (as is the common practice in barber shops and beauty salons), rather than with the shampoo running down the face into the eye in a shower.

Many patients have fewer ocular problems when they are in a moist climate than when they are in a dry one, because there is less tear evaporation when the humidity is high. Short of moving to a more humid city, the use of a room humidifier can provide similar benefits. Patients living in areas prone to wide swings in humidity, for example, due to desert winds, should increase the frequency of their drops whenever such a condition is predicted, rather than wait for the eye to become irritated by the humidity drop. Increasing Blinking The important windshield wiper effect of blinking is often more impaired during involuntary (reflex) blinking than it is during voluntary (forced or conscious) blinking. Better eye lubrication may therefore be achieved by making a conscious effort to close the eye at regular intervals, for example, at the end of every page while reading. Teach patients to “Think blink!” Chewing Gum The patient who has aberrant nerve regeneration and gets a wet eye when chewing may sometimes be able to turn this abnormality into an asset. By chewing gum at those times when the eye is dry, the patient can restore moisture to it. In some patients, spicy gum works best.

Ocular Treatment and Rehabilitation of the Patient with Facial Paralysis

not limiting vision or causing disfigurement. The surgery can be done on the side near the nose (medial) or the outer side (lateral) and will elevate the lower lid and enhance upper lid closure. In one type of lateral canthoplasty, the lower lid may be tightened by freeing the lid from its lateral attachments, pulling it taught, and reattaching it laterally. Medial and lateral canthoplasty may be used singly, together, or in combination with other procedures designed to correct ectropion or entropion of the lower lid or to animate the upper lid (Fig. 84-5). Upper Lid Entropion Repair The upper lid skin can be sutured internally to the opening muscle of the eyelid to correct entropion and return the lashes to their normal position. Fascia Lata Support of the Lower Lid When the lower lid laxity cannot be adequately corrected by canthoplasties to tighten and elevate the lid, fascia lata may be used to support the lid. It is sewn through the medial canthal tendon, threaded through the lower lid, and attached to orbital rim periosteum. Radiated donor fascia is more readily available than autologous fascia (which must be harvested), but radiated fascia may be more subject to being resorbed.

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Stent Support of the Lower Lid Auricular cartilage, hard palate, or Poret can be placed in the lower lid to provide a mechanical strut to support the lid. It is an effective procedure, but the stent may be visible in the lid and may in some cases limit adequate lid movement in down-gaze. Tarsorrhaphy A tarsorrhaphy is a procedure in which the lids are sewn together, either partially or completely. The surgery is often successful in protecting the eye, but creates obstructions to peripheral vision and is usually disfiguring. After a temporary tarsorrhaphy is removed, there is often irregularity of the lid margin and associated abnormal (inturned) lash growth. Alternative procedures, which are less disfiguring, should be used whenever possible.

Surgical Techniques to Animate the Upper Eyelid All of the prosthetic devices described here are removable. Even though they may be used for long-term problems, they can be removed if facial nerve function improves to the point that the effect provided by the surgical procedure is no longer required.

A

B

C

D

Figure 84-5. This is a 57-year-old patient with facial paralysis following removal of a right-sided acoustic neuroma. A, Eyes open: Note brow droop and lagophthalmos of lower lid. B, Attempted closure: Note failure of upper lid to close, and slight downward Bell’s phenomenon. Cornea is widely exposed. C, The brow has been elevated and the lower lid has been restored to correct position by medial and lateral canthoplasties. A palpebral spring has been placed in the upper lid and the levator tightened. D, Complete lid closure is achieved by the enhanced palpebral spring.

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Palpebral Spring In this procedure, a wire spring is implanted in the upper lid (Fig. 84-6). The force of the spring is directed to oppose the opening muscle. When the opening muscle relaxes (e.g., when the patient closes the other eye), the spring takes over and closes the affected eye. The affected eye therefore blinks synchronously with the other eye and closes during sleep. No special conscious effort is needed to open or close the eye. Frequently, surgical procedures to improve lower lid position are combined with spring implantation. Enhanced Palpebral Spring An improved palpebral spring operation has been developed that combines tightening of the opening muscle (levator superioris) of the lid with placement of a palpebral spring. Especially in those patients with severe or permanent facial paralysis, this procedure allows for the use of a stronger spring with enhanced blink speed (see Fig. 84-5).

Figure 84-6B. A 22-gauge blunted spinal needle with the stylette in place is passed from the medial end of the dissection to emerge laterally in the plane between orbicularis and tarsus. The passage should be carried out overlying midtarsus. The needle is angulated slightly downward at its lateral extent. The exit of the needle tract should be close to lateral orbital rim periosteum. The lid is everted to confirm that the needle has not inadvertently perforated the tarsus. The previously prepared wire spring (which has been autoclaved) is passed through the needle, and the needle is withdrawn.

Silastic Elastic Prosthesis (Arion Cerlage) A small (1-mm diameter) silastic rod is sewn through the tendon at the inner corner of the eye and passed through the upper and lower lids (Fig. 84-7). The arm in the lower lid serves as a hammock to support that lid. The arm in the upper lid functions similarly to the palpebral spring, simulates blinking, and provides closure. It is also often combined with a medial canthoplasty to provide maximum effect. Unlike the palpebral spring, the silastic prosthesis stretches and loses much of its effect after 6 months or a year. The palpebral spring is therefore preferred in patients in whom long-term function may be required. Either may be used in short-term situations, but the author has found the spring more effective.

spring implants, gold weight patients may need to tape their eyes shut when they are supine (e.g., at bedtime).

Surgical Elevation of the Brow It is possible to elevate a drooping brow by making an incision over the brow, suspending the brow with sutures to the covering of the bone (periosteum) of the forehead, and excising redundant skin and muscle (see Fig. 84-5). The effect is generally cosmetically pleasing, even though the brow still does not move and therefore will not match the other brow in all positions of gaze. Alternatively, the brow may be elevated by endoscopic techniques.

Gold Weights When the closure problem is not too severe and an absolutely tight lid closure is not critical, a gold weight placed in the upper lid may enhance lid closure. Because the effect of the gold weight is gravity dependent, it works best when the patient is upright. Unlike patients with

Figure 84-6A. With a protective scleral shell in place, an incision is made along the lateral two thirds of the lid crease and carried across the orbital rim laterally. Dissection is carried downward at the medial end of the incision to expose the tarsal plate. Dissection is also carried upward and laterally to expose the orbital rim.

Figure 84-6C. A cross-section of the lid illustrates placement of the needle over the midtarsus in the plane between the tarsus and orbicularis. The wire spring should be resting on the epitarsal surface.

Ocular Treatment and Rehabilitation of the Patient with Facial Paralysis

Figure 84-6D. The scleral shell is removed and the fulcrum of the spring is brought into the desired position along the orbital rim. The spring should be placed in a position where its curves conform perfectly to the eyelid contour.

Surgical Closure of the Tear Drainage System Punctal occlusion (blocking the drainage pathways for tears) is similar to putting a stopper into a sink. Plugging the openings in the lacrimal puncta, which lead into the lacrimal canaliculi, preserves the natural (or artificial) tears that are present. The effect of the procedure can be gauged by placing temporary plugs in the puncta. If the benefit appears to be significant, so-called permanent plugs can be placed. Actually, the effect of many types of permanent plugs can be easily reversed by plug removal. If tear retention is excessive, the removal of the plug from either the

Figure 84-6E. The fulcrum of the spring is secured to lateral orbital rim periosteum with three 4-0 Mersilene sutures, taking an extra bite of the periosteum with each stitch. The lower limb of the spring should terminate at the point corresponding to the medial limbus in primary distance gaze. Loops are fashioned at each end and the spring is cut to size. The loops should be flat and tightly closed to leave no sharp edges. The medial loop is enveloped in 0.2-mm-thick Dacron patch material, to which it is secured by means of three 8-0 nylon sutures tied internally. The Dacron patch material is creased in a Gel foam press before surgery and autoclaved with the other instruments. The folded Dacron envelope is cut to size at surgery. The crease in the patch material should be directed downward so that the spring and patch together provide a smooth inferior surface. The loop at the end of the inferior arm is directed upward for the same reason. Suturing of the loop to the Dacron is facilitated by resting the Dacron on a retractor.

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Figure 84-6F. The end of the spring with its Dacron envelope is repositioned into the lid between tarsus and orbicularis. In time, the end of the spring will become fixed to the tarsus by granulation tissue integrating into the Dacron patch. It is helpful to secure the patch to the tarsus directly with an additional running 8-0 nylon suture, to provide fixation until connective tissue grows into the Dacron. The tension on the spring is checked, with the patient in both the upright and supine positions. The tension can be adjusted by grasping the upper end of the spring with forceps and changing its position. When the correct tension has been determined, the upper loop of the spring is secured to the orbital rim periosteum with a 4-0 Mersilene suture. An extra bite of the periosteum may be taken in the stitch before tying. When placing sutures to secure either the fulcrum or the upper loop of the spring to the orbital rim periosteum, it is safer to sew in the direction away from the globe. Spring tension is again checked with the patient both seated and supine. Additional adjustments can be made by bending the wire or repositioning the loop. When the adjustments are completed, two additional 4-0 Mersilene sutures are placed through the upper loop in a manner similar to the initial suture. Deeper tissues overlying the spring are then closed with a 5-0 plain gut suture to ensure that the spring and the Mersilene sutures are well covered. Skin and muscle are closed with running 6-0 plain gut fast-absorbing suture.

upper or lower punctum, while leaving the other plug in place, may provide the desired effect. Plugs that only partially block the tear outflow are also available, making it possible to carefully titrate the amount of tears that remain in the eye. Surgical closure of the puncta should not be considered until a trial of plugs has demonstrated benefit and it is clear that no further change in either tear production or drainage is likely. As it turns out, in most patients with severe facial weakness, the tear drainage system is functionally closed even without placing punctal plugs. The reason for this is that the movement of tears through the drainage system depends on an active pumping mechanism (called the lacrimal pump). Without proper innervation to the orbicularis oculi muscles, this pump does not work and tears remain in the eye. Punctal occlusion, therefore, has its most useful application in patients with partial or recovering facial paralysis who require the use of tear drops more often than four times a day.

SUMMARY Most eye problems in patients with facial paralysis can be successfully managed with modern techniques. No longer is it usually necessary for patients to have their eyes sewn

Ocular Treatment and Rehabilitation of the Patient with Facial Paralysis

Morel-Fatio D, Lalardrie JP: Palliative surgical treatment of facial paralysis: The palpebral spring. Plast Reconstr Surg 33:446–456, 1964. Morel-Fatio D, Lalardrie JP: Le ressort palpebral: Contribution a 1’etude de la chirurgie plastique de la paralysie faciale. Neurochirurgie 11:303, 1965. Rosenstock TG, Hurwitz JJ, Nedzelski JM, Tator CH: Ocular complications following excision of cerebellopontine angle tumors. Can J Ophthalmol 21(4):134–139, 1986.

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Seiff SR and Chang J: Management of ophthalmic complications of facial nerve palsy. Otolaryngol Clin N Am 25(36):669–690, 1992. Wood-Smith D: Experience with the Arion prosthesis. In Tessier P (ed.): Symposium on Plastic Surgery in the Orbital Region. St. Louis, CV Mosby, 1976.

Chapter

85 Edward J. Damrose, MD Harold V. Clumeck, PhD Michael J. Kaplan, MD

T

Rehabilitation of Lower Cranial Nerve Palsies Outline Swallowing Normal Deglutition Oral Preparation Oral Transit Pharyngeal Swallow Anticipated Deficits following Otoneurologic Skull Base Surgery Cranial Nerve V Cranial Nerve VII Cranial Nerve IX Cranial Nerve X Cranial Nerve XII Evaluation

umors that neurotologists are called on to treat not infrequently affect numerous lower cranial nerves, including V, VII, IX, X, XI, and XII. Surgical resection might add to preexisting deficits or create new ones. Rehabilitation of patients with some of these lower cranial nerve deficits thus involves addressing both chronic and acute postsurgical deficits. Some of these deficits partially recover and practiced compensatory measures ameliorate others. Surgical intervention may also help protect the airway, improve phonation, animate the face, protect the eye, or aid in swallowing. Because ophthalmologic and facial nerve rehabilitation are addressed elsewhere in this book, this chapter focuses on rehabilitation of the aerodigestive tract: swallowing, voice, and the airway. Techniques for assessing and treating swallowing disorders have improved in the past 10 years. This chapter reviews the phases of normal oropharyngeal deglutition and assessment techniques and discusses treatment options and their efficacy. Evaluation techniques have added to our understanding of the pathophysiology involved, and experience has validated the efficacy of intervention and the value of various surgical rehabilitation procedures. When cranial nerves (CNs), V, VII, and especially IX, X, or XII have been affected, swallowing efficiency and airway protection are at risk. In the postoperative period, evaluation and treatment focus on initial maintenance of hydration, nutrition, airway safety, and protection of the lungs. Use of a soft feeding tube is helpful and maintaining intubation may be required. If severe and prolonged problems were present or are anticipated, initial tracheotomy and a percutaneous gastrostomy may be considered (or may have already been done). In many cases, however, the 1350

Bedside Examination Fiber-optic Laryngoscopy and Endoscopic Evaluation of Swallowing Videofluoroscopy Assessing Risk of Aspiration Manofluorography Treatment Efficacy of Compensatory Strategies Surgical Adjuncts Tracheotomy Cricopharyngeal Myotomy

Rehabilitation of the Paralyzed Vocal Cord Medialization Injection Technique Thyroplasty Technique Arytenoid Adduction Technique Reinnervation Technique Surgery for Chronic Aspiration Summary

degree to which an individual patient will be impaired is not sufficiently known or predictable. Early evaluation by a professional knowledgeable in speech and swallowing rehabilitation is essential. Subsequent reevaluation is equally critical because as compensatory mechanisms improve, increased normalization of function may be possible.

SWALLOWING Normal Deglutition Normal oropharyngeal swallowing can be divided roughly into three phases: (1) oral preparation, (2) oral transit, and (3) pharyngeal swallow (or pharyngeal response or swallow reflex). Transit of a bolus from the pharynx into the esophagus completes this swallowing stage. Oral Preparation Oral preparation begins with the introduction of material into the oral cavity, where it is formed into a cohesive bolus in preparation for a swallow. The time taken to do this varies. Labial seal (orbicularis oris, innervated by CN VII) prevents loss of material from the lips. The soft palate lowers to the back of the tongue by contraction of the palatoglossus muscle (CN VII), which helps to maintain the bolus and prevent material from escaping into the nasopharynx. At the end of the oral preparatory stage, the material is manipulated by the tongue into a cohesive bolus, which is then pressed between the anterior tongue and the hard palate.

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Mastication is performed by muscles controlled by the mandibular motor division of CN V. Sensation is routed through the mandibular and maxillary sensory divisions of CN V. Taste for the anterior two-thirds of the tongue is via the lingual nerve to the chorda tympani to CN VII.

CNs IX and X throughout the larynx and pharynx. Finally, CN XII is needed for bolus manipulation and tongue base retraction. Unilateral dysfunction of the following cranial nerves might be expected to produce characteristic problems.

Oral Transit

Cranial Nerve V

The oral transit stage begins with the tongue squeezing or rolling1 the bolus to transport it to the posterior oral cavity and it lasts about 1 second. The following must be intact for efficient oral transit: (1) labial musculature to prevent drooling, (2) lingual function to transport the bolus, and (3) buccal muscles to prevent food from falling into the lateral sulci. When the bolus reaches the posterior oral cavity, the base of the tongue retracts, which triggers the next phase.

Loss of motor and sensory functions of the mandibular division of CN V results in paresis of the muscles of mastication and reduced sensation in the anterior two-thirds of the tongue, cheek, floor of mouth, gums, soft palate, and lower lip. Oral preparation will be slower, food may not be as well chewed, and food may pocket in the lateral sulcus of the affected side. Oral transit of the bolus will be affected because of dysfunction of the mylohyoid and anterior belly of the digastric.

Pharyngeal Swallow

Cranial Nerve VII

This stage lasts less than 1 second. When the swallow is triggered, a number of events occur in nearly simultaneous rapid succession. First, the base of the tongue retracts and pushes against the posterior pharyngeal wall, generating a positive pressure that propels the bolus down through the pharynx. Second, the soft palate elevates to close the velopharyngeal port, preventing nasopharyngeal reflux. Third, the movement of the bolus past the base of the tongue pushes the epiglottis down over the laryngeal aditus. Aspiration is further prevented by closure of the laryngeal muscles at the level of the false and true vocal folds; and most important, the larynx elevates via action of the mylohyoid, geniohyoid, stylohyoid, and posterior belly of the digastric muscles. Laryngeal elevation accomplishes two functions. It tucks the laryngeal aditus against the epiglottis and the retracted base of tongue, and it leads to a slight negative pressure in the pharyngoesophageal segment, thus drawing the food into the esophagus. Thus, the bolus is moved along by a positive driving force of the tongue as well as negative pressure in the pharyngoesophageal segment, which suctions the bolus down. Next, rapid contraction of the pharyngeal constrictor muscles begins, which further serves to propel the bolus and clear the pharynx. With relaxation of the upper esophageal sphincter, the bolus then passes into the esophagus. This sphincter opening is a result of two processes: (1) muscular relaxation of the inferior constrictor muscle, the cricopharyngeal muscle, and the upper circular fibers of the esophagus, and (2) active opening by the forward and upward movements of larynx (and hyoid) elevation.

The effect of the loss of CN VII on swallowing is significant. The primary deficits on swallowing from CN VII loss are labial and buccinator weakness (secondary to loss of buccal branches) and reduced elevation of the larynx (secondary to loss of the stylohyoid). The results are an inadequate bilabial seal, which leads to escape of food material from the lips—drooling, trapping of food in the cheek secondary to loss of the buccinator muscle, and residual bolus in the pharynx after the swallow secondary to reduced laryngeal elevation during the triggering of the swallow. When CN VII is injured proximal to the takeoff of the chorda tympani, as in skull base surgery, there is diminution of taste. Although this does not affect swallow functioning per se, it may contribute to nutritional inadequacy by decreasing the motivation to eat, especially if swallowing is otherwise impaired.

Anticipated Deficits following Otoneurologic Skull Base Surgery Successful performance of the oral stages of swallowing depends on intact functioning of CNs V (sensory and motor), VII, IX, and XII. For hyoid and laryngeal elevation, CNs VII, X, and XII are important. Motor fibers of CNs IX and X are critical for palatal elevation, pharyngeal wall contraction, and cricopharyngeal sphincter opening, Sensory feedback is via CN V in the oral cavity and via

Cranial Nerve IX Loss of CN IX leads to reduced sensation in the oropharynx and the posterior one-third of the tongue. In addition, function of the stylopharyngeus is affected. The result could be reduced patient awareness to food residue in the oropharynx. An isolated CN IX deficit likely would go unnoticed but when combined, as is often the case, with sensory deficit or loss of CN X, it exacerbates the impairment. Cranial Nerve X Loss of CN X at the skull base results in reduced sensation in the larynx, epiglottis, aryepiglottic folds, pharyngeal constrictor muscles, a small area of the posterior tongue, and mucosa of the esophagus. Additionally, motor functioning of the levator veli palatini, cricopharyngeal, and intrinsic laryngeal muscles are compromised. Effects of this damage are usually significant. There is reduced palatal elevation, resulting in velopharyngeal insufficiency, with reflux of food (and air) into the nasal cavity. There is residue in the pharynx after a swallow secondary to reduced opening in the upper esophageal sphincter. There is also lack of patient awareness of this residue because of

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lack of sensory functioning, leading to failure to clear residue voluntarily by coughing. There is inadequate vocal cord closure, which both makes a cough less efficient and contributes to penetration of food or saliva into the trachea. There may be silent aspiration secondary to reduced sensation in the larynx. Cranial Nerve XII Loss of CN XII leads to compromise of motor function of the tongue, resulting in reduced oral preparation and transit, as well as reduced base-of-tongue retraction. There is the potential for late accumulation of food in the vallecula after the swallow is completed because of inefficient posterior mobilization of the bolus. Food may also be pocketed in the buccal area on the weak side. (Isolated unilateral damage to the hypoglossal nerve does not usually produce a permanent significant residual deficit because patients learn to use gravity to assist in preparing food on the opposite side and the other side of the tongue generally greatly compensates within a few weeks.) A patient with a unilateral single defect often compensates for it with little to no training. Isolated CN XII loss is sufficiently well tolerated to allow, for instance, consideration of a hypoglossal-facial anastomosis in the rehabilitation of facial nerve loss. Patients with two defects, however, may be severely affected. For example, when CN V and CN VII are both lost, corneal injury is far more likely because of corneal anesthesia, making lubrication of the conjunctivae far more critical because the patient will not sense the pain associated with corneal abrasion. Multiple sites of loss can be devastating, and many factors beyond simply the “expected” dysfunction may affect the individual patent’s loss and ability to compensate. Knowledge solely of the cranial nerves affected in a particular patent neither adequately nor reliably predicts the sum effect of multiple deficits, nor the ability to compensate for it; evaluation is essential.

EVALUATION The evaluation of swallowing dysfunction is challenging because the process involves in rapid sequence the complex interrelated motion of many muscles responding to a swallowing center. Although some disorders of swallowing occur as a result of cortical lesions,2 it is generally agreed that the swallowing center is located in the brainstem.1,3 Specifically, Miller3 reports two regions that can trigger swallowing: a dorsal area of the reticular formation, which includes the nucleus tractus solitarius, and a ventral area of reticular formation around the nucleus ambiguous. Once voluntarily initiated, the normal process of oropharyngeal deglutition is a complex series of neuromuscular events involving sensory and motor portions of many of the lower cranial nerves. Disorders could occur anywhere along the way—from placing food in the mouth, transit through the pharynx, to its entering the esophagus. Clearly, dysfunction of any of these cranial nerves may be a prime component of dysphagia. Dysfunction may lead to slow inefficient transit and poor nutrition or, when aspiration occurs, life-threatening acute or chronic pneumonitis.

Impaired laryngeal function (such as from new unilateral cord paralysis in abduction, a tracheotomy, or postoperative obtundation) may further impair protection of the lungs. The swallowing therapist must assess the patient’s swallow pathophysiology and recommend appropriate management. Many techniques exist to evaluate aspects of oropharyngeal dysphagia, including bedside clinical examination,1 fiber-optic endoscopy,4 videofluoroscopy,1 ultrasonagraphy,5 manofluorography,6–8 and scintigraphy.9 Many swallowing therapists find videofluoroscopy, supplemented with clinical examination, to be the most helpful. Knowledge of manofluorography, which quantifies many of the concepts and parameters discussed, is helpful to the skull base surgeon in understanding the complex pathophysiology and deciding when and whether surgical rehabilitative procedures might be appropriate. This chapter focuses on these three methods, as well as fiber-optic endoscopy, which is familiar to otolaryngologists.

Bedside Examination Although videofluoroscopy may allow the examiner to analyze aspects of the swallow that cannot be evaluated by clinical examination, a bedside examination of the patient3 can be highly useful. For a therapist, clinical examination begins with familiarization of the patient’s medical chart. The duration and etiology of the disorder, the physician’s evaluation of lower cranial nerve function, the patient’s respiratory and nutritional status, and the patient’s cognitive and mental status are some aspects that aid in assessing options. Noted are the presence of a tracheostomy, nasogastric feeding tube, or gastrostomy. The examination then involves an evaluation of the patient’s oral anatomy and oral-motor functioning, and it includes the patient’s trying several dry swallows and the therapist’s observing the degree of laryngeal excursion when the swallow is triggered. The patient’s attempts at swallowing food are then evaluated. Assessing aspiration by bedside examination is inaccurate. Listening to the patient’s voice sometimes suggests an aspiration risk: A gurgly voice immediately after the swallow suggests the food residue on the cords at the top of the airway. However, silent aspiration cannot be ruled out. A study of neurologic populations involving a total of 107 patients10 found that only 42% of those who aspirated during the videofluoroscopy were identified as aspirators at the clinical examination. In 1992, Logemann and colleagues11 evaluated 103 patients who had had partial laryngectomies. Either clinical examination or videofluoroscopy was used initially, and at 3 months all patients underwent videofluoroscopy. Patients who were initially evaluated clinically resumed oral intake more quickly, but those who had been evaluated initially with videofluoroscopy performed better in terms of transit times and swallow efficiencies at 3 months. An explanation for these findings is that early videofluoroscopy permitted more accurate visualization of the patient’s abnormal physiology, resulting in more tailored effective treatment. Apparently, normal bedside evaluations led to earlier resumption of eating but, by failing to identify problems for which compensatory measures could help, to less effective eating.

Rehabilitation of Lower Cranial Nerve Palsies

Fiber-optic Laryngoscopy and Endoscopic Evaluation of Swallowing Endoscopic evaluation of the vocal cords can be performed at the bedside with the fiber-optic rhinolaryngoscope. This can be inserted transnasally after application of a topical decongestant and anesthetic, and several factors should be noted. The vocal cords should be inspected for paresis or paralysis and the position of the paralyzed cord. Paresis implies persistence of some motor innervation to the affected cord and may portend spontaneous recovery of function. Noting the position of the cord in relation to midline is important to determine which surgical procedure will most effectively close the glottic gap. If the posterior commissure is open, the patient may benefit from arytenoid adduction rather than thyroplasty. Pooling of saliva in the postcricoid region may indicate dysfunction of the cricopharyngeal muscle. Gross aspiration of saliva between the vocal folds may imply a significant laryngeal sensory deficit and the patient may need a feeding tube. Swelling of the posterior commissure and interarytenoid mucosa may indicate underlying gastroesophageal reflux, although much more commonly these findings are the sequelae of endotracheal intubation. A supplemental endoscopic technique for evaluation of oropharyngeal swallow has been described by Langmore and colleagues, who refer to their procedure as fiber-optic endoscopic examination of swallowing safety, or FESS.4 It was developed in order to assess swallow function at the bedside for patients who cannot be transported to a radiology suite for a videofluoroscopy. With the scope through the nares in the nasopharynx, the patient can be asked to dry swallow so the physician can assess velopharyngeal competence. Vocal fold function as well as salivary pooling is then assessed. Finally, food consistencies are introduced, and the patient is asked to swallow. The procedure allows inspection of the pharyngeal transit of the bolus and of any material accumulated in the vallecula before the swallow. Penetration and aspiration can also be observed, and the presence or absence of silent aspiration can be noted. Although this procedure by itself does not provide information about oral preparation and oral transit, a standard clinical examination, as described earlier, coupled with endoscopic procedure yields valuable, though incomplete, information regarding a patient’s swallow function.

Videofluoroscopy This procedure was first described in detail in 1983 by Logemann,1 who has pioneered the development and use of dynamic imaging in the diagnosis of oropharyngeal swallowing disorders. The test she developed is often referred to as the modified barium swallow (MBS) and is probably the most widely used assessment technique for dysphagia. The patient is seated upright on a platform attached to a vertical fluoroscopy table to permit lateral radiologic inspection of the mouth and pharynx. The patient is given small amounts (about one-third of a teaspoon) of different barium consistencies (liquid, paste, and then a small piece of cookie spread with barium paste). For each bolus, the examiner places the material in the

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patient’s mouth and instructs the patient to hold the material there until told to swallow it. Dynamic imaging then captures the patient’s efforts to prepare and swallow the food. After lateral views have been taken, anteroposterior views are often included to examine further the pharyngeal transit of the bolus, especially in cases where unilateral weakness is suspected. Some patients cannot be able to tolerate the sitting position that is optimal for the procedure. The procedure is then done with the patient reclining and with the head elevated to a 45-degree angle. The primary purpose of the MBS is to assess the patient’s anatomy and physiology as it relates to the ability to swallow. The examiner is interested in more than whether the patient aspirated during the study; what caused the aspiration or what is preventing successful peroral nutrition is evaluated. A related and equally important purpose of the MBS is to aid the swallowing therapist in developing an individualized treatment plan for the patient. In fact, the videofluoroscopy procedure is often used to test the efficacy of strategies such as compensatory head positioning and specific swallowing techniques.12 For example, if a patient is at risk for aspiration after the swallow because of residue on one side of the pharynx, the examiner may observe the swallow with the head rotated in the direction of the weak side. If descent of the bolus down the stronger side, encouraged by this maneuver, eliminates the residue on the weak side, then this positioning during meals will obviously be recommended.13 (Other compensatory strategies are described in more detail later.) By using different consistencies of food during the MBS, the examiner can determine if certain textures pose less of an aspiration risk than others, and this determination then informs appropriate recommendations for modifications in the patient’s diet. For many patients who demonstrate a delay in triggering the swallow, liquids (especially thin liquids) are more likely to be aspirated than solids or puréed foods. This is because the latter tend to cohere to the base of the tongue without falling into the airway, whereas liquids splash more easily into the airway. It should be emphasized again, however, that there are no absolutes; the examiner must evaluate each patient individually in order to make an appropriate determination. Assessing Risk of Aspiration When material descends below the level of the vocal cords, it is said to be aspirated. (Sometimes material pools at the aditus of the larynx without going below the vocal cords. This is referred to as penetration.) If a patient aspirates, it is important to determine when he or she is most at risk relative to when the swallow is triggered. In other words, does the aspiration occur before, during, or after the swallow, or does it occur more than once? If the bolus accumulates significantly in the patient’s vallecula before the swallow and there is a delay in triggering the swallow, food material might overflow into the airway before the swallow. If the patient does not exhibit adequate laryngeal elevation during the swallow or if there is inadequate vocal fold closure, the patient might aspirate during

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the swallow. Typically, one sees a division of the bolus in two at the point the swallow is triggered, with one part descending the pharynx and the other falling into the supraglottis. If there is inadequate base-of-tongue retraction secondary to posterior lingual weakness or tongue mass atrophy (or prior resection), significant amounts of residue may remain in the vallecula (and possibly pyriform sinuses) after the swallow. Finally, if residue remains in the pyriform sinuses alone, it may indicate a problem with reduced laryngeal elevation, reduced pharyngeal wall contraction, or possibly cricopharyngeal dysfunction. Aspiration is often seen clearly in radiographic studies and is apparent symptomatically to the patient. It is critical, however, that the examiner assess silent aspiration, where material descends into the trachea without eliciting a cough. This occurs frequently in patients with reduced pharyngeal sensation secondary to CN IX and X deficits. How deeply into the tracheobronchial tree of lungs the aspirated material descends and whether there is resultant pneumonitis are not assessed by videofluoroscopy. A major advantage of videofluoroscopy is its detailed visualization of aspects of the swallow that cannot be evaluated on clinical examination. Aspects of oral transit times can be seen, repeated, and recorded with some precision. Pharyngeal transit of the bolus can be similarly analyzed, and the presences of silent aspiration and penetration can be sought.

Manofluorography Manofluorography (MFG) is an evaluation method7,8,14 that adds quantitative measures of time and pressure gradients to videofluoroscopy. Simultaneously recorded with the anatomic changes (traditional videofluoroscopy) are bolus transit times and pressures in the oropharynx, laryngeal inlet, pharyngoesophageal (PE) segment, and the esophagus. From the pressure changes, the computer generates pressure waveforms. Use of this technique allows distinction among dysfunction of tongue mobility, laryngeal elevation, and pharyngoesophageal relaxation, as well as timing flaws. Following initial laryngeal elevation, a positive-pressure base of tongue driving force (TDF) is generated, which pushes the bolus from the oral cavity into the pharynx: an oropharyngeal propulsion pump (OPP). At the same time, pressure in the PE segment, initially elevated, declines and soon becomes subatmospheric: a hypopharyngeal suction pump (HSP). (The constrictors add a secondary component to the OPP, a pharyngeal clearing force. This is applied to the tail of the bolus once it leaves the oropharynx.) The bolus then moves along by virtue of a positive OPP piston operating in the oropharynx pushing the bolus and a relaxing negative HSP in the PE segment suctioning the bolus. Rather than a muscular “peristalsis,” there is a dynamic interplay of positive and negative pressures. By quantifying and separating these parameters, a much clearer understanding of why a particular patient is experiencing dysphagia is likely. As more “typical” patients are studied (for instance, postlaryngectomy and postjugular foramen surgery), greater appreciation of the pathophysiology is also likely, and efficacy of treatment and surgical intervention should become more predictable.

TREATMENT Treatment strategies need first to determine whether peroral feeding is likely to be safe at all. This recommendation is made in conjunction with the swallowing therapist, who must take into consideration a variety of complex factors: (1) the severity of the patient’s aspiration risk; (2) the amount of oral intake the patient can tolerate (some patients with relatively mild physiologic disorders still do not take in enough food or fluids by mouth and are therefore at risk of nutritional compromise); (3) the underlying etiology; (4) the prognosis; (5) whether there is a history of aspiration pneumonia; (6) the patient’s cognitive and mental status; (7) the patient’s motivation; (8) the patient’s independence in activities of daily living, particularly his or her capacity for self-feeding; and (9) the patient’s social support and the environmental setting to which he or she will be discharged. No clear-cut ways exist to predict whether a given patient will develop aspiration pneumonia if fed by mouth. It is known1 that patients can tolerate a certain amount of aspiration without developing pneumonia. At the present time, the recommendation to attempt oral feeding is primarily a clinical judgment that takes into account all of these factors. As a general guide, if transit time is more than 10 seconds and cannot be reduced, oral feeding is likely to result in inadequate nutrition with an increased risk of aspiration. Similarly, if a patient aspirates most or all consistencies during the MBS, it is likely that oral feeding will be unsuccessful. In some instances, despite apparently adequate swallowing physiology, a patient may be a poor candidate for peroral nutrition. Following skull base procedures, prolonged confusion may delay resumption of normal feeding. If oral feeding is contraindicated, it is important to consider how long alternative nutrition is likely to be needed—a few weeks or possibly several months, or permanently. Reevaluation from time to time is important because the situation may change. If prolonged dysfunction is likely, then a gastrostomy is usually the procedure of choice. A gastrostomy provides a large reservoir for bolus feedings and does not stent open the lower esophageal sphincter. Large-diameter gastrostomy tubes rarely clog or kink, and if they do, may be replaced easily. A gastrostomy can usually be placed percutaneously with local anesthesia with the aid of a fiber-optic gastroscope.15–17 An alternative to this PEG (percutaneous endoscopic gastrostomy) is a laparoscopic gastrostomy,18 which is particularly useful when, for instance, gastroscopy is not possible or is risky. With local anesthesia, T-fasteners, introduced percutaneously, are dislodged within the stomach lumen and are used to anchor the tube to the anterior abdominal wall. A gastrostomy is then placed over a J-wire into the stomach at the secured site. Some rely solely on an inflated balloon at the end of the tube rather than use Tfasteners. A gastrostomy may be contraindicated when there is severe gastroesophageal reflux and aspiration or in patients with gastric outlet emptying problems. In such cases, a laparoscopic jejunostomy rather than a gastrostomy may be preferable.19 If a patient is judged capable of possibly resuming oral intake, therapies have been developed that hope to address

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each patient’s specific swallowing disorder.1,20 A patient, for instance, in whom food escapes from between the lips because of labial weakness is instructed in lip-strengthening exercises; a patient with problems forming a cohesive bolus and/or transporting food material to the back of the oral cavity because of lingual weakness or reduced tongue mass secondary to surgical ablation is given lingual strengthening and range-of-motion exercises. The success of these maneuvers depends, of course, on the remaining muscular innervation. For patients with delayed or absent triggering of the pharyngeal swallow, a technique called thermal stimulation may be applied.1 It is generally believed that the swallow response is triggered in the region of the anterior facial arches. It is reasoned that the application of a cold sensation to this area might stimulate a more rapid response. A small laryngeal mirror is placed in ice water, then touched lightly several times against the base of the anterior facial arches on both sides. Patients with pharyngeal transit problems and/or reduced laryngeal closure are taught compensatory strategies and maneuvers designed to clear the airway or the pharynx of food residue. A common technique is the Mendelsohn maneuver,10 designed to clear the pharynx of residue left after the swallow because of reduced laryngeal elevation, which results in minimal opening of the cricopharyngeal sphincter. The patient is instructed to begin swallowing and then, at the moment the swallow response is triggered, to maintain maximal laryngeal elevation for a couple of seconds before allowing the larynx to descend. The rationale for the technique is that the cricopharyngeus (and the rest of the upper esophageal sphincter) is being actively opened by the elevation of the larynx and when the larynx is prolonged at its maximal superior point of excursion, there is more time for the bolus to pass through the sphincter and into the esophagus. Another frequently used technique is the supraglottic swallow,1 developed to prevent aspiration of material into the airway secondary to inadequate laryngeal closure. A patient is instructed to hold his or her breath and then swallow. Still holding his or her breath, the patient is asked to cough immediately after swallowing, then to swallow again, cough again, and swallow again. The rationale for the technique is as follows. Assuming that inadequate laryngeal closure results in material going directly into the airway, holding the breath as tightly as possible will close the airway or at least generate positive pressure in the trachea. Food that has fallen onto the vocal cords is retarded from actually entering the airway. When the patient coughs immediately after swallowing, the material on the vocal cords is projected back into the oral cavity and is then reswallowed. Aspiration of the material is thus prevented or at least reduced. These two techniques are often used together effectively. In addition to these techniques, different head positions are investigated. A patient with delayed triggering of the pharyngeal swallow, for example, is asked to tilt the head slightly forward when swallowing: This action serves to increase the vallecular space so that food starting to spill into the pharynx before the swallow can accumulate in the vallecula rather than fall farther into the pharynx. As mentioned previously, a patient with unilateral pharyngeal wall

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paresis can swallow with the head rotated toward the weak side. This directs the bolus down the stronger side, reducing the residue in the pharynx after the swallow. In some hospital settings, formal multidisciplinary swallowing teams have been organized and coordinated to help the primary physician help the patient with dysphagia.21,22 Often, such a team includes members with specialties in nursing, speech pathology, occupational therapy, and dietary/nutrition, with additional input, depending on the setting, from disciplines such as radiology, gastroenterology, dentistry, neurology, otolaryngology-head and neck surgery and other surgical specialties, rehabilitation medicine, pharmacy, and social work, as appropriate.

Efficacy of Compensatory Strategies Although a number of nonsurgical treatment techniques have been proposed and are widely practiced, it is important to inquire critically about their efficacy. Do these procedures produce the intended effects? Well-controlled efficacy studies must supplement experience. Some studies address outcomes of swallowing therapy. For example, does swallowing therapy result in fewer cases of aspiration pneumonia?23 Or does a multidisciplinary swallowing program result in better nutrition and hydration in a nursing home population?24 Some studies have examined the efficacy of specific treatment techniques. For example, Rosenbek and collegues25 assessed the effectiveness of thermal stimulation in a male veteran population with multi-infarct dementia, and Logemann studied the efficacy of head rotation for dysphagia caused by unilateral pharyngeal weakness.11 A number of factors confound attempts to study efficacy, as pointed out by Wertz and colleagues26 and by Silver and colleagues.27 First, there is the issue of defining the “no treatment” group for appropriate comparison to the treated group. Second, there is the need to control for variables such as patients’ medical conditions and their severity, etiology of the swallowing disorders, prognosis, cognitive/mental status, motivation and response to therapy, and so forth. Third, treatment trials need to control for the possibility of spontaneous recovery. To date, the study by Rosenbek and colleagues25 on the efficacy of thermal stimulation (or application) is perhaps the best example of a study with a truly well controlled experimental design. Using a single-subject withdrawal or ABAB design replicated across seven male patients, the authors found no strong evidence that a month-long trial of thermal stimulation (2 weeks of stimulation alternating with 2 weeks of no stimulation) improves the swallow function after multiple strokes. The authors caution that the usefulness of thermal stimulation cannot be discounted altogether on the basis of this study and that the findings cannot be generalized to other dysphagic populations. In summary, more efficacy studies are clearly needed, but they are problematic to conduct. Published studies should be read critically for experimental design and ability to generalize beyond the studied population.

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Surgical Adjuncts Tracheotomy Patients may require a tracheotomy following skull base surgery either because of respiratory failure or for pulmonary toilet secondary to aspiration pneumonia. Tracheotomy is indicated when prolonged intubation would otherwise be necessary. This reduces sequelae of long-term intubation such as subglottic stenosis and vocal cord granulomas. When frequent tracheobronchial suctioning is required, a tracheotomy is likely to be safer than intubation. However, remember that although tracheotomy may aid in the management of aspiration, there is no doubt that it also contributes to aspiration, at times severely. The primary reason is the reduced laryngeal elevation resulting from scarring of the tracheal cartilage to the pretracheal soft tissue and skin. Some feel that a horizontal incision or a Bjork flap (an inferiorly based tracheal U-flap sutured to the inferior skin of a horizontal tracheotomy incision; prevents reinsertion of a tracheotomy into the pretracheal fascia rather than the trachea following accidental decannulation) exacerbates this problem and instead recommend vertical incisions in skin and trachea.28 The cuff of the tube also reduces the effectiveness of a cough in clearing secretions that lie above the cuff. In addition to these mechanical problems, there may be neurophysiologic effects of a tracheotomy that affect aspiration, such as desensitization of the larynx with secondary reduction in protective reflexes. Cricopharyngeal Myotomy The rationale behind a myotomy is the elimination of an abnormal (impeding) HSP, that is, the removal of the functional tightness obstructing the entry into and transit through the PE segment. This is affected both by relaxation of the PE and by anterior laryngeal elevation. A myotomy affects only the former. Normally, the subatmospheric pressure in the PE aids the positive-pressure OPP (consisting of TDF and pharyngeal wall contraction) in propelling food through the hypopharynx into the cervical esophagus. Evidence that the musculature in the area is impeding the transit of the bolus includes an HSP that fails to become relaxed to a subatmospheric pressure and a secondarily hyperelevated OPP. Abnormal PE contractions should also be seen in order to support the contention that a myotomy would improve this pathophysiology. These contractions delay entrance of the bolus into the cervical esophagus in addition to contributing to the relative obstruction. (Before considering a myotomy, it is helpful to know that the lower esophageal sphincter is intact because otherwise the myotomy, in removing the upper esophageal sphincter, may contribute to laryngeal and pulmonary sequelae of reflux.) In summary, before considering a myotomy, there should be both fluoroscopic and manometric evidence that a myotomy would be helpful. If there is such evidence, then the entire PE segment, not just the cricopharyngeus, should be incised. The muscles that should be included are the lower inferior constrictor, cricopharyngeus, and upper circular esophageal muscles. Technically, some surgeons find that esophageal intubation with a cuffed endotracheal tube aids in severing all muscular

layers down to the mucosal layer. The anesthesiologist may inflate and deflate the cuff as needed and may move the cuff superiorly or inferiorly as needed to be sure that no muscle bands remain to constrict the dilated esophageal mucosa at the conclusion of the procedure. An alternative to cricopharyngeal myotomy is chemodenervation of the muscle with botulinum toxin. This can be accomplished endoscopically under general anesthesia or simple intravenous sedation.29,30 Better control of dysphagia may be seen in patients with isolated tenth cranial nerve paralysis than in more global injuries.31 Doses up to 100 units are needed. Unfortunately, the effects of chemodenervation are short-lived, lasting on average 4 to 5 months, after which time repeat injection is needed. If there is doubt as to whether cricopharyngeal myotomy would be helpful, a trial of botulinum toxin may clarify the issue. Combined with procedures that simultaneously restore glottic closure, cricopharyngeal myotomy may be particularly helpful to restore adequate oral alimentation and alleviate dependency on a feeding tube. Montgomery has advocated early intervention with type I thyroplasty and cricopharyngeal myotomy in those patients with high vagal injuries from surgery or tumor, owing to the poor prognosis for functional recovery in these patients and the potential benefit of preventing aspiration pneumonia.32 Patients with cricopharyngeal spasm and posterior glottic insufficiency may be better served with simultaneous arytenoid adduction and cricopharyngeal myotomy. A defect in the posterior glottis allows spillage of material into the airway, which is exacerbated by the obstruction to bolus transition caused by the cricopharyngeus muscle. Woodson has shown that closure of this posterior glottic gap with removal of the obstruction presented by the cricopharyngeus muscle stops aspiration and allows resumption of full oral alimentation, with subsequent decannulation in patients who are tracheostomy and tubefeed dependent.33 The details of thyroplasty and arytenoid adduction are more fully addressed later in this chapter.

REHABILITATION OF THE PARALYZED VOCAL CORD Unilateral cord paralysis secondary to a skull base procedure is different from the more common etiologies in that both the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN) are affected.34,35 Not only is the adductory function of the cord impaired, resulting in glottic incompetence, but some degree of endolaryngeal sensory deficit can be expected as well, since the internal branch of the SLN provides this function. Both factors can contribute to hoarseness and aspiration. The timing and the degree of intervention are controversial, and no consensus exists as to the best treatment regimen. As Koufman has keenly observed, multiple factors figure into this process.36 For patients undergoing skull base surgery, the most important of these may be the severity of the patient’s symptoms, including dysphonia, aspiration, and weak cough; the position of the vocal cord, particularly in regards to whether the posterior commissure is open; the prognosis for eventual recovery of function; the likelihood

Rehabilitation of Lower Cranial Nerve Palsies

of compensation without surgical intervention; and the skill and experience of the surgeon. The timing of intervention may also be affected by the patient’s prognosis; a poor prognosis would likely prompt more immediate palliation rather than wait to see how much improvement occurs. Some would advocate an immediate procedure whenever the etiology involves an irreversible process because palliation is likely to be helpful and full recovery without intervention is not likely. When resection of the vagus nerve at the time of skull base surgery is expected, such as with resection of a glomus vagale, arytenoid adduction and possible cricopharyngeal myotomy may be appropriate during the same operation, thus saving the patient the need for a second anesthetic. Similarly, patients who preoperatively have a vagal nerve paralysis may opt for simultaneous medialization at the time of resection of the skull base lesion. For patients with no cranial nerve deficits preoperatively and for whom it is unclear if injury to the cranial nerve is permanent, management becomes controversial. If the patient demonstrates no sign of significant bronchopulmonary aspiration, some surgeons monitor voice improvement for 6 to 12 months before considering surgical intervention. In some patients vocal cord motion may recover if the nerve is intact; in others, there may be sufficient compensation by the other cord such that the voice is near normal. Bielamowicz and colleagues37 recommend early arytenoid adduction following skull base surgery for several reasons. Only 18% of patients in their series recovered vocal cord function after surgery, with recovery appearing as late as 12 months. Moreover, early arytenoid adduction, by restoring glottic closure, restores a strong cough and improves pulmonary toilet. Montgomery has noted that immediate surgical intervention may allow the patient to avoid aspiration pneumonia as well as tracheostomy and gastrostomy and a that a thyroplasty can be reversed if vocal cord function returns.32 Koufman has noted that vocal cord paralysis following skull base surgery is generally irreversible and suggests nasogastric tube feeding but no tracheostomy in the immediate postoperative period, with the patient undergoing medialization as soon as the patient can tolerate the procedure.33 Although early surgical intervention may still not prevent the temporary need for a tracheostomy in up to 33% of patients or a gastrostomy in up to 66% of patients, completing adjunctive surgery early may allow the patients to begin rehabilitation earlier and limit the number of days required for hospitalization.37 In addition, aspiration pneumonia may be avoided.37 Ultimately, a frank preoperative discussion with the patient regarding the possible postoperative cranial nerve deficits may offer the most help in planning the timing and degree of intervention.

MEDIALIZATION The paralyzed vocal fold can be medialized by injection, by thyroplasty, and by arytenoid adduction. Injection and thyroplasty can both effectively medialize the membranous portion of the vocal fold, but only arytenoid adduction can

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medialize the most posterior portion of the vocal fold. Selection of the appropriate medialization technique, therefore, depends in part on adequate assessment of the degree of posterior insufficiency. A persistent posterior glottic gap can allow continued hoarseness and aspiration despite good medialization of the membranous vocal fold.

Injection Teflon injection has been the mainstay of treatment of the paralyzed vocal fold for 40 years. Teflon can be injected transorally either under direct laryngoscopy or using the laryngeal mirror. In skilled hands, phonatory outcome can be excellent.34,35 Complications from Teflon injection can include granuloma formation and migration of the Teflon into the subglottis or cervical lymph nodes. Granuloma formation and overinjection can lead to undesired stiffness and inelasticity of the cord, both of which may be treated by cord incision under direct laryngoscopy and partial removal of the Teflon.38 A variety of newer biocompatible materials in addition to Teflon are commercially available for injection (Table 85-1). Their chief advantage over Teflon is that they may be readily injected through a small-gauge needle (25 or 27), allowing percutaneous injection in the office setting under fiber-optic guidance. Percutaneous injection can be performed either directly through the cartilage of the thyroid ala or through the cricothyroid membrane. Collagen, hyaluronic acid, and acellular human dermis allow only temporary medialization, with reabsorption varying from 3 months to longer than 1 year. Calcium hydroxyapatite gel and polydimethylsiloxane gel are readily injected through a small-gauge needle and are permanent. However, long-term data as to efficacy and complications in the latter are not yet available. Technique Under general anesthesia with a small endotracheal tube in place (5.0 mm internal diameter), a Dedo laryngoscope is TABLE 85-1. Treatment Options for Unilateral Vocal Cord Paralysis Injection With Bovine collagen (Zyplast®) Autollogous human collagen Acellular micronized human dermis (Cymetra®) Hyaluronic acid gel (Hylaform®) Calcium hydroxyapatite gel (Radiance FN®) Polydimethylsiloxane gel (Bioplastique®) Polytetrafluoroethylene (Teflon®)

Type I Thyroplasty With Cartilage Expanded polytetrafluoroethyle (Gore-Tex®) Silicone (Silastic®, Montgomery Implant System®) Hydroxyapatite

Arytenoid Adduction Reinnervation via Neuromuscular pedicle Ansa cervicalis to RLN XII to RLN

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steady pressure. The patient is asked to phonate and injection concludes when adequate medialization and good phonation are attained.

Thyroplasty Described by Isshiki and colleagues in 1974,41,42 the basic technique of thyroplasty involves creation of a window in the cartilaginous thyroid ala adjacent to the paralyzed vocal fold and insertion of an implant through that window to medialize the cord. A variety of implants have been described (see Table 85-1). The small section of cartilage created from forming the window can be removed or left in situ, according on the surgeon’s preference. The implant should be secured to the thyroid ala either by suture or by flanges attached to the implant to prevent migration and possible extrusion of the implant. Some hoarseness can be expected from transitory traumatic edema in the vocal fold, but this resolves. Interestingly, the voice quality may continue to improve for up to a year following type I thyroplasty,43 so it may be warranted to wait a year before revision thyroplasty is considered. Technique The patient is placed in a semi-Fowler position in the operating room and a rhinolaryngoscope is introduced through the nose after topical anesthesia is achieved. When the cords can be seen well, the scope is secured with tape to the nasal skin (and the scope is hung from an intravenous [IV] pole). A video camera is attached and the position of the scope is adjusted under direct vision to just above the level of the epiglottis for best inspection of the endolarynx. The neck is then prepared and sterilely draped, and 1% lidocaine with epinephrine 1:100,000 is infiltrated over the thyroid ala on the affected side. The incision is made at the lower border of the thyroid cartilage. The thyroid cartilage is exposed by dividing the strap muscles in the midline. Calipers are used to determine the

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position of the vocal cord and position of the window to be formed in the ala. The window is approximately 6 × 13 mm and is developed at the level of the true vocal cord (Fig. 85-2). This is achieved by removing the cartilage with a cutting burr or oscillating saw 5 mm lateral to the midline and 3 mm to 6 mm superior to the inferior border of the thyroid ala. The inner perichondrium is elevated and gentle pressure with a blunt elevator applied to the lateral aspect of the vocal fold. The effect of medialization on the cord can be seen on the monitor and the voice assessed. A precut wedge or T-shaped block of implant material can then be sculpted to the appropriate dimensions and placed through the window, effecting medialization of the vocal fold. Adjustments can be made to the block by positioning or removing it from the window and carving it to the ideal size and replacing it. The block is secured to the thyroid cartilage and a drain placed for 24 hours.

Arytenoid Adduction Introduced by Isshiki in 1978, arytenoid adduction involves the placement of sutures around the muscular process of the paralyzed vocal fold. The sutures then secured to the anteroinferior aspect of the thyroid ala and tightened. This mimics the pull of the lateral cricoarytenoid muscle, medializing the vocal process and allowing closure of the posterior glottis. This procedure can be coupled with simultaneous type I thyroplasty in order to address bowing of the mid vocal fold.43 When performed under general anesthesia when immediate phonatory feedback is not available, type I thyroplasty can be performed secondarily under local anesthetic should residual vocal fold bowing and dysphonia be noted.37 Technique Arytenoid adduction can be performed under local or general anesthetic. A transverse skin incision at the level of the cricothyroid membrane is made from midline to the

Figure 85-2. Positioning of window in thyroid ala during type I thyroplasty. (Koufman JA: Management of the paralyzed vocal cord. In Myers EN [ed.]: Operative Otolaryngology/Head and Neck Surgery. Philadelphia, WB Saunders, 1997, pp 380–402.)

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anterior border of the sternocleidomastoid muscle on the paralyzed side. Subplatysmal flaps are elevated superiorly to the level of the hyoid and inferiorly to the level of the cricoid cartilage. The strap muscles are divided in the midline to expose the thyroid cartilage and a Freer elevator is used to sweep the muscles from the cartilage laterally. The sternohyoid and sternothyroid muscles are divided at their insertion on the hyoid bone and reflected inferiorly. Care must be taken to avoid injury to the external branch of the superior laryngeal nerve, which runs deep to the sternohyoid muscle. Muscle fibers of the inferior constrictor are identified inserting along the oblique line and are divided with electrocautery. With the muscle fibers detached, a narrow double-pronged hook is used to grasp the posterior aspect of the thyroid ala. The larynx is then medially rotated to expose the posterior aspect of the larynx. The remaining inferior constrictor fibers are carefully detached from the posterior thyroid ala. Care must be taken not to perforate the underlying pyriform sinus mucosa. With a fine-tipped hemostat and a peanut for blunt dissection, the pyriform sinus mucosa is gently elevated posterolaterally off the underlying posterior cricoarytenoid (PCA) muscle. The PCA fibers can be followed to their insertion into the muscular process of the arytenoid. Occasionally, it is necessary to use a rongeur to remove cartilage of the thyroid ala to expose the muscular process. Two 4–0 Prolene sutures are passed through the muscular process. The cricoarytenoid joint is not opened unless it is ankylosed. As in the technique described by Bielamowicz and colleagues,44 an 18-gauge spinal needle is then inserted into the anteroinferior aspect of the thyroid ala and passed deep to the vocal cord in close proximity to the inner thyroid ala. The tip of the needle is aimed between the arytenoid and the ipsilateral thyroid ala. As the needle

tip emerges, great care must be taken not to perforate the pyriform sinus. The ends of the Prolene sutures are then passed up the bore of the needle and the needle is withdrawn. With gentle traction, the sutures are pulled anteriorly, internally rotating the arytenoid and medializing the vocal process (Fig. 85-3). The sutures are then tied over a two-hole 1.5-mm miniplate. A Penrose drain is placed and remains for 24 hours. The wound is closed in layers and a light pressure dressing is applied to the neck.

