The Official Patient's Sourcebook on Narcolepsy

THE OFFICIAL PATIENT’S SOURCEBOOK

on

ARCOLEPSY

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your physician. All matters regarding your health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The Official Patient’s Sourcebook on Narcolepsy: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83171-8 1. Narcolepsy-Popular works. I. Title.

iii

Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of narcolepsy.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to narcolepsy. All of the Official Patient’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.

v

About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to narcolepsy, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Insomnia

·

The Official Patient's Sourcebook on Restless Legs Syndrome

·

The Official Patient's Sourcebook on Sleep Apnea

To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

Contents vii

Table of Contents INTRODUCTION ................................................................................................................................. 1 Overview .................................................................................................................................... 1 Organization ............................................................................................................................. 3 Scope ............................................................................................................................................ 3 Moving Forward ...................................................................................................................... 4

PART I: THE ESSENTIALS ..................................................................... 7 CHAPTER 1. THE ESSENTIALS ON NARCOLEPSY: GUIDELINES .......................................................................................................................... 9 Overview .................................................................................................................................... 9 What Is Narcolepsy? ............................................................................................................. 12 When Should You Suspect Narcolepsy?......................................................................... 13 How Common Is Narcolepsy? ........................................................................................... 13 Who Gets Narcolepsy? ......................................................................................................... 13 What Happens in Narcolepsy? .......................................................................................... 13 How Is Narcolepsy Diagnosed? ........................................................................................ 14 How Is Narcolepsy Treated? .............................................................................................. 14 What Is Being Done to Better Understand Narcolepsy? ........................................... 15 How Can Individuals and Their Families and Friends Cope with Narcolepsy? 15 For More Information ........................................................................................................... 16 More Guideline Sources....................................................................................................... 17 Vocabulary Builder ............................................................................................................... 21

CHAPTER 2. SEEKING GUIDANCE ................................................................. 25 Overview .................................................................................................................................. 25 Associations and Narcolepsy .............................................................................................. 25 Finding More Associations ................................................................................................. 33 Finding Doctors ..................................................................................................................... 34 Selecting Your Doctor .......................................................................................................... 36 Working with Your Doctor................................................................................................. 36 Broader Health-Related Resources.................................................................................... 38 Vocabulary Builder ............................................................................................................... 38

CHAPTER 3. CLINICAL TRIALS AND NARCOLEPSY ...................... 39 Overview .................................................................................................................................. 39 Recent Trials on Narcolepsy ............................................................................................... 42 Benefits and Risks .................................................................................................................. 43 Keeping Current on Clinical Trials .................................................................................. 46 General References................................................................................................................. 47

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL ....................................................................... 49

viii Contents

CHAPTER 4. STUDIES ON NARCOLEPSY................................................... 51 Overview .................................................................................................................................. 51 The Combined Health Information Database ................................................................ 51 Federally-Funded Research on Narcolepsy .................................................................... 56 E-Journals: PubMed Central .............................................................................................. 72 The National Library of Medicine: PubMed.................................................................. 72 Vocabulary Builder ............................................................................................................... 73

CHAPTER 5. PATENTS ON NARCOLEPSY ................................................ 79 Overview .................................................................................................................................. 79 Patents on Narcolepsy .......................................................................................................... 80 Patent Applications on Narcolepsy .................................................................................. 84 Keeping Current..................................................................................................................... 84 Vocabulary Builder ............................................................................................................... 84

CHAPTER 6. BOOKS ON NARCOLEPSY ...................................................... 87 Overview .................................................................................................................................. 87 Book Summaries: Federal Agencies .................................................................................. 87 Book Summaries: Online Booksellers............................................................................... 88 The National Library of Medicine Book Index .............................................................. 89 Chapters on Narcolepsy ....................................................................................................... 91 General Home References .................................................................................................... 92 Vocabulary Builder ............................................................................................................... 92

CHAPTER 7. MULTIMEDIA ON NARCOLEPSY ..................................... 93 Overview .................................................................................................................................. 93 Bibliography: Multimedia on Narcolepsy....................................................................... 93

CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES ......... 95 Overview .................................................................................................................................. 95 NIH Guidelines ...................................................................................................................... 95 NIH Databases ....................................................................................................................... 97 Other Commercial Databases ........................................................................................... 101 The Genome Project and Narcolepsy ............................................................................. 102 Specialized References ........................................................................................................ 106

CHAPTER 9. DISSERTATIONS ON NARCOLEPSY ............................. 109 Overview ................................................................................................................................ 109 Dissertations on Narcolepsy ............................................................................................. 109 Keeping Current................................................................................................................... 110

PART III. APPENDICES .......................................................................... 111 APPENDIX A. RESEARCHING YOUR MEDICATIONS .................. 113 Overview ................................................................................................................................ 113 Your Medications: The Basics.......................................................................................... 114 Learning More about Your Medications ...................................................................... 115 Commercial Databases ....................................................................................................... 117

Contents

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Contraindications and Interactions (Hidden Dangers) ........................................... 119 A Final Warning.................................................................................................................. 120 General References............................................................................................................... 120 Vocabulary Builder ............................................................................................................. 121

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ........ 123 Overview ................................................................................................................................ 123 What Is CAM? ..................................................................................................................... 123 What Are the Domains of Alternative Medicine? ..................................................... 124 Can Alternatives Affect My Treatment?...................................................................... 127 Finding CAM References on Narcolepsy ..................................................................... 128 Additional Web Resources ................................................................................................ 132 General References............................................................................................................... 136

APPENDIX C. FINDING MEDICAL LIBRARIES ................................... 139 Overview ................................................................................................................................ 139 Preparation ............................................................................................................................ 139 Finding a Local Medical Library ..................................................................................... 140 Medical Libraries Open to the Public ............................................................................ 140

APPENDIX D. MORE ON PROBLEM SLEEPINESS ............................. 147 Overview ................................................................................................................................ 147 What Causes Problem Sleepiness? ................................................................................. 147 Sleep Disorders ..................................................................................................................... 148 Medical Conditions/Drugs ............................................................................................... 149 Problem Sleepiness and Adolescents .............................................................................. 149 What Can Help? .................................................................................................................. 151 Vocubulary Builder ............................................................................................................. 153

ONLINE GLOSSARIES............................................................................. 155 Online Dictionary Directories ......................................................................................... 158

NARCOLEPSY GLOSSARY............................................................... 159 General Dictionaries and Glossaries .............................................................................. 167

INDEX ................................................................................................................................... 169

Introduction

1

INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3

Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

2

Narcolepsy

Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Narcolepsy has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to narcolepsy, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on narcolepsy. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on narcolepsy should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate

Introduction

3

options is always up to the patient in consultation with their physician and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching narcolepsy (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to narcolepsy. It also gives you sources of information that can help you find a doctor in your local area specializing in treating narcolepsy. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with narcolepsy. Part II moves on to advanced research dedicated to narcolepsy. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on narcolepsy. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with narcolepsy or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with narcolepsy. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with narcolepsy.

Scope While this sourcebook covers narcolepsy, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that narcolepsy is often considered a synonym or a condition closely related to the following: ·

Gelineau's Syndrome

·

Narcoleptic Syndrome

·

Paroxysmal Sleep

4

Narcolepsy

·

Sleep Epilepsy

In addition to synonyms and related conditions, physicians may refer to narcolepsy using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for narcolepsy:4 ·

347 cataplexy and narcolepsy

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to narcolepsy. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with narcolepsy will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with narcolepsy is 4 This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

Introduction

5

even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. Before beginning your search for information, it is important for you to realize that narcolepsy is considered a relatively uncommon condition. Because of this, far less research is conducted on narcolepsy compared to other health problems afflicting larger populations, like breast cancer or heart disease. Nevertheless, this sourcebook will prove useful for two reasons. First, if more information does become available on narcolepsy, the sources given in this book will be the most likely to report or make such information available. Second, some will find it important to know about patient support, symptom management, or diagnostic procedures that may be relevant to both narcolepsy and other conditions. By using the sources listed in the following chapters, self-directed research can be conducted on broader topics that are related to narcolepsy but not readily uncovered using general Internet search engines (e.g. www.google.com or www.yahoo.com). In this way, we have designed this sourcebook to complement these general search engines that can provide useful information and access to online patient support groups.5 While we focus on the more scientific aspects of narcolepsy, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

For example, one can simply go to www.google.com, or other general search engines (e.g. www.yahoo.com, www.aol.com, www.msn.com) and type in “diseasex support group” to find any active online support groups dedicated to diseasex.

5

7

PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on narcolepsy. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of narcolepsy to you or even given you a pamphlet or brochure describing narcolepsy. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

CHAPTER 1. GUIDELINES

THE

ESSENTIALS

ON

9

NARCOLEPSY:

Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on narcolepsy. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on narcolepsy can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

The National Institutes of Health (NIH)6 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on narcolepsy. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

6

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Narcolepsy

There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with narcolepsy and associated conditions: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Heart, Lung, and Blood Institute (NHLBI); guidelines at http://www.nhlbi.nih.gov/guidelines/index.htm

Among these, the National Heart, Lung, and Blood Institute (NHLBI) is particularly noteworthy. The NHLBI provides leadership for a national program in diseases of the heart, blood vessels, lung, and blood; blood resources; and sleep disorders.7 Since October 1997, the NHLBI has also had administrative responsibility for the NIH Woman’s Health Initiative. The Institute plans, conducts, fosters, and supports an integrated and coordinated program of basic research, clinical investigations and trials, observational studies, and demonstration and education projects. Research is related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The NHLBI plans and directs research in development and evaluation of interventions and devices related to prevention, treatment, and rehabilitation of patients suffering from such diseases and disorders. It also supports research on clinical use of blood and all aspects of the management of blood resources. Research is conducted in the Institute’s own laboratories and by scientific institutions and individuals supported by research grants and contracts. For health professionals and the public, the NHLBI conducts educational activities, including development and dissemination of materials in the above areas, with an emphasis on prevention. Within the NHLBI, the National Center on Sleep Disorders Research (NCSDR) was established in 1993 to combat a serious public health concern.8 7 This paragraph has been adapted from the NHLBI: http://www.nhlbi.nih.gov/about/org/mission.htm. “Adapted” signifies that a passage is reproduced exactly or slightly edited for this book. 8 This paragraph has been adapted from the NCSDR: http://www.nhlbisupport.com/sleep/about/about.htm.

Guidelines 11

About 70 million Americans suffer from sleep problems; among them, nearly 60 percent have a chronic disorder. Each year, sleep disorders, sleep deprivation, and sleepiness add an estimated $15.9 billion to the national healthcare bill. Additional costs to society for related health problems, lost worker productivity, and accidents have not been calculated. Sleep disorders and disturbances of sleep comprise a broad range of problems, including sleep apnea, narcolepsy, insomnia, parasomnia, jet-lag syndrome, and disturbed biological and circadian rhythms. The Center seeks to fulfill its goal of improving the health of Americans by serving four key functions: research, training, technology transfer, and coordination. ·

Research: Sleep disorders span many medical fields, requiring multidisciplinary approaches not only to treatment, but also to basic research. The Center works with neuroscientists, cellular and molecular biologists, geneticists, physiologists, neuropsychiatrists, immunologists, pulmonary specialists, cardiologists, epidemiologists, behavioral scientists, and other experts. Ongoing research is supported by the NIH and other Federal agencies.

·

Training: Training researchers in sleep disorders is rigorous and timeconsuming. The Center seeks to support and promote formal training programs on the doctoral and postdoctoral levels. It also plans to expand existing career development paths and create new training programs for scientists in sleep disorders research.

·

Technology Transfer: The Center seeks to ensure that research results lead to health benefits. It works towards this goal by educating health care professionals about sleep disorders and research findings, encouraging medical schools to add sleep disorders to their curricula, working with leading experts to develop clinical guidelines, and sponsoring continuing medical education programs.

·

Coordination: The Center coordinates the Federal Government’s efforts on sleep disorders and works closely with other public, private, and nonprofit groups. The Center works to share information among these groups and encourage their cooperation, especially in crosscutting areas. It also seeks to improve communication among scientists, policymakers, and health care professionals.

The following patient guideline was recently published by the NHLBI and the NCSDR on narcolepsy.

12 Narcolepsy

What Is Narcolepsy?9 Narcolepsy is a chronic sleep disorder with no known cause. The main characteristic of narcolepsy is excessive and overwhelming daytime sleepiness, even after adequate nighttime sleep. A person with narcolepsy is likely to become drowsy or to fall asleep, often at inappropriate times and places. Daytime sleep attacks may occur with or without warning and may be irresistible. These attacks can occur repeatedly in a single day. Drowsiness may persist for prolonged periods of time. In addition, nighttime sleep may be fragmented with frequent awakenings. Three other classic symptoms of narcolepsy, which may not occur in all patients, are: ·

Cataplexy: Sudden episodes of loss of muscle function, ranging from slight weakness (such as limpness at the neck or knees, sagging facial muscles, or inability to speak clearly) to complete body collapse. Attacks may be triggered by sudden emotional reactions such as laughter, anger, or fear and may last from a few seconds to several minutes. The person remains conscious throughout the episode.

·

Sleep paralysis: Temporary inability to talk or move when falling asleep or waking up. It may last a few seconds to minutes.

·

Hypnagogic hallucinations: Vivid, often frightening, experiences that occur while dozing or falling asleep.

dream-like

Daytime sleepiness, sleep paralysis, and hypnagogic hallucinations can also occur in people who do not have narcolepsy. In most cases, the first symptom of narcolepsy to appear is excessive and overwhelming daytime sleepiness. The other symptoms may begin alone or in combination months or years after the onset of the daytime sleep attacks. There are wide variations in the development, severity, and order of appearance of cataplexy, sleep paralysis, and hypnagogic hallucinations in individuals. Only about 20 to 25 percent of people with narcolepsy experience all four symptoms. The excessive daytime sleepiness generally persists throughout life, but sleep paralysis and hypnagogic hallucinations may not.

9Adapted

from the National Heart, Lung, and Blood Institute: http://www.nhlbi.nih.gov/health/public/sleep/narcolep.htm.

Guidelines 13

The symptoms of narcolepsy, especially the excessive daytime sleepiness and cataplexy, often become severe enough to cause serious disruptions in a person’s social, personal, and professional lives and severely limit activities.

When Should You Suspect Narcolepsy? You should be checked for narcolepsy if: ·

You often feel excessively and overwhelmingly sleepy during the day, even after having had a full night’s sleep

·

You fall asleep when you do not intend to, such as while having dinner, talking, driving, or working

·

You collapse suddenly or your neck muscles feel too weak to hold up your head when you laugh or become angry, surprised, or shocked

·

You find yourself briefly unable to talk or move while falling asleep or waking up.

How Common Is Narcolepsy? Although it is estimated that narcolepsy afflicts as many as 200,000 Americans, fewer than 50,000 are diagnosed. It is as widespread as Parkinson’s disease or multiple sclerosis and more prevalent than cystic fibrosis, but it is less well known. Narcolepsy is often mistaken for depression, epilepsy, or the side effects of medications.

Who Gets Narcolepsy? Narcolepsy can occur in both men and women at any age, although its symptoms are usually first noticed in teenagers or young adults. There is strong evidence that narcolepsy may run in families; 8 to 12 percent of people with narcolepsy have a close relative with the disease.

What Happens in Narcolepsy? Normally, when an individual is awake, brain waves show a regular rhythm. When a person first falls asleep, the brain waves become slower and less regular. This sleep state is called non-rapid eye movement (NREM) sleep. After about an hour and a half of NREM sleep, the brain waves begin to show a more active pattern again, even though the person is in deep sleep.

14 Narcolepsy

This sleep state, called rapid eye movement (REM) sleep, is when dreaming occurs. In narcolepsy, the order and length of NREM and REM sleep periods are disturbed, with REM sleep occurring at sleep onset instead of after a period of NREM sleep. Thus, narcolepsy is a disorder in which REM sleep appears at an abnormal time. Also, some of the aspects of REM sleep that normally occur only during sleep--lack of muscle tone, sleep paralysis, and vivid dreams--occur at other times in people with narcolepsy. For example, the lack of muscle tone can occur during wakefulness in a cataplexy episode. Sleep paralysis and vivid dreams can occur while falling asleep or waking up.

How Is Narcolepsy Diagnosed? Diagnosis is relatively easy when all the symptoms of narcolepsy are present. But if the sleep attacks are isolated and cataplexy is mild or absent, diagnosis is more difficult. Two tests that are commonly used in diagnosing narcolepsy are the polysomnogram and the multiple sleep latency test. These tests are usually performed by a sleep specialist. The polysomnogram involves continuous recording of sleep brain waves and a number of nerve and muscle functions during nighttime sleep. When tested, people with narcolepsy fall asleep rapidly, enter REM sleep early, and may awaken often during the night. The polysomnogram also helps to detect other possible sleep disorders that could cause daytime sleepiness. For the multiple sleep latency test, a person is given a chance to sleep every 2 hours during normal wake times. Observations are made of the time taken to reach various stages of sleep. This test measures the degree of daytime sleepiness and also detects how soon REM sleep begins. Again, people with narcolepsy fall asleep rapidly and enter REM sleep early.

How Is Narcolepsy Treated? Although there is no cure for narcolepsy, treatment options are available to help reduce the various symptoms. Treatment is individualized depending on the severity of the symptoms, and it may take weeks or months for an optimal regimen to be worked out. Complete control of sleepiness and cataplexy is rarely possible. Treatment is primarily by medications, but

Guidelines 15

lifestyle changes are also important. The main treatment of excessive daytime sleepiness in narcolepsy is with a group of drugs called central nervous system stimulants. For cataplexy and other REM-sleep symptoms, antidepressant medications and other drugs that suppress REM sleep are prescribed. Caffeine and over-the-counter drugs have not been shown to be effective and are not recommended. In addition to drug therapy, an important part of treatment is scheduling short naps (10 to 15 minutes) two to three times per day to help control excessive daytime sleepiness and help the person stay as alert as possible. Daytime naps are not a replacement for nighttime sleep. Ongoing communication among the physician, the person with narcolepsy, and family members about the response to treatment is necessary to achieve and maintain the best control.

What Is Being Done to Better Understand Narcolepsy? Studies supported by the National Institutes of Health (NIH) are trying to increase understanding of what causes narcolepsy and improve physicians’ ability to detect and treat the disease. Scientists are studying narcolepsy patients and families, looking for clues to the causes, course, and effective treatment of this sleep disorder. The recent discovery of families of dogs that are naturally afflicted with narcolepsy has been of great help in these studies. Some of the specific questions being addressed in NIH-supported studies are the nature of genetic and environmental factors that might combine to cause narcolepsy and the immunological, biochemical, physiological, and neuromuscular disturbances associated with narcolepsy. Scientists are also working to better understand sleep mechanisms and the physical and psychological effects of sleep deprivation and to develop better ways of measuring sleepiness and cataplexy.

How Can Individuals and Their Families and Friends Cope with Narcolepsy? Learning as much about narcolepsy as possible and finding a support system can help patients and families deal with the practical and emotional effects of the disease, possible occupational limitations, and situations that might cause injury. A variety of educational and other materials are available from sleep medicine or narcolepsy organizations. Support groups exist to help persons with narcolepsy and their families.

16 Narcolepsy

Individuals with narcolepsy, their families, friends, and potential employers should know that: ·

Narcolepsy is a life-long condition that requires continuous medication.

·

Although there is not a cure for narcolepsy at present, several medications can help reduce its symptoms.

·

People with narcolepsy can lead productive lives if they are provided with proper medical care.

·

If possible, individuals with narcolepsy should avoid jobs that require driving long distances or handling hazardous equipment or that require alertness for lengthy periods.

·

Parents, teachers, spouses, and employers should be aware of the symptoms of narcolepsy. This will help them avoid the mistake of confusing the person’s behavior with laziness, hostility, rejection, or lack of interest and motivation. It will also help them provide essential support and cooperation.

·

Employers can promote better working opportunities for individuals with narcolepsy by permitting special work schedules and nap breaks.

For More Information For additional information on sleep and sleep disorders, contact the following offices of the National Heart, Lung, and Blood Institute of the National Institutes of Health: National Center on Sleep Disorders Research Two Rockledge Centre Suite 7024 6701 Rockledge Drive, MSC 7920 Bethesda, MD 20892-7920 (301) 435-0199 (301) 480-3451 (fax) The NCSDR supports research, scientist training, dissemination of health information, and other activities on sleep and sleep disorders. The NCSDR also coordinates sleep research activities with other Federal agencies and with public and nonprofit organizations. NHLBI Information Center P.O. Box 30105 Bethesda, MD 20824-0105 (301) 592-8573

Guidelines 17

(301) 592-8563 (fax) The Information Center acquires, analyzes, promotes, maintains, and disseminates programmatic and educational information related to sleep and sleep disorders. Write for a list of available publications or to order additional copies of this fact sheet. For more information about narcolepsy and patient support groups, contact: The Narcolepsy Network P.O. Box 42460 Cincinnati, OH 45242

More Guideline Sources The guideline above on narcolepsy is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to narcolepsy. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with narcolepsy. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.

Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented

18 Narcolepsy

information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on narcolepsy and related conditions. One of the advantages of CHID over other sources is that it offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·

Nature of Sleep and Its Disorders Source: Washington, DC: National Sleep Foundation. 12 p. Contact: Available from National Sleep Foundation. 1367 Connecticut Avenue NW, Suite 200, Washington, DC 20036. (202) 785-2300; FAX (202) 785-2880. Price: Free. Summary: This brochure presents general information about the physiology of sleep and describes the onset and characteristics of the following types of sleep disorders: insomnia, sleep apnea, narcolepsy, restless legs syndrome, and parasomnias. The use of sleeping pills and when to seek medical attention for a sleep disorder are briefly discussed. The role of the National Sleep Foundation also is described.

·

Understanding Narcolepsy Source: Washington, DC: National Sleep Foundation. [8 p.]. Contact: Available from National Sleep Foundation. 1367 Connecticut Avenue NW, Suite 200, Washington, DC 20036. (202) 785-2300; FAX (202) 785-2880. Price: Free. Summary: This brochure presents general information about narcolepsy, a disorder that affects the region of the central nervous system that regulates sleep and wakefulness. Symptoms can include excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, disturbed nighttime sleep, and automatic behavior. Causes, who is affected, treatment, and impact on one's daily activities also are discussed.

Guidelines 19

·

Narcolepsy: Questions and Answers Source: New York, NY: Narcolepsy Network, Inc. [8 p.]. Contact: Available from Narcolepsy Network, Inc. P.O. Box 1365, FDR Station, New York NY 10150. (914) 834-2855. Price: Free. Summary: This brochure answers commonly asked questions about narcolepsy. Topics addressed include symptoms, why and when attacks occur, diagnosis, and treatment. Complications caused by the disorder, research advances, and the role of the Narcolepsy Network are also discussed. A detachable information request form is included.

The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “narcolepsy” or synonyms. The following was recently posted: ·

Practice parameters for the treatment of narcolepsy: an update for 2000. Source: American Academy of Sleep Medicine.; 1994 (updated 2001 Jun); 16 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2159&sSearch_string=narcolepsy

Healthfinder™ Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:

20 Narcolepsy

·

Facts About Narcolepsy Summary: Narcolepsy is a chronic sleep disorder with no known cause. The main characteristic of narcolepsy is excessive and overwhelming daytime sleepiness, even after adequate nighttime sleep. Source: National Center on Sleep Disorders Research, National Heart, Lung, and Blood Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=715

·

Narcolepsy Summary: A general overview of narcolepsy that includes a description of the disorder, and treatment, prognosis and research information. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=783

·

Test Your Sleep I.Q. Summary: This true-false quiz tests what you know about sleep. Questions cover topics on snoring, narcolepsy, insomnia, restless legs syndrome, and other issues. Source: National Center on Sleep Disorders Research, National Heart, Lung, and Blood Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2384

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to narcolepsy. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific

Guidelines 21

disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing, for a nominal fee, short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is www.rarediseases.org. To see if a recent fact sheet has been published on narcolepsy, simply go to the following hyperlink: http://www.rarediseases.org/cgibin/nord/alphalist. A complete guide on narcolepsy can be purchased from NORD for a nominal fee.

Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

·

drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

·

Family Village: http://www.familyvillage.wisc.edu/specific.htm

·

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

·

Med Help International: http://www.medhelp.org/HealthTopics/A.html

·

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

·

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

·

WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter:

22 Narcolepsy

Antidepressant: An agent that stimulates the mood of a depressed patient, including tricyclic antidepressants and monoamine oxidase inhibitors. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Chronic: Of long duration; frequently recurring. [NIH] Collapse: 1. a state of extreme prostration and depression, with failure of circulation. 2. abnormal falling in of the walls of any part of organ. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dreams: A series of thoughts, images, or emotions occurring during sleep which are dissociated from the usual stream of consciousness of the waking state. [NIH] Facial: Of or pertaining to the face. [EU] Fibrosis: Process by which inflamed tissue becomes scarred. [NIH] Insomnia: Inability to sleep; abnormal wakefulness. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Paralysis: Loss or impairment of motor function in a part due to lesion of the neural or muscular mechanism; also by analogy, impairment of sensory function (sensory paralysis). In addition to the types named below, paralysis is further distinguished as traumatic, syphilitic, toxic, etc., according to its cause; or as obturator, ulnar, etc., according to the nerve part, or muscle specially affected. [EU] Pulmonary: Relating to the lungs. [NIH] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Snoring: Rough, noisy breathing during sleep, due to vibration of the uvula and soft palate. [NIH] Stimulant: 1. producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. an agent or remedy that produces stimulation. [EU] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH]

Guidelines 23

Tone: 1. the normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. a particular quality of sound or of voice. 3. to make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH]

Seeking Guidance 25

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with narcolepsy. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.10 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with narcolepsy. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Narcolepsy As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.11 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 11 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 10

26 Narcolepsy

influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·

American Sleep Disorders Association Address: American Sleep Disorders Association 1610 14th Street NW, Suite 300, Rochester, MN 55901 Telephone: (507) 287-6006 Fax: (507) 287-6008 Email: [email protected] Background: Established in 1975, the American Sleep Disorders Association (ASDA) is a voluntary, not-for-profit, medical and scientific society dedicated to quality medical care for individuals with sleep disorders and service to its individual and center members through education, research, and the development of practice standards related to the field of sleep medicine. The Association is committed to fostering professional education through meetings, courses, publications, and educational materials; defining, developing, distributing, and updating standards, guidelines, and policies that result in optimal access to and delivery of care for all patients with sleep disorders; and fostering basic and clinical sleep research. The Association is also dedicated to promoting training programs for practitioners of sleep medicine; representing the field to all government and private agencies involved in research, training, policy, practice, and healthcare delivery issues that affect the field; and educating the public about sleep disorders and related conditions. The Association offers a variety of educational and support materials including an educational slide series; manuals for physicians, healthcare professionals, medical students, sleep specialists, and other professionals, CD-ROM and computer-based information resources for professionals; an interdisciplinary medical journal entitled 'Sleep'; and patient education pamphlets. Relevant area(s) of interest: Narcolepsy

Seeking Guidance 27

·

Center for Narcolepsy Research Address: Center for Narcolepsy Research College of Nursing (M/C 802), The University of Illinois at Chicago, 845 South Damen Avenue, Room 215, Chicago, IL 60612-7350 Telephone: (312) 996-5176 Fax: (312) 996-7008 Email: [email protected] Web Site: http://www.uic.edu/depts/cnr/cnrright.ht Background: The Center for Narcolepsy Research (CNR) at the College of Nursing (University of Illinois at Chicago [UIC]) was established in 1986 to help increase knowledge and awareness of narcolepsy and to provide information and support to those affected by this disorder. Narcolepsy is characterized by abnormal drowsiness during the day, sudden extreme muscle weakness (cataplexy), hallucinations, paralysis while sleeping, and/or disrupted sleep during the night. The development and severity of symptoms vary greatly among affected individuals. The CNR staff, along with faculty and graduate students from UIC, collaborate in conducting various studies. Networking activities are undertaken with other sleep researchers and clinicians at sleep disorder centers throughout the Chicago metropolitan region. Ongoing investigations are being conducted into areas such as memory and the speed of cognitive processing, the prevalence of sleep pattern disturbance among adolescents, and appropriate symptom management. Research activities also include the measurement of biobehavioral aspects of excessive daytime sleepiness; the study of how narcolepsy symptoms develop and appropriate management techniques; the enhancement of coping skills for people with narcolepsy and their families; the study of learning, memory, and cognitive processing of people with narcolepsy; and the investigation of new methods of treatment for narcolepsy. Clinical work includes counseling and educational activities for people with narcolepsy. The Center's staff coordinates the activities of Narcoleptics and Partners (NAP), a support group for people with narcolepsy and their friends or family members. The Center also seeks to educate health care professionals about narcolepsy and other disorders of excessive sleepiness. CNR maintains a patient registry of several hundred research volunteers; this registry may serve as a model for research into other chronic neurological disorders. The Center fields questions from physicians, teachers, and nurses on current scientific knowledge about sleep disorders. CNR maintains a web site at http://www.uic.edu/depts/cnr/cnrright.htm.

28 Narcolepsy

Relevant area(s) Paroxysmal Sleep ·

of

interest:

Gelineau's

Syndrome,

Narcolepsy,

Narcolepsy and Cataplexy Foundation of America Address: Narcolepsy and Cataplexy Foundation of America 445 E. 68th Street, L12, New York, NY 10021 Telephone: (212) 570-550 Background: The Narcolepsy and Cataplexy Foundation of America (NCFA) is a voluntary not-for-profit self-help organization dedicated to providing information on Nacrolepsy and Cataplexy to affected individuals, the medical community, and the general public. Current information on treatment options and current research is available from the Foundation. Narcolepsy is a rare disorder characterized by abnormal drowsiness during the day, sudden extreme muscle weakness (cataplexy), hallucinations, paralysis while sleeping, and disrupted sleep during the night. Established in 1976, the Narcolepsy and Cataplexy Foundation of America provides referrals to physicians and treatment centers; promotes research into narcolepsy; provides referrals to support groups; and offers educational information through brochures. Relevant area(s) of interest: Narcolepsy

·

Narcolepsy Institute Address: Narcolepsy Institute Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467 Telephone: (718) 920-6799 Fax: (718) 654-958 Background: The Narcolepsy Institute is a not-for-profit, voluntary organization dedicated to providing comprehensive care to people with narcolepsy by integrating the medical, social, psychological, and spiritual dimensions of health in spirit of kindness and respect toward all, irrespective of race, creed, ethnicity, or social class. The Institute hopes that recipients of care may realize their optimal potential and live productively. Narcolepsy is a genetic disorder characterized by excessive daytime drowsiness. An individual with narcolepsy feels an irresistible urge to sleep during the day and often has disturbed nocturnal sleep as well. Established in 1985, the Institute strives to provide comprehensive psychosocial services and inform individuals about non-medical management of narcolepsy and improve the quality of their lives. The Narcolepsy Institute consists of 300 members. Educational materials include the bi-yearly newsletter 'Perspectives,' a guide entitled

Seeking Guidance 29

'Narcolepsy Primer,' as well as an informational brochure 'Narcolepsy Institute.' Program activities include referrals, crisis intervention, counseling, nutritional planning, outreach, and advocacy. Relevant area(s) of interest: Narcolepsy ·

Narcolepsy Network, Inc Address: Narcolepsy Network, Inc. 277 Fairfield Road, Suite 310B, Fairfield, NJ 07004 Telephone: (973) 276-0115 Fax: (973) 227-8224 Email: [email protected] Web Site: http://www.websciences.org/narne Background: The Narcolepsy Network is a national voluntary organization that was formed to serve the needs of people with narcolepsy. It is composed of people with narcolepsy, their families, friends, health care professionals, and other interested individuals. The Network is dedicated to improving the quality of life for people with narcolepsy and finding a cure for this disorder. To this end, the organization maintains a network of local support groups and chapters. The organization promotes programs of communication, advocacy, research, support, and education. A booklet entitled 'Narcolepsy: A Guide to Understanding' provides information on narcolepsy. Topics covered within the booklet include the symptoms, causes, diagnosis of the disorder, associated sleep apnea, treatments, and social implications. The organization also distributes a reading list, bibliography, and an educational materials order form. Relevant area(s) of interest: Narcolepsy

·

National Narcolepsy Registry Address: National Narcolepsy Registry 729 15th Street NW, 4th Floor, Washington, DC 20005 Telephone: (202) 347-3471 Fax: (202) 347-3472 Email: [email protected] Web Site: http://www.sleepfoundation.or Background: The National Narcolepsy Registry (NNR) is a not-for-profit research organization dedicated to providing researchers with information to advance research, diagnosis, and treatment of narcolepsy;

30 Narcolepsy

to finding the gene(s) that may cause or contribute to narcolepsy; and to developing better treatments, a better quality of life for affected individuals and their families; and progressing toward a cure. Narcolepsy is a rare disorder characterized by abnormal drowsiness during the day, sudden extreme muscle weakness (cataplexy), hallucinations, paralysis while sleeping, and disrupted sleep during the night. Established in 1996, NNR is a confidential database of genetic information provided by individuals with narcolepsy. It is used for the sole purpose of promoting further research on narcolepsy. The first registry of its kind, the NNR is part of the National Sleep Foundation's (NSF) 'Towards the Cause of Narcolepsy' program. The NSF urges individuals who have been diagnosed with narcolepsy and their family members to use the registry as an opportunity to contribute to narcolepsy research. Consisting of 500 members, the NNR produces educational materials including a brochure entitled 'National Narcolepsy Registry.' NNR can be reached at its e- mail address at natsleepaterols.com or its web site at http://www.sleepfoundation.org. Relevant area(s) of interest: Gelineau's Paroxysmal Sleep, Sleep Epilepsy ·

Syndrome,

Narcolepsy,

National Sleep Foundation Address: National Sleep Foundation 729 15th Street, N.W., 4th Floor, Washington, D.C. 20005 Telephone: (202) 347-3471 Fax: (202) 347-3472 Email: [email protected] Web Site: http://www.sleepfoundation.or Background: The National Sleep Foundation (NSF) is a not-for-profit organization dedicated to improving the quality of life for those who are affected by sleep disorders (e.g., Sleep Apnea, Narcolepsy, Restless Legs Syndrome, and Periodic Limb Movement Disorder) and preventing accidents related to sleep deprivation or sleep disorders. Established in 1991, the National Sleep Foundation increases public awareness of sleep disorders through all forms of media; encourages the development of patient services, community resources, and support groups for affected individuals; and creates partnerships with business and government to extend its educational reach. The National Sleep Foundation also provides referrals to regional sleep disorder centers; conducts symposia for physicians across the United States; and provides research grants and fellowships. The Foundation offers a variety of educational and supportive information through its database, brochures and pamphlets

Seeking Guidance 31

designed for physicians and the general public, a regular newsletter for physicians entitled 'Sleep Medicine Alert,' and 'NSF Connection,' a newsletter for the public. Relevant area(s) of interest: Narcolepsy ·

Sleep/Wake Disorders Canada Address: Sleep/Wake Disorders Canada 3080 Yonge Street, Suite 5055, Toronto, Ontario, M4N 3N1, Canada Telephone: (416) 483-9654 Toll-free: (800) 387-9253 Fax: (416) 483-7081 Email: [email protected] Web Site: http://www.geocities.com/~sleepwake Background: Sleep/Wake Disorders Canada (SWDC) is a national notfor-profit self-help organization of volunteers dedicated to providing information, practical support, and resources to Canadians with sleep/wake disorders. Such disorders include difficulties falling or staying asleep (insomnia); sleep apnea, a disorder in which breathing periodically ceases during sleep; narcolepsy, which is characterized by excessive daytime sleepiness, recurrent episodes of sleep during the day, and, in some cases, sudden loss of muscle tone (hypotonia) without loss of consciousness (cataplexy); and restless legs syndrome, a disorder characterized by unusual, unpleasant sensations deep in the legs, an overwhelming desire to move the legs to relieve such sensations, motor restlessness, and occurrence of such symptoms most frequently during the evening or early part of the night and while at rest. Established in 1981 and currently consisting of approximately 1,000 members, Sleep/Wake Disorders Canada has self-help chapters and contact representatives across Canada to provide local access for affected individuals and family members who seek information and peer support. The organization is committed to providing accurate and timely information on sleep/wake disorders to affected individuals and health care professionals; promoting awareness among affected families, medical professionals, and the general public concerning the implications of sleep/wake disorders in the home environment, the workplace, and the community; and promoting and supporting research on the underlying causes of such disorders to improve prevention, diagnosis, and disease management efforts. Sleep/Wake Disorders Canada has a register of sleep laboratories and sleep specialists from across Canada, holds regular group meetings, conducts an annual conference to bring together volunteers and medical professionals in order to review the current state of sleep/wake research and to plan initiatives for the

32 Narcolepsy

organization, and conducts National Sleep Awareness week activities to raise public awareness. Sleep/Wake Disorders Canada also offers a wide range of educational materials including informational brochures on insomnia, sleep apnea, narcolepsy, restless legs syndrome, and other sleep disorders; several books on sleep/wake disorders; 'Sleep Solutions,' a 10-volume informational booklet series for general practitioners; and a regular newsletter entitled 'Good Night/Good Day' that provides updates on research and chapter activities and enables affected individuals from across Canada to exchange information and mutual support. Relevant area(s) of interest: Narcolepsy ·

Young Adults With Narcolepsy Address: Young Adults With Narcolepsy 1451 West 31st Street, Third Floor, Minneapolis, MN 55408 Telephone: (612) 824-1355 EWeb Site: http://www.yawn.or Background: Young Adults with Narcolepsy (YAWN) is a nonprofit international organization that is committed to providing support, engaging in advocacy services, and promoting public awareness on the problems associated with sleep disorders, particularly narcolepsy, on behalf of young adults, family members, peers, coworkers, employers, political leaders, and teachers whose lives are affected by such disorders. Narcolepsy is a chronic sleep disorder characterized by excessive and overwhelming daytime sleepiness, even after adequate nighttime sleep. Daytime sleep attacks may occur with or without warning, often at inappropriate times and places. Some affected individuals also experience a sudden loss of muscle function (cataplexy), ranging from slight weakness to complete body collapse, while fully awake, conscious, and aware. Young Adults with Narcolepsy was founded in 1997 to serve as the voice for a growing generation of young adults with narcolepsy. The organization is committed to promoting and supporting basic and clinical research, coordinating local support groups, increasing access to rehabilitation services and social services agencies, and providing information and support through its web site. The organization's web site has a youth information and support area; discusses YAWN's advocacy and legislative efforts; offers an FAQ ('frequently asked questions') area; and provides information on obtaining support from parents, friends, and employers, joining support groups, or learning to start such groups. The site also offers an online newsletter entitled 'SNEWS,' provides

Seeking Guidance 33

linkage to additional sources of information and support, and offers access to a discussion group. Relevant area(s) of interest: Narcolepsy, Paroxysmal Sleep

Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.

The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about narcolepsy. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “narcolepsy” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “narcolepsy”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred

34 Narcolepsy

language and the format option “Organization Resource Sheet.” By making these selections and typing in “narcolepsy” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with narcolepsy. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “narcolepsy” (or a synonym) in the search box.

Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective.

Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with narcolepsy must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:12 ·

If you are in a managed care plan, check the plan’s list of doctors first.

·

Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.

12

This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

Seeking Guidance 35

·

Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.

·

Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.

Additional steps you can take to locate doctors include the following: ·

Check with the associations listed earlier in this chapter.

·

Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.

·

The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at 13 http://www.abms.org/newsearch.asp. You can also contact the ABMS by phone at 1-866-ASK-ABMS.

·

You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA’s Web site: http://www.amaassn.org/aps/amahg.htm.

If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified. 13

36 Narcolepsy

Selecting Your Doctor14 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·

Give me a chance to ask questions about narcolepsy?

·

Really listen to my questions?

·

Answer in terms I understood?

·

Show respect for me?

·

Ask me questions?

·

Make me feel comfortable?

·

Address the health problem(s) I came with?

·

Ask me my preferences about different kinds of treatments for narcolepsy?

·

Spend enough time with me?

Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.

Working with Your Doctor15 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

·

It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

14 This

section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 15 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

Seeking Guidance 37

·

Bring a “health history” list with you (and keep it up to date).

·

Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

·

Tell your doctor about any natural or alternative medicines you are taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don’t, your doctor will assume that you understood everything that was said.

·

Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

·

Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

·

Ask your doctor to draw pictures if you think that this would help you understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

·

Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

·

After leaving the doctor’s office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.

38 Narcolepsy

Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:16 ·

Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html

·

Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html

·

Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Consciousness: Sense of awareness of self and of the environment. [NIH] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Prevalence: The number of events, e.g., instances of a given disease or other condition, in a given population at a designated time. When used without qualification, the term usually refers to the situation at specific point in time (point prevalence). Prevalence is a number, not a rate. [NIH]

You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

16

Clinical Trials 39

CHAPTER 3. CLINICAL TRIALS AND NARCOLEPSY Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning narcolepsy.

What Is a Clinical Trial?17 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for narcolepsy is to try it on patients in a clinical trial.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

17

40 Narcolepsy

What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on narcolepsy.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for narcolepsy compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment. How Is a Clinical Trial Conducted?

