Disorders of the Nervous System

Disorders of the Nervous System A Primer Alexander G. Reeves, M.D. Rand S. Swenson, M.D., Ph.D.

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Dartmouth Medical School

Table of Contents Front matter

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Introduction

Part 1: The Neurologic Exam

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1. General physical examination 2. Hemispheric function 3. Cranial nerves - olfaction and vision 4. Cranial nerves - eye movements 5. Cranial nerves - facial movement and sensation 6. Cranial nerves - vestibular function and hearing 7. Cranial nerves - lower cranial nerves 8. Reflex evaluation 9. Sensory system examination 10. Motor system examination

Part 2: Neurologic disorders

11. Basic principles in neurologic disease 12. Neuromuscular system disorders 13. Epilepsy 14. Demyelinating diseases of the nervous system 15. Degenerative diseases of the nervous system 16. Dementia 17. Infectious diseases of the central nervous system 18. Disorders of basal ganglia function 19. Cerebrovascular disorders 20. Mass lesions

21. Headaches 22. Cranial and spinal trauma 23. Neurologic Tests 24. Depression of consciousness 25. Metabolic encephalopathy

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Preface

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This book is not comprehensive in scope. It is meant to be a preliminary clinical

General References

neurology text for medical students. It is the compilation of eight years experience teaching introductory neurology to second-year medical students at Dartmouth. General references to further reading are given at the end of each chapter and it is assumed that, as at Dartmouth, faculty will supplement the students' reading with current journal and textual materials when appropriate. A basic course in neural sciences has been a prerequisite and neuropathology and physical diagnosis are taught in parallel. A clerkship on the neurology wards has traditionally followed. There are two basic divisions in the text. The first six chapters constitute an introduction to neurologic diagnostic concepts. An attempt is made to introduce a basis for the neurologic evaluation and, to a lesser degree, the methods. These can be taught in parallel or subsequently in physical diagnosis courses. The remaining fourteen chapters deal with selected aspects of neurologic symptoms and disease. Well-defined principles are introduced, but there are frequent speculative constructs in neurologic pathophysiology that, it is hoped, will stimulate discussion and further reading. We are indebted to many people who have assisted in the production of this work: to our neurology residents and colleagues and many generations of medical students who have given incalculable and critical input during evolution of the text and neurology teaching at Dartmouth; to Joan Clifford and Judy Murphy for their secretarial and copyreading expertise; to the Sandoz Foundation and Dr. Craig Burrell for their timely support and advice during the preparation of the manuscript; to Drs. Louis

Caplan and Laurence Levitt for their critical and constructive review of the manuscript; and, finally, to Fred Rogers and Edward Quigley and the staff at Year Book for their editorial assistance and patient encouragement.

ALEXANDER G. REEVES, M.D.

General references Adams, R.D., Victor, M.: Principles of Neurology, ed. 5. New York, McGraw-Hill Book Co., 1993. Asbury, A., McKhann, G., McDonald, W., eds.: Diseases of the Nervous System, Clinical Neurobiology, ed. 2. Philadelphia, W.B. Saunders, 1992. Bernat J.L., Vincent, F.M.: Neurology, Problems in Primary Care, ed. 2, Los Angeles, PMIC, 1993. Brodal, A.: Neurological Anatomy in Relation to Clinical Medicine, ed. 2. New York, Oxford University Press, 1969. DeJong, R.N.: The Neurologic Examination, ed. 4. New York, Paul B. Hoeber, Inc., 1979. Elaisson, S.G., Prensky, A.L., Hardin W.B.: Neurological Pathophysiology, ed. 2. New York, Oxford University Press, 1978. Jennet, B. and Lindsay, K.: An Introduction to Neurosurgery, ed. 5. Oxford, Butterworth-Heinemann, 1994. Monrad-Krohn, G.H., Refsum, S.: The Clinical Examination of the Nervous System, ed. 12. London, H. K., Lewis & Co., 1964. Spillane, J.D.: Atlas of Clinical Neurology, ed. 3. New York, Oxford University Press, 1982. Vick, N.A.: Grinker's Neurology, ed. 7. Springfield, Il., Charles C. Thomas, Publisher, 1975.

Vinken, P.J., Bruyn, G.N. (eds.).: Disturbances of nervous function, in The Handbook of Clinical Neurology, vol. 1, New York, John Wiley & Sons, 1969. Vinken, P.J., Bruyn, G.N. (eds.): Localization in clinical neurology, in The Handbook of Clinical Neurology, vol. 2, New York, John Wiley & Sons, 1969. Walton, J.: Brain's Diseases of the Nervous System, ed. 8. New York, Oxford University Press, 1977.

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Chapter 1 - General physical examination

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In this chapter, we consider some aspects of the general physical examination that are

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especially pertinent to neurologic evaluation. In later chapters we will cover other

Vital signs

aspects of the neurologic examination, the involvements by specific disease processes, ●

Head

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Eyes

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Ears

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Neck

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Spine

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Pelvis

systems abnormalities, and symptom complexes. Not all elements of examination can (or should) be conducted on every patient. Indeed, if all the examinations that we will describe were carried out on all patients, it would be difficult to see more than several patients a day. An efficient diagnostic approach demands careful evaluation and utilization of historical data in a problem-oriented fashion. This demands that the physician focus on those parts of the physical examination that are pertinent to the

and

specific problem or problems elicited by history or by a basic screening exam. rectum

Vital Signs Of particular importance is evaluation of the respiratory rate and pattern in patients with depressed consciousness. This topic will be elaborated on in the section on the evaluation of coma in Chapter 24. Bilateral involvement of the brain stem from the diencephalon through the medulla may be associated with characteristic and therefore localizing patterns of respiration at each level of involvement. Unilateral dysfunction is usually not reflected by respiratory abnormalities. The abnormal patterns of breathing most likely represent loss of higher control of the primary medullary respiratory center.

Suppression of medullary function by metabolic or direct mechanical involvement results in hypoventilation and, ultimately, apnea. Figure 1-1 is a schematic of respiratory patterns associated with bilateral lesions at various levels in the brain stem. Blood pressure is frequently elevated considerably above pre-morbid levels when there is increased intracranial pressure and then drops when intracranial pressure is lowered (although this usually is not of much localizing value). Blood pressure is also frequently elevated during an ischemic stroke, possibly a compensatory response to loss of part of the cerebral blood supply. Typically, the blood pressure will revert to baseline level over hours to days without need of therapeutic intervention. Attempts to lower the pressure, unless at extreme levels, can be counterproductive (resulting in further ischemia). Blood pressure drops to very low levels following loss of medullary function or severe cervical spinal cord damage; however, for therapeutic purposes, severely depressed blood pressure should be assumed to be due to non-neural causes (such as cardiac abnormality or blood loss) until proved otherwise. Peripheral nervous system dysfunction (i.e., peripheral neuropathy) can produce symptomatic hypotension when the patient assumes the erect position (orthostatic hypotension). This can be related to involvement of the peripheral autonomic nervous system with loss of peripheral vasomotor tone and can be caused by many conditions that produce generalized peripheral neuropathy, such as diabetes, alcoholism, or malnutrition (see chapter 12). Orthostatic hypotension can be detected by recording blood pressure and pulse in the recumbent and upright position, looking for a drop of at least 20 mm Hg of systolic pressure, or a diastolic blood pressure decrease of at least 10 mm Hg within three minutes of standing. Symptoms of light-headedness or faintness would indicate that this was symptomatic orthostasis. If the pulse rate increases as the blood pressure drops, hypovolemia would be

more likely than autonomic failure to be causing the orthostasis. Exercise prior to testing (which causes a reactive peripheral vasodilation, lowering peripheral resistance, may exaggerate any orthostasis). Isolated central or peripheral autonomic failure secondary to medications and metabolic or degenerative disease (including Parkinson disease) can also be a cause of orthostatic hypotension or other autonomic dysfunction (decrease in urinary bladder tone, erectile dysfunction, etc). The pulse rate may be slowed (bradycardia) or accelerated (tachycardia) with increased intracranial pressure, and therefore any change must be considered in a person with central nervous system involvement. Arrhythmias, particularly sinus arrhythmias, and nonspecific ST-T wave changes are frequently seen on electrocardiograms of persons who have had subarachnoid hemorrhage or either hemorrhagic or ischemic strokes. If atrial fibrillation is present, systemic embolization of thrombus formed in the non-pulsatile left atrium should be considered the most likely cause of a stroke.

Head Changes in the shape and size of the cranium may reflect changes in the intracranial contents. In children younger than the age of closure of skull sutures, increased intracranial pressure is reflected in widened suture lines that may be palpable and quite visible in radiographs. If the pressure is prolonged, a mottled decalcification or beaten silver appearance of the skull and demineralization of the dorsum sellae may appear on x-rays. Bulging of the anterior fontanelle in the erect or seated infant is a reliable sign of increased intracranial pressure or contents. Progressively enlarging ventricles, hydrocephalus, causes enlargement of the skull, which can be observed easily. Early diagnosis of hydrocephalus is possible by measuring the cranial circumference during well-baby check-ups (comparing it with standard charts). Subdural fluid effusions, usually associated with meningitis and

subdural or epidural hematomas, also cause excessive skull enlargement in infants and toddlers who have nonfused suture lines. Premature closure of sutures causes characteristic distortions that should be recognized early because associated restriction of brain expansion may result in neuronal damage and mental retardation (Fig. 1-2). In adults, the shape and size of the cranium are less often revealing. The presence of asymmetric bony prominences contralateral to sensory motor deficits or in a person with focal seizures suggests an underlying meningioma, a benign tumor that occasionally causes secondary osteoblastic activity in proximate parts of the skull. In both adults and children who have a history of head trauma or in persons who are stuporous or comatose for unknown reason, the skull should be gingerly palpated for soft-tissue swelling, which suggests head trauma and possibly underlying fracture. Ecchymoses at the base of the occiput (Battle sign) or around the eyes but contained by the orbit (Raccoon eyes) suggest basal skull fractures. When the head is gingerly rotated from side to side, the brain, which is essentially floating in the subarachnoid cerebrospinal fluid and is tethered to the dura and contiguous skull by cranial nerves, blood vessels, and arachnoid membranes, is relatively resistant to the movement. The movement stretches the cranial nerves, the larger blood vessels and the dura. Under normal circumstances, no significant discomfort is caused by this stress. However, when the surface blood vessels or dura, which are sensitive to pain, are already distorted by a mass lesion or swollen with inflammatory edema as with migraine or arteritis, pain may be increased or experienced for the first time on shearing. The patient frequently can point to the area of involvement. Although not part of the routine exam, auscultation of the cranium (with the bell of the stethoscope) over the mastoid region, temporal region, forehead, closed eyes, or (in bald individuals) more

extensively may reveal a vascular bruit arising from an arteriovenous malformation over the brain surface. The bruit is caused by the increased, turbulent flow in the arteriovenous short-circuit that makes up the malformation. In whom should auscultation of the head be considered? The person with a history suggesting an arteriovenous malformation is one candidate. This would include patients with headaches that are always on one side of the head (most patients with migraine, for example, have at least occasional headaches on the other side) or patients with focal seizures. Of course, in both these cases, cranial imaging is important. On occasion the person with arteriovenous malformation hears a bruit, particularly at night when distractions are at a minimum. Careful auscultation of the head may help to localize that. The small child or infant with a congenital arteriovenous malformation in the area of the internal cerebral veins and the vein of Galen has a bruit that is audible over the whole head. S/he may have congestive heart failure from the high flow demands of the shunt, and also an enlarging head, the result of a communicating hydrocephalus. This is caused by the arterialization of pressure in the sagittal sinus, which increases resistance to absorption of cerebrospinal fluid through the arachnoid granulations. Compression of the aqueduct of Sylvius by the swollen vein of Galen may also be the cause of the hydrocephalus. The infant with meningitis and diffuse cerebral vasodilatation and the infant or child with severe anemia may have diffuse cranial bruits caused by high flow through the cerebral or diploic vasculature. These bruits are usually inaudible in the older child or adult whose skull is thicker and thus dampens the sound unless anemia is severe.

Eyes There are several features of the eyes that should be considered in the neurologic exam. The conjunctiva and sclera can show signs of icterus or of inflammatory, vasculitic processes. A prominent corneal arcus can suggest dyslipidema which, in turn, suggests the potential for atherosclerosis. Funduscopic examination can be very revealing. First of all, it may show whether visual abnormalities are due to refractive problems, including poor visual correction or opacities (of the lens or cornea). It is also the only place in the body where blood vessels can be directly visualized. The health of these blood vessels is a reflection of the health of small blood vessels in the nervous system (including signs of atherosclerosis or of diabetic vascular disease that can effect the brain and peripheral nerves). We will specifically discuss two phenomena or neurologic import, papilledema and subhyaloid hemorrhage. Papilledema results from increased intracranial pressure, which occurs when the contents of the cranium exceed the capacity of the intracranial physiologic mechanisms and anatomy to accommodate. The major accommodating factors are the cerebrospinal fluid space (ventricular and subarachnoid) and its ability to be drained by the venous sinuses, the venous space and its collapsibility, the ability of sutures to spread in infants and toddlers, the ability of brain tissue to be compressed and lose substance, the ability of the foramen magnum (and to a lesser degree other foramina) to transmit pressure to the extracranial spaces, and finally, the possibility of decreased production of cerebrospinal fluid from the choroid plexi when intracranial pressure rises to high levels. The major causes of increased intracranial pressure are cerebral edema, acute hydrocephalus (blockage of cerebrospinal fluid [CSF] absorption, relative or absolute), mass lesions (e.g., neoplasm, abscess, hemorrhage), and venous occlusion (e.g., sagittal or lateral sinus thrombosis). Papilledema or edema of the optic disk usually indicates increased intracranial pressure. When it is

fully developed, recognition is not difficult; swollen, blurred and elevated disk edges, engorged and pulseless veins, and increased vascularity of the disk margins are the obvious signs. This is usually bilateral. At these stages, vision is usually unaffected (outside of possible slight increase in the physiologic blind spot *). With further development, hemorrhage (both superficial and deep) and exudates appear. If the process is chronic, filmy white strands of glia proliferate in and around the disk. It is at this late stage that the patient may complain of episodic obscured vision. This precedes final occlusion of the retinal arterial supply and infarction of the retina with permanent blindness. Early recognition is important in order to diagnose the underlying cause and also in order to prevent vision loss. It is usually possible to detect early, subtle signs of intracranial hypertension. Prior to well-established and easily recognizable papilledema, the normal pulsations in the veins of the optic disc disappear with elevated pressures. These pulsations are best seen in the normal fundus where the veins disappear into the substance of the disk. They reflect the arterial pulse pressure superimposed on a baseline intraocular pressure; the veins partially collapse during systole and expand during diastole. If the pulsations are not spontaneously present (as they are in about 75% of normal individuals), a minimal amount of pressure on the globe brings them out in almost all persons who do not have increased intracranial pressure (i.e., less than 200 mm of CSF). The minimal compression partially collapses the veins and allows them to expand during diastole. If intracranial pressure is 200 mm of CSF or greater, venous pulsations usually are not present and the higher the pressure, the less likely there are to be spontaneous pulsations. ** Papillitis or inflammatory edema of the disk looks very similar to papilledema. Indeed, in most cases, they are identical. Papillitis is most often caused by demyelinating processes in young and middle-aged

persons (such as multiple sclerosis) and by optic nerve arterial involvement in older individuals. It is not associated with increased intracranial pressure. As opposed to papilledema, however, it is almost always unilateral. The visual field loss associated with papillitis is usually greatest near the center of vision, because the macular (cone vision) fibers are primarily affected. This leads to early loss of color, particularly red, vision. A central scotoma (blind area) is typically present and thus visual acuity is severely and uncorrectably limited (see Chap. 3). This is distinct from papilledema which usually only produces slight enlargement of the blind spot until quite late when the arterial supply is compromised by compression. Even then, the vision loss of papilledema is usually distinct because it starts at the periphery, with central vision preserved until late. Subhyaloid hemorrhage is a collection of extravasated blood just beneath the inner limiting membrane of the retina (Fig. 1-3). This is different from most retinal hemorrhages which occur deep to the nerve fiber layer.*** Subhyaloid hemorrhages are frequently observed close to the disk margins with an acute, catastrophic rise in intracranial pressure. This is invariably caused by intracranial arterial hemorrhage (subarachnoid or intracerebral) or head trauma with hemorrhage and brain contusion or laceration. They are often seen in "battered infant" syndrome, for example. They appear almost immediately and frequently on the background of a relatively normal-appearing retina. They are presumably caused by a rapid and excessive rise in the central retinal venous pressure, which leads to rupture of the small venular radicals near the disk. Papilledema may follow within several hours. On a normal background the hemorrhages are diagnostic and should allow the physician to avoid lumbar puncture, which, in the presence of cerebral hemorrhage or cerebral contusion or laceration, could further predispose the patient to brain herniation (see Chap. 24). Acute central retinal vein thrombosis, frequently associated with long-standing diabetes mellitus, can

also cause subhyaloid hemorrhages. In these cases, it is almost always unilateral, however, and may be very large or distributed in the segmental distribution of one or several central venous branches. The patient does not appear otherwise ill and complains only of loss of vision in the involved eye. The visual loss may be surprisingly minimal.

Ears In bacterial meningitis, particularly in children, one of the most frequent portals of entry for bacteria is the chronically or acutely infected middle ear. The presence of otitis media is readily visible on otoscopic examination as an opaque, bulging, erythematous tympanic membrane and should be looked for in all persons who are suspected of having meningitis. Successful care of the meningitis may depend on eradication of the otitis, which may necessitate puncturing the eardrum (myringotomy) for drainage in addition to administering appropriate antibiotics. The patient who is unconscious and has no history or obvious signs of etiologic significance should be suspected of having head trauma. In addition to palpation of the cranium for evidence of fracture and observation of ecchymosis, the physician should look for a bulging, blue-red tympanic membrane. If present, it indicates hemorrhage into the middle ear and is pathognomonic for severe head trauma. Basilar skull fracture with dissection through the middle ear is considered the cause; however, severe shearing of the ossicles may be enough to cause tears in blood vessels and hemorrhage. The external ear may be implicated in the person with hearing loss, especially if the deficit is of the conduction type (see Chap. 6).

Neck

The spinal cord, meninges and cervical roots are stretched slightly when the head is flexed onto the chest. This ordinarily can be done without any discomfort; however, this is not so when the meningeal sheaths of the roots are inflamed. Pain and reflex stiffening of the nuchal muscles are elicited when meningitis is present (called "nuchal rigidity" or meningismus). Because the spinal cord is pulled by this maneuver and moved upward slightly in the spinal canal, the lower lumbosacral roots are also stretched and pain may be experienced in the low back and legs as well as the neck. Occasionally, spontaneous flexion of the legs and hips occurs on neck flexion (termed Brudzinski sign). This is a reflex attempt to put some slack in the stretched lumbosacral roots (with the legs in the flexed position, the femoral and sciatic nerves and therefore their roots of origin are slackened). It is usually not symptomatically successful; however, it is a strong indication of meningitis and other causes of root irritation. A majority of the population by age 65 to 70 has x-ray evidence of degenerative disease of the cervical spine. This osteoarthritic change, frequently referred to as cervical spondylosis, appears to be a product of the constant trauma of the weight of the oversized human head on the neck when in the erect position. Despite the appearance of severe cervical osteoarthritis on x-rays, disabling symptoms do not occur in the majority of people with cervical spondylosis. Spondylosis does correlate with decreased mobility (mostly in rotation and lateral bending). Flexion is usually not terribly limited and there is usually not much (or any) pain reported by the patient. They also compensate for the loss of mobility, which occurs slowly. The most important symptoms and signs that can be caused by spondylosis result from irritation or destruction of the cervical roots and/or the spinal cord by the hypertrophic degenerative disks and joints. Nerve root involvement gives localized signs that are positive (e.g., pain and paresthesias) or negative (e.g., loss of sensation, reflexes and power) in character. Damage to the spinal cord by

spondylosis can result in motor and sensory symptoms below the lesion due to interruption of the long tracts of the spinal cord by impingement. Lhermitte's symptom (or Lhermitte's sign) includes a sensation of "electric shocks" radiating from the posterior nuchal region into the arms, trunk, and legs separately or in combination by forcibly extending or flexing the neck. This signals cervical spinal cord involvement and is probably caused by rapid distortion of the cervical cord and associated depolarization in irritated sensory nerve fibers. During extension of the neck, the spinal canal is narrowed in its anterior-posterior diameter by anterior buckling of the posterior-lying ligamentum flavum. In persons with cervical osteoarthritis, the ligamentum flavum is hypertrophied and the vertebral canal is narrowed more than it is normally on neck extension; in combination with the canal narrowing caused by posterior intervertebral disk protrusion, this may be enough to cause pressure on the ventral or dorsal surface of the cord. Lhermitte's symptoms presumably are caused by traumatic depolarization of the sensory tracts. This can happen with neck flexion as well, since the spinal cord is stretched (potentially depolarizing irritated nerve fibers). Lhermitte initially described this symptom in patients who had multiple sclerosis involving the cervical spinal cord. In this situation, neck flexion that stretches the spinal cord probably causes symptomatic depolarization in the dorsal column or spinothalamic tracts made irritable by a demyelinating plaque or other lesion (e.g., neoplasm or syrinx). In general, a physician should suspect an extramedullary lesion (i.e., pressure on the outside of the cord) if Lhermitte's symptom is elicited by extension of the neck and an intramedullary lesion if elicited by flexion. A useful maneuver for corroborating your suspicions of root irritation by posterior lateral protrusion of degenerated disk material is for you to extend the patient's neck and then press the head firmly downward, thus narrowing already narrowed spinal foramina. Frequently this elicits the patient's

symptoms and thus corroborates suspicions. More marked foraminal narrowing can be elicited by extending the head and then flexing it to left or right. On pressing the head inferiorly (Spurling's maneuver), further foraminal occlusion occurs on the side to which the head is flexed (Fig. 1-4). Direct pressure on the posterior lateral part of the neck with the thumb or index finger may also produce discomfort over the involved roots. Of course, any forced movement of the neck should be done cautiously in patients with possible spinal cord injury or injury to the cervical spinal column. Only enough force should be used to elicit the sign or symptoms and, in the case of acute injury it may be necessary to perform x-rays before any such maneuver.