Reinnervation The ideal treatment for paralysis of the vocal cord would be predictable, coordinated reinnervation of the akinetic laryngeal musculature. In practice, reinnervation has not provided such results. However, it has been established that techniques designed to provide active motor nerve stimulus to muscular tissue are successful in preventing atrophy, and thus loss of bulk, as well as providing resting muscular tone. Such observations lead to the investigation of nerve and neuromuscular transfer procedures to restore glottic function. Popularized by Tucker,45,46 the nervemuscle pedicle procedure brings the motor endplates of the ansa cervicalis-omohyoid muscle in direct contact with the intrinsic laryngeal musculature, allowing “spillover” depolarization of these muscles. Reinnervation of the paralyzed thyroarytenoid muscle may prevent long-term atrophy and preserve vocal quality improvements made by type I thyroplasty and arytenoid adduction.47 Crumley 48,49 has modified this by direct ansa cervicalis to RLN anastomosis, which suggests the advantage of eliminating endolaryngeal muscular surgical scarring and thus not interfering with subsequent medialization procedures that might become necessary. The excellent voice quality seen with Crumley’s procedure is secondary

Figure 85-3. Suture placement and direction of pull in arytenoid adduction. (Koufman JA: Management of the paralyzed vocal cord. In Myers EN [ed.]: Operative Otolaryngology/Head and Neck Surgery. Philadelphia, WB Saunders, 1997, pp 380–402.)

Rehabilitation of Lower Cranial Nerve Palsies

to a restoration of mass and tension in the thyroarytenoid muscle and stabilization of the arytenoid through a balanced reinnervation of the lateral cricoarytenoid and posterior cricoarytenoid muscles. Paniello has noted that the hypoglossal nerve is vigorously active during both phonation and swallowing, making this a potentially ideal donor nerve.50 Stronger, more complete reinnervation, more appropriate temporal activity, and sphincter-like function on swallowing may be additional advantages of the XII-RLN procedure.49 Low complication rates are reported in both procedures, but a significant delay of 2 to 6 months is expected before recovery is seen. In addition, injury to either nerve at the time of skull base surgery may preclude their use as donor nerves for a reinnervation procedure. Technique The neuromuscular pedicle technique of Tucker45,46 can be performed under local anesthesia. An incision is made over the lower border of the thyroid cartilage, and the sternocleidomastoid muscle is retracted laterally to expose the ansa hypoglossus riding over the anterior surface of the internal jugular vein. The nerve is traced to its insertion in the omohyoid muscle and the muscle is dissected gently to identify the point at which the nerve begins to arborize. A 3-mm muscular pedicle that includes the motor endplates is then gently elevated. A window is next made in the thyroid ala (as described for thyroplasty) with the outer perichondrium preserved as a posteriorly based flap. The cartilage is removed. The inner perichondrium is then incised to expose the underlying thyroarytenoid muscle. The neuromuscular pedicle is sewn directly to this muscle and the flap and skin are closed. Some immediate transient improvement, probably related to local swelling, is sometimes seen in glottic and voice function. The ansa cervicalis-RLN anastomosis is performed in a similar fashion. Crumley’s48,49 indications include intact contralateral cord abduction, an intact distal RLN, and no prior medialization procedure. The distal recurrent laryngeal nerve is identified and the distal branch of the ansa cervicalis is transected at its insertion into the sternothyroid muscle. The nerve endings are prepared and anastomosed under the operating microscope with three to four 10–0 sutures. Difficulty in identifying the RLN has been reported, particularly in the previously operated neck. The denervated sternothyroid muscle does result in some initial medialization of the thyroid lamina, slightly improving the voice immediately. Several months’ delay, however, is needed before more marked improvement has been reported. In XII-RLN anastomosis, patients are given a preoperative lidocaine block of the twelfth cranial nerve to test if loss of the nerve produces significant articulatory changes and aspiration. If the block is well tolerated, end-to-end anastomosis of the nerves is performed. The RLN stump should be at least 3 cm long to complete a tension-free anastomosis. Removing the submandibular gland may be necessary to free the full length of the twelfth nerve. A delay of up to 6 months may be necessary for reinnervation. In the interim, the patient can be temporarily medialized with an injection of Gelfoam or collagen.

1361

SURGERY FOR CHRONIC ASPIRATION Chronic, unremitting aspiration leading to repeated lifethreatening pneumonitis may be ameliorated by separating the airway from the digestive tract. A laryngectomy is the most familiar procedure that accomplishes this, but is not reversible. Some other procedures are in theory reversible and in fact have been occasionally reversed. In practice the circumstances leading to this dire predicament are usually not reversible, and a laryngectomy may be most appropriate. Alternatives to laryngectomy for chronic life-threatening aspiration have been well discussed in the otolaryngologic literature and include laryngotracheal diversion and glottic and supraglottic closure. All require a tracheotomy. In a laryngotracheal diversion, a tracheotomy is done below a blind-pouch closure of the superior cervical trachea inferior to the subglottis. Several tracheal rings are removed to allow approximation of the mucosa. In a glottic closure, via a laryngofissure, the medial surfaces of the false vocal cords (with the surface epithelium removed) are approximated, leaving a short blind pouch in the endolarynx. Similarly, the true cords are approximated, and an inferiorly based thyrohyoid muscle is interposed between them into the laryngofissure. In a supraglottic closure, the epithelium of the free superior edge of the epiglottis is removed, the inferior epiglottic cartilage is removed to allow the epiglottis to fold inferiorly, and the submucosal epiglottic edge is then sutured to the submucosal false vocal cord musculature. A minute opening may be made later with a laser to try to allow an air conduit from the airway to the mouth to facilitate speech. A major impediment to peroral nutrition has been resultant chronic aspiration; in such circumstances reevaluation of swallowing after successful separation of the airway from the digestive tract may lead to renewed attempts at eating, absent the risk of aspiration. A Blom-Singer tube following laryngectomy may also allow resumption of talking in many instances where there remains good tongue coordination for articulation.

SUMMARY Patients who undergo skull base procedures are at risk to develop or exacerbate swallowing disorders, aspiration, and phonatory abnormalities. In addition to facial reanimation and ophthalmologic protection, rehabilitation of swallowing and phonation is critical. Evaluation and intervention techniques have improved considerably in the past decade. The evaluation and treatment of an individual patient however remains very much an art, requiring the close cooperation of patient, surgeon, speech pathologist, and radiologist, as well as other health care providers.

REFERENCES 1. Logemann JA: Evaluation and Treatment of Swallowing Disorders. San Diego, College-Hill Press, 1983. 2. Perlman AL: The neurology of swallowing. Sem Speech Lang 12:171–184, 1991. 3. Miller AJ: Neurophysiological basis of swallowing. Dysphagia 1:91–100, 1986.

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4. Langmore SE, Schatz K, Olsen N: Fiberoptic endoscopic examination of swallowing safety: A new procedure. Dysphagia 2:216–219, 1988. 5. Shawker TH, Sonies B, Hall TE, Baum BF: Ultrasound analysis of tongue, hyoid, and larynx activity during swallowing. Investigative Radiol 19:82–86, 1984. 6. McConnel FMS: Analysis of pressure generation and bolus transit during pharyngeal swallowing. Laryngoscope 98:71–78, 1988. 7. McConnel FMS, Cerenko D, Mendelsohn MS: Manofluorographic analysis of swallowing. In Krespi Y, Blitzer A (eds.): Aspiration and swallowing disorders. Otolaryngol Clin North Am 21(4):625–635, 1988. 8. McConnel FMS, Logemann JA: Diagnosis and treatment of swallowing disorders. In Cummings CW, et al (eds.): Otolaryngology-Head And Neck Surgery, Update 2. St Louis, Mosby Year Book, 1990, pp 10–38. 9. Muz J, et al: Detection and quantification of laryngotracheopulmonary aspiration with scintigraphy. Laryngoscope 97:1180–1185, 1987. 10. Splaingard ML, Hutchins B, Sulton LD, Chaudhuri G: Aspiration in rehabilitation patients: Videofluoroscopy vs bedside clinical assessment. Arch Phys Med Rehabil 69:637–640, 1988. 11. Logemann JA, et al: Impact of the diagnostic procedure on outcome measures of swallowing rehabilitation in head and neck cancer patients. Dysphagia 7:179–186, 1992. 12. Logemann JA, Kahrilas PJ: Relearning to swallow after stroke— application of maneuvers and indirect biofeedback: A case study. Neurology 40:1136–1138, 1990. 13. Logemann JA, Kahrilas PJ, Kobara M, Vakil NB: The benefit of head rotation on pharyngoesophageal dysphagia. Arch Phys Med Rehabil 70:767–771, 1989. 14. McConnel FMS, Cerenko D, Jackson RT, Hersh T: Clinical application of the manofluorogram. Laryngoscope 98:705–711, 1988. 15. DeChicco RS, Matarese LE: Selection of nutrition support regimens. Nutr Clin Prac 7:239–245, 1992. 16. Jamagin WR, et al: The efficacy and limitations of percutaneous endoscopic gastrostomy. Arch Surg 127:261–264, 1992. 17. Ponsky JL, Gauderer MWL: Percutaneous endoscopic gastrostomy: Indications, limitations, techniques, and results. World J Surg 13:165–170, 1989. 18. Duh Q, Way LW: Laparoscopic gastrostomy using T-fasteners as retractors and anchors. Surg Endosc 7:60–63, 1993. 19. Duh Q, Way LW: Laparoscopic jejunostomy using T-fasteners as retractors and anchors. Arch Surg 128:105–108, 1993. 20. Logemann JA: Treatment for aspiration related to dysphagia: An overview. Dysphagia 1:34, 1986. 21. Martens L, Cameron T, Simonsen M: Effects of a multidisciplinary management program on neurologically impaired patients with dysphagia. Dysphagia 5:147–151, 1990. 22. Ravich WJ, et al: The swallowing center: Concepts and procedures. Gastrointest Radiol 10:255–261, 1985. 23. Kasprisin AT, Clumeck H, Nino-Murcia M: The efficacy of rehabilitative management of dysphagia. Dysphagia 4:48–52, 1989. 24. Musson ND, et al: Nature, nurture, nutrition: Interdisciplinary programs to address the prevention of malnutrition and dehydration. Dysphagia 5:96–101, 1990. 25. Rosenbek JC, Robbins J, Fishback B, Levine RL: Effects of thermal application on dysphagia after stroke. J Speech Hear Res 34:1257–1268, 1991. 26. Wertz RT, et al: Comparison of clinic, home, and deferred language treatment. Arch Neurol 43:653–658, 1986. 27. Silver K, DuChane AS, Kuhlemeier K: Response to Kasprisin et al: The efficacy of rehabilitative management of dysphagia. Dysphagia 5:166–168, 1990.

28. Nash M: Swallowing problems in the tracheotomized patient. In Krespi Y, Blitzer A (eds): Aspiration and swallowing disorders. Otolaryngol Clin North Am 21(4):701–709, 1988. 29. Parameswaran MS, Soliman AM: Endoscopic botulinum toxin injection for cricopharyngeal dysphagia. Ann Otol Rhinol Laryngol 111:871–874, 2002. 30. Haapaniemi JJ, Laurikainen EA, Pulkkinen J, Marttila RJ: Botulinum toxin in the treatment of cricopharyngeal dysphagia. Dysphagia 16:171–175, 2001. 31. Shaw GY, Searl JP: Botulinum toxin treatment for cricopharyngeal dysfunction. Dysphagia 16:161–167, 2001. 32. Montgomery WW, Hillman RE, Varvares MA: Combined thyroplasty type I and inferior constrictor myotomy. Ann Otol Rhinol Laryngol 103: 858–862, 1993. 33. Woodson G: Cricopharyngeal myotomy and arytenoid adduction in the management of combined laryngeal and pharyngeal paralysis. Otolaryngol Head Neck Surg 116:339–343, 1997. 34. Dedo HH: Surgery of the Larynx and Trachea. Philadelphia, Decker, 1989. 35. Dedo HH: Diagnosis of the paralyzed vocal cord and treatment with Teflon injections. In Cummings CW, et al (eds.): OtolaryngologyHead and Neck Surgery, Update 2. St Louis, Mosby Year Book, 1990, pp 86–94. 36. Koufman JA: Management of the paralyzed vocal cord. In Myers EN (ed.): Operative Otolaryngology/Head and Neck Surgery. Philadelphia, WB Saunders, 1997, pp 380–402. 37. Bielamowicz S, Gupta A, Sekhar LN: Early arytenoid adduction for vagal paralysis after skull base surgery. Laryngoscope 110:346–351, 2000. 38. Horn KL, Dedo HH: Surgical correction of the convex vocal cord after Teflon injection. Laryngoscope 90:281, 1980. 39. Berke GS, Gerratt B, Kreiman J, Jackson K: Treatment of Parkinson hypophonia with percutaneous collagen injection. Laryngoscope 109:1295–1299, 1999. 40. Green DC, Berke GS, Ward PH, Gerratt B: Point-touch technique of botulinum injection for the treatment of spasmodic dysphonia. Ann Otol Rhinol Laryngol 101:883–887, 1992. 41. Isshiki N, Morita H, Okamura H, Hiramoto M: Thyroplasty as a new phono-surgical technique. Acta Otolaryngol 78:451, 1974. 42. Isshiki N, Okamura H, Ishikawa T: Thyroplasty type I (lateral compression) for dysphagia due to vocal cord paralysis or atrophy. Acta Otolaryngol 80:465, 1974. 43. Billante CR, Clary J, Childs P, Netterville JL: Voice gains following thyroplasty may improve over time. Clin Otolaryngol 27: 89–94, 2002. 44. Bielamowicz S, Berke GS, Gerratt BR: A comparison of type I thyroplasty and arytenoid adduction. J Voice 9:466–472, 1995. 45. Tucker HM: Human laryngeal reinnervation: Long-term experience with the nerve-muscle pedicle technique. Laryngoscope 88:598, 1978. 46. Tucker H: Laryngeal innervation for unilateral vocal cord paralysis. Ann Otol Rhinol Laryngol 90:457, 1981. 47. Tucker HM: Combined surgical medialization and nerve-muscle pedicle reinnervation for unilateral vocal fold paralysis: Improved functional results and prevention of long-term deterioration of voice. J Voice 11:474–478, 1997. 48. Crumley RL: Nerve transfer technique as it relates to phonatory surgery. In Cummings CW, et al (eds.): Otolaryngology-Head and Neck Surgery, Update 2. St Louis, Mosby Year Book, 1990, pp 100–106. 49. Crumley RL: Update: Ansa cervicalis to recurrent laryngeal nerve anastomosis for unilateral laryngeal paralysis. Laryngoscope 101:384–388, 1991. 50. Paniello RC: Laryngeal reinnervation with the hypoglossal nerve: 2. Clinical evaluation and early patient experience. Laryngoscope 110(5 Pt 1):739–748, 2000.

Index

Note: Page numbers followed by f refer to figures; those followed by t refer to tables.

A A trains, in intraoperative facial nerve monitoring, 972 AAF (anterior auditory field), 59, 59f, 64, 66 AAV (adeno-associated virus) vector, 138–139, 139t, 140, 141 Abducens nerve, 218 at craniovertebral junction, 1142 intraoperative monitoring of, 976–978, 977f ocular functions of, 1340, 1341 in parasellar and cavernous sinus region, 1055, 1055f and petrous apex, 1108 Abducens nerve weakness, due to increased intracranial pressure, 524 Abducens nucleus, 84, 84f, 85, 85f, 1202f Abernathy, John, 12 ABI. See Auditory brainstem implant (ABI). ABRET (American Board of Registered Electrodiagnostics Technologists), 959 Abscess(es) Bezold’s, 22, 22f, 216 brain imaging of, 409 due to otitis media, 492, 493f, 913t, 919–920, 920f of cerebellopontine angle, 858, 859f epidural, due to otitis media, 913t, 917, 917f, 918f Absorbed dose, in Gamma Knife radiosurgery, 1167 AC. See Auditory cortex (AC). ACAD (atherosclerotic carotid artery disease), 155, 156f pulsatile tinnitus due to, 204, 208, 208t, 209 Accessory nerve, 1055f Accessory nerve schwannomas, 366–367 Accessory optic tract (AOT), 107 ACE (advanced combination encoder), 1303, 1306, 1317 Acetazolamide (Diamox) and CSF production, 525 for familial ataxia syndrome, 667 for Ménière’s disease, 628, 661–662 for migraine prophylaxis, 515 vestibular symptoms, 516 for pseudotumor cerebri, 209 Acetylsalicylate, tinnitus due to, 184, 185, 186 Acoustic feedback, with hearing aids, 1284–1285, 1289

Acoustic middle ear reflex, 70–71, 70f, 71f Acoustic nerve glioma of, 373 hamartoma of, 374 neuritis of, 374, 377f Acoustic neurofibromas, aqueduct obstruction due to bilateral, 719f Acoustic neuroma (AN), 727–773 acoustic brainstem implant for, 772 acoustic reflex decay with, 742 Antoni type A and B morphology of, 733–734, 733f with arachnoid cysts, 358, 358f audiologic diagnosis of, 742–743, 742f in auditory brainstem, 1323 auditory brainstem response with case study of, 300, 300f diagnostic, 297–299, 742–743 intraoperative monitoring of, 983–984, 983f and tumor size, 166, 166t bilateral, 738f, 772 brainstem compressive, 734, 734t, 736f, 737f of cerebellopontine angle course of, 852 differential diagnosis of, 868t imaging of, 354f, 355–360, 356f–360f meningioma vs., 809 cisternal, 356f, 734, 734t, 735f, 736f clinical presentation of, 167–172, 167t–171t, 464, 739–742, 739t “conduction block” in, 144–145, 146 conservative management of, 746–747, 746t cystic, 738f, 753 delayed diagnosis of, 746 diagnostic protocols for suspected, 745–746 differential diagnosis of, 339–340 distortion product otoacoustic emissions in, 165, 166 with dural tail, 357f, 358 duration of symptoms from onset to diagnosis of, 167, 168t dynamic posturography for, 743 dysequilibrium due to, 739t, 740, 766 dysmetria due to, 740 dysphagia due to, 739t in elderly, 537 electronystagmography for, 743 endocrine relationships for, 733 epidemiology of, 730–731 facial anesthesia and pain due to, 740 facial nerve in clinical symptoms of, 739t, 740–741 hypoglossal and spinal accessory anastomosis with, 760–761, 760f

iatrogenic injury of, 1275–1276 monitoring of, 757–758 pathologic correlates of, 144, 145f, 154, 154f postoperative palsy of, 758–761 primary reconstruction of, 759–760, 760f surgical approach to, 749, 750, 750f–752f surgical results for, 758, 758t vulnerability of, 757 facial weakness and spasm due to, 740–741 Gamma Knife radiosurgery for, 1173–1181, 1174f–1181f growth pattern of, 734, 734f–737f, 734t growth rate of, 735–738, 738f, 738t headache due to, 739t, 741, 767–768 hearing conservation with, 761–766 assessing candidacy for, 762–763 bilateral, 764–765 clinical results of, 763, 764t definition of successful result for, 763 long-term results of, 763–764 reporting results of, 742, 742f after stereotactic surgery, 770, 772t hearing loss due to, 167–172, 739–740 atypical, 739–740 audiogram shape for, 167–168, 169t contralateral, 765 course and patterns of, 164, 745 differential diagnosis of, 165–166, 166t historical background of, 163–164 incidence of, 739t mechanism of, 739 due to myelin and axon compression, 165 in neurofibromatosis 2, 786 progression of, 172 speech discrimination and, 168–170, 169t, 171t, 172 sudden or fluctuating, 170–171, 170t symmetric, 740 due to vascular compression, 164–165 hemorrhage with, 738, 738t, 741–742 postoperative, 754 histopathology of, 733–734, 733f, 788f historical background of, 27–28, 31, 31f, 728–730, 728f, 729f, 730t hydrocephalic, 358, 734, 734t, 737f imaging of, 744–745, 745f, 745t, 746 in neurofibromatosis 2, 343f, 785f intracanalicular, 354f, 355–357, 371, 734, 734f, 734t, 735f 1363

1364

INDEX

Acoustic neuroma (AN) (Continued) intraoperative cranial nerve monitoring for, 966–974 activity evoked by electrical stimulation in, 963f, 966–970, 969f–971f auditory brainstem responses in, 983–984, 983f electrode placement for, 962, 962f, 967 spontaneous and mechanically elicited activity in, 970–974, 972f, 973f labyrinthine, 339, 343f location of, 164 lower cranial nerve disorders due to, 739t, 741 malignant, 734 measurement of, 739 molecular genetics of, 135, 732 molecular mechanisms of, 732 in neurofibromatosis 1, 134 in neurofibromatosis 2 auditory changes due to, 786 clinical manifestations of, 785 endocrine relationships in, 733 epidemiology of, 730–731 hearing conservation with, 764–765 imaging of, 343f, 785f location of, 464, 785 molecular genetics of, 135, 732 molecular mechanisms of, 732 pathologic correlates of, 146, 147f risk of, 360 treatment options for, 787–788, 788f, 789f normal hearing with, 171–172, 171t nystagmus with, 743 occult, 730 otoacoustic emissions with, 165, 166, 743 papilledema due to, 739t pathogenesis of, 731–732, 731f pathologic correlates of, 144–146, 145f, 733–734, 733f pure tone and speech audiometry for, 742, 742f due to radiation therapy, 733 radiation therapy for, 768–772 conventional, 768 stereotactic, 768–772 audiovestibular function after, 770–771, 772t complications after, 771, 772f cranial nerve function after, 771 equipment for, 768–769, 769f fate of tumor after, 770, 770t, 771f, 771t fractionated, 770, 770t indications for, 772 in neurofibromatosis, 2, 788 secondary oncogenesis after, 771, 773t before and after surgery, 772 rollover with, 742 rotatory testing for, 743 signs and symptoms at time of diagnosis of, 167, 168t special testing battery for, 742 speech discrimination scores with, 168–170, 169t, 171t, 172, 745 sporadic, 730 after stereotactic surgery, 360, 360f subarachnoid hemorrhage of, 358 surgical management of CSF leak after, 926–927, 930 facial mimetic function after, 757–761, 758t, 760f headache after, 767–768 hearing conservation with, 742f, 761–766, 764t incomplete resection in, 750–753, 752f, 753f middle fossa approach in, 694f, 695

outcome of, 753–757, 754f, 755f priorities of, 695 quality of life after, 757–768 radiation therapy after, 772 retrosigmoid approach in, 686f selection of surgical approach in, 747–749, 749f social and occupational rehabilitation after, 768 technique of, 747–750, 748f–752f tinnitus after, 766 translabyrinthine approach in, 691, 691f, 747, 748, 749f, 1275–1276 vestibular rehabilitation after, 766 tinnitus due to clinical manifestations of, 740 effect of tumor removal on, 184, 766 percentage of patients with, 167, 168t, 171t, 739t, 740 trigeminal nerve disorders due to, 739t, 740, 745 vs. vestibular neuritis, 487t vestibular symptoms of, 180, 739t, 740 vestibular testing for, 743–744 vestibulo-ocular reflex with, 743, 766 visual symptoms of, 739t, 741 Acoustic reflex, in multiple sclerosis, 503–504 Acoustic reflex decay, with acoustic neuroma, 742 Acousticofacial primordium, 1199, 1200f Acquired suprathreshold asymmetry, 282 Action potential(s) (AP), 1207–1208 in animals, 67, 68, 68f compound, 1208 with cochlear implant, 1304 compound muscle, 964, 964f for facial nerve, 966–967, 1223–1228, 1224f, 1225f with facial palsy, 1247, 1247f compound nerve for cochlear nerve, 982, 984–988, 984f–986f for facial nerve, 966–967 in electrocochleography, 291 Acuity, measurement of, 217 Acute suppurative otitis media (ASOM), facial palsy due to, 1240 Acute toxic labyrinthitis, vertigo in, 177 Acyclovir (Zovirax) for facial palsy, 1250–1251 for Ramsay Hunt syndrome, 668 A/D (analogue-to-digital) converter, 1288 Ad (adenoviral) vector, 139, 139t, 140 Adaptation, vestibular, 1332 Adaptation exercises, in vestibular rehabilitation, 1336 Adaptation test center of gravity alignment in, 267–268 considerations and limitation of, 267–268 methodology for, 258–259, 260f, 261f, 261t reliability and validity of, 259 subject characteristics in, 267 Adeno-associated virus (AAV) vector, 138–139, 139t, 140, 141 Adenocarcinoma, 1031 vaginal, metastatic to cerebellopontine angle, 866 Adenoid cystic carcinoma of cerebellopontine angle, 853, 867 of temporal bone, 1031 Adenoma, ceruminous, of cerebellopontine angle, 862–863 Adenoviral (Ad) vector, 139, 139t, 140 Adolescents, cochlear implants in, 1316 Adrenal insufficiency, dizziness due to, 560

Advanced combination encoder (ACE), 1303, 1306, 1317 AEDs (antiepileptic drugs) for seizures, 520–521 for vestibular migraine, 666 AERs (auditory evoked responses) middle latency, 300–301 in multiple sclerosis, 504 Aëtius of Amida, 2 Affective disorders, tinnitus and, 188–189 Afferent visual pathways, pathology of, 233 AFP (atypical facial pain), otalgia due to, 198 Afterdischarge, 896 AGC (automatic gain control), 1289 Aging. See also Elderly. dysequilibrium of, 534–535, 535t presbycusis with, 592–593 vestibular disorders with, 533–537 alterations in function, 534 cervical vertigo, 537 epidemiology of, 533 evaluation of, 535–536, 535t, 536t labyrinthine disorders, 536 other otologic and neurotologic disorders, 536–537 presbystasis, 534–535, 535t structural changes, 533–534, 534t due to systemic disorders, 537 treatment and rehabilitation for, 537 vertebrobasilar insufficiency, 536 AI (primary auditory cortex) cross-modal activation in, 322 physiology of, 59, 59f, 64 AICA. See Anterior inferior cerebellar artery (AICA). AIED (autoimmune inner ear disease), 639–642, 640t Air embolism, 714–715 due to acoustic neuroma surgery, 754 Air travel, labyrinthine hemorrhage due to, 246 Air-conduction Rinne test, 220 Alar ligaments, 1137 Albers-Schönberg disease, 1127 Alcohol, nystagmus due to, 237 Alcohol sniff test, 216 ALDs (assistive listening devices), 1292 Alexander’s deformity, hearing loss due to, 600 Alexander’s law, 222, 223f, 231–232, 235 Alford, B., 35 Allen test, 1012 Allergy, and Ménière’s disease, 625–626, 629 Allodynia, 184, 194 Alport syndrome, hearing loss in, 129t Alprazolam, for familial ataxia syndrome, 667 American Board of Registered Electrodiagnostics Technologists (ABRET), 959 American Neurotologic Society, creation of, 39 American Society of Neurophysiological Monitoring (ASNM), 959 Amikacin, ototoxicity of, 593 Aminoglycoside(s) chemical labyrinthectomy with, 663–664 hearing loss due to, 593–594 hypersensitivity to, 126 ototoxicity of, gene transfer for protection against, 140 semicircular canal dysfunction due to, 250–251 tinnitus due to, 184, 185 vestibular symptoms of, 180 in children, 561 in elderly, 536–537

INDEX

Amitriptyline for migraine prophylaxis, 515 for vestibular migraine, 665–666 Amphetamine, for vestibular dysfunction, 669t Ampicillin, for wound infections, 721 Ampicillin sodium and sulbactam (Unasyn), for wound infections, 721 Amplification, electrophysiologic procedures to estimate benefit of, 297 Ampullary nerve(s), 76 posterior, 950f, 951, 951f Amygdala connections from auditory system to, 67 in tinnitus, 187, 188–189, 188f AN. See Acoustic neuroma (AN); Auditory neuropathy (AN). Anaerobic bacteria, and intracranial complications of otitis media, 914–915 Analogue-to-digital (A/D) converter, 1288 Ancef (cefazolin), for wound infections, 721 Ancient change, 1259 Ancient schwannoma, 734 Anemia dizziness due to, 560 with paragangliomas, 544–545 Anesthesia, and intraoperative cranial nerve monitoring, 965 Anesthesia dolorosa, 904 Aneurysm(s) angiography of, 438–439, 440f–442f carotid intrapetrous, 1121, 1122f imaging of, 389, 390f treatment of, 439, 440f–441f radiation-induced, 1190, 1191f sites of, 155–156 of cerebellopontine angle, 368–369, 368f, 369f, 863–864, 864f classification of, 438 clinical presentation of, 438 defined, 438 dissecting, pulsatile tinnitus due to, 205 of mid-basilar artery, 706, 707f prevalence of, 438 pseudo-, 438 of dural arteriovenous fistula, 447f–448f embolization of, 439 traumatic, 438, 439, 442f serpentine, pathologic correlates of, 156–157 sites of, 438 subarachnoid hemorrhage due to, 438 treatment for, 438–439, 440f–441f of vertebrobasilar system, 368–369, 368f, 369f Angelman syndrome, 127 Angiofibromas, juvenile, angiography of, 465 Angiography, 436–465 of aberrant jugular bulb, 454–455, 455f of aberrant petrous internal carotid artery, 454, 455f of aneurysms, 438–439, 440f–442f arteriography, 436 of arteriovenous fistulas direct carotid-cavernous, 451, 452f dural, 441–451, 445f–450f extracranial, 451–453, 452f, 453f scalp, 453 vertebral, 452, 453f of arteriovenous malformations, 439–441, 443f–444f of atherosclerosis, 453 of craniovertebral junction tumors, 1153, 1153f of dural arteriovenous fistulas, 938 for embolization, 437 of fibromuscular dysplasia, 453–454, 454f of glomus jugulare tumors, 1040–1041, 1040f

of hemangioblastomas, 465 intraoperative, 437 of jugular foramen meningiomas, 1044 of jugular foramen schwannomas, 1042 of jugulotympanic glomus tumors, 455–456, 457f–461f of juvenile angiofibromas, 465 magnetic resonance of cerebellopontine angle, 350, 352f of glomus jugulare tumors, 1040–1041 of lateral skull base, 384 of meningiomas, 800 for pulsatile tinnitus, 209 for major artery occlusion, 437 of malignant skull base tumors, 465 of mechanical compression of jugular vein, 455 of meningiomas, 456–464, 462f–463f, 800 foramen magnum, 826 jugular foramen, 822–823 mid-skull base, 1050 of persistent stapedial artery, 454 of petrous apex lesions, 1109–1110 of schwannomas, 464–465 of temporal bone tumors, 1030 venography, 437–438 Angular acceleration, 241 Angular vestibulo-ocular reflex (aVOR), 98–99, 99f Anisocoria, 233 Annandale, Thomas, 27, 728 Annihilation, 318 Annulus, 1219f Anosmia, 216 Anoxic encephalopathy, central processing deficits due to, 579 Ansa cervicalis-RLN anastomosis, for vocal cord paralysis, 1360, 1361 Ansa hypoglossi, 1157f Anterior arch, of atlas, 1138f, 1139f Anterior auditory field (AAF), 59, 59f, 64, 66 Anterior canal vestibulo-ocular reflex, 99–100, 99f Anterior clinoid process, 1156f Anterior cranial fossa, 998f, 1054f meningiomas of, 1050 Anterior galeal-pericranial flap, 1006–1007, 1006f, 1018, 1021f Anterior inferior cerebellar artery (AICA) aneurysms of, 368f, 369 in cerebellopontine angle, 851, 893–894, 893f, 894f in craniovertebral junction, 1143f, 1145f and facial nerve, 1205 infarcts of, 371, 373f surgical anatomy of, 678–679, 679f Anterior inferior cerebellar artery (AICA) syndrome, due to acoustic neuroma surgery, 754, 754f Anterior lobe degeneration, central balance deficits with, 263f Anterior longitudinal ligament, 1139f Anterior pericranial flap, 1006–1007, 1006f Anterior rectus of the head, 997, 999f Anterior skull base lesions, 1005, 1005f soft tissue reconstruction for, 1018, 1020t, 1021f Anterior spinal artery, 1142, 1143f Anterior ventral cochlear nucleus (AVCN) anatomy of, 60, 60f development of, 565, 565f, 566 effect of cochlear implant on, 577 Antibiotic prophylaxis, for CSF leak, 932 Antibiotics, for skull base osteomyelitis, 1103–1104

1365

Anticholinergic drugs, for vestibular dysfunction, 668, 669t, 670 Anticipation, 127 Anticonvulsants for seizures, 520–521 for vestibular migraine, 666 Antidepressants for tinnitus, 190 tricyclic for psychophysiologic dizziness, 667 for vestibular migraine, 665–666 Antidromic conduction testing, of facial nerve, 1248, 1248f Antiepileptic drugs (AEDs) for seizures, 520–521 for vestibular migraine, 666 Antihistamines for motion sickness, 670 for vertigo in elderly, 537 for vestibular dysfunction, 669t, 670 Anti-Hu, 546 Antionconeural mechanism, 547 Antiplatelet therapy, for vertebrobasilar insufficiency, 666 Antivert. See Meclizine (Antivert). Antiviral therapy, for facial palsy, 1250–1251 Anti-Yo, 546–547 Antoni type A and B morphology, of acoustic neuroma, 733–734, 733f Antrum, during mastoidectomy, 1273 Anxiety, with vestibular dysfunction, 661 AOT (accessory optic tract), 107 AP. See Action potential(s) (AP); Auditory processing (AP). AP (Audio Processor), 1297, 1297f APDs. See Auditory processing disorders (APDs). Apical air cells, fluid or mucus in, 387–388, 388f Apical ligament, 1054, 1137, 1139f Apoplexy, labyrinthine, 180, 181 APS (automatic positioning system), 1164, 1165f, 1173 Arachnoid cyst(s) of cerebellopontine angle, 364, 365f, 857, 858, 858f of posterior fossa, 944–948 classification of, 944–945, 945f clinical signs and symptoms of, 945–946 diagnosis and imaging of, 946–947, 946f management of, 947, 947f pathology and pathogenesis of, 944, 944f vestibular schwannoma with, 358, 358f Arachnoid granulations pathologic correlates of, 152–153, 153f temporal bone encephalocele due to, 1090 Arachnoiditis, lumbar, with cerebellopontine angle epidermoid cysts, 847 Archiv für Ohrenheilkunde (Archives of Otology), 19, 19f, 22 Arcuate eminence, 1002 Argyll Robertson pupil, 216 Arion cerclage, for eyelids, 1346, 1348f Ariyan, S., 1005 Arnold-Chiari malformation, 237, 1142 central processing deficits with, 578 neurotologic symptoms of, 1148–1149 Arnold’s nerve examination of, 225 in otalgia, 195 paraganglioma involving, 427 Arrhythmias, congenital, dizziness due to, 560 Arterial bleeding, during neurotologic surgery, control of, 715–717, 715f, 716f Arteriography, 436 Arteriosclerotic plaques, in internal carotid artery, 155, 156f

1366

INDEX

Arteriovenous fistulas (AVFs) carotid-cavernous, 451, 452f pulsatile tinnitus due to, 205f dural. See Dural arteriovenous fistulas (DAVFs). extracranial, 451–453, 452f, 453f pulsatile tinnitus due to, 204–205, 205f, 208, 208t, 209, 210f scalp, 453 venous drainage of, 443, 936 vertebral, 452, 453f Arteriovenous malformations (AVMs), 934–942 angiography of, 439–441, 443f–444f in cerebellopontine angle, 369, 369f classification of, 934 clinical presentation of, 439, 937–938 defined, 439, 934 dural, pathologic correlates of, 157 epidemiology of, 439 grading systems for, 936–937, 937t labyrinthine hemorrhage due to, 333, 333f location and arterial sources of, 934–935, 935f natural history of, 937 pathogenesis and pathophysiology of, 935–936, 936f pulsatile tinnitus due to, 204–205, 209 radiographic evaluation of, 439, 938 treatment for, 439–441, 938–942, 940f–941f Arteritis cerebral, central processing deficits due to, 578 temporal, vestibular symptoms of, 180 Artery(ies), of lateral skull base, 998 Artery occlusion, angiography for, 437 Arthritis, rheumatoid, of craniovertebral junction, 1147–1148, 1148f Articulation Index, and hearing aids, 1282, 1282f Artifacts, in intraoperative cranial nerve monitoring, 967, 971, 972f, 988 Artificial tears, 1341–1342, 1342t Arytenoid adduction, 1357, 1357t, 1359–1360, 1360f Ascending auditory pathway, tinnitus due to abnormalities in, 185 Ascending pharyngeal artery, 684f Ascending tract of Deiters (ATD), 79, 84, 84f, 85, 98 ASNM (American Society of Neurophysiological Monitoring), 959 ASOM (acute suppurative otitis media), facial palsy due to, 1240 ASP (automatic signal-processing), 1288–1289, 1288f Aspergillomas, of cerebellopontine angle, 857 Aspergillus spp, osteomyelitis due to, 1097, 1098 Aspiration assessing risk of, 1353–1354 bedside examination of, 1352 surgery for, 1361 Aspirin hearing loss due to, 594 tinnitus due to, 184, 185, 186 for vertebrobasilar insufficiency, 666 Assistive listening devices (ALDs), 1292 ASSR (auditory steady state responses) to estimate amplification benefit, 297 stacked derived-band, 299 Astrocytomas cerebellar, 880–883, 881f, 882f, 883t of cerebellopontine angle, 854, 857 cystic, 853, 855f juvenile pilocytic, 880–883, 881f, 882f, 883t pontine, 370, 371f facial nerve degeneration due to, 153–154, 154f

Ataxia, 225 due to cerebellopontine angle meningioma, 808 in children, 554, 560 familial, 560 episodic, and migraine, 512 pharmacotherapy for, 662t, 667 Friedreich’s, 560 central processing deficits with, 578 due to meningitis, 494 ATD (ascending tract of Deiters), 79, 84, 84f, 85, 98 Atherosclerosis angiography of, 453 radiation-induced, 1190 Atherosclerotic carotid artery disease (ACAD), 155, 156f pulsatile tinnitus due to, 204, 208, 208t, 209 Athetosis, due to foramen magnum meningioma, 826 Ativan. See Lorazepam (Ativan). Atlanto-axial dislocation, 1147, 1148 Atlanto-axial joint, 1054, 1137, 1139f Atlanto-occipital dislocation, 1147 Atlanto-occipital fusion, 1146–1147, 1147f Atlanto-occipital membrane, 1054, 1054f, 1137, 1139f Atlas, 1137, 1138f–1141f, 1144f Atropine, for vestibular dysfunction, 669t Atypical facial pain (AFP), otalgia due to, 198 Audio Processor (AP), 1297, 1297f Audiogenic seizures, 522 Audiogram shape, for acoustic neuroma, 167–168, 169t Audiologic testing, 220–221 for acoustic neuroma, 742–743, 742f for cochlear implant, 1310 in children, 1317–1318 for facial nerve tumors, 1265 for pulsatile tinnitus, 208–209 Audiology, 1281 Audiometric configuration, and hearing aids, 1283 Audiometry for acoustic neuroma, 742, 742f for Ménière’s disease, 627 for meningiomas, 799 jugular foramen, 823 for multiple sclerosis, 503 for pulsatile tinnitus, 208–209 Audiovestibular testing, for meningiomas, 799 Auditory brainstem, anatomy of, 1323–1324, 1324f Auditory brainstem implant (ABI), 1323–1330 anatomical basis for, 1323–1324, 1324f auditory performance with, 1328–1329 device for, 1324–1325, 1325f electrode-specific speech with, 1329 electrophysiologic monitoring of, 1326 historical background of, 1323 with labyrinthitis ossificans, 151–152 patient selection for, 1325 penetrating, 1329–1330, 1329f performance monitoring with, 1328, 1328f pitch assessment with, 1327–1328, 1327f postimplantation psychophysics with, 1326–1328 postoperative care after, 1326 speech processor programming for, 1326–1327 speech recognition with, 1328–1329, 1329f surgical approach and implantation procedure for, 1325–1326 for vestibular schwannoma, in neurofibromatosis 2, 788, 789f

Auditory brainstem nuclei, tinnitus due to functional changes in, 186–187 Auditory brainstem response (ABR), 291–293. See also Brainstem auditory evoked potentials (BAEPs). with acoustic neuroma case study of, 300, 300f diagnostic, 297–299, 742–743 intraoperative monitoring of, 983–984, 983f and tumor size, 166, 166t with auditory brainstem implant, 1326 in auditory neuropathy, 471, 472, 473f, 474 auditory processing testing of, 277 bandpass filter settings for, 294, 294f case studies of, 300, 300f, 301f in children, 555, 571 click-evoked, 295–296, 296f in cochlear implant surgery, 301, 302, 302f with conductive hearing loss, 573 defined, 291 for detection of hearing loss, 295–297, 296f differential amplification of, 294 discovery of, 287 efficacy of, 297 to estimate amplification benefit, 297 as far-field recording, 294 four-channel recordings of, 294–295, 295f intraoperative monitoring of, 981–984, 983f measurement criteria for diagnostic, 299 with meningioma, 799 after meningitis, 495 in multiple sclerosis, 504 vs. otoacoustic emissions, 288 parameters for, 293–294, 294t probable generators of, 293, 293f ratio of common mode noise rejected in, 294 with sensorineural hearing loss, 300, 301f signal averaging in, 294, 295f technique of, 293–295, 294f, 294t, 295f tonal stimuli of, 296–297, 296f ramped, 296 waveform peaks in, 293, 293f Auditory canal. See External auditory canal (EAC); Internal auditory canal (IAC). Auditory competence, postnatal development of, 569–570, 570f Auditory cortex (AC) in ascending pathway, 59, 59f, 64–65 development, maturation, and plasticity of, 321–322, 567, 575 Auditory discrimination, 274 Auditory evoked potentials (AEP), brainstem. See Brainstem auditory evoked potentials (BAEPs). Auditory evoked responses (AERs) middle latency, 300–301 in multiple sclerosis, 504 Auditory fatigue, in cochlear vs. retrocochlear hearing loss, 165–166 Auditory fields, 59, 59f, 64, 66 Auditory figure ground, auditory processing testing of, 274 Auditory function, objective measure(s) of, 287–303 auditory brainstem response as, 293–295, 293f–295f, 294t in cochlear implant surgery, 301–303, 302f, 303f to detect hearing loss, 295–297, 296f to diagnose acoustic neuroma, 297–300, 300f electrocochleography as, 290–293, 291f–293f to estimate amplification benefit, 297 middle latency responses as, 300–301 otoacoustic emissions as, 287–290, 289f, 290f

INDEX

Auditory language-learning disorders. See Auditory processing disorders (APDs). Auditory manifestations of migraine, 513 of multiple sclerosis, 503–504, 503f Auditory meatus external, 998f, 1054f internal, 1002 Auditory middle-latency response, auditory processing testing of, 277 Auditory nerve electrical stimulation of, 38–39 in humans vs. other animals, 69 myelination of, 567, 568f, 569f representation of frequency in, 55–58 place, 55–57, 55f–57f temporal, 57, 57f, 58 Auditory nerve dyssynchrony, otoacoustic emissions with, 289–290, 290f, 291f Auditory nerve fiber inhibitory areas of, 57, 57f phase-locking of discharge in, 57, 57f, 58 Auditory nerve section, for tinnitus, 190–191 Auditory nervous system, 58–67 ascending pathways in classical, 58–65, 59f–63f and tinnitus, 187, 188f nonclassical, 65, 65f and tinnitus, 187, 188f auditory cortex in, 59, 59f, 64–65 centrifugal pathways to cochlear nucleus and higher centers in, 66 cochlear nucleus in, 59f–62f, 60–62 connections to other nonauditory parts of brain by, 67 efferent system in, 65–66 frequency analysis in, 54–58, 54f–57f higher-order processing in, 66–67 inferior colliculus in, 59f, 62–64, 63f medial geniculate body in, 59f, 64 neural plasticity in, 66 olivocochlear bundle in, 66 parallel processing in, 66–67 stream segregation in, 66–67 superior olivary complex in, 59f, 62 tinnitus due to injuries of, 185–186 Auditory neuropathy (AN), 471–474 audiometric findings in, 472, 472t, 473f central processing deficits due to, 579 clinical presentation of, 472–473, 473f defined, 471 etiology of, 471–472 evaluation of, 473–474 and frequency discrimination, 58 future directions for, 474 genetic screening for, 474 incidence of, 471 main features of, 471, 472t otoacoustic emissions with, 289–290, 290f, 291f pathophysiology of, 472 peripheral neuropathy with, 473 treatment for, 474 vestibular function with, 473 Auditory pathways ascending classical, 58–65, 59f–63f and tinnitus, 187, 188f nonclassical, 65, 65f and tinnitus, 187, 188f efferent, 65–66 Auditory perceptual disorders. See Auditory processing disorders (APDs). Auditory potentials, in cochlear implant surgery, 301–303, 302f, 303f

Auditory processing (AP) defined, 273–274 in elderly, 281–282 Auditory processing disorders (APDs) due to deafferentation, 572, 572f, 574–578, 577f due to deprivation, 572–574, 572f prevalence of, 274 remediation of, 281 screening for, 279 subtypes of, 281 Auditory processing (AP) system development of, 563–570 abnormal, 572–579, 572f, 577f anatomic, 564–567, 564f–566f, 568f, 569f functional, 567–570, 569f pathology of, 578–579 Auditory processing (AP) testing of adults, 279 age and, 278 anatomic level of, 276, 276t of auditory brainstem response, 277 of auditory middle-latency response, 277 with background noise, 275 behavioral, 274–276, 276t binaural measures of, 275–276 brain mapping and scalp topography in, 282–283 of children, 278–279, 568–572 dichotic measures of, 276 effect of intelligence, cognition, and language on, 278 electrophysiologic, 276–278 in children, 568–572 factors affecting results of, 278 of filtered speech, 275 of frequency or duration pattern recognition, 275 of frequency-altered speech, 275 functional MRI in, 282, 321 future directions for, 282–283 gap detection tests in, 275 goals of, 274, 279 in hearing aid applications, 282 historical perspective on, 274 interpretation of, 280–281 manner of presentation in, 275–276 of masking level differences, 275–276 medications and, 278 of mismatch negativity, 277–278 monaural measures of, 275 multidisciplinary approach to, 279 of other later auditory evoked responses, 278 of P300, 277 with peripheral hearing loss, 278 PET and SPECT for, 319 for screening, 279 of sound localization, 276 for temporal processing disorders, 275 test battery components for, 279–280, 280t of time-compressed speech, 275 Auditory steady state responses (ASSR) to estimate amplification benefit, 297 stacked derived-band, 299 Aura in Ménière’s disease, 623 migraine with defined, 201, 514 without headache, 514 and neurotologic symptoms, 514 pathogenesis of, 510 symptoms of, 514 vertigo in, 514 of seizure, 518–519 Aural fullness, due to Ménière’s disease, 621, 622, 623

1367

Aural glaucoma, 27 Aural polyp, 215 Auricular branch examination of, 225 in otalgia, 195 Auriculotemporal branch, in otalgia, 195, 196 Auscultation, 216 Autenrieth, 15 Autoexcitation, 896 Autoimmune inner ear disease (AIED), 639–642, 640t Autoimmune lesions, of cerebellopontine angle, 857–858, 858f–860f Automatic gain control (AGC), 1289 Automatic positioning system (APS), 1164, 1165f, 1173 Automatic signal-processing (ASP), 1288–1289, 1288f Autonomic dysfunction, with vestibular dysfunction, 661 Autosomal-dominant inheritance, 123–125, 124f, 131t Autosomal-dominant nonsyndromic hereditary hearing loss, 134 Autosomal-recessive inheritance, 122–123, 123f, 131t AVCN. See Anterior ventral cochlear nucleus (AVCN). AVFs. See Arteriovenous fistulas (AVFs). AVMs. See Arteriovenous malformations (AVMs). aVOR (angular vestibulo-ocular reflex), 98–99, 99f Axis, 1137, 1138f, 1140f, 1144f Axon, 1206, 1208f, 1209f Axon cylinder, 1208f Axon hillock, 1208f Axonal membrane, polarization of, 1207–1208 Axonotmesis, 1208, 1209f, 1210, 1225, 1226f, 1226t, 1245 Aztreonam, for skull base osteomyelitis, 1103

B B trains, in intraoperative facial nerve monitoring, 972 Background noise, auditory processing testing with, 274 Baclofen (Lioresal) for hemifacial spasm, 902 for tinnitus, 190 Bacon, Francis, 6 Bacterial labyrinthitis, 178, 334–336, 335f, 336f Bacterial meningitis, deafness due to, 50 Baek, S. M., 1005 BAEPs. See Brainstem auditory evoked potentials (BAEPs). BAHA implantable hearing device, 1296–1297, 1296f, 1299t Bakamijian, V. Y., 1004 Balance, dynamic posturography for nonphysiologic component of, 264, 264t Ballance, Charles, 20, 24–25, 24f, 25f, 26, 27, 39, 728, 806 Bandage contact lens, 1344 Bárány, Robert, 31–32, 32f, 34 Bárány’s classic rotation test, 94, 94f Barbecue spit nystagmus, 109 Barium swallow, modified, 1353 Barker, F. G., II, 730t Barotrauma hearing loss due to, 597 labyrinthine hemorrhage due to, 246 otolith dysfunction due to, 242

1368

INDEX

Barr body, 126 Barrel roll, for benign paroxysmal positional vertigo, 650 Basal cell carcinoma (BCC), of external auditory canal and temporal bone, 415, 417f, 1030 Basilar artery, 999f, 1142, 1143f tortuous, 352f, 864 Basilar impression, 1146, 1147f Basilar membrane anatomy and physiology of, 589, 590f in frequency analysis, 54, 54f, 55, 56, 56f, 58 Basilar plexus, 1002 Basiocciput, 1054f Basisphenoid, 1054f, 1057f Battle’s sign, 215 Baudet, J., 1005 BC (brachium conjunctivum), vestibulo-ocular projections in, 84, 84f BCC (basal cell carcinoma), of external auditory canal and temporal bone, 415, 417f, 1030 BDNF (brain-derived neurotrophic factor) for aminoglycoside-induced ototoxicity, 251 transgenic expression of, 140 Beamlets, 1182 Bechterew’s phenomenon, 113 Beevor, Charles, 25 Behavioral responses, to sound, 568–570, 570f Behavioral tests, of auditory processing, 274–276, 276t Behind-the-ear (BTE) hearing aids, 1283, 1284, 1285, 1287, 1291 Bell Charles, 12–13, 13f, 14f, 167, 1199, 1230, 1230f John, 12 Bell-Magendie rule, 13 Bell’s palsy, 1230–1252. See also Facial nerve paralysis; Facial palsy(ies). in children, 1241 clinical evaluation of, 1238–1243 clinical presentation of, 1232 defined, 1232 and diabetes mellitus, 1234 electroneuronography for, 1247–1248 etiology of, 1226, 1236–1238 historical background of, 13 with HIV, 1234 immunologic injury and, 1237 incidence of, 1233 ischemia and, 1237 nerve decompression for, 1234–1235, 1236f, 1251–1252 pathophysiology of, 1234–1236, 1235f, 1236f, 1238 predicting prognosis for, 1227–1228, 1227t, 1228t, 1243 during pregnancy, 1234 radiologic evaluation of, 431, 433f, 1243 recurrence of, 1232, 1239 risk factors for, 1233–1234 sequelae and natural history of, 1243–1244, 1243t, 1244f steroid treatment of, 1249–1250 viral infection and, 1236–1237 Benign paroxysmal positional vertigo (BPPV), 644–656 background of, 644–645 canalithiasis and cupulolithiasis in, 644–645, 645f diagnosis of, 647–648 differential, 648 Dix-Hallpike maneuver for, 223–224, 224f, 647, 647f

in elderly, 536, 646 epidemiology of, 646 etiology of, 646 history of, 647 after inner ear surgery, 646 vs. labyrinthitis, 648 lateral (horizontal) canal diagnosis of, 611, 648 management of, 650 pathophysiology of, 645–646, 646t linear canal sensitivity in, 95 management of, 648–656 barrel roll for, 650 liberatory maneuver for, 648–649, 649f log roll for, 650 mastoid vibration for, 651–652 nonsurgical, 648–652, 649f, 650f, 651t particle repositioning maneuver for, 649–650, 650f, 651t posterior semicircular canal occlusion for, 652–656, 653f–656f prolonged position maneuver for, 650 singular neurectomy for, 652 surgical, 652–656, 653f–656f vestibular habituation therapy for, 648 Ménière’s disease and, 646 migraine with, 511, 646 nystagmus in, 231 objective, 648, 652 pathophysiology of, 645–646, 645f, 646t permanent, 647 pharmacotherapy for, 670 posterior canal, 645, 645f, 647, 647f vs. posterior fossa tumor, 648 post-traumatic, 249, 646 primary (idiopathic), 646 recurrent, 647 secondary, 646, 647 self-limited, 647 subjective, 648, 652 superior canal, 647–648 symptoms of, 178, 179 vestibular evoked myogenic potentials in, 271 after vestibular neuritis, 486, 487 vs. vestibular neuritis, 487t, 648 vestibular rehabilitation therapy for, 1334 Benign paroxysmal vertigo (BPV), of childhood, 557, 559 Benign positional vertigo, of childhood, 665 Benign recurrent vertigo (BRV), migraine with, 511–512 Bennett, Alexander, 24 Benzathine penicillin, for otosyphilis, 665 Benzodiazepines for psychophysiologic dizziness, 667 for tinnitus, 190 for vestibular dysfunction, 668, 669t for vestibular symptoms of migraine, 516 Bergen, Baron, 12 Berry aneurysm AICA, 368f sites for, 438 BET (behind-the-ear) hearing aids, 1283, 1284, 1285, 1287, 1291 Beta-blockers for migraine prophylaxis, 515 for vestibular dysfunction, 669t for vestibular migraine, 665, 666 Betahistine for Ménière’s disease, 628–629, 662 for vestibular dysfunction, 668, 669t Bezold, Friedrich, 22 Bezold’s abscess, 22, 22f, 216 Bezold’s mastoiditis, 22, 22f