Various organizations support clinical trials at medical centers, hospitals, universities, and doctors’ offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on narcolepsy carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on narcolepsy. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This

Clinical Trials 41

treatment, like a placebo, has no effect on narcolepsy and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how narcolepsy develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for narcolepsy. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial’s investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo

42 Narcolepsy

surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Narcolepsy The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to narcolepsy.18 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

Sleep Disorders of Patients with Diseases of the Nervous System Condition(s): Hypersomnia; Narcolepsy; Nervous System Disease; Sleep Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this study is to assist training doctors about different diseases of the nervous system affecting sleep. Patients selected to participate in this study will have any of a variety of sleep disorders. They will undergo several tests including an overnight recording of brain activity, eye movement, leg movement, breathing, heart rate, and other measures. Results of these tests will be used to better understand diseases causing sleep disorders and may be used to develop better treatments for them. Study Type: Interventional

18

These are listed at www.ClinicalTrials.gov.

Clinical Trials 43

Contact(s): Maryland; National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800411-1222 [email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00001664

Benefits and Risks19 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment for narcolepsy. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

·

If the treatment is effective, then it may improve health or prevent diseases or disorders.

·

Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

·

People who take part in trials contribute to scientific discoveries that may help other people with narcolepsy. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial’s risks and benefits, the researcher’s expectations of you, and your rights as a patient.

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f291. 19

44 Narcolepsy

What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you receive may cause side effects that are serious enough to require medical attention.

How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital’s Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent. What Are a Patient’s Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

·

Know how the researchers plan to carry out the study, for how long, and where.

·

Know what is expected of you.

·

Know any costs involved for you or your insurance provider.

·

Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

·

Talk openly with doctors and ask any questions.

Clinical Trials 45

After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

·

Receive any new information about the new treatment.

·

Continue to ask questions and get answers.

·

Maintain your privacy. Your name will not appear in any reports based on the study.

·

Know whether you participated in the treatment group or the control group (once the study has been completed). What about Costs?

In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don’t have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care. What Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

·

What are the standard treatments for narcolepsy? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

·

What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

·

How long will the treatment last? How often will I have to come back for follow-up exams?

·

What are the treatment’s possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

46 Narcolepsy

·

Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

·

How will my health be monitored?

·

Where will I need to go for the clinical trial? How will I get there?

·

How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

·

Will I be able to see my own doctor? Who will be in charge of my care?

·

Will taking part in the study affect my daily life? Do I have time to participate?

·

How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “narcolepsy” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

Clinical Trials 47

·

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

·

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment : Today’s Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

·

A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

·

The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

·

The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

·

Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

·

Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

48 Narcolepsy

·

Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

49

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on narcolepsy. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on narcolepsy. In Part II, as in Part I, our objective is not to interpret the latest advances on narcolepsy or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with narcolepsy is suggested.

Studies 51

CHAPTER 4. STUDIES ON NARCOLEPSY Overview Every year, academic studies are published on narcolepsy or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on narcolepsy. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on narcolepsy and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and narcolepsy, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the

52 Narcolepsy

format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “narcolepsy” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·

Evaluation of a Single Seizure: Guidelines for Advance Practice Nurses Source: Journal of the American Academy of Nurse Practitioners. 12(4):141-145, April 2000. Summary: The authors provide guidelines for advance practice nurses on how to evaluate the occurrence of a single seizure. About 10 percent of people in the United States will experience a single seizure at some point in their lives. Factors that lead to the diagnosis of a seizure are (1) abrupt onset, (2) brief duration of 1 to 3 minutes, (3) altered consciousness, (4) purposeless or involuntary movements, (5) postictal confusion, and (6) lack of recall. Common episodes that mimic seizures are (1) syncope, (2) transient ischemic attacks, (3) panic attacks, (4) narcolepsy, and (5) pseudo-seizures. Syncope should be considered if a client presents with loss of consciousness and muscle tone at the time of the seizure. Common symptoms of transient ischemic attacks are weakness, numbness, and alterations in speech or vision. Symptoms of panic attacks include anxiety, dizziness, and a sense of fear. Patients with narcolepsy report dreaming during attacks and can be aroused during the event. Pseudoseizures are clinical presentations of seizure-like activity accompanied by normal electroencephalography (EEG) findings. Evaluation of a patient with a single seizure includes (1) a thorough history, (2) neurological examination, (3) appropriate blood work, (4) neuroimaging studies, and (5) an EEG. Once a seizure has been diagnosed, the focus should be on identifying the seizure type. Partial seizures are abnormal neuronal discharges originating from one part of the brain. Generalized seizures involve the entire cortex. Nurses should also evaluate patients for the risk of recurrent seizures or epilepsy. Febrile convulsions, central nervous system infections, cerebral trauma, brain tumors, cerebrovascular disease, and family history are all associated with the development of epilepsy. Patients diagnosed with epilepsy should begin antiepileptic drug (AED) therapy. Primary care providers should consider referring patients with epilepsy to specialists if the following 10 conditions exist: (1) Uncertain of diagnosis, (2) uncomfortable with plan of care, (3) complicated AED changes, (4) discontinuing AED's, (5) partial-onset seizures, (6) focal or

Studies 53

structural lesions on imaging studies, (7) abnormal neurological examination, (8) prenatal counseling, (9) pregnancy, and (10) lack of immediate response to AED's. 2 tables, 23 references. ·

Differential Diagnosis of Epilepsy Source: Seminars in Neurology. 10(4):321-327, December 1990. Summary: A physician discusses methods of evaluation and diagnosis for people with suspected epilepsy. Seizures are diagnosed mainly by history. The goal of a patient history is to get a precise description of a seizure. Physical examination provides important etiological clues. A normal electroencephalogram (EEG) does not exclude epilepsy, and epileptiform discharges do not prove that episodes are epileptic. Additional testing, including computed tomography, magnetic resonance imaging, and psychologic or psychiatric evaluation, may be needed. The differentiation of syncope from seizure is a common problem. The diagnosis of syncope is supported if episodes (1) occur exclusively while standing or sitting; (2) are precipitated by anxiety or pain; (3) are associated with paleness and sweating; and (4) are not associated with tonic-clonic movements and tongue biting, and postepisodic confusion, lethargy, and headache. Transient ischemic attacks cause brief, episodic neurologic dysfunction, and are usually distinguished from seizures. Migraines may be misdiagnosed as epilepsy because both are episodic, paroxysmal discharges with neurologic symptoms. Movement disorders, such as tics, are sometimes misdiagnosed as focal motor seizures. Sleep attacks and excessive daytime sleepiness are the main symptoms of narcolepsy, but these episodes can be diagnosed as atonic, absence, or complex partial seizures. Hypoglycemia causes episodic dizziness, tremulousness, obtundation, stupor, coma, confusion, bizarre behavior, seizures, and sudden hemiparesis. Hormonal disorders may cause seizures and behavioral changes. Prescribed and illicit drugs can cause central nervous system disorders, including seizures, syncope, psychoses, and movement disorders. The diagnosis of abdominal epilepsy is sometimes made incorrectly after gastrointestinal studies and an EEG are normal. Psychogenic seizures are common among patients with epilepsy with medically refractory seizures. Differentiating psychogenic from complex partial and generalized tonic-clonic seizures is often difficult. The author concludes that the clinical features produced by seizures leave physicians with an extensive differential diagnosis, but a careful history will provide the essential information for a correct diagnosis. 65 references.

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·

Driving Impairment Caused by Episodic Brain Dysfunction: Restrictions for Epilepsy and Syncope Source: Archives of Neurology. 43(6):558-564, June 1986. Summary: The authors discuss the limitations of current driving restrictions for persons with epilepsy and other episodic brain illnesses, and propose new guidelines based on medical experience and a review of published studies on prognostic factors and the likelihood of recurrence. The first section discusses issues rising from a lack of clarity in reporting requirements and the failure to distinguish epilepsy from other conditions that may cause abrupt weakness or disruption of thought and pose a threat to driving safety. The second section reviews estimated accident rates for persons with epilepsy, recurrence rates, and methods of predicting recurrence including electroencephalography, clinical data, and epidemiologic data. The third section discusses the incidence of syncope as a cause of driving accidents, precipitating events, the likelihood of recurrence, and prognostic factors. The fourth section reviews other conditions that may cause abrupt severe weakness and unexpected disruptions of cognition, including drop attacks, pseudoepileptic attacks, cataplexy and narcolepsy, and transient global amnesia. The remaining sections present the proposed guidelines for driving restrictions on persons with epilepsy and syncope. Guidelines are not presented for driving restrictions on persons with senility or transient global amnesia, since little data are available concerning driving risks with these populations. Separate driving recommendations are made for specific subgroups of patients based primarily on etiology and the number of seizures in the previous 2 years. For example, in persons with well-defined absence attacks who experience clearly documented immediate elimination of seizures with medication, the waiting period would be reduced to 3 months for driving to school or work. If a seizure occurs after a remission of a year or more, shortly after a change in the antiepilepsy regimen, the authors recommend that the person be restricted for 1 month from driving to school or work and for 3 months from full privileges. In syncope, persons with reliable auras or premonitions of 15 seconds or more during multiple seizures could be allowed to drive sooner. A separate restriction schedule for each of the causes of syncope is not practical and the clinical research to support such a schedule has not been performed. 2 tables, 100 references.

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Comparison of the Psychosocial Effects of Epilepsy and Narcolepsy/Cataplexy: A Controlled Study Source: Epilepsia. 25(4):423-433, 1984.

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Summary: Researchers compared the life effects attributed to epilepsy with those attributed to narcolepsy. A group of 60 individuals with epilepsy from the Epilepsy Clinic at Ottawa General Hospital participated. Researchers matched those 60 individuals with 60 individuals who had narcolepsy/cataplexy and with age- and sexmatched controls. The study assessed psychosocial effects using a questionnaire with over 160 items that inquired about the effects of epilepsy o n work, education, driving, occupational and household accidents, recreation, personality, and interpersonal relationships. It also included questions about other symptoms that could have important socioeconomic consequences (e.g., memory difficulty, visual problems, changes in sexual activity, and somatic symptoms). Data analysis indicated that epilepsy had deleterious effects on work, education, occupational and household accidents, recreation, personality, interpersonal relations, and other parameters. The psychosocial problems due t o epilepsy were pronounced when comparing the group with epilepsy to the control group. Comparisons of individuals with epilepsy and narcolepsy showed that, in general, persons with narcolepsy were even more psychosocially impaired. They had greater frequencies of disease-attributed reduced performance at work, poorer driving records, higher accident rates from smoking, greater problems in planning recreation, and other significant differences. Dissimilar profiles of psychosocial impairment characterized the two conditions. The only areas in which individuals with epilepsy showed greater problems than individuals with narcolepsy were in educational achievement and ability to maintain a driving license. Most of the intergroup differences remained significant even for smaller groups matched for age. The somewhat greater psychosocial impact of narcolepsy appeared to be due to the continuous excessive daytime sleepiness that persisted between diagnostic attacks, whereas persons with epilepsy were relatively alert between seizures. The researchers concluded that epilepsy doe s have major life effects, but these are no greater than for at least one other chronic neurological condition, narcolepsy/cataplexy, which appears to have a greater overall psychosocial impact. Age and duration of illness for individuals with epilepsy have relatively little effect on life parameters. 7 tables, 42 references. ·

Guidelines and Contraindications for Teaching Relaxation as a Stress Management Technique Source: Journal of the Institute of Health Education. 30(1):25-30, 1992. Summary: A researcher provides recommendations for teaching stress management techniques within an educational or group setting, and

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highlights some contraindications for such techniques. Health professionals must consider training issues that may arise before and during a course, such as the aims and objectives of the course, the environment, boundaries (e.g., is it training or a therapy session?), contracts and ground rules, course content and members, insurance for the health professional against liability, the use of pair work, limitations of the trainer, organization (internal politics of an in-house course), and how to deal with potential problems. Guidelines offered include (1) prevent outside disturbances during relaxation training by using do-notdisturb signs, (2) do not attempt deep relaxation techniques after a heavy meal, (3) allow participants to choose their own visualizations, (4) avoid reading from a relaxation script and do not rush, and (5) warn the group of the existence of relaxation-induced anxiety and how to alleviate its effects (usually by opening one's eyes). Progressive relaxation (tensing and untensing muscles) is contraindicated for persons with certain medical conditions, including those with chest pains, myocardial infarction, hypertension, and some cardiac disorders. The instructor should also be cautious with persons who have anxiety and panic attacks, asthma, depression, diabetes mellitus, drug addiction, epilepsy, glaucoma, some hormonal disorders such as thyroid disorders, hypoglycemia, narcolepsy, other mental disorders, and alcohol or substance abuse. No one should teach relaxation who has not been through a controlled experience himself. 1 table, 27 references.

Federally-Funded Research on Narcolepsy The U.S. Government supports a variety of research studies relating to narcolepsy and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.20 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally-funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to narcolepsy and related conditions.

20 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally-funded studies use animals or simulated models to explore narcolepsy and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for narcolepsy: ·

Project Title: Center for Narcolepsy and Related Disorders Principal Investigator & Institution: Mignot, Emmanuel J.; Director; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2000; Project Start 1-JUL-1986; Project End 1-MAY2005 Summary: Narcolepsy is a disabling neurological disorder affecting more than 1 in 2,00 Americans. This program project is the only existing NIH funded multi-disciplinary program focusing on this disorder. Our previous funding has led to significant advances such as the identification and genetic characterization of canine narcolepsy [the only known animal model for this condition], the dissection of the mode of action of currently prescribed narcolepsy treatments and the discovery that HLA- DBQ1*0602, rather than the previously identified HLA-DR2 antigen, is a genuine human narcolepsy susceptibility gene. A neuroanatomical map of the structures and neurotransmitters involved in the pathophysiology of narcolepsy is also being established. A solid linkage marker for the canine narcolepsy gene, canarc-1 was also identified and the genomic segment containing the deficient gene was flanked and physically cloned using a Bacterial Artificial Chromosome (BAC) genomic library build specifically for this purpose. In the next funding period, a new project, Project B, will be initiated in Wisconsin Sleep Cohort. The goal of this project is to define the spectrum of narcolepsy and its symptoms in the general population using HLA typing in the context of an epidemiological approach. Once completed, this project will have direct clinical applications. It will provide the scientific community with the first prevalence estimate for narcolepsy without cataplexy. It will help clinicians and researchers to better define and thus treat this disorder at a time when new stimulant treatments are being increasingly used (and perhaps misused) for the treatment of narcolepsy. The second and third projects are direct continuations of our previous efforts. Project D will further characterize the neuroanatomical and neurophysiological approach. Project C will complete the cloning of canarc-1 and study the function of this deficient gene. Based on the rapid

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pace of our previous progress, we are confident that we will identify canarc-1 during the next funding period. Whether or not this gene is involved in human narcolepsy, the identification of canarc-1 will be a landmark in our understanding of narcolepsy and sleep control. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Epidemiology of Narcolepsy Principal Investigator & Institution: Longstreth, W T.; Associate Professor; Neurology; University of Washington 3935 University Way Ne Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 1-AUG-2001; Project End 1-JUL2005 Summary: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy, an episodic loss of muscle tone triggered by intense emotions. The disease usually manifests by adolescence. Almost all patients with narcolepsy carry the DQB1 0602 gene, an HLA marker for the haplotype associated with narcolepsy. Like other investigators, we hypothesize that although genetic factors may predispose people to develop narcolepsy, environmental exposures between conception and adolescence are essential for expression of the disease. We propose to test this hypothesis and examine other epidemiologic features of narcolepsy with four interrelated epidemiologic studies. First of all, we will estimate the prevalence of narcolepsy using several overlapping methods of case ascertainment and create a registry of all patients who have narcolepsy, as of 2001 July 1, among the close to 1.7 million residents of King County, Washington. Secondly, we will characterize the clinical features and functional consequences of narcolepsy in all patients in the narcolepsy registry. Thirdly, we will survey sleep complaints among a sample of King County residents identified through random-digit dialing. We will determine whether or not these subjects carry a marker for narcolepsy susceptibility, namely the DQB1 0602 gene. If any patients with narcolepsy are identified, they will be added to the narcolepsy registry. For subjects without narcolepsy, the study will yield estimates for the prevalence of sleep complaints among those who do and do not carry the DQB1 0602 gene in this sample of the general population. Finally, and most importantly, we will evaluate potential risk factors for narcolepsy by means of a population-based case-control study. Cases will come from patients in the narcolepsy registry, and control subjects will be the subset of those identified through random-digit dialing who carry the DQB1 0602 gene. We will assess environmental risk factors in genetically susceptible individuals by requiring all subjects, both cases and controls,

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to carry the DQB1 0602 gene. Exposures occurring before late adolescence, especially to chemicals that can affect brain function, will be studied. Although narcolepsy is not known to shorten one's life, it is a lifelong disorder that can cause severe disability. The long- term goals of these four interrelated epidemiologic studies are to learn more about the etiology of narcolepsy and to reduce its occurrence by identifying potentially modifiable, risk factors. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Management of Excessive Daytime Sleepiness in Narcolepsy Principal Investigator & Institution: Rogers, Ann E.; Associate Professor; None; University of Pennsylvania 1 College Hall Philadelphia, Pa 19104 Timing: Fiscal Year 2000; Project Start 0-FEB-1997; Project End 1-JAN2002 Summary: (Adapted from investigator's abstract) Many of the psychological and economic consequences of narcolepsy can be directly attributed to sleep attacks and excessive daytime sleepiness. Uncontrollable episodes of daytime sleep make driving difficult or hazardous, affect the individual's ability to continue an education and pursue a career, and often interfere with interpersonal relationships. Although treatment of narcolepsy can improve symptoms dramatically in some patients, up to a third of patients with narcolepsy obtain little or no benefit from current therapies. Studies have shown widespread dissatisfaction with current pharmacologic treatments; some patients report being undermedicated, that their symptoms are not adequately controlled with stimulant medications, and that they are not satisfied by with treatment regimes that require daytime naps and/or drug holidays. Differences between responders and non-responders and the bases for those differences are unknown. In addition, the identification of patients who are less likely to respond to stimulant medications, will allow clinicians to concentrate more efforts on improving treatment regimes for these patients. The identification of an instrument that is reliable, sensitive to treatment effects, and easy to administer would be of great value for assessing patient's responses to treatment. Thus, the aims of this proposed multicenter study are to: 1) Develop profiles of those patients who respond to stimulant medications and those who do not respond; and 2) evaluate two brief questionnaires (Narcolepsy Symptom Status Questionnaire and Epworth Sleepiness Scale) to see if they can be used to assess treatment efficacy in a clinical setting. Two groups of narcoleptic subjects (135 established patients and 85 newly diagnosed patients) will be recruited from 5 accredited sleep disorders centers. A profile of

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subjects who respond to stimulant medications and those who do not will be developed from demographic data, symptom severity measures, and 24-hr ambulatory polysomnographic recordings made in the subject's usual environment. Compliance with stimulant medications will also be evaluated. In order to evaluate whether or not the NSSQ and ESS are sensitive to treatment effects, newly diagnosed subjects will be tested prior to starting stimulant medications, after 3 months of treatment and after one year of treatment. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Narcolepsy--Multicenter Genetic and Family Study Principal Investigator & Institution: Mitler, Merrill M.; Professor; Scripps Research Institute 10550 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2000; Project Start 1-JUL-1999; Project End 1-MAY2004 Summary: Narcolepsy, as presently understood, is a central nervous system disorder characterized by disabling dysregulation of sleep and wakefulness. Narcolepsy is not rare and afflicts about 1 of every 1000 to 2000 North Americans. While the inheritance of narcolepsy is not known, the disorder is strongly, but NOT always, associated with subtypes of the HLA region chromosome 6 [HLA-DR15(DRB1*1501) and HLADQ6(DQBl*0602)]. Thus, the presence of HLA-associated and non-HLA associated forms indicates that narcolepsy is at least two disorders. Further, both the HLA associated (H+) and the non-HLA associated ( H ) form occur as sporadic isolated cases (F-) and family history positive cases. It is possible that each of the four types, (H+F-),(H+F+), (H-F-), (HF+) represent different etiologies. This Multi-Center Clinical Study grant is based on several key findings: (a) the strong association with the same HLA alleles across several populations indicates a probable role for these alleles/haplotypes, ( b ) only 70 percent of the probands with narcolepsy have the HLA-associated alleles and they tend not to have affected relatives, (c) the majority of families with multiple affected members do not have the associated HLA haplotypes, (d) one pair of MZ twins differs with respect to clinical symptoms, with/without cataplexy, and (e) sleep studies of first degree relatives of probands reveal subtle sleep disturbances. Our overall goals are: (i) Ascertain an additional 113 probands and their families via a sequential sampling scheme which requires that all patients selected as probands meet the strict clinical criteria for narcolepsy (ignoring HLA type) and that all first degree relatives of probands be studied. Rigorous sampling in this manner avoids bias due to selecting "interesting" families and permits accurate evaluation of the proportion of narcoleptics patients with the associated