Extremities Movements of the lower extremity beyond a certain point will stretch lumbar plexus and nerve roots. Straight leg raising (i.e., passive flexion of the straightened leg on the hip), or the reverse, extension of the leg on the hip, is used to indicate the presence or absence of irritative or destructive lesions involving the lumbosacral plexus and roots. When the leg is flexed on the hip, the posterior-lying sciatic nerve, which originates in the lower lumbar and upper sacral roots (L4-S2), is stretched and therefore also stretches the plexus and roots (Fig. 1-5A). This stretching usually begins after about 30 degrees of flexion. Extension of the leg on the hip (with the patient lying on the side or prone) stretches the anterior-lying femoral nerve, which originates from the middle lumbar roots (L2-4) (Fig. 1-5B). Any mass or inflammatory process impinging on the nerve, plexus, or roots is likely to bind or irritate these structures and cause pain in the peripheral distribution of the nerve. This pain is often in the muscle and bone distribution of the nerves as opposed to the skin or dermatomal distribution. Buttock, posterior thigh, calf, as well as heel discomforts are characteristic of sciatic system involvement,

whereas groin and anterior thigh pains are characteristic of femoral system involvement. If there is skin involvement, loss of sensation occurs in appropriate dermatomes or peripheral nerve distribution. However, loss of sensation or weakness will only occur if the lesion is destructive. Paresthesias (pinsand-needles sensations) are more common symptoms of dermatomal involvement than is actual loss of sensation. A symptomatic irritative lesion may not cause any actual loss of nerve function. Low-back pain with or without radiation to the leg or legs is the most common cue for the physician to do the straight leg raising test. A common cause of low-back pain is lumbosacral disk disease and, if pain radiates into the leg, a herniated disk is usually the cause. Ninety-five percent of involved disks are between the L4-5 or L5-S1 vertebral bodies. Therefore, because the L5 and S1 roots exist at these spaces, straight leg raising with the patient supine, causing sciatic stretch, is the maneuver of choice. Four percent of lower spine disk problems occur at L3-4 or L2-3, whereas the remaining 1% incidence is shared by L1-2 and thoracic disks. With the higher lumbar protrusions, femoral stretching is the maneuver of choice. Positive test results reproduce or increase the patient's complaints of leg pain. An increase of back pain, alone, is not considered an indication of nerve root involvement and is considered a negative straight leg raising test. Such a "negative test" may still cause pain, but this is from stretching irritated tendons, joints and muscles in the back. Also, a true positive test must be distinguished from tightness of the hamstring muscles, which can produce discomfort during straight leg raising. Acute or chronic arthritis of the hip, on occasion, causes referred pain in the knee and, less commonly, in the foot. Straight leg raising may irritate a damaged hip joint and may give a misleading impression of sciatic root irritation. This can be detected by rotating the femur on the hip while the knee and hip are flexed. This flexion of the knee puts slack on the sciatic and femoral nerves (Fig. 1-6). Pain caused or

increased by this maneuver (Patrick maneuver) suggests hip disease, and appropriate x-rays can confirm this suspicion. Flexion of the head on the chest (chin on chest) pulls the spinal cord upward and stretches the lumbosacral roots somewhat. Lumbosacral root irritation may therefore be increased, causing reproduction or exacerbation of the patient's low back and leg pain. This maneuver would not change the symptoms of hip disease. Meningitis manifests itself throughout the subarachnoid space, and therefore straight leg raising has positive results because the lumbosacral roots and investments are inflamed. In fact, there may be involuntary flexion of the knees during attempted straight leg raise (Kernig sign). This can easily be inferred from our earlier discussion of Brudzinski sign.

Spine Pathologic processes (degenerative, neoplastic, or inflammatory) in or near the spinal column frequently give rise to local muscle spasm and pain. If the process is unilateral, muscle spasm, presumably the result of direct or indirect irritation of the dorsal sensory and/or motor branches to the paraspinal muscles, causes characteristic distortion of the spine in addition to palpable firmness and tenderness. When the paraspinal muscles contract unilaterally, they bow the spine laterally; the concave side of the bow appears on the side of increased muscle tension (Fig. 1-7B). This lateral bowing is called scoliosis and can be observed most easily when the patient is erect. Observation is further facilitated by making a mark with a pen on the palpable top of the dorsal spinous processes of the vertebrae. The only exception to the rule of contralateral bowing occurs at the lumbosacral junction where the paraspinal muscles are broadly attached to the sacrum and the ilium. The bowing occurs to

the side of the spasm in this instance (Fig. 1-7A). Percussion of the spine to elicit point tenderness is routinely carried out with the hypothenar portion of the fist. Because a large area is covered with each blow to the spine and there is diffusion to several vertebral segments, it is more reasonable to use a percussion hammer and tap each spinous process. Often this accurately localizes the segments involved.

Abdomen, Pelvis and Rectum Every general medical evaluation should include examinations of the abdomen, pelvis and rectum. However, on neurologic evaluation these examinations are not called for unless the patient cues them by certain complaints. The most common cue is the complaint of low-back pain with or without radiation into the legs. Even though disk and spine or paraspinous disorders are the usual cause of this complaint, several common pelvic neoplastic disorders give rise to very similar complaints and may be associated with positive straight leg raising. Carcinoma of the cervix is the most common form of female pelvic neoplasm. It spreads by local extension and therefore (by invading the pelvic [lumbosacral] plexus) may first become symptomatic as low-back and/or leg pain. Carcinoma of the prostate is the most common male pelvic tumor and also spreads by local extension. Low-back and/or leg pain may be the symptom that brings a patient for medical attention. Rectal carcinoma occasionally gives rise to lowback pain because of spread to and enlargement of local lymph nodes. Rectal and pelvic examinations are mandatory when low back pain is a complaint, especially in middle-aged and older adults in the age range when the incidence of neoplasia increases. The lumbar and sacral spine are also common sites of metastasis of these cancers and this must be considered in the patient with a history of cancer or in older individuals with new lower back pain.

Low back pain or, for that matter, bone pain involving all levels of the spinal axis in women mandates breast examination to rule out carcinoma of the breast which frequently metastasizes to the spine and other long bones. Acute, new back pain should give rise to consideration of possible abdominal aortic aneurysm (often palpable or visible on lumbar x-rays and measurable by ultrasound). Renal disease should be considered in patients with flank pain and, particularly, if the pain is colicky. When urinary or fecal incontinence is present or a complaint, rectal examination is indicated to evaluate both reflex and voluntary anal sphincter function.

*The retina is very sensitive to mechanical pressure. You may demonstrate this by pressing very lightly on the lateral side of one of your eyes. The depolarization block caused by minimal compression of the retina creates a blind spot (scotoma) in the contralateral field (i.e., next to your nose). In like manner, early and poorly visible swelling of the disk margin depolarizes and blocks the proximate retina and enlarges the physiologic blind spot. The blind spot represents the retina-deficient optic disk and is routinely plotted and of fairly uniform size when formal visual fields are studied with a tangent screen or perimeter (see Chap. 3).

**The mechanism for loss of venous pulsations is presumed to be an increase in venous backpressure subsequent to intracranial hypertension. It is presumed that papilledema is a function of the ratio of intracranial (and, therefore, intravenous) pressure to intraocular pressure; elevation of the former or depression of the latter is adequate to abolish pulsations and elicit edema of the disk. For practical purposes, papilledema is almost always the result of increased intracranial pressure. Increased intraocular pressure (glaucoma) should delay the appearance of papilledema, and this is so; it can be the source of some diagnostic confusion.

***In persons with long-standing diabetes mellitus or systemic hypertension, the blot-like hemorrhages may be present but are usually associated with other abnormalities of the retina, including hemorrhages of the nerve fiber layer (flame-shaped or striated), narrowing and atherosclerotic distortion of the arteries, exudates, capillary aneurysms, and vascular proliferation (neovascularization).

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Chapter 2 - Hemispheric function

On this page ●

The cerebral hemispheres, particularly in large and redundant cerebral cortical mantle, are the anatomical substrates of the uniqueness of Man. The cortex of

Diffuse bilateral functions

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the cerebral hemispheres embodies the higher integrative or intellectual

Specific hemispheric

capacities of man and its expanse in area and neuronal numbers far outstrips

regions

the same parameters of our nearest phylogenetic cousin, the chimpanzee. The ❍

complexity of neuronal ramification and interconnection is fantastic! It is

Left hemisphere

estimated that there are nine billion neurons in each cerebral hemisphere and ❍

Right

each neuron has between five and ten thousand interconnections with other hemisphere

neurons neighboring and distant. The mathematical dimensions are staggering, ❍

Limbic system

❍

Frontal lobes

little short of infinite. The latest generation of man-made brains, in all their circuit complexity cannot compare. ●

References

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Questions

The higher integrative functions can be divided into those functions having diffuse representation in the cortex and those with more focal representation.

Some functions are in both hemispheres and some are unilaterally represented. Obviously, all of this affects the symptoms produced by damage to the brain.

Diffuse Bilateral Functions According to Harold Wolff, diffuse bilateral functions include: "(a) the capacity to express appropriate

feelings, appetites and drives; (b) the capacity to employ effectively the mechanism of goal achievement (learning, memory, logic, etc.); (c) the capacity to maintain appropriate thresholds and tolerance for frustration and failure, and to recover promptly from their effects; (d) the capacity to maintain effective and well-modulated defense reactions (i.e., repression, denying, pretending, rationalization, blaming, withdrawal, fantasy, depersonalization, obsessive compulsive behavior and bodily reaction patterns involving alimentation, respiration, metabolism, etc.)." These are the kind of functions that are lost only after diffuse and bilateral injuries to the brain, such as occur in the dementing disorders. Dementia is defined as a progressive loss of intellectual and higher emotional capacities. Many of the early changes in rational and emotional behavior are nonspecific for cerebral dysfunction; that is, they can be the reflection of severe psychological stress and disorder not of clear-cut organic origin but of the psychiatric sphere (which have been termed "pseudodementia"). Condensing the above further, one can see that man's major intellectual achievement has been the rational control by inhibitory modulation of the basic drives of self and species preservation common to all animals: feeding, fighting, fleeing and procreation. The complexity and variability of these rational and emotional drives and behavior becomes greater and greater as one ascends the phylogenetic scale, culminating with man. The manifestations of functional loss, reversible or irreversible, therefore become more complex and subtle as the functional anatomy of the nervous system ascends through phylogeny. As neuronal diffuse dysfunction becomes more advanced, obvious and unmistakable changes occur. There are deficits in emotional response, often with a tendency toward apathy and flatness of affect, alternating with wide and inappropriate swings of emotional behavior. The latter reflects a loss of rational inhibitory control of the basic emotional drives mediated by the limbic system. Defects in

learning and memory, particularly the former, abstract thinking, general information and capabilities, and in judgment are easily detectible in patients with diffuse bilateral involvement. It may be difficult to distinguish patients with certain psychiatric disorders from those with early diffuse cortical degeneration. It may be impossible to test cognitive functions in patients who are psychotically depressed or catatonic due to schizophrenia. Fortunately, organic cerebral hemispheric deterioration frequently uncovers primitive reflexes that can be elicited without cooperation from the patient. Most of these complex reflexes occur in infants and are suppressed during normal cortical development. These reflexes reappear with dementia (that is, they become disinhibited). There is a long list of regressive reflexes has evolved. The most commonly sought and elicited are the feeding or mouthing phenomena including involuntary snouting, sucking, rooting, and biting in response to tactile or visual stimuli, forced grasping with the hands and the feet, and extension of the great toe on plantar stimulation (Babinski response). Patients with dementia often show motor perseveration, inappropriately repeating the same movement due to loss of ability to inhibit ongoing activity. This may be observed with repetition of words or ideas (this can occasionally be seen in normal individuals when fatigued or under emotional strain). Another manifestation of this perseveration can be seen when testing resting muscle tone. The patient appears to have an inability to relax, termed paratonia, when the examiner is attempting to passively move a body part. This can be quite frustrating to the examiner, since it appears that the patient is willfully resisting passive movement. This perseveration of tone can meld into a perseveration of movement as the patient overcomes initial inertia and gets into rhythm with the examiners testing movements. The examiner becomes aware of this when releasing the patient's arm or leg and instead of dropping relaxed to the bed, it continues the supposed passive movements. These abnormalities of tone, labeled

paratonia (or gegenhalten), can be seen in infants and young children so may also represent a regression of function. It can be seen in normal individuals, but is much more common in patients with dementia, and therefore has been included with other things as a "soft sign" of dementia. Historically, diffuse hemispheric disease (i.e., dementia) has been considered to be a progressive and hopeless condition of old age. Twenty years ago, current knowledge and therapeutics accepted just that attitude with few fortunate exceptions. Today the number of treatable and potentially reversible disorders of the cerebral hemispheres is growing although the majority of cases of dementia are not reversible. Additionally, some of the previously untreatable dementias are yielding partially to new therapies. New diseases are not appearing; old entities are being recognized as treatable with the expansion of etiologically and therapeutically oriented research in dementia. Obviously, the treatable causes of dementia must take diagnostic priority though they may be statistically unlikely.

Specific Hemispheric Regions and Structures Some brain functions are localized to specific hemispheric regions. For example, there are areas of primary motor and sensory function that are highly localized. On the motor side, skilled movements (particularly of the distal upper limbs) of the contralateral side of the body are initiated by the primary motor cortex in the precentral gyrus. There are areas of highly localized sensory function, including the somatosensory cortex in the postcentral gyrus and the visual cortex of the occipital lobe. damage to there areas can affect the ability to feel things or see things on the contralateral side of the body. The ability to hear and smell are bilaterally represented, and therefore are generally unaffected by unilateral brain injury. There are several more complex functions that lateralize. Included among these functions are language, handedness and visuospatial orientation and, as already alluded to above, learning,

emotionality, and behavioral inhibitory control.

Left hemisphere In 97% of the population language is represented in the left hemisphere, with little if any contribution from the right hemisphere. Only three in one hundred people will have significant right hemispheric representation of speech functions; of those three, two will have significant bilateral representation of speech, with only one individual having right hemisphere dominance. It is known that early brain injury (the earlier the better, but generally before the age of about 4), is associated with transference of language function to the spared hemisphere. With increasing age and gradual lateralization and anatomical fixation of speech functions to the left hemisphere, less and less flexibility remains. The areas involved in the central organization of language, which is man's most advanced capability, are appropriately the most advanced and latest developed neocortical zones. It is not too surprising that this highest function would localize in the most advanced regions and further still that this function would tend to utilize the greatest expanse of advanced cortex, which happens to be, in most, localized on the left. The above is interesting but grossly speculative. "Why unilaterality?" might be the next question. No one has proposed a fully satisfactory answer to this teleological question. It is possible that this is for efficiency, such that language function does not have to occupy similarly large areas on both sides of the brain (leaving more cortex for other functions). However, this is speculative. Man appears to be, with rare exception, the only animal with significant lateralization of such an important function (some birds apparently have lateralization of their singing capabilities). Handedness correlates fairly closely with language dominance. Ninety percent of the population is right-

handed; of 1,000 right-handed people only one will be right hemisphere dominant for speech; overwhelmingly, to be right-handed is to be left brained for language. Ten percent of the population is left-handed; 7 of 10 left-handed individuals are left-brain dominant for speech, essentially breaking down the nice speech-handedness correlations seen in right-handed individuals. The remaining 3 lefthanders will be those with either bilateral representation of speech (2) or with right hemisphere dominance (1). Functional Magnetic Resonance Imaging (fMRI) has added the capability to study regional metabolic activities in the brain, which is adding to and corroborating past findings determined by traditional methods (see Chap. 23). We have learned most that we know about speech functions and localization from disease processes involving the brain. Some minor contribution has come from stimulation studies and observations of the effects of drugs. Table 2-1 summarizes the effects of destructive lesions of the classic anatomical speech areas of Broca and Wernicke. Dysfunctions of language are called dysphasias, complete loss of some component of language function is called aphasia. Testing of the patient with a suspected language disorder requires several steps. These include: observation of the characteristics of spontaneous production; response to variably complex commands; the ability to repeat complex phrases; the ability to name objects and parts of objects; and the ability to read and write. Testing of these functions will usually quite accurately localize the area of involvement. The finding of other areas of cortical damage can also help localize the process, since some functions are located close to the language areas of the cortex. For example, a patient with verbal language dysfunction, homonymous hemianopsia and little motor deficit, will more than likely have a receptive (Wernicke) dysphasia. A patient with a verbal language dysfunction, marked hemimotor and hemisensory deficit and no visual abnormality will probably have an expressive (Broca) dysphasia.

For practical purposes it is worth noting that the majority of patients with dysphasia will have a combination of both expressive and receptive dysfunctions (called global dysphasia). This is because the majority of patients who are dysphasic are so because of cerebral infarction and the infarction, usually patchy, involves the middle cerebral artery territory, which encompasses both language areas as well as the pathway connecting them, the arcuate fasciculus (see Fig. 2-1). Damage to the arcuate fasciculus can disconnect the area of the brain that comprehends language (Wernicke area) from the area that is generating language (Broca area). This would abolish the ability to repeat a complex phrase, since the comprehension of the phrase could not be transmitted to the area generating the words. An even more unusual "disconnection syndrome" occurs when the areas around the primary language areas are damaged, leaving the primary language areas intact (Fig. 2-2). This "disconnects" the language areas from the rest of the cortex, which is contributing to the thought processes that are then being expressed through the primary language areas. Such individuals would be able to repeat, but would have problem spontaneously generating meaningful language. Damage to the entire corpus callosum can cause a very striking disconnection syndrome (sometimes termed "split brain"), although it may not be observed unless the proper functions are tested. One of the most striking features of the fully expressed "split brain" is the inability to verbally tell you what an article is, if it is placed in the left hand (assuming left hemisphere dominance and that the patient is prevented from looking at it). Additionally, this individual will be unable to understand written language if the writing is presented only to the left visual field. This material reaches only the right hemisphere and cannot be transferred to the left or verbal hemisphere, for interpretation. A rather striking and frequently-quoted example is that of the woman with corpus callosum transection who snickered when a risqué picture was presented to her left field. When asked why she laughed her

left hemisphere answered, "It's a funny test." When the picture was flashed into the right visual field, and therefore seen by the left hemisphere, the patient quipped "You didn't tell me I was going to have to see this kind of a picture." During the first presentation of the picture, the right hemisphere saw the picture and laughed. The left hemisphere rationalized that the laugh must have been because the test was funny. From the above it is obvious that the right and left cerebral hemispheres, to some degree, are able to function as two separate individuals if disconnected. In addition to having visual transfer problems, transection of the corpus callosum will prevent transfer of auditory verbal commands from the left hemisphere to the right. Commands to do chores with the left hand will therefore be carried out imperfectly or not at all. These examples and the observation of the patient with a split brain pulling the pant leg up with the right hand and down with the left (as if the right and left hemispheres were in competition) reinforce the assumption of a partial schizo cerebration which comes to light only when the major connection, the corpus callosum, is destroyed. It is noteworthy that there may be other connections between the left and right hemisphere, especially if damage to the corpus callosum occurs early in life (such as agenesis).