BIC (brachium of inferior colliculus), in ascending pathway, 59, 59f BICROS device, after acoustic neuroma surgery, 765 Bielschowsky head-tilt test, 217 Bilger, R. C., 39 Billroth, Theodor, 15 Bill’s bar, 950, 1203f Bill’s island, 690 Binasal hemianopsia, 217f Binaural hearing central nucleus of inferior colliculus in, 64 superior olivary complex in, 47–48, 62 Binaural measures, of auditory processing testing, 275–276 Binaural release from masking, 274 Binaural squelch, 1285 Binaural summation, 1285 Bing test, 220–221 Bing-Siebenmann deformity, hearing loss due to, 600 Binocular single vision, area of, 236 Biofeedback, for tinnitus, 191 Biofilms, and intracranial complications of otitis media, 915 Biopolymers, 1025 Birth injury, facial palsy due to, 1231t, 1241, 1277 Bitemporal hemianopsia, 217f Bithermal caloric test, 608, 613–615, 614f, 615f, 615t Biventral lobule, 1141f Blackout, differential diagnosis of, 518 Blink reflex with facial palsy, 1249 for intraoperative cranial nerve monitoring, 989, 989f Blinking increasing, 1343 reduced, 1340, 1341 Blood oxygenation level-dependent (BOLD) contrast imaging, 320 Blood perfusion imaging using inversion recovery, 320–321 using vascular contrast agents, 320 Blood transfusions, during neurotologic surgery, 717–718 Blue eardrum, 1111 Blurring of vision, with facial paralysis, 1340 Bochdalek’s basket, 855 Body-borne hearing aids, 1283 Boettcher, A., 27 Bojrab maneuver, 611–612, 612f BOLD (blood oxygenation level-dependent) contrast imaging, 320 “Bomber potentials,” in intraoperative facial nerve monitoring, 972, 973 Bone resorption, and intracranial complications of otitis media, 915 Bone scan, of osteoradionecrosis, 1188 Bone spicules, within hemangioma, 426, 428f Bone-anchored hearing devices, 1295, 1296–1297, 1296f, 1299t Bone-conduction hearing devices, 1295, 1296–1297, 1296f, 1299t Bone-conduction Rinne test, 220 Bony septum, 1055f BOR (branchio-oto-renal) syndrome, hearing loss in, 124, 129t Borchardt, M., 729 Borderline node, 895 Borrelia burgdorferi cerebellopontine angle lesions due to, 857, 858 facial palsy due to, 1240

INDEX

Bottleneck principle, of auditory processing, 280 Botulinum toxin (Botox) for hemifacial spasm, 902 for migraine prophylaxis, 515 for swallowing dysfunction, 1356 Boutons, terminal, 1206, 1208f Boxcar designs, for function MRI, 321 BPPV. See Benign paroxysmal positional vertigo (BPPV). BPV (benign paroxysmal vertigo), of childhood, 557, 559 Brachium, of inferior colliculus, myelination of, 567, 568f Brachium conjunctivum (BC), vestibulo-ocular projections in, 84, 84f Brachium of inferior colliculus (BIC), in ascending pathway, 59, 59f Brain abscess imaging of, 409 due to otitis media, 492, 493f, 913t, 919–920, 920f Brain damage, due to meningitis, 494 Brain herniation. See Encephalocele. Brain mapping, 309f, 310–312 advantages and disadvantages of, 311 for auditory processing testing, 282–283 clinical applications of, 311–312 information provided by, 311 technical aspects of, 310–311 Brain prolapse. See Encephalocele. Brain retraction, in combined craniotomy of middle and posterior cranial fossae, 700, 700f Brain retractors, 678 Brain tumors radiation-induced, 1192 seizures due to, 519 vertigo due to, in children, 559–560 Brain-derived neurotrophic factor (BDNF) for aminoglycoside-induced ototoxicity, 251 transgenic expression of, 140 Brainstem auditory processing tests for, 276t cochlear nuclei of, 45, 46f, 47 descending pathways of, 49–50 effects of hearing loss on, 50 facial nerve and, 1201–1202, 1202f generation of evoked potentials in, 46–47 inferior colliculus of, 45, 46f, 48–49 information processing in, 47–50 lemniscal nuclei of, 45, 46f, 48 superior olivary complex of, 45, 46f, 47–48 topography of, 45, 46f ventral surface of, surgical approach to, 699–704, 700f, 701f, 703f Brainstem auditory evoked potentials (BAEPs), 68–70. See also Auditory brainstem response (ABR). in acoustic neuroma, 171, 171t, 172 with auditory brainstem implant, 1326 in cochlear implant surgery, 301–303, 302f, 1304 in cochlear vs. noncochlear hearing loss, 166, 166t in cochleovestibular nerve compression syndrome, 906, 906t display of, 68, 69f generation of, 46–47, 69–70, 70f interpretation of, 52–53 in pulsatile tinnitus, 209 uses of, 68–69 Brainstem auditory pathway, 45, 46f development of, 565–567, 565f, 566f Brainstem dysfunction, due to craniovertebral junction anomalies, 1148

Brainstem encephalitis, 546 Brainstem gliomas, 876–880, 878f, 879f, 880t Brainstem medulloblastoma, facial palsy due to, 1238f Branchio-oto-renal (BOR) syndrome, hearing loss in, 124, 129t Bray, C. W., 38 Breast carcinoma, metastatic to cerebellopontine angle, 865, 865f, 866f to petrous apex, 1120, 1121f to posterior fossa, 888f to temporal bone, 150f Breuer, Joseph, 27 Brief Smell Identification Test (B-SIT), 216 Brown, Lester A., 35 Brown’s sign, 35 Brown-Séquard, Charles-Édouard, 15, 24 Bruns’ nystagmus, 222, 231 BRV (benign recurrent vertigo), migraine with, 511–512 B-SIT (Brief Smell Identification Test), 216 BT (burst-tonic) cells, 102, 103–104, 104f, 105, 106f Buccal nerve, 1224f Buncke, H. J., Jr., 1004, 1005 Bungner bands, 1210 Burkland, C. W., 1028 Burst activity, in intraoperative facial nerve monitoring, 971–972, 973, 973f, 988 Burst neurons, 105, 106f Burst-tonic (BT) cells, 102, 103–104, 104f, 105, 106f Butyrophenones, for vestibular dysfunction, 669, 669t

C C trains, in intraoperative facial nerve monitoring, 972 Cadwell Cascade, 960, 961f CAEPs (cortical auditory evoked potentials) in children, 571 to estimate amplification benefit, 297 Cairns, Hugh, 33, 730 Calcification, of meningiomas, 802, 802f Calcitonin, for Paget’s disease of temporal bone, 1130–1131 Calcium (Ca2+) channel blockers for vestibular dysfunction, 669t for vestibular migraine, 665, 666 Caloric response(s), 614–615, 614f, 615f in elderly, 534 in multiple sclerosis, 503 normal, 614 Caloric stimulation, canal response to linear acceleration during, 95 Caloric test, bithermal, 608, 613–615, 614f, 615f, 615t Calvarium, outer, 1006f Campbell, E. H., 1028 Canal nerves, 77f, 80 Canalith jam, 645 Canalith repositioning procedure (CRP), 649 Canalithiasis, 610f, 611, 644 lateral canal, 646, 646t posterior canal, 645, 645f Cancellation, of vestibulo-ocular reflex, 110 CANS (central auditory nervous system). See Central auditory system (CAS). Canthoplasty, 1344–1345, 1345f Canthus, 1344 CAP (compound action potential), 1208 with cochlear implant, 1304 CAPDs (central auditory processing disorders). See Auditory processing disorders (APDs).

1369

Carbogen inhalation therapy, for idiopathic sudden sensorineural hearing loss, 596 Carbonic anhydrase inhibitors, for Ménière’s disease, 661–662 Carboplatin, hearing loss due to, 594 Carcinoembryonic antigen (CEA), in meningiomas, 798, 799 Carcinoid syndrome, 543–544 Carcinoma adeno-, 1031 vaginal, metastatic to cerebellopontine angle, 866 adenoid cystic of cerebellopontine angle, 853, 867 of temporal bone, 1031 basal cell, of external auditory canal and temporal bone, 415, 417f, 1030 breast, metastatic to cerebellopontine angle, 865, 865f, 866f to petrous apex, 1120, 1121f to posterior fossa, 888f to temporal bone, 150f of endolymphatic sac, labyrinthine hemorrhage due to, 333, 333f epidermoid, of cerebellopontine angle, 866 involving facial nerve, 427 lung, metastatic to cerebellopontine angle, 865, 866f, 867f mucoepidermoid, 1031 oropharyngeal, metastatic to cerebellopontine angle, 866 paraneoplastic syndromes associated with, 546–547 pharyngeal, metastasis of, 150–151 squamous cell from cerebellopontine angle epidermoid cysts, 847 of external auditory canal and temporal bone, 415, 417f, 1030 involving facial nerve, 427 primary intracranial, 866 Carcinomatosis, leptomeningeal, 867f Carhart, Raymond, 1281 Carhart method, for hearing aids, 1286 Caroticotympanic artery, 1055f Caroticotympanic nerves, in otalgia, 195 Carotid aneurysm(s) intrapetrous, 1121, 1122f imaging of, 389, 390f treatment of, 439, 440f–441f radiation-induced, 1190, 1191f sites of, 155–156 Carotid artery(ies) aberrant, 406–407, 410f external, surgical anatomy of, 1000, 1157f and facial nerve, 1220f internal. See Internal carotid artery (ICA). and petrous apex, 1108, 1108f radiation-induced rupture of, 1190–1191 vasospasm of, 716–717 Carotid artery disease, atherosclerotic, 155, 156f pulsatile tinnitus due to, 204, 208, 208t, 209 Carotid canal anatomy of, 399, 998f, 1054f, 1137f surgical, 1000 invasion by meningioma of, 148f Carotid occlusive disease, radiation-induced, 1190 Carotid sympathetic plexus, in otalgia, 195 Carotid-cavernous fistulas (CCFs) classification of, 935, 935f clinical presentation of, 451 defined, 934 diagnosis of, 451, 452f direct, 451, 935

1370

INDEX

Carotid-cavernous fistulas (CCFs) (Continued) indirect, 935 location and arterial sources of, 935, 935f pathology and pathogenesis of, 451, 936 pulsatile tinnitus due to, 205f treatment for, 451, 452f, 938, 939f, 942 Carotid-jugular compression therapy, for dural arteriovenous fistulas, 447 Carrel, Alexis, 1004 Carvedilol, for vestibular dysfunction, 668, 669t CAS. See Central auditory system (CAS). Cascade effect, 896 Cascade system, 960, 961f Cataracts, in neurofibromatosis 2, 786 Caudal vestibulospinal tract (CVST), 104, 117–118 Caudate nucleus, 1201f Cavernous artery, inferior, 1055f Cavernous malformations, 934 Cavernous sinus dural arteriovenous fistulas of, 443 neuromas of, 1051, 1051f surgical anatomy of, 1001–1002, 1054–1055, 1055f venous bleeding from, during neurotologic surgery, 715 Cavernous sinus thrombosis, 217 Cavitron ultrasonic surgical aspirator, 678 Cawthorne, Terence, 33–34, 33f, 35, 37, 661 Cawthorne’s exercises, for elderly, 537 CCFs. See Carotid-cavernous fistulas (CCFs). CCK (cholecystokinin), with paragangliomas, 544 CCR (cerivocollic reflex), 540 CDR (cortical discriminative response), in children, 571 CEA (carcinoembryonic antigen), in meningiomas, 798, 799 Cefazolin (Ancef), for wound infections, 721 Cefepime, for skull base osteomyelitis, 1103 Ceftazidime (Fortaz) for skull base osteomyelitis, 1103 for wound infections, 721 Cell body, of neuron, 1206, 1207, 1208f Center of gravity (COG), in dynamic posturography, 257, 267–268 Centimorgans (cM), 126 Central activation, facial nerve assessment with, 1248–1249, 1248f Central auditory nervous system (CANS). See Central auditory system (CAS). Central auditory processing disorders (CAPDs). See Auditory processing disorders (APDs). Central auditory system (CAS) development of, 563–570 abnormal, 572–579, 572f, 577f anatomic, 564–567, 564f–566f, 568f, 569f functional, 567–570, 569f general aspects of, 564–565, 564f influence of environmental factors on, 572–578 pathology during, 578–579 temporal ordering of neuron generation in, 564–565, 564f redundancy in, 274–275 Central auditory testing. See Auditory processing (AP) testing. Central balance deficits, dynamic posturography for, 263–264, 263f Central nervous system disorders, vestibular dysfunction due to, 177, 180–181 Central nervous system nerve fibers, 894–895, 895f Central nervous system plasticity, and vestibular rehabilitation, 1331–1332

Central neuropathic pain, and tinnitus, 187 Central nucleus of inferior colliculus (ICC, CNIC) development of, 566–567 effect of cochlear implant on, 577 physiology of, 59f, 62–64, 63f, 66 Central presbycusis, 281–282 Central sensitization, 194–195 Central skull base, defined, 383 Centrifugal pathways, to cochlear nucleus and higher centers, 66 Cephalocele, of petrous apex, 1115–1116, 1116f Cerebellar artery inferior anterior. See Anterior inferior cerebellar artery (AICA). posterior. See Posterior inferior cerebellar artery (PICA). vascular loop of, 157f superior anatomy of, 893, 894, 1145f surgical, 679, 679f Cerebellar astrocytomas, 880–883, 881f, 882f, 883t Cerebellar degeneration, paraneoplastic, 546–547 Cerebellar fastigial projection, 87 Cerebellar injury, due to acoustic neuroma surgery, 755, 755f Cerebellar lesions, of cerebellopontine angle, 856–857 Cerebellar loop, 102, 102f Cerebellar lymphoma, 370, 372f Cerebellar peduncles, 1145f Cerebellar retraction, in retrosigmoid approach, 687, 689 Cerebellomedullary fissure vein, 893 Cerebellomesencephalic fissure vein, 893 Cerebellopontine angle (CPA) anatomy of, 806, 850–851 microsurgical, 892–893, 893f vascular, 893–894, 894t arteriovenous malformations in, 369, 369f direct extension of skull base lesions to, 861–863, 862f–864f embryology of, 850 and facial nerve, 893, 1202, 1203f surgical approach to, 1212–1215, 1213f–1217f heteroglial tissue of, 853 imaging of, 349–377 computed tomography for, 349 MRI for, 349–354, 350f–354f, 354t normal structures in, 351f–352f technical considerations in, 349–354, 350f–354f, 354t salivary gland heterotopia of, 853 vasculature of, 851 Cerebellopontine angle (CPA) cyst(s) arachnoid, 364, 365f, 857, 858, 858f colloid, 853 congenital, 364 cysticercosis, 364, 365f, 858 dermoid, 852 enterogenous, 853 epidermoid, 841–848, 852 clinical signs of, 842 diagnosis of, 842–844, 842f, 843f differential diagnosis of, 841 embryology of, 841–842 epidemiology of, 841 historical background of, 841 imaging of, 362, 363f, 364f pathology of, 842 surgical treatment of, 844–847, 845t unusual complications of, 847 respiratory epithelial, 853

Cerebellopontine angle (CPA) lesions abscess as, 858, 859f aspergilloma as, 857 cerebellar, 856–857 cholesterol granulomas as, 858, 860f classifications and incidence of, 354–355, 355t congenital malignant degeneration of, 866–867 rest, 852–853, 852f diagnosis of, 809–810, 809f extradural, 370, 370f, 371f gummas as, 857–858 hearing loss due to, 164, 167–172, 167t–171t inflammatory and autoimmune, 857–858, 858f–860f intracanalicular, 371–374, 373t, 374f–377f due to Lyme disease, 857, 858 metastatic, 865–866 from extracranial sources, 865–866, 865f–867f from intracranial sources, 865 due to osteoradionecrosis, 858 rare, 850–868, 851t sarcoidosis as, 857 tuberculoma as, 857 vascular, 349–350, 352f, 367–369, 368f, 369f, 863–865, 864f Cerebellopontine angle (CPA) meningioma(s), 806–811 audiovestibular testing for, 799 classification of, 806–807 clinical presentation of, 807–809, 807t complications of, 811 defined, 807 diagnosis of, 809–810, 809f epidemiology of, 806 facial nerve preservation with, 803, 811, 832–833, 833t hearing preservation with, 828–832, 828t, 829f–831f, 829t historical background of, 806 imaging of, 359f, 361–362, 361f–363f, 809–810, 809f origin of, 806 pathologic correlates of, 147, 147f preoperative evaluation of, 804 surgical management of, 810–811, 810t vs. vestibular schwannomas, 809 Cerebellopontine angle (CPA) syndrome, 850–852 Cerebellopontine angle (CPA) tumor(s) adenoid cystic carcinoma as, 867 astrocytomas as, 854, 857 cystic, 853, 855f ceruminous adenomas as, 862–863 cholesteatomas as, 851 chondromas and chondrosarcomas as, 862f, 863 chordoma as, 863 choroid plexus papilloma as, 855–856 classifications and incidence of, 354–355, 355t craniopharyngioma as, 863 cylindroma as, 853 ependymomas as, 854–855 epidermoid carcinoma as, 866 fibrosarcoma as, 863 fibrous histiocytoma as, 863 glioblastomas as, 857 gliomas as, 854 leptomeningeal, 853 glomus jugulare, 353f, 366–367, 367f, 862, 862f, 863f hamartomas as, 853 hemangioendotheliomas, hemangioblastomas, and hemangiosarcomas as, 856–857 hydrocephalus due to, 526, 526f, 527f

INDEX

Cerebellopontine angle (CPA) tumor(s) (Cont.) intra-axial, 370–371, 371f–373f intraoperative cranial nerve monitoring for, 966–974 activity evoked by electrical stimulation in, 963f, 966–970, 969f–971f electrode placement for, 962, 962f, 967 spontaneous and mechanically elicited activity in, 970–974, 972f, 973f lipomas as, 364, 365f, 852–853, 852f lymphoma as, 867 medulloblastoma as, 856 medullomyoblastoma as, 853, 867 melanoma as, 866 vs. Ménière’s disease, 628 MRI of, 349–351 oligodendrogliomas as, 854 osteoma as, 863, 864f osteosarcoma as, 863 plasmacytomas as, 867 primary brain neoplasms as, 853–856, 855f rare, 850–868, 851t rhabdomyosarcoma as, 856 schwannomas as, 858–861 facial nerve, 366, 367f, 371, 423, 859 lower cranial nerve, 860–861, 861f nonvestibular posterior fossa, 366–367, 366f, 367f trigeminal nerve, 859–860, 860f vestibular, 354f, 355–360, 356f–360f, 852, 868t seizures due to, 519 surgical approach to, 685f, 686 extended middle fossa, 696, 696f middle fossa-transpetrous apex, 696–698, 697f presigmoid, 686 retrolabyrinthine, 685f, 686, 689–691, 690f retrosigmoid, 686, 687–689 transcochlear, 685f, 686, 702–704, 703f translabyrinthine, 685f, 686, 691–693, 691f teratomas as, 853, 866–867 xanthogranuloma as, 853 Cerebellopontine fissure vein, 893, 894 Cerebellum, 1139f, 1142, 1160f aging effect on, 534, 534t Cerebral angiography, of meningiomas, 456–464, 462f–463f, 800 Cerebral arteritis, central processing deficits due to, 578 Cerebral cortex auditory processing tests for, 276t facial nerve and, 1200, 1201f Cerebral edema, postoperative, 719–720, 719f Cerebral hernia. See Encephalocele. Cerebral radiation necrosis (CRN), 1191 Cerebritis, due to otitis media, 913t, 919–920 Cerebrospinal fluid (CSF) formation, flow, and absorption of, 524–525, 525f relationship to inner ear of, 525–526 Cerebrospinal fluid (CSF) drainage for cerebral edema, 719 continuous lumbar, for CSF lead, 931 for CSF leak, 721 Cerebrospinal fluid (CSF) findings in multiple sclerosis, 506 in neurosarcoidosis, 476 in superficial siderosis, 479 Cerebrospinal fluid (CSF) leak due to acoustic neuroma surgery, 755–756, 755f in Chiari malformation, 1146 due to cochlear implantation, 1312 with cranial base surgery, 707–708 due to pacchionian body, 153

postoperative, 720–721, 721f in retrosigmoid approach, 689 due to temporal bone encephalocele, 1090–1091 of temporal bone origin, 926–932 acquired, 926, 927t adjunctive measures for, 931–932 antibiotic prophylaxis for, 932 classification of, 926, 927t with cochlear dysplasia, 927–928, 928f, 931 congenital, 926, 927t continuous lumbar CSF drainage for, 931 diagnosis of, 928–929, 929f, 930f etiology of, 926–928, 927f, 928f intraoperative fluorescein for, 932 intraoperative glue for, 931 due to labyrinthine and perilabyrinthine abnormalities, 927–928, 928f neoplastic, 927, 931 postinfectious, 927, 931 postoperative, 926–927, 927f, 929–930 post-traumatic, 927, 929–931 spontaneous, 928, 930–931 due to trauma, 927, 929–931, 1082–1083 treatment for, 929–931 with transjugular craniotomy, 698 in translabyrinthine approach, 693 with vestibular neurectomy, 956 Cerebrospinal fluid (CSF) pressure, normal, 527 Cerivocollic reflex (CCR), 540 Certification in Neurophysiological Intraoperative Monitoring (CNIM), 959 Ceruminous adenoma, of cerebellopontine angle, 862–863 Cervical adenocarcinoma, metastatic to cerebellopontine angle, 866 Cervical injury, vestibular symptoms of, 181 Cervical lymphadenopathy, 216 Cervical nerve(s), 1224f in otalgia, 195 Cervical plexus, in otalgia, 195 Cervical proprioceptive dysfunction, 540–542, 541t Cervical proprioceptive function, 540 Cervical vertigo, 181, 540–542 cervical proprioceptive function and, 540 clinical evidence of, 540–541, 541t defined, 540 differential diagnosis of, 541, 541t in elderly, 537 treatment for, 541–542 Cervicogenic headache, otalgia due to, 201 Cervicomedullary junction, 1141f Cervico-ocular reflex (COR), 540 CFs (climbing fibers), 102, 102f, 111, 117 Chalk bone disease, 1127 CHAPS (Children’s Auditory Performance Scale), 279 Characteristic frequency, 55 Charcot’s triad, in multiple sclerosis, 504–505 Chemical labyrinthectomy, for Ménière’s disease, 630–631, 662–664 Chemical teratogens, hearing loss due to, 594–595 Chemodectomas, 1039 angiography of, 455–456 of jugular foramen. See Glomus jugulare tumors. Chemotherapy, for medulloblastoma, 876 Chewing, tearing while, 1340, 1343 Chiari malformation, 1142–1146, 1146f, 1148–1149

1371

Chief cells, of paragangliomas, 543 Children auditory processing testing of, 278–279, 568–572 development of auditory competence in, 569–570, 570f development of vestibular system in, 553–554 dizziness in, 553–561 due to ataxia, 554, 560 due to benign paroxysmal vertigo, 557, 559 due to benign positional vertigo, 665 with congenital and hereditary hearing loss, 556 with congenital anomalies, 556 due to congenital nystagmus, 560 development of vestibular system and, 553–554 diagnosis of, 554–556 functional, 561 due to labyrinthitis, 559 due to Ménière’s disease, 557 due to meningitis, 559 due to metabolic/systemic disease, 560 due to migraine, 557, 559 due to multiple sclerosis, 560 due to neurosyphilis, 560 due to otitis media, 556–557 due to perilymphatic fistula, 558–559 toxic, 561 due to trauma, 557–558 due to tumors, 559–560 due to vertiginous seizures, 559 due to vestibular neuronitis, 559 due to vestibular vertigo, 522 facial nerve neoplasms in, 1262 facial palsy in, 1241 iatrogenic facial nerve injuries in, 1277 meningiomas in, 793 nystagmus in, 554–555 skull base osteomyelitis in, 1099 temporal bone trauma in, 1074 Children’s Auditory Performance Scale (CHAPS), 279 “Chinese flap,” 1012 CHL. See Conductive hearing loss (CHL). Chloromas, 151 Chlorpromazine (Thorazine), for vestibular dysfunction, 669, 669t Cholecystokinin (CCK), with paragangliomas, 544 Cholesteatoma(s) of cerebellopontine angle, 852 congenital. See Epidermoid cysts. dizziness due to, 556–557 in elderly, 536 of external auditory canal, 415, 416f due to fibrous dysplasia of temporal bone, 1125, 1127, 1127f intracranial complications of, 409–410, 412f–414f and intracranial complications of otitis media, 914, 917, 920f involving facial nerve avoiding injury with, 1274, 1275f facial paralysis due to, 432 surgical approach to, 1217–1218, 1218f, 1219f middle ear, 340, 345f, 407–408, 412f of petrous apex, 1114–1115, 1115f hearing loss due to, 173 due to radiation therapy, 1188f, 1190 temporal bone encephalocele due to, 1090 due to temporal bone fracture, 1083, 1083f trigeminal neuralgia due to, 903

1372

INDEX

Cholesterol granuloma(s) of cerebellopontine angle, 858, 860f involving facial nerve, 427 of petrous apex, 370, 370f, 1111–1114, 1112f, 1113f hearing loss due to, 173 imaging of, 384–385, 385f, 386f Cholinergic system, central, in compensation of loss of labyrinth function, 114 Chondroma, of cerebellopontine angle, 862f, 863 Chondromyxoid fibromas, of petrous apex, 1121 Chondromyxosarcoma, otitis media due to, 151f Chondrosarcoma(s) of cerebellopontine angle, 863 jugular fossa involvement in, 407 of petroclival junction, 681–683, 682f of petrous apex, 370, 371f, 1117–1118, 1118f imaging of, 389–393, 392f, 393f Chorda tympani nerve anatomy of, 1204, 1215, 1217f–1219f, 1218, 1271f anomalies of, 1206 development of, 1199 functional testing of, 1245 iatrogenic injury of, 1277 Chordoma(s) of cerebellopontine angle, 863 chondroid, 1048–1049, 1049f clival (spheno-occipital), 1048–1049 imaging of, 1048–1049, 1049f, 1064f Le Fort I osteotomy for, 1059f pathology of, 1048, 1048f surgical approach to, 682f, 683 transcervical-retropharyngeal, 1062–1063, 1062f, 1063f transoral-transpalatal, 1056–1058, 1056f, 1057f transpalatal, 1058, 1058f, 1059f of jugular fossa, 407 of petrous apex, 1118–1119, 1119f imaging of, 389–393, 391f radiation therapy for, 1053 Choristomas, middle ear salivary gland, facial nerve involvement in, 430 Choroid plexus, 1140f, 1141f, 1145f, 1324f Choroid plexus papillomas, 371, 373f, 855–856 Choroid plexus tumors, 883–885, 886f, 886t Chromatolysis, 1210 Chronic paroxysmal hemicrania, otalgia due to, 202 Chronic suppurative otitis media (CSOM), facial palsy due to, 1240 CI(s). See Cochlear implant(s) (CIs). CIC (completely in-the-canal) hearing aids, 1283, 1284, 1285 CII System, 1305, 1309 Ciprofloxacin, for skull base osteomyelitis, 1103 Circular sinus, 1054 Circular vection, 107 CIS (continuous interleaved sampling), 1303, 1305, 1306, 1307, 1317 CIS+ coding strategy, 1307 CIS PRO+ speech processor, 1307 Cisplatin-induced ototoxicity gene transfer for protection against, 140 hearing loss due to, 594 semicircular canal dysfunction due to, 251–252 Cisternography, of posterior fossa arachnoid cysts, 947 Clarion cochlear implant, 1305, 1309, 1313 for children, 1317 Clarke, Robert Henry, 1024 Claustrum, 1201f Clement VII, Pope, 3

Climbing fibers (CFs), 102, 102f, 111, 117 Clindamycin phosphate (Cleocin), for wound infections, 721 Clival chordoma, 1048–1049 imaging of, 1048–1049, 1049f, 1064f Le Fort I osteotomy for, 1059f MRI of, 1064f pathology of, 1048, 1048f surgical approach to, 682f, 683 transcervical-retropharyngeal, 1062–1063, 1062f, 1063f transoral-transpalatal, 1056–1058, 1056f, 1057f transpalatal, 1058, 1058f, 1059f Clival cysts, 945 Clival meningioma(s), 812–818 approach selection for, 815, 815f–817f challenges of, 812–813 clinical presentation of, 813–814, 1049–1050 defined, 813 diagnosis of, 814, 1050 extension of, 713f, 813 frontal-temporal/lateral facial approach for, 1063–1066, 1064f, 1065f grading system for, 814, 814t imaging of, 1153f mortality and quality of life with, 816–818 origin and classification of, 813 pathology of, 1049 preoperative considerations for, 814–815, 814t recurrent, 462f–463f resection of, 816, 817t, 1050 surgical history of, 815 Clival tumors, 682f, 683, 1047–1063 interventional radiology for, 1053 pathology of, 1047–1052, 1048f–1052f radiation therapy for, 1052–1053 surgical anatomy of, 1053–1055, 1054f surgical approach to, 701f, 1055, 1055t lateral, 1060–1063, 1061f–1063f midline, 1055–1060, 1056f–1060f Clivus anatomy of, 1137f, 1139f, 1140f surgical, 1053–1054, 1054f, 1158f, 1159f defined, 683, 1074 transsphenoidal approach to, 1156, 1157f Clonazepam (Klonopin), for vestibular dysfunction, 668, 669t Cluster headache, otalgia due to, 201–202 cM (centimorgans), 126 CMAPs. See Compound muscle action potentials (CMAPs). CMs. See Cochlear microphonics (CMs). CMV (cytomegalovirus) central processing deficits due to, 578 congenital, hearing loss due to, 598 CN. See Cochlear nucleus(i) (CN). CNAP (compound nerve action potential) for cochlear nerve, 982, 984–988, 984f–986f for facial nerve, 966–967 CNC (consonant nucleus consonant) words, 1310 CNCS. See Cochleovestibular nerve compression syndrome (CNCS). CNIC. See Central nucleus of inferior colliculus (ICC, CNIC). CNIM (Certification in Neurophysiological Intraoperative Monitoring), 959 CNS. See Central nervous system entries Cocaine test, 234 COCB (crossed olivocochlear bundle), 66 Cochlea active and passive filtering by, 589 anatomy of, 1216f congenital malformations of, 332

contrast enhancement of, 338f–341f as frequency analyzer, 54–55, 54f incomplete partition of, hearing loss due to, 600 invasion by meningioma of, 147f labyrinthitis ossificans of, 151–152, 152f malignant neoplasms of, 340, 344f metastasis to, 344f physiology of, 589–591, 590t, 591t radiation effect on, 1190 sound conduction to, 53–54 Cochlear aplasia, hearing loss due to, 600 Cochlear aqueduct, 525 enlargement of, 601 patent, CSF leak from, 928 Cochlear basal turn dysplasia, hearing loss due to, 600 Cochlear dysplasia cochlear implants with, 1318, 1319 CSF leak with, 927–928, 928f, 931 Cochlear hearing loss, 589–603 autoimmune, 639–642, 640t congenital causes of, 599–602 idiopathic sudden, 595–596 infectious causes of, 597–599 metabolic, 602 noise-induced, 591–592 noncochlear vs., 165–166, 166t due to otic capsule bony diseases, 602–603 due to ototoxicity, 593–595 pathophysiology of, 589–591, 590f, 591f presbycusis as, 592–593 due to temporal bone trauma, 596–597 Cochlear hydrops, 621–622 due to syphilis, 627f Cochlear hypoplasia, hearing loss due to, 600 Cochlear implant(s) (CIs) in adolescents, 1316 in adults, 1309–1314 audiologic criteria for, 1310 in children, 1317–1318 for auditory neuropathy, 474 bilateral, 1307 birth of, 38–39 and central auditory system, 576–578, 577f in children, 1315–1320 patient selection for, 1315–1316, 1316t Clarion, 1305, 1309, 1313 for children, 1317 counseling for, 1310 defined, 1301 development of, 1301 dipole source analysis for, 316, 318f electrodes for, 1303–1304, 1303f, 1305, 1306, 1307 functional MRI of, 322 future of, 1307–1308 with labyrinthitis ossificans, 151–152 Med-El (Combi 40+), 1306–1307, 1309, 1313 for children, 1317, 1319 microphones for, 1302, 1302f minimum response level of, 1304 Nucleus, 1305–1306, 1309 for children, 1315, 1317, 1319 patient selection for, 1309–1310 positron emission tomography for, 318 program or map of, 1304 programming of, 1304 promontory stimulation for, 1310 receiver-stimulator of, 1302, 1302f, 1305, 1306, 1307 selection of side for, 1311 speech processor and coding strategies for, 1302–1303, 1302f, 1305, 1306, 1307

INDEX

Cochlear implant(s) (CIs) (Continued) systems for, 1305–1307 in children, 1316–1317 technology basics for, 1301–1304 threshold of, 1304 Cochlear implant surgery in adolescents, 1316 in adults, 1309–1314 complications of, 1312 considerations for, 1310–1312 medical evaluation for, 1310 patient selection for, 1309–1310 procedure for, 1311–1312, 1311f professional requirements for, 1313–1314 radiologic evaluation for, 1310 rehabilitation after, 1312 results of, 1313 auditory potentials in, 301–303, 302f, 303f in children, 1315–1320 with aberrant facial nerve, 1319 audiologic assessment for, 1317–1318 with cochlear dysplasia, 1318, 1319 complications of, 1319 historical background of, 1315 with intracochlear ossification, 1319 medical assessment for, 1318 patient selection for, 1315–1316, 1316t with previous auditory experience, 1316 psychological assessment for, 1318 results of, 1319––1320 technique for, 1318–1319 unusual considerations with, 1319 very young, 1315–1316, 1316t facial nerve injury during, 1276–1277 Cochlear injuries, tinnitus due to, 185 Cochlear microphonics (CMs) in auditory neuropathy, 471, 472, 473f in electrocochleography, 291, 291f intraoperative, 986 in evoked potentials, 67, 68, 68f in frequency analysis, 56 history of, 38 Cochlear nerve acoustic neuroma invasion of, 761–762 compression of hearing loss due to, 173 vestibular symptoms of, 180 examination of, 220–221, 221f and facial nerve, 1203f intraoperative monitoring of, 981–988 analogue vs. digital filtering in, 982 auditory brainstem response recording for, 981–984, 983f, 987–988 compound nerve action potentials in, 982, 984–988, 984f–986f direct action potentials in, 984–985, 984f–986f electrocochleography for, 986–988, 986f electrodes for, 981–982, 984–985, 985f evoked potentials in, 987 historical background of, 959 interpretation of, 982–983 near-field recordings in, 982 and nerve preservation, 987–988 and postsurgical auditory function, 984 reducing electrical and acoustic interference with, 982 stimulus and recording parameters for, 981–982 during vestibular schwannoma surgery, 983–984, 983f and vestibular nerve, 951, 951f, 953, 955f in vestibular schwannoma, 144–145, 145f, 983–984, 983f Cochlear nerve preservation, cochlear nerve monitoring and, 987–988

Cochlear neuritis, 374, 377f Cochlear nucleus(i) (CN) anatomy of, 45, 46f, 81f, 1323–1324, 1324f auditory brainstem implant in, 1323–1324 in central auditory system, 564, 565–566, 565f, 566f centrifugal pathways to, 66 connections between, 62 effects of conductive hearing loss on, 573 information processing in, 47, 61, 61f physiology of, 59f–62f, 60–62 response areas of, 60–61, 61f tonotopic organization of, 60, 60f ventral anterior anatomy of, 60, 60f development of, 565, 565f, 566 effect of cochlear implant on, 577 with auditory brainstem implant, 1323–1324 in brainstem auditory pathway, 45, 46f, 47 posterior, 60, 60f development of, 565, 565f Cochlear ossificans, 491 Cochlear otosclerosis, 1130f, 1132t, 1133t Cochlear schwannomas, 339, 342f Cochleariform process, 1204f, 1218f, 1219f, 1271f Cochleosaccular degeneration, deafness due to, 50 Cochleosaccular dysplasia, hearing loss due to, 600 Cochleosacculotomy, for Ménière’s disease, 631 Cochleovestibular cleavage plain, 951, 953 Cochleovestibular nerve (CVN) anatomy of, 893, 893f microvascular decompression of, 899–900, 899f, 900f, 901 transition zone of, 895, 895f Cochleovestibular nerve compression syndrome (CNCS), 906–908 clinical features of, 906, 906t, 907f diagnostic evaluation of, 907 histopathology of, 898–899 historical background of, 906, 906f Ménière’s disease due to, 906, 906f pathologic correlates of, 157, 157f pathophysiology of, 898 site of lesion for, 906–907 symptoms of, 180 treatment for, 907–908 Cochleovestibular neurectomy, translabyrinthine approach to, 691 Cockayne’s syndrome, central processing deficits with, 578 Cocktail party phenomenon, 62 COG (center of gravity), in dynamic posturography, 257, 267–268 Cogan’s syndrome, 233 labyrinthitis due to, 336, 337f vs. Ménière’s disease, 627 Coincidence detectors, in medial superior olivary nucleus, 62 Collagen vascular diseases, vestibular dysfunction with, 180 Collet-Sicard syndrome, 822 Colloid cysts, of cerebellopontine angle, 853 Color perception, 217 Combi 40+ cochlear implant, 1306–1307, 1309, 1313 for children, 1317 Comitant deviation, 235 Commissural projections, of vestibular nuclei, 82f, 83, 83f, 105–106, 106f in compensation of loss of labyrinth function, 113–114

1373

Commissure of Probst, 64 Common cavity deformity, hearing loss due to, 600–601 Comparative approach, to hearing aids, 1286 Compazine (prochlorperazine) for vertigo in elderly, 537 for vestibular dysfunction, 668–669, 669t Compensation, vestibular assessment of, 1333–1334 dynamic, 1332–1333 functional, 1334 physiologic, 1333–1334 static, 1332 Complete penetrance, 123, 124, 124f Completely in-the-canal (CIC) hearing aids, 1283, 1284, 1285 Complex partial seizures, vestibular symptoms of, 181 Compound action potential (CAP), 1208 with cochlear implant, 1304 Compound muscle action potentials (CMAPs), 964, 964f of facial nerve, 969, 1223–1228, 1224f, 1225f with facial palsy, 1247, 1247f of trigeminal nerve, 978 Compound nerve action potential (CNAP) for cochlear nerve, 982, 984–988, 984f–986f for facial nerve, 966–967 Compression circuits, for hearing aids, 1289–1290, 1289f Compression therapy, for arteriovenous malformations, 938–939 Compton effect, in Gamma Knife radiosurgery, 1168 Computed tomography (CT) of acoustic neuroma, 744, 745t, 746 of arteriovenous malformations, 439, 938 of cerebellopontine angle, 349 of cerebellopontine angle epidermoid cysts, 843–844, 843f of cochlear implants, 1310 in children, 1318 of congenital malformations of inner ear, 332 of craniovertebral junction tumors, 1152, 1152f of CSF leak, 929, 929f, 930f of facial nerve, 419–421, 420f, 421f of facial nerve tumors, 1265 of facial palsy, 1242, 1242f of glomus jugulare tumors, 1039, 1039f of hydrocephalus, 527 of jugular foramen meningiomas, 1044 of jugular foramen schwannomas, 1042, 1043f of labyrinthitis ossificans, 334 of lateral skull base, 383, 384 of Ménière’s disease, 345, 627 of meningiomas, 457–458, 800–803, 802f vs. acoustic neuroma, 745t cerebellopontine angle, 809 clival and petroclival, 814 foramen magnum, 826 jugular foramen, 822 Meckel’s cave, 819–820 mid–skull base, 1050 after meningitis, 495 of otosclerosis, 345, 346f of petrous apex lesions, 1109, 1109f, 1110f of posterior fossa arachnoid cysts, 946 for pulsatile tinnitus, 209 single-photon emission, 53 of skull base osteomyelitis, 1101–1102, 1101f of temporal bone encephalocele, 1091–1092, 1091f of temporal bone trauma, 1076, 1076f of temporal bone tumors, 1029

1374

INDEX

Computerized dynamic posturography. See Dynamic posturography. Concurrent validity, of dynamic posturography, 259–260 Concussion, labyrinthine, 179, 249, 557–558 Conditioned orienting response testing (COR), after meningitis, 495 Conditioning activities, in vestibular rehabilitation, 1336 Conductive hearing loss (CHL), 164 anatomic effects of, 573 development of central auditory system with, 572–574, 572f physiologic responses to, 574 due to temporal bone trauma, 1084–1085, 1084t Condylar canal, 998f, 1054f Condylar emissary vein, 1038 Conformal radiation, 1181 Congenital anomalies of facial nerve, 1205–1206, 1205f–1207f, 1272, 1274f iatrogenic injury due to, 1277 imaging of, 421–423, 423f, 424f of inner ear hearing loss due to, 599–601 imaging of, 332 with vestibular dysfunction, 556 Congenital facial palsy, 1241 Congenital heart disease, dizziness due to, 560 Congenital infections, hearing loss due to, 598 Congenital perilymph fistula, 249 Congenital rest lesions, of cerebellopontine angle, 852–853, 852f Congenital syphilis, 250 Conley, J., 1005 Connexin 26 (CX26), in nonsyndromic hereditary hearing loss, 131, 132–133 Connexin genes, 602 Consanguineous mating, 123, 123f Consonant nucleus consonant (CNC) words, 1310 Construct validity, of dynamic posturography, 260–262 Contact lens, bandage, 1344 Continuous interleaved sampling (CIS), 1303, 1305, 1306, 1307, 1317 Contour electrode array, 1306, 1317 Contralateral routing of sound (CROS) amplification, 1285–1286 after acoustic neuroma surgery, 765 Contrast enhancement, of labyrinth, 337–338, 338f–341f Coogan’s syndrome, vestibular symptoms of, 180 Cooper, Astley, 12, 15 COR (cervico-ocular reflex), 540 COR (conditioned orienting response testing), after meningitis, 495 Corneal irritation, tearing due to, 1341 Corneal reflex(es), 218 with acoustic neuroma, 740, 741 Corneal sensation, loss of, 1341 Corneoretinal potentials, 608, 609f “Cornflaking,” 690 Coronal forehead flap, 1006f Corpus callosum, 1201f Corti, Marquis Alfonso, 19–20, 19f Cortical auditory evoked potentials (CAEPs) in children, 571 to estimate amplification benefit, 297 Cortical discriminative response (CDR), in children, 571 Cortical mastoidectomy, 1032 Cortical vestibular projection, 87–88 Corticobulbar tract, 1200

Corticosteroids for autoimmune inner ear disease, 641–642 for cerebral edema, 719–720 for facial palsy, 1249–1250 for idiopathic sudden sensorineural hearing loss, 595–596 for Ménière’s disease, 629, 664 for otosyphilis, 665 for sarcoidosis, 476 side effects of, 1250 Cotugno, Domenico, 9, 9f, 10f Counseling for cochlear implant, 1310 for iatrogenic facial nerve injury, 1277–1278 Count-the-dots version, of Articulation Index, and hearing aids, 1282, 1282f CPA. See Cerebellopontine angle (CPA). Cranial base. See Skull base. Cranial nerve(s) microscopic anatomy of, 894–895, 895f in otalgia, 195 physiology of, Sir Charles Bell and, 12–13, 13f radiation effect on, 1191 vascular compression of, tinnitus due to, 187 Cranial nerve I, 216 Cranial nerve II, 216–217, 217f Cranial nerve III, 217, 1055, 1055f intraoperative monitoring of, 976–978, 977f Cranial nerve IV, 217, 1055, 1055f intraoperative monitoring of, 976–978, 977f Cranial nerve V. See Trigeminal nerve. Cranial nerve VI. See Abducens nerve. Cranial nerve VII. See Facial nerve (FN). Cranial nerve VIII. See Vestibulocochlear nerve. Cranial nerve IX. See Glossopharyngeal nerve. Cranial nerve X. See Vagus nerve. Cranial nerve XI. See Spinal accessory nerve. Cranial nerve XII. See Hypoglossal nerve. Cranial nerve dysfunction, due to craniovertebral junction anomalies, 1148 Cranial nerve function, after stereotactic surgery, 771 Cranial nerve injuries, during neurotologic surgery, 722–724, 722f–724f Cranial nerve monitoring, 712, 958–989 anesthesia and, 965 blink reflex for, 989, 989f channels for, 961–962, 968 of cochlear nerve, 981–988 analogue vs. digital filtering in, 982 auditory brainstem response recording for, 981–984, 983f, 3988 compound nerve action potentials in, 982, 984–988, 984f–986f direct action potentials in, 984–985, 984f–986f electrocochleography for, 986–988, 986f electrodes for, 981–982, 984–985, 985f evoked potentials in, 987 historical background of, 959 interpretation of, 982–983 near-field recordings in, 982 and nerve preservation, 987–988 and postsurgical auditory function, 984 reducing electrical and acoustic interference with, 982 stimulus and recording parameters for, 981–982 during vestibular schwannoma surgery, 983–984, 983f communication and report generation in, 965–966 constant voltage vs. constant current for, 963 electrical safety for, 964

electrodes for recording, 960–962, 962f, 964 stimulating, 962–963, 963f of facial nerve, 966–976 for activity evoked by electrical stimulation, 967–970, 969f, 970f artifacts in, 967, 971, 972f, 988 to assess functional status, 969–970 common site of injury and, 968 to identify and map nerve, 958f, 967–969 to identify nervus intermedius, 970, 970f, 971f limitations of, 974 during microvascular decompression, 974–975, 975f during middle ear surgery, 975 modalities for, 966–967 and nerve preservation, 976 during parotidectomy, 975 patterns of activity in, 971–972, 973f in prediction of outcome, 973–974 for spontaneous and mechanically elicited activity, 970–974, 972f, 973f with vestibular schwannoma and other cerebellopontine angle tumors, 962, 962f, 966–974, 969f–973f future directions for, 988–989, 989f of glossopharyngeal, vagus, and spinal accessory nerves, 979–981, 979f, 980f history and context of, 958–959 instrumentation for, 960, 960f, 961f of oculomotor, trochlear, and abducens nerves, 976–978, 977f patient preparation for, 964, 965f personnel for, 959–960 quality control for, 964–965 search vs. threshold modes in, 966 stimulus duration for, 963–964, 964f of trigeminal nerve, 978–979 Cranial nerve palsies facial. See Facial palsy(ies). lower, rehabilitation of, 1350–1361 Cranial neuropathies due to glomus jugulare, 1039 due to meningitis, 494 due to skull base osteomyelitis, 1102 Cranial settling, 1148 Craniectomy, 1021 Craniopharyngioma, 1051–1052, 1052f of cerebellopontine angle, 863 radiation therapy for, 1053 Cranioplasty, 1021–1024 Craniotomy(ies) vs. craniectomy, 1021 of middle and posterior cranial fossae combined, 699–702, 700f, 701f middle fossa, 694, 695 for superior semicircular canal dehiscence, 245 for vestibular schwannoma, in neurofibromatosis 2, 788 retrolabyrinthine, 689, 690f retrosigmoid, 686f, 687, 687f, 689 for vestibular schwannoma, in neurofibromatosis 2, 788, 788f transjugular, 698–699, 699f translabyrinthine, 691f, 692–693 Craniovertebral junction, 1136–1162 congenital and acquired malformations of, 1142–1150 management of, 1149–1150, 1150f neural, 1142–1146, 1146f osseous, 1146–1148, 1147f, 1148f radiographic evaluation of, 1149 signs and symptoms of, 1148–1149, 1148t

INDEX

Craniovertebral junction (Continued) surgical anatomy of, 704–705, 1054, 1054f, 1136–1142 neural relationships in, 1137–1142, 1140f–1141f osseous relationships in, 1136–1137, 1137f–1139f vascular relationships in, 1142, 1143f–1145f surgical approaches to, 1153–1162, 1155t anterior, 1155–1156, 1155f–1157f endoscopic, 1161–1162, 1161f extreme lateral, 1159, 1160f infratemporal fossa Fisch D, 1158–1159, 1159f type C, 1158, 1158f lateral, 704–705, 704f, 705f, 1156–1159, 1157f–1160f posterior, 1159–1161, 1160f subfrontal-transbasal, 1156, 1156f suboccipital, 1159–1161, 1160f transcervical, 1156–1158, 1157f transoral, 1155–1156, 1155f transsphenoidal, 1156, 1157f tumors of, 1150–1154 clinical findings with, 1151–1152 frequency and site of, 1150–1151, 1150t, 1151t radiographic evaluation of, 1152–1153, 1152f, 1153f surgical therapy for, 1153–1154, 1154t Cretinism, cochlear hearing loss due to, 602 Cribigrams, after meningitis, 495 Cribriform plate, 998f, 1054f, 1156f CSF leak from dehiscent, 928 Cricopharyngeal myotomy, for swallowing dysfunction, 1356 Cristae ampullaris, 75 reflex projections of, 82f Critical period, 572, 573 CRN (cerebral radiation necrosis), 1191 Crockett, E. A., 31 Crocodile tearing, 1210 CROS (contralateral routing of sound) amplification, 1285–1286 after acoustic neuroma surgery, 765 Cross cover testing, 235–236 Cross-Cultural Smell Identification Test, 216 Crossed olivocochlear bundle (COCB), 66 Cross-modal activation, in primary auditory cortex, 322 Cross-talk, with trigeminal nerve, 978 Crouzon syndrome, hearing loss in, 129t CRP (canalith repositioning procedure), 649 Cruciate ligament, 1054 Cruciform ligament, 1137, 1139f Crum-Brown, Alexander, 27 Cruveilhier’s pearly tumors, 841 CSDs (current source densities), 310, 311 CSF. See Cerebrospinal fluid (CSF). CSOM (chronic suppurative otitis media), facial palsy due to, 1240 CT. See Computed tomography (CT). Cupula anatomy of, 75 deflection of, 75, 94, 94f, 96f Cupulolithiasis, 610f, 611 in benign paroxysmal positional vertigo, 178, 644 lateral canal, 646, 646t posterior canal, 645, 645f due to head injury, 179 liberatory maneuver for, 648–649, 649f due to temporal bone trauma, 1086

Current source densities (CSDs), 310, 311 Cushing, Harvey, 22, 26, 28, 28f, 30, 31, 37, 163, 728, 729, 729f, 730, 730t, 792, 1043 Cushing reflex, 751 Cushing response, 28 “Cut film” technique, 436 CVN. See Cochleovestibular nerve (CVN). CVST (caudal vestibulospinal tract), 104, 117–118 CX26 (connexin 26), in nonsyndromic hereditary hearing loss, 131, 132–133 CyberKnife stereotactic radiosurgery, 1182–1185 for acoustic neuroma, 769, 769f dose distribution in, 1183, 1183f localization in, 1183–1184, 1184f, 1185f outcomes with, 1164–1165, 1165f, 1184–1185 overview of treatment planning in, 1182–1183 treatment delivery in, 1184–1185 Cyclizine (Marezine), for vestibular dysfunction, 669t, 670 Cyclophosphamide, for autoimmune inner ear disease, 642 Cylindroma, of cerebellopontine angle, 853 Cyst(s) arachnoid of cerebellopontine angle, 364, 365f, 857, 858, 858f of posterior fossa, 944–948 classification of, 944–945, 945f clinical signs and symptoms of, 945–946 diagnosis and imaging of, 946–947, 946f management of, 947, 947f pathology and pathogenesis of, 944, 944f vestibular schwannoma with, 358, 358f cholesterol. See Cholesterol granuloma(s). colloid, of cerebellopontine angle, 853 congenital, of cerebellopontine angle, 364 cysticercosis, of cerebellopontine angle, 364, 365f, 858 dermoid of cerebellopontine angle, 852 epidermoid vs., 841 enterogenous, of cerebellopontine angle, 853 epidermoid of cerebellopontine angle, 841–848, 852 clinical signs of, 842 diagnosis of, 842–844, 842f, 843f differential diagnosis of, 841 embryology of, 841–842 epidemiology of, 841 historical background of, 841 imaging of, 362, 363f, 364f pathology of, 842 surgical treatment of, 844–847, 845t unusual complications of, 847 involving facial nerve, 426–427, 429f–431f otic, 91 respiratory epithelial, of cerebellopontine angle, 853 Cyst fenestration, for posterior fossa arachnoid cysts, 947, 947f Cystic astrocytomas, of cerebellopontine angle, 853, 855f Cystic fibrosis, multifactorial inheritance in, 128 Cystic lesions, of petrous apex, 1111–1116, 1112f, 1113f, 1115f, 1116f Cysticercosis, of cerebellopontine angle, 364, 365f, 858 Cystoperitoneal shunting, for posterior fossa arachnoid cysts, 947 Cytomegalic inclusion disease, acute labyrinthitis due to, 178

1375

Cytomegalovirus (CMV) central processing deficits due to, 578 congenital, hearing loss due to, 598 Czermak, Johann, 15