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HLA types, segregation analysis for narcolepsy and the related clinical subtypes, as well as linkage analyses. (ii) Identify the modes of inheritance for the two familial forms of narcolepsy. Determine the familial aggregation and inheritance of the related sleep disorder symptoms (e.g., excessive daytime sleepiness). (iii) Using both the proband series families and selected "high density" pedigrees, map the location of the non-HLA associated familial form via a genome DNA marker screen and linkage analyses. (iv) Examine the role of the HLAassociated alleles in narcolepsy through both co-segregation and association studies. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Oral Modafinil in Narcolepsy Principal Investigator & Institution: Pack, Allan I.; Professor of Medicine; University of Pennsylvania 1 College Hall Philadelphia, Pa 19104 Timing: Fiscal Year 2000 Summary: This multicenter study examines the effects of an experimental drug, Modafinil, in the treatment of Narcolepsy. The study is being carried out in approximately 26 sites around the US. Subjects with a history of Narcolepsy are screened to assume absense of other significant medical problems and drug-free status. They are then brought into the CRC and sleep lab for overnight sleep studies and daytime tests to confirm the diagnosis of Narcolepsy and to establish the level of baseline functioning. Subjects are then treated in a nine week, double-blind, placebo-controlled paradigm with Modafinil, 200mg or 400mg. Follow up studies of sleep and daytime functioning are carried out at two other times during the protocol. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Pharmacological Studies of Human and Canine Narcolepsy Principal Investigator & Institution: Nishino, Seiji; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2000; Project Start 5-JUL-1998; Project End 0-JUN2003 Summary: (Applicant's abstract): This proposal is a request for a K01 Mentored Research Scientist Development Award. The candidate is a neuropsychiatrist who is experienced in neurochemistry and neuropharmacology. The candidate proposes to gain experience in clinical and basic neuropharmacology. His goal is to develop better pharmacological treatments for human narcolepsy. Human narcolepsy is

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a sleep disorder affecting 0.05-0.16% of the general population. The objective of this proposal is to dissect the neurochemical control of sleep in narcolepsy using a pharmacological approach and to apply this knowledge to improve the treatment for human narcolepsy. This will not only benefit narcoleptic patients but also provide critical information on the neurochemical mechanisms generating normal sleep. The research is greatly facilitated by the use of a unique animal model of narcolepsy in which the condition is transmitted as a fully penetrant autosomal recessive trait. In the past several years, the candidate has focused on the pharmacological control of canine cataplexy, a pathological manifestation of REM sleep atonia. The results indicate that this symptom, as REM sleep, is mainly controlled by cholinergic and monoaminergic systems. Several receptor subtypes that mediate this neuropharmacological control (muscarinic M2, adrenergic alpha-lb and alpha-2/D2(3)) have been identified. In this award period, the candidate will: (1) apply the knowledge that the adrenergic system is the most important monoaminergic system for the control of cataplexy obtained using the canine model to improve the treatment of human cataplexy, (2) test the hypothesis that the wake-promoting effects of amphetamine-like compounds are mediated via presynaptic stimulation of the dopaminergic transmission by attempting to correlate the in vivo effects on sleep and in vitro binding affinities for dopamine transporter site, in vitro potencies of dopamine uptake inhibition and in vivo effects on dopamine efflux of various wake-promoting compounds, and (3) determine the sites of action of wake-promoting compounds. This will involve local drug injection and in vivo microdialysis experiments. As preliminary results suggest the involvement of the mesolimbocortical dopaminergic system in narcolepsy, the candidate will principally focus on this anatomical system. Results from the canine model concerning excessive sleepiness could also apply to human narcoleptics at a later stage. With this Research Scientist Development Award, the candidate will contribute to the development or better pharmacological treatments of human narcolepsy while also furthering the candidate's career objective to be an independent scientist. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Spectrum of Narcolepsy and its Symptoms Principal Investigator & Institution: Young, Terry B.; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2000; Project Start 1-JUL-1986; Project End 1-MAY2005

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Summary: The overall goal of the epidemiology study proposed here is to provide population-based knowledge on the occurrence and correlates of narcolepsy-related symptoms and polygraphic signs as a foundation for characterizing and refining the working definition of human narcolepsy. We propose the collection of new data from participants enrolled in the Wisconsin Sleep Cohort Study, a longitudinal epidemiology study of the natural history of sleep disorders. This will be established by: a) administering a narcolepsy-related symptom questionnaire to a sample of 5000 middle-aged men and women; b) on a subsample of 820, conducting multiple-sleep latency tests (MSLTs) designed to detect episodes of sleep-onset rapid eye movement sleep periods (SOREMPs); and c) HLA typing to determine DQP1 positivity These new data will be added to extensive subjective and objective data on a sample of 1400, including baseline and follow-up polysomnography, experimental MSLTs, and other tests collected previously and currently as part of the Wisconsin Sleep Cohort Study. The anticipated results will be of direct application to the development of more specific and more sensitive guidelines for diagnosis and treatment of narcolepsy. In addition, the expected new knowledge on the spectrum and correlates of narcolepsy symptoms and signals will provide a foundation for further research on risk factors and adverse health outcomes on narcolepsy. The specific aims are: 1. To determine in the general adult population the distribution and correlates of narcolepsy-related symptoms (cataplexy, sleep paralysis, hypnagogic hallucinations, automatic behavior, excessive daytime sleepiness, and disturbed nocturnal sleep), and polygraphic signs including SOREMPs; 2. To confirm that HLA-DQ polymorphisms in the general population influence nocturnal sleep architecture; 3. To evaluate the influence of HLA susceptibility alleles on narcolepsy-related symptoms and signals, diagnostic groupings, and symptom clusters. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Circadian and Aminergic Regulation of Orexin Neurons Principal Investigator & Institution: Scammell, Thomas E.; Professor; Beth Israel Deaconess Medical Center 330 Brookline Ave Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 5-AUG-2001; Project End 1-JUL2006 Summary: (provided by applicant): The neuropeptide orexin (also known as hypocretin) plays a central role in the regulation of sleep/wake behavior and the pathology of narcolepsy. People with narcolepsy have difficulty maintaining wakefulness and often have intrusions of REM sleep-like phenomena into wakefulness. These individuals often have decreased numbers of orexin neurons and undetectable concentrations of

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orexin in cerebrospinal fluid, and mice and dogs with mutations in the genes for orexin or its receptors have a phenotype resembling narcolepsy. As orexin appears necessary for the normal maintenance of wakefulness and suppression of REM sleep, it is critical that we identify the factors that influence the activity of orexin neurons. We propose a model in which orexin neurons promote wakefulness and inhibit REM sleep by activating aminergic arousal regions, and, in turn, the orexin neurons are activated by these aminergic regions. Thus, orexin neurons should be active during wakefulness, and this orexin neuron activity should further increase the activity of aminergic arousal regions, thereby promoting and stabilizing wakefulness. By increasing aminergic activity, orexin neurons also should inhibit REM sleep. In the absence of this positive feedback, the amount of wakefulness should be reduced, bouts of wakefulness should be shorter, and the amount of REM sleep should be increased. Wakefulness and REM sleep are tightly regulated by circadian factors, and we also propose that orexin neurons are influenced by circadian factors, thus contributing to the circadian regulation of sleep/wake behavior. In rats, this circadian signal would facilitate the activation of orexin neurons during the night phase, thereby promoting wakefulness and suppressing REM. In the absence of orexin, the circadian influence on wakefulness and REM should be lost. Our proposed experiments will test the roles of these aminergic and circadian influences. We will first determine whether orexin neurons are active during wakefulness and whether this activation is dependent upon circadian phase. We will use the expression of Fos protein and c-fos mRNA in orexin neurons as well as the concentration of orexin in CSF as indicators of orexin neuron activity, and we will correlate these measures with sleep/wake behavior. We then will determine whether orexin mediates circadian influences on sleep/wake architecture by studying rodents in a light/dark cycle or in constant darkness; these experiments will use two models of orexin deficiency: orexin knockout mice and transgenic rats with an acquired loss of orexin neurons similar to human narcolepsy. Next, we will determine whether orexin neurons are innervated by aminergic arousal regions and express excitatory amine receptors. To test the importance of these aminergic afferents, we will study the response to amphetamine of orexin knockout mice and transgenic rats lacking orexin neurons. By investigating these circadian and aminergic influences on orexin neurons, we will gain critical insights into the normal function of orexin neurons that should provide new perspectives on normal behavioral state control and the neurobiology of narcolepsy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: CORE--Clinical/Laboratory Data Base and Tissue Bank Principal Investigator & Institution: Dement, William C.; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2000 Summary: The Stanford Narcoleptic Canine Colony is an indispensable research resource for this program project, other NIH grants and other investigators. In this Core, we are requesting funds to maintain the colony and research canines required for this program project and collaborating investigators. The canine database contains information on almost 500 animals. This includes disease status, severity of the symptoms of narcolepsy if applicable, genetic and pedigree information, tissue collection (nature and location, if any) and other information relevant to the health of the animal. A pharmaceutical compound database recording the observed effects of more than 200 compounds on the symptoms of narcolepsy is also maintained. The Core is also the primary source of information and tissue for human narcolepsy subjects and relatives. Clinical files containing medical history, pedigree information, questionnaire data and HLA typing results are the primary source of the data. The human narcolepsy database contains genetic and clinical information on more than 1,800 subjects. It is the responsibility of the Principal Investigator to assure that the Center for Narcolepsy scientists work as an integrated team and that through this scientific leadership, pursuit of overall goals of the program is consistent. A weekly research meeting is held to facilitate communication among the investigators and between the research staff and administrative staff. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Hypocretin Release in Disease States and Behavior Principal Investigator & Institution: Siegel, Jerome M.; Professor; None; University of California Los Angeles 405 Hilgard Ave Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 1-AUG-2001; Project End 1-JUL2005 Summary: Recent work in our laboratory has indicated that a degenerative loss of hypocretin (orexin) neurons underlies most cases of human narcolepsy. Several chronic diseases have symptomatic similarities to narcolepsy. This suggests that they may share abnormalities in the operation of the hypocretin (Hcrt) system. For example, patients with unipolar depression and schizophrenia exhibit REM sleep at sleep onset, one of the defining characteristics of narcolepsy. Nighttime sleep is frequently disrupted in both disorders, as

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in narcolepsy. The age of onset of both of these disorders is similar to that of narcolepsy. Many patients with schizophrenia have hallucinations resembling the hypnagogic hallucinations of narcolepsy. Alzheimer's disease, like narcolepsy, is characterized by daytime sleepiness and nighttime sleep disruption. This "sundowning" and related hallucinatory mentation is the most frequent cause of institutionalization. We have developed a far more sensitive assay for Hcrt than that used in prior published studies and have access to a large number of cerebrospinal fluid (CSF) samples from these three groups of patients and suitable controls. We will determine if low Hcrt levels are unique to narcolepsy or if they are present in one or more of these other disorders. We will determine if an Hcrt blood test can be developed to detect narcolepsy. Such a test would have an enormous impact upon the diagnosis and treatment of sleep disorders and on sleep research in general. We will compare blood Hcrt levels in narcoleptics, sleep apneics, REM sleep behavior disorder patients and controls. In parallel animal studies, we will determine the effect of behavior, including motor activity, feeding and short term sleep deprivation upon CSF Hcrt levels. Finally, we will use in vivo microdialysis to determine the pattern of Hcrt release in locus coeruleus, hypothalamus and ventrolateral preoptic area across the sleep wake cycle. We will contrast release patterns in active vs. quiet waking and REM vs. nonREM sleep. These studies will help define the role of this newly identified neurotransmitter system in relation to motor behavior, the sleep wake cycle and in human disease. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Hypocretins and Their Role in the Control of Sleep Principal Investigator & Institution: Maki, Richard A.; Senior Staff Scientist; Neurocrine Biosciences, Inc. 10555 Science Center Dr San Diego, Ca 92121 Timing: Fiscal Year 2001; Project Start 5-SEP-2001; Project End 1-AUG2002 Summary: Desription: (Adapted from the Applicant?s Abstract) Insomnia is one of the more prevalent sleep disorders in the US, affecting about 10 percent of the population. Other sleep disorders include obstructive sleep apnea, restless leg syndrome and narcolepsy. Recently, a mutation in the G-protein coupled receptor hypocretin receptor-2 has been linked to the development of narcolepsy in dogs. In addition, the disruption of a gene in mice for the neuropeptide hypocretin led to the development of narcolepsy in those mice. These two results have focused attention on the hypocretin system as an important modulator of sleep in humans. The applicant organization, Neurocrine Biosciences, has developed a series of

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small molecule antagonists to the hypocretin receptor-2. The focus of this application is to first characterize these small molecule antagonists in vitro. The antagonists will be tested in competitive binding assays and cell-based functional assays. Second, the small molecule antagonists will be tested in vivo. Both rat and dog models will be set up and evaluated for the effect of the small molecule antagonists on sleep and wakefulness. The specificity of the effects of the small molecule antagonists will be further evaluated by comparing normal dogs with hypocretin receptor-2 mutated narcoleptic dogs. The results of this study will be valuable in determining the effectiveness of a hypocretin receptor antagonist in the control of sleep. These studies will also help to prepare the groundwork for the future development of hypocretin receptor-2 agonist as a possible treatment for narcolepsy. PROPOSED COMMERCIAL APPLICATION: A potential application for the research proposed is in the field of insomnia (an estimated 10% of the population suffers from chronic insomnia). Based on the available data, it is reasonable to hypothesize that hypocretin receptor antagonists will promote non-REM and REM sleep. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Hypothalamic Regulation of Sleep Principal Investigator & Institution: Shiromani, Peter J.; Associate Professor; Neurology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 3-SEP-1997; Project End 0-JUN2006 Summary: (provided by applicant): Human narcolepsy was recently associated with a decline in orexin/hypocretin containing neurons. These neurons are located only in the lateral hypothalamus, a region not previously implicated in narcolepsy or REM sleep. How could destruction of these cells lead to narcoleptic behavior? One way to answer this question would be to determine whether lesion of the target neurons produces narcoleptic symptoms. However, there are no studies demonstrating which hypocretin/orexin innervation to what target area regulates which aspect of sleep-wake behavior. To target the cells which express the hypocretin/orexin receptors in adult animals, we have conjugated the ribosome inactivating protein, saporin, to hypocretin2/orexin B. We will utilize the orexin-saporin to test the overall hypothesis that hypocretin/orexin via its innervation of specific targets promotes wakefulness and inhibits REM sleep. Specific aim 1 will test the hypothesis that orexin/hypocretin innervation to the dorsolateral pons regulates REM sleep and cataplexy. Historically, the dorsolateral pontine area has been implicated in regulating REM sleep. Since narcoleptic

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canines and the orexin gene knockout mice show cataplexy and rapid onset of REM sleep, destruction of the hypocretin/orexin-receptor containing neurons should result in cataplexy and REM sleep. Specific aim 2 will test the hypothesis that the orexin/hypocretin neuronal innervation of the TMN is important for wakefulness. Since narcoleptics are excessively sleepy, it is possible that the hypocretin/orexin influence on wakefulness may come via innervation of neurotransmitter containing populations such as the TMN, LC and basal forebrain. Specific aim 3 will examine the effects of orexin-saporin applied to the basal forebrain on sleep and wakefulness. Besides the TMN, wake-active neurons located in the basal forebrain are also hypothesized to promote wakefulness, and hypocretin/orexin fibers innervate this region. It is also hypothesized that degenerating axon in this region might underlie the emotional triggering of cataplectic attacks in narcolepsy (Siegel et al., 1999). Since application of orexin-saporin destroys orexin-receptor bearing neurons, this is an excellent method that can be used to evaluate the degenerating axon hypothesis. Specific aim 4 will examine the effects of orexin-saporin applications to the VLPO-preoptic area. In the previous cycle we demonstrated that lesions of the sleep-active cells in VLPO produce longlasting insomnia. Since hypocretin/orexin fibers innervate this area it is necessary to determine whether orexin-saporin administered to the VLPO produces long-lasting hypersomnia. Specific aim 5 will determine the effects of the orexin-saporin on neurons containing the hypocretin-1 versus hypocretin-2 receptors. This will determine which receptor subtype containing neurons are affected by the saporin conjugate. Our findings will provide a framework for integrating the hypocretin/orexin cells within an overall model of sleep regulation. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Orexin and the Control of Sleep and Wakefulness Principal Investigator & Institution: Mccarley, Robert W.; Professor; Psychiatry; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 1-MAR-2001; Project End 8-FEB2006 Summary: (applicant's abstract): Orexins/Hypocretins are newly discovered hypothalamic peptides that studies in canine inherited narcolepsy and mouse knock-out experiments link to cataplexy/narcolepsy, which may be regarded as disorders of REM sleep and wakefulness. Indeed, orexin neurons in the lateral hypothalamus have widespread projections to regions important in control of sleep and wakefulness. The broad objective of this program of research is to

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understand the physiological and pharmacological mechanisms by which orexin modulates behavioral state and thereby to provide a sound basis for the understanding and treatment of human sleep disorders, especially narcolepsy. The key techniques to be used are novel combinations of multi-disciplinary methods including the use of microdialysis perfusion of antisense against mRNA of orexin receptors combined with electrographic recording of behavioral states, measurement of extracellular levels of orexin peptides using enzyme linked immunosorbent assay (ELISA), and a method combining extracellular single unit recording with microdialysis-delivered orexinA and B in freely behaving rats. Our broad hypotheses are that (1)orexin/hypocretin controls/regulates REM sleep and cataplexy via selective action on brainstem neurons, primarily those in the nucleus sub-coeruleus alpha, and that this action is mediated by the orexin II receptor; and (2)that orexin/hypocretin regulates wakefulness through the forebrain sites of the cholinergic basal forebrain and tubero-mammillary nucleus (TMN), with mediation by the orexin II receptor. Microdialysis perfusion of antisense against the mRNA of orexin receptors will be used to reduce the levels of orexin receptors, producing a "reversible knockout." We will test the hypothesis that, in accord with our preliminary data, orexin-B has a major effect on REM-related phenomena via orexin type II receptors in the subcoeruleus region of the pontine reticular formation, and that antisense to this receptor will increase muscle atonia and the REM phase of sleep, as well as cataplexy. We hypothesize that orexin acts via type I receptors in the locus coeruleus and dorsal raphe, predicting that antisense to type I receptors will increase REM sleep but not cataplexy. Conversely, we predict that microdialysis application of orexin B and A (relatively selective for type I receptors) respectively to these regions will decrease REM sleep. Microdialysis applications of antisense and orexin-B in brainstem muscle inhibitory pathways will test for the presence of predicted orexin modulatory effects on cataplexy. For mesopontine cholinergic neurons, we predict that orexin-B mediates arousal via activating neurons preferentially active in both wakefulness and REM sleep, and this will be tested via microdialysis-applied orexin-B combined with unit recording. In the forebrain, we hypothesize that orexin promotes wakefulness by excitatory actions on basal forebrain and histaminergic neurons preferentially active in this state, and modulated by orexin II receptors, a hypothesis supported by our preliminary data on basal forebrain microdialysis perfusion of orexin peptide. In experiments whose logic parallels those in the brainstem (but with wakefulness as the primary variable), we will use perfusion of antisense, orexin-B and electrographic and unit recording to test this hypothesis. Throughout all brainstem and forebrain sites, we predict that the extracellular levels of

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orexin-A will be highest during the dark (active) phase compared with the light phase and orexin-B will be highest in wakefulness as compared to non-REM phases of sleep. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Pupillometric Sleepiness in Treated Sleep Disorders Principal Investigator & Institution: Merritt, Sharon L.; Medical-Surgical Nursing; University of Illinois at Chicago at Chicago Chicago, Il 60612 Timing: Fiscal Year 2000; Project Start 5-MAY-2000; Project End 9-FEB2004 Summary: Patients with obstructive sleep apnea and narcolepsy can experience a diminished quality of life, decreased productivity, and workplace and traffic accidents due to the pathologic excessive daytime sleepiness (EDS) associated with these disorders. Currently, the extent of EDS is determined by polysomnography and the Multiple-Sleep Latency Test (MSLT), two EEG-based physiologic sleepiness measures that are labor intensive, time-consuming, expensive and receive limited health insurance coverage. As people become sleepy, their pupils oscillate widely and decrease in size. In this study, the Pupil Unrest Index (PUI) will be calculated to estimate sleepiness using desk top pupillometry, an efficient, convenient, non-invasive and easily repeatable technique. The PUI quantitatively describes the extent of pupillary oscillation during 15 minutes of alertness testing. Quantitative data comparing the PUI to other physiologic sleepiness measures are not available. The subject cohorts for this repeated measures, known groups methodologic study will consist of normal controls, and obstructive sleep apnea and narcolepsy subjects before and after usual treatment. The specific aims are to (1) correlate the PUI with MSLT sleep latencies among the subject groups; 92) compare the PUI to the MSLT in detecting sleepiness among the three subject groups; and (3) compare the PUI and the MSLT to other objective and subjective sleepiness measures between subject groups, and before and after usual treatment among the OSA and narcolepsy subjects. MANOVA will be used to examine the linear relationship between the PUI and the MSLT among the subject groups, and the differences in measures of perceived sleepiness, sleep quantity, sleep quality and continuity, mood and functional status between the subject groups, and pre-post-treatment fore subjects with OSA and narcolepsy. The sensitivity and specificity of the PUI in detecting sleepiness will be estimated using the MSLT results as the "gold standard" for classifying subjects. MLR will be used to estimate the relationship between the PUI or the MSLT, and other objective and subjective sleepiness measures. Results will provide evidence about the PUI as a reliable and valid