Right hemisphere The right hemisphere must be considered functionally inferior to the left since it lacks significant speech representation. Therefore it has been termed the "non-dominant" hemisphere. However, certain functions do tend to localize to the right hemisphere. For example, the ability to recognize loss of function, visuospatially oriented perception and behavior, and musicality all appear to be predominantly functions of the right cerebral hemisphere. Also, the ability to generate verbal inflections and to detect tone of voice appears to be localized to the right hemisphere.

The patient with severe right hemispheric dysfunction (e.g., subsequent to infarction, trauma, hemorrhage, or tumor) will manifest rather obvious deficits in elementary hemispheric functions: s/he will have a hemiweakness, hemisensory depression, and various abnormalities of cranial nerve function. These deficits are not at all surprising based on cortical localization. However, particularly if the non-dominant parietal lobe is involved, the capacity to acknowledge or recognize loss is severely impaired; for example, the patient may not know that there is anything wrong and therefore will deny the allegation that there is a deficit. When asked to move the left arm they may say that they have done so even though no visible movement has occurred. More bizarrely they may reach for the left arm and grasp the examiner's, which has been slipped in the path, and claim that it is their own. Also they may deny that their arm actually belongs to them; this abnormality probably depends to some degree upon the amount of sensory depression on the left. Some time ago, a patient with severe right hemisphere dysfunction due to a stroke was examined at the VA hospital. When turned onto his right side for the purpose of carrying out a lumbar puncture he vociferously objected to the presence of another person who was lying on top of him; the other person was his own left side! The term applied to the lack of appreciation (or neglect) of deficits is "anosognosia" is the term applied to this deficit. In time, anosognosia fades, compensated by recovery of right cerebral function or some transfer of this function to the left hemisphere. However, there are usually some remnants of neglect unless the pathology completely reverses (e.g., the patient, when asked what is wrong, might answer, "The doctors tell me I am weak on the left," etc.). These patients, as you may surmise, tend to be poor rehabilitation candidates because their neglect decreases their motivation for improvement. The patient with a similar motor disorder in the right limbs from left hemispheric damage, despite the fact that they may have severe language deficits, is quite conscious of the motor loss and quite willing, even insisting, to

rehabilitate him- or herself. Lesions of the right hemisphere, particularly when they involve the confluence of the parietal, occipital and temporal lobes are frequently associated with visuospatial disorientation of a disabling degree. This can be tested at the bedside by having the patient fill in well-known cities such as San Francisco, New York and Washington on a map of the United States or by having the patient copy a two dimensional rendition of a cube. At a practical level, visuospatial disorientation creates problems with following directions, reading maps and when an unfamiliar place is encountered navigation may become grossly disordered. Penfield described a patient, who after right temporal lobectomy was lost as soon as he lost sight of home. he was forced to take a job in the post office across the street from home in order to avoid daily confusion (Fig. 2-3). Musicality is also a predominance of the right hemisphere. Lesions, particularly of the temporaloccipital-parietal confluence on the right, cause variable deficits in tune learning and reproduction. Leftsided destruction can leave the patient without speech but musical ability will frequently remain intact with the patient readily and correctly reproducing tunes if s/he is cued by the examiner.

Frontal lobes The frontal lobes include the areas of the motor cortex and the premotor cortex posteriorly, and the prefrontal cortex anteriorly. The motor and premotor cortices are involved in the planning and initiating of movements. Damage to medial areas of the premotor cortex (supplementary motor area) can prevent the ability to initiate voluntary actions (abulia) that can be so severe as to prevent any movement (akinesia). Additionally, Broca area is part of the premotor cortex in the dominant hemisphere.

The prefrontal cortex has more complex functions. Broadly, we divide this part of the cortex into dorsolateral prefrontal cortex and the orbitomedial prefrontal cortex. The dorsolateral prefrontal cortex is involved in what has been called executive functions. Osborn described these functions as: "The ability to organize thoughts and work, to create plans and successfully execute them, to manage the administrative functions of one's life. Individuals with impaired executive function may appear to live moment-to-moment, fail to monitor their activities or social interactions to make sure plans are carried out (or even made). With diminished ability to create strategies, to handle more than one task at a time, to be effective, reliable, and productive, the simplest job may be too challenging." Damage to this area also can affect "working memory" which is the ability to hold something in the mind while manipulating it (such as repeating a string of numbers backward) and also inhibits the ability to perform several tasks simultaneously. The orbitomedial prefrontal cortex is involved in control of impulses and behavior. Damage to this area severely affects personality. Patients display poor judgment, inadequate planning, and little motivation. With more advanced disease, they may become inappropriately jocular ("Witzelsucht") and irritable and lose their social graces. It has been proposed that the orbitomedial prefrontal cortex is anatomically situated (in terms of their connections) between the perceptual motor systems of the hemispheres and the limbic system. Lesions in this area might then divorce perception and action from motivation. A classic example of this was described by Harlow after prolonged observation of a patient, Phineas Gage, who had sustained severe damage to the orbitomedial prefrontal cortex. “The equilibrium or balance, so to speak, between his intellectual faculties and animal propensities, seems to have been destroyed. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom) manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his

desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operation, which no sooner arranged than they are abandoned… in this regard his mind was radically changed, so decidedly that his friends and acquaintances said that he was ‘no longer Gage.’” There are a variety of physical findings that are common, but not specific, for prefrontal cortex lesions. Grasp, sucking and snout reflexes are common. Paratonia (gegenhalten) and perseveration of actions or speech are often seen. As described above, paratonia (gegenhalten) refers to an increase in tone; instead of relaxing, the patient either resists or tries to help when the examiner attempts to move the limbs passively. Perseveration refers to the repetition of a response when it is no longer appropriate. A person may raise their hand on command, for example, and then continue to raise their hand when asked to point to the floor or touch the nose. Verbal responses can similarly demonstrate perseveration. Perseveration may occur for a variety of reasons: inability to make the correct response, failure to check the response against the question, or lack of attention to the task. However, it may also be an inability to terminate or change ongoing motor activity or postures. This has been considered more likely to occur with loss of the inhibitory influences of the frontal lobes. A number of tests have proved sensitive to the akinesia of patients with frontal lobe disease, and to their tendency to persist in incorrect behavior even when they know they are wrong. A test of word fluency can easily be given at the bedside. The patient is asked to produce as many words as they can that begin with a given letter (excluding proper nouns) in a one minute period. Normal individuals can produce 14 +/- 5, words using the letters A, F, or S. Patients with left frontal lobe lesions produce fewer words, and often repeat words or persist in using proper nouns.

Limbic system

The limbic system, in addition to subserving higher emotional functions, appropriately subserves a major component of the memory system, declarative memory (memory for facts or relationships that can be expressed verbally or symbolically). The ability to imprint new material (short term memory) is lost with bilateral destruction of most of the major paired structures of the limbic system including the cingulate gyri, hippocampi (and adjacent medial temporal lobes), fornices, mammillary bodies and anterior and medialis dorsalis nuclei of the thalamus. The patient with these lesions will be able to retain material as long as they are concentrating on it; this attentive or immediate memory probably depends upon the integrity of the major sensory pathways, the reticular activating system of the upper brainstem and the dorsolateral prefrontal neocortex. If, however, attention is distracted, s/he will have difficulty or be unable to recall the presented material. In fact, the patient may ask, "What three words?" when asked to reproduce three unrelated words such as table, red, 23 Broadway after a period of distraction. There are several conditions that can produce isolated bilateral depression or destruction of limbic structures involved in short term memory. For example, it can occur as the result of herpes simplex encephalitis, bilateral posterior cerebral artery occlusive disease or may be the result of unilateral temporal lobectomy if the patient has a previously damaged (e.g., from birth trauma) contralateral temporal lobe. Bilateral temporal lobe involvement may be an early and prominent sign of Alzheimer's disease. The limbic system is also much more susceptible to metabolic insults such as hypoxia and thiamin deficiency, the latter being most often seen in malnourished alcoholics. In the case of alcoholic effects on the brain, which probably result from bilateral damage to the dorsomedial nucleus of the thalamus, the memory deficit may be accompanied by confabulation (a tendency to respond to memory tasks by "making up" plausible answers).

Of course, if things cannot be remembered over minutes to hours, they can not be remembered longterm. However, well-learned material is probably represented diffusely and is very resistant to focal destruction. Indeed, well-established memories fail last in patients with diffuse bilateral hemispheric dysfunction. Animal experiments suggest that intermediary or less well-established material is first stored in the temporal lobes and becomes more widespread or redundant in localization with reinforcement. Some clinical corroboration of this is seen in patients with bilateral temporal lobe lesions who have variable and patchy retrograde amnesia. When testing a patient for problems with learning and memory, it suffices to ask for:

1. reproduction of three unrelated words immediately and then after a period of distraction; 2. a description of recent past events, for example front page news items, the contents of breakfast (if not stereotyped fare) and what they have been doing recently (assuming that the examiner knows the answers to these questions); and; 3. a description of some well learned past material such as the past 4 or 5 presidents, birth dates of patients and family, anniversaries, number and location of children and grandchildren, etc.

References

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Benson, DF. Aphasia, Alexia, and Agraphia. New York, Churchill Livingstone, 1979.

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Geschwind, N. Selected papers on Language and the Brain. Boston, Reidel, 1974

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Vinken PJ and Bruyn, F.W. (eds). Disorders of speech perception and symbolic behavior, in:

Handbook of Clinical Neurology, Vol. 4. New York, John Wiley & Sons, 1969.

Questions Define the following terms:

agnosia, agnosagnosia, apraxia, receptive aphasia, expressive aphasia, global aphasia, alexia, agraphia, dysinhibition, dysnomia, paraphasic, paratonia, perseveration.

2-1. Name some cerebral cortical functions that are well localized and unilateral. (unilaterally or bilaterally) and some that are diffuse. 2-2. Name some cerebral cortical functions that are well localized and represented bilaterally. 2-3. Name some cerebral cortical functions that are diffusely represented in the cerebral cortex. 2-4. Damage to which cerebral cortex produce aphasia? 2-5. What can you say about the ability to write in patients with aphasia? 2-6. What can you say about the ability of a patient with expressive receptive or global aphasia to repeat complex phrases? 2-7. What can you say about the ability of a patient with transcortical aphasia to repeat complex phrases? 2-8. What problems will a patient with a transcortical aphasia have? 2-9. What are the characteristics of the patient with an expressive aphasia (Broca's). 2-10. What are the characteristics of the patient with a receptive aphasia (Wernicke's). 2-11. What is the most common lesion to produce alexia without agraphia (can write but can't read)? 2-12. What area is involved in immediate recall (for example of a phone number).

2-13. What area is involved in short term memory? 2-14. Where is long-term memory stored? 2-15. What are "executive functions" and where are they primarily located? 2-16. Where are the areas involved in most of emotional control and "personality"? 2-17. Damage to which hemisphere is more likely to produce depression? Which will more likely produce mania? 2-18. Neglect of one side of the world is most commonly due to damage to what area? 2-19. Agnosagnosia most often results from damage to what area? 2-20. What "primitive responses" would be expected to be uncovered by damage to the frontal lobes? 2-21. Paratonia is a sign of what? 2-22. What would you expect to see in the patient with a split corpus callosum? 2-23. The neocortex provides inhibitory modulation of what four basic drives? 2-24. What is the clinical term used to describe diffuse hemispheric disease (one word)? 2-25. What are the clinical signs of advanced dementia? 2-26. What regressive reflexes emerge with loss of cortical inhibition? 2-27. What what are the functions of the limbic areas of the brain? 2-28. Of 100 people, how many will have significant R hemispheric representation of speech functions? Of these, how many will have bilateral speech representation? 2-29. What percentage of R-handed people are L-hemisphere dominant for speech? 2-30. What percentage of L-handed people are L-hemisphere dominant for speech? 2-31. Below what age can speech function be recovered if the dominant hemisphere is damaged? 2-32. What are dysfunctions of speech called? What is a complete loss of speech called?

2-33. A patient with verbal language dysfunction, homonymous hemianopsright visual field deficit and little motor deficit most likely has what type of dysphasia? 2-34. A patient with verbal language dysfunction, marked hemimotor and hemisensory deficit, and no visual abnormality most likely has what type of dysphasia? 2-35. Where is Broca's area located? Where is Wernicke's area located? Name the fasciculus that links the two of them. 2-36. What gyrus is important in language, especially in word retrieval? 2-37. Do most patients with dysphasia have Broca's, Wernicke's, or a combination of both? Why is this so? 2-38. What language abnormalities are manifested with a lesion to Broca's area? Wernicke's area? Angular gyrus? Arcuate (superior longitudinal) fasciculus? 2-39. What part of the corpus callosum transfers COMPLEX [i.e., verbal] visual info between the two hemispheres? 2-40. What are the predominant functions of the R cerebral hemisphere? 2-41. Which patient will be more motivated to recover from a hemispheric lesion, one with damage on the L or the R? 2-42. Where is the location of a lesion that causes visuospatial disorientation? How does this manifest itself? 2-43. What type of lesion will result in the loss of the ability to imprint new information? 2-44. Can well-learned material be easily destroyed by a focal lesion? Why or why not? 2-45. What three categories of questions need to be asked when testing a patient for problems with learning and memory?

2-46. What evidence would lead to the conclusions that a demented patient has disease localized primarily in the frontal lobes (i.e., what are the manifestations of lesions to the frontal lobes)? 2-47. What is the effect of lesions localized to the medial aspect of the frontal lobes (parasagittal frontal cortex - supplementary motor area)?

* The patient is stood or seated with eyes closed in front of the examiner. The examiner rotates the patient's shoulders. The uninhibited response consists of the patient's head remaining straight.

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Chapter 3 - Olfaction and Vision

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Vision and olfaction are two of the special senses. While patients usually easily

Olfaction

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recognize loss of vision, loss of olfaction may not be recognized without testing.

Olfactory pathway

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Olfactory

I. Olfaction testing

Unilateral depression or loss of olfaction (anosmia) is most commonly due to ❍

Disorders of

obstruction of the nasal passages. When it is due to damage to neural olfaction

structures, it must affect the olfactory pathway at or rostral to the olfactory ●

Vision

trigone (Fig. 3-1). Therefore, dysfunction must be in the olfactory tract, bulbs, ❍

Visual deficits

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Vision testing

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Visual acuity

The olfactory pathway divides immediately anterior to the anterior perforated

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Visual field

substance to travel via (1) the lateral olfactory stria to the primary olfactory

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Double

nerve filaments, or olfactory mucosa in the roof of the nasal passage.

Olfactory pathway

cortex (prepiriform-piriform) in the ipsilateral mesial part of the temporal

simultaneous

lobe, (2) the anterior limb or stria that dives into the anterior perforated

stimulation

substance to join the anterior commissure, which carries it to the contralateral

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References

olfactory cortex, and (3) the medial olfactory stria, which travels medially from

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Questions

the trigone to distribute to limbic cortex in the septal, subcallosal, and

parasagittal frontal regions. Damage to the olfactory epithelium, the olfactory filiments, the olfactory bulb or olfactory tract can cause unilateral anosmia. Destruction of olfactory cortex or olfactory pathways posterior to the trigone (where the tracts divide) must be bilateral to depress olfactory function. Potentially irritative lesions (tumor, post-traumatic or ischemic scarring, arteriovenous abnormalities, etc.) in the olfactory cortical regions may be the source of epileptic activity and cause olfactory symptoms; that is, the patient may complain of hallucinations of smell. Typically, these olfactory hallucinations are described as acrid and unpleasant and are not lateralized by the patient.

Testing of olfaction Olfaction is tested by having a patient with eyes closed, sniff a relatively familiar odor from a small vial, occluding the nares alternately to test each side separately. Substances such as acetic acid and ammonia should not be used for testing because they cause strong trigeminal stimulation and can therefore be sensed by an anosmic person. Coffee grounds are popular because they are recognized by approximately 80% of normal individuals and cause minimal trigeminal stimulation. Three distinct levels of function can be determined: (1) cannot smell, (2) can smell something, and (3) recognizes coffee. In addition, a person may recognize an asymmetry of sensitivity despite an inability to recognize the substance. Lack of recognition is not significant if the patient responds by saying that they smell a substance bilaterally; recognition on one side suggests contralateral hyposmia if the patient claims to smell but not recognize something on the opposite side.

Disorders affecting olfaction

Examples of disease processes that cause or are associated with decreased or otherwise abnormal smell are as follows:

1. Mechanical. ❍

a. Common cold with occlusion of nasal passages (most common cause of hyposmia).

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b. Unilateral occlusion by deviated nasal septum.

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c. Occipital head trauma with shearing effect on olfactory nerve filaments passing through cribriform plate (Fig. 3-2).

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d. Frontal head trauma, if it results in a fracture line through the cribriform plate, causes anosmia by tearing the fine olfactory nerve filaments. (In the absence of fracture, frontal head trauma is less likely to cause hyposmia.)

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e. Tumors (most commonly meningioma) on the mid-portion of the sphenoid ridge or in the olfactory groove, both capable of pressing on the olfactory tract. If the tumor is on the sphenoid ridge so that, in addition to pushing up on the olfactory tract, it compresses down on the optic nerve, it causes the syndrome of ipsilateral anosmia, optic atrophy, and possibly also contralateral papilledema because of increased intracranial pressure caused by the tumor mass effect (Foster-Kennedy syndrome).

2. Metabolic. ❍

a. Pernicious anemia (vitamin B12 deficiency) is frequently associated with bilateral decreased olfaction.

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b. Vitamin A deficiency is associated with hyposmia and dysosmia (odors are unpleasant), possibly the result of nasal mucosal abnormalities.

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c. Zinc deficiency has been associated with hyposmia and dysosmia.

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d. Diabetes mellitus. Presumably, this hyposmia is secondary to demyelination in the olfactory tracts or loss of the peripheral olfactory neuron.

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e. Multiple sclerosis is a rare cause of hyposmia, presumably on the basis of olfactory tract demyelination.

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f. Herpes simplex encephalitis, which tends to localize in the temporal lobes and cause severe hemorrhagic necrotic destruction, may cause anosmia secondary to bilateral olfactory cortex destruction or alternatively, because the virus may enter the nervous system via the olfactory mucosa, may destroy one or both olfactory nerves and bulbs in the process. The presentation of acute-onset anosmia and a severe memory-encoding deficit (the latter secondary to bilateral mesial temporal lobe destruction) in a person who is febrile suggests the possibility of herpes simplex encephalitis, a treatable disorder.

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g. Hepatic disease, particularly acute hepatitis, is frequently associated with an unpleasantness of odors (dysosmia).

Unilateral destructive or compressing (mass) lesions in the anterior temporal lobe may cause olfactory hallucinations, a focal epileptiform discharge that often spreads to involve other portions of the limbic system and neocortex (see Chap.13).

II. Vision For a more detailed elaboration of visual system anatomy and function, refer to a neuroanatomy text. Figure 3-3 shows diagrammatic representations of the visual pathway including expected abnormalities of vision caused by lesions of its various parts.

Visual deficits Unilateral lesions of the retina and optic nerves cause monocular defects. Lesions from the chiasm back give rise to binocular field defects because of crossing of the nasal half of the retinal fibers from each eye. An exception to this rule occurs when there is involvement of the fibers representing the nasal retinal (temporal field) peripheral crescents. The fibers from this portion of the retina have no homonymous counterpart in the opposite peripheral temporal retina (nasal field). The peripheral crescents, therefore, remain monocular in representation from the retina to the visual cortex (Figs. 3-3, 3-4 and 3-5).