D D/A (digital-to-analogue) converter, 1288 Dandy, Walter, 30–31, 30f, 31f, 33, 37, 728–729, 730, 730t, 949 Dandy’s vein, 679, 701 Dandy-Walker syndrome, 1142 Daniel, R. K., 1005 Dark cells, 92 Darwin, Erasmus, 14, 235 DAVFs. See Dural arteriovenous fistulas (DAVFs). David, Pauline, 287 DAVMs (dural arteriovenous malformations), pathologic correlates of, 157 Dawson, G. D., 287 DCN. See Dorsal cochlear nucleus (DCN). DCS (decompression sickness), 247 hearing loss due to, 597 De Aquaeductibus Auris Humanae Internae Anatomica Dissertatio, 9, 9f, 10f De Humanis Corporis Fabrica, 3, 5 De Structura Fenestrae Rotundae, 10, 11f Deafferentation, and development of central auditory system, 572, 572f, 574–578, 577f Deafness. See Hearing loss. “Deafness genes,” 128–131 Decompensation, 1333, 1335 in vestibular neuritis, 487–488 Decompression sickness (DCS), 247 hearing loss due to, 597 Degeneration, of nerves, 1210 Deglutition. See Swallowing. Deiters nucleus, 77f, 78, 78f, 81f, 83, 116–117 Delayed hydrops, 626 Deleau, Nicholas, 15 Demyelinating diseases. See also Multiple sclerosis (MS). classification of, 500t neuro-ophthalmic manifestations of, 237 Dendrites, 1208f Denervation, 1223 total, 1226 Denervation potential, 1225 Dental disorders, otalgia due to, 196–197 Dentate ligaments, 1140f, 1141f, 1142, 1160f Depakene (valproic acid) for migraine prophylaxis, 515 for vestibular migraine, 666 Depakote (divalproex sodium), for vestibular migraine, 666 Depression, long-term, 660 Deprivation, and development of central auditory system, 572–574, 572f Derlacki, E. L., 36, 36f Dermoid cysts of cerebellopontine angle, 852 epidermoid vs., 841 Descending pathways, in information processing, 49–50 Descending vestibular nucleus, 77f, 79, 79f, 81f Desired sensation level (DSL), with hearing aids, 1286, 1287 Developmental period, 572 Dexamethasone for cerebral edema, 719–720 for Ménière’s disease, 629 intratympanic, 664 Dextroamphetamine, for motion sickness, 670 DFN3 gene, 125

1376

INDEX

DFNA1 gene, 124 DFNA17, 134 DHI (Dizziness Handicap Inventory), 622 Diabetes mellitus Bell’s palsy and, 1234 cochlear hearing loss due to, 602 malignant otitis externa in, 1097 Diamox. See Acetazolamide (Diamox). DIAPH1 gene, 124 Diazepam (Valium) for autonomic dysfunction, 661 for status epilepticus, 521t for vertigo in elderly, 537 for vestibular dysfunction, 668, 669, 669t Dichotic digits test, 278 Dichotic measures, of auditory processing testing, 276 Dichotic Sentence Identification (DSI) test, 278 Diet, for vestibular migraine, 665 Diffuse neuroendocrine system (DNES), cells of, 543, 544t Diffuse osseous lesions, of temporal bone, 1125–1133 Diffusion-weighted images (DWI), of lateral skull base, 384 Digastric muscle, 1204 posterior belly of, 997, 999f Digastric ridge, 1204–1205 Digastric ridge method, of identifying facial nerve, 1273 Digenic individuals, 123 Digital hearing aids, 1288, 1289, 1290–1291 Digital signal-processing (DSP) unit, 1288 Digitally programmable hearing aids, 1288, 1289, 1290–1291 Digital-to-analogue (D/A) converter, 1288 Dimenhydrinate (Dramamine) for familial ataxia syndrome, 667 for motion sickness, 670 for vertigo in elderly, 537 for vestibular dysfunction, 668, 669t, 670 Diphosphonates, for Paget’s disease of temporal bone, 1131 Diplacusis, in Ménière’s disease, 623 Diplopia, 230, 234 due to acoustic neuroma, 741 with facial paralysis, 1341 in multiple sclerosis, 501 vertical, 243 Dipole source localization, 313, 316 Dipole source modeling, 312–316, 312f clinical applications of, 316, 318f early methods of, 313 spatiotemporal advantages and disadvantages of, 315–316 technical aspects of, 313–315, 314f, 317f–318f Direct carotid-cavernous fistulas, 451, 452f Direct System implantable hearing device, 1297–1298, 1298f, 1299t Directional hearing, central nucleus of inferior colliculus in, 64 Diseases of the Ear, 16, 16f Disorientation, 177 due to perilymph fistula, 179 Disquisitiones Anatomicae de Auditu et Olfactu, 10 Dissecting aneurysms, pulsatile tinnitus due to, 205 Dissection tools, 677 Distortion product otoacoustic emissions (DPOAEs), 287–288, 289f, 290f with acoustic neuroma, 165, 166

Diuretics for cerebral edema, 720 loop hearing loss due to, 594 semicircular canal dysfunction due to, 251 for Ménière’s disease, 628, 661 Divalproex sodium (Depakote), for vestibular migraine, 666 Diving, labyrinthine hemorrhage due to, 246 Diving barotrauma, hearing loss due to, 597 Dix-Hallpike maneuver, 608–611 abnormal response to, 609–611, 611f, 611t canalithiasis and cupulolithiasis in, 610f, 611 in elderly, 536 eye movements evoked by, 224f limitations of, 537 normal response to, 609 procedure for, 223–224, 608–609, 610f Dizziness, 177 with acoustic neuroma, 171t in childhood, 553–561 due to ataxia, 560 due to benign paroxysmal vertigo, 557, 559 due to benign positional vertigo, 665 with congenital and hereditary hearing loss, 556 with congenital anomalies, 556 due to congenital nystagmus, 560 development of vestibular system and, 553–554 diagnosis of, 554–556 functional, 561 due to labyrinthitis, 556, 559 due to Ménière’s disease, 557 due to meningitis, 559 due to metabolic/systemic disease, 560 due to migraine, 557, 559 due to multiple sclerosis, 560 due to neurosyphilis, 560 due to otitis media, 556–557 due to perilymphatic fistula, 558–559 toxic, 561 due to trauma, 557–558 due to tumors, 559–560 due to vertiginous seizures, 559 due to vestibular neuronitis, 559 due to vestibular vertigo, 522 common causes and mechanisms of, 659–661, 660t due to dysequilibrium, 660t in elderly, 533, 534–537, 535t, 536t after head injury, 541, 541t multisensory, 660t nonspecific post-traumatic, 558 pharmacotherapy for, 659–670, 662t for specific etiologies, 661–668, 662t symptomatic, 668–670, 669t due to presyncopal lightheadedness, 660t psychiatric, 667 psychophysiologic, pharmacotherapy for, 662t, 667 due to vertigo, 660t due to visual distortion, 660t Dizziness Handicap Inventory (DHI), 622 Djourno, A., 38 DLL (dorsal nucleus of lateral lemniscus) in brainstem auditory pathway, 45, 46f, 565f, 566f in information processing, 48 DMD (Duchenne’s muscular dystrophy), multifactorial inheritance in, 128 DNES (diffuse neuroendocrine system), cells of, 543, 544t Dolichoectasia, 156–157 vertebrobasilar, 352f, 367–368, 368f

Doll’s eye maneuver, 222f Dorello’s canal, 1108 Dormant synapses, unmasking of, 187 Dorsal cochlear nucleus (DCN) anatomy of, 45, 46f, 47 with auditory brainstem implant, 1323–1324 development of, 565, 565f, 566 physiology of, 60, 60f, 62, 63, 65, 65f tuning curves from, 60f Dorsal cortex, of inferior colliculus, 49, 59f Dorsal ganglion, 1141f Dorsal meningeal artery, 1055f Dorsal nucleus of lateral lemniscus (DLL) in brainstem auditory pathway, 45, 46f, 565f, 566f in information processing, 48 Dorsum sellae, 1002 Dose, in Gamma Knife radiosurgery, 1167 Double heterozygotes, 123 “Double ring” sign, 602 Down syndrome, central processing deficits with, 578 Downbeat nystagmus, 232, 611 Doxycycline, for otosyphilis, 250, 665 Doyle, James, 38 DP-gram, 288 DPOAEs (distortion product otoacoustic emissions), 287–288, 289f, 290f with acoustic neuroma, 165, 166 DPT (duration patterns test), 274 Dramamine. See Dimenhydrinate (Dramamine). Drobnik, T., 26 Drop attacks, 179, 622 Droperidol (Inapsine), for vestibular dysfunction, 669, 669t Drug-induced seizures, 519 Dry eyes, 1340 management of, 1341–1343, 1342t, 1343f DSI (Dichotic Sentence Identification) test, 278 DSL (desired sensation level), with hearing aids, 1286, 1287 DSP (digital signal-processing) unit, 1288 Duchenne, G. B. A., 1223 Duchenne’s muscular dystrophy (DMD), multifactorial inheritance in, 128 Duel, A. B., 26 Dumping, 109 Dupuytren, Guillaume, 26 Dura, 1054f, 1139f–1141f Dural arteriovenous fistulas (DAVFs), 441–451 in anterior cranial fossa, 935 vs. arteriovenous malformation, 441–443 of cavernous sinus, 443 clinical presentation of, 443–444, 937–938, 938t complex transverse sinus, 445f–446f defined, 441, 934 diagnosis of, 444–447 of ethmoidal groove, tentorium, and vein of Galen, 444 foramen magnum, 447f–448f grading system for, 936–937, 937t hemorrhage of, 443, 445f–448f inferior petrosal sinus, 449f–450f location and arterial sources of, 443, 934–935, 935f natural history of, 937 pathogenesis and pathophysiology of, 443, 935–936 posterior fossa, 934–935 pseudoaneurysm of, 447f–448f pulsatile tinnitus due to, 443 radiographic evaluation of, 938

INDEX

Dural arteriovenous fistulas (DAVFs) (Cont.) of transverse, sigmoid, and petrosal sinuses, 443, 449f–450f, 934–935, 935f treatment for, 447–451, 938–942, 940f–941f venous drainage of, 443, 936 Dural arteriovenous malformations (DAVMs), pathologic correlates of, 157 Dural herniation. See Encephalocele. Dural tail due to idiopathic hypertrophic pachymeningitis, 363f due to meningeal metastases, 362f meningioma with, 357f, 358, 359f, 361, 399f vestibular schwannoma with, 357f, 358 Dural tears, control of bleeding due to, 713 Dural venous sinus thrombophlebitis, due to otitis media, 913t, 918–919, 919f Duration patterns test (DPT), 274 Duverney, Joseph Guichard, 6–7, 7f, 8f, 15 DWI (diffusion-weighted images), of lateral skull base, 384 Dyazide (triamterene), for Ménière’s disease, 628 Dynamic compensation, 1332–1333 Dynamic eye motion, 222 Dynamic posturography, 256–268 for acoustic neuroma, 743 applications of, 262–266 for central balance deficits, 263–264, 263f for children, 555 considerations and limitation of, 266–268 for elderly, 534 for establishing and monitoring treatment, 264–266, 266f for evaluation of physiologic compensation, 1334 historical perspective on, 256 limits of stability test in, 257–258, 259f methodology for, 256–262 motor control/adaptation tests in considerations and limitation of, 267–268 methodology for, 258–259, 260f, 261f, 261t for nonphysiological component of balance, 264, 264t, 265f reliability and validity of, 259–262 for risk of falls in older adults, 262 sensory organization test in considerations and limitation of, 266–267, 267f methodology for, 257, 257t, 258f for vestibular deficits, 262, 262t, 263t Dynamic range, 1287 Dysarthria due to cerebellopontine angle meningioma, 808 in multiple sclerosis, 504–505 Dysautonomia, dizziness due to, 560 Dysequilibrium, 177 due to acoustic neuroma, 739t, 740, 766 of aging, 534–535, 535t, 536 due to cerebellopontine angle meningioma, 808 defined, 535 due to perilymph fistula, 179 Dysesthesia, defined, 194 Dysgeusia due to iatrogenic injury or chorda tympani nerve, 1277 in multiple sclerosis, 505 Dysmetria, due to acoustic neuroma, 740 Dysphagia, 1351–1352 due to acoustic neuroma, 739t, 741 as complication of neurotologic surgery, 724 evaluation of, 1352–1354 treatment of, 1354–1356 Dysphonia, spasmodic, 225

E EA-1 (episodic ataxia type 1), and migraine, 512 EA-2 (episodic ataxia type 2), and migraine, 512 EABR (evoked auditory brainstem responses). See Brainstem auditory evoked potentials (BAEPs). EAC. See External auditory canal (EAC). Eagle’s syndrome, otalgia due to, 197 EAPs (electric auditory potentials), 303, 303f Ear(s) frequency analysis in, 54–58, 54f–57f sensory innervation to, 194 sound conduction in, 53–54 Ear canal, in sound conduction, 53 Earache. See Otalgia. Eardrum artificial, 17 blue, 1111 Earmold, for hearing aid, 1287–1288, 1288f Earphones, for intraoperative monitoring of auditory brainstem responses, 981–982 EBNs (excitatory burst neurons), 105, 106f EBP50/NHE-RF, in acoustic neuroma, 732 Eccentric gaze, ability to maintain, 229, 235 Eccentric yaw rotation, 243 ECoG. See Electrocochleography (ECoG). Ectopic excitation, 895–896, 896f Ectropion, 1340 Edema with meningioma, 802 postauricular, 215 postoperative cerebral, 719–720, 719f Edwards’ syndrome, central processing deficits with, 578 EEG (electroencephalography) of scalp activity, 308 of seizures, 519 EEMG (evoked electromyography), of facial nerve, 1247–1248, 1247f Efferent vestibular pathway, 85–86, 86f Efferent visual pathways, examination of, 234–235 EFI (electric field imaging), 1305 EHV (eye-head velocity) neurons, 104 Elderly. See also Aging. auditory brainstem response to detect hearing loss in, 295–297 dynamic posturography for risk of falls in, 262 orthostatic hypotension in, 535 risk of falls in, dynamic posturography for, 262 vestibular neurectomy in, 950 Electric auditory potentials (EAPs), 303, 303f Electric field(s), 307–308 Electric field imaging (EFI), 1305 Electrical field theory forward problem in, 312 inverse problem in, 312 Electrical multichannel recordings, 309–310, 309f Electrical potential, 307 Electrical safety, with intraoperative cranial nerve monitoring, 964 Electrical stimulation activity evoked by, 967–970, 969f–971f for tinnitus, 189 Electrical testing, of facial nerve, 1223–1228 comparison of tests for, 1226–1228 evolution of, 1223 for facial palsy, 1244–1249, 1245f, 1247f, 1248f general considerations in, 1228, 1228f interpretation of, 1225–1226, 1226f, 1226t limitations of, 1079 methods of, 1078, 1223–1225, 1224f, 1225f for prognosis, 1078–1079, 1227–1228, 1227t, 1228t purpose of, 1223

1377

Electrically elicited stapedial muscle reflex (ESR), 1304 Electrocautery, near facial nerve, 1270 Electrocochleography (ECoG), 290–293, 291f–293f with acoustic neuroma, 166 to assess treatment efficacy, 292–293, 293f clinical applications of, 291–293, 292f, 293f clinical criteria for, 291–292 in cochlear implant surgery, 302, 303f components of, 291 defined, 290 as diagnostic tool, 292, 292f evoked potentials in, 67–68, 68f intraoperative, 986–987, 986f of Ménière’s disease, 292–293, 292f, 293f, 627 recording technique for, 290, 291, 291f SP/AP ratio in, 291 Electrode(s) in auditory brainstem implant, 1327–1328, 1327f, 1329 in cochlear implants, 1303–1304, 1303f, 1305, 1306, 1307 for cranial nerve monitoring of cochlear nerve, 984–985, 985f, 986 with electrocochleography, 986 needle, 960–961, 964 recording, 960–962, 962f, 964 stimulating, 962–963, 963f surface, 960–961 Electrode positioning system (EPS), 1305, 1312 Electrode-specific speech, with auditory brainstem implant, 1329 Electrodiagnostic testing. See Electrical testing. Electroencephalography (EEG) of scalp activity, 308 of seizures, 519 Electrogustometry, 1265 Electromagnetic stimulation, of facial nerve, 1248–1249 Electromotility, of hair cells, 590–591, 591f, 601 Electromyographic (EMG) endotracheal tube, 979–980, 980f Electromyography (EMG) evoked. See Electroneuronography (ENOG). of facial nerve, 1223, 1225 for facial palsy, 1246–1248, 1247f intraoperative, 966–975 for intraoperative cranial nerve monitoring of activity evoked by electrical stimulation, 963f, 966–970, 969f–971f artifacts in, 967, 971, 972f, 988 to assess functional status of nerves following tumor removal, 969–970 electrode placement for, 962, 962f, 967 of extraocular muscles, 976–978, 977f of facial nerve, 966–975 future directions for, 988 to identify and map nerves in relation to tumor, 967–969, 969f limitations of, 974 of lower cranial nerves, 979–981, 979f, 980f patterns of activity in, 971–972, 973f to predict postoperative outcome, 973–974 of spontaneous and mechanically elicited activity, 970–974, 972f, 973f of trigeminal nerve, 978–979 in motor control/adaptation tests, 259, 261f, 261t

1378

INDEX

Electroneuronography (ENOG), of facial nerve comparison of, 1226–1227 for facial nerve tumors, 1265 for facial palsy, 1247–1248, 1247f general considerations for, 1228, 1228f interpretation of results of, 1225–1226 methods of, 1223, 1224–1225, 1224f, 1225f and nerve decompression, 1252 for temporal bone trauma, 1078–1079 Electronystagmography (ENG), 607–617 for acoustic neuroma, 743 benefits of, 608t bithermal caloric test in, 608, 613–615, 614f, 615f, 615t Bojrab maneuver in, 611–612, 612f of children, 555 defined, 235, 607 Dix-Hallpike maneuver in, 608–611, 610f, 611f, 611t of elderly, 534 for evaluation of physiologic compensation, 1333–1334 eye movement recording equipment for, 607–608, 609f, 610f gaze test in, 608, 612, 613f indications for, 607 limitations of, 616–617 with meningiomas, 799 optokinetic test in, 608, 616, 616f positional test in, 608, 612–613, 613f, 614f pursuit tests in, 608, 616, 616f routine components of, 608 saccade test in, 608, 615, 616f tracking test in, 608, 616, 616f Electro-oculography (EOG), 607–608, 609f Electrophysiologic measure(s), 287–303 auditory brainstem response as, 293–295, 293f–295f, 294t in cochlear implant surgery, 301–303, 302f, 303f to detect hearing loss, 295–297, 296f to diagnose acoustic neuroma, 297–300, 300f of auditory processing, 276–278 electrocochleography as, 290–293, 291f–293f to estimate amplification benefit, 297 for facial nerve tumors, 1265 for facial palsy, 1245–1246, 1245f middle latency responses as, 300–301 otoacoustic emissions as, 287–290, 289f, 290f Elsberg, Charles, 729 ELSTs (endolymphatic sac tumors), 340 facial nerve involvement in, 427, 432f EMA (epithelial membrane antigen), in meningiomas, 798 Embolization for aneurysm, 438–439, 440f–441f angiography for, 437 of arteriovenous malformations, 441, 939 of carotid-cavernous fistulas, 451, 452f of dural arteriovenous fistulas, 445f–450f, 447–451 of glomus jugulare tumors, 456, 457f–461f of hemangioblastomas, 465 of juvenile angiofibromas, 465 of malignant skull base tumors, 465 of meningiomas, 460–464 of scalp arteriovenous fistulas, 453 of schwannomas, 464–465 of vertebral fistulas, 452, 453f Embolus(i), air, 714–715 due to acoustic neuroma surgery, 754 Embryonal rhabdomyosarcoma, 1031 facial nerve involvement in, 427–430 EMG. See Electromyography (EMG).

Empyema, subdural, due to otitis media, 913t, 922–923 Encephalitis, brainstem, 546 Encephalocele defined, 1089 epidemiology of, 1089 imaging of, 410–414, 412f–414f temporal bone, 1089–1094 causes of, 1089 clinical presentation of, 1090–1091, 1091f epidemiology of, 1089 pathogenesis of, 1089–1090 radiology of, 1091–1092, 1091f, 1092f surgical treatment of, 1092–1094, 1093f Encephalomalacia, due to acoustic neuroma surgery, 755, 755f Encephalomeningocele, defined, 1089 Encephalomyelitis, paraneoplastic, 546–547 Encephalopathy acute radiation, 1191 anoxic, central processing deficits due to, 579 Wernicke’s, vestibular symptoms of, 181 End-bulb of Held, 566 Endolymph, discovery of, 10 Endolymphatic hydrops, 178–179 imaging of, 345–347, 346f and Ménière’s disease, 623–626, 624f, 625f otolith dysfunction due to, 242 post-traumatic, 249, 1087 Endolymphatic potential, 92, 591, 601 Endolymphatic sac carcinoma of, labyrinthine hemorrhage due to, 333, 333f contrast enhancement of, 340f historical background of, 27, 32, 32f Endolymphatic sac surgery (ESS), for Ménière’s disease, 629–630, 633–634 Endolymphatic sac tumors, of petrous apex, 1121 imaging of, 396 Endolymphatic sac tumors (ELSTs), 340 facial nerve involvement in, 427, 432f Endoneurium, 894, 895, 1208, 1209f Endoscopic evaluation of craniovertebral junction, 1161–1162, 1161f of swallowing, 1353 of temporal bone encephalocele, 1093–1094 of vocal cords, 1353 Endoscopic fenestration, for posterior fossa arachnoid cysts, 947 Endotheliomas, 792 Endotracheal tube, EMG, 979–980, 980f Endovascular therapy for aneurysm, 438–439, 440f–441f for arteriovenous malformations, 441, 939 for dural arteriovenous fistulas, 445f–450f, 447–451 ENG. See Electronystagmography (ENG). Engelman’s disease, 1128f ENOG. See Electroneuronography (ENOG). Enterogenous cysts, of cerebellopontine angle, 853 Entropion repair, upper lid, 1345 Envoy implantable hearing device, 1298–1299, 1299f, 1299t EOAEs (evoked otoacoustic emissions), 287 transiently, 287, 288, 289f EOG (electro-oculography), 607–608, 609f EP16, 960 Ependymomas of cerebellopontine angle, 371, 372f, 854–855 of posterior fossa, 883, 884f, 885t Ephaptic transmission, 896, 896f

Ephedrine for motion sickness, 670 for vestibular dysfunction, 669t Epidemic vertigo. See Vestibular neuritis (VN). Epidermoid carcinoma, of cerebellopontine angle, 866 Epidermoid cysts of cerebellopontine angle, 841–848, 852 clinical signs of, 842 diagnosis of, 842–844, 842f, 843f differential diagnosis of, 841 embryology of, 841–842 epidemiology of, 841 historical background of, 841 imaging of, 362, 363f, 364f pathology of, 842 surgical treatment of, 844–847, 845t unusual complications of, 847 involving facial nerve, 426–427, 429f–431f Epidermoid tumors of middle ear, 408–409 of petrous apex, 385–386, 387f Epidural abscess, due to otitis media, 913t, 917, 917f, 918f Epilepsy. See also Seizures. classification of, 518, 520t defined, 518 petit mal, 518 reflex, 522 Epineurium, 894, 1208, 1209f Episodic ataxia type 1 (EA-1), and migraine, 512 Episodic ataxia type 2 (EA-2), and migraine, 512 Epistatic effects, 128 Epithelial cysts, respiratory, of cerebellopontine angle, 853 Epithelial membrane antigen (EMA), in meningiomas, 798 Epitympanic fixation, of ossicles, 1084t, 1085 Epoch 2000, 960 EPS (electrode positioning system), 1305, 1312 Equivalent current dipole(s), 307 in dipole source modeling, 312–313, 312f in spatiotemporal source modeling, 313–315, 314f, 317f–318f ERP (event-related potential), 68 ERP (event-related potential) topography, 282–283 Erythrocyte sedimentation rate (ESR), with skull base osteomyelitis, 1104 Erythromycin, for otosyphilis, 665 Esophageal disorders, otalgia due to, 196t, 197 Esprit speech processor, 1306, 1317 ESR (electrically elicited stapedial muscle reflex), 1304 ESR (erythrocyte sedimentation rate), with skull base osteomyelitis, 1104 ESS (endolymphatic sac surgery), for Ménière’s disease, 629–630, 633–634 Essays on Surgery of the Temporal Bone, 25, 25f Estrogen, in acoustic neuroma growth, 733 Etanercept, for autoimmune inner ear disease, 642 Ethacrynic acid hearing loss due to, 594 ototoxicity of, 251 Ethanol, congenital hearing loss due to, 594 Ethmoidal groove, dural arteriovenous fistulas of, 444 Eustachian tube discovery of, 4–5, 9 and facial nerve, 1204f, 1217f, 1271f patency of, 216 surgical anatomy of, 1000, 1055f, 1158f, 1159f Eustachio, Bartholommeo, 3–5, 4f, 9 Event-related designs, for function MRI, 321

INDEX

Event-related potential(s) (ERP), 68 Event-related potential (ERP) topography, 282–283 Evoked auditory brainstem responses (EABR). See Brainstem auditory evoked potentials (BAEPs). Evoked electromyography (EEMG), of facial nerve, 1247–1248, 1247f Evoked otoacoustic emissions (EOAEs), 287 transiently, 287, 288, 289f Evoked potentials from auditory nervous system, 68–70, 69f, 70f brainstem auditory. See Brainstem auditory evoked potentials (BAEPs). electrocochleographic, 67–68, 68f to stimulation of vestibular nerve, 987 transcranial motor, 988 visual, in multiple sclerosis, 504, 505 Excitation, ectopic, 895–896, 896f Excitatory burst neurons (EBNs), 105, 106f Exercise, for vertigo in elderly, 537 Exostosis, of external auditory canal, 415, 416f, 1276 Exposure keratitis, 1232, 1233f Extended middle fossa approach, to cerebellopontine angle, 696, 696f External auditory canal (EAC) anatomy of, 1029, 1216f cholesteatoma of, 415, 416f drainage pathways of, 1029 exostosis, 415, 416f, 1276 facial nerve injury during surgery of, 1276 imaging of, 415–417, 415f–418f keratosis obturans of, 415, 415f malignant lesions of, 415–416, 417f, 418f malignant otitis of, 416–417 osteoma of, 415, 416f radiation effect on, 1189 tumors of clinical management of, 1031–1034, 1032f–1034f diagnostic evaluation of, 1029–1030, 1029t, 1030t pathobiology of, 1030–1031, 1030t, 1031t staging of, 1029, 1029t, 1030t External auditory meatus, 998f, 1054f External capsule, 1201f External carotid artery, surgical anatomy of, 1000, 1157f External cortex, 49 External ear drainage pathways of, 1029 examination of, 215 External laryngeal nerve, 1157f External nucleus of inferior colliculus (ICX), 59f, 62, 63, 65, 65f External occipital crest, 1137f External occipital protuberance, 1137f, 1160f External otitis, malignant (necrotizing). See Malignant external otitis (MEO). Extracranial arteriovenous fistulas, 451–453, 452f, 453f Extra-dural lesions, 370, 370f, 371f Extraocular muscles innervation of, 217–218 intraoperative monitoring of, 976–978, 977f Extratemporal segment, of facial nerve, surgical approach to, 1218–1220, 1220f Extreme lateral approach, to craniovertebral junction, 1159, 1160f EYA1 gene, 124 Eye glasses, recalibration of vestibulo-ocular reflex gain with, 110–111

Eye movement(s), 84–85, 84f, 85f examination of, 221–225, 223f–225f, 235 reasons for, 228 recording equipment for, 607–608, 609f, 610f vestibular system in, 228 Eye ointments, 1342, 1342t Eye problems, with facial paralysis, 1339–1348 nonsurgical management of, 1341–1344, 1342t, 1343f, 1344f reasons for, 1339–1340 surgical management of, 1344–1347, 1345f–1348f types of, 1340–1341 Eye saccade, 111–112, 112f Eyebrows poor position of, 1340 surgical elevation of, 1345f, 1346f Eyedrops, with facial paralysis, 1341–1342, 1342t Eyeglass hearing aids, 1283 Eye-head coordination, 111–112, 112f Eye-head velocity (EHV) neurons, 104 Eyelid(s) lower canthoplasty of, 1344–1345, 1345f fascia lata support of, 1345 poor position of, 1340 stent support of, 1345 taping of, 1342, 1343f poor position of, 1340 surgical techniques for, 1344–1345, 1345f temporary closure of, 1344, 1344f, 1345 upper entropion repair of, 1345 gold weights for, 1346 incomplete closure of, 1340 palpebral spring for, 1346, 1346f–1347f poor position of, 1340 silastic elastic prosthesis for, 1346, 1348f surgical techniques to animate, 1345–1346, 1346f–1348f “Eyes-closed turning test,” 225 Eye-tracking reflexes, 109–110, 109f Eyries, C., 38

F F wave in antidromic conduction testing, 1248 of nasal muscle, intraoperative monitoring of, 967 Facial anesthesia, due to acoustic neuroma, 740 Facial mimetic function, after acoustic neuroma surgery, 757–761, 758t, 760f Facial motor nucleus, aplasia of, 423, 424f Facial myokymia, in multiple sclerosis, 504 Facial nerve (FN), 219–220 aberrant course of, 1205, 1205f cochlear implant with, 1319 in acoustic middle ear reflex, 71 in acoustic neuroma clinical symptoms of, 739t, 740–741 hypoglossal and spinal accessory anastomosis with, 760–761, 760f monitoring of, 757–758 pathologic correlates of, 144, 145f, 154, 154f postoperative palsy of, 758–761 primary reconstruction of, 759–760, 760f surgical approach to, 749, 750, 750f–752f surgical results for, 758, 758t vulnerability of, 757 anatomy of, 1200–1205, 1271, 1271f bifurcation of, 1205, 1206f blood supply to, 1205 central pathways of, 1200–1202, 1201f–1203f

1379

cerebellopontine angle segment of, 893, 1202, 1203f surgical approach to, 1212–1215, 1213f–1217f congenital anomalies of, 1205–1206, 1205f–1207f, 1272, 1274f iatrogenic injury due to, 1277 imaging of, 421–423, 423f, 424f and craniovertebral junction, 1142, 1158f, 1159f degeneration of, 1210 patterns of, 153–154, 154f, 155f dehiscence of, 1217, 1219f, 1271, 1272f, 1272t bony, 1205–1206, 1205f electrical testing of, 1223–1228 with central activation, 1248–1249, 1248f comparison of tests for, 1226–1228 with electromyography, 966–975, 1223, 1225, 1246–1248, 1247f with electroneuronography. See Electroneuronography (ENOG). electrophysiologic, 1245–1246, 1245f evolution of, 1223 for facial palsy, 1244–1249, 1245f, 1247f, 1248f general considerations in, 1228, 1228f interpretation of, 1225–1226, 1226f, 1226t limitations of, 1079 with maximal stimulation test. See Maximal stimulation test (MST). methods of, 1078, 1223–1225, 1224f, 1225f with nerve excitability test, 1223–1224, 1226, 1227, 1246 for prognosis, 1078–1079, 1227–1228, 1227t, 1228t purpose of, 1223 topognostic, 1244–1245 with transtympanic stimulation, 1248 embryology of, 1199–1200, 1200f examination of, 210–220, 220t extratemporal segment of, surgical approach to, 1218–1220, 1220f in facial nucleus and brainstem, 1201–1202, 1202f fallopian canal and, 1202–1205, 1203f, 1204f grafting of, 1214, 1214f, 1217f, 1220–1221, 1221f, 1252 hemifacial spasm of, 432–434, 433f horizontal segment of, 1204 surgical approach to, 1215–1218, 1217f–1219f hypoglossal and spinal accessory anastomosis with, 760–761, 760f imaging of, 419–434 choice of modality for, 419–420 normal anatomy in, 419, 420f–422f technique for, 420–421 inflammation of, 431–432, 433f internal auditory canal segment of, 1202, 1203f surgical approach to, 1212–1215, 1213f–1217f intraoperative monitoring of, 966–976, 1212 with acoustic neuroma, 757–758 for activity evoked by electrical stimulation, 967–970, 969f, 970f artifacts in, 967, 971, 972f, 988 to assess functional status, 969–970 common site of injury and, 968 electrode placement for, 1212 and facial nerve preservation, 976 historical background of, 958, 959 to identify and map nerve, 958f, 967–969

1380

INDEX

Facial nerve (FN) (Continued) to identify nervus intermedius, 970, 970f, 971f limitations of, 974, 1212 during microvascular decompression, 974–975, 975f during middle ear surgery, 975 modalities for, 966–967 during parotidectomy, 975 patterns of activity in, 971–972, 973f in prediction of outcome, 973–974 for spontaneous and mechanically elicited activity, 970–974, 972f, 973f during vestibular neurectomy, 952 with vestibular schwannoma and other cerebellopontine angle tumors, 962, 962f, 963f, 966–974 labyrinthine segment of, 1202–1204 surgical approach to, 1212–1215, 1213f–1217f and lateral skull base, 998–999 mastoid segment of, 1204 surgical approach to, 1215–1218, 1217f–1219f meningiomas affecting, 154, 155f, 808 motor and sensory branches of, 219–220, 219f, 1201, 1202f normal variants of and iatrogenic injury, 1271–1272, 1272f, 1272t, 1273f imaging of, 421–422, 423f, 424f ocular functions of, 1339, 1340–1341 and parasellar and cavernous sinus region, 1055f and petrous apex, 1108 physiology of, 219–220, 1206–1208, 1208f, 1209f posterior lateral displacement of, 1205, 1206f primary reconstruction of, 759–760, 760f radiation effect on, 1190 regeneration of, 1210 abnormal, 1210 neurotrophic growth factors and, 1210 rerouting of, 1214, 1214f, 1220 in skull base osteomyelitis, 1098 and stylomastoid artery, 715 supranuclear pathways of, 1200, 1201f surgical approaches to, 1212–1220 for extratemporal segment, 1218–1220, 1220f for facial recess, 1218, 1219f for horizontal segment, 1215–1218, 1217f–1219f for labyrinthine segment, 1212–1215, 1213f–1217f middle fossa, 1215, 1215f–1217f retrosigmoid, 1214 translabyrinthine, 693, 1213–1214, 1213f, 1214f transmastoid (tympanomastoid), 1215–1218, 1217f–1219f temporal bone and, 1202–1205, 1203f, 1204f topographic testing of, 1078 tympanic segment of, 219, 1204 surgical approach to, 1215–1218, 1217f–1219f vertical segment of, 1204 surgical approach to, 1215–1218, 1217f–1219f and vestibular nerve, 950f, 951, 951f, 953, 955f Facial nerve canal (FNC) normal variants of, 421–422, 423f, 424f paragangliomas of, 154, 155f, 427, 432f

Facial nerve compression, due to schwannomas, 1260 Facial nerve decompression for Bell’s palsy, 1234–1235, 1236f, 1251–1252 for facial nerve tumors, 1267 Facial nerve injury(ies) classification of, 1208–1210, 1209f iatrogenic, 1231t, 1270–1278 during acoustic neuroma surgery, 1275–1276 in children, 1277 during cochlear implantation, 1276–1277 with congenital anomalies, 1277 counseling for, 1277–1278 diagnosis and management of, 1275 during mastoidectomy, 1272–1274 mechanisms of, 1270 during middle fossa surgery, 1276 normal anatomy and variations and, 1271–1272, 1271f–1273f, 1272t prevention of, 1270–1271 during resection of paraganglioma, 1277 during surgery for cholesteatoma, 1274, 1275f during surgery for otitis media, 1271 during surgery of external auditory canal, 1276 swallowing disorder due to, 1351 due to temporal bone trauma, 1077–1082 evaluation of, 1075, 1077–1079, 1078t imaging of, 430–431, 433f, 1076, 1079 pathology of, 1077, 1077t surgical management of, 1079–1082, 1079f, 1080t, 1081t Facial nerve paralysis. See also Facial palsy(ies). acute. See Bell’s palsy. due to fibrous dysplasia of temporal bone, 1126 due to osteopetrosis, 1127–1128, 1129 due to temporal bone infection, 722f due to temporal bone trauma, 1077–1082 evaluation of, 1075, 1077–1079, 1078t imaging of, 430–431, 433f, 1076, 1079 immediate vs. delayed, 1077–1078, 1078t pathology of, 1077, 1077t surgical management of, 1079–1082, 1079f, 1080t, 1081t Facial nerve preservation facial nerve monitoring and, 976 with meningioma, 803, 811, 832–833, 833t Facial nerve schwannomas (FNSs) in cerebellopontine angle, 366, 367f, 371, 423, 859 dumbbell-shaped, 424, 425f geniculate ganglion, 424–425, 426f hearing loss due to, 173 histopathology of, 1258–1260, 1260f imaging of, 423–424, 424f–428f in internal auditory canal, 423–424 in posterior and middle cranial fossae, 424, 425f topography of, 1259–1260, 1260f tympanic, 424, 426f types of, 423, 424f, 1258–1259 Facial nerve surgery 19th-century advances in, 25–26 overview of, 1212–1221 Facial nerve testing, 1223–1228 with central activation, 1248–1249, 1248f comparison of tests for, 1226–1228 with electromyography, 966–975, 1223, 1225, 1246–1248, 1247f with electroneuronography. See Electroneuronography (ENOG). electrophysiologic, 1245–1246, 1245f

evolution of, 1223 for facial palsy, 1244–1249, 1245f, 1247f, 1248f general considerations in, 1228, 1228f interpretation of, 1225–1226, 1226f, 1226t limitations of, 1079 with maximal stimulation test. See Maximal stimulation test (MST). methods of, 1078, 1223–1225, 1224f, 1225f with nerve excitability test, 1223–1224, 1226, 1227, 1246 for prognosis, 1078–1079, 1227–1228, 1227t, 1228t purpose of, 1223 topognostic, 1244–1245 with transtympanic stimulation, 1248 Facial nerve trauma. See Facial nerve injury(ies). Facial nerve tumor(s), 1258–1268 carcinomas, 427 in children, 1262 cholesterol cysts, 427 clinical presentation of, 1262–1265, 1264f decompression surgery for, 1267 diagnostic evaluation of, 1265–1266 epidermoid cysts, 426–427, 429f–431f fibroangioma, 1261 glomus, 1261 granular cell, 1261 hemangiomas, 425–426, 428f, 429f, 1261, 1261f histopathology of, 1258–1262, 1260f, 1261f imaging of, 423–430 metastatic, 1262 neurofibromas, 1259 neuromas clinical presentation of, 1264, 1264f facial palsy due to, 1239, 1242, 1242f, 1243f histopathology of, 1258 traumatic, 1260 paragangliomas, 149f, 150f, 154, 155f, 427, 432f parotid, 1262, 1263, 1264, 1267 peripheral nerve sheath, 1258 pseudo-, 1272, 1272f, 1273f rare, 427–430, 432f schwannoma. See Facial nerve schwannomas (FNSs). of temporal bone, 1261–1262 transdural-middle fossa resection of, 1266–1267 translabyrinthine-transcochlear approaches to, 1267 transmastoid approach to, 1266 transmastoid-middle cranial fossa surgery for, 1266 treatment of, 1266–1268 vascular, 425–426, 428f, 429f watchful waiting with interval scanning for, 1267 Facial nucleus anatomy of, 1201, 1202f in vestibulo-ocular reflex pathway, 100, 100f Facial nucleus reorganization, 896–897 Facial numbness, in multiple sclerosis, 505 Facial pain due to acoustic neuroma, 740 atypical, otalgia due to, 198 Facial palsy(ies), 1230–1252. See also Bell’s palsy; Facial nerve paralysis. after acoustic neuroma surgery, 758–761 bilateral, 1231, 1232t due to birth injury, 1231t, 1241, 1277 care of eye in, 761

INDEX

Facial palsy(ies) (Continued) childhood, 1241 due to cochlear implantation, 1312 as complication of neurotologic surgery, 722f, 723–724, 723f congenital, 1241 differential diagnosis of, 1238–1241, 1238f, 1239f etiology of, 1231, 1231t, 1232t exposure keratitis due to, 1232, 1233f eye problems with, 1339–1348 nonsurgical management of, 1341–1344, 1342t, 1343f, 1344f reasons for, 1339–1340 surgical management of, 1344–1347, 1345f–1348f types of, 1340–1341 facial nerve testing for, 1244–1249, 1245f, 1247f, 1248f genetic and metabolic causes of, 1231t grading of, 1232, 1232t due to herpes zoster oticus, 1232–1233, 1233f historical background of, 1230, 1230f iatrogenic, 1231t, 1270–1278 idiopathic, 1231t idiopathic isolated peripheral, 13, 431, 433f due to infection, 1231t, 1236–1237 due to Lyme disease, 432, 1240 due to mastoiditis, 1240 due to Melkersson-Rosenthal syndrome, 1239–1240, 1239f due to metastasis, 151 due to necrotizing (malignant) otitis externa, 432, 1240–1241 due to neoplasm, 1231t, 1238–1239, 1238f, 1263, 1264 neurologic causes of, 1231t due to otitis media, 915–917, 1240 radiologic evaluation of, 1241–1243, 1242f, 1243f sequelae and natural history of, 1243–1244, 1243t, 1244f toxic causes of, 1231t due to trauma, 1231t treatment for, 723–724, 723f, 1249–1252 unilateral, 1231, 1231t vascular causes of, 1231t Facial paralysis. See Facial palsy(ies). Facial paresis, 1210 Facial recess, surgical approach to facial nerve in, 1218, 1219f Facial recess method, of identifying facial nerve, 1273 Facial spasm, 1210 due to acoustic neuroma, 740–741 Facial weakness due to acoustic neuroma, 740–741 in multiple sclerosis, 504 Facioacoustic primordium, 1199, 1200f Fall(s), by elderly, 533 dynamic posturography for, 262 Falling, 116 Fallopian bridge approach, to jugular foramen, 684, 684f Fallopian bridge technique, 1219–1220, 1220f Fallopian canal CSF leak from, 928 dehiscence of, 1205–1206, 1205f, 1271, 1272f, 1272t discovery of, 5 and facial nerve, 1202–1205, 1203f, 1205f invasion by meningioma of, 147, 148f Fallopio, Gabrielle, 5, 5f Fallopius, Gabriel, 1199 Famciclovir (Famvir), for Ramsay Hunt syndrome, 668

Familial ataxia, 560 pharmacotherapy for, 662t, 667 Familial episodic ataxia, and migraine, 512 Familial paragangliomas, 135–138 Faradic stimulation, 1223 Fascia lata support, of lower lid, 1345 Fasciocutaneous flap, radial forearm, 1012, 1013f, 1014f Fastigial nucleus, 87 Fastigiovestibular projection, 87 Faure, 26 Fenestration, for posterior fossa arachnoid cysts, 947, 947f Fenestration operation, history of, 34–35 Ferrier, David, 24, 25 Fetal alcohol syndrome, hearing loss due to, 594 Fetus, hearing by, 568–569 FFR (frequency-following response), 68 FGF (fibroblast growth factor), in acoustic neuroma, 732 Fiber-optic endoscopic examination of swallowing safety (FESS), 1353 Fiber-optic laryngoscopy, for swallowing dysfunction, 1353 Fibrillation potential, 1225 Fibrin glue, for CSF leak, 931 Fibroangioma, of facial nerve, 1261 Fibroblast growth factor (FGF), in acoustic neuroma, 732 Fibrocytoma, of cerebellopontine angle, 863 Fibrohistiocytoma, malignant, 1126f Fibromas, chondromyxoid, of petrous apex, 1121 Fibromatosis, aggressive, of cerebellopontine angle, 863 Fibromuscular dysplasia (FMD) angiography of, 453–454, 454f pulsatile tinnitus due to, 208 Fibrosarcomas of cerebellopontine angle, 863 radiation-induced, 1192 Fibrous dysplasia cochlear hearing loss due to, 602–603 magnetic resonance imaging of, 347 of petrous apex, 393, 395f–397f of temporal bone, 1125–1127 atypical, 1126f clinical manifestations of, 1125–1126, 1132t complications of, 1127, 1127f monostotic, 1126f radiologic findings in, 1126, 1126f, 1133t treatment of, 1126–1127 Fibrous histiocytoma of cerebellopontine angle, 863 malignant radiation-induced, 1192f Fibrous septum, 1055f Fifth nerve sheath tumor. See Trigeminal neuromas. Filatov, V. P., 1004 Filtered speech, auditory processing testing of, 274 Filtering bands, multiple, in hearing aids, 1288 Fisch, Ugo, 695 Fisch D infratemporal fossa approach, to craniovertebral junction, 1158–1159, 1159f Fistula(e,s) arteriovenous. See Arteriovenous fistulas (AVFs). carotid-cavernous. See Carotid-cavernous fistulas (CCFs). perilymphatic. See Perilymphatic fistula (PLF). vertebral, 452, 453f

1381

Fistula sign, 248 Fistula test, 248 Fixation, 221 Flare sign. See Dural tail. Flaxman, John, 12–13 Floating mass transducer (FMT), 1297, 1297f Floccular target neurons (FTN), 104, 105 Flocculus anatomy of, 893, 893f, 1141f, 1145f projection from, 87 in vestibulo-ocular reflex, 102 Flourens, Marie-Jean Pierre, 15, 15f, 26, 228 Flunarizine (Sibelium) for familial ataxia syndrome, 667 for vestibular dysfunction, 668, 669t for vestibular migraine, 666 Fluorescein, for CSF leak, 932 Fluoroquinolones, for skull base osteomyelitis, 1103 FM. See Foramen magnum (FM). FMD (fibromuscular dysplasia) angiography of, 453–454, 454f pulsatile tinnitus due to, 208 fMRI. See Functional magnetic resonance imaging (fMRI). FMT (floating mass transducer), 1297, 1297f FN. See Facial nerve (FN). FNC (facial nerve canal) normal variants of, 421–422, 423f, 424f paragangliomas of, 154, 155f, 427, 432f FNSs. See Facial nerve schwannomas (FNSs). “Fool’s fascia,” 1007 Foramen lacerum and craniovertebral junction, 1137f and lateral skull base, 998f, 1001 and parasellar and cavernous sinus region, 1054f, 1055, 1055f and petrous apex, 1108 Foramen magnum (FM) and craniovertebral junction, 1137f, 1140f, 1141f, 1159f and lateral skull base, 998f, 1002 and parasellar and cavernous sinus region, 1054f surgical approach to, 704–706, 705f, 706f, 826–827, 827f Foramen magnum meningiomas, 824–828 anatomy of, 824–825 classification of, 825 clinical presentation of, 825–826 diagnosis of, 826, 826f epidemiology of, 825 history of, 825 surgical approach to, 826–827, 827f surgical results for, 827–828 Foramen of Luschka, 1140f, 1141f, 1323–1324, 1324f Foramen of Magendie, 1141f Foramen ovale and craniovertebral junction, 1137f, 1158 and lateral skull base, 998f, 1002 and parasellar and cavernous sinus region, 1054f, 1055, 1055f trigeminal neuroma of, 1051f Foramen rotundum, 1002 Foramen spinosum and craniovertebral junction, 1137f, 1158f, 1159f and lateral skull base, 998f, 1002 and parasellar and cavernous sinus region, 1054f, 1055, 1055f Forebrain, projections from vestibular organs to, 118 Forehead flaps, 1009 “Forehead sparing,” 1201

1382

INDEX

Fortaz (ceftazidime) for skull base osteomyelitis, 1103 for wound infections, 721 Fortification spectrum, 201 in migraine, 514 Forward problem, in electrical field theory, 312 Fossa incudis method, of identifying facial nerve, 1273 Fourth ventricle, 1145f, 1160f, 1324f Foveal alignment, 228 Foveolae granulares, 153 Fowler, Edmund, 34 FPT (frequency patterns test), 274 Fractionated stereotactic radiosurgery, 770, 770t, 1174, 1178f, 1181 for acoustic neuroma, 770, 770t Fracture(s) clivus, 1074–1075, 1075f temporal bone. See Temporal bone fracture(s). Fragile X syndrome (FRAXA), anticipation in, 127 Frederick II, Emperor, 2–3 Free flap(s), for skull base reconstruction, 1011–1018, 1013f–1020f gastro-omental, 1013f, 1015–1016, 1018f lateral thigh, 1013f, 1016–1018, 1020f lateral upper arm, 1013f, 1016, 1019f latissimus dorsi, 1013f, 1016, 1019f radial forearm, 1012, 1013f, 1014f rectus abdominis, 1012–1015, 1013f, 1015f–1017f Frenzel’s lenses, 611 Frequency characteristic, 55 representation of, 55–58 place, 55–57, 55f–57f temporal, 57, 57f, 58 of sound, 54n Frequency analysis, in auditory system, 54–58, 54f–57f Frequency patterns test (FPT), 274 Frequency shaping bands, multiple, in hearing aids, 1288 Frequency threshold curves (FTCs). See Tuning curves. Frequency-altered speech, auditory processing testing of, 274 Frequency-following response (FFR), 68 Frey’s syndrome, 1210 Friedreich’s ataxia central balance deficits with, 263, 263f central processing deficits with, 578 vertigo due to, 560 Fronto-temporal/lateral facial approach, for parasellar tumors, 1063–1066, 1064f, 1065f FTCs (frequency threshold curves). See Tuning curves. FTN (floccular target neurons), 104, 105 Fukuda stepping tests, 225 Functional compensation, 1334 Functional imaging, 306–323 magnetic resonance. See Functional magnetic resonance imaging (fMRI). of neuroelectrical and neuromagnetic scalp activity, 307–316 background and principles of, 307–308, 307f brain maps for, 310–312 dipole source modeling for, 312–316, 312f, 314f, 317f–318f electric fields in, 307–308 magnetic fields in, 308 need for multichannel recordings in, 308–310, 309f positron emission tomography for, 318–320

Functional magnetic resonance imaging (fMRI), 53, 320–323 advantages and disadvantages of, 322–323 for auditory processing testing, 282, 321 auditory studies using, 321–322 background and general principles of, 320–322 boxcar vs. event-related designs for, 321 clinical applications of, 323 of cochlear implants, 322 of cortical development, maturation, and plasticity, 321–322 of cross-modal activation in primary auditory cortex, 322 with magnetoencephalography, 323 with positron emission tomography, 323 in speech and language studies, 322 for tinnitus, 322 Fundoscopy, 217 Furosemide (Lasix) for cerebral edema, 720 hearing loss due to, 594 ototoxicity of, 251 for pseudotumor cerebri, 209 Furstenberg, A. C., 33 Fusional vergence, 235–236

G GABA. See γ-aminobutyric acid (GABA). Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), in functional MRI, 320 Gain, with vestibulo-ocular reflex, 109–111, 109f loss and recovery of, 113 Gait ataxia due to acoustic neuroma, 740 in children, 554 Gait disorders, 225 Galea, 1006f Galeal-pericranial flap, anterior, 1006–1007, 1006f, 1018, 1021f Galen, Claudius, 2 Gallium scan, for skull base osteomyelitis, 1100–1101 Galvanic stimulation, 1223 Gamma Knife radiosurgery, 1164–1181 for acoustic neuromas, 1173–1181, 1174f–1181f applications and outcomes of, 1173–1181, 1174t, 1175f–1181f for arteriovenous malformations, 942 automatic positioning system for, 1164, 1165f, 1173 basic concepts of, 1167–1168, 1168f–1170f biologic effects of, 1170–1171, 1171f collimator helmets in, 1166–1167, 1167f, 1168–1169, 1169f complications of, 1193 equipment for, 768, 769f, 1164, 1165f exporting in, 1173 fine-tuning of, 1172, 1172f frame attachment for, 1166–1167, 1166f, 1167f grouping shots in, 1173 historical background of, 1164–1165, 1165f irradiation technique in, 1168–1169, 1169f, 1170f manually setting coordinates for, 1173 for meningiomas, 836 MRI with, 1174, 1177f for parasellar and clival neoplasms, 1052 peripheral isodose in, 1172–1173 placing shots in, 1171, 1172f plugging in, 1172, 1173f

protocols for, 1173 quality assurance for, 1169–1170 quantity absorbed dose in, 1167 quantity radioactivity in, 1167 radiation physics of, 1167–1171, 1168f software “wizard” in, 1171 stereotactic vs., 1164–1165, 1165f training in, 1165 treatment planning for, 1171–1173, 1172f, 1173f treatment procedures in, 1173 γ-aminobutyric acid (GABA) in cochlear nuclei, 47 in dorsal lemniscal nucleus, 48 in tinnitus, 190 Gap detection tests, for temporal processing disorders, 274 Gardner-Robertson hearing classification system, 1174t, 1177f Gastro-omental free flap, 1013f, 1015–1016, 1018f Gastrostomy, for swallowing dysfunction, 1354 Gaucher’s disease, central processing deficits due to, 579 Gaze saccade, 111–112, 112f Gaze test, 608, 612, 613f Gaze-holding, 221, 222, 223f GC (granule cells), in vestibulo-ocular reflex, 102, 102f Gd-DTPA (gadolinium diethylenetriamine pentaacetic acid), in functional MRI, 320 GDNF (glial cell line-derived neurotrophic factor), 140 and facial nerve regeneration, 1210 Gene(s) segregation of, 125–126 therapeutic, 138–141, 139t Gene therapy, intracochlear, 138–141, 139t Gene transfer therapy, 668 Gene transfer vectors, 132t, 138–141, 139t General sensory afferents (GSAs), 1202 General visceral afferents (GVAs), 1202 General visceral efferents (GVEs), 1201 Genetic basis for facial palsy, 1231t for Ménière’s disease, 626 for sensorineural hearing loss, 601–602 Genetic screening, for auditory neuropathy, 474 Genetic testing, for neurofibromatosis 2, 789 Genetics, molecular. See Molecular genetics. Geniculate ganglion development of, 1199, 1200f and facial nerve, 219, 1202f–1204f, 1216f and facial palsies, 1235f and iatrogenic facial nerve injuries, 1271f and parasellar and cavernous sinus region, 1055f Geniculate ganglion hemangiomas, 425, 426, 429f Geniculate ganglion lesions, 424–425, 428f, 429f Geniculate ganglion schwannomas, 424–425, 426f Geniculate neuralgia, 905–906 Genomic imprinting, 127, 127f, 138 Gentamicin for Ménière’s disease, 630–631, 664 ototoxicity of, 251, 593 for wound infections, 721–722 Giant aneurysms, 369, 369f Gillies, Harold, 1004 Glandular tumors, of external auditory canal, 1031 Glasscock, M. E., 730t