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objective outcome measure of waking tendency among controls, and prepost-treatment for OSA and narcolepsy subjects. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Synaptic Modulation Of Mesopontine Cholinergic Neurons Principal Investigator & Institution: Leonard, Christopher S.; Profesor; Physiology; New York Medical College Elmwood Hall Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 1-DEC-1991; Project End 1-JAN2006 Summary: (provided by applicant): Chronic or intermittent sleep disorders such as narcolepsy, sleep apnea, and insomnia afflict nearly 40 million people in the United States. Yet the neural mechanisms controlling both normal sleep and its pathologies remain poorly understood. Considerable evidence indicates that mesopontine cholinergic neurons are critical for this control and that their disregulation is involved in narcolepsy, Parkinson's disease, supranuclear palsy and depression. The long-term goal of this project is to understand the synaptic and non-synaptic mechanisms regulating activity of mesopontine cholinergic neurons. Recent compelling evidence indicates that disruption of the novel Hypocretin/Orexin (Hcrt/Orx) peptide system results in narcolepsy - a sleep disorder characterized by excessive daytime sleepiness, sleep fragmentation and the intrusion of rapid eye movement sleep behaviors into wakefulness. Anatomical evidence and our data indicate that mesopontine cholinergic neurons are important targets of these peptides. This proposal focuses on identifying the mechanisms by which Hcrt/Orx acts upon mesopontine cholinergic neurons and associated sleep-related neurons. We will investigate the general hypothesis that Hcrt/Orx peptides regulate both the short-term and long-term excitability of sleep-related neurons. To do so we will use whole-cell recording and calcium imaging methods in brain slices obtained from control mice and mice lacking the two known orexin receptors. We will address this hypothesis by 1) characterizing the ionic currents responsible for the post-synaptic excitatory actions of Hcrt/Orx peptides; 2) Identifying the sources and consequences of intracellular [Ca2+] changes produced by Hcrt/Orx peptides; 3) Identifying the specific roles of each orexin receptor by utilizing single and double receptor knockout mice and 4) Investigating possible alterations in neuron excitability in the mouse double orexin receptor knockout model of narcolepsy. Collectively, these results will advance the understanding

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of the molecular and cellular mechanisms underlying sleep regulation and its pathology. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

E-Journals: PubMed Central21 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).22 Access to this growing archive of e-journals is free and unrestricted.23 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “narcolepsy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for narcolepsy in the PubMed Central database: ·

ApoE polymorphisms in narcolepsy by Martin Gencik, Norbert Dahmen, Stefan Wieczorek, Meike Kasten, Alexandra Gencikova, and Jorg T. Epplen; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=55694

·

Genetic Linkage of Autosomal Recessive Canine Narcolepsy with a [mu] Immunoglobulin Heavy-Chain Switch-Like Segment by E Mignot, C Wang, C Rattazzi, C Gaiser, M Lovett, C Guilleminault, WC Dement, and FC Grumet; 1991 April 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51470

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine. The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 22 With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 23 The value of PubMed Central, in addition to its role as an archive, lies the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 21

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references. It is also free to the public.24 If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with narcolepsy, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “narcolepsy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “narcolepsy” (hyperlinks lead to article summaries): ·

Attentive and preattentive processing in narcolepsy as revealed by event-related potentials (ERPs). Author(s): Naumann A, Bierbrauer J, Przuntek H, Daum I. Source: Neuroreport. 2001 September 17; 12(13): 2807-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11588581&dopt=Abstract

·

Non-pharmacological approaches to the treatment of narcolepsy. Author(s): Garma L, Marchand F. Source: Sleep. 1994 December; 17(8 Suppl): S97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7701208&dopt=Abstract

Vocabulary Builder Abdominal: Pertaining to the abdomen. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

24

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Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU]

Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized Tlymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Aura: A subjective sensation or motor phenomenon that precedes and marks the of a paroxysmal attack, such as an epileptic attack on set. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cholinergic: Resembling acetylcholine in pharmacological stimulated by or releasing acetylcholine or a related compound. [EU]

action;

Clonic: Pertaining to or of the nature of clonus. [EU] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Confusion:

Disturbed orientation in regard to time, place, or person,

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sometimes accompanied by disordered consciousness. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dorsal: 1. pertaining to the back or to any dorsum. 2. denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electroencephalography: The recording of the electric currents developed in the brain, by means of electrodes applied to the scalp, to the surface of the brain (intracranial e.) or placed within the substance of the brain (depth e.). [EU]

Enzyme: Substance, made by living cells, that causes specific chemical changes. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Extracellular: Outside a cell or cells. [EU] Febrile: Pertaining to or characterized by fever. [EU] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Hypertension: High blood pressure (i.e., abnormally high blood pressure tension involving systolic and/or diastolic levels). The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines hypertension as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or taking hypertensive medication. The cause may be adrenal,

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benign, essential, Goldblatt's, idiopathic, malignant pate, portal, postpartum, primary, pulmonary, renal or renovascular. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Infarction: 1. the formation of an infarct. 2. an infarct. [EU] Innervation: 1. the distribution or supply of nerves to a part. 2. the supply of nervous energy or of nerve stimulus sent to a part. [EU] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with

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the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Perfusion: The passage of fluid through an organ. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The entire physical, biochemical, and physiological makeup of an individual as determined by his or her genes and by the environment in the broad sense. [NIH] Prenatal: Occurring before birth. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Progressive: Increasing in severity. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU]

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Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refractory: Not readily yielding to treatment. [EU] Remission: A diminution or abatement of the symptoms of a disease; also the period during which such diminution occurs. [EU] Schizophrenia: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, hallucinations, emotional disharmony, and regressive behavior. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Senility: Old age; the physical and mental deterioration associated with old age. [EU] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Surgical: Of, pertaining to, or correctable by surgery. [EU] Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Syncope: Fainting; temporary loss of consciousness. [NIH] Tomography: The recording of internal body images at a predetermined plane by means of the tomograph; called also body section roentgenography. [EU]

Tonic: 1. producing and restoring the normal tone. 2. characterized by continuous tension. 3. a term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU]

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CHAPTER 5. PATENTS ON NARCOLEPSY Overview You can learn about innovations relating to narcolepsy by reading recent patents and patent applications. Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.25 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available to patients with narcolepsy within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available to patients with narcolepsy. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information.

25Adapted

from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Patents on Narcolepsy By performing a patent search focusing on narcolepsy, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on narcolepsy: ·

Human narcolepsy gene Inventor(s): Olafsdottir; Berglind Ran (Reykjavik, IS), Gulcher; Jeffrey (Chicago, IL) Assignee(s): deCODE genetics ehf. (Reykjavik, IS) Patent Number: 6,319,710 Date filed: January 7, 2000 Abstract: The gene for hypocretin (orexin) receptor 1 (HCRTR1), which is associated with narcolepsy, is disclosed. Also described are methods of diagnosis of narcolepsy, pharmaceutical compositions comprising nucleic acids comprising the HCRTR1 gene, as well as methods of therapy of narcolepsy. Excerpt(s): Narcolepsy, a disorder which affects approximately 1 in 2,000 individuals, is characterized by daytime sleepiness, sleep fragmentation, and symptoms of abnormal rapid eye movement (REM) sleep that include cataplexy (loss of muscle tone), sleep paralysis, and hypnagogic hallucinations (Aldrich, M. S., Neurology 42:34-43 (1992); Siegel, J. M., Cell 98:409-412 (1999)). In humans, susceptibility to narcolepsy has been associated with a specific human leukocyte antigen (BLA) alleles, including DQB1*0602 (Mignot, E., Neurology 50:S16-22 (1998); Kadotani, H. et al., Genome Res. 8:427-434 (1998); Faraco, J. et al., J. Hered. 90:129132 (1999)); however, attempts to verify narcolepsy as an autoimmune disorder have failed (Mignot, E. et al., Adv. Neuroimmunol. 5:23-37 (1995); Mignot, E., Curr. Opin. Pulm. Med. 2:482-487 (1996)). In a canine model of narcolepsy, the disorder is transmitted as an autosomal recessive trait, canarc-1 (Foutz, A. S. et al., Sleep 1:413-421 91979); Baker, T. L. and Dement, W. C., Brain Mechanisms of Sleep (D. J. McGinty et al., eds.s, New York: Raven Press, pp. 199-233 (1985)). The possibility of

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linkage between canarc-1 and the canine major histocompatibility complex has been excluded (Mignot, E. et al., Proc. Natl. Acad. Sci. USA 88:3475-3478 (1991)). ... A mutation in the hypocretin (orexin) receptor 2 gene in canines has been identified in narcolepsy (Lin, L. et al., Cell 98:365-376 (1999)); Hypocrexins/orexins (orexin-A and -B) are neuropeptides associated with regulation of food consumption (de Lecea, L., et al., Proc. Natl. Acad. Sci. USA 95:322-327 (1998); Sakurai, T. et al, Cell 92:573-585 (1998)) as well as other possible functions (Peyron, C. et al., J. Neurosci. 18:9996-10015 (1998)). Human cDNA of receptors for orexins have been cloned (Sakurai, T. et al., Cell 92:573-585 (1998)), however, full human genes for the orexin receptors have not yet been identified. ... Diagnosis of narcolepsy is difficult, as it is necessary to distinguish narcolepsy from other conditions such as chronic fatigue syndrome or other sleep disorders (Ambrogetti, A. and Olson, L. C., Med. J. Aust. 160:426-429 (1994); Aldrich, M. S., Neurology 50:S2-7 (1998)). Methods of diagnosing narcolepsy based on specific criteria would facilitate identification of the disease, reduce the time and expense associated with diagnosis, and expedite commencement of treatment. Web site: http://www.delphion.com/details?pn=US06319710__ ·

Treatment of narcolepsy with immunosuppressants Inventor(s): Siegel; Jerome M. (Northridge, CA), Boehmer; Lisa N. (Northridge, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,204,245 Date filed: September 17, 1999 Abstract: The invention provides compositions and methods for treatment of narcolepsy or isolated cataplexy. Such methods entail administering a therapeutically effective regime of at least one immunosuppressive agent. The methods are particularly useful for prophylactic and therapeutic treatment of narcolepsy or isolated cataplexy. Excerpt(s): This invention resides in the fields of neurology, immunology, and medicine and relates to the treatment of narcolepsy, and immunosuppressive agents and compositions useful therein. ... Narcolepsy is a disabling neurological disorder that was first recognized 118 years ago by Gelineau, J. B. (De la narcolepsie, Gazette des Hopitaux Paris (1880) 53: 626-628). For a review of narcolepsy, see generally Chokroverty, S. (ed.), Sleep Disorders Medicine: Basic Science, Technical Considerations, and Clinical Aspects, 2.sub.2 nd edition, Butterworth

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Heinemann, Boston, Mass. U.S.A. 1999; Aldrich, M., Sleep Medicine, Oxford University Press, New York, N.Y. U.S.A. 1999; Vgnotzas, A. N. et al., Annu. Rev. Med. (1999) 50:387-400; and Guillenminault, C., Narcolepsy Syndrome in Principles and Practice of Sleep Medicine, 2.sup.nd edition (Kryger, M. H., et al. (eds.), (W. B. Saunders Philadelphia, Pa. U.S.A. 1989), pages 338-246). The symptoms of narcolepsy include excessive daytime sleepiness (EDS), hypnagogic and hypnopompic hallucinations (hallucinations during transitions into and out of sleep, respectively), cataplexy (sudden and reversible loss of muscle tone), sleep paralysis (an inability to move at sleep onset or awakening) and REM sleep at sleep onset (Guilleminault, C. 1989). In narcoleptics, sleep occurs at inappropriate times and in dangerous and embarrassing situations. Although total sleep time is near normal, nighttime sleep is disrupted by frequent awakenings (Mitler, M. et al., Psych Clin. N. Amer. (1987) 10:593-606). Cataplexy, a temporary, partial or complete paralysis due to a sudden loss of muscle tone, with unimpaired consciousness, is typically triggered by sudden strong emotions, such as those accompanying laughter, anger and embarrassment. In some patients, status cataplecticus, or periods of repetitive loss of muscle tone, occurs and can last for hours or days. ... Narcolepsy has also been reported to occur in other animals and has been most intensively studied in canines (Foutz, A. S., et al., (1979) Sleep 1:413421; Nishino, S. and Mignot, E. (1997) Prog. Neurobiol. 52:27-78; Cederberg, R., et al., (1998) Vet. Rec. 142, 31-36). Canine narcolepsy in Doberman pinschers and Labrador Retrievers is transmitted as an apparently single gene autosomal recessive trait with full penetrance, canarc-1 (Foutz, A. S., et al., (1979) Sleep 1:413-421; Baker, T.L. and Dement, W. C. (1985), Canine narcolepsy-cataplexy syndrome: evidence for an inherited monoaminergic-cholinergic imbalance in Brain Mechanisms of Sleep, D. J. McGinty, R. Drucker-Colin, A. Morrison, and P. L. Parmeggiani, eds. (New York: Raven Press), pages 199-233). A large number of physiological and pharmacological studies have demonstrated a close similarity between human and canine narcolepsy (Baker, T. L. and Dement, W. C. (1985) and Nishino, S. and Mignot, E. (1997)). These animals have all the major symptoms defining narcolepsy in humans, including episodes of cataplexy. Canine narcoleptics also exhibit excessive daytime sleepiness and interrupted sleep periods (Kaitin, K. I. et al., Electroenceph. Clin. Neurophysiol. (1986) 64:447-454). Cholinergic antagonists block cataplexy in both canine and human narcoleptics (Delashaw et al., (1979) Exp. Neurology 66:745-757). .alpha.1 blockers (such as prazosin) exacerbate cataplexy in dogs and humans and can produce status cataplecticus in both species (Mignot et al., (1988) Brain Res. 444:184-188; Guilleminault et al., (1988) The Lancet 2: 511). Drugs

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used to treat cataplexy and excessive sleepiness in humans are also effective in narcoleptics dogs (Baker and Dement, 1985). Narcolepsy usually does not develop until adolescence in humans, but it can be seen as early as three or as late as 45 years of age or older (Yoss and Daly, (1960) Pediatrics 25:1025-1033; Billiard, (1985) Ann. Clin.Res 17:220-226). The appearance of cataplexy, as a proxy variable for the onset of narcolepsy/cataplexy, in canine narcolepsy, develops between 4 and 24 weeks of age. Web site: http://www.delphion.com/details?pn=US06204245__ ·

Method and composition for treating obesity, drug abuse, and narcolepsy Inventor(s): Hohenwarter; Mark (Mobile, AL) Assignee(s): Serotonin Industries of Charleston (Charleston, SC) Patent Number: 4,843,071 Date filed: December 5, 1986 Abstract: Compositions and methods are disclosed for the treatment of obesity, depression, drug abuse, and narcolepsy. The compositions comprise a norepinephrine precursor such as L-tyrosine or Lphenylalanine in combination with a norepinephrine re-uptake inhibitor such as desipramine. In another embodiment of the invention, the compositions further comprise enzymatic cofactors for the biosynthesis of norepinephrine. Excerpt(s): This invention relates to compositions comprising a norepinephrine precursor, such as L-tyrosine or L-phenylalanine in combination with a norepinephrine re-uptake inhibitor such as desipramine. The compositions are useful in controlling obesity, depression, drug abuse, and narcolepsy in animals. The invention also relates to said compositions further comprising one or more enzymatic cofactors for the biosynthesis of norepinephrine. This invention further relates to a method of controlling obesity, depression, drug abuse, or narcolepsy in an animal comprising administering an effective amount of the compositions of this invention to said animal. ... Thus, a medicament comprising the combination of a norepinephrine precursor and a norepinephrine re-uptake inhibitor, said medicament useful for the treatment of obesity, depression, drug abuse, or narcolepsy is not taught or suggested by the prior art. ... This invention relates to methods and compositions for the treatment of obesity, depression, drug abuse, and narcolepsy. The compositions comprise a norepinephrine precursor such as L-tyrosine or L-phenylalanine in combination with a norepinephrine

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re-uptake inhibitor such as desipramine. The compositions may further comprise an effective amount of enzymatic cofactors for the biosynthesis of norepinephrine. Web site: http://www.delphion.com/details?pn=US04843071__

Patent Applications on Narcolepsy As of December 2000, U.S. patent applications are open to public viewing.26 Applications are patent requests which have yet to be granted (the process to achieve a patent can take several years).

Keeping Current In order to stay informed about patents and patent applications dealing with narcolepsy, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “narcolepsy” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on narcolepsy. You can also use this procedure to view pending patent applications concerning narcolepsy. Simply go back to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] 26

This has been a common practice outside the United States prior to December 2000.

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Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU]

Medicament: A medicinal substance or agent. [EU] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH]

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CHAPTER 6. BOOKS ON NARCOLEPSY Overview This chapter provides bibliographic book references relating to narcolepsy. You have many options to locate books on narcolepsy. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on narcolepsy include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “narcolepsy” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on narcolepsy:

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·

Narcolepsy: A Funny Disorder That's No Laughing Matter Source: New York, NY: Narcolepsy Network, Inc. 1995. 166 p. Contact: Available from Narcolepsy Network, Inc. P.O. Box 1365, FDR Station, New York, NY 10150. (914) 834-2855. PRICE: $12.00. ISBN: 0964332809. Summary: This book is intended to help individuals and their families understand and cope with narcolepsy. The book includes facts as well as stories about the author's personal experience with the disorder. The topics discussed include the symptoms of narcolepsy, psychosocial effects, diagnostic procedures, medical treatment, management of symptoms, narcolepsy in children, normal sleep processes, causes of narcolepsy, coping strategies, support groups, benefits and legal concerns, and sources of information. 19 references.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes & Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). The following have been recently listed with online booksellers as relating to narcolepsy (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

Forever Ahbra by Mary, Anderson; ISBN: 0689308396; http://www.amazon.com/exec/obidos/ASIN/0689308396/icongroupin terna

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HLA in Narcolepsy by Y. Honda, T. Juji (Editor) (1988); ISBN: 0387189564; http://www.amazon.com/exec/obidos/ASIN/0387189564/icongroupin terna

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HLA in Narcolepsy (1988); ISBN: 3540189564; http://www.amazon.com/exec/obidos/ASIN/3540189564/icongroupin terna

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Narcolepsy by C. Guilleminault (Editor) (1976); ISBN: 0883311615; http://www.amazon.com/exec/obidos/ASIN/0883311615/icongroupin terna

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Narcolepsy and Hypersomnia by Bedrich Roth; ISBN: 380550490X; http://www.amazon.com/exec/obidos/ASIN/380550490X/icongroupi nterna

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·

Narcolepsy: Proceedings of the First International Symposium on Narcolepsy, July 1975, Montpellier, France by 1st, Montpellier, France, 1975. International Symposium on Narcolepsy; ISBN: 0470151242; http://www.amazon.com/exec/obidos/ASIN/0470151242/icongroupin terna

·

Psychosocial Aspects of Narcolepsy by Meeta Goswami (Editor), et al; ISBN: 0789060477; http://www.amazon.com/exec/obidos/ASIN/0789060477/icongroupin terna

·

Sleep disorders : hearing before a Subcommittee of the Committee on Appropriations, United States Senate, One Hundred Second Congress, second session, special hearing ; ISBN: 0160415993; http://www.amazon.com/exec/obidos/ASIN/0160415993/icongroupin terna

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Sleep Disorders: Insomnia and Narcolepsy by Henry Kellerman; ISBN: 0876302649; http://www.amazon.com/exec/obidos/ASIN/0876302649/icongroupin terna

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The sleepwatchers by William C. Dement; ISBN: 0964933802; http://www.amazon.com/exec/obidos/ASIN/0964933802/icongroupin terna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “narcolepsy” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:27