Testing of vision Formal testing of vision divides this function into two basic aspects: (1) central or cone vision, and (2) peripheral or rod vision. Peripheral vision is the greatest part of the visual field, whereas central vision represents a relatively small segment of the projected visual world. Nevertheless, it is mainly central vision that is responsible for visual acuity and color vision. However, cones require a lot of light in order to function effectively. Peripheral vision also subserves a major function of directing central vision by visual-oculomotor responses toward the peripheral stimuli. The more peripheral the field, the less capable of form or figure perception it becomes, which is in keeping with the centrifugal thinning out of the population of peripheral field receptors (rods) in the retina. At the far periphery one is capable of perceiving only moving objects, although reflex movements of the eye (directing the eyes toward a moving stimulus) can be elicited from this region. Rods have a very low threshold for activation by light as compared with cones and are thus more suited for night vision. In daylight, pigment "bleaches" and the rods are insensitive. The cones, which have a high threshold for pigment bleaching by light, are

relatively useless in the dark.

Visual acuity

Visual acuity is first tested by having a person read a chart (Snellen chart) containing standard-sized figures (numbers, letters or other forms) as perceived at a standard distance. The notation 20/20 vision means that the patient can recognize objects at 20 ft. that a normal person can recognize at that distance. The designation 20/70 means that the patient, at best, can only recognize at 20 feet what abnormal individual can recognize at 70 feet. This type of testing is not practical at the bedside, so charts have been developed to be presented at 14 in. (Fig. 3-6). These give an extrapolated visual acuity in terms of 20 ft. and are adequate to detect neurologic visual dysfunction, but may miss refraction errors, particularly nearsightedness (myopia). For quick screening, it is useful to know that recognition of small-case newsprint at 14 in. is equivalent to 20/30 vision. Visual acuity can be depressed by changes in the refractive structures of the eye anterior to the retina. In neurologic practice, we are not concerned with refractive problems and, therefore, it is important to have a way to detect these causes of loss of visual acuity. If a person customarily wears glasses, s/he should be tested with them on. If difficulties still exist, then further testing is warranted. Ophthalmoscopic examination should detect corneal opacities or cataracts. It would also detect intraocular problems, such as hemorrhage, which could obscure vision. Refractive errors commonly affect visual acuity. However, conditions such as myopia (near-sightedness) or hyperopia (farsightedness) can be corrected with a series of lenses. Alternatively, at the bedside, most simple refractive errors can be corrected by having the patient look through a cluster of pin-holes (Fig. 3-7). This works by only permitting parallel light rays to pass the pin-hole. This markedly increases the dept

of focus since parallel rays do not have to be focused. Pinholes would make inexpensive but impractical glasses, however, because peripheral vision, most central vision, and a great amount of light are eliminated. If visual acuity is not substantially corrected by the pinhole and if no problems exist with the refractive media of the eye (on ophthalmoscopic examination), it can be assumed there is a neurological (i.e., cone system) central visual defect. A further way to estimate refractive errors, which is particularly useful in the uncooperative patient, is to determine the diopters (e.g., +3, -3) of ophthalmoscope adjustment necessary to focus on the macula or optic nerve head. This assumes "0" to be equivalent to normal acuity.

Visual field

After determining that the visual deficit is not a refraction or occlusive problem one can deduce, by default, it is a dysfunction in the neural visual apparatus. In order to localize the lesion, it is necessary to evaluate the visual field integrity. Visual field loss tends not to be an all-or-nothing phenomenon. The patient frequently has a partial deficit, particularly in the central field, and can see larger objects after small objects are no longer perceived. Testing that utilizes small objects is more sensitive. Formal testing of visual field can be done in several ways. There are automated tests, such as "Goldman visual field testing" in which the patient is asked to push a button when a flash of light is detected. "Tangent screen" testing is an older method in which the patient fixates on a central target at a distance of 3 meters while objects are moved into the screen. Of course, each eye has to be tested independently (Fig. 3-8). At the bedside, "confrontation" is the most commonly employed method for evaluating visual field. This can be quite accurate if carefully done. One eye is covered and the person is asked to fix their vision on

the examiner's pupil at a distance of approximately 1.5 ft. A small, colored object (for example a 3 mm red object such as a fireplace match) is moved into the visual field in a plane halfway between the patient and the examiner. The patient is asked to indicate when s/he sees the object and when it turns red as well as whether it disappears or loses its color anywhere in the field. This technique allows the examiner to compare the patient's vision with their own (presumably normal). Additionally, it is critical to observe whether the patient is fixating on the central object (i.e., examiner's pupil) during the examination. A colored object is used because it defines the major extent of cone vision. On occasion, a partial loss of central vision manifests itself more in depression of color perception than in actual loss of visual acuity. For example, optic neuritis often diminishes the ability to see red objects ("red desaturation"). Screening to test all peripheral quadrants with both of the patient's eyes open and fixating on the examiner's nose reveals all peripheral defects except the rare cases of nasal hemianopias and hemianopias with temporal crescent sparing (see Figs. 3-3 and 3-4). Monocular testing does not miss any peripheral defects but takes twice as long. If there has been damage to optic nerve fibers for more than a couple of weeks, ophthalmoscopic visualization of the optic disk may reveal evidence of "atrophy" of the temporal portion of the optic nerve head (optic disk). This part of the optic disk transmits the optic nerve fibers from the macula (representing central vision). Atrophy causes the disk to change from its slightly yellowish appearance to a brighter white owing to gradual replacement of myelinated nerve fibers by glial scarring. Comparison with the opposite disk is useful in borderline cases when changes are minimal and the problem is monocular. There is a normal, oval scotoma (the "physiologic blind spot") in the temporal portion of the visual field (see Fig. 3-8). This is the visual representation of the optic nerve head (the disk), which does not

contain rods or cones. When a 3 mm object is passed over this area, a person usually says it disappears. It is often helpful to suggest to the patient that the object will likely disappear in some part of the visual field since most of us are completely unaware of the presence of a blind spot. If the object is moving midway between the examiner and the patient and both are fixating on each other's pupils, their blind spots should be superimposed. The ability of the test to pick up the physiologic blind spot is a good check on the reliability of the mode of testing of the visual field. An early sign of edema or swelling of the optic disk (papilledema) is enlargement of the blind spot. This is because the retina is extremely sensitive to mechanical pressure and minimal, unobservable edema of the optic nerve head causes significant dysfunction in the bordering receptive retina and, therefore, enlargement of the blind spot. Also, glaucoma will tend to push out on the optic disk, producing expansion of the optic cup (at the center of the disk) and also some expansion of the blind spot. More severe glaucoma can destroy the retina thorough pressure. Peripheral visual fields are formally tested using the tangent screen (Fig. 3-8) and more completely using a perimeter (Fig. 3-9), which takes into account that the total visual field is an arc (see Fig. 3-5). A tangent screen is flat and so cannot demonstrate the total extent of the peripheral visual field. A relatively large, white (color is not useful with rod vision testing) object (approximately 10 mm in diameter) is moved along the perimeter from the outside in and the peripheral field is mapped out in degrees. The outside limits represent where the patient, while fixing on a central target, first sees the moving object. A simple and more practical technique is used at the bedside. The patient is asked to fixate on the examiner's pupil as in testing central vision, and a large object, frequently the examiner's index finger, tip first, is moved into the patient's visual field (confrontation) from a position lateral to the patient's head. This is a rapid and easy way to approximate peripheral visual fields (Fig. 3-10).

Double simultaneous stimulation

It is useful at the bedside to use tachistoscopic double simultaneous stimulation (TDSS) of the visual fields. This entails the rapid momentary presentation of two objects simultaneously into opposite visual fields. In practice, a momentary movement of the tip of the index finger in both fields is suitable (see Fig. 3-10). TDSS testing is advantageous because minor partial field deficits, which may not be picked up on unilateral stimulation become apparent; the object in the abnormal field is extinguished. A rapid single excursion of the examiner's index fingers in the peripheral fields is adequate (see Fig. 3-10). Extinction in the visual field may represent either a partial dysfunction in the visual pathways or may be due to inattention phenomenon to one side of the body. This latter difficulty is usually part of a broader syndrome of hemispatial inattention (neglect), usually resulting from contralateral parietal (and occasionally frontal) association cortices.

References

●

Brodal, A.: Neurological Anatomy in Relation to Clinical Medicine, ed. 2. New York, Oxford University Press, 1969.

●

Cogan, D.G.: Neurology of the Ocular Muscles, ed. 2. Springfield, IL, Charles C. Thomas, Publisher, 1956.

●

Monrad-Krohn, G.H., Refsum, S.: The Clinical Examination of the Nervous System, ed. 12. London, H.K. Lewis & Co., 1964.

●

Spillane, J.D.: The Atlas of Clinical Neurology, ed. 2. New York, Oxford University Press, 1975.

●

Walsh, F.B, Hoyt, W.F.: Clinical Neuro-ophthalmology, ed. 3. Baltimore, Williams & Wilkins Co., 1969.

Questions Define the following terms:

anosmia, homonomous, hemianopsia, quadrantanopsia, scotoma, papilledema, papillitis, optic neuritis.

3-1. How do you test olfaction? 3-2. What is the most common cause of unilateral anosmia? 3-3. In whom is it particularly important to test olfaction? 3-4. How can you determine if visual acuity problems are due to refractive or to nerve problems? 3-5. What is the significance of finding a monocular visual loss? 3-6. What is the significance of finding a homonomous visual field deficit? 3-7. Where would a lesion that produced bitemporal hemianopsia be located? 3-8. How can lesions of the parietal or temporal lobes produce vision loss? What kind of loss would you expect to find? 3-9. Where on the visual cortex is the representation of the center of vision? 3-10. What artery supplies the visual cortex? 3-11. How can you distinguish papilledema from papillitis?

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Chapter 4 - Extraocular movement

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Eye movements are controlled by muscles innervated by cranial nerves III, IV

Eye movement

❍

and VI. In this chapter, the testing of these cranial nerves will be discussed. The

Eye muscle functions

most common symptom of damage to these nerves is double vision. The ❍

oculomotor nerve has the additional function of control of the pupil and

Central control of

therefore this will be discussed here as well. Eye movements are carefully

movement

controlled by other systems. Some of these will be discussed here, while others, ●

Pupillary function

such as the vestibular system, will primarily be discussed in other chapters. ❍

reflexes

Cranial nerves III, IV, VI. Ocular Motility ❍

Oculomotor function can be divided into two categories: (1) extraocular muscle

oblique, and levator palpebrae muscles, all innervated by the oculomotor nerve (III); the superior oblique muscle, innervated by the trochlear nerve (IV); and

Horner's syndrome

function and (2) intrinsic ocular muscles (controlling the lens and pupil). The extraocular muscles include: the medial, inferior, and superior recti, the inferior

Pupillary

●

Amblyopia

●

References

●

Questions

the lateral rectus muscle, innervated by the abducens nerve (VI). The intrinsic eye muscles are innervated by the autonomic systems and include the iris sphincter and the ciliary muscle (innervated by the parasympathetic component of cranial nerve III), and the radial pupillodilator muscles (innervated by the ascending cervical sympathetic system with its long course

from spinal segments T1 through T3).

Extraocular muscle function

The muscles of the eye are designed to stabilize and move the eyes. All eye muscles have a resting muscle tone that is designed to stabilize eye position. During movements, certain muscles increase their activity while others decrease it. The movements of the eye include: adduction (the pupil directing toward the nose); abduction (the pupil directed laterally); elevation (the pupil directed up); depression (the pupil directed down; intorsion (the top of the eye moving toward the nose); and extorsion (the superior aspect of the eye moving away from the nose). Horizontal eye movements are rather simple. Increased activity of the lateral rectus will direct the pupil laterally, while increased activity of the medial rectus will direct it medially. However, movements of the eyes above or below the horizontal plane are complicated and require, at the minimum, activation of pairs of muscles. This is because the obit is not directed straight forward in the head and, therefore, there is no one muscle positioned to direct the eye straight up or down without the simultaneous occurence of unwanted movements. Because of this, the protocol for testing eye movements is somewhat more complicated than might be expected. Figure 4-1 illustrates the correct eye positions for testing the extraocular muscles in relative isolation. As can be seen in Figures 4-1 and 4-2, a lateral position of the eyeball is necessary for testing the inferior and superior recti, whereas a medial position is necessary for testing the inferior and superior oblique. This is because, in the position of lateral gaze, the superior and inferior rectus muscles are in line with the axis of the globe, "straightening out the pull" of these muscles and allowing them to move the eye straight up or down. When the eye is directed nasally (medially), the oblique muscles align with

the axis of the globe and are, therefore, the prime muscles for vertical gaze when the eye is adducted. Vertical gaze from the neutral position (Fig. 4-1) is accomplished by simultaneous activation of the superior rectus and inferior oblique (for upgaze) and of the inferior rectus and superior oblique (for downgaze). It is not necessary to have the patient look straight up and down in order to test each of the extraocular muscles. However, this may reveal evidence of vertical nystagmus (a sign of brain stem vestibular damage) and to determine the integrity of the midbrain center for vertical gaze (which may be defective despite adequate individual muscle activity). illustrates the expected findings with isolated loss of function of cranial nerves III, IV, and VI. Since there is resting tone in all of the eye muscles, isolated weakness in one muscle results in deviation of the eye due to the unopposed action of all of the remaining muscles. This typically results in double vision when the person tries to look straight ahead (although some patient may ignore the input from one eye). The afflicted person often adjusts their head position in an attempt to ameliorate the double vision caused by the muscle imbalance. The position that their head assumes is one that permits them to use their "good eye" to line up with the affected one. This is often successful in cases of isolated damage to cranial nerve IV or VI, with the head assuming the position shown in Figure 4-3. In this figure, the dashed vector lines show which directions of muscle pull are lost. The solid vector lines indicate the resting tonus of the remaining extraocular muscles. Note that the head is tilted in CN IV damage. This is the classic position from which the English phrase "cockeyed" is derived. When cranial nerve III is involved, there may be enough ptosis to close the eye (preventing diplopia). However, if the eye is open, there is usually too much imbalance to overcome by head positioning and patients usually have diplopia. The person with an extraocular muscle defect of recent onset usually complains of double vision

(diplopia). This results from the inability to fuse the images on the macular regions (central vision) of both eyes. Since the weak muscle is unable to bring the eye to a position in which the object is focused on the macula, the image falls on a more peripheral part of the retina. The person sees the object in the field appropriate to the new retinal position (i.e., always farther toward the periphery in the direction of attempted gaze. Additionally, because the image falls on retinal region with fewer cones, it is less distinct. The patient may compare it to the "ghost images" seen on maladjusted television sets. Sometimes it is very obvious which eye is not moving sufficiently when you perform the "6 positions of gaze". Also, the direction of the diplopia can give clues about weakness. For example, horizontal diplopia (where the images are separated horizontally) is due to problems with the medial and lateral recti, while vertical diplopia is due to problems with one or more of the other muscles. When it is not obvious on observation, one can delineate which extraocular muscle or muscles are defective by determining which eye sees the abnormal image (i.e., the blurry image that is farthest toward the periphery in direction of eye movement). This can be done by placing a transparent red piece of plastic or glass in front of one eye and asking the patient (who is observing a small light source such as a penlight or white object) which image is red, the inside or outside, lower or upper, depending on whether the diplopia is maximum in the vertical or lateral field of gaze. Figure 4-4 demonstrates the findings in one patient with medial rectus dysfunction and in one with lateral rectus dysfunction. The abnormal image in both cases is laterally displaced in the field of gaze and blurred (even though different eyes are involved in each case). Alternatively, if a red glass is not available, you can use the cover test to determine which eye is involved. In this case you will need to ask the patient to identify which image disappears when you cover one eye. Again, the eye that is projecting the image most off to the periphery is the one that is affected. The red glass and cover tests are particularly useful in

delineating minimal muscle dysfunction, in which it is frequently difficult to determine which muscles are involved by observation on primary muscle testing.

Central control of eye movement It is worthwhile at this point to review the anatomy of the central pathways of the oculomotor system. Figures 4-5 and 4-6 schematically outline the major central pathways that are important to conjugate lateral gaze, conjugate vertical gaze and convergence. Additionally, the deficits caused by destructive lesions in various parts of these systems are diagrammed. The central control of eye movement can be distilled into the principle types of functions. These include voluntary, conjugate horizontal gaze (looking side-to-side); voluntary, conjugate vertical gaze (looking up and down); smoothly tracking objects; convergence; and eye movements resulting from head movements. These latter movements, are part of the vestibular reflexes for eye stabilization and will be discussed with the vestibular nerve. The vestibular chapter is also where nystagmus (a to-and-fro movement of the eye) will be discussed. The movements of they eyes produce by the central nervous system are conjugate (i.e., both eyes moving in the same direction in order to keep the eyes focused on a target) except for convergence, which adducts the eyes to focus on near objects. Voluntary horizontal gaze in one direction begins with the contralateral frontal eye fields (located in the premotor cortex of the frontal lobe). This region has upper motor neurons that project to the contralateral paramedian pontine reticular formation (PPRF), which is the organizing center for lateral gaze in the brain stem. The PPRF projects to the ipsilateral abducens nucleus (causing eye abduction on that side). There are fibers extending from the abducens nucleus, which is located in the caudal pons, to the contralateral oculomotor nucleus of the midbrain.

The projection pathway is the medial longitudinal fasciculus (MLF). The oculomotor nucleus then activates the medial rectus, adducting the eye in order to follow the abducting eye. This is illustrated schematically in figure 4-9 for voluntary horizontal gaze to the left. Damage to the frontal eye-fields will initially prevent voluntary gaze away from the injured frontal lobe. However, that improves with time. Damage to the PPRF will abolish the ability to look toward the side of the lesion. Damage to the MLF produces the curious finding of “internuclear ophthalmoplegia” in which the patient will be able to abduct the eye, but the adducting eye will not follow. Additionally, there will be some nystagmus in the abducting eye. Vertical gaze (Fig. 4-10) does not have one center in the cerebral cortex. Diffuse degeneration of the cortex (such as with dementia) can diminish the ability to move the eyes vertically (particularly upward). There is a brain stem center for vertical gaze (in the midbrain – the rostral interstitial nucleus [of Cajal]). Degeneration of this nucleus (such as can occur in rare conditions like progressive supranuclear palsy) can abolish the ability to look up or down. Additionally, there are connections between the two sides that traverse the posterior commissure. Pressure on the dorsum of the midbrain, such as by a pineal tumor, can interrupt these fibers and prevent upgaze (Parinaud syndrome). Smooth tracking eye movements are mediated through a more circuitous pathway that includes the visual association areas (necessary in order to fix interest on a visual target) and the cerebellum. Cerebellar damage often produces jerky, uncoordinated movements of the eyes.

Pupillary function The iris receives both sympathetic and parasympathetic innervation: (1) the sympathetic nerves innervate the pupillary dilator muscles; and (2) the parasympathetic nerve fibers (from CN III)

innervate the pupillary constrictor (sphincter) muscles as well as the ciliary apparatus for lens accommodation. Figures 4-7 and 4-8 show the origins and courses of these two systems. During the normal waking state the sympathetics and parasympathetics are tonically active. They also mediate reflexes depending in part on emotionality and ambient lighting. Darkness increases sympathetic tone and produces pupillodilation. Increased light produces increased parasympathetic tone and therefore pupilloconstriction (this also accompanies accommodation for near vision). During sleep, sympathetic tone is depressed and the pupils are small. Normal waking pupil size with average ambient illumination is 2 to 6 mm. With age, the average size of the pupil decreases. Approximately 25% of individuals have asymmetric pupils (anisocoria), with a difference of usually less than 0.5 mm in diameter. This must be kept in mind when attributing asymmetry to disease, particularly if there are no other signs of neurologic dysfunction. At the bedside, the first step in evaluating pupil dysfunction is observation of the resting size and shape. A small pupil suggests sympathetic dysfunction; a large pupil, parasympathetic dysfunction. Loss of both systems would leave one with a nonreactive, midposition pupil, 4-7 mm in diameter, with the size varying from individual to individual. This is seen most often in persons with lesions that destroy the midbrain (see Chap. 24).