INDEX

Glasses, protective, 1342 Glaucoma, aural, 27 Glial cell line-derived neurotrophic factor (GDNF), 140 and facial nerve regeneration, 1210 Glioblastoma of cerebellopontine angle, 857 of pons, facial nerve degeneration due to, 153–154, 154f Gliomas of acoustic nerve, 373 brainstem, 876–880, 878f, 879f, 880t of cerebellopontine angle, 854 leptomeningeal, 853 radiation-induced, 1192 Glomus bodies, 1039 Glomus faciale, 154, 155f, 427, 432f Glomus jugulare tumors, 1039–1042 angiography of, 455–456, 457f–461f of cerebellopontine angle, 353f, 366–367, 367f, 862, 862f, 863f classification of, 1041 clinical presentation of, 456, 1039 cranial neuropathies due to, 1039 defined, 455 diagnosis of, 456 embolization of, 456, 457f–461f epidemiology of, 1039 of facial nerve, 1261 facial nerve injury during surgery for, 1277 familial, 1039 genomic imprinting of, 127 hearing loss due to, 173, 1039 histology of, 1039 historical background of, 35, 1039 imaging of, 400, 406f–407f, 1039–1041, 1039f, 1040f paraneoplastic syndromes with, 543–546, 544t pathologic correlates of, 148–150, 149f, 149t, 150f preoperative embolization of arterial feeders to, 715, 715f pulsatile tinnitus due to, 208, 208t, 209–211, 1039 radiation therapy for, 1041 resection of, 684, 684f, 1041 history of, 35 stereotactic radiosurgery for, 1041–1042 treatment of, 456, 457f–461f, 1041–1042 vasoactive, 455–456 vestibular, molecular genetics of, 134–138 Glomus jugulotympanicum tumor, 400 Glomus tympanicum tumor, 400, 405f, 414 of facial nerve, 1261 Glomus vagale, 402, 408f Glossopharyngeal nerve, 225 and craniovertebral junction, 1142 intraoperative monitoring of, 979, 979f and jugular foramen, 1037–1038, 1038f and lateral skull base, 999 and parasellar and cavernous sinus region, 1055f and petrous apex, 1108 Glossopharyngeal nerve injury, swallowing disorder due to, 1351 Glossopharyngeal neuralgia (GPN), 905 clinical features of, 905 diagnosis and treatment of, 905 histopathology of, 898 historical background of, 905 idiopathic, 905 otalgia due to, 199–200 site of lesion for, 905 trigeminal neuralgia with, 903

Glossopharyngeal schwannomas, 366–367, 860–861 Glottic closure, for chronic aspiration, 1361 Glucocorticoids, for facial palsy, 1249–1250 Glucose, for status epilepticus, 521t Glycine, in cochlear nuclei, 47 Godlee, Rickman, 24, 27 Gold weights, for eyelids, 1346 Goldmann perimeter, 236 Goltz, Friedrich Leopold, 26–27, 27f Gorlin’s syndrome, 856 Gowers, William, 24 GPN. See Glossopharyngeal neuralgia (GPN). Gradenigo’s syndrome, 218, 230, 234, 1116 Grafting, of facial nerve, 1214, 1214f, 1217f, 1220–1221, 1221f, 1252 Granular cell tumors, of facial nerve, 1261 Granulation tissue, due to otitis media, 913t, 917, 917f Granule cells (GC), in vestibulo-ocular reflex, 102, 102f Granuloma(s), cholesterol of cerebellopontine angle, 858, 860f of petrous apex, 1111–1114, 1112f, 1113f hearing loss due to, 173 imaging of, 370, 370f, 384–385, 385f, 386f Granulomatosis, Wegener’s labyrinthitis due to, 336 vestibular symptoms of, 180 Great vessels, radiation effect on, 1190–1191, 1191f Greater auricular nerve, for facial nerve grafting, 1220–1221, 1221f Greater petrosal nerve, 1002, 1055f, 1158f Greater superficial petrosal nerve (GSPN) anatomy of, 219, 1204, 1216f–1218f, 1235f, 1271f development of, 1199 during vestibular neurectomy, 952 Grid sector analysis (GSA), 311 Group B streptococcus, meningitis due to, 490t, 491 Group E nucleus, 98 Group F nucleus, 80, 87 Group L nucleus, 79 Group X nucleus, 80, 86, 87 Group Y nucleus, 78f, 79, 80f, 81f, 85 Group Z nucleus, 80, 86 Gruber, Joseph, 19 GSA (grid sector analysis), 311 GSAs (general sensory afferents), 1202 GSPN. See Greater superficial petrosal nerve (GSPN). Guild, Stacy, 35 Guilford, F. A., 35 Gummas, of cerebellopontine angle, 857–858 Gusher ear, 332 Gustatory sweating, 1210 Guyot, E. G., 12 GVAs (general visceral afferents), 1202 GVEs (general visceral efferents), 1201

H Habituation, 1332 rotational, 897 of vestibular nystagmus, 112 Habituation exercises, in vestibular rehabilitation, 1336, 1337 HAC (hydroxyapatite cement), for CSF leak, 931 Haemophilus influenzae type B (HiB), meningitis due to, 490, 490t, 491, 496 Hair cell(s) (HC) afferent neurons to, 95–96, 96f aging effect on, 533

1383

anatomy and physiology of, 92–94, 93f, 589–591, 590f, 591f development of, 91–92 efferent neurons of, 98 electromotility of, 590–591, 591f, 601 in frequency analysis, 54–55 genetic mutations in, 601 ion recycling by, 590, 590f labyrinth fluid spaces and, 92 mechanoelectrical transduction by, 93–94, 93f, 590, 590f neurotransmission by, 590, 590f noise-induced damage to, 591–592 orientation of, 96, 96f in otolith organs, 242 type 1 and type 2, 75–76, 76f, 92, 93f Half-life, in Gamma Knife radiosurgery, 1168 Hallpike, C. S., 33 Hallpike maneuver. See Dix-Hallpike maneuver. Haloperidol (Haldol), for vestibular dysfunction, 669, 669t Halsted, William, 28 Hamartomas of acoustic nerve, 374 of cerebellopontine angle, 853 Hamulus, 998f, 1054f Handbuch der Pathologischen Anatomie, 17 Haploinsufficiency, 125 Harashina, T., 1005 Harii, K., 1005 Harless, 15 Hasse, S., 27 HBO (hyperbaric oxygen) therapy for osteoradionecrosis, 1188 for skull base osteomyelitis, 1104 HC. See Hair cell(s) (HC). HD (Huntington’s disease), anticipation in, 127 Head autorotation testing, for ototoxicity, 252 “Head heaves,” side-to-side, 222 Head injury dizziness or vertigo after, 541, 541t vestibular dysfunction due to, 179 Head posturing, 234 Head shadow effect, 1285 Head thrust test, 222, 222f Head velocity command, 105 Headache(s) due to acoustic neuroma, 739t, 741, 767–768 cervicogenic, otalgia due to, 201 cluster, otalgia due to, 201–202 due to increased intracranial pressure, 524 migraine. See Migraine. otalgia due to, 197t, 200–202 after retrosigmoid craniotomy, 689 tension-type, otalgia due to, 201 traction and inflammatory, otalgia due to, 201–202 Head-eye coordination, 111–112, 112f Head-eye dyscoordination, 177 Head-shaking nystagmus (HSN), 222–223 Hearing, functions of, 589 Hearing aid(s), 1281–1292 acoustic feedback with, 1284–1285, 1289 after acoustic neuroma surgery, 765 audiometric configuration and, 1283 for auditory neuropathy, 474 auditory processing testing for, 282 automatic signal-processing, 1288–1289, 1288f behind-the-ear, 1283, 1284, 1285, 1287, 1291 binaural summation with, 1285 body-borne, 1283 candidacy for, 1281–1283, 1282f comparative approach (Carhart method) for, 1286

1384

INDEX

Hearing aid(s) (Continued) completely in-the-canal, 1283, 1284, 1285 deep canal fittings for, 1291 degree of loss and, 1282–1283, 1282f desired sensation level with, 1286 digital vs. digitally programmable, 1288, 1289, 1290–1291 disposable and entry-level, 1291–1292 earmold acoustics for, 1287, 1288f eyeglass, 1283 fitting flexibility for, 1288–1289, 1288f, 1289f head shadow effect with, 1285 historical background of, 1281 history of selection procedures for, 1286–1287, 1286f, 1287f hybrid, 1288, 1289, 1291 in-the-canal, 1283, 1284, 1285, 1287, 1291 in-the-ear, 1283, 1284, 1285, 1287, 1289 loudness control for, 1289–1290, 1289f modern prescriptive formulas for, 1286 monaural vs. binaural, 1285–1286 multiple filtering bands in, 1288 multiple frequency shaping bands in, 1288 multiple programs in, 1289, 1289f noise reduction for, 1288, 1290, 1291f occlusion effect with, 1284, 1284f otometrics for, 1286 real ear (probe tube) methods for, 1286–1287, 1286f, 1287f selective amplification with, 1286 for sensorineural hearing loss, 1281–1282 sensory deprivation with, 1285–1286 sound pressure level with, 1287 speech discrimination ability and, 1283 squelch with, 1285 style and type of, 1283–1285, 1284f technological advances in, 1287–1291 use gain with, 1286 variable screw potentiometers in, 1288 Hearing classification schemes, 828–829, 828t, 829t Hearing Handicap Inventory for Adults (HHI), 622 Hearing in noise test (HINT), 1287, 1310 Hearing loss, 163–174 due to acoustic neuroma, 171–176, 739–740 atypical, 739–740 audiogram shape for, 167–168, 169t contralateral, 765 course and patterns of, 164, 745 differential diagnosis of, 165–166, 166t historical background of, 163–164 incidence of, 739t mechanism of, 739 due to myelin and axon compression, 165 in neurofibromatosis 2, 786 progression of, 172 rehabilitation of, 765–766 speech discrimination and, 168–170, 169t, 171t, 172 sudden or fluctuating, 170–171, 170t symmetric, 740 due to vascular compression, 164–165 auditory brainstem response to detect, 295–297, 296f due to cerebellopontine angle lesions, 164, 167–172, 167t–171t due to cerebellopontine angle meningioma, 808 due to cholesteatomas and cholesterol granulomas of petrous apex, 173 cochlear (sensory). See Cochlear hearing loss. due to cochlear nerve compression, 173 as complication of neurotologic surgery, 724 conductive. See Conductive hearing loss (CHL).

due to craniovertebral junction anomalies, 1149 effect on brainstem of, 50 epidemiology of, 589 due to facial nerve schwannoma, 173 due to fibrous dysplasia of temporal bone, 1125–1126 due to glomus jugulare tumors, 173, 1039 hereditary nonsyndromic, 128–134, 131t syndromic, 129t–130t due to lesions of olivocochlear system or auditory efferents, 165 due to lesions other than acoustic neuroma, 173 due to lipomas, 173 due to Ménière’s disease, 621, 622, 623 due to meningiomas, 799 due to meningitis, 489–496 epidemiology of, 489–491, 490t pathophysiology and histopathology of, 491–492, 492f–494f signs and symptoms of, 492–494, 494t testing for, 495 types of, 493–494 due to migraine, 513 due to multiple sclerosis, 173, 503, 503f noise-induced, 591–592 noncochlear (retrocochlear, neural), 164 cochlear vs., 165–166, 166t nonsyndromic hereditary, 128–134, 131t due to osteogenesis imperfecta, 1131 due to osteopetrosis, 1128 due to Paget’s disease, 1129 due to posterior fossa meningioma, 173 progression of, 172 due to pseudotumor cerebri, 530 due to radiation therapy, 1190 sensorineural. See Sensorineural hearing loss (SNHL). sudden or fluctuating, 170–171, 170t syndromic, 129t–130t due to temporal bone trauma, 596–597, 1084–1086, 1085t types and mechanisms of, 164–165 with vestibular dysfunction, 556 Hearing preservation with acoustic neuroma, 761–766 assessing candidacy for, 762–763 bilateral, 764–765 clinical results of, 763, 764t definition of successful result for, 763 long-term results of, 763–764 reporting results of, 742, 742f after stereotactic surgery, 770, 772t with meningiomas, 828–832 classification schemes for, 828–829, 828t, 829t indications for, 803–804, 832 location and, 829–830, 831f results of, 831–832 size and, 830–831 surgical approaches for, 829, 829f, 830f tumor extension and, 831 and vestibulocochlear dysfunction, 831–832 Hearing tests for children, 555 after meningitis, 495 Heart disease, congenital, dizziness due to, 560 Heermann, Joachim, 34, 36, 36f Hemangioblastomas angiography of, 465 of cerebellopontine angle, 856–857 of posterior fossa, 885–887, 887f, 887t

Hemangioendotheliomas, of cerebellopontine angle, 856–857 Hemangiomas of cerebellopontine angle, 864–865 of facial nerve, 425–426, 428f, 429f, 1261, 1261f intracanalicular, 374f, 375f ossifying, of petrous apex, 393, 398f Hemangiopericytoma, of cerebellopontine angle, 865 Hemangiosarcomas, of cerebellopontine angle, 856–857 Hematologic malignancies, of petrous apex, 1121 Hematomas, postoperative, 717 Hemianopsia binasal, 217f bitemporal, 217f homonymous, 217f Hemicrania, chronic paroxysmal, otalgia due to, 202 Hemifacial spasm (HFS), 901–902 clinical features of, 901 diagnostic evaluation of, 902 histopathology of, 898 historical background of, 901 imaging of, 432–434, 433f microvascular decompression for, 901, 902 cranial nerve monitoring during, 974–975, 975f in multiple sclerosis, 504 pathophysiology of, 897, 897f site of lesion in, 902 and tinnitus, 184, 186–187 treatment of, 902 with trigeminal neuralgia, 903, 905 Hemoglobin ßS mutation, 128 Hemorrhage with acoustic neuroma, 738, 738f, 741–742 postoperative, 754 into cerebellopontine angle, 865 labyrinthine, 180–181, 246–247 imaging of, 332–334, 332f–334f with meningioma, 803 postoperative, 717–718, 717f subarachnoid due to aneurysm, 438 hydrocephalus due to, 526 of vestibular schwannoma, 358 Hemosiderin, in superficial siderosis, 478 Hemostasis, for neurotologic surgery, 678 Hemotympanum, idiopathic, 1111 Hennebert’s sign, 224, 248, 399 Henschen, Folke, 730 Heparin, for vertebrobasilar insufficiency, 666 Herb’s fold, 951, 953 Hereditary hearing loss (HHL) nonsyndromic, 128–134, 131t syndromic, 129t–130t Herniation, of brain. See Encephalocele. Herpes simplex virus (HSV) and Bell’s palsy, 1236–1237 congenital, hearing loss due to, 598 and Ménière’s disease, 625 in vestibular neuritis, 485, 668 Herpes simplex virus-1 (HSV-1) vectors, 140 Herpes virus vector, 139t Herpes zoster acute labyrinthitis due to, 178 otalgia due to, 200 Herpes zoster oticus clinical presentation of, 1232–1233, 1233f defined, 1232 electroneuronography for, 1247–1248 etiology of, 1237 imaging of, 431

INDEX

Herpes zoster oticus (Continued) pathophysiology of, 1234–1236 steroid treatment of, 1249–1250 Herson-Todd scoring method, 493, 494t Hess screen, 236 Heterochromatization, 126 Heteroglial tissue, of cerebellopontine angle, 853 Heteroplasmia, 126 Heterozygotes, double, 123 Heyer, 1028 HFS. See Hemifacial spasm (HFS). HHI (Hearing Handicap Inventory for Adults), 622 HHL (hereditary hearing loss) nonsyndromic, 128–134, 131t syndromic, 129t–130t HiB (Haemophilus influenzae type B), meningitis due to, 490, 490t, 491, 496 HiFocus, 1305, 1313, 1317 Higher central vestibular centers, 87 Higher-order processing, 66–67 High-frequency rotational chair testing, for ototoxicity, 252 High-resolution computed tomography (HRCT) of cochlear implants, 1310 in children, 1318 of CSF leak, 929, 929f, 930f of facial nerve, 419–421, 420f, 421f of glomus jugulare tumors, 1039, 1040f of lateral skull base, 384 after meningitis, 495 of temporal bone trauma, 1076, 1076f of temporal bone tumors, 1029 High-resolution neural response imaging (HR-NRI), 1305 High-threshold nociceptive-specific neurons, 194 Hilding, D., 1028 Hilger Facial Nerve Stimulator, 1223, 1246 HINT (hearing in noise test), 1287, 1310 Histamine for Ménière’s disease, 628, 662 for vestibular dysfunction, 668, 669t Histiocytoma, fibrous of cerebellopontine angle, 863 malignant radiation-induced, 1192f Histiocytosis, Langerhans cell facial nerve involvement in, 427 of petrous apex, 397, 415 History of Otology, 20 Hitselberger, William, 37, 1020 HIV (human immunodeficiency virus) Bell’s palsy with, 1234 hearing loss due to, 599 Holmgren, Gunnar, 29–30, 30f, 34, 35 Homologous recombination, 126 Homonymous hemianopsia, 217f Homoplasmia, 126 Hooke, Robert, 29 Horizontal canal nerve, 77f, 80 Horizontal canal vestibulo-ocular reflex, 98–99, 99f Horizontal eye movements, 84, 84f, 85 Horizontal segment, of facial nerve, 1204 surgical approach to, 1215–1218, 1217f–1219f Horner’s syndrome, 217, 233–234 Horsley, Victor, 23–24, 24f, 25, 27, 728, 730t, 1024 House, William F., 36, 36f, 37–38, 37f, 675, 695, 729–730, 949, 1020, 1275, 1315 House-Brackmann facial nerve grading system, 220, 220t for facial palsy, 1232, 1232t House-Urban rotatory dissector, 678 HRCT. See High-resolution computed tomography (HRCT).

HR-NRI (high-resolution neural response imaging), 1305 HSN (head-shaking nystagmus), 222–223 HSP (hypopharyngeal suction pump), 1354, 1356 HSV. See Herpes simplex virus (HSV). Human immunodeficiency virus (HIV) Bell’s palsy with, 1234 hearing loss due to, 599 Humidity, and ocular problems, 1343 Hun, Henry, 17 Hunter, John, 12 Huntington’s disease (HD), anticipation in, 127 Huschke’s foramen, 1028 Hydrencephalomeningocele, 1089 Hydrocarbon solvents, neuro-ophthalmic manifestations of, 237 Hydrocephalic acoustic neuroma, 358, 734, 734t, 737f Hydrocephalus acute vs. chronic, 524 arrested, 524 clinical manifestations of, 526 communicating vs. noncommunicating, 524 diagnosis of, 527 with elevated CSF pressure, 524, 526–528, 526f–530f etiology of, 526 normal-pressure, 528–530 obstructive, 524 otitic, 524, 1231 due to otitis media, 913t, 920–921, 921f treatment for, 527–528, 528f–530f, 529–530 due to vestibular schwannoma, 358 Hydrochlorothiazide, for Ménière’s disease, 628 Hydrodynamic theory, 1146 Hydrops cochlear, 621–622 delayed, 626 endolymphatic, 178–179 imaging of, 345–347, 346f and Ménière’s disease, 623–626, 624f, 625f otolith dysfunction due to, 242 post-traumatic, 249, 1087 perilymphatic, 332 Hydrostatic equilibrium theory, 27 Hydroxyamphetamine (Paredrine) test, 217, 234 Hydroxyapatite cement (HAC), for CSF leak, 931 Hyperacusis, 183, 184 Hyperalgesia, defined, 194 Hyperbaric oxygen (HBO) therapy for osteoradionecrosis, 1188 for skull base osteomyelitis, 1104 Hyperbilirubinemia central processing deficits due to, 579 cochlear hearing loss due to, 602 Hypercalcemia, infantile, 183 Hypercholesterolemia, cochlear hearing loss due to, 602 Hyperkinesis, after facial nerve injury, 1210 Hyperlipidemia, cochlear hearing loss due to, 602 Hypermethylation, in genomic imprinting, 127 Hyperosmolar agents, for cerebral edema, 720 Hyperostosis, meningioma with, 796, 800 Hyperpathia, 184 Hypertension, intracranial benign, 524, 530–531 otogenic, 524 Hyperventilation, for cerebral edema, 720 Hyperventilation-induced nystagmus, 224 Hypoglossal canal and craniovertebral junction, 1137f and jugular foramen lesions, 407, 411f

1385

and lateral skull base, 998f, 1001 and parasellar region, 1053, 1054f Hypoglossal nerve, 225–226 and craniovertebral junction, 1142 intraoperative monitoring of, 979f, 981 and lateral skull base, 999 lesions involving, 407, 411f and parasellar region, 1055f Hypoglossal nerve injury, swallowing disorder due to, 1352 Hypoglossal nerve-RLN anastomosis, for vocal cord paralysis, 1360–1361 Hypoglossal schwannoma, 367 Hypoglossal-facial anastomoses, 760–761, 760f Hypoglycemia, dizziness due to, 560 Hyponatremia, seizures due to, 519 Hypoperfusion, syncope due to, 177, 177t Hypopharyngeal suction pump (HSP), 1354, 1356 Hypotension orthostatic, in elderly, 535 spontaneous intracranial, 480 Hypothyroidism, cochlear hearing loss due to, 602 Hypotympanic triangle, extension of paraganglioma to, 149, 150f Hypoxia, cochlear hearing loss due to, 602 Hyrtl’s fissure, CSF leak with, 928

I IAC. See Internal auditory canal (IAC). Iatrogenic injury of chorda tympani nerve, 1277 of facial nerve, 1270–1278, 1273t during acoustic neuroma surgery, 1275–1276 in children, 1277 during cochlear implantation, 1276–1277 with congenital anomalies, 1277 counseling for, 1277–1278 diagnosis and management of, 1275 during mastoidectomy, 1272–1274 mechanisms of, 1270 during middle fossa surgery, 1276 normal anatomy and variations and, 1271–1272, 1271f–1273f, 1272t prevention of, 1270–1271 during resection of paraganglioma, 1277 during surgery for cholesteatoma, 1274, 1275f during surgery for otitis media, 1271 during surgery of external auditory canal, 1276 Iatrogenic temporal bone encephalocele, 1090 IBNs (inhibitory burst neurons), 105, 106f IC. See Inferior colliculus (IC). ICA. See Internal carotid artery (ICA). ICC. See Central nucleus of inferior colliculus (ICC, CNIC). ICS (implantable cochlear stimulator), 1305 ICX (external nucleus of inferior colliculus), 59f, 62, 63, 65, 65f Idea of a New Anatomy of the Brain, 13 Idiopathic, progressive, bilateral sensorineural hearing loss (IPBSNHL), 639–642, 640t Idiopathic hypertrophic cranial pachymeningitis (IHCP), 480–482 clinical presentation of, 480 dural tail due to, 363f evaluation of, 481, 481f, 481t histopathology of, 480, 480f incidence and etiology of, 480 outcomes for, 481–482 treatment for, 481

1386

INDEX

Idiopathic isolated peripheral facial palsy, 13, 431, 433f Idiopathic sudden sensorineural hearing loss, 595–596, 640 IFC (infracerebellar nucleus), 79, 80f, 82f, 84f, 85 IGF-II, in genomic imprinting, 127 IHDs. See Implantable hearing devices (IHDs). IM (incudomalleal) joint, trauma to, 1084 Imbalance, 177 in elderly, 535 due to medication, 536t IMEHDs (implantable middle ear hearing devices), 1295–1296, 1297–1299, 1298f, 1299f, 1299t Imipramine, for vestibular migraine, 665–666 Imitrex (sumatriptan), for migraine, 666 Immune-mediated labyrinthitis, 336–337, 337f, 338f Immunologic factors, in Ménière’s disease, 624–626 Immunologic injury, and Bell’s palsy, 1237 Immunosuppressive therapy, for autoimmune inner ear disease, 641–642 Impedance audiometry, for pulsatile tinnitus, 209 Implantable cochlear stimulator (ICS), 1305 Implantable hearing devices (IHDs), 1295–1299 BAHA, 1296–1297, 1296f, 1299t bone-anchored, 1295, 1296–1297, 1296f, 1299t defined, 1295 Direct System, 1297–1298, 1298f, 1299t Envoy, 1298–1299, 1299f, 1299t indications for, 1295 issues with, 1296 middle ear, 1295–1296, 1297–1299, 1298f, 1299f, 1299t Middle Ear Transducer, 1298, 1298f, 1299t overview of, 1295–1296 Vibrant Soundbridge, 1297, 1297f, 1299t Implantable middle ear hearing devices (IMEHDs), 1295–1296, 1297–1299, 1298f, 1299f, 1299t Imprinting, genomic, 127, 127f, 138 IMRT (intensity-modulated radiation therapy), 1181–1182, 1182f In vivo gene therapy, 668 Inapsine (droperidol), for vestibular dysfunction, 669, 669t INC (interstitial nucleus of Cajal) anatomy of, 82f, 87 in vestibulo-ocular reflex pathway, 100, 100f Incisura, 701 Incomplete penetrance, 123, 124, 124f Increased risk, 128 Incudomalleal (IM) joint, trauma to, 1084 Incudostapedial (IS) joint separation, 1084, 1084t Incus, massive dislocation of, 1084–1085, 1084t Independent assortment, 125–126 Indium-111 scan, for skull base osteomyelitis, 1100 Infancy auditory brainstem response to detect hearing loss in, 295–297 development of auditory competence in, 569–570, 570f paroxysmal torticollis of, 557, 559 Infantile hypercalcemia, 183 Infarct, lateral medullary, vestibular symptoms of, 181 Infection(s) central processing deficits due to, 578–579 cochlear hearing loss due to, 597–599

CSF leak due to, 927, 931 facial palsy due to, 1231t, 1236–1237 of petrous apex, 1116–1117, 1117f postoperative, 721–722, 722f Infectious mononucleosis, acute labyrinthitis due to, 178 Inferior articular facet, 1138f Inferior cavernous artery, 1055f Inferior cerebellar artery, vascular loop of, 157f Inferior cerebellar peduncle, 1141f Inferior colliculus (IC) anatomy of, 45, 46f in central auditory system, 565f, 566–567, 566f central nucleus of development of, 566–567 effect of cochlear implant on, 577 physiology of, 59f, 62–64, 63f, 66 external nucleus of, 59f, 62, 63, 65, 65f in information processing, 48–49 myelination of brachium of, 567, 568f physiology of, 59f, 62–64, 63f tuning curves from, 60f Inferior medullary velum, 1144f Inferior nuchal line, 1137f Inferior oblique muscle (IO) innervation of, 84, 85f in vestibulo-ocular reflex pathway, 99–100, 99f, 100f Inferior orbital fissure, 998f, 1054f Inferior petrosal sinus, 1001, 1038, 1108 Inferior pharyngeal constrictor, 1157f Inferior rectus muscle (IR) innervation of, 84, 85f in vestibulo-ocular reflex pathway, 99–100, 99f, 100f Inferior sagittal sinus, 1139f Inflammation, of facial nerve, 431–432, 433f Inflammatory headache, otalgia due to, 201–202 Inflammatory lesions of cerebellopontine angle, 857–858, 858f–860f neuro-ophthalmic manifestations of, 236–237 Inflammatory middle ear disease, imaging of, 407–414, 412f–414f Information processing, in brainstem, 47–50 Infracerebellar nucleus (IFC), 79, 80f, 82f, 84f, 85 Infrared (IR) oculography, 608 Infrared (IR) tracking, 235 Infratemporal fossa approach, 684–685, 685f Fisch D, to craniovertebral junction, 1158–1159, 1159f type B, for clival tumors, 1060–1062, 1061f, 1062f type C to craniovertebral junction, 1158, 1158f for parasellar tumors, 1066 Infratemporal lesions, direct extension to petrous apex of, imaging of, 396 Ingrassia, Giovanni, 3, 4f Inheritance patterns, 122–118 autosomal-dominant, 123–125, 124f autosomal-recessive, 122–123, 123f genomic imprinting in, 127, 127f linkage and recombination in, 126 mitochondrial, 126, 126f multifactorial, 128 trinucleotide repeat expansion in, 127 variations on Mendelian principles of, 125–128, 126f, 127f X chromosome inactivation in, 125, 126–127 X-linked, 125, 125f Inhibitory burst neurons (IBNs), 105, 106f Inion response, 270 Inner ear autoimmune disease of, 639–642, 640t cerebrospinal fluid relationship to, 525–526

congenital anomalies of hearing loss due to, 599–601 imaging of, 332 lesions of, 1031t noise-induced damage to, 591–592 Inner ear surgery, benign paroxysmal positional vertigo after, 646 Inner hair cells anatomy and physiology of, 590f in frequency analysis, 55 noise-induced damage to, 591 Inner table, 1006f Inner-ear decompression sickness, hearing loss due to, 597 Innominate fascia, 1006, 1006f, 1007 INO (internuclear ophthalmoplegia) dissociative nystagmus in, 233 in multiple sclerosis, 501, 501f Instrumentation, for neurotologic surgery, 677–678 Intensity cues, in superior olivary complex, 48 Intensity-modulated radiation therapy (IMRT), 1181–1182, 1182f Intention tremor, due to acoustic neuroma, 740 Interaural intensity differences, in superior olivary complex, 62 Interaural time difference, in superior olivary complex, 48, 62 Intercalated nucleus, 117 Intercollicular area, 49 Intermediary neurons, during nystagmus, 106, 106f Intermediate lemniscal nucleus, in information processing, 48 Internal acoustic meatus, 1137f Internal auditory artery, thrombosis of, vestibular symptoms of, 181 Internal auditory canal (IAC) and facial nerve, 1202, 1203f surgical approach to, 1212–1215, 1213f–1217f facial nerve schwannomas of, 423–424 fundus of, 1213f intracanalicular lesions of, 354f, 371–374, 373t, 374f–377f meningiomas of, 811–812 audiovestibular testing of, 799 clinical presentation of, 811t epidemiology of, 812 historical background of, 811–812 origin of, 811, 831 preoperative considerations for, 804 surgical management of, 804, 811t metastasis to, 344f MRI of, 349, 350f, 354t narrow, hearing loss with, 601 osseous decompression of, 765 small, 1318 surgical anatomy of, 1002 surgical approach to, 685–696 middle fossa, 694–696, 694f, 695f retrolabyrinthine, 685f, 686, 689–691, 690f retrosigmoid, 685, 685f, 686–689, 686f, 687f transcochlear, 685f, 686 translabyrinthine, 685f, 686, 691–693, 691f transpetrosal (transtemporal), 685f, 686, 689–693, 690f, 691f during vestibular neurectomy, 952, 954–955, 956 vestibular schwannomas of, 354f, 355–360, 356f–360f widening of hearing loss with, 601 due to vestibular schwannoma, 146

INDEX

Internal auditory canal (IAC) decompression, for vestibular schwannoma, in neurofibromatosis 2, 788 Internal auditory meatus, 1002 Internal capsule, 1201f Internal carotid artery (ICA), 155, 156f aberrant petrous, 454, 455f aneurysm of, 155–156, 439, 440f–441f arteriosclerotic plaques in, 155, 156f bleeding from, during neurotologic surgery, 715 congenitally ectopic, 155 control of bleeding from, 716, 716f in craniovertebral junction, 1140f, 1143f, 1158f, 1159f diminution with aging of, 155, 156f and jugular foramen, 1038f in lateral skull base, 998, 1000, 1001, 1002 in otalgia, 195 paragangliomas of, 156, 157f in parasellar and cavernous sinus regions, 1055, 1055f pathologic correlates of, 155–156, 156f, 157f pseudoaneurysm of, 439, 442f Internal jugular vein (IJV) control of bleeding from, 715–716 in craniovertebral junction, 1140f, 1143f, 1145f and jugular foramen, 1038f in parasellar and cavernous sinus regions, 1055f in pulsatile tinnitus, 204 Internal laryngeal nerve, 1157f Internal maxillary artery, 1001 Internuclear ophthalmoplegia (INO) dissociative nystagmus in, 233 in multiple sclerosis, 501, 501f Intersinus septum, 1157f Interstitial nucleus of Cajal (INC) anatomy of, 82f, 87 in vestibulo-ocular reflex pathway, 100, 100f Interstitial nucleus of the vestibular nerve (NIV), 77f, 79, 81f Interventional radiology, for parasellar and clival neoplasms, 1053 In-the-canal (ITC) hearing aids, 1283, 1284, 1285, 1287, 1291 In-the-ear (ITE) hearing aids, 1283, 1284, 1285, 1287, 1289 Intra-axial tumors, 370–371, 371f–373f Intracanalicular lesions, 354f, 371–374, 373t, 374f–377f Intracanalicular vestibular schwannoma, 354f Intracochlear ossification, cochlear implant with, 1319 Intracochlear transgene expression, 138–141, 139t Intracranial bruits, 216 Intracranial complications, of neurotologic surgery, 718–720, 718f–720f Intracranial hypertension benign, 524, 530–531 otogenic, 524 Intracranial pressure factors that determine, 524 increased, 524–531 due to hydrocephalus, 524, 526–528, 526f–530f manifestations of, 524 due to pseudotumor cerebri, 524, 530–531 Intracranial tumors, transbasal approaches to, 685–706 involving craniovertebral junction, 704–706, 705f, 706f

involving internal auditory canal and cerebellopontine angle, 685–699, 685f middle fossa approach, 694–696, 694f–696f middle fossa-transpetrous apex approach, 696–698, 697f retrosigmoid approach, 686–689, 686f, 687f transpetrosal approaches, 689–693, 690f, 691f involving intracranial aspect of jugular foramen, 698–699, 698f, 699f involving Meckel’s cave, 704, 704f, 705f involving ventral surface of brainstem, 699–704, 700f, 701f, 703f involving vertebrobasilar lesions, 706, 707f Intracranial vascular abnormalities, pulsatile tinnitus due to, 204–205, 205f, 208, 208t, 209, 210f Intrafunicular pressure, 1208 Intraoperative cranial nerve monitoring, 958–989 anesthesia and, 965 blink reflex for, 989, 989f channels for, 961–962, 968 of cochlear nerve, 981–988 analogue vs. digital filtering in, 982 auditory brainstem response recording for, 981–984, 983f, 987–988 compound nerve action potentials in, 982, 984–988, 984f–986f direct action potentials in, 984–985, 984f–986f electrocochleography for, 986–988, 986f electrodes for, 981–982 evoked potentials in, 987 historical background of, 959 interpretation of, 982–983 near-field recordings in, 982 and nerve preservation, 987–988 and postsurgical auditory function, 984 reducing electrical and acoustic interference with, 982 stimulus and recording parameters for, 981–982 during vestibular schwannoma surgery, 983–984, 983f communication and report generation in, 965–966 constant voltage vs. constant current for, 963 electrical safety for, 964 of facial nerve, 966–976 for activity evoked by electrical stimulation, 967–970, 969f, 970f artifacts in, 967, 971, 972f, 988 to assess functional status, 969–970 common site of injury and, 968 to identify and map nerve, 958f, 967–969 to identify nervus intermedius, 970, 970f, 971f limitations of, 974 during microvascular decompression, 974–975, 975f during middle ear surgery, 975 modalities for, 966–967 and nerve preservation, 976 during parotidectomy, 975 patterns of activity in, 971–972, 973f in prediction of outcome, 973–974 for spontaneous and mechanically elicited activity, 970–974, 972f, 973f with vestibular schwannoma and other cerebellopontine angle tumors, 962, 962f, 963f, 966–974, 969f–973f

1387

future directions for, 988–989, 989f of glossopharyngeal, vagus, and spinal accessory nerves, 979–981, 979f, 980f history and context of, 958–959 instrumentation for, 960, 960f, 961f of oculomotor, trochlear, and abducens nerves, 976–978, 977f patient preparation for, 964, 965f personnel for, 959–960 quality control for, 964–965 recording electrodes for, 960–962, 962f, 964 search vs. threshold modes in, 966 stimulating electrodes for, 962–963, 963f stimulus duration for, 963–964, 964f of trigeminal nerve, 978–979 Intrapetrous carotid aneurysm, 389, 390f, 1121, 1122f Intratympanic aminoglycoside (ITAG), for Ménière’s disease, 663–664 Intratympanic dexamethasone, for Ménière’s disease, 664 Intratympanic steroid treatment, for Ménière’s disease, 629, 664 Inverse problem, in electrical field theory, 312 Inversion recovery (IR), blood perfusion imaging using, 320–321 IO (inferior oblique muscle) innervation of, 84, 85f in vestibulo-ocular reflex pathway, 99–100, 99f, 100f Ion recycling, by hair cells, 590, 590f IPBSNHL (idiopathic, progressive, bilateral sensorineural hearing loss), 639–642, 640t IR (inferior rectus muscle) innervation of, 84, 85f in vestibulo-ocular reflex pathway, 99–100, 99f, 100f IR (inversion recovery), blood perfusion imaging using, 320–321 IR (infrared) oculography, 608 IR (infrared) tracking, 235 Irregular neurons in otolith organs, 97, 97f in semicircular canals, 95–96, 96f Irritable pattern, in intraoperative facial nerve monitoring, 972 Irritants, ocular, 1343 IS (incudostapedial) joint separation, 1084, 1084t Ischemia and Bell’s palsy, 1237 syncope due to, 177–178 Isosorbide dinitrate, for Ménière’s disease, 662 Isotretinoin, congenital hearing loss due to, 595 ITAG (intratympanic aminoglycoside), for Ménière’s disease, 663–664 Itard, J. M. G., 26 ITC (in-the-canal) hearing aids, 1283, 1284, 1285, 1287, 1291 ITE (in-the-ear) hearing aids, 1283, 1284, 1285, 1287, 1289

J Jackson, John Hughlings, 24 Jacobsen, J. H., 1004 Jacobson’s nerve anatomy of, 1271f examination of, 225 in otalgia, 195 Jacobson’s nerve schwannoma, 1260 JAFs (juvenile angiofibromas), angiography of, 465 “Janus” double-surface flaps, 1024, 1025f

1388

INDEX

Jarisch-Herxheimer reaction, 665 Jasser, 11 Jaw jerk reflex, 218 Jervell and Lange-Nielsen syndrome, hearing loss in, 129t JF. See Jugular foramen (JF). Jones, N. F., 1005 JPA (juvenile pilocytic astrocytoma), 880–883, 881f, 882f, 883t Jugular bulb anatomy of, 157–158, 1037 and craniovertebral junction, 1144f dehiscent, 399, 403f and facial nerve, 1204, 1220f high (enlarged, aberrant), 157f, 158, 158t angiography of, 454–455, 455f and parasellar and cavernous sinus spaces, 1055f pathologic correlates of, 157–158, 157f, 158t Jugular dural fold, 951, 953 Jugular foramen (JF) anatomy of, 683, 683f, 821, 1037–1038, 1038f and craniovertebral junction, 1137f, 1141f, 1145f intracranial aspect of, surgical approach to, 698–699, 698f, 699f and lateral skull base, 998f, 1000, 1001–1002 and parasellar and cavernous sinus spaces, 1054f pars nervosa of, 1037 pars vascularis of, 1037 resection of, 683–684, 683f, 684f Jugular foramen meningiomas, 821–824, 1043–1044 blood supply to, 1043 classification of, 821, 821f, 822f clinical presentation of, 822, 1043–1044 diagnosis of, 822–823, 1044, 1044f pathologic correlates of, 147, 148, 149f primary, 821, 821f secondary, 821, 822f surgical approach to, 699, 823, 823f, 824f, 1044 surgical management of, 823–824, 1044 Jugular foramen schwannomas, 366–367, 860–861, 1042–1043 clinical presentation of, 1042 epidemiology of, 1042 imaging of, 367f, 411f, 861f, 1042, 1042f, 1043f pathogenesis of, 1042 surgical approach to, 699, 699f, 1042–1043 Jugular foramen syndrome, due to skull base osteomyelitis, 1102 Jugular foramen tumors, 683, 1039–1044 Jugular fossa anatomy of, 399, 403f imaging of, 399–407 normal appearance on, 399–400, 403f involvement in chondrosarcomas and chordomas of, 407 and lateral skull base, 998f nerve sheath tumors in, 405–406, 409f and parasellar and cavernous sinus spaces, 1054f venous sinus thrombosis of, 400, 404f Jugular fossa meningiomas, 407 Jugular paraganglioma, 353f Jugular spine, 1137f Jugular tubercle, 1137f Jugular vein bleeding from, during neurotologic surgery, 715 and facial nerve, 1220f internal. See Internal jugular vein (IJV). mechanical compression of, 455

Jugular vein thrombosis, 409–410, 413f Jugulotympanic glomus tumors, angiography of, 455–456, 457f–461f Jugulotympanic paragangliomas, neural infiltration by, 149, 149f, 149t, 150f Juvenile angiofibromas (JAFs), angiography of, 465 Juvenile pilocytic astrocytoma (JPA), 880–883, 881f, 882f, 883t

K Kamanycin, ototoxicity of, 593 Kawase approach, to ventral pons and anterior cerebellopontine angle, 696–698, 697f Kcc4 gene, 601–602 KCNQ4 gene, 601 Keen, William, 793 Kennedy, 26 Keratitis exposure, 1232, 1233f nonsyphilitic interstitial, vestibular symptoms of, 180 Keratitis neuroparalytica, 904–905 Keratosis obturans, 415, 415f, 1276 KHRI-3 antibody, 639–640, 642 Kindling phenomenon, 186 Kindling theory, 896, 897 Kinocilium(ia), 75, 76, 76f, 92, 93f, 242, 590f Klippel-Feil syndrome central processing deficits with, 578 sensorineural hearing loss in, 1149 synostoses in, 1147 Klonopin (clonazepam), for vestibular dysfunction, 668, 669t Knapp, H., 27 Koch, R., 20 Kramer, Wilhelm, 21, 21f, 26 Krankheiten des Ohres, 18f Krause, Fedor, 728, 730, 730t, 958 Krizek, T. J., 1004 Kurze, T., 37

L Labbé’s vein, 679–680, 679f, 680f, 702 Labyrinth anatomy of, 221f congenital malformations of, 332 development of, 91–92 endolymphatic hydrops of, 345–347, 346f imaging of, 331–347 for congenital malformations, 332 contrast enhancement for, 337–338, 338f–341f CT for, 331–332 for endolymphatic hydrops, 345–347, 346f for hemorrhage, 332–334, 332f–334f for labyrinthitis, 334–337, 334f–338f MRI techniques for, 331 for neoplasms, 339–341, 342f, 343f for perilymphatic fistula, 338–339, 341f for postoperative changes, 341–345 invasion by paraganglioma of, 149 metastasis to, 340, 344f MRI of, 331–332 perilymphatic fistula of, 338–339, 341f postoperative changes in, 341–345 symptoms of disorders of, 178–179 Labyrinth fluid spaces, physiology of, 92 Labyrinth function, compensation for loss of, 112–114 Labyrinth reflexes, tonic, 115–116, 115f Labyrinthectomy chemical, for Ménière’s disease, 630–631, 662–664 transcanal, for Ménière’s disease, 631

transmastoid history of, 33–34 for Ménière’s disease, 632 Labyrinthine abnormalities, CSF leak due to, 927–928, 928f Labyrinthine aplasia, complete, hearing loss due to, 600 Labyrinthine apoplexy, 180, 181 Labyrinthine concussion, 179, 249, 557–558 Labyrinthine disorders, in elderly, 536 Labyrinthine fluid pressure, 526 Labyrinthine hemorrhage, 179–180, 246–247 imaging of, 332–334, 332f–334f Labyrinthine injury, vestibular symptoms of, 179 Labyrinthine neoplasms, imaging of, 339–341, 342f–345f Labyrinthine schwannomas, imaging of, 339–340, 342f, 343f Labyrinthine segment, of facial nerve, 1202–1204 surgical approach to, 1212–1215, 1213f–1217f Labyrinthitis acute. See Vestibular neuritis (VN). bacterial, 178, 334–336, 335f, 336f vs. benign paroxysmal positional vertigo, 648 in children, 556, 559 in Cogan’s syndrome, 336, 337f defined, 334 imaging of, 334–337, 334f–338f immune-mediated, 336–337, 337f, 338f otogenic suppurative, 336 otolith dysfunction due to, 247 pneumococcal, 334 primary autoimmune, 336 in relapsing polychondritis, 336–337, 338f serous, otolith dysfunction due to, 247 suppurative, otolith dysfunction due to, 247 syphilitic, 334, 336, 336f vs. vestibular neuritis, 487t viral, 334, 334f, 335f acute hemorrhagic, 333, 334f contrast enhancement for, 337, 338f, 339f otolith dysfunction due to, 247 viral neuro-, pharmacotherapy for, 662t Labyrinthitis ossificans (LO), 334 pathologic correlates of, 151–152, 152f, 491 Lacrimal drainage, failure of, 1341 Lacrimal function, evaluation of, 219 Lacrimal pump, 1341 Lacrimal puncta, plugging of, 1347 Lacriserts (slow release ophthalmic inserts), 1342, 1342t Lactoferrin, and biofilms, 915 Lake, R., 31, 33 Lamina, 1138f Lamotrigine, for vestibular symptoms of migraine, 516 Lancaster red-green test, 236 Langerhans cell histiocytosis facial nerve involvement in, 427 of petrous apex, 397, 415 Language studies, functional MRI in, 322 Large vestibular aqueduct (LVA), 133, 332 endolymphatic hydrops due to, 345 Laryngeal nerve, 1157f examination of, 225 in vocal cord paralysis, 1356 Laryngectomy, for chronic aspiration, 1361 Laryngofissure, for chronic aspiration, 1361 Laryngoscopy, fiber-optic, for swallowing dysfunction, 1353 Laryngotracheal diversion, for chronic aspiration, 1361

INDEX

Larynx, disorders of, otalgia due to, 196t, 197 Laser surgery, near facial nerve, 1270 Lasix. See Furosemide (Lasix). Late auditory evoked potentials, in children, 571 Late vertex response (LVR), in multiple sclerosis, 504 Late-onset auditory deprivation, 282 Lateral canal nerve, 77f, 80 Lateral gaze, paralysis of, 218 Lateral lemniscus (LL) in brainstem auditory pathway, 45, 46f, 59, 59f, 62–63 development of, 565f, 566, 566f in information processing, 48 Lateral mass, of atlas, 1138f Lateral medullary infarct, vestibular symptoms of, 181 Lateral medullary plate syndrome of Wallenberg, 236 Lateral olivary nucleus in brainstem auditory pathway, 45 stimulus intensity cues in, 48 Lateral olivocochlear system, 49 Lateral orbital rim, 1347f Lateral pericranial flap, 1006 Lateral pterygoid muscle, 997, 999f Lateral pterygoid plate, 1001 Lateral pterygoid process, 998f, 1054f Lateral recess, 1144f, 1323, 1324f Lateral rectus muscle (LR) anatomy of, 997, 999f innervation of, 85 in vestibulo-ocular reflex pathway, 98, 99, 99f Lateral semicircular canal, dysplasia of, hearing loss due to, 601 Lateral semicircular canal-vestibule dysplasia (LCVD), 332 Lateral sinus, 1144f Lateral sinus thrombosis, due to otitis media, 918 Lateral skull base anatomy of, 997–1002 general, 997–999, 998f, 999f surgical, 1000–1002 arteries of, 998 defined, 383, 1005, 1005f imaging of, 383–418 in external auditory canal, 415–417 in jugular and carotid region, 399–407 in middle ear and mastoid regions, 407–415 in petrous apex, 384–399 technical considerations in, 383–384 muscles of, 997, 999f nerves of, 998–999 osteoradionecrosis of, 1187, 1188f veins of, 997–998 Lateral superior olivary nucleus (LSO), 565f, 566, 566f, 575 Lateral thigh free flap, 1013f, 1016–1018, 1020f Lateral transtemporal procedure, operating room setup for, 677f Lateral upper arm flap, 1013f, 1016, 1019f Lateral ventricle, 1201f Lateral vestibular nucleus, 77f, 78, 78f, 81f, 83, 116–117 Lateral vestibulospinal tract (LVST) anatomy of, 82f, 83–84, 116, 116f physiology of, 104, 116–117 Laterocerebellar cysts, 945, 945f Latissimus dorsi free flap, 1013f, 1016, 1019f Latissimus dorsi myocutaneous flap, 1009, 1009f, 1010f

Lawrence Merle, 38 W., 1028 LCVD (lateral semicircular canal-vestibule dysplasia), 332 Le Fort I osteotomy, for clival tumors, 1058–1060, 1059f, 1060f “Leaf” electrode, 290 Lehrbuch der Ohrenheilkunde, 19 Leksell, Lars, 1164 Leksell Gamma Knife, 1165, 1167–1170 Leksell GammaPlan, 1167, 1171–1173 Leksell Stereotactic System, 1165 Lemniscal nuclei in brainstem auditory pathway, 45, 46f in information processing, 48 Lempert, Julius, 34–35, 35f, 1028 Lenticular nucleus, 1201f Lentiviral vector, 139, 139t Leptomeningeal carcinomatosis, 867f Leptomeningeal extension, of malignant tumors, 151 Leptomeningeal metastasis, loculated, 362–363, 362f, 364f Lermoyez, Marcel, 34 Lermoyez’s syndrome, 622 Leukemias labyrinthine hemorrhage in, 332, 332f metastasis of, 150 Leukodystrophies, central processing deficits due to, 579 Levator veli palatini muscle anatomy of, 997, 999f myoclonic contractions of, pulsatile tinnitus due to, 207 Lewis, J. S., 1028 Lhermitte’s symptom, 501 Liberatory maneuver, for benign paroxysmal positional vertigo, 648–649, 649f Lidocaine (Lignocaine, Xylocaine, Procaine), for tinnitus, 189–190 Ligamentum flavum, 1054 Ligamentum nuchae, 1054 Light sensitivity, with facial paralysis, 1340 Lightheadedness, 177 presyncopal, 660t Lignocaine (lidocaine), for tinnitus, 189–190 Limbic system, connections from auditory system to, 67 Limits of stability (LOS) test methodology for, 257–258, 259f reliability and validity of, 259–262 for risk of falls in older adults, 262 Linear acceleration, 241 Linear accelerator (LINAC), in stereotactic radiosurgery, 768–769, 769f CyberKnife, 1184 Linear vection, 107 Linkage, 126 Lioresal (baclofen) for hemifacial spasm, 902 for tinnitus, 190 Lipochoristomas, intracanalicular, 373, 376f Lipomas of cerebellopontine angle, 364, 365f, 852–853, 852f hearing loss due to, 173 intracanalicular, 373, 376f Liposome vectors, 139, 139t Lister, Joseph, 20, 24, 25 Listeria, neuro-ophthalmic manifestations of, 237 Listeria monocytogenes, meningitis due to, 490, 490t, 491 Lithium, nystagmus due to, 237 Littmann, Hans, 36 LL. See Lateral lemniscus (LL).