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of

27

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·

Abnormalities of sleep in man; proceedings of the XVth European Meeting on Electroencephalography. Edited by H. Gastaut [et al.]. Author: Réunion européene d'information électroencéphalographique, 15th, Bologna, 1967; Year: 1968; Bologna, Gaggi, 1968

·

HLA in narcolepsy. Author: Y. Honda, T. Juji (eds.); Year: 1988; Berlin; New York: Springer-Verlag, c1988; ISBN: 0387189564 (U.S.) http://www.amazon.com/exec/obidos/ASIN/0387189564/icongroupin terna

·

Narcolepsy: proceedings of the First International Symposium on Narcolepsy, July 1975, Montpellier, France. Author: edited by Christian Guilleminault, William C. Dement, Pierre Passouant; Year: 1976; New York: SP Books Division of Spectrum Publications: distributed by Halsted Press, c1976; ISBN: 0470151242 http://www.amazon.com/exec/obidos/ASIN/0470151242/icongroupin terna

·

Narcolepsy and hypersomnia. Author: Bedrich Roth; English translation edited and 5 chapters co-authored by Roger Broughton; Year: 1980; Basel; New York: Karger, 1980; ISBN: 380550490X http://www.amazon.com/exec/obidos/ASIN/380550490X/icongroupi nterna

·

Narcolepsy. Author: Daniels, Luman Elmer; Year: 1932; [Minneapolis] 1932

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Narcolepsy. Author: Cave, Harry Allan, 1899-; Year: 1929; [Minneapolis, Minn.] 1929

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Psychosocial aspects of narcolepsy. Author: Meeta Goswami ... [et al.], editors; Jill C. Crabtree, editor for the Foundation of Thanatology; Year: 1992; New York: Haworth Press, [c1992]; ISBN: 1560242221 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/1560242221/icongroupin terna

·

Sleep disorders: insomnia and narcolepsy. Author: by Henry Kellerman; Year: 1981; New York: Brunner/Mazel, c1981; ISBN: 0876302649 http://www.amazon.com/exec/obidos/ASIN/0876302649/icongroupin terna

information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Chapters on Narcolepsy Frequently, narcolepsy will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with narcolepsy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and narcolepsy using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” By making these selections and typing in “narcolepsy” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on narcolepsy: ·

First Seizure and the Diagnosis of Epilepsy Source: in Epilepsy: The Facts. Second Edition. Hopkins A.; Appleton, R. Oxford, England, Oxford University Press, pp. 46-60, 1996. Contact: Oxford University Press, Walton Street, Oxford OX2 6DP, England. Summary: First Seizure and the Diagnosis of Epilepsy, a chapter in Epilepsy: The Facts, discusses the steps taken by a physician when a patient has experienced a first seizure. If the doctor suspects that this seizure has been an early manifestation of an acute and important illness, immediate admission to the hospital will be arranged. More often, however, a dose of diazepam will raise the seizure threshold and make a second seizure unlikely for some hours, providing time for some consideration on long-term policy decisions. Many times the patient is referred to a specialist, often because it is difficult for a patient to accept a diagnosis based on a description of the episode by a bystander. At times a potential eye witness is given a list of various check points and encouraged to use a video camera to record subsequent seizures or attacks, particularly in the case of infants and young children. A large number of conditions may be misdiagnosed as epilepsy, particularly in children. Some of these other conditions include (1) simple faints (syncope; vasovagal attacks), (2) reflex anoxic seizures, (3) breath-holding attacks, (4) cardiac dysrhythmia, (5) localized reductions in cerebral blood flow, (6) narcolepsy, (7) drop attacks, (8) jumping legs (myoclonic jerks, hypnotic jerks), (9) vertigo, (10) rigors, (11) night terrors, (12) rage attacks (outbursts of temper), (13) tics, (14) habits, (15) ritualistic movements, (16) colic, (17) overbreathing, and (18) simulated seizures.

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General Home References In addition to references for narcolepsy, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · 100 Questions About Sleep and Sleep Disorders by Sudhansu Chokroverty, M.D.; Paperback - 110 pages, 1st edition (February 15, 2001), Blackwell Science Inc; ISBN: 0865425833; http://www.amazon.com/exec/obidos/ASIN/0865425833/icongroupinterna · The Bible Cure for Sleep Disorders by Don Colbert; Paperback - 96 pages (March 2001), Siloam Press; ISBN: 0884197484; http://www.amazon.com/exec/obidos/ASIN/0884197484/icongroupinterna · Sleep and Its Disorders : What You Should Know by Robert G. Hooper, M.D., Melissa Mulera (Illustrator); Paperback - 176 pages (January 2001), Just Peachy Press; ISBN: 0970002645; http://www.amazon.com/exec/obidos/ASIN/0970002645/icongroupinterna · Sleep Disorders Sourcebook: Basic Consumer Health Information About Sleep and Its Disorders, Including Insomnia, Sleepwalking, Sleep Apmea, Restless) by Jenifer Swanson (Editor); Library Binding - 600 pages (January 1999), Omnigraphics, Inc.; ISBN: 0780802349; http://www.amazon.com/exec/obidos/ASIN/0780802349/icongroupinterna · Sleeping Well: The Sourcebook for Sleep and Sleep Disorders (The Facts for Life) by Michael J. Thorpy, M.D., Jan Yager; Paperback - 342 pages (October 2001), Checkmark Books; ISBN: 0816040907; http://www.amazon.com/exec/obidos/ASIN/0816040907/icongroupinterna

Vocabulary Builder Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Reflex: 1; reflected. 2. a reflected action or movement; the sum total of any particular involuntary activity. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU]

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CHAPTER 7. MULTIMEDIA ON NARCOLEPSY Overview Information on narcolepsy can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on narcolepsy. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine. If you see an interesting item, visit your local medical library to check on the availability of the title.

Bibliography: Multimedia on Narcolepsy The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in narcolepsy (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on narcolepsy. For more information, follow the hyperlink indicated: ·

Convulsive and allied conditions. Source: by S. Philip Goodhart and Benjamin H. Balser; Year: 1944; Format: Motion picture; [New York]: Neuropsychiatric Division, Montefiore Hospital, [1944]

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·

Dreaming brain. Source: produced by Twenty Twenty Television for Channel 4 Television and Discovery Channel; Year: 1998; Format: Videorecording; New York: Ambrose Video Publishing, 1998

·

Evaluation and treatment of sleep disorders by the general physician. Source: Sleep Research and Treatment Center Pennsylvania State University, The Milton S. Hershey Medical Center; Year: 1976; Format: Motion picture; Hershey: The University, 1976

·

Journey into sleep 1997 . Year: 1997; Format: Electronic resource; [United States]: Kryger, c1997

·

Keep us awake. Source: William C. Dement, with the cooperation of the Association of Sleep Disorders Centers, and the American Narcolepsy Association; produced by James B. Maas; Year: 1978; Format: Motion picture; [Ithaca, N. Y.]: Cornell University: [for loan and sale by its Dept. of Psychology Film Unit], c1978

·

Narcolepsy . Year: 2000; Format: Videorecording; Boston, MA: Fanlight Productions, c2000

·

Narcolepsy, migraine headache. Source: T. J. Murray; [made by] Sigma Information; Year: 1975; Format: Sound recording; Leonia, N.J.: Sigma, c1975

·

Neurology. Source: Howard Simon, Douglas R. Gracey; Year: 1977; Format: Sound recording; [Park Ridge, Ill.]: ASCME, p1977

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Sleep disorders. Source: Films for the Humanities & Sciences; produced for Discovery Health Channel by Big Rock Productions; Year: 2002; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2002

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Sleeping well. Source: a presentation of Films for the Humanities & Sciences; Year: 1997; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1997

·

Wake up, America : a sleep alert. Source: a presentation of Films for the Humanities & Sciences; a presentation of WKRC-TV and Medstar Communications, Inc; Year: 1995; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c1995

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CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help patients with their conditions. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.

NIH Guidelines For the more common diseases, The National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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The NHLBI, in particular, suggests the following publications to physicians: Sleep Disorders ·

Restless Legs Syndrome: Detection and Management in Primary Care: http://www.nhlbi.nih.gov/health/prof/sleep/rls_gde.htm

·

Sleep Apnea: Is Your Patient at Risk?: http://www.nhlbi.nih.gov/health/prof/sleep/slpaprsk.htm

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Insomnia: Assessment and Management in Primary Care: http://www.nhlbi.nih.gov/health/prof/sleep/insom_pc.htm

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Problem Sleepiness in Your Patient: http://www.nhlbi.nih.gov/health/prof/sleep/pslp_pat.htm

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Working Group Report on Problem Sleepiness: http://www.nhlbi.nih.gov/health/prof/sleep/pslp_wg.htm

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National Center on Sleep Disorders Pamphlet: http://www.nhlbi.nih.gov/health/prof/sleep/sleep.txt Sleep in Youth

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Awake At the Wheel Materials: http://www.nhlbi.nih.gov/health/public/sleep/aaw/awake.htm

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Educating Youth About Sleep and Drowsy Driving: http://www.nhlbi.nih.gov/health/prof/sleep/dwydrv_y.htm

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Drowsy Driving and Automobile Crashes: http://www.nhlbi.nih.gov/health/prof/sleep/drsy_drv.htm Additional Resources

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National Center on Sleep Disorders Research Web Site: http://www.nhlbi.nih.gov/about/ncsdr/index.htm

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Trans-NIH Sleep Research Coordinating Committee Annual Report: http://www.nhlbi.nih.gov/health/prof/sleep/sleep00.htm

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Sleep Disorders Research Advisory Board (SDRAB): http://www.nhlbi.nih.gov/meetings/sdrab/index.htm

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National Sleep Disorders Research Plan: http://www.nhlbi.nih.gov/health/prof/sleep/reschpln.htm

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List of Publications: http://www.nhlbi.nih.gov/health/pubs/index.htm

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·

Information Center: http://www.nhlbi.nih.gov/health/infoctr/index.htm

·

Sleep Information for Patients/Public: http://www.nhlbi.nih.gov/health/public/sleep/index.htm

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.28 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:29 ·

Bioethics: Access to published literature on the ethical, legal and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

·

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

·

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

·

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

·

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs,

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 29 See http://www.nlm.nih.gov/databases/databases.html. 28

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fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html ·

Cancer Information: Access to caner-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

·

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

·

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

·

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

·

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

·

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

·

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

·

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

While all of the above references may be of interest to physicians who study and treat narcolepsy, the following are particularly noteworthy.

The Combined Health Information Database A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to “Brochure/Pamphlet,” “Fact Sheet,” or “Information Package” and narcolepsy using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years,” select your preferred language, and the format option “Fact Sheet.” By

Physician Guidelines and Databases 99

making these selections and typing “narcolepsy” (or synonyms) into the “For these words:” box above, you will only receive results on fact sheets dealing with narcolepsy. The following is a sample result: ·

Narcolepsy: A Guide to Understanding Source: New York, NY: Narcolepsy Network, Inc. 28 p. Contact: Available from Narcolepsy Network, Inc. P.O. Box 1365, FDR Station, New York NY 10150. (914) 834-2855. PRICE: $4.75. Summary: This booklet report by the Narcolepsy Network describes narcolepsy, its incidence and impact on those affected by the disorder. Symptoms, causes, diagnosis, and its relation to sleep apnea are described. Information is also presented about possible treatments for the disorder and the social implications of having narcolepsy. 28 References.

The NLM Gateway30 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing “one-stop searching” for many of NLM’s information resources or databases.31 One target audience for the Gateway is the Internet user who is new to NLM’s online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, researchers, librarians, students, and, increasingly, patients, their families, and the public.32 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “narcolepsy” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x. The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 32 Other users may find the Gateway useful for an overall search of NLM’s information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 30 31

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Results Summary Category Items Found Journal Articles 1885 Books / Periodicals / Audio Visual 32 Consumer Health 70 Meeting Abstracts 0 Other Collections 0 Total 1987

HSTAT33 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.34 HSTAT’s audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-reference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.35 Simply search by “narcolepsy” (or synonyms) at the following Web site: http://text.nlm.nih.gov. Coffee Break: Tutorials for Biologists36 Some patients may wish to have access to a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. To this end, we Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. The HSTAT URL is http://hstat.nlm.nih.gov/. 35 Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration’s Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force’s Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 36 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 33 34

Physician Guidelines and Databases 101

recommend “Coffee Break,” a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.37 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.38 This site has new articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. You can access the Coffee Break Web site at http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are a few examples that may interest you: ·

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

·

Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center’s MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.

·

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

·

MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.

·

Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language generally used by caregivers into terms from formal, controlled vocabularies; see http://www.lexical.com/Metaphrase.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 38 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 37

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The Genome Project and Narcolepsy With all the discussion in the press about the Human Genome Project, it is only natural that physicians, researchers, and patients want to know about how human genes relate to narcolepsy. In the following section, we will discuss databases and references used by physicians and scientists who work in this area.

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).39 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. Go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html to search the database. Type “narcolepsy” (or synonyms) in the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. By following these links, especially the link titled “Database Links,” you will be exposed to numerous specialized databases that are largely used by the scientific community. These databases are overly technical and seldom used by the general public, but offer an abundance of information. The following is an example of the results you can obtain from the OMIM for narcolepsy: ·

Cerebellar Ataxia, Deafness, and Narcolepsy Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?604121

·

Disseminated Sclerosis with Narcolepsy Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?223300

Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

39

Physician Guidelines and Databases 103

·

Narcolepsy Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?161400

·

Narcolepsy, Hla-associated Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?605841 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by the system of the body associated with it. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to re-visit it from time to time. The following systems and associated disorders are addressed: ·

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, Atherosclerosis, Best disease, Gaucher disease, Glucose galactose malabsorption, Gyrate atrophy, Juvenile onset diabetes, Obesity, Paroxysmal nocturnal hemoglobinuria, Phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

·

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

·

Nervous System: Mind and body. Examples: Alzheimer disease, Amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, Fragile X syndrome, Friedreich’s ataxia, Huntington disease, NiemannPick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, Spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

·

Signals: Cellular messages. Examples: Ataxia telangiectasia, Baldness, Cockayne syndrome, Glaucoma, SRY: sex determination, Tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

104 Narcolepsy

·

Transporters: Pumps and channels. Examples: Cystic Fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

·

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

·

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

·

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

·

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

·

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

·

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

·

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

·

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

·

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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·

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” In the box next to “for,” enter “narcolepsy” (or synonyms) and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database40 This online resource can be quite useful. It has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html you can also search across syndromes using an alphabetical index:. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html you can search by keywords.

The Genome Database41 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 41 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html#mission. 40

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continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “narcolepsy” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms). This database is extremely technical as it was created for specialists. The articles are the results which are the most accessible to non-professionals and often listed under the heading “Citations.” The contact names are also accessible to non-professionals.

Specialized References The following books are specialized references written for professionals interested in narcolepsy (sorted alphabetically by title, hyperlinks provide rankings, information, and reviews at Amazon.com): · Clinical Companion to Sleep Disorders Medicine Second Edition by Sudhansu Chokroverty; Paperback - 232 pages, 2nd edition (April 2000), Butterworth-Heinemann Medical; ISBN: 0750696877; http://www.amazon.com/exec/obidos/ASIN/0750696877/icongroupinterna · Concise Guide to Evaluation and Management of Sleep Disorders (Concise Guides) by Martin Reite, et al; Paperback 3rd edition (April 2002), American Psychiatric Press; ISBN: 1585620459; http://www.amazon.com/exec/obidos/ASIN/1585620459/icongroupinterna · The Encyclopedia of Sleep and Sleep Disorders, Second Edition by Michael J. Thorpy, M.D, Jan Yager; Library Binding - 352 pages, 2nd Updated edition (May 2001), Facts on File, Inc.; ISBN: 0816040893; http://www.amazon.com/exec/obidos/ASIN/0816040893/icongroupinterna · Sleep Disorders (Encyclopedia of Psychological Disorders) by Linda N. Bayer, et al; Library Binding (October 2000), Chelsea House Pub (Library); ISBN: 0791053148; http://www.amazon.com/exec/obidos/ASIN/0791053148/icongroupinterna · Sleep Disorders: Diagnosis and Treatment by J. Steven Poceta (Editor), Merrill Morris Mitler (Editor); Hardcover - 232 pages, 1st edition (June 15, 1998), Humana Press; ISBN: 0896035271; http://www.amazon.com/exec/obidos/ASIN/0896035271/icongroupinterna

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· Sleep Disorders and Neurological Disease by Antonio Culebras (Editor); Hardcover - 422 pages, 1st edition (October 15, 1999), Marcel Dekker; ISBN: 0824776054; http://www.amazon.com/exec/obidos/ASIN/0824776054/icongroupinterna · Sleep Disorders Handbook by Peretz Lavie, M.D., et al; Paperback (March 2002), Boston Medical Pub Inc; ISBN: 1841840556; http://www.amazon.com/exec/obidos/ASIN/1841840556/icongroupinterna · Sleep Disorders Medicine: Basic Science, Technical Considerations, and Clinical Aspects by Sudhansu Chokroverty (Editor), Robert B. Daroff (Introduction); Hardcover - 781 pages, 2nd edition (January 15, 1999), Butterworth-Heinemann Medical; ISBN: 075069954X; http://www.amazon.com/exec/obidos/ASIN/075069954X/icongroupinterna

Dissertations 109

CHAPTER 9. DISSERTATIONS ON NARCOLEPSY Overview University researchers are active in studying almost all known diseases. The result of research is often published in the form of Doctoral or Master’s dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to narcolepsy. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.

Dissertations on Narcolepsy ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to narcolepsy. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with narcolepsy: ·

Having Narcolepsy: the Experience and Treatment in Children, Adolescents and Young Adults by Zafarlotfi, Susan, Phd from City University of New York, 1997, 210 pages http://wwwlib.umi.com/dissertations/fullcit/9732989

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Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to narcolepsy is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.

111

PART III. APPENDICES

ABOUT PART III Part III is a collection of appendices on general medical topics which may be of interest to patients with narcolepsy and related conditions.

Researching Your Medications 113

APPENDIX A. RESEARCHING YOUR MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to patients with narcolepsy. While a number of hard copy or CD-Rom resources are available to patients and physicians for research purposes, a more flexible method is to use Internet-based databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your medications. You may also want to research medications that you are currently taking for other conditions as they may interact with medications for narcolepsy. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of narcolepsy. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

114 Narcolepsy

Your Medications: The Basics42 The Agency for Health Care Research and Quality has published extremely useful guidelines on how you can best participate in the medication aspects of narcolepsy. Taking medicines is not always as simple as swallowing a pill. It can involve many steps and decisions each day. The AHCRQ recommends that patients with narcolepsy take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions early, you may avoid problems later. Here are some points to cover each time a new medicine is prescribed: ·

Ask about all parts of your treatment, including diet changes, exercise, and medicines.

·

Ask about the risks and benefits of each medicine or other treatment you might receive.

·

Ask how often you or your doctor will check for side effects from a given medication.

Do not hesitate to ask what is important to you about your medicines. You may want a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost, or how the medicine might affect how you live or work. Or, you may want the medicine your doctor believes will work the best. Telling your doctor will help him or her select the best treatment for you. Do not be afraid to “bother” your doctor with your concerns and questions about medications for narcolepsy. You can also talk to a nurse or a pharmacist. They can help you better understand your treatment plan. Feel free to bring a friend or family member with you when you visit your doctor. Talking over your options with someone you trust can help you make better choices, especially if you are not feeling well. Specifically, ask your doctor the following: ·

The name of the medicine and what it is supposed to do.

·

How and when to take the medicine, how much to take, and for how long.

·

What food, drinks, other medicines, or activities you should avoid while taking the medicine.

·

What side effects the medicine may have, and what to do if they occur.

·

If you can get a refill, and how often.

42

This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.

Researching Your Medications 115

·

About any terms or directions you do not understand.

·

What to do if you miss a dose.

·

If there is written information you can take home (most pharmacies have information sheets on your prescription medicines; some even offer large-print or Spanish versions).

Do not forget to tell your doctor about all the medicines you are currently taking (not just those for narcolepsy). This includes prescription medicines and the medicines that you buy over the counter. Then your doctor can avoid giving you a new medicine that may not work well with the medications you take now. When talking to your doctor, you may wish to prepare a list of medicines you currently take, the reason you take them, and how you take them. Be sure to include the following information for each: ·

Name of medicine

·

Reason taken

·

Dosage

·

Time(s) of day

Also include any over-the-counter medicines, such as: ·

Laxatives

·

Diet pills

·

Vitamins

·

Cold medicine

·

Aspirin or other pain, headache, or fever medicine

·

Cough medicine

·

Allergy relief medicine

·

Antacids

·

Sleeping pills

·

Others (include names)

Learning More about Your Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications your doctor has recommended for narcolepsy. One such source

116 Narcolepsy

is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the “U.S. Pharmacopeia (USP).” Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database.43 While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopoeia (USP). It is important to read the disclaimer by the USP (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided. Of course, we as editors cannot be certain as to what medications you are taking. Therefore, we have compiled a list of medications associated with the treatment of narcolepsy. Once again, due to space limitations, we only list a sample of medications and provide hyperlinks to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to narcolepsy: Amphetamines ·

Systemic - U.S. Brands: Adderall; Desoxyn; Desoxyn Gradumet; Dexedrine; Dexedrine Spansule; DextroStat http://www.nlm.nih.gov/medlineplus/druginfo/amphetaminess ystemic202031.html

Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.