Pupillary reflexes

Next, the integrity of the papillary reflex section is evaluated. Parasympathetic function is tested by having the patient accommodate, first looking at a distant object, which tends to dilate the pupils and then quickly looking at a near object, which should cause the pupils to constrict. Additionally, the pupils constrict when the patient is asked to converge, which is most easily done by having them look at their

nose. There are rare conditions damaging the pretectal region that differentially affect the constriction produced by convergence from that produced by accomodation. More common is the loss of the light reflex with preservation of accommodation and convergence pupilloconstriction (this has been termed the Argyll-Robertson pupil). This may be caused by lesions in the peripheral autonomic nervous system or lesions in the pretectal regions of the midbrain. Variable amounts of sympathetic involvement are usually present, leaving the pupil small in the resting state. Although this was commonly associated with tertiary syphilis in the past, the Argyll-Robertson pupil is seen most often associated with the autonomic neuropathy of diabetes mellitus. The light reflex is tested by illuminating first one eye and then the other. Both the direct reaction (constriction in the illuminated eye) and the consensual reaction (constriction in the opposite eye) should be observed. The direct and consensual responses are equal in intensity because of equal bilateral input to the pretectal region and Edinger-Westphal nuclei from each retina (see Fig. 4-7). Pupillodilation, which can be tested by darkening the room or simply shading the eye, occurs due to activation of the sympathetic nervous system, with associated parasympathetic inhibition. A sudden noxious stimulus, such as a pinch (particularly to the neck or upper thorax), causes active bilateral pupillodilation. This is called the cilio-spinal reflex and depends predominantly on the integrity of the sensory nerve fibers from the area, the upper thoracic sympathetic motor neurons (T1- T3 lateral horn) and the ascending cervical sympathetic chain (see Fig. 4-8). Interruption of the descending sympathetic pathways in the brain stem frequently has no effect on the reflex. Therefore, if the patient has a constricted pupil presumably secondary to loss of sympathetic tone, absence of the ciliospinal reflex suggests peripheral sympathetic denervation or, if other neurologic signs are present, damage to the upper thoracic spinal cord. Presence of the reflex despite depressed resting sympathetic tone suggests

damage to the descending central sympathetic pathways. Horner's syndrome is a constellation of signs caused by lesions in the sympathetic system. Sweating is depressed in the face on the side of the denervation, the upper eyelid becomes slightly ptotic and the lower lid is slightly elevated due to denervation of Muller's muscles (the smooth muscles that cause a small amount of lid-opening tone during alertness). Vasodilation is transiently seen over the ipsilateral face, and the face may be flushed and warm. These abnormalities, in addition to pupilloconstriction, are seen in conjunction with peripheral cervical sympathetic system damage. The final neuron in the cervicocranial sympathetic pathway arises in the superior cervical ganglion and sends its axons to the head as plexuses surrounding the internal and external carotid arteries. Lesions involving the internal carotid artery plexus (as in the middle-ear region) cause miosis (a small pupil) and ptosis and loss of sweating only in the forehead region - the area of the face supplied by the internal carotid system. Lesions of the superior cervical ganglion cause the same problems, except that loss of sweating occurs over the whole side of the face. Destruction of the external carotid plexus causes sweating loss over the face that spares the forehead, without pupillary or eyelid changes. Lesions of the lower portion of the cervical sympathetic chain (e.g., carcinoma of thyroid) cause a Horner's syndrome with loss of sweating in the face and neck, and if the lesion is at the thoracic outlet (such as tumors of the apex of the lung), loss of sweating extends to the upper extremity. Lesions of the brainstem and cervical spinal cord descending sympathetic pathways cause a Horner's syndrome with depression of sweating over the whole side of the body. Lesions of the spinal cord below T1- T3 cause a loss of sweating below the level of the lesion but no Horner's syndrome. Testing for sweating defects can therefore be very useful in localization of the lesion. A simple, but messy way to test sweating is to warm the patient and watch for asymmetrical loss of sweating using starch and iodine. The parts to be tested

are painted with an iodine preparation (e.g., forehead, cheek, neck, hand and foot) and then when they are dry, the areas are dusted with starch. When the patient sweats after being warmed with blankets (covering the tested areas with plastic is useful), the iodine runs into the starch and blackens it. Asymmetries are relatively easy to observe.

Amblyopia

Before concluding this discussion of eye movements it would be appropriate to say a few words about "amblyopia" (literally, "dim eye"). This is a condition in which one eye obviously drifts off target (some have called it a "wandering eye"). However, the patient is unaware of this and does not see double. This is most serious in children and occurs for one of two reasons. First of all, it may occur due to severe muscle weakness or scarring. In this case the child cannot keep the two eyes fixed on the same target. The other cause is poor vision (usually in one eye). The reason that there is no double vision is that the brain "turns off" input from the bad eye. The reason this is so bad in young children is that, up until late childhood, functionally "turned off" synapses will actually loose their connections with neurons at the level of the visual cortex. These synapses will be replaced by synapses of fibers from the intact eye and the patient will become permanently blind in that eye. "Turning off" an eye for one continuous month for each year of life (i.e., for 5 straight months in a 5-year old) is enough to cause permanent blindness. This does not happen in adolescence or adulthood because synapses have stabilized. Interestingly, the pupillary light reflex is unaffected since the projections from the retina to the pretectum are intact. The treatment is to force the patient to use the eye at least part of the day (while providing as much visual correction as possible for the affected eye). This is often done by patching the "good eye" during school time (in a more controlled environment).

References

●

Brodal, A.: Neurological Anatomy in Relation to Clinical Medicine, ed. 2. New York, Oxford University Press, 1969.

●

Cogan, D.G.: Neurology of the Ocular Muscles, ed. 2. Springfield, IL, Charles C. Thomas, Publisher, 1956.

●

Monrad-Krohn, G.H., Refsum, S.: The Clinical Examination of the Nervous System, ed. 12. London, H.K. Lewis & Co., 1964.

●

Spillane, J.D.: The Atlas of Clinical Neurology, ed. 2. New York, Oxford University Press, 1975.

●

Walsh, F.B, Hoyt, W.F.: Clinical Neuro-ophthalmology, ed. 3. Baltimore, Williams & Wilkins Co., 1969.

Questions Define the following terms:

strabismus, abduction, adduction, elevation, depression, convergence, accomodation, diplopia, meiosis, mydriasis, myopia, hyperopia, conjugate, consensual, extraocular, amblyopia, ptosis, anisocorea.

4-1. Which muscles would be active in the right and left eye when looking up and to the right? 4-2. Which muscles would be active in the right and left eye when looking down and to the left? 4-3. What position will the patient's head assume (in order to prevent diplopia) if their right trochlear nerve is damaged?

4-4. When a patient has double vision, in which position will they have the furthest separation of the images? 4-5. What is the significance of horizontal diplopia (where the images are side-by-side) as opposed to vertical diplopia? 4-6. Which eye (the one that is moving normally or the weak one) will see the image that is furthest displaced from the center of vision? 4-7. Where is the cortical center that controls lateral gaze? Where is the lateral gaze center in the brain stem? 4-8. Is there a vertical gaze center in the cerebral cortex? Is there a brain stem vertical gaze center? 4-9. What are the potential causes of ptosis? 4-10. What are the components of Horner's syndrome? 4-11. What are the functions of sympathetic and parasympathetic nerves to the orbit? 4-12. Where is the brain stem center for the pupillary light reflex?

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Chapter 5: Facial sensations & movements

On this page ●

In this chapter, the functions of the trigeminal (CN V) and facial (CN VII) nerves

Trigeminal nerve

❍

will be discussed. Symptoms of damage to the trigeminal system are mainly loss

Facial sensation

of sensation in the face, although the mandibular division of the trigeminal ❍

Jaw motion

❍

Corneal

nerve also controls jaw motion. Damage to the facial nerve mainly manifests as weakness of muscles of facial expression, although it may also affect taste

reflex

sensation in the anterior part of the tongue. It is critical to distinguish damage of ❍

Trigeminal

the facial nerve from damage to the connections from the cerebral cortex to the neuralgia

brain stem, which selectively weakens muscles of the lower portion of the face, ●

Facial nerve

contralateral to the side of damage. ❍

expression

V. Trigeminal Nerve The three divisions of the fifth nerve (I. Ophthalmic, II. Maxillary, and III. Mandibular) are the source for somatic sensation over the entire face (Figs. 5-1

❍

Taste

❍

Stapedius muscle

and 5-2), the eye, the nasal passages and the oral cavity. ❍

Facial sensations Facial sensation can be tested simply at the bedside by having the patient close their eyes and respond affirmatively to touch with a light wisp of cotton over the

Facial

Somatic sensations

●

References

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Questions

three divisions of the trigeminal nerve. The patient should be asked to compare the perception on the two sides. Pain perception as tested by a pin can be similarly checked, although temperature sensation (which is mediated by the same pathways, can replace the use of a pin. Sensory testing is, by nature, subjective (i.e., the examiner depends on the reliability of the subject). It is important to define the pattern and distribution of sensory alteration since that can go a long way to both localizing the lesion and also validating the sensory findings. The patient with hysterical or feigned sensory loss in the face frequently has bizarre perceptive patterns such as a hairline or perfect midline demarcation of hyposensitivity. Neither pattern can be explained on the basis of the central or peripheral distribution of the trigeminal system (see Fig. 5-1). Additionally, the inability to detect the vibrations of a tuning fork placed on one side of the head (when the other side can detect it) is not physiological since the entire head vibrates. The subjective tests of facial sensation can be objectified by examining certain reflex responses such as the corneal reflex (where the eye briskly closes in response to a wisp of cotton touching the cornea). Asymmetries of this are a good sign of sensory impairment at least in the distribution of the ophthalmic division of the trigeminal nerve (see below).

Jaw movements The temporalis, masseter, and pterygoid muscles (muscles of mastication) are supplied by the motor division of the mandibular branch of cranial nerve V and subserve jaw movement. Supranuclear innervation of these muscles (hemispheric and brainstem pyramidal and extrapyramidal systems) is essentially symmetrically bilateral. A unilateral lesion above the level of the fifth-nerve motor nucleus, therefore, does not cause any obvious weakness of jaw motion. Large bilateral lesions of the hemisphere or brain stem (above the fifth-nerve nucleus) can cause bilateral weakness of voluntary jaw movement.

If the bilateral involvement lies above the brain stem, very basic brain stem-mediated chewing reflexes may remain and actually become hyperactive. The jaw jerk reflex is a muscle stretch reflex in which both the sensory and motor nerve fibers are contained in the trigeminal nerve. This is elicited by lightly tapping the relaxed open jaw in a downward direction. This would be lost after trigeminal nerve damage and hyperactive with injury above the pons (see Chap. 10). The paired temporalis and masseter muscles function in jaw closure, and the medial pterygoid muscle closes the jaw and moves it from side-to-side (grinding motion). The lateral pterygoid muscles (along with some of the upper neck muscles) open the jaw in concert with a downward and opposing inward motion (Fig. 5-3). When one lateral pterygoid is weak, the jaw deviates toward the weak side on opening, with the inward vector of the opposite pterygoid being unopposed (Fig. 5-4). Observation of temporal region for atrophy and palpation of the symmetry of muscle bulk and tension during tight jaw closure test the innervation of the temporalis and masseter muscles.

Corneal reflex The corneal reflex is mediated by sensory fibers in the trigeminal nerve and motor fibers in the facial nerve. It consists of a bilateral blink response when the edge of the cornea is touched from the side with a wisp of cotton. The examiner should approach from the extreme corner of the eye in order to avoid a visually evoked blink response. It is a useful and objective test for evaluating simultaneously the ophthalmic division of the fifth-nerve (the afferent limb) and the seventh-nerve motor innervation of the orbicularis oculi (the efferent limb). Both the eye that is touched and the opposite eye are observed since they should both close equally and consensually (a consensual reflex is one in which the motor response is bilateral to a unilateral stimulus. The corneal reflex is a sensitive and objective indicator of

fifth- and seventh-nerve dysfunction. A good example of dysfunction occurs with eight-nerve tumors (acoustic neuromas), which comprise approximately 5% of all intracranial tumors in adults (see Fig. 52). Patients may present with unilateral hearing loss, and on routine neurologic evaluation the only other indication of involvement may be depression of the ipsilateral direct and contralateral consensual corneal reflex. This results from pressure by the tumor, which lies in the angle between the cerebellum and pons, on the superficially positioned descending tract and nucleus of the trigeminal nerve (which mediates pain and temperature sense from the face). If the depression of the reflex were secondary to seventh-nerve hypofunction, only the direct response would be depressed; the contralateral consensual response would be full because the sensory limb of the reflex, mediated by the trigeminal nerve, would be intact.

Trigeminal neuralgia An instructive example of trigeminal nerve dysfunction is trigeminal neuralgia (tic douloureux), an irritation of the nerve that probably occurs due to contact with anomalous intracranial blood vessels. This process causes severe paroxysms of pain in one or more divisions of the trigeminal nerve, with the maxillary division being most often affected and the ophthalmic least. In the past, surgeons attempted to cut the various peripheral branches of the trigeminal root. However, this would result in "numbness" and pain would usually return some months later. At one time, complete damage to the root became a popular form of permanent cure. A great difficulty with both of these procedures is that the area of anesthesia can become spontaneously painful (denervation hypersensitivity, a form of neuropathic pain). Also, the eye and face can be damaged because of the loss of sensitivity. These destructive surgical procedures have fallen out of favor.

Fortunately, various medications (mostly in the family of anticonvulsants) suppress the excess excitability in the trigeminal neurons and are successful in relieving tic in many persons for long periods of time. Nonetheless, there are patients who do not get adequate response to medications and several other interventions can be successful in relieving these medically refractory patients. Glycerol, injected into the region around the trigeminal ganglion, often produces relief that extends for years after the procedure (it is thought to produce some selective nerve damage). A radiofrequency probe can be placed into the trigeminal ganglion (percutaneously, through the foramen ovale) and selective lesions can be made to the nerve fibers from the painful region of the face. The most elegant surgical treatment (but most invasive) involves approaching the trigeminal nerve from an occipital craniotomy and placing some Teflon between any irritating arteries and the trigeminal nerve root. This often results in permanent relief of the symptoms.

VII. Facial Nerve Most of the facial nerve is comprised of motor innervation of the muscles of facial expression. In addition, it subserves several other functions including: taste perception from the anterior two-thirds of the tongue; perception of cutaneous stimuli in the external auditory canal and over part of the pinna and mastoid region; innervation of the stapedius muscle in the middle ear; and innervation of the lacrimal gland and two of the salivary glands (the submaxillary and submandibular). Many of these functions are difficult to test and more difficult to quantify (such as salivation and lacrimation (Fig. 5-5). However, some of these functions can be tested and give clues as to the location of facial nerve damage. Taste in the anterior tongue is tested with application of a thick sugar solution on a Q-tip to the

protruded tongue. Care must be taken to prevent this from spreading to the other side and the mouth must be rinsed out thoroughly between trials. The chorda tympani (the branch mediating this sensation) leaves the parent nerve, crossing through the middle ear (where it can also be damaged by severe infections, etc). Loss of function of the stapedius muscle may reflect as "hyperacusis", i.e., perception of sound as excessively loud an irritating on the side of damage. This branch also arises at the level of the middle ear.

Facial expression The great majority of facial nerve fibers are involved in producing facial expressions. Careful observation of the patient's face during conversation and at rest almost always reveals facial weakness. Additionally, the face may "droop" on the side of damage due to the effects of gravity. The nerve can be further tested by: having the patient close their eyes and lips tightly (the force of closure can be felt by manually trying to open them); having the patient grimace (show their teeth); having the patient look up (elevating the eyebrows and creasing the forehead); and also having the patient fill their cheeks with air with their lips tightly pursed. If one or both sides of the face are weak, s/he will have difficulty holding the air in. Tapping each cheek accentuates the difficulty on the appropriate side. The most common cause of facial weakness is Bell's palsy, an idiopathic condition that may result from viral infection-induced inflammatory swelling of the facial nerve in its canal. Since the canal is very long and tight, swelling can put pressure on the nerve, resulting in damage either by direct effects or by impairing blood flow in the nerve. In some cases, facial palsy is produced by a very clear viral infection with Herpes Zoster, often associated with ear pain and vesicles on the tympanic membrane. Lyme

disease also has a proclivity to produce facial palsy, sometimes bilateral. The hallmark of peripheral facial palsy is that it involves the entire side of the face, including weakness of the forehead muscles as well as those around the eye and mouth. This is because fibers to all of these regions of the face are packed together in the facial canal. Most cases of uncomplicated Bell's palsy recover quite well. In its most severe form, infarction of the nerve may occur with a prolonged and not infrequently incomplete process of regeneration. This is more common when a longer course of the nerve is affected, accompanied by ageusia (loss of taste) and hyperacusis. The facial nerve begins at the facial motor nucleus of the caudal pons. It is not common to damage this nucleus and due to the proximity of many sensory and motor pathways running through the brain stem, there are almost always other signs of neurologic damage (hemiparesis, hemihypesthesia, gaze palsy, etc) when the facial nerve is affected here. It should be obvious that face movement is under voluntary control. However, it is also under control of the limbic system, where strong emotions can be seen in face involuntarily. Accordingly, there is more than one pathway for "supranuclear" control of the face and these pathways can be damaged independently. Corticobulbar (pyramidal) projections from the motor cortex (precentral gyrus) through the genu of the internal capsule are the major substrate for voluntary facial movement (Fig. 5-6). The cerebral cortical projections to the facial motor neurons innervating the upper face are essentially bilateral (i.e., each cortical hemisphere provides innervation to both sides). Therefore, unilateral lesions (such as a stroke affecting one hemisphere or the internal capsule) will not produce weakness of the upper face muscles. On the other hand, facial motor neurons that innervate the muscles of the lower face receive input largely from the contralateral hemisphere (i.e., the right hemisphere activates motor neurons of the left facial nucleus, and vice-versa). Therefore, a lesion involving the right motor cortex (e.

g., carotid-middle cerebral arterial system occlusion and hemispheric infarction) causes a weakness of voluntary left lower facial movement that is especially noticeable while the patient is talking, grimacing (usually elicited by asking the patient to bare their teeth or gums), or resting. In the latter instance, the corner of the mouth droops and there may be some widening of the palpebral fissure (eye) (Fig. 5-7). On the other hand, the forehead is normally creased when a person raises their eyebrows or looks toward the ceiling. This distinguishes the "supranuclear" weakness of the face from the weakness of the whole side of the face, due to damage of the peripheral facial nerve, as seen with Bell's palsy. Interestingly, despite severe weakness around the mouth with "supranuclear facial palsy", the mouth may actually move more than normal with emotional triggers (hypermimia, Fig. 5-7). This illustrates that limbic motor pathways (governing postures and movements in response to strong emotion) are distinct from the more usual motor pathways that we employ for normal voluntary movements. When there is bilateral damage to voluntary motor pathways, the face may be markedly overexpressive and may not actually reflect the patient's consciously perceived emotions. This is termed a "pseudobulbar affect".

Somatic sensation The facial nerve has only a very small cutaneous distribution to the skin of the external auditory canal and over the tympanic membrane, where it overlaps with the small somatic branches of cranial nerves IX, X, and possibly V. Additionally, nerve VII variably supplies small branches to the ear lobe and the mastoid, which overlaps with the distributions of the trigeminal nerve and cervical nerves 2 and 3. It is not surprising with the considerable overlap of dermatomes that sensory testing seldom reveals hypoesthesia when the facial nerve is damaged. However, patients with Bell's palsy may complain of

pain in the external canal and over the mastoid region due to irritation of these nerve fibers. Herpes zoster infection may afflict the geniculate ganglion (the sensory ganglion of the facial nerve) and manifests itself as pain and vesicular eruption over the preceding distribution. Facial weakness or paralysis is common with geniculate zoster due to swelling.

References

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Brodal, A.: Neurological Anatomy in Relation to Clinical Medicine, ed. 2. New York, Oxford University Press, 1969.

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Cogan, D.G.: Neurology of the Ocular Muscles, ed. 2. Springfield, IL, Charles C. Thomas, Publisher, 1956.

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Monrad-Krohn, G.H., Refsum, S.: The Clinical Examination of the Nervous System, ed. 12. London, H.K. Lewis & Co., 1964.

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Spillane, J.D.: The Atlas of Clinical Neurology, ed. 2. New York, Oxford University Press, 1975.

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Walsh, F.B, Hoyt, W.F.: Clinical Neuro-ophthalmology, ed. 3. Baltimore, Williams & Wilkins Co., 1969.

Questions Define the following terms:

hyperacusis, agusia.

5-1. Which division of the trigeminal nerve has motor fibers? 5-2. What are some good ways to distinguish hysterical sensory loss on the face?

5-3. Where is the trigeminal ganglion located? 5-4. Where does the trigeminal nerve root enter the brain? 5-5. What modalities would test the integrity of the spinal tract of the trigeminal nerve? 5-6. Where do pain and temperature nerve fibers in the trigeminal nerve run after entering the pons? 5-7. What is the pathway of the corneal reflex? 5-8. What are the symptoms of Bell's palsy? 5-9. How can you distinguish weakness of the face that is due to damage to the brain (such as with a stroke) from weakness due to damage of the facial nerve? 5-10. Describe the reflex arc of the jaw-jerk reflex.