1389

LO (labyrinthitis ossificans), 334 pathologic correlates of, 151–152, 152f, 491 Local anesthetics, for tinnitus, 189–190 Local transposition flaps, for skull base reconstruction, 1006–1009, 1006f–1009f Localization defined, 274 testing of, 276 Loch, W. E., 1028 Locus minoris resistae, 895 Log roll, for benign paroxysmal positional vertigo, 650 Longissimus muscle, 997, 999f Long-term depression, 660 Longus capitis muscle, 1157f Longus coli muscle, 1157f Loop diuretics hearing loss due to, 594 semicircular canal dysfunction due to, 251 Lorazepam (Ativan) for autonomic dysfunction, 661 for status epilepticus, 521t for vestibular dysfunction, 669t LOS test. See Limits of stability (LOS) test. Loudness control, for hearing aids, 1289–1290, 1289f Loudness matching, for quantification of tinnitus, 183 Louis, Antoine, 792 Lower cranial nerve disorders, due to acoustic neuroma, 739t, 741 Lower cranial nerve palsies, rehabilitation of, 1350–1361 Lower eyelid canthoplasty of, 1344–1345, 1345f fascia lata support of, 1345 poor position of, 1340 stent support of, 1345 taping of, 1342, 1343f Lower trapezius myocutaneous flap, 1009–1010, 1011f Low-pass filtering, in auditory processing testing, 274 Low-threshold mechanoreceptors (LTM), 194 LR (lateral rectus muscle) anatomy of, 997, 999f innervation of, 85 in vestibulo-ocular reflex pathway, 98, 99, 99f LSO (lateral superior olivary nucleus), 565f, 566, 566f, 575 LTM (low-threshold mechanoreceptors), 194 Lubbers, J., 35 Luetic vestibulopathies, 249–250 Lumbar arachnoiditis, with cerebellopontine angle epidermoid cysts, 847 Lumbar puncture, for hydrocephalus, 527 Lumboperitoneal shunt for hydrocephalus, 527, 530f for pseudotumor cerebri, 209 Lung cancer, metastatic to cerebellopontine angle, 865, 866f, 867f Luxford, W. M., 730t LVA (large vestibular aqueduct), 133, 332 endolymphatic hydrops due to, 345 LVR (late vertex response), in multiple sclerosis, 504 LVST (lateral vestibulospinal tract) anatomy of, 82f, 83–84, 116, 116f physiology of, 104, 116–117 Lyme disease cerebellopontine angle lesions due to, 857, 858 facial palsy due to, 432, 1240 vestibular symptoms of, 180

1390

INDEX

Lymphatics, of external ear, 1029 Lymphomas of brain, 370, 372f of cerebellopontine angle, 867 intracanalicular, 373 metastasis of, 150 Lymphoplasmacyte-rich tumors, 798 Lyon, Mary, 126–127 Lyonization, 125, 126–127

M Macewen, William, 22–23, 23f, 25 Macewen’s sign, 216 Mach, Ernst, 27 Macula afferents, 97, 97f Macula sacculi, 75, 76, 242 Macula utriculi, 75, 76, 242 Maddox rod, 236 Maffucci syndrome, 863 Magendie, François, 13 Magnetic evoked potentials (MEP), 53 Magnetic fields, 307f, 308 Magnetic multichannel recordings, 310 Magnetic resonance angiography (MRA) of cerebellopontine angle, 350, 352f of glomus jugulare tumors, 1040–1041 of lateral skull base, 384 of meningiomas, 800 for pulsatile tinnitus, 209 Magnetic resonance imaging (MRI) of acoustic neuroma, 744–745, 745f, 745t, 746 of arachnoid cysts, 364, 365f of arteriovenous malformations, 439, 938 of cerebellopontine angle, 349–354, 350f–354f, 354t for epidermoid cysts, 844, 844f for meningiomas, 359f, 361–362, 361f–363f, 809–810, 809f for vascular lesions, 349–350, 352f, 367–369, 368f, 369f of chordoma, 1048–1049, 1049f of congenital malformations of inner ear, 332 contraindications to, 354 of craniovertebral junction malformations, 1149 of craniovertebral junction tumors, 1152–1153, 1153f of CSF leak, 929, 930f of cysticercosis, 364, 365f of endolymphatic hydrops, 345–347, 346f of endolymphatic sac tumors, 340 of epidermoid cysts, 362, 363f, 364f of facial nerve, 419, 420, 422f of facial nerve tumors, 1265–1266 of facial palsy, 1242–1243, 1243f of fibrous dysplasia, 347 functional. See Functional magnetic resonance imaging (fMRI). with Gamma Knife radiosurgery, 1174, 1177f of glomus jugulare tumors, 1039–1040, 1040f of hydrocephalus, 527 of jugular foramen meningiomas, 1044, 1044f of jugular foramen schwannomas, 1042, 1042f of labyrinth, 331–332 of labyrinthine hemorrhage, 332–334, 332f–334f of labyrinthine neoplasms, 339–341, 342f–345f of labyrinthine schwannomas, 339–340, 342f, 343f of labyrinthitis, 334–337, 334f–338f of lateral skull base, 383–384 of lipomas, 364, 365f of Ménière’s disease, 345, 627

of meningiomas, 458 vs. acoustic neuroma, 745t of cerebellopontine angle, 359f, 361–362, 361f–363f, 809–810, 809f clival and petroclival, 814 foramen magnum, 826, 826f jugular foramen, 822 Meckel’s cave, 820, 820f mid-skull base, 1050, 1050f of posterior fossa and skull base, 800–803, 801f after meningitis, 495 of middle ear cholesteatoma, 340, 345f of multiple sclerosis, 505 of neuromas, 1051, 1051f of perilymphatic fistula, 338–339, 341f of petrous apex lesions, 1109, 1109f, 1110f of posterior fossa arachnoid cysts, 946, 946f for pulsatile tinnitus, 209 of skull base osteomyelitis, 1102 of temporal bone encephalocele, 1092, 1092f of temporal bone trauma, 1076 of temporal bone tumors, 1030 of vascular lesions, of cerebellopontine angle, 349–350, 352f, 367–369, 368f, 369f Magnetic resonance venography (MRV) of glomus jugulare tumors, 1040–1041 for pulsatile tinnitus, 209 Magnetic search coil, 235, 608 Magnetic stimulation, of facial nerve, 1248–1249 Magnetoencephalography (MEG), 53 with functional MRI, 323 of scalp activity, 308 Malignant external otitis (MEO), 416–417, 1096 in children, 1099 complications of, 1102 diagnosis of, 1098–1099 etiology and pathogenesis of, 1097 facial paralysis due to, 432, 1240–1241 imaging of, 1099–1102 nomenclature for, 1096–1097 staging of, 1099 treatment of, 1102–1104 Malleus, fracture of, 1084t, 1085 Malpighi, Marcello, 7 Mandibular division, 218 Mandibular nerve, 1055, 1055f, 1224f Mannitol, for cerebral edema, 720 Manofluorography (MFG), for swallowing dysfunction, 1354 Map, of cochlear implant, 1304 Marble bone disease, 1127 Marcus, Richard, 39 Marcus-Gunn pupil, 230 Marezine (cyclizine), for vestibular dysfunction, 669t, 670 Marfan syndrome, multifactorial inheritance in, 128 Marginal sinus, 1143f Marx, H., 729 Masking for quantification of tinnitus, 183 for tinnitus, 189 Masking level differences (MLDs) with history of conductive hearing loss, 573 testing of, 274–275 Masseter muscle, 997, 999f Mastication, 1351 Masticatory muscles, innervation of, 195 Mastoid process, 998f, 1054f, 1137f

Mastoid segment, of facial nerve, 1204 surgical approach to, 1215–1218, 1217f–1219f Mastoid trephination, 10–12, 11f Mastoid vibration, for benign paroxysmal positional vertigo, 651–652 Mastoidectomy cortical, 1032 facial nerve injuries during, 1272–1274 resurrection of, 20–22, 20f, 21f temporal bone encephalocele after, 1090 Mastoiditis Bezold’s, 22, 22f coalescent, 22 facial palsy due to, 1240 intracranial complications of, 409–410 Matching, for quantification of tinnitus, 183 Maxillary division, 218 Maxillary nerve, 1001, 1055, 1055f Maximal nerve excitability test. See Maximal stimulation test (MST). Maximal stimulation test (MST), of facial nerve comparison of, 1226–1227 for facial palsy, 1246 general considerations with, 1228 method for, 1223, 1224, 1224f prognostic value of, 1227–1228, 1227t, 1228t for temporal bone trauma, 1078–1079 Maximum-length sequences, 277 MBS (modified barium swallow), 1353 McBurney, Charles, 27, 728 McCune-Albright syndrome, 1125, 1126 McGraw, J. B., 1005 McGregor, I. A., 1004, 1005 McKenzie, K. G., 949, 950 McLean, D. H., 1005 MCT. See Motor control test (MCT). MD. See Ménière’s disease (MD). MD (muscular dystrophy), anticipation in, 127 MDH (medullary dorsal horn), in otalgia, 194 Measles, acute labyrinthitis due to, 178 Meatal foramen, in facial palsy, 1234, 1235f, 1236 Mechanical presbycusis, 592 Mechanoelectrical transduction, by hair cells, 93–94, 93f, 590, 590f Meckel’s cave in middle fossa-transpetrous apex approach, 697, 697f and petrous apex, 1108 surgical anatomy of, 1001, 1055 surgical approach to, 704, 704f, 705f Meckel’s cave meningiomas, 701, 818–821, 819f, 820f Meclizine (Antivert) for vertigo in elderly, 537 for vestibular dysfunction, 668, 669t, 670 for vestibular neuritis, 487 Med-El cochlear implant, 1306–1307, 1309, 1313 for children, 1317, 1319 Medial geniculate body (MGB) development of, 567 physiology of, 59f, 64, 65, 66 Medial longitudinal fasciculus (MLF) anatomy of, 82f, 84, 84f, 85 rostral interstitial nucleus of, 105 in vestibulo-ocular reflex, 99, 100 Medial nucleus of trapezoid body (MNTB), development of, 566, 575 Medial olivary nucleus in brainstem auditory pathway, 45, 46f in spatial location, 48 Medial olivocochlear system, 49 Medial pterygoid muscle, 997, 999f

INDEX

Medial pterygoid plate, 1001 Medial pterygoid process, 998f, 1054f Medial rectus muscle (MR) innervation of, 84, 84f, 85, 85f in vestibulo-ocular reflex pathway, 98, 99, 99f Medial superior olivary (MSO) nucleus in central auditory system, 565f, 566, 566f, 575 physiology of, 62 Medial vestibular nucleus, 77f–79f, 78–79, 81f, 85 Medial vestibulospinal tract (MVST) anatomy of, 82f, 83, 84 physiology of, 104, 117 Medialization, for vocal cord paralysis, 1357–1360 Median anterior spinal vein, 1143f Median posterior spinal vein, 1144f, 1145f, 1160f Medulla, 1139f–1141f, 1160f Medullary bone, 1006f Medullary dorsal horn (MDH), in otalgia, 194 Medullary infarct, lateral, vestibular symptoms of, 181 Medulloblastomas of cerebellopontine angle, 856 facial palsy due to, 1238f of posterior fossa, 875–876, 877f, 878t Medullomyoblastoma, of cerebellopontine angle, 853, 867 MEG (magnetoencephalography), 53 with functional MRI, 323 of scalp activity, 308 Mehringer’s maneuver, 452f Meiosis, 126 Melanoma of cerebellopontine angle, 866 intracanalicular melanotic, 373 Melkersson-Rosenthal syndrome, 1231t, 1239–1240, 1239f Membranous labyrinth elucidation of, 9–10, 10f malformations of, hearing loss due to, 600–601 Membranous labyrinthine dysplasia, hearing loss due to, 600 Mendelian principles, variations on, 125–128, 126f, 127f Mendelian trait, 128 Mendelsohn maneuver, 1355 Ménière, Prosper, 26, 26f, 557, 949 Ménière’s disease (MD), 621–634 allergy and, 625–626, 629 audiometric findings in, 627 auditory nerve section for, 190–191 and benign paroxysmal positional vertigo, 646 chemical labyrinthectomy for, 630–631, 662–664 in children, 557 clinical evaluation of, 626–627 clinical presentation and natural history of, 623 cochlear, 512 due to cochleovestibular nerve compression syndrome, 906, 906f CT and MRI in, 627 defined, 621–622 due to delayed hydrops, 626 differential diagnosis of, 627–628, 627f in elderly, 536 electrocochleography of, 292–293, 292f, 293f, 627 endolymphatic hydrops and, 345, 346f, 623–626, 624f, 625f

etiology and pathophysiology of, 623–626, 624f, 625f evaluation of, 622, 622t familial, 626 genetic basis for, 626 herpes simplex virus and, 625 historical background of, 26, 31–34, 32f immunologic factors in, 624–626 incidence of, 622–623 management protocol for, 633f medical management of, 628–629 vs. migraine, 512 otolith dysfunction due to, 242 pharmacotherapy for, 661–664, 662t post-traumatic, 626 prophylaxis for, 628 reporting criteria for, 622, 622t sodium restriction for, 628 stages of, 622, 622t surgical management of, 629–634 outcomes of, 632–634 and quality of life, 634 techniques of, 629–632 symptoms of, 177, 179 vestibular, 512 vestibular evoked myogenic potentials in, 271 vestibular neurectomy for, 949–950 vs. vestibular neuritis, 487t vestibular rehabilitation therapy for, 1335 vestibular testing for, 627 viral/immune theory of, 624–625 Meniette device, 292, 293f Meningeal artery dorsal, 1055f middle, 1216f posterior, 1141f, 1142, 1144f Meningeal inflammation, 374, 376f Meningeal metastasis loculated, 362–363, 362f, 364f vs. meningioma, 362–363, 362f, 364f Meningeal sign. See Dural tail. Meningioma(s), 792–836 anaplastic, 797, 797t, 798 angiography of, 456–464, 462f–463f, 800 angiomatous, 797–798 arterial supply of, 458, 461 atypical, 796f–798f, 797, 797t, 798 calcification of, 802, 802f cerebellopontine angle, 806–811 audiovestibular testing for, 799 classification of, 806–807 clinical presentation of, 807–809, 807t complications of, 811 diagnosis of, 809–810, 809f epidemiology of, 806 facial nerve preservation with, 803, 811, 832–833, 833t hearing preservation with, 828–832, 828t, 829f–831f, 829t historical background of, 806 imaging of, 359f, 361–362, 361f–363f, 809–810, 809f origin of, 806 pathologic correlates of, 147, 147f preoperative evaluation of, 804 surgical management of, 810–811, 810t vs. vestibular schwannomas, 809 cerebral edema due to, 719, 719f cerebral venography of, 458–459 childhood, 793 chordoid, 797f, 798 classic (typical), 796–798, 796f, 797t classification of, 796–798, 797t clear-cell, 797f, 798

1391

clinical presentation of, 456–457 clival and petroclival, 812–818 challenges of, 812–813 clinical presentation of, 813–814, 1049–1050 defined, 813 diagnosis of, 814, 1050, 1050f extension of, 713f, 813 grading system for, 814, 814t imaging of, 1153f mortality and quality of life with, 816–818 origin and classification of, 813 pathology of, 1049 preoperative considerations for, 814–815, 814t recurrent, 462f–463f resection of, 816, 817t, 1050 surgeon’s view of, 812f surgical approach for, 815, 815f–817f surgical history of, 815 of craniovertebral junction, 1151, 1151t, 1152f, 1153f, 1161f CT and MRI of, 457–458, 745t, 800–803, 801f, 802f cystic, 803 defined, 456, 1043 diagnosis of, 799–803 audiovestibular testing in, 799 differential, 362–363, 362f–364f radiologic, 457–459, 799–803, 801f, 802f, 1050, 1050f with dural tail, 357f, 358, 359f, 361 edema with, 802 embolization of, 460–464 en plaque, 795 epidemiology of, 793, 1043 etiology of, 793–795, 1043 facial nerve involvement in, 154, 155f facial nerve preservation with, 803, 811, 832–833, 833t fibrous (fibroblastic), 797 foramen magnum, 824–828, 826f, 827f general surgical principles for, 803–804 grading of, 796–798, 797t hearing preservation with, 828–832 classification schemes for, 828–829, 828t, 829t indications for, 803–804, 832 location and, 829–830, 831f results of, 831–832 size and, 830–831 surgical approaches for, 829, 829f, 830f tumor extension and, 831 and vestibulocochlear dysfunction, 831–832 hemorrhage with, 803 hereditary, 795 histologic subtypes of, 457, 1043 historical background of, 792–793, 1043 hormonal factors in, 794–795 hydrocephalus due to, 526f, 527f immunohistochemistry of, 798–799 internal auditory canal, 811–812 audiovestibular testing of, 799 clinical presentation of, 811t epidemiology of, 812 historical background of, 811–812 origin of, 811, 831 preoperative considerations for, 804 surgical management of, 804, 811t intracanalicular, 371 invasive, 796, 796f jugular foramen, 821–824, 1043–1044, 1044f blood supply to, 1043 classification of, 821, 821f, 822f

1392

INDEX

Meningioma(s) (Continued) clinical presentation of, 822, 1043–1044 diagnosis of, 822–823, 1044, 1044f pathologic correlates of, 147, 148, 149f primary, 821, 821f secondary, 821, 822f surgical approach to, 699, 823, 823f, 824f, 1044 surgical management of, 823–824, 1044 of jugular fossa, 407 location of, 456–457 lymphoplasmacyte-rich, 798 Meckel’s cave, 701, 818–821, 819f, 820f meningothelial, 797 metaplastic, 798 microcystic, 796f, 798 middle and anterior cranial fossa, 1050 molecular pathogenesis of, 795 necrosis with, 802–803 in neurofibromatosis 2, 786, 787, 787f papillary, 798 parasellar, 1049–1050, 1050f pathogenesis of, 456 pathology of, 147–148, 147f–149f, 795–799, 1043 gross, 795–796, 795f microscopic, 796–798, 796f–798f, 797t of petrous apex, 393–396, 398f–399f posterior fossa, 804–806 classification of, 805–806, 805f epidemiology of, 804–805 hearing loss due to, 173 recurrence of, 835 preoperative considerations with, 804 psammomatous, 797 radiation therapy for, 836 radiation-induced, 793–794, 1192 recurrence of, 833–836, 834t rhabdoid, 798 secretory, 796f, 798, 799 stereotactic photon-beam radiosurgery for, 836 therapy for, 459–464 transitional (mixed), 796f, 797 due to trauma, 794 vascular compromise by, 802 due to viruses, 795 Meningitis due to acoustic neuroma surgery, 756–757 bacterial central processing deficits due to, 578 deafness due to, 50 central processing deficits due to, 578, 579 with cerebellopontine angle epidermoid cysts, 847 cochlear implant after, 1319 due to cochlear implantation, 1312 hearing loss due to, 597–598 labyrinthitis ossificans due to, 152, 153f microbiology of, 491 mortality due to, 490, 490t other neurologic abnormalities due to, 494 due to otitis media, 492–493, 913t, 921–922 otologic and neurotologic sequelae of, 489–496 epidemiology of, 489–491, 490t pathophysiology and histopathology of, 491–492, 492f–494f signs and symptoms of, 492–494, 494t testing for, 495 due to temporal bone trauma, 492, 492f, 493f, 1083 treatment of, 495–496 vertigo due to, in children, 559 Meningocele(s) defined, 1089 of petrous apex, 388, 388f

Meningo-hypophyseal trunk, 1055f MEO. See Malignant external otitis (MEO). MEP (magnetic evoked potentials), 53 MEP (motor evoked potential), transcranial, 988 Merlin, 135 in acoustic neuroma, 732 in meningiomas, 795 MET (Middle Ear Transducer), 1298, 1298f, 1299t Metabolic cochlear hearing loss, 602 Metabolic disease facial palsy due to, 1231t neuro-ophthalmic manifestations of, 237 vertigo due to, in children, 560 vestibular symptoms of, 180 Metabolic presbycusis, 592 Metabolic work-up, for pulsatile tinnitus, 209 Metastasis(es) to cerebellopontine angle, 865–866, 865f–867f intracanalicular, 373, 375f involving facial nerve, 154, 155f, 1262 to labyrinth, 340, 344f meningeal loculated, 362–363, 362f, 364f vs. meningioma, 362–363, 362f, 364f pathologic correlates of, 150–151, 150f, 151f to petrous apex, 150, 151f, 1120, 1121f imaging of, 397 of pharyngeal carcinoma, 150–151 to posterior fossa, 887–889, 888f, 889t Methotrexate, for autoimmune inner ear disease, 641–642 Methylation, in genomic imprinting, 127 Methylphenidate (Ritalin), auditory processing with, 278 Methylprednisolone, for sarcoidosis, 476 Metronidazole hydrochloride, for wound infections, 721 Mexiletine, for tinnitus, 190 MF. See Middle fossa. MF (mossy fiber) inputs, 117 MFG (manofluorography), for swallowing dysfunction, 1354 MGB (medial geniculate body) development of, 567 physiology of, 59f, 64, 65, 66 Michel deformity, 1318 Michel’s deafness, 600 Michelson, Robin, 38 Microbial virulence factors, and intracranial complications of otitis media, 914 Microphone, for cochlear implant, 1302, 1302f Microphonics. See Cochlear microphonics (CMs). Microscope, operating, historical background of, 28–30, 29f, 30f, 35–37, 36f Microvascular decompression (MVD), 899–901 for cochleovestibular nerve compression syndrome, 907–908 controversy surrounding, 900–901 cranial nerve monitoring during, 974–975, 975f for hemifacial spasm, 901, 902 surgical technique of, 899–900, 899f, 900f for tinnitus, 185–186, 190 tinnitus due to, 184 for trigeminal neuralgia, 190, 904–905 Microvascular free flaps, for skull base reconstruction, 1011–1018, 1013f–1020f Mid-basilar artery aneurysms, 706, 707f

Middle cerebellar peduncle vein, 894 Middle cranial fossa, 998f, 1002, 1054f meningiomas of, 1050 surgical exposure of, 699–702, 700f, 701f Middle ear anatomy of, 1216f cholesteatomas of, 340, 345f, 407–408, 412f epidermoid tumors of, 408–409 inflammatory disease of, 407–414, 412f–414f radiation effect on, 1189–1190 in sound conduction, 53 tumors of, 414–415 Middle ear reflex, acoustic, 70–71, 70f, 71f Middle ear salivary gland choristomas, facial nerve involvement in, 430 Middle ear space, lesions of, 1030t Middle ear surgery, facial nerve monitoring during, 975 Middle Ear Transducer (MET), 1298, 1298f, 1299t Middle fossa approach to acoustic neuroma, 694f, 695, 747, 749, 749f to cerebellopontine angle, 696, 696f to facial nerve, 1215, 1215f–1217f to internal auditory canal, 694–696, 694f, 695f to vestibular neurectomy, 695f, 952, 952f, 953f Middle fossa craniotomy(ies), 694, 695 for superior semicircular canal dehiscence, 245 for temporal bone encephalocele, 1092–1093, 1093f for vestibular schwannoma, in neurofibromatosis 2, 788 Middle fossa procedure facial nerve injury during, 1276 operating room setup for, 677f Middle fossa/transmastoid approach, to facial nerve, 1215, 1215f Middle fossa-transpetrous apex approach, to ventral pons and anterior cerebellopontine angle, 696–698, 697f Middle latency responses (MLRs), 68, 300–301 auditory processing testing of, 277 in children, 571 in multiple sclerosis, 504 Middle meningeal artery, 1216f Middle skull base lesions, 1005, 1005f soft tissue reconstruction for, 1019–1020, 1020t, 1022f Midline skull base, surgical anatomy of, 1053–1055, 1054f, 1055f Miehlke syndrome, 1231t Migraine, 510–516 with auditory symptoms, 513 with aura defined, 201, 514 without headache, 514 and neurotologic symptoms, 514 pathogenesis of, 510 symptoms of, 514 vertigo in, 514 basilar, 513, 514 with benign paroxysmal positional vertigo, 511, 646 in children, 557, 559 diagnostic criteria for, 511t epidemiology of, 510, 511f etiology and pathogenesis of, 510–511 and familial episodic ataxia, 512 without headache, 514 management of, 514–516 vs. Ménière’s disease, 512

INDEX

Migraine (Continued) with motion sickness, 513 with neurotologic disorders, 511–513 with neurotologic symptoms, 513–514 management of, 516 otalgia due to, 201 prophylaxis for, 515 and stroke, 513 vs. transient ischemic attacks, 512–513 with vertigo, 181, 513 during aura, 514 benign paroxysmal positional, 511 benign recurrent, 511–512 vs. Ménière’s disease, 628 vestibular, 181 pharmacotherapy for, 662t, 665–666 Migraine accompaniments, 514 Migraine equivalent, 514 vestibular symptoms of, 181 Millard-Gubler syndrome, 1231t Milligan, W., 33 Minimal nerve excitability test (NET), 1223–1224, 1226, 1227, 1246 Minimum response level, of cochlear implant, 1304 Mismatch negativity (MMN), auditory processing testing of, 277–278 in children, 571 Mithramycin, for Paget’s disease of temporal bone, 1131 Mitochondrial complex II, 136, 137 Mitochondrial inheritance, 126, 126f, 129t MLDs (masking level differences) with history of conductive hearing loss, 573 testing of, 274–275 MLF. See Medial longitudinal fasciculus (MLF). MLRs. See Middle latency responses (MLRs). MMN (mismatch negativity), auditory processing testing of, 277–278 in children, 571 MNTB (medial nucleus of trapezoid body), development of, 566, 575 Möbius syndrome, 218 absence of facial nerve in, 423 Modified barium swallow (MBS), 1353 Modifier genes, 128 Modulation transfer function (MTF), in cochlear nucleus, 61–62, 62f Moebius syndrome, 1231t Mohr-Tranebjaerg syndrome, hearing loss in, 129t Moisture chambers, 1342–1343, 1343f Molecular genetics, 122–141 of acoustic neuromas, 732 of familial paragangliomas, 135–138 of glomus tumors, 134–138 of inheritance patterns, 122–128 autosomal-dominant, 123–125, 124f autosomal-recessive, 122–123, 123f genomic imprinting in, 127, 127f linkage and recombination in, 126 mitochondrial, 126, 126f multifactorial, 128 trinucleotide repeat expansion in, 127 variations on Mendelian principles of, 125–128, 126f, 127f X chromosome inactivation in, 125, 126–127 X-linked, 125, 125f of intracochlear transgene expression, 138–141, 139t of neurofibromatosis type 1, 134 type 2, 135, 784–785

of nonsyndromic hereditary hearing loss, 128–135, 132t connexin 26 in, 131, 132–133 myosins in, 131–132, 133–134 pendrin in, 132, 133 of syndromic hearing loss, 129t–130t Monaural measures, of auditory processing testing, 275 Mondini’s malformation, 332 hearing loss due to, 600, 601 and meningitis, 492 Monoamine oxidase inhibitors, for psychophysiologic dizziness, 667 Monoaminergic drugs, for vestibular dysfunction, 669t, 670 Mononucleosis, infectious, acute labyrinthitis due to, 178 Monosyllable Trochee Spondee (MTS) word test scores, with auditory brainstem implant, 1328f Monro-Kellie doctrine, 524 Morgagni, Giovanni Battista, 8, 8f, 9–10 Morgan, Thomas Hunt, 126 Morton, William, 20 Mosaicism, 125 Mossy fiber (MF) inputs, 117 Motion sickness, 118 migraine and, 513 prophylaxis of, 670 Motoneurons anatomy and physiology of, 1206–1208, 1208f, 1209f during nystagmus, 106, 106f in signal transformation, 102–103, 103f Motor control test (MCT) center of gravity alignment in, 267–268 considerations and limitation of, 267–268 methodology for, 258–259, 260f, 261f, 261t for nonphysiological component of balance, 264 reliability and validity of, 259 subject characteristics in, 267 Motor evoked potential (MEP), transcranial, 988 Motor myelopathy, due to craniovertebral junction anomalies, 1148 Motor neurons. See Motoneurons. Motor output system, evaluation of, 1334 Motor system, connections from auditory system to, 67 MPD (myofascial pain dysfunction), otalgia due to, 197–198 MPEAK (multipeak extraction) coding strategy, 1317 MPS (multiple pulsatile sampling), 1303, 1305 MR (medial rectus muscle) innervation of, 84, 84f, 85, 85f in vestibulo-ocular reflex pathway, 98, 99, 99f MRA. See Magnetic resonance angiography (MRA). MRI. See Magnetic resonance imaging (MRI). MRV (magnetic resonance venography) of glomus jugulare tumors, 1040–1041 for pulsatile tinnitus, 209 MS. See Multiple sclerosis (MS). MSO (medial superior olivary) nucleus in central auditory system, 565f, 566, 566f, 575 physiology of, 62 MST. See Maximal stimulation test (MST). MTF (modulation transfer function), in cochlear nucleus, 61–62, 62f MTS (Monosyllable Trochee Spondee) word test scores, with auditory brainstem implant, 1328f

1393

Mucocele(s), of petrous apex, 1115 imaging of, 386–387 Mucoepidermoid carcinoma, 1031 Müller’s muscle, paralysis of, 217 Multifactorial inheritance, 128 Multipeak extraction (MPEAK) coding strategy, 1317 Multiple myeloma, imaging of, 389, 394f Multiple pulsatile sampling (MPS), 1303, 1305 Multiple sclerosis (MS), 499–507 acoustic reflex in, 503–504 auditory evoked responses in, 504 auditory manifestations of, 503–504, 503f cerebellopontine angle in, 350, 353f, 371 cerebral, 501 clinical features of, 500–501, 500t, 501t CSF finding in, 506 diagnostic criteria for, 506, 506t, 507t differential diagnosis of, 506, 506t epidemiology of, 499, 500t facial numbness in, 505 facial weakness in, 504 frequency of symptoms of, 501t hearing loss due to, 173 internuclear ophthalmoplegia in, 501, 501f loss of taste and dysgeusia in, 505 management of, 506–507 optic neuritis in, 505 pathology and pathophysiology of, 499–500 primary progressive, 500 radiologic imaging of, 505 relapsing-remitting, 500 risk factors for, 499, 500t secondary progressive, 500 speech disorders in, 504–505 trigeminal neuralgia in, 505 vertigo due to, in children, 560 vestibular manifestations of, 181, 501–503, 502f visual evoked potentials in, 505 Multisensory dizziness, 660t Mumps labyrinthitis, 178, 334, 335f Muscle(s), of lateral skull base, 997, 999f Muscle contraction headache, otalgia due to, 201 Muscle myoclonus, pulsatile tinnitus due to, 207, 209 Muscular dystrophy (MD), anticipation in, 127 MVD. See Microvascular decompression (MVD). MVST (medial vestibulospinal tract) anatomy of, 82f, 83, 84 physiology of, 104, 117 Myelin sheath, 1206, 1208f Myelination, 567, 568f, 569f Myelography, of craniovertebral junction tumors, 1152 Myeloma, multiple, imaging of, 389, 394f MYH9 gene, mutations in, 134 Myoclonic contractions, pulsatile tinnitus due to, 207, 209 Myocutaneous flap, 707, 708f latissimus dorsi, 1009, 1009f, 1010f lower trapezius, 1009–1010, 1011f pectoralis major, 1010–1011, 1011f, 1012f Myofascial pain dysfunction (MPD), otalgia due to, 197–198 Myokymia, superior oblique, 234 Myosins in genetic hearing loss, 601 in nonsyndromic hereditary hearing loss, 131, 133–134

N N1, auditory processing testing of, 278 N2, auditory processing testing of, 278

1394

INDEX

N24k (nucleus 24k), 1306 N400, in children, 571–572 NAOT (nuclei of the accessory optic tract), 107 Nasal examination, 216 Nasal muscle F wave, intraoperative monitoring of, 967 Nasopharyngeal cancer, skull base invasion by, 396, 401f, 402f National Acoustics Laboratory of Australia, 1286 ND (nucleus of Dankschewitz), 82f, 87 Near-field recordings, of cochlear nerve, 982 Neck reflexes, tonic, 115–116, 115f Necrosis with meningioma, 802–803 osteoradio-, 1187–1189, 1188f, 1189f of cerebellopontine angle, 858 Necrotizing otitis externa (NOE). See also Malignant external otitis (MEO). defined, 1096 facial paralysis due to, 432, 1240–1241 Neisseria meningitides, meningitis due to, 490t, 491, 496 Neomycin-induced ototoxicity, 593 gene transfer for protection against, 140 Neonates auditory brainstem response to detect hearing loss in, 295–297 development of auditory competence in, 569 Neoplasm(s) of cerebellopontine angle, 853–856, 855f cochlear, 340, 344f CSF leak due to, 927, 931 facial palsy due to, 1231t, 1238–1239, 1238f, 1263, 1264 labyrinthine, 339–341, 342f–345f otalgia due to, 202 of parasellar space, 1047–1066 of petrous apex, 1117–1121, 1118f–1120f vertigo due to, in children, 559–560 Nerve(s), of lateral skull base, 998–999 Nerve decompression for Bell’s palsy, 1234–1235, 1236f, 1251–1252 for facial nerve tumors, 1267 Nerve excitability test (NET) maximal. See Maximal stimulation test (MST). minimal, 1223–1224, 1226, 1227, 1246 Nerve fibers, peripheral vs. central nervous system, 894–895 Nerve impulses, reflection of, 896 Nerve injury, classification of and electrical testing, 1225–1226, 1226t, 1245–1246, 1245f and related outcomes, 1208–1210, 1209f Nerve Integrity Monitor (NIM), 960, 960f Nerve sheath tumors in jugular fossa, 405–406, 409f radiation-induced, 1192 Nerve-muscle pedicle procedure, for vocal cord paralysis, 1360, 1361 Nervous System of the Human Body, The, 13, 14f Nervus intermedius anatomy of, 1201, 1202f development of, 1199 intraoperative identification of, 970, 970f, 971f and vestibular nerve, 951 NET (nerve excitability test) maximal. See Maximal stimulation test (MST). minimal, 1223–1224, 1226, 1227, 1246 Neumann’s sign, 916 Neural integrator, in signal transformation, 103, 103f

Neural plasticity, 66 and tinnitus, 187 Neural presbycusis, 592 Neural response telemetry (NRT), 303, 303f with cochlear implant, 1304, 1320 Neuralgia glossopharyngeal, otalgia due to, 199–200 otalgia due to, 197t, 198–200 postherpetic, otalgia due to, 200 trigeminal. See Trigeminal neuralgia (TGN, TN). vagal and superior laryngeal, otalgia due to, 200 Neurectomy cochleovestibular, translabyrinthine approach to, 691 singular, for benign paroxysmal positional vertigo, 652 vestibular. See Vestibular neurectomy (VN). Neurilemma, 1208f Neurilemmoma. See also Schwannoma(s). intracranial, 1048–1049 Neurinomas, 1258 of craniovertebral junction, 1151, 1151t Neuritis cochlear, 374, 377f optic, 217 in multiple sclerosis, 505 vestibular. See Vestibular neuritis (VN). Neuroblastoma, oscillopsia due to, 234 Neurocristopathic syndromes, 545 Neurocristopathy, 545 Neuroectodermal tumors, primitive, 370 Neuroelectrical scalp activity background and principles of, 307–308, 307f multichannel recordings of, 309–310, 309f Neurofibromas, of facial nerve, 1259 Neurofibromatosis 1 (NF1) vs. neurofibromatosis 2, 783 paraneoplastic syndromes in, 545 vestibular schwannomas in, 134 Neurofibromatosis 2 (NF2), 783–789 acoustic neuromas in auditory changes due to, 786 clinical manifestations of, 785 endocrine relationships in, 733 epidemiology of, 730–731 hearing conservation with, 764–765 imaging of, 343f, 785f location of, 464, 785 molecular genetics of, 135, 732 molecular mechanisms of, 732 pathologic correlates of, 146, 147f risk of, 360 treatment options for, 787–788, 788f, 789f auditory brainstem implant for, 1325 clinical characteristics of, 783–785, 786t diagnostic criteria for, 783–784, 784t epidemiology of, 731 family history of, 785 genetic testing for, 789 hearing loss in, 129t management of, 789 meningiomas in, 786, 787, 787f mild (Gardner) form of, 784 molecular genetics of, 784–785 MRI of, 349 vs. neurofibromatosis 1, 783 prevalence and incidence of, 784, 784f screening for, 785 severe (Wishart) form of, 784 spinal tumors in, 786, 787, 787f tumor types in, 785–787, 786t Neurofibromin, as tumor suppressor, 134 Neurogenic tumors, of petrous apex, 1120, 1120f

Neurolabyrinthitis, viral, pharmacotherapy for, 662t Neurolabyrinthitis epidemica. See Vestibular neuritis (VN). Neurologic complications, of radiation therapy, 1191 Neurologic disorders facial palsy due to, 1231t otalgia due to, 197t, 198–200 Neuroma(s) acoustic. See Acoustic neuroma (AN). facial clinical presentation of, 1264, 1264f facial palsy due to, 1239, 1242, 1242f, 1243f histopathology of, 1258 traumatic, 1260 intracranial, 1050–1051, 1051f of petrous apex, 1120 trigeminal of foramen ovale and cavernous sinus, 1051f of petrous apex, 396, 400f Neuromagnetic scalp activity background and principles of, 307f, 308 multichannel recordings of, 310 Neuromyography (NMG), 1227 Neuron(s) anatomy and physiology of, 1206–1208, 1208f, 1209f degeneration of, 1210 regeneration of, 1210 abnormal, 1210 Neuronal filters, 106f Neuronitis, vestibular. See Vestibular neuritis (VN). Neuro-ophthalmic examination, 234–236 Neuro-ophthalmic manifestation(s), of neurotologic disease, 228–237 afferent system pathology as, 233 decreased visual acuity as, 220–230 diplopia as, 230 evaluation of, 234–236 Horner’s syndrome as, 233–234 misalignment of visual axes as, 233, 235 nystagmus as, 230–233 ocular stabilizing systems and, 228–229 oscillopsia as, 230 pain as, 230 in specific disease processes, 236–237 vestibulo-ocular reflexes and, 229 Neuropathic pain, and tinnitus, 184, 187 Neuropathy(ies) auditory. See Auditory neuropathy (AN). cranial. See Cranial neuropathies. Neuroplasticity, 66, 896–897 of auditory system, 322, 575, 576–578, 577f and tinnitus, 187 of vestibular nucleus, 897 and vestibular rehabilitation, 1331–1332 of vestibulo-ocular reflex, 110–111, 897f Neuropraxia, 1208, 1209f, 1225, 1226f, 1226t, 1245 Neurosarcoidosis, 474–477 Neurosciences, in mid-19th century, 15 Neurosurgery, birth of, 23–24 Neurosyphilis of cerebellopontine angle, 857–858 in children, 560 Neurotmesis, 1209f, 1210, 1225, 1226f, 1226t, 1245 Neurotologic examination, 215–226 of cranial nerve I, 216 of cranial nerve II, 216–217, 217f of cranial nerves III, IV, VI, 217–218 of cranial nerve V, 218–219, 218f

INDEX

Neurotologic examination (Continued) of cranial nerve VII, 219–220, 219f, 220t of cranial nerve VIII, 220–225 cochlear segment, 220–221, 221f oculomotor examination in, 221–225, 223f–226f vestibular segment, 221 of cranial nerves IX and X, 225 of cranial nerve XI, 225 of cranial nerve XII, 225–226 general physical examination in, 215–216 Neurotologic skull base surgery contemporary concept of, 675–676, 676f fundamental considerations for, 676–680 hemostasis for, 678 instrumentation for, 677–678 for intracranial tumors, 685–706 involving craniovertebral junction, 704–706, 705f, 706f involving internal auditory canal and cerebellopontine angle, 685–699, 685f middle fossa approach to, 694–696, 694f–696f middle fossa-transpetrous apex approach to, 696–698, 697f retrosigmoid approach to, 686–689, 686f, 687f transpetrosal approaches to, 689–693, 690f, 691f involving intracranial aspect of jugular foramen, 698–699, 698f, 699f involving Meckel’s cave, 704, 704f, 705f involving ventral surface of brainstem, 699–704, 700f, 701f, 703f involving vertebrobasilar lesions, 706, 707f for lesions primarily in cranial base, 680–685 involving clivus, 682f, 683 involving infratemporal fossa, 684–685, 685f involving jugular foramen, 683–684, 683f, 684f involving petrous apex, petroclival junction, and foramen lacerum, 681–683, 681f, 682f involving temporal bone, 680–681, 681f overview of, 675–708 patient positioning for, 676–677, 677f for reconstruction of cranial base, 706–708, 707f, 708f special operating room requirements for, 676 vascular considerations in, 678–680, 679f, 680f Neurotologic surgery complication(s) in, 712–724 cerebral edema as, 719–720, 719f cerebral spinal fluid leak as, 720–721, 721f cranial nerve injuries as, 722–724, 722f–724f hemorrhage as, 717–718, 717f infections as, 721–722, 722f intracranial, 718–720, 718f–720f pneumocephalus as, 720, 720f seizures as, 720 stroke as, 718–719, 718f control of bleeding during, 713–717 arterial, 715–717, 715f, 716f venous, 713–715, 714f perioperative considerations for, 713, 714f preoperative neuroradiographic assessment for, 712, 713f, 714f Neurotology, history of, 1–39 prior to European Renaissance, 2–3 in sixteenth century, 3–5, 3f–5f in seventeenth century, 5–7, 6f, 7f in eighteenth century, 7–12, 7f–11f

in nineteenth century, 12–27 early, 12–15, 13f–15f mid-, 15–22, 16f–21f late, 22–27, 22f–27f in twentieth century, 27–39 early, 27–32, 28f–32f mid-, 33–39, 33f–37f Neurotransmission, by hair cells, 590, 590f Neurotrophic growth factors, and facial nerve regeneration, 1210 Neurotrophin(s), transgenic expression of, 140 Neurotrophin-3 (NT3) for aminoglycoside-induced ototoxicity, 251 transgenic expression of, 140 Newborns auditory brainstem response to detect hearing loss in, 295–297 development of auditory competence in, 569 NF1. See Neurofibromatosis 1 (NF1). NF1 gene, 134 NF2. See Neurofibromatosis 2 (NF2). NF2 gene, in meningiomas, 795 Nicotine, nystagmus due to, 237 NIM (Nerve Integrity Monitor), 960, 960f NIM-Response, 960, 960f Nissl bodies, degeneration of, 1210 NIV (interstitial nucleus of the vestibular nerve), 77f, 79, 81f NMG (neuromyography), 1227 NMR (nuclear magnetic resonance) signals, 320 Nociceptive-specific (NS) neurons, high-threshold, 194 Nociceptors, 194 Nodes of Ranvier, 1206–1207, 1208f Nodulus projection, 87 NOE. See Necrotizing otitis externa (NOE). Noise, and ototoxic drugs, 592 Noise reduction, for hearing aids, 1288, 1290, 1291f Noise-induced hearing loss, 591–592 Noise-induced tinnitus, 184 Noise-induced trauma, gene transfer for protection against, 140 Nonchromaffin paragangliomas, 1039 genomic imprinting of, 127 Noncochlear hearing loss, cochlear vs., 165–166, 166t Nondominant hemisphere, auditory processing tests for, 276t Nonsyndromic hereditary hearing loss, 128–134, 131t connexin 26 in, 131, 132–133 myosins in, 131–132, 133–134 pendrin in, 132, 133 Nonsyphilitic interstitial keratitis, vestibular symptoms of, 180 Norell, H., 949 Norrie’s disease central processing deficits with, 578 hearing loss in, 125, 129t Novalis Shaped Beam Surgery system, 1182f Novum Organum, 6 NPH. See Nucleus prepositus hypoglossi (NPH). NRT (neural response telemetry), 303, 303f with cochlear implant, 1304, 1320 NS (nociceptive-specific) neurons, highthreshold, 194 NT3 (neurotrophin-3) for aminoglycoside-induced ototoxicity, 251 transgenic expression of, 140 Nuclear magnetic resonance (NMR) signals, 320 Nuclei of the accessory optic tract (NAOT), 107

1395

Nucleus, of nerve, 1208f Nucleus 24k (N24k), 1306 Nucleus basalis, neural plasticity in, 66 Nucleus cochlear implant, 1305–1306, 1309 for children, 1315, 1317, 1319 Nucleus multichannel auditory brainstem implant, 1324–1325, 1325f Nucleus of Dankschewitz (ND), 82f, 87 Nucleus prepositus hypoglossi (NPH) anatomy of, 84f neural integrator in, 103 in vestibulo-ocular reflex pathway, 99, 100 Nylén, Carl-Olaf, 29, 29f, 35 Nystagmus due to acoustic neuroma, 741, 743 barbecue spit, 109 in benign paroxysmal positional vertigo, 231 linear canal sensitivity in, 95 Bruns,’ 222, 231 central, 232 centripetal, 222 in children, 554–555, 560 classification of, 231 congenital, 222, 231–232, 560 conjugate vs. disconjugate, 230 due to craniovertebral junction anomalies, 1149 defined, 221, 230 degrees of, 231 dissociative, 232–233 downbeat, 232, 611 electronystagmography of. See Electronystagmography (ENG). end-point, 222, 233 examination of, 235 gaze-evoked (gaze paretic), 222, 231 gaze-holding, 222 head-shaking, 222–223 horizontal vestibular, 109 hyperventilation-induced, 224 jerk, 222, 231 after labyrinthectomy, 113 in multiple sclerosis, 502f, 503 neuron activity during, 106, 106f in neurotologic disease, 234, 230–233 optokinetic, 107–109, 107f optokinetic-after-, 107f, 108, 109, 233 pendular, 222, 231 periodic alternating, 222, 233 physiologic, 233 physiological mechanisms of, 221–225 positional (sustained), 222–233, 233f direction-changing, 613, 614f paroxysmal, 609–611, 611f positioning (transient), 223–224, 224f Dix-Hallpike maneuver for, 608–611, 610f, 611f rebound, 222 reversal, 645 seesaw, 232 spontaneous, 612–613, 613f due to superior semicircular canal dehiscence, 245 torsional, 645 upbeat, 232, 612, 613f Valsalva-induced, 224 vertical, 109–110 vestibular, 231 habituation of, 112 vestibular system in, 222

O OAEs. See Otoacoustic emissions (OAEs). Obersteiner-Redlich (OR) zone, 895 in vestibular schwannoma, 146

1396

INDEX

Obesity, and pseudotumor cerebri, 205–206, 209 Oblique alar ligaments, 1054 Oblique eye movements, 85 Observationes Anatomicae, 5, 5f Observer-based psychoacoustic procedure (OPP), 569 OCB (olivocochlear bundle), in descending auditory pathway, 66 Occipital bone, 1136–1137, 1137f Occipital condyle, 998f, 1001, 1053, 1054f, 1137f, 1140f Occipital lobe, 998f, 1054f Occipital sinus, 1144f Occipito-atlanto-axial joint, 1137, 1139f Occipitomastoid suture, 1137f Occlusion effect, with hearing aids, 1284, 1284f Occupational rehabilitation, after acoustic neuroma surgery, 768 Octreotide, for paragangliomas, 545 Ocular flutter, 234 Ocular irritants, protecting against, 1343 Ocular lubricants, 1342, 1342t Ocular misalignment, 233, 235 Ocular motoneurons (OMNs), in signal transformation, 102–103, 103f Ocular motor apparatus, 102 Ocular rehabilitation, with facial paralysis, 1339–1348 nonsurgical management of, 1341–1344, 1342t, 1343f, 1344f reasons for, 1339–1340 surgical management of, 1344–1347, 1345f–1348f types of, 1340–1341 Ocular stabilizing systems, 228–229 Ocular tilt reaction (OTR), 243, 248 Oculoacousticocerebral degeneration, central processing deficits with, 578 Oculomotor examination, 221–225, 223f–225f Oculomotor nerve, 217, 1055, 1055f intraoperative monitoring of, 976–978, 977f Oculomotor neurons (OMNs), in signal transformation, 102–103, 103f Oculomotor nucleus, 84, 84f, 85f OD (optical density), in Gamma Knife radiosurgery, 1170 Odontoid process, 1138f, 1139f anomalies of, 1147 Off-vertical axis rotation (OVAR), 109, 243 Ofloxacin, for skull base osteomyelitis, 1103 OHCs. See Outer hair cells (OHCs). Oilier’s disease, 863 OK (optokinetic system), 106–107, 107f OK (optokinetic) drum, 107, 107f OKAN (optokinetic-after-nystagmus), 107f, 108, 109, 233 OKN (optokinetic nystagmus), 107–109, 107f Older adults. See Aging; Elderly. Olfaction, evaluation of, 216 Olfactory nerve, 216 Oligodendrogliomas, of cerebellopontine angle, 854 Olivari, N., 1005 Olive, 1140f Olivecrona, Herbert, 730, 730t Olivocochlear bundle (OCB), in descending auditory pathway, 66 Olivocochlear system, 49–50 OMNs (oculomotor neurons), in signal transformation, 102–103, 103f Omohyoid muscle, 1157f Oncogenesis, radiation-induced, 1191–1192, 1192f OOR (otolith-ocular reflexes), 241–242

Operating microscope, historical background of, 28–30, 29f, 30f, 35–37, 36f Operating room setup, for neurotologic surgery, 676–677, 677f Opercular syndrome, 1231t Ophthalmic division, 218 Ophthalmic nerve, 1055, 1055f Ophthalmologic manifestations, of acoustic neuroma, 739t, 741 Ophthalmoplegia, internuclear dissociative nystagmus in, 233 in multiple sclerosis, 501, 501f OPP (observer-based psychoacoustic procedure), 569 OPP (oropharyngeal propulsion pump), 1354, 1356 Opsoclonus, 234 Optic atrophy, 230 Optic canal, 998f, 1002, 1054f Optic nerve, 216–217, 217f Optic neuritis, 217 in multiple sclerosis, 505 Optical density (OD), in Gamma Knife radiosurgery, 1170 Optokinetic (OK) drum, 107, 107f Optokinetic nystagmus (OKN), 107–109, 107f Optokinetic system (OK), 106–107, 107f Optokinetic test, 608, 616, 616f Optokinetic-after-nystagmus (OKAN), 107f, 108, 109, 233 Opton microscope, 36, 36f Opuscula Anatomica, 4–5 OR (Obersteiner-Redlich) zone, 895 in vestibular schwannoma, 146 Oral portion of ventroposterolateral nucleus (VPLo), 118 Oral preparation stage, of swallowing, 1350–1351 Oral transit stage, of swallowing, 1351 Orbicularis oculi, 1224f, 1346f Ordinary pattern, in intraoperative facial nerve monitoring, 972 Organ of Corti anatomy and physiology of, 589, 590f elucidation of, 19–20 Orientation to sound, intercollicular area in, 49 ORN (osteoradionecrosis), 1187–1189, 1188f, 1189f of cerebellopontine angle, 858 Orofacial pain disorders, otalgia due to, 196–198, 196t, 197t Oropharyngeal carcinoma, metastatic to cerebellopontine angle, 866 Oropharyngeal propulsion pump (OPP), 1354, 1356 Orthostatic hypotension, in elderly, 535 Os odontoideum malformation, 1147 Oscillopsia, 230, 234 Oscilloscopy, after chemical labyrinthectomy, 663 Osler, William, 28 Osseous decompression, of internal auditory canal, 765 Osseous lesions, diffuse, of temporal bone, 1125–1133 Ossicles epitympanic fixation of, 1084t, 1085 in sound conduction, 53 trauma to, 1084–1085, 1084t Ossicular reconstruction, 1085 Ossifying hemangiomas, of petrous apex, 393, 398f Osteitis deformans, of temporal bone, 1129–1131, 1130f, 1132t, 1133t Osteodystrophy, of petrous apex, 1121

Osteogenesis imperfecta cochlear hearing loss due to, 602 of temporal bone, 1131–1133, 1132f, 1132t, 1133t Osteoma of cerebellopontine angle, 863, 864f of external auditory canal, 415, 416f intracanalicular, 373, 376f Osteomyelitis, of skull base, 1096–1105 in children, 1099 complications of, 1102 diagnosis of, 1098–1099 etiology of, 1097 imaging of, 1099–1102, 1101f involving petrous apex, 1117 nomenclature for, 1096–1097 staging of, 1099 treatment of, 1102–1104 Osteopetroses, of temporal bone, 1127–1129, 1128f, 1132t, 1133t Osteoradionecrosis (ORN), 1187–1189, 1188f, 1189f of cerebellopontine angle, 858 Osteosarcoma of cerebellopontine angle, 863 of petrous apex, 1121 radiation-induced, 1192 of temporal bone, 1130 Otalgia, 194–202 acute, 196–197, 196t anatomic basis for, 195–196 due to atypical facial pain, 198 characteristics of, 194–195 chronic, 197, 197t due to chronic paroxysmal hemicrania, 202 defined, 194, 196 due to glossopharyngeal neuralgia, 199–200 due to headaches, 197t, 200–202 cervicogenic, 201 cluster, 201–202 migraine, 201 tension-type, 201 traction and inflammatory, 201–202 due to neoplastic disease, 202 due to neurologic disorders, 197t, 198–200 due to orofacial pain disorders, 196–198, 196t, 197t due to postherpetic neuralgia, 200 primary, 196 referred (secondary), 195–197, 196t, 197t, 216 due to temporomandibular disorders, 197–198 due to trigeminal neuralgia, 199 due to vagal and superior laryngeal neuralgia, 200 Otic capsule, malformations of, hearing loss due to, 600–601 Otic capsule bony disease, hearing loss due to, 602–603 Otic cyst, 91 Otic pit, 91 Otic placode, development of, 1199, 1200f Otitic hydrocephalus, due to otitis media, 913t, 920–921, 921f Otitis externa, malignant (necrotizing). See Malignant external otitis (MEO). Otitis media complication(s) of, 912–923 with acute vs. chronic disease, 914 anaerobic bacteria and, 914–915 biofilms and, 915 bone resorption and, 915 brain abscess or cerebritis as, 492, 493f, 913t, 919–920, 920f cholesteatoma and, 914

INDEX

Otitis media (Continued) dural venous sinus thrombophlebitis as, 913t, 918–919, 919f epidemiology of, 912–913, 913t epidural abscess or granulation tissue as, 913t, 917, 917f, 918f facial paralysis as, 915–917, 1240 historical background of, 913 meningitis as, 492–493, 913t, 921–922 microbial virulence factors and, 914 microbiology of, 914–915 opacification of middle ear as, 407 otitic hydrocephalus as, 913t, 920–921, 921f predisposing factors for, 914 signs of impending or early, 915 subdural empyema as, 913t, 922–923 and development of central auditory system, 572, 573 dizziness due to, 556–557 in elderly, 536 facial paralysis due to, 432 hearing loss due to, 599 iatrogenic injury due to surgery for, 1271 due to metastasis, 151, 151f temporal bone encephalocele due to, 1090 Otoacoustic emissions (OAEs), 287–290, 289f, 290f in acoustic neuroma, 165, 166, 743 advantages of, 288 vs. auditory brainstem response, 288 in auditory neuropathy, 471, 472 clinical applications of, 288–290, 289f–291f defined, 287 distortion product, 287–288, 289f, 290f evoked, 287 procedure for, 288 in sensory vs. neural hearing loss, 164 stimulus frequency, 287 types of, 287–288 variables affecting, 288 Otoconia, 96–97, 242 aging effect on, 533, 534t in otolith dysfunction, 243 Otoconial crystals, 242 Otogenic suppurative labyrinthitis, 336 Otolaryngologic examination, 216 Otolith(s), 75, 96–97 anatomy of, 242–243, 242f defined, 242 Otolith function, testing of, 243–244 Otolith neurons, tilt response of, 97, 97f Otolith organs, 96–98, 96f, 97f dysfunction of, 241–244, 243f Otolith vestibulo-ocular reflex, 100–101, 101f Otolith-ocular reflexes (OOR), 241–242 Otology father of modern, 18–19, 18f, 19f in mid-19th century, 15 Otomastoiditis, facial paralysis due to, 432 Otometrics, 1286 Otorrhea, 215 Otosclerosis cochlear, 1130f, 1132t, 1133t cochlear hearing loss due to, 602 endolymphatic hydrops due to, 345, 346f history of surgery for, 34–35 mechanism of hearing impairment in, 53 pulsatile tinnitus due to, 209 Otoscopic examination, 215–216 Otosyphilis, 249–250 pharmacotherapy for, 662t, 664–665 Ototoxicity gene transfer for protection against, 140 hearing loss due to, 593–595

monitoring during drug administration for, 595 and noise, 592 prevention of, 252 semicircular canal dysfunction due to, 250–253 tinnitus due to, 184, 185, 186 vestibular symptoms of, 180 in elderly, 537 OTR (ocular tilt reaction), 243, 248 Outer calvarium, 1006f Outer hair cells (OHCs) in acoustic neuropathy, 472 anatomy and physiology of, 590f, 591, 591f in frequency analysis, 54–55, 56 noise-induced damage to, 591 OVAR (off-vertical axis rotation), 109, 243 Owens, N., 1004 Oxidized cellulose (Surgicel), 678 Oxygen therapy, hyperbaric for osteoradionecrosis, 1188 for skull base osteomyelitis, 1104