43

Researching Your Medications 117

Antidepressants, Tricyclic ·

Systemic - U.S. Brands: Anafranil; Asendin; Aventyl; Elavil; Endep; Norfranil; Norpramin; Pamelor; Sinequan; Surmontil; Tipramine; Tofranil; Tofranil-PM; Vivactil http://www.nlm.nih.gov/medlineplus/druginfo/antidepressantst ricyclicsystem202055.html

Fluoxetine ·

Systemic - U.S. Brands: Prozac; Sarafem http://www.nlm.nih.gov/medlineplus/druginfo/fluoxetinesyste mic202247.html

Methylphenidate ·

Systemic - U.S. Brands: Concerta; Ritalin; Ritalin-SR http://www.nlm.nih.gov/medlineplus/druginfo/methylphenidat esystemic202361.html

Modafinil ·

Systemic - U.S. Brands: Provigil http://www.nlm.nih.gov/medlineplus/druginfo/modafinilsyste mic203466.html

Pemoline ·

Systemic - U.S. Brands: Cylert http://www.nlm.nih.gov/medlineplus/druginfo/pemolinesystem ic202444.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. You may be able to access these sources from your local medical library or your doctor’s office.

Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html. The following

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medications are listed in the Reuters’ database as associated with narcolepsy (including those with contraindications):44 ·

Amphetamine http://www.reutershealth.com/atoz/html/Amphetamine.htm

·

Amphetamine (Racemic Amphetamine Sulfate) http://www.reutershealth.com/atoz/html/Amphetamine_(Racemic_A mphetamine_Sulfate).htm

·

Dextroamphetamine Sulfate http://www.reutershealth.com/atoz/html/Dextroamphetamine_Sulfate .htm

·

Ephedrine http://www.reutershealth.com/atoz/html/Ephedrine.htm

·

Fluoxetine HCl http://www.reutershealth.com/atoz/html/Fluoxetine_HCl.htm

·

Methylphenidate HCl http://www.reutershealth.com/atoz/html/Methylphenidate_HCl.htm

·

Pemoline http://www.reutershealth.com/atoz/html/Pemoline.htm

Mosby’s GenRx Mosby’s GenRx database (also available on CD-Rom and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Information in Mosby’s GenRx database can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html.

Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm.

44

Adapted from A to Z Drug Facts by Facts and Comparisons.

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Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. which allows users to download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.

Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for patients with narcolepsy--not because they are used in the treatment process, but because of contraindications, or side effects. Medications with contraindications are those that could react with drugs used to treat narcolepsy or potentially create deleterious side effects in patients with narcolepsy. You should ask your physician about any contraindications, especially as these might apply to other medications that you may be taking for common ailments. Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it’s especially important to read the label every time you use a medication. When your doctor prescribes a new drug, discuss all over-thecounter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals you take as well as the foods you eat. Ask your pharmacist for the package insert for each prescription drug you take.

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The package insert provides more information about potential drug interactions.

A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for patients with narcolepsy. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt you. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to improve the health of patients with narcolepsy. The FDA warns patients to watch out for45: ·

Secret formulas (real scientists share what they know)

·

Amazing breakthroughs or miracle cures (real breakthroughs don’t happen very often; when they do, real scientists do not call them amazing or miracles)

·

Quick, painless, or guaranteed cures

·

If it sounds too good to be true, it probably isn’t true.

If you have any questions about any kind of medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Complete Guide to Prescription and Nonprescription Drugs 2001 (Complete Guide to Prescription and Nonprescription Drugs, 2001) by H. Winter Griffith, Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/039952634X/icongroupinterna

45

This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.

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·

The Essential Guide to Prescription Drugs, 2001 by James J. Rybacki, James W. Long; Paperback - 1274 pages (2001), Harper Resource; ISBN: 0060958162; http://www.amazon.com/exec/obidos/ASIN/0060958162/icongroupinterna

·

Handbook of Commonly Prescribed Drugs by G. John Digregorio, Edward J. Barbieri; Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/0942447417/icongroupinterna

·

Johns Hopkins Complete Home Encyclopedia of Drugs 2nd ed. by Simeon Margolis (Ed.), Johns Hopkins; Hardcover - 835 pages (2000), Rebus; ISBN: 0929661583; http://www.amazon.com/exec/obidos/ASIN/0929661583/icongroupinterna

·

Medical Pocket Reference: Drugs 2002 by Springhouse Paperback 1st edition (2001), Lippincott Williams & Wilkins Publishers; ISBN: 1582550964; http://www.amazon.com/exec/obidos/ASIN/1582550964/icongroupinterna

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PDR by Medical Economics Staff, Medical Economics Staff Hardcover 3506 pages 55th edition (2000), Medical Economics Company; ISBN: 1563633752; http://www.amazon.com/exec/obidos/ASIN/1563633752/icongroupinterna

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Pharmacy Simplified: A Glossary of Terms by James Grogan; Paperback 432 pages, 1st edition (2001), Delmar Publishers; ISBN: 0766828581; http://www.amazon.com/exec/obidos/ASIN/0766828581/icongroupinterna

·

Physician Federal Desk Reference by Christine B. Fraizer; Paperback 2nd edition (2001), Medicode Inc; ISBN: 1563373971; http://www.amazon.com/exec/obidos/ASIN/1563373971/icongroupinterna

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Physician’s Desk Reference Supplements Paperback - 300 pages, 53 edition (1999), ISBN: 1563632950; http://www.amazon.com/exec/obidos/ASIN/1563632950/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH]

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Ephedrine: A sympathomimetic drug that stimulates thermogenesis in laboratory animals and humans. Animal studies show that it may reduce fat content and, therefore, body weight by mechanisms that probably involve increased expenditure and reduced food intake. [NIH] Fluoxetine: An antidepressant drug used to promote weight loss whose action is mediated by highly specific inhibition of serotonin reuptake into presynaptic neurons. Serotonin acts in the brain to alter feeding and satiety by decreasing carbohydrate intake, resulting in weight reduction. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH]

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APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview Complementary and alternative medicine (CAM) is one of the most contentious aspects of modern medical practice. You may have heard of these treatments on the radio or on television. Maybe you have seen articles written about these treatments in magazines, newspapers, or books. Perhaps your friends or doctor have mentioned alternatives. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to narcolepsy. Finally, at the conclusion of this chapter, we will provide a list of readings on narcolepsy from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine’s (NCCAM) overview of complementary and alternative medicine.

What Is CAM?46 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also known as “preventive,” which means that the practitioner educates and 46

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is.

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treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture.

What Are the Domains of Alternative Medicine?47 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each. Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are

47

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.

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practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and disease, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India’s traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body’s defense mechanisms and healing processes in order to treat illness. Naturopathic medicine is based on the theory that disease is a manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than disease treatment. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology.

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Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind’s capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing.

Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine’s use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.

Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body’s systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues.

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Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch. Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects the patient’s recovery and that healing is promoted when the body’s energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields.

Can Alternatives Affect My Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your medical treatment. It becomes all the more important to speak with your doctor who can offer advice on the use of alternatives. Official sources confirm this view. Though written for women, we find that the National Women’s Health Information Center’s advice on pursuing alternative medicine is appropriate for patients of both genders and all ages.48

48

Adapted from http://www.4woman.gov/faq/alternative.htm.

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Is It Okay to Want Both Traditional and Alternative Medicine? Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires knowledge of both conventional and alternative therapies you are taking for the practitioner to have a complete picture of your treatment plan. The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.

Finding CAM References on Narcolepsy Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for narcolepsy. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required. National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov) has created a link to the National Library of Medicine’s databases to allow patients to search for articles that specifically relate to narcolepsy and complementary medicine. To search the database, go to the following Web site: www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “narcolepsy” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine (CAM) that are related to narcolepsy:

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·

A note on distinguishing between hypnotic "sleep" and narcoleptic "sleep". Author(s): McCord H. Source: J Am Soc Psychosom Dent Med. 1967 April; 14(2): 55-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=5229395&dopt=Abstract

·

A parasomnia overlap disorder involving sleepwalking, sleep terrors, and REM sleep behavior disorder in 33 polysomnographically confirmed cases. Author(s): Schenck CH, Boyd JL, Mahowald MW. Source: Sleep. 1997 November; 20(11): 972-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9456462&dopt=Abstract

·

Attentive and preattentive processing in narcolepsy as revealed by event-related potentials (ERPs). Author(s): Naumann A, Bierbrauer J, Przuntek H, Daum I. Source: Neuroreport. 2001 September 17; 12(13): 2807-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11588581&dopt=Abstract

·

Circadian distribution of motor activity and immobility in narcolepsy: assessment with continuous motor activity monitoring. Author(s): Middelkoop HA, Lammers GJ, Van Hilten BJ, Ruwhof C, Pijl H, Kamphuisen HA. Source: Psychophysiology. 1995 May; 32(3): 286-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7784537&dopt=Abstract

·

Clinical and polygraphic study of the cataplectic attacks. Author(s): Corfariu O, Popoviciu L. Source: Rev Roum Neurol Psychiatr. 1974; 11(1): 3-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4364223&dopt=Abstract

·

Complex event-related potentials (P300 and CNV) and MSLT in the assessment of excessive daytime sleepiness in narcolepsy-cataplexy. Author(s): Aguirre M, Broughton RJ.

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Source: Electroencephalography and Clinical Neurophysiology. 1987 October; 67(4): 298-316. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2441963&dopt=Abstract ·

Effects of startle and laughter in cataplectic subjects: a neurophysiological study between attacks. Author(s): Lammers GJ, Overeem S, Tijssen MA, van Dijk JG. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 July; 111(7): 1276-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10880803&dopt=Abstract

·

Functional echoplanar brain imaging correlates of amphetamine administration to normal subjects and subjects with the narcoleptic syndrome. Author(s): Howard RJ, Ellis C, Bullmore ET, Brammer M, Mellers JD, Woodruff PW, David AS, Simmons A, Williams SC, Parkes JD. Source: Magnetic Resonance Imaging. 1996; 14(9): 1013-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9070991&dopt=Abstract

·

Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil. Author(s): Ellis CM, Monk C, Simmons A, Lemmens G, Williams SC, Brammer M, Bullmore E, Parkes JD. Source: Journal of Sleep Research. 1999 June; 8(2): 85-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10389090&dopt=Abstract

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Hypnotherapy for narcolepsy. Author(s): Schneck JM. Source: Int J Clin Exp Hypn. 1980 April; 28(2): 95-100. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7364526&dopt=Abstract

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·

Hypnotherapy in the control of cataplexy in a narcoleptic subject. Author(s): Price R. Source: Am J Clin Hypn. 1987 January; 29(3): 201-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3825977&dopt=Abstract

·

Immobility reactions: a modified classification. Author(s): Reese WG, Angel C, Newton JE. Source: Pavlov J Biol Sci. 1984 July-September; 19(3): 137-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6541777&dopt=Abstract

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Medical-psychological implications of recent sleep research. Author(s): Pearlman CA, Greenberg R. Source: Psychiatry Med. 1970 October; 1(4): 261-76. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4402296&dopt=Abstract

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Method of promoting blood circulation to eliminate stasis in treatment of narcolepsy. Report of 4 cases. Author(s): Chen JH, Gao Y. Source: J Tradit Chin Med. 1982 March; 2(1): 67-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6765692&dopt=Abstract

·

Narcolepsy: pathogenesis and nursing care. Author(s): Bergstrom DL, Keller C. Source: J Neurosci Nurs. 1992 June; 24(3): 153-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1645038&dopt=Abstract

·

Neurological aspects of hallucinogenic drugs. Author(s): Logan WJ. Source: Adv Neurol. 1975; 13: 47-78. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=814800&dopt=Abstract

·

Non-pharmacological approaches to the treatment of narcolepsy. Author(s): Garma L, Marchand F.

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Source: Sleep. 1994 December; 17(8 Suppl): S97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7701208&dopt=Abstract ·

RTMS induces brief events of muscle atonia in patients with narcolepsy. Author(s): Hungs M, Mottaghy FM, Sparing R, Zuchner S, Boroojerdi B, Topper R. Source: Sleep. 2000 December 15; 23(8): 1099-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11145324&dopt=Abstract

·

Sleep disorders. Author(s): Silber MH. Source: Neurologic Clinics. 2001 February; 19(1): 173-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11471763&dopt=Abstract

·

Sleep disorders. Author(s): Yousaf F, Sedgwick P. Source: Br J Hosp Med. 1996 March 20-April 2; 55(6): 353-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8696635&dopt=Abstract

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Sleep paralysis and hallucinosis. Author(s): Stores G. Source: Behavioural Neurology. 1998; 11(2): 109-112. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11568409&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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·

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.thedacare.org/healthnotes/

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Open Directory Project: http://dmoz.org/Health/Alternative/

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TPN.com: http://www.tnp.com/

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

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WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

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WellNet: http://www.wellnet.ca/herbsa-c.htm

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

The following is a specific Web list relating to narcolepsy; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·

General Overview Narcolepsy Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsLookups/Uses/nar colepsy.html

·

Herbs and Supplements Antioxidants Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Aspirin Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Coleus Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html

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Coleus forskohlii Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Ephedra Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000154.html Ephedra Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Ephedrine and Pseudoephedrine Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Evening Primrose Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Forskolin Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Grindelia Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Insulin Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/SleepA pneacc.html Lobelia Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Lobelia inflata Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html

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Ma Huang Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Methylphenidate Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Methylphenidate.htm Mixed Amphetamines Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Mixed_Amphetamines.h tm Prednisone Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Tylophora Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Tyrosine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Tyro sinecs.html ·

Related Conditions Asthma Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000266.html Sleep Apnea Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/SleepA pneacc.html

136 Narcolepsy

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at: www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Alternative Medicine for Dummies by James Dillard (Author); Audio Cassette, Abridged edition (1998), Harper Audio; ISBN: 0694520659; http://www.amazon.com/exec/obidos/ASIN/0694520659/icongroupinterna ·

Complementary and Alternative Medicine Secrets by W. Kohatsu (Editor); Hardcover (2001), Hanley & Belfus; ISBN: 1560534400; http://www.amazon.com/exec/obidos/ASIN/1560534400/icongroupinterna

·

Dictionary of Alternative Medicine by J. C. Segen; Paperback-2nd edition (2001), Appleton & Lange; ISBN: 0838516211; http://www.amazon.com/exec/obidos/ASIN/0838516211/icongroupinterna

·

Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating by Walter C. Willett, MD, et al; Hardcover - 352 pages (2001), Simon & Schuster; ISBN: 0684863375; http://www.amazon.com/exec/obidos/ASIN/0684863375/icongroupinterna

· Encyclopedia of Natural Medicine, Revised 2nd Edition by Michael T. Murray, Joseph E. Pizzorno; Paperback - 960 pages, 2nd Rev edition (1997), Prima Publishing; ISBN: 0761511571; http://www.amazon.com/exec/obidos/ASIN/0761511571/icongroupinterna ·

Integrative Medicine: An Introduction to the Art & Science of Healing by Andrew Weil (Author); Audio Cassette, Unabridged edition (2001), Sounds True; ISBN: 1564558541; http://www.amazon.com/exec/obidos/ASIN/1564558541/icongroupinterna

·

New Encyclopedia of Herbs & Their Uses by Deni Bown; Hardcover - 448 pages, Revised edition (2001), DK Publishing; ISBN: 078948031X; http://www.amazon.com/exec/obidos/ASIN/078948031X/icongroupinterna

· Textbook of Complementary and Alternative Medicine by Wayne B. Jonas; Hardcover (2003), Lippincott, Williams & Wilkins; ISBN: 0683044370; http://www.amazon.com/exec/obidos/ASIN/0683044370/icongroupinterna

Researching Nutrition 137

For additional information on complementary and alternative medicine, ask your doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218

Finding Medical Libraries 139

APPENDIX C. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, your local public library and medical libraries have Interlibrary Loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. NLM’s interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.49

49

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

140 Narcolepsy

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located):50 ·

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

·

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute), http://www.asmi.org/LIBRARY.HTM

·

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

·

California: Kris Kelly Health Information Center (St. Joseph Health System), http://www.humboldt1.com/~kkhic/index.html

·

California: Community Health Library of Los Gatos (Community Health Library of Los Gatos), http://www.healthlib.org/orgresources.html

·

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

·

California: Gateway Health Library (Sutter Gould Medical Foundation)

·

California: Health Library (Stanford University Medical Center), http://www-med.stanford.edu/healthlibrary/

50

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 141

·

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

·

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

·

California: San José PlaneTree Health Library, http://planetreesanjose.org/

·

California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html

·

California: University of California, Davis. Health Sciences Libraries

·

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html

·

California: Washington Community Health Resource Library (Washington Community Health Resource Library), http://www.healthlibrary.org/

·

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm

·

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

·

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

·

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital), http://www.waterburyhospital.com/library/consumer.shtml

·

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute), http://www.christianacare.org/health_guide/health_guide_pmri_health _info.cfm

·

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine), http://www.delamed.org/chls.html

·

Georgia: Family Resource Library (Medical College of Georgia), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

·

Georgia: Health Resource Center (Medical Center of Central Georgia), http://www.mccg.org/hrc/hrchome.asp

·

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library), http://hml.org/CHIS/

142 Narcolepsy

·

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center), http://www.nicon.org/DeArmond/index.htm

·

Illinois: Health Learning Center of Northwestern Memorial Hospital (Northwestern Memorial Hospital, Health Learning Center), http://www.nmh.org/health_info/hlc.html

·

Illinois: Medical Library (OSF Saint Francis Medical Center), http://www.osfsaintfrancis.org/general/library/

·

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital), http://www.centralbap.com/education/community/library.htm

·

Kentucky: University of Kentucky - Health Information Library (University of Kentucky, Chandler Medical Center, Health Information Library), http://www.mc.uky.edu/PatientEd/

·

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation), http://www.ochsner.org/library/

·

Louisiana: Louisiana State University Health Sciences Center Medical Library-Shreveport, http://lib-sh.lsuhsc.edu/

·

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital), http://www.fchn.org/fmh/lib.htm

·

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center), http://www.cmmc.org/library/library.html

·

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare), http://www.emh.org/hll/hpl/guide.htm

·

Maine: Maine Medical Center Library (Maine Medical Center), http://www.mmc.org/library/

·

Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library

·

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center), http://www.smmc.org/services/service.php3?choice=10

·

Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html

·

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml

Finding Medical Libraries 143

·

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Md., Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

·

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

·

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://medlibwww.bu.edu/library/lib.html

·

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

·

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital), http://www.nebh.org/health_lib.asp

·

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital), http://www.southcoast.org/library/

·

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

·

Massachusetts: UMass HealthNet (University of Massachusetts Medical School), http://healthnet.umassmed.edu/

·

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

·

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

·

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

·

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center), http://www.cancer.med.umich.edu/learn/leares.htm

·

Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41

144 Narcolepsy

·

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

·

National: National Network of Libraries of Medicine (National Library of Medicine) - provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

·

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

·

Nevada: Health Science Library, West Charleston Library (Las Vegas Clark County Library District), http://www.lvccld.org/special_collections/medical/index.htm

·

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

·

New Jersey: Consumer Health Library (Rahway Hospital), http://www.rahwayhospital.com/library.htm

·

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center), http://www.englewoodhospital.com/links/index.htm

·

New Jersey: Meland Foundation (Englewood Hospital and Medical Center), http://www.geocities.com/ResearchTriangle/9360/

·

New York: Choices in Health Information (New York Public Library) NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

·

New York: Health Information Center (Upstate Medical University, State University of New York), http://www.upstate.edu/library/hic/

·

New York: Health Sciences Library (Long Island Jewish Medical Center), http://www.lij.edu/library/library.html

·

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

·

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

·

Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp

Finding Medical Libraries 145

·

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center), http://www.mcmc.net/phrc/

·

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center), http://www.hmc.psu.edu/commhealth/

·

Pennsylvania: Community Health Resource Library (Geisinger Medical Center), http://www.geisinger.edu/education/commlib.shtml

·

Pennsylvania: HealthInfo Library (Moses Taylor Hospital), http://www.mth.org/healthwellness.html

·

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System), http://www.hsls.pitt.edu/chi/hhrcinfo.html

·

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

·

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System), http://www.shscares.org/services/lrc/index.asp

·

Pennsylvania: Medical Library (UPMC Health System), http://www.upmc.edu/passavant/library.htm

·

Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/

·

South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm

·

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

·

Texas: Matustik Family Resource Center (Cook Children’s Health Care System), http://www.cookchildrens.com/Matustik_Library.html

·

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

·

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/

More on Problem Sleepiness 147

APPENDIX D. MORE ON PROBLEM SLEEPINESS Overview51 Everyone feels sleepy at times. However, when sleepiness interferes with daily routines and activities, or reduces the ability to function, it is called “problem sleepiness.” A person can be sleepy without realizing it. For example, a person may not feel sleepy during activities such as talking and listening to music at a party, but the same person can fall asleep while driving home afterward. The following appendix is reproduced and adapted from the National Heart, Lung, and Blood Institute publication dedicated to problem sleepiness.