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Chapter 6 - Auditory & Vestibular Function

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In this chapter, the functions and clinical examination of the vestibulocochlear nerve (CN VIII) and its central connections will be discussed. The two distinct

Auditory nerve

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Testing

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Weber's test

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Rinne test

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Pathology

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Tinnitus

functions are in hearing and in control of balance. In the case of the auditory part of CN VIII, the symptoms are deafness or tinnitus (ringing in the ears). In the case of the vestibular part of CN VIII, the symptoms are vertigo or imbalance, although visual disturbance when moving may also be a complaint. ●

Auditory function

Vestibular nerve

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Caloric testing

Testing

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Caloric testing

The vast majority of hearing problems result from peripheral disease, i.e., involvement of the eighth nerve or inner ear. Testing of the peripheral system at

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"Doll's eyes"

the bedside is simple and rewarding. For screening persons who do not complain

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Causes of

of hearing loss, asking them to compare the sound of rustling fingers or a ticking watch in the two ears is a useful test of acuity. This, combined with the Weber

vertigo

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Central vs.

test (see below), is adequate. To this might be added the use a whispered voice,

peripheral

which represents midrange frequencies that frequently are involved in neural

nystagmus

deafness.

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Positional

Two basic instruments can aid in testing the auditory system: a C512 tuning fork (C256 is adequate but not as sensitive; C128 is inadequate except for testing for

vertigo

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References

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Questions

hyperacusis and cutaneous and bony vibratory perception), and a mechanical watch (watch-ticking is in the 1,500 cps range). The watch is placed next to the

patient's ear and gradually moved away. The distance at which the patient ceases to hear the tick is noted and compared with the distance from the opposite side. If the examiner has normal hearing, a useful comparison can be made. High-tone deafness is measured by this test. The C512 (or C256) fork is then used to test for lower tone falloff and, more important, to determine whether hearing loss is caused by defects in the conduction system (conductive deafness) or by damage to the inner ear-auditory nerve system (sensorineural deafness). This distinction is important since different types of conditions produce these types of deafness and the Weber test and Rinne test permit bedside differentiation of these conditions. More detailed clinical evaluation including special audiometric testing is carried out in otolaryngological laboratories and can be very useful in differentiating cochlear (inner ear) disease from direct eighth-nerve involvement.

Weber test Both the Weber and Rinne tests are most valuable in the patient with a documented hearing loss (see above). These tests are particularly focused on determining whether the loss is sensorineural or conductive. In the Weber test, the stem of a tuning fork is placed gently against a midline structure of the skull (i.e., the maxillary incisor teeth or vertex of the cranium or forehead) and the patient is asked where s/he hears the sound. Sound is transmitted to both ears through the air but particularly through

the vibrations of the bones of the skull. If sound is transmitted to both sides equally, the sound is heard in the midline and it can be presumed that the conduction and neural apparatus is intact. With neural deafness, the sound transmits best to the normal side and the patient lateralizes the sound to that side. With conduction deafness, sound transmits best to the side of the deafness. This is thought to occur because ambient sound is prevented from getting to the cochlea on the blocked side. This causes the nervous system to amplify sounds on that side by sensitizing cochlear transduction. In conductive deafness, the patient hears the tuning fork better on the affected side because sound on the normal side is relatively depressed and extinguished. You can demonstrate this yourself by plugging an ear with your finger, causing conduction deafness, and then humming. The sound will be heard better on the occluded side. By the way, you notice the effects of ambient sound on hearing acuity when you must talk to a friend at the top of your voice in a noisy, crowded room and then continue talking and walk into a silent room where you find yourselves shouting at each other.

Rinne test In some cases the Rinne test can provide some additional information. This tests both bone and air conduction. The examiner places the butt of a vibrating tuning fork on the mastoid region, and when the patient ceases to hear the vibration, the examiner places the tines close to the external auditory meatus to check air conduction. Vibrations perceived through air are heard twice as long as those perceived through bone, so the normal individual reports, for example, hearing the bone vibration for 30 seconds and then continues to hear the vibration through air for another 30-60 seconds altogether. If there is conductive deafness, bony conduction is either normal or slightly enhanced, whereas air

conduction is decreased. If there is neural deafness, both bone conduction and air conduction are equally suppressed. As with the watch tick, the examiner should compare the ability of both sides to perceive the fork. A comparison of the patient's ability to perceive the fork, as well as the watch tick, with the examiner's ability is also useful (Schwabach test).

Pathology Conductive deafness results from processes that occlude the sound conduction pathways (the external auditory canal, tympanic membrane, middle ear or the ossicles). These may be easily detected when they result from conditions that are visible with the otoscope (blockage of the external canal or rupture or scarring of the tympanic membrane). Some conditions of the middle ear, such as supperative otitis media (where there is pressure in the middle ear due to infection), or serous otitis media (where there is obstruction of the auditory tube with a vacuum in the middle ear and retraction of the ear drum and accumulation of some serous fluid), may be visible, as well. Other conditions, such as otosclerosis, which results in progressive fusion of the ossicles, may not be detectible by observation and may require more testing. There are many conditions that can damage the delicate hair cells of the organ of Corti or the auditory component of CN VIII. These conditions produce "sensorineural" hearing loss. By far, the most common cause of this is exposure to loud noises, which typically affects high-tone hearing. Other conditions should be considered in acute sensorineural hearing loss, including: infectious (usually viral) or inflammatory attack on the inner ear; ischemia (the labyrinthian artery usually arises from the anterior inferior cerebellar artery); or trauma (especially with fracture of the skull base). A more insidious loss of hearing can occur with Meniere syndrome. This condition occurs due to buildup of

pressure in the inner ear due to obstructed resorption of endolymph. This pressure can cause "blowouts" of the membranes, with attacks of sudden vertigo that improves over hours (see the vestibular system below). It also affects hearing, with tinnitus (usually a buzz or hum) and hearing loss (usually of low tones). The hearing loss can be detected even in between attacks of vertigo. While damage to the cochlear nuclei, located at the lateral aspect of the pontomedullary junction (where CN VIII enters the brain) can cause unilateral hearing loss, damage to other regions of the central nervous system is unlikely to cause recognizable hearing loss. Beyond the cochlear nuclei the auditory system makes multiple decussations in the brainstem up to the level of the medial geniculate, and therefore auditory signals are bilaterally distributed in the brainstem, thalamus and primary auditory cortex (Heschl's gyri of the posterior-superior temporal lobes). Significant loss of hearing therefore, does not occur following unilateral lesions of the auditory system above the cochlear nuclei. Bilateral lesions may affect hearing but are usually so devastating as to preclude clinical testing of hearing (there are laboratory tests of hearing, described in Chap. 23, that may help localize brain stem lesions and do not require patient cooperation). Damage to the central nervous system occasionally impairs localization of sound, even without affecting acuity. For example, localization difficulty can occur with large unilateral cerebral cortical lesions. Deficits in sound localization is most likely to occur when the primary auditory cortex is involved but is less frequently observed with large lesions of the frontal and/or parietal cortex. Such patients are unable, with eyes closed, to localize an auditory stimulus with their eyes closed in the auditory field opposite the damaged hemisphere. This can be tested at the bedside by asking the patient to reach for a sound (such as snapping fingers) with their eyes closed. Double simultaneous stimulation (DSS) can also be useful; the patient may extinguish (ignore) the stimulus opposite the lesioned hemisphere (some

of this may be a neglect phenomenon, especially when the frontal and parietal lobes are involved).

Tinnutus Tinnitus (ringing or buzzing in the ears) is a common complaint. It is usually due to some damage of cochlear hair cells, with spontaneous nerve activity being produced by the damaged cells. High-pitched tinnitus is most commonly due to damage to cells at the base of the cochlea due to excessive sound exposure. However, it can also result from virtually any cause of inner ear or CN VIII damage. Low pitch tinnitus (buzzing or humming) is less common in general, but may result from excessive pressure in the inner ear (conditions such as Meniere syndrome). Pulsatile tinnitus is most often due to turbulence in the carotid blood flow. This can be normal but it can also occur with carotid bruits (turbulence due to arterial narrowing). Tinnitus that is not accompanied by hearing loss can result from medications (notably high doses of aspirin), but often defies diagnosis. There is no cure for tinnitus (unless a curable cause of inner ear damage is identified), although it can occasionally be masked with other sounds.

Vestibular function The vestibular apparatus of the inner ear is specialized to detect movement of the head and, to a lesser extent, position in space. The vestibular portion of CN VIII conveys these signals to the vestibular complex of the dorsolateral brainstem at the pontomedullary junction and also to the vestibulocerebellum (Fig. 6-1). The chief symptom of damage to the system is vertigo, i.e., the illusion of movement. Stabilization of the eyes is a critical function of the vestibular system. It is largely through this effect on eye movement that we can objectively evaluate the vestibular system. The fundamental

reflex that we will discuss is the vestibulo-ocular reflex (VOR), which moves the eyes opposite to head movement in order to stabilize vision. Without a vestibular system, we would be unable to see anything clearly while the head is moving. There is another reflex, the fixation reflex, that we will discuss as well. This reflex attempts to fix the image of an object on the retina. Between these two reflexes our vision is actually quite good even when the head is moving (try reading a sign while nodding your head or shaking your head "no" and you are using these reflexes, predominantly the VOR). We are particularly good at detecting angular acceleration (i.e., spinning, pitching or tumbling). If you think about it, these are the movements that would be most important to compensate for, since they would tend to move your eyes off of a visual target. Smooth, linear motion would not tend to blur vision as much, nor would acceleration in a straight line (linear acceleration). The organs of the inner ears that detect angular acceleration are the cristae within the semicircular canals. Since the canals are at right angles to one another in three major planes, angular acceleration in any direction will move fluid in the particular canals that are in the plane of movement because of flow of endolymph (actually, in normal movements, the endolymph stays behind and the inner ear moves with the skull). At rest, the hair cells are tonically active, releasing transmitter that activates the peripheral end of the vestibular nerve fibers. The tonic activity on one side is balanced by the tonic activity in the other ear and the patient perceives that they are stable. Differential movement of fluid in one direction in the semicircular canal increases this activity in one ear and decreases it in the corresponding canal of the other ear, leading to a perception of movement and reflex movement of the eyes. Most diseases of the inner ear or vestibular nerve are destructive in nature, decreasing input from that ear. Therefore, the tonic firing level of the opposite canal system is no longer opposed and the patient perceives motion. Additionally, there will be VOR-induced eye movements that result from the brain attempting to move the eyes opposite to the

direction of perceived motion. This will trigger competing reflexes (as part of the visual fixation reflex) that will result in eye movement in an attempt to maintain a stable image. This to-and-fro motion is termed nystagmus. Actually, there are two major types of nystagmus, "jerk nystagmus" and "pendular nystagmus". The first type (and they type that is generated by the vestibular system) is" jerk nystagmus". In this type of nystagmus, there is relatively slow eye drift to one side produced by the VOR, with a fast compensatory "jerk" of the eyes to reacquire the visual target. Jerk nystagmus is named according to the direction of the fast movement, since this is the easiest to see. This type of nystagmus can normally be seen when an individual spins around. Here the nystagmus is initiated by the VOR produced by head movement. Spontaneous nystagmus is produced by vestibular damage because of the imbalance of inputs from the ears. Jerk nystagmus can also be elicited by the visual input of objects passing by rapidly (for example, if one stares out the side window of a moving vehicle with posts or trees flashing past). In this case, the nystagmus is elicited by the fixation reflex that is attempting to lock onto and track objects visually. This type of jerk nystagmus has been termed "optokinetic" nystagmus or "railway" nystagmus. The other major type of nystagmus is termed "pendular" nystagmus. This type of oscillation of the eyes does not have a fast and slow direction of movement but rather consists of an even motion from side to side. This is most often due to poor visual acuity (especially when young), and the fixation reflexes that stabilize the eyes are, therefore, poorly formed. This is more of a tremor of the eyes and does not reflect problems with the vestibular system. If the two inner ears are damaged symmetrically, there is little in the way of vertigo or nystagmus. If the horizontal canals are damaged, there is predominantly horizontal nystagmus (see Fig. 6-1), while damage to the anterior and posterior canals will tend to produce rotary nystagmus (clockwise or

counterclockwise) due to the addition of a vertical component to the horizontal nystagmus. Damage to the inner ear does not produce vertical nystagmus. Rather, this suggests damage to the brain stem vestibular apparatus. As an illustration of what happens with unilateral vestibular damage, let's consider the effects of sudden loss of the right labyrinthine system, for example, as in vestibular neuronitis (a common affliction presumably viral in origin). In this example (Fig. 6-2), the normal response of the now unopposed opposite (left) horizontal canal system is to tonically drive the eyes conjugately to the right. In an alert individual, there is a reflex attempt to contain the abnormal tonic drive. This checking attempt is called the fast component and in combination with the tonic or slow component, forms the rhythmic to-andfro movement - nystagmus. The tonic component encompasses the vestibular-oculomotor brain stem systems, whereas the fast component depends on the integrity of the cerebral hemispheres. The right hemisphere, including cortex, basal ganglia, and diencephalon, is responsible for the fast component to the left and the left hemisphere for the fast component to the right, just as for voluntary and visual tracking horizontal gaze (see Figs. 4-5 and 4-6). With loss of hemispheric function and preservation of basic brain stem functions (e.g., in a coma from sedative overdose), the fast component becomes weak, irregular, and finally disappears, leaving only tonic deviation of the eyes following vestibularoculomotor activation. With acute unilateral hemispheric depression, such as caused by a middle cerebral artery occlusion, the fast component to the opposite side is depressed. The tonic component is predominant during vestibular-oculomotor activation and drives the eyes toward the side of the abnormal hemisphere, which is capable of little, if any, checking. It is important to note that the brain has compensatory mechanisms for damage to the vestibular system. Therefore, with chronic, slowly progressive disease such as an acoustic neuroma (a tumor

arising from the neurolemmal sheaths of the eighth nerve at the internal auditory meatus), a person is much less likely to complain of vertigo or to have significant nystagmus. This is true also in persons following recovery from an acute destructive process despite the lack of effective function in the destroyed system. Compensation for even massive damage to an inner ear is quite effective. The lack of symptoms and signs is due to central compensation and in large part, though not entirely, depends on visual fixation. If a patient with chronic disease or compensated acute disease closes their eyes, the examiner may be able to detect the reappearance of the nystagmus by using and electrical test of eye position (the electronystagmogram) or simply by feeling the elevated corneas move through the closed lids. Vertigo usually does not reappear, which suggests that there are means other than visual for suppressing the illusion of movement. An excellent example of the suppression of nystagmus and vertigo is seen in the figure skater who is subjected to marked acceleration and deceleration of the horizontal endolymph-cristae systems during every spin. Using visual fixation (a fix on one object as long as possible while spinning), skaters learn to suppress after-spin nystagmus and vertigo almost entirely. Imagine what figure skating would like if this were not possible!

Examination On examining a patient with suspected vestibular dysfunction, observation for nystagmus is of primary importance prior to formal testing. A person with, for example, acute right vestibular apparatus destructive disease has horizontal nystagmus with the tonic component toward the diseased right side (release of the normal left) and the fast component toward the left (see Fig. 6-2). Usually s/he complains of vertigo (illusion of movement of self or environment), saying that the room is spinning in the direction of the fast component, to the left -- an illusion caused by the forced tonic movement of the

eyes and retinae. This should be called object vertigo as opposed to subject vertigo, which is the sensation that the subject is spinning and which occurs almost exclusively with the eyes closed. Subject vertigo is the true vestibular illusion, unsuppressed by the retinal image. The patient usually complains that s/he feels s/he is rotating in the direction of the clinically observed fast component of the nystagmus. Testing of the inner ear is not a simple matter. Asking the patient to focus on your nose while using your hands to rapidly move the head to either side ("head thrust") can provide some information. Usually, individuals are able to maintain good focus if the inner ears are intact since the head thrust activates the VOR. Inability to maintain fixation when doing this indicates damage to the inner ear. Another test of vestibular function employs rotation of the patient in a spinning chair (a Barany chair). It is very awkward to do this in the clinic and creates considerable discomfort for the subject, particularly nausea. Additionally, it cannot test each ear individually (since the whole head is spinning and since both ears are moved simultaneously). Because of these limitations, the use of a spinning chair has largely been replaced by caloric testing, which is easier to carry out and tends to be less noxious. In addition, only one horizontal canal is involved and therefore evaluated in routine caloric testing, whereas both are involved in Barany rotation. Barany rotation is more useful for testing the vertical canals; this can also be done with bilateral simultaneous caloric testing with, however, some inconsistency in the results. Vertical canal testing is rarely necessary, so a rotating barber's chair need not be part of a physician's clinical armamentarium.

Caloric testing Caloric testing is an elegant method for evaluating the integrity of the vestibular apparatus of each ear,

independently. Caloric testing is carried out most simply by irrigating the external auditory canal (observed by otoscope to be unobstructed by wax, not infected, and with no tympanic perforation) with water warmer or colder than body temperature, the presumed resting temperature of the labyrinths. The differential warming or cooling of the horizontal semicircular canal where it lies closest to the external auditory canal causes a decrease or increase, respectively, in the specific gravity of the endolymph at that point. If the head is positioned so that the horizontal canal is vertical (see the position of the canal in Fig. 6-3), significant convection currents are caused in the canal by the induced changes in specific gravity (Figs. 6-4 and 6-5). Vertical upward currents are caused by warming because of the decreased specific gravity and, with the patient supine, the current in the horizontal canal is toward the ampulla and crista (see Fig. 6-5). This direction of flow is excitatory to the crista, causing increased firing over the pathways diagrammed in Figures 6-1, 6-2, and 6-5. This results in vertigo (in which the patient feels that they are spinning toward the ear being irrigated with warm water), and there will be VOR-induced reflex movement of the eyes away from that ear. If the patient is awake and alert, the drift of vision that is produced by the VOR will result in a rapid corrective "jerk" of the eyes to try to keep them focused on a target. Nystagmus is the result (remember, nystagmus is named by the direction of the fast phase). Nystagmus "to the right" means nystagmus with the fast component to the right. In order to maintain clarity, many examiners use the term "right-beating" to clarify that they are referring to the direction of the fast phase. Cold-water irrigation will have opposite effects. With the horizontal canal in the vertical position (i.e., patient supine with their head on a slight pillow), coldwater irrigation increases the specific gravity of the endolymph closest to the external auditory canal. Therefore the fluid sinks and a current is created away from the crista/ampulla (see Fig. 6-5). This decreases the spontaneous firing of the ipsilateral horizontal canal vestibular system and causes an

imbalance with the resting tone of the opposite horizontal canal system becoming dominant. The eyes are thus driven tonically toward the irrigated side and the checking or fast component is opposite in direction. This same nystagmus (and concomitant vertigo) is seen in persons with destructive lesions of the vestibular apparatus (see Fig. 6-2). In performing caloric tests with warm water, 20 cc of approximately 48 degrees C water (higher temperature is painful) is irrigated into the external auditory canal, which should be clear of wax, uninfected, and with no tympanic membrane perforation (Fig. 6-6). Each auditory canal should be irrigated separately for the same duration (30 seconds is convenient), and the time of onset of nystagmus from the beginning of irrigation, as well as its duration and direction should be recorded. The findings from the two sides should be compared; a difference of approximately 20% is considered significantly abnormal. At least five minutes should elapse between irrigations to allow the stimulated canal to return to body temperature. The patient should be asked whether s/he is experiencing spinning sensations or nausea and whether there is a difference between the two sides. If there is less vertigo on one side, you must consider that there is hypofunction of the inner ear on that side. You may have already surmised that vestibular-oculomotor testing has considerable diagnostic usefulness in the unconscious patient since it is objective and not dependent on patient cooperation. The vestibular-oculomotor reflex pathway encompasses an expanse of the brain stem (upper medulla through mesencephalon) that contains much of the reticular formation necessary for the maintenance of consciousness. Caloric testing is good at assessing the integrity of the brain stem (see Chap. 24). There are two basic causes of depression of consciousness: diffuse bilateral hemispheric dysfunction; or dysfunction of the brain stem reticular formation (patients can have both). Caloric testing provides a method for rapidly screening to determine which of these causes is producing the depressed

consciousness. From our discussion of the mechanisms of the VOR it can be surmised that the patient with an intact reflex has an intact brain stem. Also, since the fast phase of nystagmus is mediated by activity in the cerebral cortex, a vestibulo-ocular reflex with tonic eye deviation but no fast, corrective movement, indicates that the brain stem is intact and that the cause of depressed consciousness is diffuse cortical depression. This is most often related to toxic, metabolic or drug-related effects. This occurs because the brain stem response is more resistant to these effects than is cerebral cortical function (of course, if brain activity is sufficiently depressed by toxic or metabolic upsets, even the brain stem can be ultimately affected). In cases of encephalopathy (i.e., depressed consciousness due to diffuse cerebral cortical suppression), caloric irrigation thus elicits only tonic deviation of the eyes. Warm caloric irrigation causes tonic conjugate deviation of the eyes to the side opposite the irrigation, and cold irrigation elicits deviation of the eyes toward the irrigated ear (Fig. 6-7A). An interesting and important observation is the finding of normal oculocephalic test results in the patient who is apparently in "coma". The normal slow component of nystagmus indicates the integrity of the brain stem and the normal rapid phase indicates that the cerebral cortex is awake, alert and functional. Therefore this "coma" is actually fictitious and the patient is more appropriately labeled as "catatonic". Brain stem damage produces variable effects on the reflex depending on the location of the reflex. For example, a destructive process (e.g., infarction, hemorrhage or tumor) at the midbrain level involves the oculomotor complex with subsequent loss of the medial rectus portion of conjugate horizontal deviation, with preserved lateral rectus deviation during irrigation (Fig. 6-7B). A bilateral lesion of the pons, involving the abducens nuclei and the proximate medial longitudinal fasciculi, destroys the

vestibular-oculomotor reflexes entirely (Fig. 6-7C). What effect would be seen after complete transection of the basis pontis sparing the tegmentum (see Figs. 4-5 and 6-1)?