P P1, auditory processing testing of, 278 P2, auditory processing testing of, 278 P3, auditory processing testing of, 277, 278 P300, auditory processing testing of, 277 in children, 571 PABI (penetrating auditory brainstem implant), 1329–1330, 1329f PAC (primary auditory cortex) cross-modal activation in, 322 physiology of, 59, 59f, 64 Pacchionian bodies, pathologic correlates of, 152–153, 153f Pachymeningitis, idiopathic hypertrophic cranial. See Idiopathic hypertrophic cranial pachymeningitis (IHCP). PAF (posterior auditory field), physiology of, 59, 59f, 64, 66 Paget’s disease cochlear hearing loss due to, 602 of temporal bone, 1129–1131, 1130f, 1132t, 1133t Pain acute vs. chronic, 195 characteristics of, 194–195 due to facial nerve neoplasm, 1263 neuropathic, and tinnitus, 184, 187 in neurotologic disease, 230 referred, 194–197, 196t, 197t Palatal myoclonus, pulsatile tinnitus due to, 207, 209 Palatine maxilla, 998f, 1054f Palpebral spring, 1346, 1346f–1347f PAN (periodic alternating nystagmus), 222, 233 Panic attacks dizziness with, 667 with vestibular dysfunction, 661 Panje, W. R., 1005 Panse, Rudolph, 729 Papilledema, 217 due to acoustic neuroma, 739t, 741 due to increased intracranial pressure, 524 Papillomas, choroid plexus, 371, 373f, 855–856 Paracervical musculature, 1054 Paraganglioma(s) (PGLs) angiography of, 455–456 of cerebellopontine angle, 350, 353f, 370 of facial canal, 158, 159f, 427, 432f facial nerve injury during surgery for, 1277 familial, molecular genetics of, 135–138

1397

immunohistochemical markers for, 543, 544t of internal carotid artery, 156, 157f involving hypoglossal nerve, 411f jugular, 353f, 400–405, 405f–408f of middle ear, 400, 405f, 414 nonchromaffin, 1039 genomic imprinting of, 127 octreotide for, 545 paraneoplastic syndromes with, 543–546, 544t pathologic correlates of, 148–150, 149f, 149t, 150f Paraldehyde, for status epilepticus, 521t Parallel processing, 66–67 Paralysis facial nerve. See Facial nerve paralysis. vestibular. See Vestibular neuritis (VN). Parametric adjustments, 111 Paraneoplastic cerebellar degeneration (PCD), 546–547 Paraneoplastic encephalomyelitis (PEM), 546–547 Paraneoplastic syndrome(s) (PNSs), 543–547 associated with carcinoma, 546–547 of cerebellopontine angle, 866 defined, 543 from disorders associated with neurotologic tumors, 545–546 generated by neurotologic tumors, 543–545, 544t oscillopsia due to, 234 Parasellar skull base, surgical anatomy of, 1053–1055, 1054f, 1055f Parasellar space neoplasms, 1047–1066 interventional radiology for, 1053 pathology of, 1047–1052, 1048f–1052f radiation therapy for, 1052–1053 surgical approach to, 1055, 1055t, 1063 frontal-temporal/lateral facial, 1063–1066, 1064f, 1065f infratemporal fossa, type C, 1066 Paré, Ambrose, 10–11 Paredrine test, 217, 234 Parent-specific transmission, 127, 127f, 138 Paresthesias defined, 194 in migraine, 514 Parietal bone, 998f, 1054f Parotid gland, and facial nerve, 1220f Parotid tumors, involving facial nerve, 1262, 1263, 1264, 1267 Parotidectomy, facial nerve monitoring during, 975 Paroxysmal torticollis of infancy (PTI), 557, 559 Parry, R. H., 33 Pars nervosa, 1037, 1137f Pars vascularis, 1037 Pars venosa, 1137f Parsons, J., 1028 Particle repositioning maneuver (PRM), for benign paroxysmal positional vertigo, 649–650, 650f, 651t Pasteur, Louis, 20 Patau’s syndrome, central processing deficits with, 578 Pathologic amplifier, 896 Pathologic responses, habituation of, 1336 Patient education, in vestibular rehabilitation, 1336 Patient positioning, for neurotologic surgery, 676–677, 677f Pause cells, 104, 105, 106f Pava, A., 730 PC (Purkinje cells), 102, 106f, 117 aging effect on, 534

1398

INDEX

PCA (posterior cricoarytenoid) muscle, 1360 PCD (paraneoplastic cerebellar degeneration), 546–547 PDGF (platelet-derived growth factor), in acoustic neuroma, 732 PDGFR (platelet-derived growth factor receptor), in acoustic neuroma, 732 PDS gene, 133 Pearly tumors, 841 Pecchioli, Zanobi, 793 Pectoralis major flap, 1010–1011, 1011f, 1012f Pediatric patients. See Children. Pedicle, 1138f PEG (percutaneous endoscopic gastrostomy), for swallowing dysfunction, 1354 PEM (paraneoplastic encephalomyelitis), 546–547 Pendred’s syndrome cochlear hearing loss due to, 602 hearing loss in, 129t, 132, 133 Pendrin, in nonsyndromic hereditary hearing loss, 132, 133 Pendrin gene, 602 Penetrating auditory brainstem implant (PABI), 1329–1330, 1329f Penetration, 1353 Penicillin, for otosyphilis, 665 Penicillin G, for otosyphilis, 665 Pennington, D. G., 1005, 1012 Pentobarbital, for status epilepticus, 521t Pentoxifylline (Trental), for vertebrobasilar insufficiency, 666 Percutaneous endoscopic gastrostomy (PEG), for swallowing dysfunction, 1354 Percutaneous injection, for vocal cord paralysis, 1357–1358, 1357t, 1358f Percutaneous stimulatory nerve excitability tests, 1223 Pericranial flap anterior, 1006–1007, 1006f lateral, 1006 temporoparietal, 1007, 1007f–1009f, 1008–1009 Perilabyrinthine abnormalities, CSF leak due to, 928, 928f Perilymphatic fistula (PLF), 247–249 in children, 558–559 congenital, 249 defined, 247 diagnosis and testing for, 248 in elderly, 536 etiology of, 247–248 hearing loss due to, 596–597 imaging of, 338–339, 341f management of, 248–249 pathogenesis of, 248 symptoms of, 179, 248 traumatic, 1086–1087 Perilymphatic hydrops, 332 Perinatal facial palsy, 1231t, 1241 Perineurium, 894, 1208, 1209f Periodic alternating nystagmus (PAN), 222, 233 Periodontal disorders, otalgia due to, 196 Periolivary nuclei, development of, 566 Periolivary region, in information processing, 48 Periosteum, 1006f Peripheral hearing loss, auditory processing testing with, 278 Peripheral isodose, in Gamma Knife radiosurgery, 1172–1173 Peripheral nerve fibers, 894, 895, 895f Peripheral neuropathy, with acoustic neuropathy, 473 Peripheral sensitization, 194

Persson, 29 PET. See Positron emission tomography (PET). Petit, Jean-Louis, 10, 11f, 12 Petit mal epilepsy, 518 Petroclival junction, chondrosarcoma of, 681–683, 682f Petroclival meningioma(s), 812–818, 1119–1120 cerebral edema due to, 719f challenges of, 812–813 clinical presentation of, 813–814, 1049–1050 defined, 813 diagnosis of, 814, 1050, 1050f extension of, 713f, 813 grading system for, 814, 814t mortality and quality of life with, 816–818 MRI of, 1061f, 1119, 1119f origin and classification of, 813 pathology of, 147, 1049 preoperative considerations for, 814–815, 814t recurrent, 462f–463f resection of, 816, 817t, 1050, 1119–1120 surgeon’s view of, 812f surgical approach to, 815, 815f–817f surgical history of, 815 Petromastoid canal, CSF leak from, 928, 928f Petro-occipital fissure, 1137f Petrosal approaches, 1111 Petrosal nerve greater, 1002, 1055f, 1158f greater superficial. See Greater superficial petrosal nerve (GSPN). Petrosal sinus(es) anatomy of, 1108 bleeding from, during neurotologic surgery, 715 dural arteriovenous fistulas of, 443, 449f–450f Petrosal vein, 679, 701 Petrous apex anatomy of, 1107–1108, 1108f aneurysms of, 1121, 1122f imaging of, 389, 390f treatment of, 439, 440f–441f anterior, 1108, 1108f benign vascular tumors of, 393, 398f bone lesions in, 370, 370f, 371f breast adenocarcinoma metastatic to, 866f cavernous sinus hemangiomas of, 396 cephalocele of, 1115–1116, 1116f cholesteatomas of, 1114–1115, 1115f hearing loss due to, 173 cholesterol cysts or granulomas of, 370, 370f, 1111–1114, 1112f, 1113f hearing loss due to, 173 imaging of, 384–385, 385f, 386f chondroma of, extension into cerebellopontine angle of, 862f chondrosarcomas of, 681–683, 682f, 1117–1118, 1118f imaging of, 389–393, 391f–394f chordomas of, 1118–1119, 1119f imaging of, 389–393, 391f–394f defined, 384, 681 direct extension from nasopharyngeal and infratemporal lesions to, 396, 401f, 402f effusion of, 1110f endolymphatic sac tumors of, 396 epidermoids of, 385–386, 387f fibrous dysplasia of, 393, 395f–397f fifth nerve sheath tumors of, 396, 400f fluid or mucus in, 387–388, 388f hematologic systemic malignancy of, 1121 imaging of, 384–399

invasion by meningioma of, 148f Langerhans’ cell histiocytosis of, 397 lesions of, 1107–1121 cystic, 1111–1116, 1112f, 1113f, 1115f, 1116f diagnosis of, 1108–1110, 1109f, 1109t, 1110f epidemiology of, 1108 historical background of, 1107 imaging of, 1109–1110, 1109f, 1109t, 1110f infectious, 1116–1117, 1117f neoplastic, 1117–1121, 1118f–1120f surgical approaches to, 1110–1111 symptoms of, 1108 meningiomas of. See Petroclival meningioma(s). meningoceles of, 388, 388f metastasis to, 150, 151f, 1120, 1121f imaging of, 397 mucoceles of, 1115 imaging of, 386–387 neurogenic tumors of, 1120, 1120f neuromas of, 1120 normal fat of, 387, 387f osteodystrophy of, 1121 osteomyelitis of, 1117 plasmacytomas of, 397 posterior, 1108, 1108f pseudolesions of, 387–388, 387f, 388f schwannomas of, 1120, 1120f solid tumors of, 1121 superior semicircular canal dehiscence of, 399, 403f surgery of, 681–683, 681f, 682f Petrous apicectomy, 681, 682f Petrous apicitis, 1116–1117, 1117f imaging of, 389, 389f Petrous apicotomy, 681, 681f Petrous carotid aneurysm, 389, 390f, 1121, 1122f Petrous ridge, 1137f PF. See Posterior fossa (PF). PGL(s). See Paraganglioma(s) (PGLs). PGL loci, genetic mapping of, 136 PGL1 gene, 136–137 PGL2 gene, 137 PGL3 gene, 137 PGL4 gene, 137 PH (prepositus hypoglossi) nucleus. See Nucleus prepositus hypoglossi (NPH). Phantom perception, tinnitus as, 188 Pharmacotherapy for familial ataxia syndrome, 662t, 667 future perspectives on, 667–668 for Ménière’s disease, 661–664, 662t for otosyphilis, 662t, 664–665 for psychophysiologic dizziness, 662t, 667 for vertebrobasilar insufficiency, 662t, 666–667 for vestibular dysfunction, 659–670, 662t causes and mechanisms of, 659–661, 660t due to specific disease entities, 661–668 symptomatic, 668–670, 669t for vestibular migraine, 662t, 665–666 for viral neurolabyrinthitis, 662t Pharyngeal artery, ascending, 684f Pharyngeal carcinoma, metastasis of, 150–151 Pharyngeal swallow, 1351 Pharyngeal tubercle, 1137f Pharynx, disorders of, otalgia due to, 196t, 197 Phase-locking, in auditory nerve fiber, 57, 57f, 58 Phenergan. See Promethazine (Phenergan).

INDEX

Phenobarbital, for status epilepticus, 521t Phenothiazines, for vestibular dysfunction, 668, 669t Phenylketonuria (PKU), multifactorial inheritance in, 128 Phenytoin, for status epilepticus, 521t Phonemic regression, 281–282 Phonophobia, 183 in migraine, 513 Phoria, 235–236 Photoelectric effect, in Gamma Knife radiosurgery, 1168 Photopsia, in migraine, 514 Physaliferous cell, 1048, 1048f Physical examination, general, 215–216 Physical therapy, for cervical vertigo, 541 Physiologic compensation, 1333–1334 “Piano-playing fingers,” due to foramen magnum meningioma, 826 PICA. See Posterior inferior cerebellar artery (PICA). PISCC (primary intracranial squamous cell carcinoma), 866 Pitch assessment, with auditory brainstem implant, 1327–1328, 1327f, 1329 Pittsburgh staging system, for external auditory canal tumors, 1029t PKU (phenylketonuria), multifactorial inheritance in, 128 Place representation, of frequency, 55–57, 55f–57f, 58 Plant, the, 102 Plasmacytomas of cerebellopontine angle, 867 of petrous apex, 397 Plasticity of auditory system, 322, 575, 576–578, 577f central nervous system, and vestibular rehabilitation, 1331–1332 neural, 66, 896–897 and tinnitus, 187 of vestibular nucleus, 897 of vestibulo-ocular reflex, 110–111, 897f Platelet-derived growth factor (PDGF), in acoustic neuroma, 732 Platelet-derived growth factor receptor (PDGFR), in acoustic neuroma, 732 Plater, Felix, 792 Play audiometry, after meningitis, 495 PLF. See Perilymphatic fistula (PLF). Plugging, in Gamma Knife radiosurgery, 1172, 1173f PNETs (primitive neuroectodermal tumors), 370 Pneumocephalus due to acoustic neuroma surgery, 756 postoperative, 720, 720f tension due to acoustic neuroma surgery, 756 due to temporal bone encephalocele, 1091 Pneumococcal labyrinthitis, 334 Pneumosinus dilatans, in meningioma, 799 PNSs. See Paraneoplastic syndrome(s) (PNSs). Pocket Smell Test, 216 Politzer, Adam, 18–19, 18f, 19f, 20, 22, 31 Polyarteritis nodosa, labyrinthitis due to, 336 Polychondritis, relapsing, vestibular symptoms of, 180 Polygenic interaction, 128 Polyp, aural, 215 Polysensory pathway, tinnitus and, 187, 188f Pons, 1139f facial nerve projections within, 1201, 1202f ventral, middle fossa-transpetrous apex approach to, 696–698, 697f Pontine astrocytoma, 370, 371f facial nerve degeneration due to, 153–154, 154f

Pontomedullary junction, in brainstem auditory pathway, 45 Pontomedullary sulcus, 1142 Pool, J., 730 “Popcorn” activity, in intraoperative facial nerve monitoring, 972, 973f Portio major, of trigeminal nerve, 893 Portio minor, of trigeminal nerve, 893 Portmann, Georges, 32, 32f Porus acousticus, 1108 Positional test, 608, 612–613, 613f, 614f Positional vertigo, 178, 179 Position-vestibular-pause (PVP) neurons, 104, 105 Positron emission tomography (PET), 53, 318–320 advantages and disadvantages of, 318–319 background and general principles of, 318 clinical applications of, 319–320 for cochlear implants, 319 with functional MRI, 323 for tinnitus, 319–320 Postauricular edema, 215 Postauricular nerve, 1205 Postauricular response, 270 Posterior ampullary nerve, 950f, 951, 951f Posterior arch, of atlas, 1138f, 1139f Posterior auditory field (PAF), physiology of, 59, 59f, 64, 66 Posterior canal nerve, 77f, 80 Posterior canal vestibulo-ocular reflex, 100, 100f Posterior condylar emissary vein, 1144f, 1145f Posterior cranial fossa, 998f, 1002, 1054f surgical exposure of, 699–702, 700f, 701f Posterior cranial vault reconstruction, 1020–1024, 1024f Posterior cricoarytenoid (PCA) muscle, 1360 Posterior fossa (PF) arachnoid cysts of, 944–948 classification of, 944–945, 945f clinical signs and symptoms of, 945–946 diagnosis and imaging of, 946–947, 946f management of, 947, 947f pathology and pathogenesis of, 944, 944f meningiomas of, 804–806 classification of, 805–806, 805f epidemiology of, 804–805 hearing loss due to, 173 recurrence of, 835 nonvestibular schwannomas of, 366–367, 366f, 367f Posterior fossa tumors, 875–889 vs. benign paroxysmal positional vertigo, 648 brainstem gliomas, 876–880, 878f, 879f, 880t cerebellar astrocytomas, 880–883, 881f, 882f, 883t choroid plexus tumors, 883–885, 886f, 886t ependymomas, 883, 884f, 885t hemangioblastomas, 885–887, 887f, 887t medulloblastomas, 875–876, 877f, 878t metastatic, 887–889, 888f, 889t Posterior fossa vestibular neurectomy, 953 Posterior inferior cerebellar artery (PICA) anatomy of, 893 surgical, 678, 679f in cervicovertebral junction, 1141f, 1142, 1143f–1145f, 1160f giant aneurysm of, 369f Posterior longitudinal ligament, 1139f Posterior meningeal artery, 1141f, 1142, 1144f Posterior petrous bone, meningioma of, 147 Posterior semicircular canal occlusion, for benign paroxysmal positional vertigo, 652–656, 653f–656f

1399

Posterior skull base lesions, 1005–1006, 1005f soft tissue reconstruction for, 1020, 1020t, 1023f Posterior spinal artery, 1141f, 1142, 1145f, 1160f Posteroventral cochlear nucleus (PVCN), 60, 60f development of, 565, 565f Postherpetic neuralgia, otalgia due to, 200 Postinfectious CSF leak, 927, 931 Postnatal development, of auditory competence, 569–570, 570f Postoperative CSF leak, 926–927, 927f, 929–930 Poststapedectomy sensorineural hearing loss, 599 Post-stimulus time (PST) histograms, for cochlear nucleus, 61, 61f Post-traumatic. See Trauma. Postural control exercises, 1336 Postural dysfunction, 177 Postural sway, measurement of. See Dynamic posturography. Postural vertigo, 178, 179 Posturography. See Dynamic posturography. Potassium-sparing diuretics, for Ménière’s disease, 661 Potentiometers, variable screw, in hearing aids, 1288 POU3F4 gene, 125 Prader-Willi syndrome, 127 Predisposition, 128 Prednisone for autoimmune inner ear disease, 641 for facial palsy, 1250 for idiopathic sudden sensorineural hearing loss, 595–596 for otosyphilis, 250, 665 Pregnancy, Bell’s palsy during, 1234 Prepositus hypoglossi (PH) nucleus. See Nucleus prepositus hypoglossi (NPH). Presbycusis, 592–593 central, 281–282 Presbystasis, 534–535, 535t Presigmoid approach, to cerebellopontine angle, 686 Pressurization, labyrinthine hemorrhage due to, 246 Prestin proteins, 591, 601 Presyncopal lightheadedness, 660t Primary auditory cortex (AI, PAC) cross-modal activation in, 322 physiology of, 59, 59f, 64 Primary autoimmune labyrinthitis, 336 Primary intracranial squamous cell carcinoma (PISCC), 866 Primitive neuroectodermal tumors (PNETs), 370 PRM (particle repositioning maneuver), for benign paroxysmal positional vertigo, 649–650, 650f, 651t Probe tube methods, for hearing aids, 1286–1287, 1286f, 1287f Procaine (lidocaine), for tinnitus, 189–190 Procaine penicillin, for otosyphilis, 665 Prochlorperazine (Compazine) for vertigo in elderly, 537 for vestibular dysfunction, 668–669, 669t Progesterone, in acoustic neuroma growth, 733 Program, of cochlear implant, 1304 Programming of auditory brainstem implant, 1326–1327 of cochlear implant, 1303–1304 Progressive spastic quadriparesis, due to foramen magnum meningioma, 825–826 Prolactinoma, invasive, 389

1400

INDEX

Prolonged position maneuver, for benign paroxysmal positional vertigo, 650 Promethazine (Phenergan) for motion sickness, 670 for vestibular dysfunction, 668, 669t, 670 for vestibular symptoms of migraine, 516 Promontory stimulation, for cochlear implant, 1310 Prophylaxis, for Ménière’s disease, 628 Propranolol, for vestibular migraine, 666 Protective devices, for eyes, 1342–1343, 1343f Proton beam radiation for acoustic neuroma, 769, 771t for parasellar and clival neoplasms, 1053 Protympanic triangle, extension of paraganglioma to, 149–150, 150f Psammoma(s), 792 Psammoma bodies, 795, 796f, 797, 1049, 1050f Pseudoaneurysms, 438 of dural arteriovenous fistula, 447f–448f traumatic, 438 Pseudolesions, of petrous apex, 387–388, 387f, 388f Pseudomonas aeruginosa facial palsy due to, 1240–1241 osteomyelitis due to, 1096, 1097, 1098, 1099, 1103–1104 Pseudotumor cerebri increased intracranial pressure in, 524, 530–531 pulsatile tinnitus due to, 205–207, 206t, 207f, 208, 208t, 209 PST (post-stimulus time) histograms, for cochlear nucleus, 61, 61f Psychiatric dizziness, 667 Psychophysiologic dizziness causes and mechanisms of, 659–661, 660t pharmacotherapy for, 662t, 667 PT. See Pulsatile tinnitus (PT). PTA (pure tone averages), with acoustic neuroma, 167, 168–169, 168t, 169t, 170, 171, 171t, 172 Pterygoid plexus of veins, 1055f Pterygoid processes, 998f, 1054f Pterygopalatine fossa, 1158f PTI (paroxysmal torticollis of infancy), 557, 559 Ptosis, 217 “Pull” fibers, 270 Pulsatile tinnitus (PT), 204–211 cause(s) of, 182, 204–207, 216 arterial, 204–205, 206t atherosclerotic carotid artery disease as, 204, 208, 208t, 209 dural arteriovenous fistula as, 443 glomus tumors as, 208, 208t, 209–211, 1039 intracranial vascular abnormalities as, 204–205, 205f, 208, 208t, 209, 210f nonvascular, 207 otosclerosis as, 209 palatal, stapedial, and tensor tympani muscle myoclonus as, 207, 209 pseudotumor cerebri syndrome as, 205–207, 206t, 207f, 208, 208t, 209 venous, 205–207, 206t, 207f, 207t evaluation of, 208–209, 208t, 210f idiopathic (essential), 207, 211 illustrative case histories of, 205, 205f internal jugular vein in, 204 management of, 209–211, 210f objective vs. subjective, 204 pathophysiology and classification of, 204–207, 205f, 206t, 207f, 207t

Punctal occlusion, 1347 Pupil Argyll Robertson, 216 Marcus-Gunn, 230 Pupillary reflex, 216 Pure tone audiometry, for acoustic neuroma, 742 Pure tone averages (PTA), with acoustic neuroma, 167, 168–169, 168t, 169t, 170, 171, 171t, 172 Purkinje cells (PC), 102, 106f, 117 aging effect on, 534 Purkyne, J. E., 15 Pursuit tests, 608, 616, 616f “Push” fibers, 270 PVCN (posteroventral cochlear nucleus), 60, 60f development of, 565, 565f PVP (position-vestibular-pause) neurons, 104, 105 Pyogenic Infective Diseases of the Brain and Spinal Cord, 23 Pyramid, 1141f, 1144f

Q Quadriparesis, progressive spastic, due to foramen magnum meningioma, 825–826 Quality control, with intraoperative cranial nerve monitoring, 964–965 Quantity absorbed dose, in Gamma Knife radiosurgery, 1167 Quantity radioactivity, in Gamma Knife radiosurgery, 1167 Queckenstedt test, 527, 918 QuickSIN test, 274 Quillen, C. G., 1005 Quinine, hearing loss due to, 594 Quix, F. H., 729

R Radial forearm fasciocutaneous flap, 1012, 1013f, 1014f Radiation exposure, meningiomas due to, 793–794, 1192 Radiation necrosis, 1187–1189, 1188f, 1189f of skull base, 415–416, 418f Radiation therapy for acoustic neuroma, 768–772 acoustic neuroma due to, 733 for arteriovenous malformations, 942 for brainstem gliomas, 880 for chordoma, 1049 complications of, 1187–1193 neurologic, 1191 effects of on great vessels, 1190–1191, 1191f on soft tissues of ear, 1189–1190 for glomus jugulare tumors, 1041 intensity-modulated, 1181–1182, 1182f for medulloblastoma, 876 for meningiomas, 836 osteoradionecrosis due to, 1187–1189, 1188f, 1189f for parasellar and clival neoplasms, 1052–1053 for posterior fossa metastases, 888 secondary oncogenesis due to, 1191–1192, 1192f stereotactic. See Stereotactic radiosurgery (SR). for temporal bone tumors, 1034 three-dimensional conformal, 1182

Radicular artery, 1144f Radioactivity, 1167 Radiofrequency lesioning, for trigeminal neuralgia, 904 Radiologic evaluation. See also Magnetic resonance imaging (MRI); specific modalities, e.g., Computed tomography (CT). of cochlear implant, 1310 of facial nerve tumors, 1265–1266 of meningiomas, 799–803, 801f, 802f of pulsatile tinnitus, 209 Radionuclide studies of glomus jugulare tumors, 1041 of skull base osteomyelitis, 1100–1101 of temporal bone tumors, 1030 Radiosurgery for arteriovenous malformations, 942 Gamma Knife. See Gamma Knife radiosurgery. for meningiomas, 836 stereotactic. See Stereotactic radiosurgery (SR). Radiotherapy. See Radiation therapy. Ramsay Hunt syndrome, 431, 668–669, 1233–1234 Random Gap Detection Test (RGDT), 274 RCT. See Rotational chair test (RCT). REA (right ear advantage), 276 Real ear aided response (REAR), 1286–1287, 1286f Real ear insertion response (REIR), 1286–1287, 1287f Real ear measures, for hearing aids, 1286–1287, 1286f–1288f Real ear occluded response (REOR), 1287, 1288f Real ear saturation response (RESR), 1287 Real ear unaided response (REUR), 1286–1287, 1286f–1288f REAR (real ear aided response), 1286–1287, 1286f Receiver-stimulator, of cochlear implant, 1302, 1302f, 1305, 1307 Recombination, 126 Reconstruction, of cranial base, 706–708, 707f, 708f Recording electrodes, for cranial nerve monitoring, 960–962, 962f, 964 Rectus abdominis free flap, 1012–1015, 1013f, 1015f–1017f Rectus muscles innervation of, 84, 85f in vestibulo-ocular reflex pathway, 99–100, 99f, 100f Recurrent laryngeal nerve (RLN) examination of, 225 in vocal cord paralysis, 1356 Red eyes, with facial paralysis, 1340, 1341 Referred otalgia, 195–197, 196t, 197t, 216 Referred pain, 194–195 Referred signs and symptoms, from vestibular pathways to visceral sites, 661 Reflection, of nerve impulses, 896 Reflex decay, with acoustic neuroma, 742 Reflex epilepsy, 522 Regeneration, of nerves, 1210 abnormal, 1210 Regional transposition flaps, for skull base reconstruction, 1009–1011, 1009f–1012f Regular neurons in otolith organs, 97, 97f in semicircular canals, 95–96, 96f Regulon, 914 Rehabilitation after cochlear implantation, 1312 of lower cranial nerve palsies, 1350–1361

INDEX

Rehabilitation (Continued) ocular, with facial paralysis, 1339–1348 nonsurgical management of, 1341–1344, 1342t, 1343f, 1344f reasons for, 1339–1340 surgical management of, 1344–1347, 1345f–1348f types of, 1340–1341 vestibular, 1331–1337 after acoustic neuroma surgery, 766 as adjunctive modality, 1335 common techniques of, 1335–1336 dynamic posturography to monitor, 265–266 expected results of, 1337 inappropriate candidates for, 1335 patient selection criteria for, 1334 physiologic rationale for, 1331–1333 as primary treatment modality, 1334 role of neurotologist in, 1337 as therapeutic trial, 1335 for vestibular symptoms of migraine, 516 Reichert’s cartilage, 1205 Reinnervation, for vocal cord paralysis, 1360–1361 REIR (real ear insertion response), 1286–1287, 1287f Reissner’s membrane, MRI of, 345 Relapsing polychondritis labyrinthitis in, 336–337, 338f vestibular symptoms of, 180 Renaissance medical thought prior to, 2–3 otologic anatomists of, 3–5, 4f, 5f Renal disease, cochlear hearing loss due to, 602 REOR (real ear occluded response), 1287, 1288f Repositioning maneuvers, for benign paroxysmal positional vertigo, 648–652, 649f, 650f, 651t Respiratory epithelial cysts, of cerebellopontine angle, 853 RESR (real ear saturation response), 1287 Resting potential, 1207 Reticular formation, vestibulo-ocular projections to, 84, 86 Retinal slip, 111, 113, 1332 Retinal slip velocity, 107 Retinitis pigmentosa (RP), multifactorial inheritance in, 128 Retrocerebellar cysts, 944–945, 945f Retrofacial cell tract method, of identifying facial nerve, 1273 Retrolabyrinthine (RL) approach to internal auditory canal and cerebellopontine angle, 685f, 686, 689–691, 690f to vestibular neurectomy, 954, 954f, 956 Retrolabyrinthine (RL) craniotomy, 689, 690f Retrolabyrinthine-middle fossa approach, 700, 700f, 701f Retrolabyrinthine-retrosigmoid vestibular neurectomy (RRVN), 955, 955f, 955t, 956 Retrosigmoid (RS) approach to acoustic neuroma, 747–748, 749, 749f advantages of, 689 to cerebellopontine angle, 686, 687–689 disadvantages of, 689 to facial nerve, 1214 indications for, 687, 687f to internal auditory canal, 685, 685f, 686–689 to intracranial aspect of jugular foramen, 698, 698f surgical exposure in, 686–687, 686f technical considerations with, 687–689

Retrosigmoid (RS) craniotomy, 686f, 687, 687f, 689 for vestibular schwannoma, in neurofibromatosis 2, 788, 788f Retrosigmoid-internal auditory canal (RSG-IAC) approach, for vestibular neurectomy, 954–955, 956 REUR (real ear unaided response), 1286–1287, 1286f–1288f RGDT (Random Gap Detection Test), 274 Rh incompatibility, cochlear hearing loss due to, 602 Rhabdomyosarcoma (RMS) alveolar, 1031 botryoid, 1031 of cerebellopontine angle, 856 embryonal, 1031 facial nerve involvement in, 427–430 pleomorphic, 1031 of temporal bone, 1031 Rheumatoid arthritis, of craniovertebral junction, 1147–1148, 1148f Rheumatoid basilar invagination, 1147–1148 Rhinorrhea, 928, 929 Rhomboencephalitis, 237 Rhomboid lip, 1140f, 1141f Rifampin, for skull base osteomyelitis, 1103 Right ear advantage (REA), 276 Righting response, in children, 555 riMLF (rostral interstitial nucleus of medial longitudinal fasciculus), 105 Rinne test, 220 Ritalin (methylphenidate), auditory processing with, 278 RL approach. See Retrolabyrinthine (RL) approach. RLN (recurrent laryngeal nerve) examination of, 225 in vocal cord paralysis, 1356 RMS. See Rhabdomyosarcoma (RMS). Rokitansky, Karl, 17, 18, 19 Rollover, with acoustic neuroma, 742 Romberg test, 224–225, 256 Rosen, S., 36, 36f, 37 Rosen knife, 36 Rosenwasser, Harry, 35 Rostral fastigial nucleus, in vestibulo-ocular reflex, 104 Rostral interstitial nucleus of medial longitudinal fasciculus (riMLF), 105 Rotation flap, 707, 707f Rotational chair test (RCT), 617–620, 618f, 619f for acoustic neuroma, 743 advantages of, 608t for children, 555 clinical indications for, 620 for elderly, 534 for evaluation of physiologic compensation, 1333 for ototoxicity, 252 Rotational habituation, 897 Rotatory eye movements, 84, 84f Round window, ossification of, cochlear implant with, 1319 Round window membrane (RWM), gene transfer across, 139–140 RP (retinitis pigmentosa), multifactorial inheritance in, 128 RRVN (retrolabyrinthine-retrosigmoid vestibular neurectomy), 955, 955f, 955t, 956 RS approach. See Retrosigmoid (RS) approach. RSG-IAC (retrosigmoid-internal auditory canal) approach, for vestibular neurectomy, 954–955, 956

1401

Rubella, congenital central processing deficits with, 578 hearing loss due to, 598 Rubella labyrinthitis, 334, 334f RWM (round window membrane), gene transfer across, 139–140

S S-100, in meningiomas, 799 SAAT (Selective Auditory Attention Test), 279 Saccade(s), 221, 222 in multiple sclerosis, 503 Saccade test, 608, 615, 616f Saccadic system, 106, 111–112, 112f Saccular macula orientation of, 96, 96f reflex projections of, 82f Saccular nerve, 76, 77f, 81f, 951 Saccule aging effect on, 533 anatomy of, 242–243, 242f in otolith-ocular reflexes, 241 Sacculus, anatomy of, 221f Saccus endolymphaticus, historical background of, 27, 32, 32f SAH. See Subarachnoid hemorrhage (SAH). Salicylates for aminoglycoside-induced ototoxicity, 251 hearing loss due to, 594 semicircular canal dysfunction due to, 251 tinnitus due to, 184, 185, 186 Salivary gland choristomas, of middle ear, facial nerve involvement in, 430 Salivary gland heterotopia, of cerebellopontine angle, 853 Salivary gland tumors, radiation-induced, 1192 Salpingopharyngeus muscle, myoclonic contractions of, pulsatile tinnitus due to, 207 Salt restriction, for Ménière’s disease, 661 Saltatory conduction, 1208, 1208f Sandifort, E., 27–28 Sarcoidosis, 474–477 of cerebellopontine angle, 857 clinical presentation of, 475 CSF findings in, 476 defined, 474 differential diagnosis of, 475 etiology of, 475 evaluation of, 475–476, 476t histopathology of, 475, 475f imaging of, 476, 477f incidence of, 474–475 outcomes for, 476–477 pathophysiology of, 475 treatment for, 476 Sarcomas, radiation-induced, 1192 SAS (simultaneous analog sampling/simulation), 1303, 1305, 1317 Saturation sound pressure level (SSPL), with hearing aids, 1287 SBMA (spinal and bulbar muscular atrophy), anticipation in, 127 SBO. See Skull base osteomyelitis (SBO). SC (superior colliculus), physiology of, 60 SCA (superior cerebellar artery), anatomy of, 893, 894, 1145f surgical, 679, 679f Scala media, enlarged, 332 Scala vestibuli, enlarged, 332 Scalp arteriovenous fistulas of, 453 layered anatomy of temporal and parietal, 1006, 1006f palpation of, 216

1402

INDEX

Scalp flaps, 1009 Scalp topography, 310–312 for auditory processing testing, 282–283 Scalp-positive peak, 300 SCAN-C Test for Auditory Processing Disorders in Children—Revised, 274 SCAN-S Test for Auditory Processing Disorders in Adolescents and Adults, 274 Scarpa, Antonio, 9–10, 10f, 11f, 19 Scarpa’s fluid, 10 Scarpa’s ganglion, 76, 77f, 221f aging effect on, 533–534, 534t SCCA. See Squamous cell carcinoma (SCCA). SCD (superior semicircular canal dehiscence syndrome), 244–246, 245f, 399, 403f Scheibe’s deformity, hearing loss due to, 600 Scheibe’s degeneration, deafness due to, 50 Schirmer’s tear test, 1245, 1265 modified, 219 Schizophrenia, vestibular dysfunction with, 667 Schramm, V. L., 1005 Schuknecht, Harold, 38 Schwabach test, 221 Schwann cell, 1208, 1208f Schwannoma(s) ancient, 734 angiography of, 464–465 arterial supply of, 464 of cerebellopontine angle, 858–861 clinical presentation of, 464 cochlear, 339, 342f CT scan of, 464 defined, 464 embolization of, 464–465 facial nerve, 423–424, 424f–428f in cerebellopontine angle, 366, 367f, 371, 859 dumbbell-shaped, 424, 425f geniculate ganglion, 424–425, 426f hearing loss due to, 173 histopathology of, 1258–1260, 1260f in internal auditory canal, 423–424 in posterior and middle cranial fossae, 424, 425f topography of, 1259–1260, 1260f tympanic, 424, 426f types of, 423, 424f, 1258–1259 hypoglossal, 367 Jacobson’s nerve, 1260 jugular foramen, 366–367, 860–861, 1042–1043 clinical presentation of, 1042 epidemiology of, 1042 imaging of, 367f, 411f, 1042, 1042f, 1043f pathogenesis of, 1042 surgical approach to, 699, 699f, 1042–1043 labyrinthine, 339–340, 342f, 343f lower cranial nerve, 366–367, 367f, 860–861, 861f MRI of, 464 nonvestibular posterior fossa, 366–367, 366f, 367f of petrous apex, 1120, 1120f trigeminal, 366, 366f of cerebellopontine angle, 366, 366f, 859–860, 860f MRI of, 714f surgical approach to, 704f, 705f vestibular. See Acoustic neuroma (AN). Schwannomin, 135 in acoustic neuroma, 732 Schwartze, Hermann, 12, 19, 21–22, 21f, 25, 26 Scintillating scotomata, 201, 514

Scopolamine for motion sickness, 670 for vertigo in elderly, 537 for vestibular dysfunction, 669t, 670 Scotomata, scintillating, 201, 514 Screening Instrument for Targeting Educational Risk (SIFTER), 279 SDHA gene, 137 SDHB gene, 137 SDHC gene, 137 SDHD gene, 136–137, 138 SDS (speech discrimination scores) with acoustic neuroma, 168–170, 169t, 171t, 172, 745 with sensory vs. neural hearing loss, 164 Second-order vestibular neurons, 104–105, 107, 107f Segregation, of genes, 125–126 Seidenberg, B., 1004 Seizures, 518–523 audiogenic, 522 classification of, 518, 519t diagnosis and evaluation of, 518–519 epidemiology of, 518 etiology of, 518 generalized, 518, 519t management of, 520–521 neurotogenic manifestations of, 521–522 partial, 518, 519t postoperative, 720 reactive, 518 vertiginous, in children, 559 vestibular, 181, 521–522 vestibulogenic, 522 Sekhar-Monacci grading system, for clival and petroclival meningiomas, 814, 814t Selective amplification, with hearing aids, 1286 Selective Auditory Attention Test (SAAT), 279 Selective serotonin reuptake inhibitors (SSRIs) auditory processing with, 278 for psychophysiologic dizziness, 667 for vestibular dysfunction, 668 Selker, R., 1028 Sella turcica, 1157f Sellae tuberculumi, 998f, 1054f Semicircular canal(s) afferent neurons to, 95–96, 96f aging effect on, 533 anatomy of, 221f congenital malformations of, 332 coplanar pairs of, 94 crista ampullaris of, 75 and facial nerve, 1220f hydrodynamics of, 94, 94f innervation of, 76 physiology of, 94–95 discovery of, 15 sensitivity to linear accelerations of, 95 time constant for, 94, 94f Semicircular canal aplasia, hearing loss due to, 601 Semicircular canal dysfunction, 244–253 due to labyrinthine hemorrhage, 246–247 due to labyrinthitis, 247 due to luetic vestibulopathies, 249–250 due to ototoxicity, 250–253 due to perilymph fistula, 247–249 due to post-traumatic vertigo, 249 due to superior semicircular canal dehiscence syndrome, 244–246, 245f, 399, 403f Semispinalis capitis muscle, 1160f Sensitive period, 572 Sensitization central, 194–195 peripheral, 194 Sensitized speech tests, 274

Sensorimotor error signal, 660 Sensorineural hearing loss (SNHL), 168 with arteriovenous fistulas, 936 auditory brainstem response with, 300, 301f autoimmune, 639–642, 640t development of central auditory system with, 572, 572f, 574–578, 577f genetic basis for, 601–602 hearing aids for, 1281–1282 idiopathic, progressive, bilateral, 639–642, 640t idiopathic sudden, 595–596, 640 due to otitis media, 599 due to ototoxicity, 593–595 poststapedectomy, 599 presbycusis as, 592–593 prevalence of, 128 due to temporal bone trauma, 1085–1086 Sensory abnormalities, due to craniovertebral junction anomalies, 1148 Sensory deprivation, with hearing aids, 1285–1286 Sensory hearing loss. See Cochlear hearing loss. Sensory innervation, to ear, 194 Sensory organization test (SOT) age and, 266, 267f for central balance deficits, 263 considerations and limitation of, 266–267, 267f for diagnosis, 267 methodology for, 257, 257t, 258f to monitor treatment, 266 for nonphysiological component of balance, 264, 265f reliability and validity of, 259–262 for risk of falls in older adults, 262 for vestibular deficits, 262 Sensory presbycusis, 592 Sensory substitution, 1332–1333 Sensory-useless hand, 501 Sentence in noise (SIN) test, 1287 Serous labyrinthitis otolith dysfunction due to, 247 vertigo due to, 556 Serous otitis media, dizziness due to, 556 Serpentine aneurysms, pathologic correlates of, 156–157 Sex hormones, in acoustic neuroma growth, 733 Sex-specific transmission, 127, 127f, 138 SFOAEs (stimulus frequency otoacoustic emissions), 287 SGCs (spiral ganglion cells) development of, 564, 564f effect of cochlear implant on, 576–578, 577f Shambaugh, George E., Jr., 35, 36, 36f, 37 Sharif, A., 1004 Shea, John, 36f, 37 Sherrington, Charles, 25 Shingles, 200 Shunts, for hydrocephalus, 527–528, 528f–530f SIADH (syndrome of inappropriate antidiuretic hormone), seizures due to, 519 Sibelium. See Flunarizine (Sibelium). Sickle cell anemia, labyrinthine hemorrhage in, 246 Siderosis, superficial. See Superficial siderosis (SS). Side-to-side “head heaves,” 222 SIFTER (Screening Instrument for Targeting Educational Risk), 279 Sigmoid sinus anatomy of, 998f, 1054f, 1055f, 1144f, 1145f, 1160f bleeding from, during neurotologic surgery, 714f, 715

INDEX

Sigmoid sinus (Continued) dural arteriovenous fistulas of, 443, 934–935, 935f and facial nerve, 1204, 1220f in retrolabyrinthine approach, 690 in retrosigmoid approach, 688 in translabyrinthine approach, 691 Sigmoid sinus thrombosis, due to otitis media, 918–919, 919f Sigmoid sulcus, 1137f Sign(s), of neurotologic disease, 230–233 Signal transformation, 102–103, 103f Signal-to-noise (S/N) ratios in auditory processing testing, 274 with hearing aids, 1290 Significance probability mapping (SPM), 311 SIH (spontaneous intracranial hypotension), 480 Silastic elastic prosthesis, for eyelids, 1346, 1348f “Silent current,” 591 Silent pattern, in intraoperative facial nerve monitoring, 972 Silverstein, H., 949 Simmons, Blair, 38 Simpson-Hall, 35 Simultaneous analog sampling/simulation (SAS), 1303, 1305, 1317 SIN (sentence in noise) test, 1287 Single-photon emission computed tomography (SPECT), 53 of cochlear implant, 319 of skull base osteomyelitis, 1100 Singular nerve, 950–951, 952f, 953f Singular neurectomy, for benign paroxysmal positional vertigo, 652 Sinus exposure, control of bleeding due to, 713–715, 714f Sinus tympani, 1219f SIT (Smell Identification Test), 216 Skew deviation, 222 Skin flaps, 707, 707f, 708f Skull base central, defined, 383 extracranial anatomy of, 997, 998f, 1054f intracranial anatomy of, 997, 998f, 1002, 1054f lateral. See Lateral skull base. reconstruction of, 706–708, 707f, 708f Skull base lesions classification of, 1005–1006, 1005f direct extension to cerebellopontine angle of, 861–863, 862f, 863f Skull base osteomyelitis (SBO), 1096–1105 in children, 1099 complications of, 1102 diagnosis of, 1098–1099 etiology and pathogenesis of, 1097 imaging of, 1099–1102, 1101f nomenclature for, 1096–1097 of petrous apex, 1117 staging of, 1099 treatment of, 1102–1104 Skull base surgery contemporary concept of, 675–676, 676f fundamental considerations for, 676–680 hemostasis for, 678 history of, 22–25, 23f–25f, 28, 28f, 37–38 instrumentation for, 677–678 for intracranial tumors, 685–706 involving craniovertebral junction, 704–706, 705f, 706f involving internal auditory canal and cerebellopontine angle, 685–699, 685f middle fossa approach to, 694–696, 694f–696f

middle fossa—transpetrous apex approach to, 696–698, 697f retrosigmoid approach to, 686–689, 686f, 687f transpetrosal approaches to, 689–693, 690f, 691f involving intracranial aspect of jugular foramen, 698–699, 698f, 699f involving Meckel’s cave, 704, 704f, 705f involving ventral surface of brainstem, 699–704, 700f, 701f, 703f involving vertebrobasilar lesions, 706, 707f for lesions primarily in cranial base, 680–685 involving clivus, 682f, 683 involving infratemporal fossa, 684–685, 685f involving jugular foramen, 683–684, 683f, 684f involving petrous apex, petroclival junction, and foramen lacerum, 681–683, 681f, 682f involving temporal bone, 680–681, 681f overview of, 675–708 patient positioning for, 676–677, 677f for reconstruction of cranial base, 706–708, 707f, 708f soft tissue reconstruction in, 1004–1025 classification of defects for, 1005–1006, 1005f future developments in, 1024–1025, 1025f historical perspectives on, 1004–1005 local transposition flaps for, 1006–1009, 1006f–1009f microvascular free flaps for, 1011–1018, 1013f–1020f regional transposition flaps for, 1009–1011, 1009f–1012f by site, 1018–1024, 1020t, 1021f–1024f vascularized flap hierarchy for, 1006, 1006t special operating room requirements for, 676 vascular considerations in, 678–680, 679f, 680f Skull base trauma, 1070–1087 anatomy and classification of, 1070–1073, 1071f–1073f cholesteatoma due to, 1083, 1083f of clivus, 1074–1075, 1075f CSF leak due to, 927, 929–931, 1082–1083 facial nerve injury due to, 1077–1082 evaluation of, 1077–1079, 1078t imaging of, 430–431, 433f, 1076, 1079 pathology of, 1077, 1077t surgical management of, 1079–1082, 1079f, 1080t, 1081t hearing loss due to, 596–597, 1084–1086, 1085t histology of, 1073–1074, 1074f imaging of, 1075–1076, 1076f meningitis due to, 1083 patient evaluation for, 1075 pediatric, 1074 vertigo due to, 1086–1087 Skull base tumors, malignant, angiography of, 465 Skull trephination, 10, 11f SLC26A4 gene, 133 Sleeve resection, of external auditory canal tumors, 1031–1032, 1032f SLN (superior laryngeal nerve) examination of, 225 in vocal cord paralysis, 1356 Slow harmonic acceleration test, 617–620, 618f, 619f

1403

Slow release ophthalmic inserts (Lacriserts), 1342, 1342t Small internal auditory canal syndrome, 1318 SMAS (superficial musculo-aponeurotic system), 1276 Smell disorders, in multiple sclerosis, 505 Smell Identification Test (SIT), 216 Smell Threshold Test, 216 Smooth pursuit, 221, 222 Smooth pursuit system (SP), 106–107, 107f, 108, 229 S/N (signal-to-noise) ratios in auditory processing testing, 274 with hearing aids, 1290 SNHL. See Sensorineural hearing loss (SNHL). SO (superior oblique muscle), in vestibuloocular reflex pathway, 99–100, 100f SO (suboccipital) approach, 687 to craniovertebral junction, 1159–1161, 1160f SOC. See Superior olivary complex (SOC). Social rehabilitation, after acoustic neuroma surgery, 768 Sodium etidronate, for Paget’s disease of temporal bone, 1131 Sodium restriction, for Ménière’s disease, 628 Soft tissue(s), of ear, radiation effect on, 1188–1189 Soft tissue reconstruction, in skull base surgery, 1004–1025 classification of defects for, 1005–1006, 1005f future developments in, 1024–1025, 1025f historical perspectives on, 1004–1005 local transposition flaps for, 1006–1009, 1006f–1009f microvascular free flaps for, 1011–1018, 1013f–1020f regional transposition flaps for, 1009–1011, 1009f–1012f by site, 1018–1024, 1020t, 1021f–1024f vascularized flap hierarchy for, 1006, 1006t Solid tumors, of petrous apex, 1121 Somatosensory input, 65 Somatosensory system, in tinnitus, 187, 188 Somatostatin receptors, in paragangliomas, 545 SOT. See Sensory organization test (SOT). Sound conduction, to cochlea, 53–54 Sound lateralization, defined, 274 Sound localization defined, 274 testing of, 276 Sound pressure, 53 Sound pressure level (SPL), with hearing aids, 1287 Sound-activated neural pathways, tinnitus and, 187, 188f Source analysis, 312 Sourdille, Maurice, 34, 34f, 35 Sourdille’s flap, 34 SP (smooth pursuit system), 106–107, 107f, 108, 229 SP (speech processor), for cochlear implant, 1302–1303, 1302f, 1305, 1306, 1307 SP (summating potential), 67, 68, 68f in electrocochleography, 291 Space and motion phobia, 661 Space and motor discomfort, 661 SP/AP (summating potential/action potential) ratio, 291, 292, 292f, 986, 986f Spasmodic dysphonia, 225 Spatial disorientation, 177 due to perilymph fistula, 179 Spatial location inferior colliculus in, 49 superior olivary complex in, 47–48

1404

INDEX

Spatiotemporal source modeling (STSM) advantages and disadvantages of, 315–316 clinical applications of, 316, 318f technical aspects of, 313–315, 314f, 317f–318f Special visceral afferents (SVAs), 1201–1202 SPECT (single-photon emission computed tomography), 53 of cochlear implant, 319 of skull base osteomyelitis, 1100 Spectral peak extraction (SPEAK) coding strategy, 1302, 1306, 1317, 1325 “Spectral sharpening,” 55 Spectrum, of sound, 54n Speech filtered, auditory processing testing of, 274 frequency-altered, auditory processing testing of, 274 time-compressed, auditory processing testing of, 274 Speech audiometry, for acoustic neuroma, 742 Speech discrimination ability, and hearing aids, 1283 Speech discrimination scores (SDS) with acoustic neuroma, 168–170, 169t, 171t, 172, 745 with sensory vs. neural hearing loss, 164 Speech disorders, in multiple sclerosis, 504–505 Speech in competition, auditory processing testing of, 274 Speech Perception in Noise (SPIN) test, 274 Speech processor (SP), for cochlear implant, 1302–1303, 1302f, 1305, 1306, 1307 Speech processor programming for auditory brainstem implant, 1326–1327 for cochlear implant, 1303–1304 Speech reception threshold (SRT) in acoustic neuroma, 169t and hearing aids, 1282, 1282f Speech recognition, with auditory brainstem implant, 1328–1329, 1329f Speech recognition in noise, auditory processing testing of, 274 Speech rehabilitation, after cochlear implantation, 1312 Speech studies, functional MRI in, 322 Speech-coding strategy, for cochlear implant, 1302–1303, 1305, 1306, 1307 Sphenoid bone, 998f, 1054f Sphenoid sinus, 1156f, 1157f Spheno-occipital chordoma. See Clival chordoma. Sphenopalatine ganglion, 1158f SPIN (Speech Perception in Noise) test, 274 Spinal accessory nerve, 225, 893, 893f intraoperative monitoring of, 979f, 980–981 in jugular foramen, 1037–1038, 1038f, 1142 in lateral skull base, 999 and petrous apex, 1108 schwannoma of, 860–861, 861f Spinal accessory-facial anastomoses, 761 Spinal and bulbar muscular atrophy (SBMA), anticipation in, 127 Spinal influences, on vestibulo-ocular reflex, 101–102 Spinal puncture, for hydrocephalus, 527 Spinal tumors, in neurofibromatosis 2, 786, 787, 787f Spinal vestibular nucleus, 77f, 79, 79f Spinal vestibular projections, 86 Spinous process, 1138f, 1139f Spiral ganglion cells (SGCs) development of, 564, 564f effect of cochlear implant on, 576–578, 577f

Spirochetal disorders, vestibular symptoms of, 180 SPL (sound pressure level), with hearing aids, 1287 SPM (significance probability mapping), 311 Spontaneous intracranial hypotension (SIH), 480 Spread of comitance, 235 Sprint speech processor, 1306, 1317, 1324, 1325, 1325f Squamous cell carcinoma (SCCA) from cerebellopontine angle epidermoid cysts, 847 of external auditory canal and temporal bone, 415, 417f, 1030 involving facial nerve, 427 primary intracranial, 866 Squelch, 1285 SQUID (superconducting quantum interference device) magnetometers, 308 SR. See Stereotactic radiosurgery (SR). SR (superior rectus muscle) innervation of, 84, 85f in vestibulo-ocular reflex pathway, 99–100, 99f, 100f SRT (speech reception threshold) in acoustic neuroma, 169t and hearing aids, 1282, 1282f SS. See Superficial siderosis (SS). SSI (Synthetic Sentence Identification) test, 278 SSI-ICM (Synthetic Sentence Identification— Ipsilateral Competing Message) test, 274 SSPL (saturation sound pressure level), with hearing aids, 1287 SSRI(s). See Selective serotonin reuptake inhibitors (SSRIs). SSRI discontinuation syndrome, 669 Stacke, Ludwig, 22 Staderini’s nucleus, 117 Staggered Spondaic Word (SSW) test, 278 Stapedectomy sensorineural hearing loss after, 599 for tinnitus, 191 Stapedial arch, fracture of, 1084t, 1085 Stapedial artery, persistent, 422, 424f, 454, 1206 Stapedial muscle reflex, electrically elicited, 1304 Stapedial reflex measurements, for facial nerve tumors, 1265 Stapedial vein, persistent, 1206 Stapedius muscle innervation of, 220 myoclonic contractions of, pulsatile tinnitus due to, 207, 209 in otalgia, 195 in sound conduction, 53–54 Stapedius reflex, 70–71, 70f, 71f decay of or absent, in cochlear vs. retrocochlear hearing loss, 165–166 Stapes, fracture of, 1084t, 1085 Staphylococcus aureus meningitis due to, 491 osteomyelitis due to, 1096 Staphylococcus epidermidis, osteomyelitis due to, 1096 Static compensation, for peripheral vestibular lesions, 1332 Statoconia, 96–97 with aging, 533 Status epilepticus, management of, 521, 521t Stellate cells, 1048 Stent support, of lower lid, 1345 Stenvers, H., 730