What Causes Problem Sleepiness? You may have problem sleepiness if you: ·

Consistently do not get enough sleep

·

Get poor quality sleep

·

Fall asleep while driving

·

Struggle to stay awake when inactive such as when watching television or reading

·

Have difficulty paying attention or concentrating at work, school, or home

·

Have performance problems at work or school

Adapted from the National Heart, Lung, and Blood Institute: http://www.nhlbi.nih.gov/health/public/sleep/pslp_fs.pdf.

51

148 Narcolepsy

·

Are often told by others that you are sleepy

·

Have difficulty remembering

·

Have slowed responses

·

Have difficulty controlling your emotions

·

Must take naps on most days

Sleepiness can be due to the body’s natural daily sleep-wake cycles, inadequate sleep, sleep disorders, or certain drugs.

Sleep-Wake Cycle Each day there are two periods when the body experiences a natural tendency toward sleepiness: during the late night hours (generally between midnight and 7 a.m.) and again during the midafternoon (generally between 1 p.m. and 4 p.m.). If people are awake during these times, they have a higher risk of falling asleep unintentionally, especially if they haven’t been getting enough sleep.

Inadequate Sleep The amount of sleep needed each night varies among people. Each person needs a particular amount of sleep in order to be fully alert throughout the day. Research has shown that when healthy adults are allowed to sleep unrestricted, the average time slept is 8 to 8.5 hours. Some people need more than that to avoid problem sleepiness; others need less. If a person does not get enough sleep, even on one night, a “sleep debt” begins to build and increases until enough sleep is obtained. Problem sleepiness occurs as the debt accumulates. Many people do not get enough sleep during the work week and then sleep longer on the weekends or days off to reduce their sleep debt. If too much sleep has been lost, sleeping in on the weekend may not completely reverse the effects of not getting enough sleep during the week.

Sleep Disorders Sleep disorders such as sleep apnea, narcolepsy, restless legs syndrome, and insomnia can cause problem sleepiness. Sleep apnea is a serious disorder in

More on Problem Sleepiness 149

which a person’s breathing is interrupted during sleep, causing the individual to awaken many times during the night and experience problem sleepiness during the day. People with narcolepsy have excessive sleepiness during the day, even after sleeping enough at night. They may fall asleep at inappropriate times and places. Restless legs syndrome (RLS) causes a person to experience unpleasant sensations in the legs, often described as creeping, crawling, pulling, or painful. These sensations frequently occur in the evening, making it difficult for people with RLS to fall asleep, leading to problem sleepiness during the day. Insomnia is the perception of poor-quality sleep due to difficulty falling asleep, waking up during the night with difficulty returning to sleep, waking up too early in the morning, or unrefreshing sleep. Any of these sleep disorders can cause problem sleepiness.

Medical Conditions/Drugs Certain medical conditions and drugs, including prescription medications, can also disrupt sleep and cause problem sleepiness. Examples include: ·

Chronic illnesses such as asthma, congestive heart failure, rheumatoid arthritis, or any other chronically painful disorder.

·

Some medications to treat high blood pressure, some heart medications, and asthma medications such as theophylline.

·

Alcohol—Although some people use alcohol to help themselves fall asleep, it causes sleep disruption during the night, which can lead to problem sleepiness during the day. Alcohol is also a sedating drug that can, even in small amounts, make a sleepy person much more sleepy and at greater risk for car crashes and performance problems.

·

Caffeine—Whether consumed in coffee, tea, soft drinks, or medications, caffeine makes it harder for many people to fall asleep and stay asleep. Caffeine stays in the body for about 3 to 7 hours, so even when taken earlier in the day it can cause problems with sleep at night.

·

Nicotine from cigarettes or a skin patch is a stimulant and makes it harder to fall asleep and stay asleep.

Problem Sleepiness and Adolescents Many U.S. high school and college students have signs of problem sleepiness, such as: ·

Difficulty getting up for school

150 Narcolepsy

·

Falling asleep at school

·

Struggling to stay awake while doing homework

The need for sleep may be 9 hours or more per night as a person goes through adolescence. At the same time, many teens begin to show a preference for a later bed time, which may be due to a biological change. Teens tend to stay up later but have to get up early for school, resulting in their getting much less sleep than they need. Many factors contribute to problem sleepiness in teens and young adults, but the main causes are not getting enough sleep and irregular sleep schedules. Some of the factors that influence adolescent sleep include: ·

Social activities with peers that lead to later bedtimes

·

Homework to be done in the evenings

·

Early wake-up times due to early school start times

·

Parents being less involved in setting and enforcing bedtimes

·

Employment, sports, or other extracurricular activities that decrease the time available for sleep

Teens and young adults who do not get enough sleep are at risk for problems such as: ·

Automobile crashes

·

Poor performance in school and poor grades

·

Depressed moods

·

Problems with peer and adult relationships

Many adolescents have part-time jobs in addition to their classes and other activities. High school students who work more than 20 hours per week have more problem sleepiness and may use more caffeine, nicotine, and alcohol than those who work less than 20 hours per week or not at all.

Shift Work And Problem Sleepiness About 20 million Americans (20 to 25 percent of workers) perform shift work. Most shift workers get less sleep over 24 hours than day workers. Sleep loss is greatest for night shift workers, those who work early morning shifts, and female shift workers with children at home. About 60 to 70 percent of shift workers have difficulty sleeping and/or problem sleepiness.

More on Problem Sleepiness 151

The human sleep-wake system is designed to prepare the body and mind for sleep at night and wakefulness during the day. These natural rhythms make it difficult to sleep during daylight hours and to stay awake during the night hours, even in people who are well rested. It is possible that the human body never completely adjusts to nighttime activity and daytime sleep, even in those who work permanent night shifts. In addition to the sleep-wake system, environmental factors can influence sleepiness in shift workers. Because our society is strongly day-oriented, shift workers who try to sleep during the day are often interrupted by noise, light, telephones, family members, and other distractions. In contrast, the nighttime sleep of day workers is largely protected by social customs that keep noises and interruptions to a minimum. Problem sleepiness in shift workers may result in: ·

Increased risk for automobile crashes, especially while driving home after the night shift

·

Decreased quality of life

·

Decreased productivity (night work performance may be slower and less accurate than day performance)

·

Increased risk of accidents and injuries at work

What Can Help? Sleep—There Is No Substitute! Many people simply do not allow enough time for sleep on a regular basis. A first step may be to evaluate daily activities and sleep-wake patterns to determine how much sleep is obtained. If you are consistently getting less than 8 hours of sleep per night, more sleep may be needed. A good approach is to gradually move to an earlier bedtime. For example, if an extra hour of sleep is needed, try going to bed 15 minutes earlier each night for four nights and then keep the last bedtime. This method will increase the amount of time in bed without causing a sudden change in schedule. However, if work or family schedules do not permit the earlier bedtime, a 30- to 60-minute daily nap may help.

152 Narcolepsy

Medications/Drugs In general, medications do not help problem sleepiness, and some make it worse. Caffeine can reduce sleepiness and increase alertness, but only temporarily. It can also cause problem sleepiness to become worse by interrupting sleep. While alcohol may shorten the time it takes to fall asleep, it can disrupt sleep later in the night, and therefore add to the problem sleepiness. Medications may be prescribed for patients in certain situations. For example, the short-term use of sleeping pills has been shown to be helpful in patients diagnosed with acute insomnia. Long-term use of sleep medication is recommended only for the treatment of specific sleep disorders.

If You’re Sleepy—Don’t Drive! A person who is sleepy and drives is at high risk for an automobile crash. Planning ahead may help reduce that risk. For example, the following tips may help when planning a long distance car trip: ·

Get a good night’s sleep before leaving

·

Avoid driving between midnight and 7 a.m.

·

Change drivers often to allow for rest periods

·

Schedule frequent breaks

If you are a shift worker, the following may help: ·

Decreasing the amount of night work

·

Increasing the total amount of sleep by adding naps and lengthening the amount of time allotted for sleep

·

Increasing the intensity of light at work

·

Having a predictable schedule of night shifts

·

Eliminating sound and light in the bedroom during daytime sleep

·

Using caffeine (only during the first part of the shift) to promote alertness at night

·

Possibly using prescription sleeping pills to help daytime sleep on an occasional basis (check with your doctor)

More on Problem Sleepiness 153

If you think you are getting enough sleep, but still feel sleepy during the day, check with your doctor to be sure your sleepiness is not due to a sleep disorder.

Vocubulary Builder ECG: Measurement of electrical activity during heartbeats. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Rheumatoid: Resembling rheumatism. [EU] Somnolence: Sleepiness; also unnatural drowsiness. [EU]

Online Glossaries 155

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries and glossaries. The National Library of Medicine has compiled the following list of online dictionaries: ·

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

·

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

·

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

·

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

·

On-line Medical Dictionary (CancerWEB): http://www.graylab.ac.uk/omd/

·

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

·

Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html

Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a) and drkoop.com (http://www.drkoop.com/). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to narcolepsy and keep them on file. The NIH, in particular, suggests that patients with narcolepsy visit the following Web sites in the ADAM Medical Encyclopedia: ·

Basic Guidelines for Narcolepsy Narcolepsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000802.htm

156 Narcolepsy

·

Signs & Symptoms for Narcolepsy Apnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Hallucinations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003258.htm Hypersomnia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Inability to speak Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003204.htm Insomnia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Paralysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003190.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Sleepiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm

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Sleepy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Somnolence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Wakefulness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm ·

Diagnostics and Tests for Narcolepsy ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm EEG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003931.htm Polysomnogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003932.htm Polysomnography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003932.htm Sleep studies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003932.htm

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·

Background Topics for Narcolepsy Aggravated by Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002227.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Genetics Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002048.htm Stimulants Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002308.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries and glossaries: ·

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

·

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

·

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

Glossary 159

NARCOLEPSY GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU]

Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Antidepressant: An agent that stimulates the mood of a depressed patient, including tricyclic antidepressants and monoamine oxidase inhibitors. [EU] Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized Tlymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anxiety: The unpleasant emotional state consisting of psychophysiological

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responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Ataxia: Failure of muscular coordination; irregularity of muscular action. [EU]

Aura: A subjective sensation or motor phenomenon that precedes and marks the of a paroxysmal attack, such as an epileptic attack on set. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Cholinergic: Resembling acetylcholine in pharmacological stimulated by or releasing acetylcholine or a related compound. [EU]

action;

Chronic: Of long duration; frequently recurring. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Confusion: Disturbed orientation in regard to time, place, or person, sometimes accompanied by disordered consciousness. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Consciousness: Sense of awareness of self and of the environment. [NIH] Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Desipramine:

A tricyclic dibenzazepine compound that potentiates

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neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dorsal: 1. pertaining to the back or to any dorsum. 2. denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dreams: A series of thoughts, images, or emotions occurring during sleep which are dissociated from the usual stream of consciousness of the waking state. [NIH] ECG: Measurement of electrical activity during heartbeats. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electroencephalography: The recording of the electric currents developed in the brain, by means of electrodes applied to the scalp, to the surface of the brain (intracranial e.) or placed within the substance of the brain (depth e.). [EU]

Enzyme: Substance, made by living cells, that causes specific chemical changes. [NIH] Ephedrine: A sympathomimetic drug that stimulates thermogenesis in laboratory animals and humans. Animal studies show that it may reduce fat content and, therefore, body weight by mechanisms that probably involve increased expenditure and reduced food intake. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Extracellular: Outside a cell or cells. [EU] Facial: Of or pertaining to the face. [EU] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fibrosis: Process by which inflamed tissue becomes scarred. [NIH] Fluoxetine: An antidepressant drug used to promote weight loss whose action is mediated by highly specific inhibition of serotonin reuptake into presynaptic neurons. Serotonin acts in the brain to alter feeding and satiety by decreasing carbohydrate intake, resulting in weight reduction. [NIH]

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Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Hypertension: High blood pressure (i.e., abnormally high blood pressure tension involving systolic and/or diastolic levels). The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines hypertension as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or taking hypertensive medication. The cause may be adrenal, benign, essential, Goldblatt's, idiopathic, malignant PATE, portal, postpartum, primary, pulmonary, renal or renovascular. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Immunosuppressant: An agent capable of suppressing immune responses. [EU]

Infarction: 1. the formation of an infarct. 2. an infarct. [EU] Innervation: 1. the distribution or supply of nerves to a part. 2. the supply of nervous energy or of nerve stimulus sent to a part. [EU] Insomnia: Inability to sleep; abnormal wakefulness. [EU] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Lesion: Any pathological or traumatic discontinuity of tissue or loss of

Glossary 163

function of a part. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Medicament: A medicinal substance or agent. [EU] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at

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nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Paralysis: Loss or impairment of motor function in a part due to lesion of the neural or muscular mechanism; also by analogy, impairment of sensory function (sensory paralysis). In addition to the types named below, paralysis is further distinguished as traumatic, syphilitic, toxic, etc., according to its cause; or as obturator, ulnar, etc., according to the nerve part, or muscle specially affected. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Perfusion: The passage of fluid through an organ. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The entire physical, biochemical, and physiological makeup of an individual as determined by his or her genes and by the environment in the broad sense. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU]

Glossary 165

Prevalence: The number of events, e.g., instances of a given disease or other condition, in a given population at a designated time. When used without qualification, the term usually refers to the situation at specific point in time (point prevalence). Prevalence is a number, not a rate. [NIH] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH] Pulmonary: Relating to the lungs. [NIH] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reflex: 1; reflected. 2. a reflected action or movement; the sum total of any particular involuntary activity. [EU] Refractory: Not readily yielding to treatment. [EU] Remission: A diminution or abatement of the symptoms of a disease; also the period during which such diminution occurs. [EU] Rheumatoid: Resembling rheumatism. [EU] Schizophrenia: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, hallucinations, emotional disharmony, and regressive behavior. [NIH] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic

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phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Senility: Old age; the physical and mental deterioration associated with old age. [EU] Snoring: Rough, noisy breathing during sleep, due to vibration of the uvula and soft palate. [NIH] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Stimulant: 1. producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. an agent or remedy that produces stimulation. [EU] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Surgical: Of, pertaining to, or correctable by surgery. [EU] Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Syncope: Fainting; temporary loss of consciousness. [NIH] Systemic:

Relating to a process that affects the body generally; in this

Glossary 167

instance, the way in which blood is supplied through the aorta to all body organs except the lungs. [NIH] Tomography: The recording of internal body images at a predetermined plane by means of the tomograph; called also body section roentgenography. [EU]

Tone: 1. the normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. a particular quality of sound or of voice. 3. to make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. producing and restoring the normal tone. 2. characterized by continuous tension. 3. a term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU]

Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH]

General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna

·

Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna

·

A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna

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·

Dorland’s Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna

·

Dorland’s Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna

·

Dorland’s Pocket Medical Dictionary (Dorland’s Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618

·

Melloni’s Illustrated Medical Dictionary (Melloni’s Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC PressParthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna

·

Stedman’s Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna

·

Stedman’s Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna

·

Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co, ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna

Index 169

INDEX A Abdominal................................53, 92, 160 Abrupt ..............................................52, 54 Adolescence ......58, 73, 83, 150, 159, 164 Adrenergic ...............................62, 85, 164 Adverse .................................................63 Alleles ........................................60, 63, 80 Amnesia.................................................54 Amphetamine ..........................62, 64, 130 Antidepressant.......................15, 122, 161 Antiepileptic ...........................................52 Antigen ............................................57, 80 Anxiety.........................52, 53, 56, 77, 164 Apnea ..11, 18, 29, 31, 66, 70, 71, 99, 148 Assay...............................................66, 69 Ataxia...................................................103 B Biochemical ...............15, 74, 77, 159, 164 Biosynthesis ..........................................83 C Cardiac ............................................56, 91 Cerebral...........................................52, 91 Cerebrospinal ..................................64, 66 Cerebrovascular ....................................52 Cholinergic...........62, 69, 71, 82, 153, 164 Chronic ..11, 12, 20, 27, 32, 55, 65, 67, 81 Clonic.....................................................53 Cognition ...............................................54 Colic.......................................................91 Collapse.....................................12, 13, 32 Conception ............................................58 Confusion ........................................52, 53 Conjugated ............................................67 Consciousness .......22, 31, 52, 75, 78, 82, 160, 161, 166 Cortex ....................................................52 D Degenerative .........................................65 Desipramine ..........................................83 Dizziness ...........................52, 53, 92, 167 Dorsal ....................................................69 Dreams ..................................................14 E Efficacy ....................................59, 75, 161 Electroencephalography..................52, 54 Enzyme..................................................69 Epidemiological .....................................57 Extracellular.............................69, 76, 163 F Facial .....................................................12 Fatigue.....................74, 81, 122, 160, 164

Fibrosis ................................................. 13 G Gastrointestinal ....................... 53, 75, 162 H Haplotypes ............................................ 60 Histocompatibility.................................. 81 Holidays ................................................ 59 Hormonal .............................................. 56 Hypertension............. 56, 75, 85, 162, 164 Hypnotic ........................................ 91, 129 Hypothalamic ........................................ 68 Hypothalamus ............. 66, 67, 68, 76, 162 Hypotonia.............................................. 31 I Infarction ............................................... 56 Innervation ............................................ 67 Insomnia .... 11, 18, 20, 31, 67, 68, 71, 90, 148, 152 Institutionalization ................................. 66 Intermittent ............................................ 71 Invasive................................................. 70 L Lesion ..................................... 22, 67, 164 Lethargy ................................................ 53 M Medicament .......................................... 83 Microdialysis ............................. 62, 66, 69 Modulator .............................................. 66 Molecular .... 11, 72, 77, 97, 101, 102, 165 N Neural ....................... 22, 71, 84, 161, 164 Neurology.............................................. 81 Neuromuscular ..................................... 15 Neuronal ........................... 52, 68, 85, 163 Neurons ... 63, 65, 67, 68, 71, 76, 85, 122, 153, 161, 163, 164 Neuropeptides ........................ 81, 85, 163 Neuropharmacology ............................. 61 Neurotransmitter . 66, 68, 77, 85, 163, 164 Nicotine ............................................... 150 Norepinephrine .. 73, 77, 83, 84, 159, 161, 163 P Panic ............................................... 52, 56 Paralysis .... 12, 14, 18, 22, 27, 28, 30, 63, 80, 82, 132, 164 Paroxysmal ............................. 53, 74, 160 Pathogenesis ...................................... 131 Pathophysiology ................................... 57 Perfusion............................................... 69 Pharmacologic ...................................... 59

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Phenotype .............................................64 Phenylalanine ........................................83 Prazosin.................................................82 Precursor .........................83, 85, 164, 167 Prenatal .................................................53 Presynaptic..............62, 77, 122, 161, 163 Prevalence...................27, 38, 57, 58, 165 Proxy .....................................................83 Psychiatric .............................................53 Psychogenic ..........................................53 Pulmonary ...............................11, 76, 162 R Receptor .....62, 66, 68, 69, 71, 74, 80, 81, 159 Recurrence ............................................54 Reflex ....................................................91 Refractory ..............................................53 Remission................................54, 78, 165 Rheumatoid .........................................149 S Schizophrenia........................................65 Sclerosis ........................................13, 103 Seizures....38, 52, 53, 54, 55, 78, 91, 164, 166

Senility .................................................. 54 Snoring.................................................. 20 Somatic ................................... 55, 73, 159 Species ................................... 82, 85, 166 Spectrum......................................... 57, 63 Sporadic................................................ 60 Stasis .................................................. 131 Stimulant .. 57, 59, 74, 122, 149, 159, 163, 164 Stupor ..................................... 53, 76, 163 Symptomatic ........................... 65, 78, 166 Syncope .............................. 52, 53, 54, 91 T Tomography.......................................... 53 Tone... 14, 31, 38, 52, 58, 78, 80, 82, 162, 167 Tonic ..................................................... 53 Tyrosine ................................................ 83 V Vertigo..................................... 91, 92, 167 W Wakefulness .... 14, 18, 22, 60, 63, 67, 68, 71, 151, 162

Index 171

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Index 173

174 Narcolepsy