"Doll's eyes" The poorly named "doll's eye" maneuver is a simple mechanical test that is particularly useful in the patient with depressed consciousness. More appropriately called the oculocephalic maneuver, it is composed of a rapid passive rotation of the head laterally, which causes an inertial flow of the horizontal canal endolymph in the opposite direction of the head rotation. As seen in Figure 6-8, the eyes are driven in a direction opposite the head rotation. If the patient is awake, the hemispheric checking component (this has the same substrate as the fast component of the nystagmus) keeps the eyes from deviating from midposition and actually may drive the eyes beyond the midposition toward the direction of turning. If the patient is in a coma due to bilateral hemispheric suppression, such as with toxic or metabolic disease (e.g., sedative overdose or uremia), the checking component (also the fast component of nystagmus) is lost. In this case, the eyes deviate away from the direction of head rotation in an unchecked manner (the reflex response is not inhibited by cerebral cortical input). Of course, if dysconjugate gaze is produced during the maneuver, damage to the brain stem in areas that control brain stem extraocular function must be assumed.

Conditions affecting vestibular function There are a large number of conditions that can affect the vestibular apparatus. Broadly, these can be divided into peripheral causes and central causes. These two types of causes can often be distinguished on clinical grounds (see below). Peripheral causes include conditions damaging the inner ear or the

vestibulocochlear nerve while central causes affect the brain stem, vestibulocerebellum or, in rare cases, the cortex. The most common cause of peripheral vertigo has been termed acute labyrinthitis or vestibular neuronitis. While there may be subtle distinctions between these conditions, the presumed etiology is inflammation. In this condition the vertigo comes on quickly and patients often have severe nausea and can't walk. They are at their worst in a matter of hours and then there is slow improvement over days to weeks. There is usually no hearing loss. If it comes on very rapidly (and particularly if there is hearing loss), you should consider that the condition might result from infarction due to occlusion of the labyrinthian artery. Meniere syndrome is not uncommon. It is believed to result from obstructed drainage of endolymph, resulting in increased pressure due to continued production. The pressure damages the delicate hair cells (both vestibular and auditory) with loss of sensitivity. The clinical course is punctuated by paroxysms of sudden vertigo (often with worsened tinnitus), lasting hours with spontaneous resolution. This is believed to occur due to sudden puncture of the membranes, with resolution of symptoms dependent on sealing the puncture and reestablishment of the normal equilibrium between the fluid compartments of the inner ear. These attacks of vertigo (which can occasionally be triggered by loud noises) can be violent enough to throw the patient to the ground, though, in between attacks, there may be little residual other than some low-tone hearing loss. Perilymph fistula is another cause of peripheral vertigo that is due to leakage of fluid. This condition is often precipitated by barotrauma (abrupt pressure changes) and individual attacks can occasionally be precipitated by pressure changes (including Valsalva maneuver, coughing, sneezing, airplanes, scuba diving, etc). Fluid usually leaks around the round window into the middle ear (and can occasionally be seen there).

Acoustic neuroma (actually a neurolemmoma) is a common tumor that grows on the vestibular nerve. Ironically, despite the fact that it damages vestibular nerve fibers, it is a rare cause of vertigo. This is because it progresses slowly, with ample time for compensation of deficits. Positional vertigo will be discussed below. Central causes of vertigo include damage to the brain stem or vestibulocerebellum. Stroke, usually involving the posterior inferior cerebellar artery (which supplies the lateral brain stem and part of the cerebellum) often produces severe vertigo (along with diminished pain and temperature sensations in the face). Isolated infarction or hemorrhage in the cerebellum can produce vertigo. These are particularly important to recognize because they can produce swelling and mass effect that can occasionally be fatal due to brain stem damage. Both of infarction and hemorrhage often produce occipital headache (particularly common with hemorrhage). It is important to consider this before attributing vertigo to vestibular neuronitis, which shouldn't produce headache. Neoplasms of the cerebellum and brain stem usually don't produce much vertigo (for the same reason of slow growth with compensation that we invoked with acoustic neuroma). Inflammatory disease (such as MS or rare conditions such as neurosarcoid) can produce vertigo although this is usually not severe. Paroxysmal vertigo can result from the aura of migraine or seizure. This is presumed to result from activation of the part of the sensory cortex that perceives motion. If vertigo is the only symptom, it is difficult to diagnose seizure or migraine until or unless more characteristic features arise. We will consider positional vertigo below.

Peripheral versus central vertigo As can be seen in preceding section, there are quite different conditions producing central and

peripheral vertigo. Fortunately, it is usually possible to distinguish central from peripheral vertigo on clinical grounds (Table 6-1). First of all, acute central vestibular involvement (as contrasted with acute peripheral disease) is associated with less severe vertiginous symptoms and less nausea. Additionally, central disease often produces more severe nystagmus than peripheral conditions. As distinct from central conditions, where the nystagmus is out of proportion to the vertiginous sensations, with peripheral conditions it is usually possible to predict how vertiginous the patient is by examining the nystagmus. Furthermore, central vertigo often is quite bizarre, changing directions depending on the way that the patient is looking. That does not occur with peripheral vertigo, which is unidirectional and most evident when the patient endevors to look in the direction of the fast phase of the nystagmus. Vertical (upward or downward) nystagmus does not occur with any normal lesion of the peripheral vestibular apparatus. Therefore, vertical nystagmus must be presumed to be central. If not present on forward gaze, vertical nystagmus is best observed by having the patient look directly up or down (Fig. 69). Horizontal and rotary nystagmus can occur with either peripheral or central disease and are therefore not of value in differentiation.

Positional vertigo Positional nystagmus and vertigo are relatively common disorders associated which have several potential causes (both peripheral and central). The patient complains of vertigo only when the head is in certain positions, commonly looking up. The vertigo may persist if the head is kept in the same position (this is particularly true with central disease) or it may rapidly fade (typical of the more common peripheral disease). The most common single cause of positional vertigo is so-called "benign paroxysmal positional vertigo" (BPPV). The characteristic complaint is of vertigo, which is severe and

relatively brief, after turning in bed. This can also be triggered by looking up, lying back, getting up quickly or bending to tie the shoes (either when bending forward or, more commonly, when bringing the head back up). This condition results from loose otoliths in the inner ear. When these are in the semicircular canals, position-induced movement of the stones can produce severe vertigo that resolves in under a minute (often leaving the patient quite shaky and nauseated). This can occur after head trauma but is increasingly common with age where the otoliths are less securely anchored to the macula. Testing for positional nystagmus and vertigo is done by rapidly dropping the patient backward as in Figure 6-10 (the Hall Pike or Barany maneuver). The patient's head is held right side down, left side down, and in the midline on each of three trials. Vertigo and attendant rotatory nystagmus are seen usually beginning after a few seconds and terminating in less than a minute. The condition usually is self-limiting (in months, with dissolution of the stones). However, the "canalith repositioning maneuver" can often move these stones to a less sensitive part of the inner ear, terminating the attacks. Some examples of etiologic significance are head trauma, frequently of only minor severity, vertebrobasilar distribution ischemia, and acoustic neurolemmoma, the latter involving both the nerve directly and the brain stem by compression. The most commonly affected individual is the elderly patient with no predisposing factors and no threatening pathology. Presumably the dysfunction, which is called benign positional vertigo, is caused by aging and minor asymmetrical degenerative changes in the macula-otolith apparatus. Cervical problems can produce positional vertigo by either of two mechanisms: by impairing blood flow through the vertebral artery system; or by activating sensory nerves from cervical muscles. With aging, cervical osteoarthritis becomes common. Occasionally, the bony overgrowth impinges on the transverse foramina through which the vertebral arteries course. Turning the head may increase the foraminal

narrowing and compress the vertebral arteries to such a degree that brain stem ischemia occurs. Vertigo on head turning may be the presenting symptom, but usually other evidences of brain stem involvement clarify the picture. The vertigo and other symptoms and signs should be reproducible by turning the head; it is usually not necessary to go through the whole Barany maneuver (see Fig. 6-10). In the case of vascular insufficiency, the vertigo and nystagmus usually take significantly longer to develop than with other causes of positional vertigo, up to 20-30 seconds. However, the nystagmus is variable in type, persists for longer periods, and is associated with only mild vertigo. It has been shown that sensory nerve fibers coming from the cervical musculature have connections with the vestibular nuclei. These connections probably mediate head-neck-trunk axis orientation information. Disorders of the neck that are associated with abnormal muscle tightness or spasm can produce vertigo with head movement even without impairing the circulation.

References

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Brodal, A.: Neurological Anatomy in Relation to Clinical Medicine, ed. 2. New York, Oxford University Press, 1969.

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Cogan, D.G.: Neurology of the Ocular Muscles, ed. 2. Springfield, IL, Charles C. Thomas, Publisher, 1956.

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Monrad-Krohn, G.H., Refsum, S.: The Clinical Examination of the Nervous System, ed. 12. London, H.K. Lewis & Co., 1964.

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Spillane, J.D.: The Atlas of Clinical Neurology, ed. 2. New York, Oxford University Press, 1975.

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Walsh, F.B, Hoyt, W.F.: Clinical Neuro-ophthalmology, ed. 3. Baltimore, Williams & Wilkins Co., 1969.

Questions Define the following terms:

conductive hearing loss, sensorineural hearing loss, tinnitus, vertigo, nystagmus.

6-1. What brain lesions will cause loss of hearing in one ear? 6-2. What kind of hearing loss will be produced by damage to the inner ear? 6-3. What do you call problems in which the sound wave can not reach the inner ear? 6-4. What would it mean if Weber's test lateralized to the left? 6-5. What is the most common symptom of damage to the vestibular system? 6-6. What does it mean when someone says that nystagmus was in a particular direction? 6-7. How can you distinguish vertigo from inner ear damage from that causes by damage to the central nervous system? 6-8. What is the only way to examine the integrity of the vestibular system on one side? 6-9. What would you anticipate finding during cold-water caloric testing in the intact patient who is awake? 6-10. What would you expect to find in the comatose patient whose brain stem was still working if icewater was infused into the right ear? 6-11. Damage to the inner ear produces response that look like (cold/warm) water caloric testing (choose one)?

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Chapter 7 - Lower cranial nerve function

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The lower cranial nerves are involved in pharynx and larynx function as well

Glossopharyngeal & Vagus Nerves

as in movements of the neck and tongue. Damage usually manifests as

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problems with speech and swallowing. These nerves arise from the medulla

Pharynx and palate

and, in the case of the accessory nerve (CN XI), the spinal cord. These nerves ❍

Gag reflex

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Larynx

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Central vs.

are commonly affected by conditions damaging the medulla but bilateral damage to corticobulbar connections can create motor problems that effect tongue and pharynx movement and speech.

peripheral

IX, X. Glossopharyngeal and Vagus Nerves

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Taste

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Sensation

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Baroreceptor

These two nerves are considered together because exit from the brain stem side by side, and have similar and frequently side-by-side and overlapping

reflex

functional and anatomical distributions in the periphery. Also, these nerves connect with many of the same brain stem nuclei (dorsal motor nucleus of the

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Nerve

vagus, nucleus ambiguus, nucleus solitarius, spinal nucleus of the trigeminal) and are often damaged together.

Pharynx and palate The pharynx is innervated by nerves IX and X, with motor and sensory

Spinal Accessory

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Hypoglossal nerve

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References

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Questions

contributions from both. In general, the vagus nerve is motor to the palate elevators and constrictors of the pharynx (as occurs in swallowing and gagging). The glossopharyngeal contains more sensory fibers, including from the posterior part of the tongue and pharynx down to the level of the larynx (where the vagus nerve begins to take over). The entire palate, including the soft palate, has a sensory distribution from the maxillary division of the trigeminal nerve. Contraction of the paired and fused muscles of both sides of the soft palate causes superolateral movement vectors (Fig. 7-1). The sum vector is an upward, midline movement of the palate to seal the nasopharynx when swallowing and making certain sounds (such as "guh"). When examining palate elevation, look at the point of attachment of the uvula to see if it remains in the midline. Also, if there is deviation, inspect the palate to make sure this is not simply due to scaring of the soft palate due to prior throat surgery. If the vagus nerve of one side is damage (e.g., by a tumor at the jugular foramen), the palate elevates asymmetrically, being pulled up toward the strong side (i.e., away from the weak side of the palate, Fig. 7-2). If both sides of the palate are weak, as can occur in certain muscle diseases or if the vagus is damaged bilaterally (such as from invasion by a retropharyngeal carcinoma at the base of the skull), the palate does not elevate normally during phonation and a hypernasal quality is imparted to the voice (especially noted when making a "G" sound). Air usually emanates from the nose when the patient tries to puff up the cheeks and liquid tends to regurgitate into the nose when swallowing. Rarely, a similar finding of bilateral weakness can be seen in patients with bilateral supranuclear lesions (such as by bilateral cortical damage or bilateral damage to the corticobulbar tracts. In this case, the patient will often show signs of "pseudobulbar" affect (see Chapt. 5).

Gag reflex The gag reflex involves a brisk and brief elevation of the soft palate and bilateral contraction of pharyngeal muscles evoked by touching the posterior pharyngeal wall. It is tested on the left and the right sides and the reflex response should be consensual (i.e., the elevation of the soft palate should be symmetrical regardless of the side touched). As with all reflexes, the gag reflex has a sensory and a motor limb. The sensory limb is mediated predominantly by CN IX. The motor limb by CN X. Touching the soft palate can lead to a similar reflex response. However, in this case, the sensory limb of the reflex is the trigeminal nerve. In very sensitive individuals, much more of the neuraxis may be involved; a simple gag may enlarge to retching and vomiting in some. The gag response varies greatly from individual to individual but is relatively constant in any one person. In some individuals, this reflex is under such strong voluntary control that probing causes very little or no response. This could make differentiation of normal suppression of the gag from symmetric pathologic depression of motor and/or sensory function difficult. However, actual damage can usually be determined by asking the patient count to 10 immediately after rapidly swallowing 4 oz. of water. If there were bilateral sensory and/or motor deficit, one would anticipate that fluid would penetrate into the unprotected larynx, producing a "wet voice" often with choking and coughing. The waterswallowing test is also a useful screen in detecting which patients with neurologic deficit are likely to have trouble eating (neurologic disease is more likely to affect swallowing of thin liquids, like water, than it is to affect the wallowing of pudding consistencies, which are easiest). In glossopharyngeal nerve (sensory) involvement, there will be no response when touching the affected side. With vagal nerve damage, the soft palate will elevate and pull toward the intact side regardless of the side of the pharynx that is touched. If both CN IX and X are damaged on one side (not uncommon),

stimulation of the normal side elicits only a unilateral response, with deviation of the soft palate to that side; no consensual response is seen. Touching the damaged side produces no response at all.

Larynx The vagus nerve is both the sensory and motor innervation of the larynx. Sensory and motor nerve fibers reach the larynx by different courses, with the superior laryngeal nerve being sensory and the recurrent laryngeal nerve being motor. The recurrent laryngeal nerves take a long, circuitous route before reaching the larynx, with the left nerve passing all the way around the aortic arch. Mediastinal lesions (e.g., carcinoma of the esophagus, cancerous lymph nodes or aortic aneurysms) may be first evidenced by hoarseness due to paralysis of the left vocal cord. The same can be true on either side for malignancies in the neck, such as thyroid cancer, since both the left and right recurrent laryngeal nerves pass posterior to that gland to reach the larynx. Loss of function of one or both recurrent laryngeal nerves causes "hoarseness". Persistent, painless hoarseness should alert the examiner to the possibility of unilateral or bilateral vocal cord weakness or paralysis. This warrants examination of laryngeal appearance and function. This can either be done by fiberoptic laryngoscopy or by indirect laryngoscopy with a simple curved dental mirror and a light source (a bedside lamp shining over the physician's shoulder or a flashlight held by an assistant) (Fig. 73). The mirror must be warmed to prevent fogging. The tongue is held protruded with cotton gauze or is depressed with a tongue blade, and the mirror is then placed face down just below the soft palate, not touching the pharyngeal walls to avoid gagging. It is sometimes useful to spray the nasopharynx with a small amount of a weak topical anesthetic, such as 1% Xylocaine. The mirror allows a view of the superior aspect of the larynx covered by the epiglottis. The patient is asked to say "aah." The epiglottis

then uncovers the vocal cords, which should be in a relatively open position. The patient then attempts to say "eee," a high pitched sound, the cords should closely appose unless they are paralyzed on one or both sides (see Fig. 7-3). Laryngoscopy (direct or indirect) is not part of a routine bedside examination, however. It should be done only when phonation changes are persistent.

Central vs. peripheral involvement To differentiate between involvement of the peripheral portion of a cranial nerve and the brain stem portions, it is important to consider whether there is associated involvement of other cranial nerves or evidence of damage to cerebellar functions or the tracts that course through the brain stem (corticospinal or the lemniscal or spinothalamic sensory paths). It is unusual for brain stem lesions to involve one or two cranial nerves in isolation, without also affecting the contiguous long-tract and cerebellar system structures. Motor neuron disease (a degenerative condition involving upper and lower motor neurons) is an exception to this rule as is poliomyelitis (a rare condition today). Supranuclear motor pathways to the palate, pharyngeal, and laryngeal musculature are bilateral. Therefore, unilateral lesions, even large strokes, rarely produce any persistent problem with lower cranial nerve function (there may be some transient swallowing trouble). Bilateral acute or subacute loss of hemispheric connections to the medullary nuclei causes difficulty with swallowing, phonating and, initially, a depressed gag reflex. In time, the gag reflex may become uncontrollably hyperactive (as do many other skeletal and autonomic reflexes when they are no longer under supranuclear control).

Taste Both the glossopharyngeal and vagus nerves (CN IX and X) have taste and somatic sensory functions

that are not routinely examined. However, the taste function in the glossopharyngeal nerve (CN IX) can be examined if there is suspicion of damage to the nerve (vagus nerve taste function can not be tested). A saturated solution of salt, a substance normally tasted best by the posterior and lateral taste buds (sweet is tasted best by the anterior and midline tastebuds), is used in the testing with the same technique described for the facial nerve (CN VII, see Chapt. 5).

Somatic sensation The glossopharyngeal and vagus nerves (along with the facial nerve) supply tiny sensory branches to the external auditory canal. This extensive overlap (which also includes some contributions from the trigeminal nerve and the 2nd cervical nerve) precludes detecting loss of sensation caused by lesions of any one of these nerves. However, pain in the ear may be a prominent early symptom of irritation of any one of these cranial nerves. If the vagus or glossopharyngeal nerve is involved, the pain often extends into the pharyngeal region, helping to differentiate from the pain of seventh-nerve irritation (which would be confined to the ear and mastoid region). If facial weakness is present, this would be a clue to facial nerve irritation, while depression of the gag reflex would suggest vagus or glossopharyngeal nerve involvement. Trigeminal involvement is differentiated by pain in the face and deficits in sensation in the trigeminal distribution; involvement of the upper cervical nerves is indicated by hypoesthesia or pain in the scalp and upper back of the neck.