Stepping test, for children, 555 Stereocilia, 75, 76, 76f, 92–94, 93f, 590f Stereotactic navigational systems, 712, 713f, 714f and skull base reconstruction, 1024–1025, 1025f Stereotactic photon-beam radiosurgery, for meningiomas, 836 Stereotactic radiosurgery (SR) for acoustic neuroma, 768–772 audiovestibular function after, 770–771, 772t complications after, 771, 772f cranial nerve function after, 771 equipment for, 768–769, 769f fate of tumor after, 770, 770t, 771f, 771t fractionated, 770, 770t indications for, 772 in neurofibromatosis 2, 788 secondary oncogenesis after, 771, 773t before and after surgery, 772 auditory brainstem implant after, 1324 complications of, 1193 CyberKnife. See CyberKnife stereotactic radiosurgery. for facial nerve tumors, 1267 fractionated, 770, 770t, 1174, 1178f, 1181 Gamma Knife vs., 1164–1165, 1165f for glomus jugulare tumors, 1041–1042 for parasellar and clival neoplasms, 1052 for posterior fossa metastases, 888 for vestibular schwannoma, 360, 360f Sternocleidomastoid muscle, 997, 999f, 1157f innervation of, 225 Steroids. See Corticosteroids. Stevens, S. S., 38 Stickler’s syndrome, hearing loss in, 125, 129t Stimulating electrodes, for cranial nerve monitoring, 962–963, 963f Stimulus frequency otoacoustic emissions (SFOAEs), 287 Stimulus intensity cues, in superior olivary complex, 48 Storage diseases, central processing deficits due to, 579 Stray pattern, in intraoperative facial nerve monitoring, 972 Stream segregation, 66–67 Street neurosis, 661 Streptococcus pneumoniae, meningitis due to, 490, 490t, 491, 496 Streptomycin for Ménière’s disease, 664 ototoxicity of, 251, 593 Stria vascularis, cochlear, 591 Strial presbycusis, 592 Striolae, in otolith organs, 242 Stroke migraine and, 513 postoperative, 718–719, 718f STSM. See Spatiotemporal source modeling (STSM). Styloglossus muscle, 997, 999f Stylohyoid ligament, 999f Stylohyoid muscle, 997, 999f Styloid process, 998f, 1001, 1054f, 1137f Stylomastoid artery, control of bleeding from, 715 Stylomastoid foramen anatomy of, 1137f, 1205 surgical approach to, 1213f, 1217f, 1218–1220, 1220f Stylopharyngeal muscle, 997, 999f Stylopharyngeal septum, 1001 Suarez, E. L., 1004

INDEX

Subarachnoid hemorrhage (SAH) due to aneurysm, 438 hydrocephalus due to, 526 of vestibular schwannoma, 358 Subdural empyema, due to otitis media, 913t, 922–923 Subfrontal-transbasal approach, to craniovertebral junction, 1156, 1156f Subjective vertical visual (SVV) test, 243 Submandibular gland, 1157f Subnucleus caudalis, in otalgia, 194 Suboccipital (SO) approach, 687 to craniovertebral junction, 1159–1161, 1160f Suboccipital craniotomy, CSF leak after, 926–927, 927f Subtemporal approach, 694–696, 694f–696f Subtlety principle, of auditory processing, 280 Suction instruments, 677 Sumatriptan (Imitrex), for migraine, 666 Summating potential (SP), 67, 68, 68f in electrocochleography, 291 Summating potential/action potential (SP/AP) ratio, 291, 292, 292f, 986, 986f Superconducting quantum interference device (SQUID) magnetometers, 308 Superficial musculo-aponeurotic system (SMAS), 1276 Superficial siderosis (SS), 477–479 of cerebellopontine angle, 350, 353f, 369 clinical presentation of, 478–479, 478t, 479f, 479t CSF findings in, 479 etiology of, 478 hydrocephalus due to, 526 imaging of, 479, 479f, 479t incidence of, 477 outcomes for, 479 pathology of, 478 pathophysiology of, 478 treatment for, 479 Superior alveolar nerves, 1158f Superior articular facet, 1138f Superior canal dehiscence syndrome, 179 vestibular evoked myogenic potentials in, 271 Superior canal nerve, 77f, 80 Superior cerebellar artery (SCA), anatomy of, 893, 894, 1145f surgical, 679, 679f Superior colliculus (SC), physiology of, 60 Superior constrictor muscle, myoclonic contractions of, pulsatile tinnitus due to, 207 Superior lacrimal nuclei, 1202f Superior laryngeal nerve (SLN) examination of, 225 in vocal cord paralysis, 1356 Superior laryngeal neuralgia, otalgia due to, 200 Superior oblique muscle (SO), in vestibuloocular reflex pathway, 99–100, 100f Superior oblique myokymia, 234 Superior occipital artery, control of bleeding from, 715 Superior olivary complex (SOC) anatomy of, 45 brainstem auditory evoked potentials in, 69 in central auditory system, 565f, 566, 566f information processing in, 47–48 physiology of, 59, 59f, 60, 62 Superior orbital fissure, 998f, 1002, 1054f Superior orbital rim, 1347f Superior petrosal sinus, 1055f, 1108, 1145f, 1216f

Superior rectus muscle (SR) innervation of, 84, 85f in vestibulo-ocular reflex pathway, 99–100, 99f, 100f Superior sagittal sinus, 1139f Superior salivatory nuclei, 1202f Superior semicircular canal, 1216f Superior semicircular canal dehiscence syndrome (SCD), 244–246, 245f, 399, 403f Superior temporal gyrus, vestibular projections to, 118 Superior thyroid artery, 1157f Superior vestibular nucleus, 77–78, 77f, 78f, 80f, 81f Supermarket syndrome, 661 Suppurative labyrinthitis otolith dysfunction due to, 247 vertigo due to, 556 Supracerebellar cysts, 944, 945f Supraglottic closure, for chronic aspiration, 1361 Supraglottic swallow, 1355 Supranuclear pathways, of facial nerve, 1200, 1201f Supraspinous ligaments, 1054 Suprathreshold asymmetry, acquired, 282 Sural nerve, for facial nerve grafting, 1221, 1221f Surgical drill, 678 Surgical neurotology contemporary concept of, 675–676, 676f fundamental considerations for, 676–680 hemostasis for, 678 instrumentation for, 677–678 for intracranial tumors, 685–706 involving craniovertebral junction, 704–706, 705f, 706f involving internal auditory canal and cerebellopontine angle, 685–699, 685f middle fossa approach to, 694–696, 694f–696f middle fossa-transpetrous apex approach to, 696–698, 697f retrosigmoid approach to, 686–689, 686f, 687f transpetrosal approaches to, 689–693, 690f, 691f involving intracranial aspect of jugular foramen, 698–699, 698f, 699f involving Meckel’s cave, 704, 704f, 705f involving ventral surface of brainstem, 699–704, 700f, 701f, 703f involving vertebrobasilar lesions, 706, 707f for lesions primarily in cranial base, 680–685 involving clivus, 682f, 683 involving infratemporal fossa, 684–685, 685f involving jugular foramen, 683–684, 683f, 684f involving petrous apex, petroclival junction, and foramen lacerum, 681–683, 681f, 682f involving temporal bone, 680–681, 681f overview of, 675–708 patient positioning for, 676–677, 677f for reconstruction of cranial base, 706–708, 707f, 708f special operating room requirements for, 676 vascular considerations in, 678–680, 679f, 680f Surgicel (oxidized cellulose), 678 Susceptibility, 128 Sushruta, 1004 SVAs (special visceral afferents), 1201–1202

1405

SVV (subjective vertical visual) test, 243 Swallowing, 225 deficits in, 1351–1352 as complication of neurotologic surgery, 724 evaluation of, 1352–1354 treatment of, 1354–1356 normal stages of, 1350–1351 Sweating, gustatory, 1210 Sylvester’s disease, central processing deficits with, 578 Sympathectomy, for tinnitus, 191 Symptoms, of neurotologic disease, 229–230 Synaptic jitter, 58 Syncope, 177–178, 177t Syndrome of inappropriate antidiuretic hormone (SIADH), seizures due to, 519 Syndromic hearing loss, 129t–130t Synkinesis, after facial nerve injury, 1210 Synostoses, 1146–1147, 1147f Synthetic Sentence Identification (SSI) test, 278 Synthetic Sentence Identification—Ipsilateral Competing Message (SSI-ICM) test, 274 Syphilis cerebellopontine angle lesions due to, 857–858 hearing loss due to, 598–599 vs. Ménière’s disease, 627, 627f otologic, 249–250 vestibular symptoms of, 180 pharmacotherapy for, 664–665 Syphilitic labyrinthitis, 334, 336, 336f Syringomyelia, in Chiari malformation, 1146 Syrinx, 237 Systemic disease, vertigo due to, in children, 560

T Taenia, 1324 Tandem walking, 225 Tansini, Iginio, 1005 Taping, of eyes, 1342, 1343t Tarsorrhaphy, 1344, 1344f, 1345 for facial palsy, 761 Tarsus, 1346f Taste buds, 219–220 Taste disorders, in multiple sclerosis, 505 Taylor, G. I., 1005 TC (transcochlear) approach, 685f, 686, 702–704, 703f tcMEP (transcranial motor evoked potential), 988 TCST (Time Compressed Sentence Test), 274 TDF (tongue driving force), 1354, 1356 Tear(s) artificial, 1341–1342, 1342t increased evaporation of, 1340 Tear drainage system, surgical closure of, 1347 Tear film, 1340 Tear lacus, 1340 Tearing crocodile, 1210 excessive, 1340–1341 inadequate, 1340, 1341 while chewing, 1340, 1343 Technetium scan, for skull base osteomyelitis, 1100 Tectorial membrane, 1054, 1054f, 1137 Tectorial membrane matrix, genetic defects in, 602 Teflon injection, for vocal cord paralysis, 1357–1358, 1358f Tegmen, during mastoidectomy, 1273 Tegmen tympani, 1002

1406

INDEX

Teichopsia, in migraine, 514 Tela, 1141f Telangiectasia, 934 Tempo+ speech processor, 1307 Temporal arteritis otalgia due to, 202 vestibular symptoms of, 180 Temporal bone anatomy of, 1028–1029 diffuse osseous lesions of, 1125–1133 Eustachio’s illustrations of, 4f and facial nerve, 1202–1205, 1203f, 1204f fibrous dysplasia of, 1125–1127, 1126f, 1127f, 1132t, 1133t invasion by meningioma of, 147–148, 147f, 148f mastoid portion of, 1028 metastasis to, 150–151, 150f, 151f osteogenesis imperfecta of, 1131–1133, 1132f, 1132t, 1133t osteopetroses of, 1127–1129, 1128f, 1132t, 1133t osteoradionecrosis of, 1187–1188, 1188f, 1189f Paget’s disease of, 1129–1131, 1130f, 1132t, 1133t petrous portion of, 998f, 1002, 1028, 1054f squamous portion of, 1028 tympanic portion of, 1028 in vestibular schwannoma, 145 Temporal bone encephalocele, 1089–1094 causes of, 1089 clinical presentation of, 1090–1091, 1091f congenital, 1089 epidemiology of, 1089 iatrogenic, 1090 idiopathic, 1089–1090 nontraumatic (spontaneous), 1089–1090 pathogenesis of, 1089–1090 radiology of, 1091–1092, 1091f, 1092f surgical treatment of, 1092–1094, 1093f Temporal bone fracture(s). See also Temporal bone trauma. facial nerve repair after, 1215, 1216f, 1217f longitudinal, 1071, 1071f, 1072f mixed and oblique, 1072 otic capsule—sparing and otic capsule— disrupting, 1072–1073, 1074, 1077, 1082 transverse, 1071–1072, 1072f Temporal bone resection, 680–681, 681f background of, 1028 lateral, 1032–1033, 1032f, 1033f sleeve, 1031–1032, 1032f subtotal, 1033–1034, 1034f total, 1034 Temporal bone trauma, 1070–1087 anatomy and classification of, 1070–1073, 1071f–1073f cholesteatoma due to, 1083, 1083f CSF leak due to, 927, 929–931, 1082–1083 facial nerve injury due to, 1077–1082 evaluation of, 1075, 1077–1079, 1078t imaging of, 430–431, 433f, 1076, 1079 pathology of, 1077, 1077t surgical management of, 1079–1082, 1079f, 1080t, 1081t hearing loss due to, 596–597, 1084–1086, 1085t histology of, 1073–1074, 1074f imaging of, 1075–1076, 1076f meningitis due to, 492, 492f, 493f, 1083 pathogenesis of, 1070–1071 patient evaluation for, 1075 pediatric, 1074 penetrating vs. blunt, 1070, 1073, 1073f vertigo due to, 179, 1086–1087

Temporal bone tumor(s), 1028–1035 clinical management of, 1031–1034 diagnostic evaluation of, 1029–1030, 1029t, 1030t involving facial nerve, 1261–1262 pathobiology of, 1030–1031, 1030t, 1031t radiation therapy for, 1034 resection of background of, 1028 lateral, 1032–1033, 1032f, 1033f sleeve, 1031–1032, 1032f subtotal, 1033–1034, 1034f total, 1034 staging of, 1029, 1029t, 1030t Temporal integration, defined, 274 Temporal lobe seizures, vestibular symptoms of, 181 Temporal masking, defined, 274 Temporal nerve, 1224f Temporal ordering, defined, 274 Temporal processing disorders, gap detection tests for, 274 Temporal representation, of frequency, 57, 57f, 58 Temporal resolution, defined, 274 Temporal venous infarction, postoperative, 718f Temporalis fascia, 1006f Temporalis muscle, 997, 999f, 1006f Temporalis muscle rotation flap, 707, 707f, 1007–1009 Temporally based programs, for cochlear implant, 1302–1303 Temporomandibular disorders (TMD), otalgia due to, 197–198 Temporomandibular joint (TMJ) pain, otalgia due to, 197–198 Temporoparietal fascia, 1006, 1006f Temporoparietal pericranial flap, 1007, 1007f–1009f, 1008–1009 TENS (transdermal electric nerve stimulation), for tinnitus, 189 Tension pneumocephalus due to acoustic neuroma surgery, 756 due to temporal bone encephalocele, 1091 Tension-type headache, otalgia due to, 201 Tensor palati muscle, innervation of, 195 Tensor tympani muscle in acoustic middle ear reflex, 70–71 and facial nerve, 1204f, 1217f, 1219f, 1271f myoclonic contractions of, pulsatile tinnitus due to, 207, 209 in otalgia, 195 in sound conduction, 53 tendon of, 1204f, 1218f, 1271f Tensor veli palatini muscle, 997, 999f myoclonic contractions of, pulsatile tinnitus due to, 207 Tentorial artery, 1055f Tentorial notch, 701 Tentorium, dural arteriovenous fistulas of, 444 Tentorium cerebelli, 700 TEOAEs (transiently evoked otoacoustic emissions), 287, 288, 289f Teratomas, of cerebellopontine angle, 853, 866–867 Terminal boutons, 1206, 1208f Test-retest reliability, of dynamic posturography, 259 Tetracycline, for otosyphilis, 665 TGN. See Trigeminal neuralgia (TGN, TN). Thalamus, 1201f Thalidomide, congenital hearing loss due to, 594 “Therapeutic gene,” 138–141, 139t Thermal stimulation, 1355

THI (Tinnitus Handicap Inventory), 622 Thiamine, for status epilepticus, 521t Thiazide diuretics, for Ménière’s disease, 661 Third nerve palsy, 217 Thorazine (chlorpromazine), for vestibular dysfunction, 669, 669t Three-dimensional conformation radiation therapy (3D CRT), 1182 Threshold, of cochlear implant, 1304 Thrombophlebitis, dural venous sinus, due to otitis media, 913t, 918–919, 919f Thrombosis cavernous sinus, 217 of internal auditory artery, vestibular symptoms of, 181 jugular vein, 409–410, 413f venous sinus, 400, 404f, 409–410, 413f Thyroid disease, dizziness due to, 560 Thyroid tumors, radiation-induced, 1192 Thyroplasty, for vocal cord paralysis, 1357t, 1359, 1359f TIAs (transient ischemic attacks) vs. migraine, 512–513 pharmacotherapy for, 666–667 Tic convulsif, 903, 905 Tic douloureux. See Trigeminal neuralgia (TGN). Ticlopidine (Ticlid), for vertebrobasilar insufficiency, 666 Tilt, in environment, 234, 236 Time Compressed Sentence Test (TCST), 274 Time-compressed speech, auditory processing testing of, 274 Tinnitus, 182–191 due to abnormalities in auditory nerve or ascending auditory pathway, 185 due to abnormalities in ear, 185 due to acoustic neuroma clinical manifestations of, 740 effect of tumor removal on, 184, 766 percentage of patients with, 167, 168t, 171t, 739t, 740 as presenting symptom, 167t, 185 and affective disorders, 188–189 benign, 182–183 due to cerebellopontine angle meningioma, 808 due to cochlear injury, 185 due to functional changes in auditory brainstem nuclei, 186–187 functional MRI for, 322 due to injuries to auditory nervous system, 185–186 interaction of other sensory systems with, 188 location of anatomic abnormality that causes, 184–185 due to Ménière’s disease, 621, 622, 623 due to microvascular decompression, 184 due to multiple sclerosis, 503 and neural pathways activated by sound, 187, 188f and neuropathic pain, 184, 187 noise-induced, 184 objective, 182 and other phantom sensations, 188 due to ototoxic agents, 184, 185 positron emission tomography for, 318–319 due to posterior fossa meningioma, 173 pulsatile, 204–211 cause(s) of, 182, 204–207, 216 arterial, 204–205, 206t atherosclerotic carotid artery disease as, 204, 208, 208t, 209 dural arteriovenous fistula as, 443 glomus tumor as, 208, 208t, 209–211, 1039

INDEX

Tinnitus (Continued) intracranial vascular abnormalities as, 204–205, 205f, 208, 208t, 209, 210f nonvascular, 207 otosclerosis as, 209 palatal, stapedial, and tensor tympani muscle myoclonus as, 207, 209 pseudotumor cerebri syndrome as, 205–207, 206t, 207f, 208, 208t, 209 venous, 205–207, 206t, 207f, 207t evaluation of, 208–209, 208t, 210f idiopathic (essential), 207, 209 illustrative case histories of, 205, 205f internal jugular vein in, 204 management of, 209–211, 210f objective vs. subjective, 204 pathophysiology and classification of, 204–208, 205f, 206t, 207f, 207t quantification of, 183–184 subjective defined, 182 nature of, 183 pathogenesis of, 184 pathophysiology of, 184–189 treatment of, 189–191 due to vascular compression, 184, 185–186, 187 Tinnitus Handicap Inventory (THI), 622 Tinnitus retraining (TRT), 189 Tiptrode, 290, 982 TL approach. See Translabyrinthine (TL) approach. TMD (temporomandibular disorders), otalgia due to, 197–198 TM-ECHochGtrode, 290 TMJ (temporomandibular joint) pain, otalgia due to, 197–198 TN. See Trigeminal neuralgia (TGN, TN). TO (transotic) approach, 702, 703 to acoustic neuroma, 747 Tobramycin, ototoxicity of, 593 Toby-Ayer test, 918 Tocainide, for tinnitus, 190 Tongue, examination of, 225–226 Tongue driving force (TDF), 1354, 1356 Tonic activity, in intraoperative facial nerve monitoring, 972, 973, 973f, 988 Tonic cells, 105, 106f Tonic labyrinth reflexes, 115–116, 115f Tonic neck reflexes, 115–116, 115f Tonic vestibular pause cell, 106f Tonotopy, in inferior colliculus, 48–49 Tonsil, 1144f Topical otic preparations, hearing loss due to, 594 Topognostic testing, of facial nerve, 1244–1245 Topographic mapping, 310–312 Topographic testing, of facial nerve, 1078 Torok, Nicholas, 39 Torsion vestibulo-ocular reflex (tVOR), 100–101 Torticollis, paroxysmal, of infancy, 557, 559 Towne, E., 730 Toxicity facial palsy due to, 1231t oto-. See Ototoxicity. vertigo due to, in children, 561 vestibulo-, 560 Toxoplasmosis, 237 congenital, hearing loss due to, 598 Toynbee, Joseph, 15, 16–18, 16f, 19, 20 Toynbee tube, 216 Tracheotomy, for swallowing dysfunction, 1356 Tracking test, 608, 616, 616f

Traction and inflammatory headache, otalgia due to, 201–202 Tractus de Aure Humana (Treatise of the Human Ear), 8, 8f Tractus solitarius, 1202f “Train” activity, in intraoperative facial nerve monitoring, 972, 973, 973f, 988 Traite de l’organe de l’ouie (Treatise on the Organ of Hearing), 6, 6f, 7f Transantral-transnasal approach, to clival tumors, 1056 Transbasal approaches, to intracranial tumors, 685–706 involving craniovertebral junction, 704–706, 705f, 706f involving internal auditory canal and cerebellopontine angle, 685–699, 685f middle fossa approach, 694–696, 694f–696f middle fossa-transpetrous apex approach, 696–698, 697f retrosigmoid approach, 686–689, 686f, 687f transpetrosal approaches, 689–693, 690f, 691f involving intracranial aspect of jugular foramen, 698–699, 698f, 699f involving Meckel’s cave, 704, 704f, 705f involving ventral surface of brainstem, 699–704, 700f, 701f, 703f involving vertebrobasilar lesions, 706, 707f Transcanal labyrinthectomy, for Ménière’s disease, 631 Transcervical approach, to craniovertebral junction, 1156–1158, 1157f Transcervical-retropharyngeal approach, for clival tumors, 1062–1063, 1062f, 1063f Transcochlear (TC) approach, 685f, 686, 702–704, 703f Transcranial motor evoked potential (tcMEP), 988 Transcranial stimulation, of facial nerve, 1248–1249 Transdermal electric nerve stimulation (TENS), for tinnitus, 189 Transdermal scopolamine (Transderm-Scop), for motion sickness, 670 Transdural-middle fossa resection, for facial nerve tumors, 1266–1267 Transgene expression, intracochlear, 138–141, 139t Transient ischemic attacks (TIAs) vs. migraine, 512–513 pharmacotherapy for, 666–667 Transiently evoked otoacoustic emissions (TEOAEs), 287, 288, 289f Transit time, 1354 Transition zone (TZ), between peripheral and central nervous system, 893, 895, 895f, 900 Transjugular craniotomy, 698–699, 699f Translabyrinthine (TL) approach to acoustic neuroma, 691, 691f, 747, 748, 749f, 1275–1276 to facial nerve, 693, 1213–1214, 1213f, 1214f to internal auditory canal and cerebellopontine angle, 685f, 686, 691–693 advantages of, 693 disadvantages of, 693 indications for, 691–692, 691f surgical exposure in, 691, 691f technical considerations with, 692–693 Translabyrinthine (TL) craniotomy, 691f, 692–693

1407

Translabyrinthine surgery, CSF leak after, 926 Translabyrinthine vestibular nerve section, for Ménière’s disease, 632 Translabyrinthine/suboccipital approach, to vestibular schwannoma, in neurofibromatosis 2, 788 Translabyrinthine-transcochlear approaches, to facial nerve tumors, 1267 Transmantle pressure, 525 Transmastoid approach, to facial nerve, 1215–1218, 1217f–1219f, 1266 Transmastoid labyrinthectomy history of, 33–34 for Ménière’s disease, 632 Transmastoid-middle cranial fossa approach, for facial nerve tumors, 1266 Transmastoid/middle fossa approach, for temporal bone encephalocele, 1093, 1093f Transoral approach, to craniovertebral junction, 1155–1156, 1155f Transoral-transpalatal approach, for clival tumors, 1056–1058, 1056f, 1057f Transotic (TO) approach, 702, 703 to acoustic neuroma, 747 Transpalatal approach, for clival tumors, 1058, 1058f, 1059f Transpetrosal approach, to internal auditory canal and cerebellopontine angle, 686, 689–693 retrolabyrinthine, 685f, 686, 689–691, 690f translabyrinthine, 685f, 686, 691–693, 691f Transposition flaps, for skull base reconstruction local, 1006–1009, 1006f–1009f regional, 1009–1011, 1009f–1012f Transseptal-transsphenoidal approach, for clival tumors, 1056 Transsphenoidal approach, to craniovertebral junction, 1156, 1157f Transtemporal approach, to internal auditory canal and cerebellopontine angle, 686, 689–693 retrolabyrinthine, 685f, 686, 689–691, 690f translabyrinthine, 685f, 686, 691–693, 691f Transtemporal-middle fossa procedures, 700 Transtympanic stimulation, of facial nerve, 1248 Transverse crest, 1203f Transverse foramen, 1138f Transverse ligament, 1054, 1137, 1138f Transverse process, 1138f Transverse sinus bleeding from, during neurotologic surgery, 715 dural arteriovenous fistulas of, 443, 934–935, 935f Trapezius muscle, 1160f innervation of, 225 Trapezius myocutaneous flap, 707, 708f Trapezoid body in brainstem auditory pathway, 45, 46f tuning curves from, 60f Trapezoidal fibers, myelination of, 567, 568f Trauma aneurysms due to, 439, 442f CSF leak due to, 927, 929–931 to facial nerve, 430–431, 433f facial palsy due to, 1231t neuromas due to, 1260 Ménière’s disease due to, 626 meningiomas due to, 794 otolith dysfunction due to, 242 pseudoaneurysms due to, 438 to skull base. See Skull base trauma. temporal bone. See Temporal bone trauma.

1408

INDEX

Trauma (Continued) vertigo due to, 249 benign paroxysmal positional, 249, 646 cervical proprioceptive function and, 541, 541t in children, 557–558 with perilymph fistula, 1086–1087 with temporal bone fracture, 179, 1086–1087 vestibular dysfunction due to, 179 Treacher Collins syndrome, hearing loss in, 129t Treatise on the Organ of Hearing, 6, 6f, 7f Trendelenburg, Friedrich, 25 Trental (pentoxifylline), for vertebrobasilar insufficiency, 666 Treponema pallidum, 249–250 Triamterene (Dyazide), for Ménière’s disease, 628 Tricyclic antidepressants for psychophysiologic dizziness, 667 for vestibular migraine, 665–666 Trigeminal impression. See Meckel’s cave. Trigeminal nerve, 218–219, 218f in cerebellopontine angle, 893, 893f intraoperative monitoring of, 978–979 in lateral skull base, 998 nucleus of, 1202f ocular functions of, 1339, 1341 in parasellar and cavernous sinus region, 1055, 1055f and petrous apex, 1108 Trigeminal nerve artifact, 1224–1225 Trigeminal nerve dysfunction due to acoustic neuroma, 739t, 740, 745 due to cerebellopontine angle meningioma, 808 Trigeminal nerve injury, swallowing disorder due to, 1351 Trigeminal nerve sheath tumors. See Trigeminal neuromas. Trigeminal neuralgia (TGN, TN), 902–905 clinical features of, 903 diagnostic evaluation of, 904 with glossopharyngeal neuralgia, 903 with hemifacial spasm, 903, 905 histopathology of, 898 historical background of, 902–903 idiopathic (primary, essential, major), 903, 904 microvascular decompression for, 190, 904–905 in multiple sclerosis, 505 otalgia due to, 199 pathophysiology of, 897 prevalence of, 903 site of lesion for, 903–904 symptomatic, 903–904 and tinnitus, 184, 186–187 treatment for, 904–905 trigger for, 199, 903 Trigeminal neuromas of foramen ovale and cavernous sinus, 1051f of petrous apex, 396, 400f Trigeminal schwannoma of cerebellopontine angle, 366, 366f, 859–860, 860f MRI of, 714f surgical approach to, 704f, 705f Trigeminofacial reflex, 1249 Trigger, for trigeminal neuralgia, 199, 903 Trigger points, myofascial, 198, 201 Trinucleotide repeat expansion, 127 Triptans, for migraine, 515 Trisomy 13, central processing deficits with, 578

Trisomy 18, central processing deficits with, 578 Trisomy 21, central processing deficits with, 578 Trochlear nerve, 217, 1055, 1055f intraoperative monitoring of, 976–978, 977f Trochlear nucleus anatomy of, 84, 84f, 85 in vestibulo-ocular reflex pathway, 100, 100f Trophic function, loss of, 1341 Tropia, 235–236 TRT (tinnitus retraining), 189 Tryptophan, metabolism of, 543, 544t Tuberculoma, of cerebellopontine angle, 857 Tullio’s phenomenon, 224, 242, 243, 245, 399 Tumarkin otolithic crisis, 242, 622 Tumors. See Neoplasm(s). Tumors of the Nervus Acusticus and the Syndrome of the Cerebello-Pontine Angle, 28, 28f Tuning curves, 55, 55f–57f, 56, 57 in cochlear nucleus, 60, 60f in inferior colliculus, 60f, 63, 63f in trapezoidal body, 60f Tuning fork tests, 220–221 tVOR (torsion vestibulo-ocular reflex), 100–101 Two-tone inhibition, 57 Tympanic branch, in otalgia, 195 Tympanic membrane anatomy of, 1219f, 1220f perforation of, mechanism of hearing impairment in, 53 in sound conduction, 53 Tympanic plexus, 1218f in otalgia, 195 Tympanic ring, 1028 Tympanic segment, of facial nerve, 219, 1204 surgical approach to, 1215–1218, 1217f–1219f Tympanogenic labyrinthitis, 151 Tympanomastoid approach, to facial nerve, 1215–1218, 1217f–1219f Tympanomastoid surgery, CSF leak after, 926 Tympanometry, 53 Tyrosine, metabolism of, 543, 544t TZ (transition zone), between peripheral and central nervous system, 893, 895, 895f, 900

U Ultrasonic aspirator, 678 Ultrasound studies, for pulsatile tinnitus, 209 Unasyn (ampicillin sodium and sulbactam), for wound infections, 721 Uncrossed olivocochlear bundle (UOCB), 66 Underwater diving, labyrinthine hemorrhage due to, 246 University of Cincinnati grading system, for external auditory canal tumors, 1030t Unmasking, of dormant synapses, 187 Unsteadiness, 177 Upbeat nystagmus, 232, 612, 613f Upper eyelid entropion repair of, 1345 gold weights for, 1346 incomplete closure of, 1340 palpebral spring for, 1346, 1346f–1347f poor position of, 1340 silastic elastic prosthesis for, 1346, 1348f surgical techniques to animate, 1345–1346, 1346f–1348f Urinary abnormalities, due to craniovertebral junction anomalies, 1148 Use gain, with hearing aids, 1286 Usher syndrome, hearing loss in, 129t–130t

Utricle aging effect on, 533 anatomy of, 221f, 242–243, 242f in otolith-ocular reflexes, 241 Utricular function, assessment of, 243 Utricular macula orientation of, 96, 96f reflex projections of, 82f Utricular nerve, 76, 77f, 81f Utricular neuron, static response to various positions in sagittal plane of, 97, 97f Uvula, 1141f

V Vaccinia vector, 139t Vagal neuralgia, otalgia due to, 200 Vaginal adenocarcinoma, metastatic to cerebellopontine angle, 866 Vagus nerve anatomy of, 893, 893f in craniovertebral junction, 1142 intraoperative monitoring of, 979–980, 979f, 980f in jugular foramen, 1037–1038, 1038f in lateral skull base, 999 in parasellar and cavernous sinus region, 1055f and petrous apex, 1108 physiology of, 225 Vagus nerve injury swallowing disorder due to, 1351–1352 symptoms of, 225 Vagus nerve sheath tumor, imaging of, 409f Vagus schwannomas, 366–367, 860–861 Valacyclovir (Valtrex), for Ramsay Hunt syndrome, 668 Valium. See Diazepam (Valium). Valproic acid (Depakene) for migraine prophylaxis, 515 for vestibular migraine, 666 Valsalva, Antonio Maria, 5, 7–9, 7f, 8f, 15 Valsalva maneuver, 8f, 9, 235 van Leeuwenhoek, Anton, 6, 7, 29 Vancomycin hydrochloride, for wound infections, 721 Variable expressivity, 123, 124–125 Varicella-zoster virus (VZV) herpes zoster oticus due to, 1237 postherpetic neuralgia due to, 200 Varix, 934 Vascular causes, of facial palsy, 1231t Vascular compression syndrome(s), 892–908 anatomic considerations for, 892–895, 893f, 894t, 895f of cochleovestibular nerve, 906–908, 906f, 906t, 907f defined, 892 geniculate neuralgia as, 905–906 glossopharyngeal neuralgia as, 905 hemifacial spasm as, 901–902 histopathology of, 898–899 vs. Ménière’s disease, 628 microvascular decompression for, 899–901, 899f, 900f pathophysiology of, 895–899, 896f, 897f tic convulsif as, 905–906 tinnitus due to, 184, 185–186, 187 trigeminal neuralgia as, 902–905 Vascular considerations, with neurotologic surgery, 678–680, 679f, 680f Vascular contrast agents, blood perfusion imaging using, 320 Vascular disorders, vestibular symptoms of, 181 Vascular lesions, of cerebellopontine angle, 349–350, 352f, 367–369, 368f, 369f, 863–865, 864f

INDEX

Vascular loop syndrome. See Cochleovestibular nerve compression syndrome (CNCS). Vascular management, in neurotologic surgery, 713–717 arterial, 715–717, 715f, 716f venous, 713–715, 714f Vascular symptoms, of craniovertebral junction anomalies, 1148 Vascular tumors benign, of petrous apex, 393, 398f intracanalicular, 373, 374f, 375f involving facial nerve, 425–426, 428f, 429f Vasodilators for idiopathic sudden sensorineural hearing loss, 596 for Ménière’s disease, 628–629, 662 Vasovagal reactions, dizziness due to, 560 VBD (vertebrobasilar dolichoectasia), 352f, 367–368, 368f VCN. See Ventral cochlear nucleus (VCN). VCR (vestibulocollic reflex), 114–115, 540 Vection, 107 Vein(s), of lateral skull base, 997–998 Vein of cerebellopontine fissure, 1145f Vein of Galen, dural arteriovenous fistulas of, 444 Vein of Labbé, 679–680, 679f, 680f, 702 Velocity storage system, 94 VEMP. See Vestibular evoked myogenic potentials (VEMP). Venography, 437–438 of meningiomas, 458–459 Venous bleeding, during neurotologic surgery, control of, 713–715, 714f Venous hum, 207 Venous infarction, due to acoustic neuroma surgery, 754 Venous malformation, 934 Venous sinus occlusion, postoperative, 718 Venous sinus thrombosis, 400, 404f, 409–410, 413f Ventral cochlear nucleus (VCN) anterior anatomy of, 60, 60f development of, 565, 565f, 566 effect of cochlear implant on, 577 with auditory brainstem implant, 1323–1324 in brainstem auditory pathway, 45, 46f, 47 posterior, 60, 60f development of, 565, 565f Ventral medial geniculate body (vMGB), in ascending pathway, 58–59, 64 Ventral nucleus of lateral lemniscus (VLL) in brainstem auditory pathway, 565f, 566f in information processing, 48 Ventricular shunts, for hydrocephalus, 527 Ventriculoatrial shunt, for hydrocephalus, 527, 529f Ventriculoperitoneal shunt, for hydrocephalus, 527, 528, 528f Ventriculostomy, for hydrocephalus, 528 Ventroposteroinferior nucleus (VPI), 118 Ventroposterolateral nucleus (VPL), 118 VEPs (visual evoked potentials), in multiple sclerosis, 504, 505 Verapamil, for vestibular migraine, 666 Vermian tumors, 370 Vermis, 1142 Vernet’s syndrome due to jugular foramen meningioma, 822 due to skull base osteomyelitis, 1102 Verocay body, 733, 733f, 1259 VERs (visual evoked responses), in multiple sclerosis, 504, 505

Vertebral artery in craniovertebral junction, 1140f, 1141f, 1142, 1143f–1145f, 1160f groove for, 1138f in lateral skull base, 999f Vertebral artery stenosis, 216 Vertebral fistulas, 452, 453f Vertebral venous plexus, 1143f, 1145f Vertebrobasilar aneurysms, 368–369, 368f, 369f Vertebrobasilar dolichoectasia (VBD), 352f, 367–368, 368f Vertebrobasilar insufficiency in elderly, 536 pharmacotherapy for, 662t, 666–667 Vertebrobasilar ischemia, vestibular symptoms of, 181 Vertebrobasilar junction, 1155f Vertebrobasilar lesions, surgical approach to, 706, 707f Vertical acceleration test, in infants, 555 Vertical diplopia, 243 Vertical eye movements, 84, 84f, 85 Vertical segment, of facial nerve, 1204 surgical approach to, 1215–1218, 1217f–1219f Vertiginous seizures, in children, 559 Vertigo due to acoustic neuroma, 739t, 740 benign paroxysmal of childhood, 557, 559 positional (postural). See Benign paroxysmal positional vertigo (BPPV). benign positional, of childhood, 665 benign recurrent, migraine with, 511–512 central causes of, 659–661, 660t due to central nervous system disorders, 177, 180–181 due to cerebellopontine angle meningioma, 808 cervical, 181, 540–542 cervical proprioceptive function and, 540 clinical evidence of, 540–541, 541t defined, 540 differential diagnosis of, 541, 541t in elderly, 537 treatment for, 541–542 in childhood, 553–561 due to ataxia, 560 benign paroxysmal, 557, 559 benign positional, 665 with congenital and hereditary hearing loss, 556 with congenital anomalies, 556 due to congenital nystagmus, 560 development of vestibular system and, 553–554 diagnosis of, 554–556 functional, 561 due to labyrinthitis, 556, 559 due to Ménière’s disease, 557 due to meningitis, 559 due to metabolic/systemic disease, 560 due to migraine, 557, 559 due to multiple sclerosis, 560 due to neurosyphilis, 560 due to otitis media, 556–557 due to perilymphatic fistula, 558–559 toxic, 561 due to trauma, 557–558 due to tumors, 559–560 due to vertiginous seizures, 559 vestibular, 522 due to vestibular neuronitis, 559 due to cochleovestibular nerve compression syndrome, 906, 906t common causes and mechanisms of, 659–661, 660t

1409

defined, 177 disabling positional, 906, 906t dizziness due to, 660t in elderly, 534–537, 535t, 536t due to endolymphatic hydrops, 178–179 epidemic. See Vestibular neuritis (VN). historical background of, 14–15 due to labyrinthine hemorrhage, 179–180 due to labyrinthitis, 247 acute, 178 toxic, 177 due to Ménière’s disease, 177, 179, 621, 622, 623 due to metabolic derangements, 180 migraine with, 181, 513 during aura, 514 benign paroxysmal positional, 511 benign recurrent, 511–512 vs. Ménière’s disease, 628 onset and duration of, 177 due to perilymph fistula, 179, 1086–1087 peripheral causes of, 659, 660t pharmacotherapy for, 659–670, 662t for specific etiologies, 661–668, 662t symptomatic, 668–670, 669t positional (postural) benign of childhood, 665 paroxysmal. See Benign paroxysmal positional vertigo (BPPV). disabling, 906, 906t after radiation therapy, 1190 rotational, in elderly, 535 severity of, 177 due to superior canal dehiscence syndrome, 179 due to trauma, 249 benign paroxysmal positional, 249, 646 cervical proprioceptive function and, 541, 541t in children, 557–558 with perilymph fistula, 1086–1087 of temporal bone, 179, 1086–1087 due to vestibular disease, 177 whirling, 179 Vesalian revolution, 3 Vesalius, Andreas, 3, 3f Vestibular adaptation, 1332 Vestibular aqueduct, 525–526 large, 133, 332 endolymphatic hydrops due to, 345 hearing loss due to, 601 vertigo with, 556 Vestibular centers, higher central, 87 Vestibular compensation assessment of, 1333–1334 dynamic, 1332–1333 functional, 1334 physiologic, 1333–1334 static, 1332 symptoms during stages of, 176–177, 176t Vestibular decompensation, 1333, 1335 Vestibular disorders due to acoustic neuroma, 739t, 740 with aging, 533–537 due to alterations in function, 534 cervical vertigo as, 537 epidemiology of, 533 evaluation of, 535–536, 535t, 536t labyrinthine disorders as, 536 other otologic and neurotologic disorders as, 536–537 presbystasis as, 534–535, 535t due to structural changes, 533–534, 534t due to systemic disorders, 537

1410

INDEX

Vestibular disorders (Continued) treatment and rehabilitation for, 537 vertebrobasilar insufficiency as, 536 autonomic dysfunction with, 661 common causes and mechanisms of, 659–661, 660t central, 659–661, 660t peripheral, 659, 660t developmental effects of, 556 dynamic posturography for, 262, 262t, 263t due to meningitis, 494 in multiple sclerosis, 181, 501–503, 502f pharmacotherapy for, 659–670, 662t for specific etiologies, 661–668, 662t symptomatic, 668–670, 669t primary vs. secondary, 176 symptom(s) of, 176–181, 176t, 177t acute, 176 chronic or progressive, 176 with CNS dysfunction, 180–181 dizziness as, 177 episodic, 176 imbalance as, 177 with labyrinth dysfunction, 178–180 syncope as, 177–178, 178t vertigo as, 177 with vestibular nerve dysfunction, 180 Vestibular drop attacks, otolith dysfunction in, 242 Vestibular efferents, 98 Vestibular epithelium, aging effect on, 533, 534t Vestibular evoked myogenic potentials (VEMP), 270–272 basic physiology of, 270 clinical applications of, 271 defined, 270 discovery of, 270 future directions for, 271–272 measurement of, 270–271, 271f normal, 271, 271f Vestibular exercise programs, for elderly, 537 Vestibular function with acoustic neuropathy, 473 aging effect on, 534 after stereotactic surgery, 770–771 Vestibular glomus tumors, molecular genetics of, 134–138 Vestibular habituation therapy, for benign paroxysmal positional vertigo, 648 Vestibular migraine, pharmacotherapy for, 662t, 665–666 Vestibular nerve anatomy of, 76–77, 77f, 221f, 950–951, 950f, 951f central termination of, 80–81, 81f evoked potentials to stimulation of, 987 inferior anatomy of, 950, 950f, 951, 951f and facial nerve, 1203f during vestibular neurectomy, 952, 952f, 953f superior anatomy of, 950, 950f, 951, 951f, 1216f and facial nerve, 1203f during vestibular neurectomy, 952, 952f, 953f symptoms of disorders of, 180 Vestibular nerve function, vestibular evoked myogenic potentials and, 271 Vestibular nerve section (VNS). See Vestibular neurectomy (VN). Vestibular neurectomy (VN), 949–957 anatomic basis for, 950–951, 950f, 951f for cochleovestibular nerve compression syndrome, 907

combined retrolabyrinthine-retrosigmoid approach for, 955, 955f, 955t, 956 complications of, 956–957 in elderly patients, 950 historical perspective on, 949 indications and contraindications for, 949–950 for Ménière’s disease, 630, 633, 634 middle fossa, 695f, 952, 952f, 953f nerve identification and nerve section technique for, 953–954 nerve monitoring and anesthesia for, 952 posterior fossa, 953 postoperative care after, 955–956 results of, 956 retrolabyrinthine approach for, 689, 690, 954, 954f, 956 retrosigmoid approach for, 687f retrosigmoid-internal auditory canal approach for, 954–955, 956 surgical technique for, 952–956, 952f–955f, 955t for tinnitus, 191 translabyrinthine, for Ménière’s disease, 632 Vestibular neuritis (VN), 484–488. See also Labyrinthitis. vs. benign paroxysmal positional vertigo, 487t, 648 in children, 559 clinical features of, 485–486 “decompensation” in, 487–488 diagnosis of, 486–487, 487t differential, 486, 487t in elderly, 536 future directions for, 488 historical background of, 484–485, 485f location of, 485 vs. Ménière’s disease, 627–628 pathophysiology of, 485, 486f pharmacotherapy for, 662t, 667–668 prognosis for, 488 symptoms of, 180 toxic, 177 treatment for, 487–488 vestibular evoked myogenic potentials in, 271 viral infection in, 484–485, 486 Vestibular neuron(s), second-order, 104–105, 107, 107f Vestibular neuronitis. See Vestibular neuritis (VN). Vestibular nucleus(i) (VN) afferent projections to, 86–87 aging effect on, 534, 534t anatomy of, 77–80, 77f–80f commissural projections of, 82f, 83, 83f denervation hypersensitivity of, 113 efferent projections of, 81–86, 82f–86f neural integrator in, 103 neuroplasticity of, 897 during nystagmus, 106, 106f in vestibulo-ocular reflex pathway, 98–99, 100, 102 Vestibular nystagmus, habituation of, 112 Vestibular paralysis. See Vestibular neuritis (VN). Vestibular pathway efferent, 85–86, 86f higher centers of, 87 Vestibular pause cells, 104, 105, 106f Vestibular rehabilitation therapy (VRT), 1331–1337 after acoustic neuroma surgery, 766 as adjunctive modality, 1335 common techniques of, 1335–1336

dynamic posturography to monitor, 265–266 expected results of, 1337 inappropriate candidates for, 1335 patient selection criteria for, 1334 physiologic rationale for, 1331–1333 as primary treatment modality, 1334 role of neurotologist in, 1337 as therapeutic trial, 1335 for vestibular symptoms of migraine, 516 Vestibular schwannoma (VS). See Acoustic neuroma (AN). Vestibular science early 19th-century advances in, 14–15 late 19th-century advances in, 26–27, 26f, 27f early 20th-century advances in, 31–32, 32f Vestibular seizures, 181, 521–522 Vestibular sensory organs, 75–76, 76f, 94–98, 94f, 96f, 97f Vestibular suppressants, in elderly, 537 Vestibular system aging effect on, 533–534, 534t anatomy of, 75–88 congenital malformations of, 332 development of, 553–554 examination of, 221 in eye movements, 228 in nystagmus, 222 physiology of, 91–118 radiation effect on, 1190 Vestibular testing for acoustic neuroma, 743–744 for assessment of vestibular compensation, 1333 of elderly, 534 for facial nerve tumors, 1265 for Ménière’s disease, 627 Vestibular vertigo, in children, 522 Vestibular-only (VO) cells, 104 Vestibulocerebellar connections, 81–83 Vestibulocerebellar inhibition, 102 Vestibulocerebellar lesion, central balance deficits with, 263, 263f Vestibulocerebellar projections, 87 Vestibulocochlear nerve, 1055f, 1142 examination of, 220–225, 221f, 223f–225f and petrous apex, 1108 Vestibulocochlear nerve dysfunction, due to cerebellopontine angle meningioma, 808, 831–832 Vestibulocochlear nerve trauma, vertigo due to, 249 Vestibulocochlear neuritis, 374 Vestibulocollic reflex (VCR), 114–115, 540 Vestibulofacial fibers of Rasmussen, 951 Vestibulogenic seizures, 522 Vestibulo-ocular pathway, 79 Vestibulo-ocular projections, 82f, 84–85, 84f, 85f Vestibulo-ocular reflex (VOR) with acoustic neuroma, 743, 766 adaptation exercises for, 1336 adaptive plasticity of, 110–111, 897 angular, 98–99, 99f anterior (vertical) canal, 99–100, 99f, 229 central neurons of, 103–105, 104f commissural connections in, 105–106, 106f defined, 607 dynamics of, 98 in elderly, 534 eye glasses and, 110–111 gain with, 109–111, 109f loss and recovery of, 113 habituation of, 111 horizontal, 98

INDEX

Vestibulo-ocular reflex (Continued) horizontal canal (angular), 98–99, 99f, 229 in neurotologic diagnosis, 229, 235 in nystagmus, 221–222 otolith, 100–101, 101f and otolith canal interactions, 242 pathways of, 98–102 posterior canal, 100, 100f, 229 purpose of, 98 rotational chair test of, 617–618, 618f signal transformation in, 102–103, 103f spinal influences on, 101–102 suppression (cancellation) of, 110 torsion, 100–101 visual and cerebellar influence on, 102, 102f visual vestibular interactions in, 106–110, 107f, 109f Vestibulo-ocular reflex (VOR) neurons, 107, 107f Vestibulopathy(ies) luetic, 249–250 recurrent, 512 Vestibuloreticular projections, 86 Vestibulospinal projections, 82f, 83–84 Vestibulospinal reflexes, 114 examination of, 224–225 mediation of, 116–118, 116f Vestibulospinal system, examination of, 224–225 Vestibulotoxic medications, 560 Vestibulovisual interactions, 106–110, 107f, 109f VHL (von Hippel-Lindau) disease hemangioblastomas in, 857, 885 papillary adenomas in, 863 Vibrant Soundbridge implantable hearing device, 1297, 1297f, 1299t Vibrating Ossicular Prosthesis (VOP), 1297, 1297f Video monitoring, of intraoperative facial nerve function, 966 Videofluoroscopy, for swallowing dysfunction, 1353–1354 Videonystagmography (VNG), 608 Video-oculography, 608, 610f Vidian nerve, 1158f Vienna Medical School, 17–18, 17f Viking Select and Endeavor, 960 Viral infection, and Bell’s palsy, 1236–1237 Viral labyrinthitis, 334, 334f, 335f acute hemorrhagic, 333, 334f contrast enhancement for, 337, 338f, 339f otolith dysfunction due to, 247 Viral neurolabyrinthitis, pharmacotherapy for, 662t Virchow, Rudolf, 17, 19, 22, 25 Virulence factors, and intracranial complications of otitis media, 914 Virus(es), meningiomas due to, 795 Visual acuity, 217 decreased, 229–230, 234 Visual axes dissociation of, 236 misalignment of, 233, 235 Visual distortion, dizziness due to, 660t Visual disturbances with acoustic neuroma, 739t, 741 in multiple sclerosis, 505

Visual evoked potentials (VEPs), in multiple sclerosis, 504, 505 Visual evoked responses (VERs), in multiple sclerosis, 504, 505 Visual field defects, 233 Visual field testing, 217, 217f Visual fixation, 221 Visual-vestibular interactions, 106–110, 107f, 109f in vestibular rehabilitation, 1336 VLL (ventral nucleus of lateral lemniscus) in brainstem auditory pathway, 565f, 566f in information processing, 48 vMGB (ventral medial geniculate body), in ascending pathway, 58–59, 64 VN. See Vestibular neurectomy (VN); Vestibular neuritis (VN); Vestibular nucleus(i) (VN). VNG (videonystagmography), 608 VNS (vestibular nerve section). See Vestibular neurectomy (VN). VO (vestibular-only) cells, 104 Vocal cord(s), endoscopic evaluation of, 1353 Vocal cord paralysis, 1356–1361 arytenoid adduction for, 1357, 1357t, 1359–1360, 1360f as complication of neurotologic surgery, 724, 724f injection for, 1357–1387, 1357t, 1358f reinnervation for, 1360–1361 thyroplasty for, 1357t, 1359, 1359f Vocational rehabilitation, after acoustic neuroma surgery, 768 Voicing, 225 Volk, B. M., 1028 Volta, Alexander, 38 Voltage maps, 310–312 Vomer, 1137f, 1155f, 1158f von Békésy, G., 54 von Bergmann, Ernst, 25 von Eiselsberg, A., 728, 730t von Graefe, Albrecht, 22 von Hippel-Lindau (VHL) disease hemangioblastomas in, 857, 885 papillary adenomas in, 863 von Recklinghausen’s disease neurofibromata of facial nerve in, 1259 paraneoplastic syndromes in, 545 vestibular schwannomas and glomus tumors in, 134 von Schmiegelow, E., 729 von Tröltsch, Anton Friedrich, 12, 15, 17, 18f, 19, 21, 22 VOP (Vibrating Ossicular Prosthesis), 1297, 1297f VOR. See Vestibulo-ocular reflex (VOR). VPI (ventroposteroinferior nucleus), 118 VPL (ventroposterolateral nucleus), 118 VPLo (oral portion of ventroposterolateral nucleus), 118 VRT. See Vestibular rehabilitation therapy (VRT). VS (vestibular schwannoma). See Acoustic neuroma (AN). VZV (varicella-zoster virus) herpes zoster oticus due to, 1237 postherpetic neuralgia due to, 200

1411

W Waardenburg’s syndrome (WS) hearing loss in, 130t multifactorial inheritance in, 128 type I, 125, 132 Walking, tandem, 225 Wallenberg’s syndrome, 464 vestibular symptoms of, 181 Wallerian degeneration, 1210 Ward, G. E., 1028 Warfarin, for vertebrobasilar insufficiency, 666 Watchful waiting, for facial nerve tumors, 1267 Watson, J. S., 1005 WDR (wide dynamic range) neurons, 194 Weaver, E. G., 38 Weber test, 220 Wegener’s granulomatosis labyrinthitis due to, 336 vestibular symptoms of, 180 Wernicke’s encephalopathy, vestibular symptoms of, 181 Whiplash injuries, vestibular symptoms of, 558 Whirling vertigo, 179 Whiting, F., 22 Wide dynamic range (WDR) neurons, 194 Wilde, William, 19, 20–21, 20f Williams syndrome, 183 “Wind-up” phenomenon, 184, 187 Woolsey, George, 729 Wooziness, 177 Word recognition ability, and hearing aids, 1283 Word recognition test, 221 Wound infections, postoperative, 721–722, 722f WS. See Waardenburg’s syndrome (WS). Wullstein, Hörst, 36

X X chromosome inactivation, 125, 126–127 Xanthogranuloma, of cerebellopontine angle, 853 Xanthomas, of petrous apex, 1121 X-linked congenital sensorineural hearing loss, 125 X-linked high-frequency sensorineural hearing loss, 125 X-linked inheritance, 125, 125f, 131t XY gonadal dysgenesis (XYGD), 128 Xylocaine (lidocaine), for tinnitus, 189–190

Z Zange, J., 729 Zaufal, Emanuel, 22 Zeiss OpMi-1 binocular dissecting microscope, 36, 36f Zeiss-Opton, 36, 36f Zeitschrift für Wissenschaftliche Zoologie, 20 Zöllner, Fritz, 36 Zoster sine eruptione, 1237 Zoster sine herpete, 1237 Zovirax (acyclovir) for facial palsy, 1250–1251 for Ramsay Hunt syndrome, 668 Zwislocki, Jozef, 54 Zygomatic arch, 1159f Zygomatic process, 998f, 1054f, 1224f