Carotid sinus (baroreceptor) reflex The baroreceptor reflex is mediated by sensory fibers in the glossopharyngeal nerve and motor fibers in the vagus nerve. The normal reflex detects increased blood pressure in the carotid sinus, triggering a

slowing of the heart and lowering of blood pressure. Because the receptor works as a mechanical transducer, any kind of distortion of the carotid sinus can cause slowing of the pulse and hypotension. Firm massaging of the carotid bifurcation while monitoring pulse and blood pressure is the bedside technique for testing the reflex. However, this is hazardous due to the potential for excessive slowing of the heart and for disrupting any athersclerotic plaque that might be in the carotid sinus region (potentially producing embolic stroke).

XI. Spinal Accessory Nerve Technically, the accessory nerve (CN XI) has two components: (1) a central branch arising from medullary nuclei, and (2) a spinal accessory branch arising in the first five to six cervical spinal segments from the lateral portion of the ventral horn. The central branch joins the vagus immediately after leaving the brain stem and is involved in innervation of the laryngeal musculature. We typically consider this component with the vagus nerve and have discussed examination of the larynx and pharynx (above). The spinal accessory branch has an unusual course. It arises from motor neurons in the upper 6 cervical segments. These neurons send their nerve roots to exit the spinal cord laterally (not with the ventral motor nerve root). The nerve roots that comprise the spinal accessory nerve ascend the vertebral canal adjacent to the lateral side of the spinal cord and they enter the skull by passing upward through the foramen magnum. This nerve then turns laterally to pass through the jugular foramen along with cranial nerves IX and X. The spinal accessory nerve provides the motor innervation of the sternocleidomastoid (SCM) muscle before passing through the posterior triangle of the neck to reach the trapezius muscle (which it also innervates). Cervical nerves provide sensory innervation of these

muscles. When examining the SCM muscle, the bulk and outline of the muscle should be observed. Atrophy is common in damage to the nerve and fasciculations may be seen especially if the motor neurons are diseased. The SCM muscle rotates the head away from the side of contraction. Testing entails having the subject turn their head against the examiner's hand, which is pressed against the patient's chin (Fig. 7-4). The bulk of the muscle is then easily seen and palpated, and its strength can be determined. Having the patient attempt to bring their chin toward their chest can test the left and right SCM as they work together in this action. Paralysis of this muscle will produce weakness, although not complete loss of ability to rotate the head away from the lesion. This is because there are other muscles that are able to partially compensate. For this same reason, the resting head position is usually not affected by isolated SCM paralysis. Rarely, the patient will hold their head turned slightly toward the side of lesion. The two sternomastoids contracting together will flex the head toward the chest. Bilateral weakness may prevent the patient from lifting their head off a pillow and the head may be inclined posteriorly for lack of flexor tone. Bilateral weakness suggests muscle or neuromuscular disease. Spasmodic torticollis is a condition that often affects the tone of the SCM muscle, although it can affect several other cervical muscles as well. In this condition, there is an excessive activity of unknown etiology in one (rarely both) of the sternomastoids. This results in an obvious deviation of head postion. The subject's head is spasmodically turned away from the involved muscle, which usually shows hypertrophy. One rather striking observation is that the patient can often terminate the spasm by simply touching the opposite side of the chin or cheek. The head drifts back into its dystonic position once the touch is removed. The spinal accessory nerve innervates the trapezius muscles, which elevate the shoulders and rotate the

scapula upward during abduction of the arm. Denervation is evidenced by atrophy and often fasciculations. The shoulder droops on the side of the weak muscle and there is downward displacement of the scapula posteriorly. Shrugging the shoulders against resistance is the standard way of testing the upper trapezius (Fig. 7-4). Both the SCM and the trapezius muscles are under voluntary control, requiring some input from the corticospinal system. The projections from the cerebral cortex to the motor neurons innervating the SCM are bilateral. Therefore, even large unilateral lesions do not produce weaknes of the SCM or any deficits in head turning. However, in the case of corticospinal innervation of trapezius motor neurons there is usually a contralateral predominance. This contributes to mild to moderate contralateral weakness of shoulder elevation following large, unilateral injuries of corticospinal systems. This is rarely very severe, however

XII. Hypoglossal Nerve The hypoglossal nerve (CN XII) has an entirely motor function, innervating the muscles of the tongue. It originates from the columns of motor neurons located near the midline in the dorsal aspect of the medulla. The nerve exits the ventral side of the medulla as a row of small nerve rootlets adjacent to the pyramid. After a short course through the subarachnoid space, the rootlets come together as a single nerve that passes through the hypoglossal foramen in the base of the skull. Ultimately it reaches the tongue and innervates the intrinsic and extrinsic tongue muscles. The tongue is under voluntary control. Accordingly, corticobulbar pathways activate hypoglossal motor neurons. As with most cranial nerves, these corticobulbar projections are bilateral, although there is a slight contralateral predominance. Therefore, large lesions to the corticobulbar system, such as large strokes, can produce

slight weakness of the contralateral tongue. Weakness of the tongue manifests itself as a slurring of speech. The patient complains that their tongue feels "thick", "heavy", or "clumsy." Lingual sounds (i.e., l's, t's, d's, n's, r's, etc.) are slurred and this is obvious in conversation even before direct examination. Examination of the tongue first involves observation for atrophy and fasciculations. With supranuclear lesions, weakness, frequently mild, is not accompanied by loss of muscle mass or fasciculations. Lesions of the nerve (e.g., hypoglossal neurolemmoma, nasopharyngeal tumor along the base of the skull, basal skull fracture) or of the nucleus in the brain stem (e.g., medullary stroke, motor neuron disease or bulbar poliomyelitis) the tongue displays weakness, atrophy and, possibly, fasciculations on the side of the involvement (Fig. 7-5). Atrophy and fasciculations in combination suggest disease or damage to the motor neurons of the brain stem, but can be seen with peripheral nerve damage, as well. Fasciculations are fine, random, multifocal twitches of muscle. They are evaluated by observing the tongue while it is at rest in the floor of the mouth. They are best seen along the lateral aspect of the tongue. Protrusion frequently causes a fine tremor in the normal tongue, which can obscure or mimic fasciculations. Simply having the patient protrude their tongue in the midline tests strength of the tongue. The normal vectors of protrusion are illustrated in Figure 7-5. When one side of the tongue is weak, it protrudes toward the weakened side (Fig. 7-5). A repetitive or complex lingual sound (e.g., "la la la la" or "Methodist artillery") often shows impediment when any part of the vocal apparatus is affected (e.g., Broca's region, motor cortex, basal ganglia, cerebellum, brain stem, nucleus, or nerve). The most common process causing major involvement of the hypoglossal nerve is motor neuron disease (amyotrophic lateral sclerosis). This is a degenerative disease that has a predilection for early and severe involvement of the hypoglossal motor neurons. The involvement is almost always bilaterally

symmetrical. Unilateral damage of the hypoglossal nerve can be produced by tumors or trauma involving the base of the skull, whereas stroke damaging corticobulbar projections is the usual cause of unilateral supranuclear dysfunction.

References

●

Brodal, A.: Neurological Anatomy in Relation to Clinical Medicine, ed. 2. New York, Oxford University Press, 1969.

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Cogan, D.G.: Neurology of the Ocular Muscles, ed. 2. Springfield, IL, Charles C. Thomas, Publisher, 1956.

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Monrad-Krohn, G.H., Refsum, S.: The Clinical Examination of the Nervous System, ed. 12. London, H.K. Lewis & Co., 1964.

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Spillane, J.D.: The Atlas of Clinical Neurology, ed. 2. New York, Oxford University Press, 1975.

●

Walsh, F.B, Hoyt, W.F.: Clinical Neuro-ophthalmology, ed. 3. Baltimore, Williams & Wilkins Co., 1969.

Questions Define the following terms:

dysarthria, dysphonia, dysphagia.

7-1. What are the main functions of the glossopharyngeal nerve? 7-2. What would be the effect on soft palate movement of unilateral damage to the vagus nerve? 7-3. What would be the effect of unilateral damage to the vagus nerve on larynx function?

7-4. Describe the course of the spinal accessory nerve. 7-5. What does the spinal accessory nerve innervate? 7-6. What does the hypoglossal nerve innervate? 7-7. What would be the findings in unilateral damage to the hypoglossal nerve? 7-8. What would be the effect of a large stroke in the motor cortex on tongue movement? 7-9. What is the reflex pathway of the gag reflex? 7-10. What is the reflex pathway of the cough reflex? 7-11. What is the reflex pathway of the barroreceptor reflex?

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Chapter 8 - Reflex evaluation

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Reflexes are the most objective part of the neurologic examination and they are very helpful in helping to determine the level of damage to the nervous

Myotatic (muscle stretch) reflexes

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Superficial reflexes

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"Pathological reflexes"

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Evaluation of reflex

system. We will first discuss the various reflexes used in clinical practice and will conclude the chapter with a discussion of the significance of the findings. In some situations reflexes may be the major part of the examination (e.g.,

changes

the comatose patient). They have the value of requiring minimal cooperation ❍

Muscle

❍

Neuromuscular

on the part of the patient and of producing a response that can be objectively evaluated by the examiner. A list of all possible reflexes would be almost junction

endless and a tangle of eponymic jargon for those with an historical bent. It ❍

Peripheral nerve

❍

Nerve root

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Spinal cord &

is necessary to know the most commonly elicited reflexes and this knowledge is not terribly difficult to acquire. However, the interpretation of the reflex response requires some discussion. Table 8-1 is a list of many reflexes, some brain stem

of them in common clinical use (and some less common). As a group, these ❍

Cerebellum

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Basal ganglia

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Cerebral cortex

reflexes can aid in evaluation of most of the segmental levels of the nervous system from the cerebral hemisphere through the spinal cord. In this chapter we will discuss the evaluation of commonly tested reflexes of the spinal cord. We have previously considered reflexes involving the cranial

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References

nerves such as the pupillary light reflex, the jaw-jerk reflex, the baroreceptor

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Questions

reflex and gag. We have also discussed reflex eye movements and many of the autonomic reflexes (such as the oculocardiac and the pupillary light reflex). Here we will consider muscle stretch reflexes and superficial reflexes that are used to evaluate sensorimotor function of the body. All reflexes, when reduced to their simplest level, are sensorimotor arcs. At the minimum, reflexes require some type of sensory (afferent) signal, and some motor response. While the simplest of reflexes involve direct synapse between the sensory fiber and the motor neuron (monosynaptic), many reflexes have several neurons interposed (polysynaptic reflexes). It is important to note that, even with the simplest of reflexes, there are multiple inhibitory and facilitatory influences affect that can affect the excitability of the motor neuron and thus amplify or suppress the response. These influences can arise from various levels of the nervous system. There are intrasegmental and intersegmental connections in the spinal cord, as well as descending influences from the brain stem, cerebellum, basal ganglia and cerebral cortices. All of these can influence the excitability of motor neurons, thereby altering reflex response. Lesions that damage the sensory or motor limb of a reflex arc will diminish that reflex. This can occur at any level of the sensory or motor pathway (in the case of the muscle stretch reflex, for example, this can include: the peripheral nerve and receptors; the dorsal root or dorsal root ganglion; the spinal cord gray matter; the ventral root; the peripheral nerve; the neuromuscular junction; or the muscle). Most of the pathways that descend the spinal cord have a tonic inhibitory effect on spinal reflexes. For this reason, the net result of lesions that damage the descending tracts is facilitation of reflexes that are mediated at only the level of the spinal cord (a classic example being the muscle stretch reflex). With few exceptions, this means that these spinally-mediated reflexes become hyperactive. After acute

lesions, spinal reflexes often pass through an initial stage of hypoactivity. This stage has been called "spinal shock" or diaschesis and is more severe and long lasting in proportion to the degree of damage. For example, transection of the spinal cord removes the greatest amount of higher influence and may be associated with weeks of hypoactivity. Small lesions may have little effect on reflexes. When reflexes return after spinal transection, they become extremely hyperactive. Some reflexes, such as the muscle stretch reflex, are semiquantitatively graded. This is also true for some responses as the pupillary light reflex, where the speed of reaction may indicate a "sluggish" response. On the other hand, many reflexes are simply noted as present or absent. This is true of the superficial reflexes (see Table 8-1) and the "primitive reflexes" that are associated with diffuse bilateral hemispheric dysfunction. In this latter case the reflexes are often designated as "dysinhibited" because these are infantile responses that are suppressed in the normal adult nervous system.

Examination of myotatic ("deep tendon") reflexes The muscle stretch (myotatic) reflex is a simple reflex, with the receptor neuron having direct connections to the muscle spindle apparatus in the muscle and with the alpha motor neurons in the central nervous system that send axons back to that muscle (Fig. 8-1). Normal muscle stretch reflexes result in contraction only of the muscle whose tendon is stretched and agonist muscles (i.e., muscles that have the same action). There is also inhibition of antagonist muscles. Reflexes are graded at the bedside in a semiquantitative manner. The response levels of deep tendon reflexes are grade 0-4+, with 2+ being normal. The designation "0" signifies no response at all, even after reinforcement. Reinforcement requires a maximal isometric contraction of muscles of a remote part of the body, such as clenching the jaw, pushing the hands or feet together (depending on whether

an upper or lower limb reflex is being tested), or locking the fingers of the two hands and pulling (termed the Jendrassik maneuver). This kind of maneuver probably amplifies reflexes by two mechanisms: by distracting the patient from voluntarily suppressing the reflex and by decreasing the amount of descending inhibition. The designation 1+ means a sluggish, depressed or suppressed reflex, while the term trace means that a barely detectible response is elicited. Reflexes that are noticeably more brisk than usual are designated 3 +, while 4+ means that the reflex is hyperactive and that there is clonus present. Clonus is a repetitive, usually rhythmic, and variably sustained reflex response elicited by manually stretching the tendon. This clonus may be sustained as long as the tendon is manually stretched or may stop after up to a few beats despite continued stretch of the tendon. In this case it is useful to note how many beats are present. One sign of reflex hyperactivity is contraction of muscles that have different actions while eliciting a muscle stretch reflex (for example, contraction of thigh adductors when testing the patellar reflex or contraction of finger flexor muscles when testing the brachioradialis reflex). This has been termed "pathological spread of reflexes." Practice observing normal reflexes in patients and initially among students is an excellent way to determine the range of normalcy. Almost any grade of reflex (outside of sustained clonus) can be normal. Asymmetry of reflexes is a key for determining normalcy when extremes of response do not make the designation obvious. The patient's symptoms may facilitate the determination of which side is normal, i.e., the more active or the less active side. If this is a problem, the remainder of the neurologic examination and findings usually clarify the issue. Decreased reflexes should lead to suspicion that the reflex arc has been affected. This could be the

sensory nerve fiber but may also be the spinal cord gray matter or the motor fiber. This motor fiber (the anterior horn cell and its motor axon coursing through the ventral root and peripheral nerve) is termed the "lower motor neuron" (LMN). LMN lesions result in decreased reflexes. The descending motor tracts from the cerebral cortex and brain stem are termed the "upper motor neurons" (UMN). Lesions of the UMNs result in increased reflexes at the spinal cord by decreasing tonic inhibition of the spinal segment. Lesions of the cerebellum and basal ganglia in humans are not associated with consistent changes in the muscle stretch reflex. Classically, destruction of the major portion of the cerebellar hemispheres in humans is associated with pendular deep-tendon reflexes. The reflexes are poorly checked so that when testing the patellar reflex, for example, the leg may swing to-and-fro (like a pendulum). In normal individuals, the antagonist muscles (in this example, the hamstrings) would be expected to dampen the reflex response almost immediately. However, this is not a common sign of cerebellar disease and many other signs of cerebellar involvement are more reliable and diagnostic (see Chapt. 10). Basal ganglia disease (e.g., parkinsonism) usually is not associated with any predictable reflex change; most often the reflexes are normal.

Superficial reflexes Superficial reflexes are motor responses to scraping the skin. They are graded simply as present or absent although markedly asymmetrical responses should be considered abnormal as well. These reflexes are quite different than the muscle stretch reflexes in that the sensory signal has to not only reach the spinal cord, but also must ascend the cord to reach the brain. The motor limb than has to descend the spinal cord to reach the motor neurons. As can be seen from the description, this is a

polysynaptic reflex. This can be abolished by severe lower motor neuron damage or destruction of the sensory pathways from the skin that is stimulated. However, the utility of superficial reflexes is that they are decreased or abolished by conditions that interrupt the pathways between the brain and spinal cord (such as with spinal cord damage). Classic examples of superficial reflexes include the abdominal reflex, the cremaster reflex and the normal plantar response. The abdominal reflex includes contraction of abdominal muscles in the quadrant of the abdomen that is stimulated by scraping the skin tangential to or toward the umbilicus. This contraction can often be seen as a brisk motion of the umbilicus toward the quadrant that is stimulated. The cremaster reflex is produced by scratching the skin of the medial thigh, which should produce a brisk and brief elevation of the testis on that side. Both the cremaster reflex and the abdominal reflex can be affected by surgical procedures (in the inguinal region and the abdomen, respectively). The normal planter response occurs when scratching the sole of the foot from the heel along the lateral aspect of the sole and then across the ball of the foot to the base of the great toe. This normally results in flexion of the great toe (a "down-going toe") and, indeed, all of the toes. The evaluation of the plantar response can be complicated by voluntary withdrawal responses to plantar stimulation. The "anal wink" is a contraction of external anal sphincter when the skin near the anal opening is scratched. This is often abolished in spinal cord damage (along with other superficial reflexes).

"Pathological reflexes" The best known (and most important) of the so-called "pathological reflexes" is the Babinski response (upgoing toe; extensor response). The full expression of this reflex included extension of the great toe

and fanning of the other toes. This is actually a superficial reflex that is elicited in the same manner as the plantar response (i.e., scratching along the lateral aspect of the sole of the foot and then across the ball of the foot toward the great toe). This is a primitive withdrawal type response that is normal for the first few months of life and is suppressed by supraspinal activity sometime before 6 months of age. Damage to the descending tracts from the brain (either above the foramen magnum or in the spinal cord) promotes a return of this primitive protective reflex, while at the same time abolishing the normal plantar response. The appearance of this reflex suggests the presence of an upper motor neuron lesion.

Evaluation of reflex changes We now list the reflex changes associated with dysfunction at various levels of the nervous system.

1. Muscle: Stretch reflexes are depressed in parallel to loss of strength. 2. Neuromuscular junction: Stretch reflexes are depressed in parallel to loss of strength. 3. Peripheral Nerve: Stretch reflexes are depressed, usually out of proportion to weakness (which may be minimal). This is because the afferent arc is involved early in neuropathy. 4. Nerve root: Stretch reflexes subserved by the root are depressed in proportion to the contribution that root makes to the reflex. Superficial reflexes are rarely depressed since there is extensive overlap in the distribution of individual nerve roots of the skin and muscle tested in the superficial reflexes. However, extensive nerve root damage can depress superficial reflexes in proportion to the amount of sensory loss in the dermatomes tested or the motor loss in the involved muscles. 5. Spinal cord and brain stem: Stretch reflexes are hypoactive at the level of the lesion and hyperactive below the level of the lesion. As noted, during the initial state of spinal shock

following acute lesions, the spinal reflexes below the lesion are also hypoactive or absent. ❍

Superficial reflexes are hypoactive at and below the level of the lesion and normal above. The abdominal superficial reflexes are not reliably present in normal individuals who are excessively obese, who have abdominal scars, or who have had multiple pregnancies, and they are frequently poorly elicited in otherwise normal elderly persons. Therefore, though classically depressed in persons with corticospinal system involvement, one should not place great emphasis on depressed abdominal reflexes if they are the only abnormality found in the examination. The plantar response is exceptional and is abnormal, extensor (Babinski response), when the descending tracts (upper motor neurons) are involved.

6. Cerebellum: Classically the stretch reflexes are hypoactive and pendular as mentioned above. When this is so, the test is reliable; however, more often than not, the reflexes are not visibly abnormal. 7. Basal ganglia: There are no consistent deep-tendon or superficial reflex changes. There may be the appearance of some of the "primitive reflexes" (e.g., the glabellar, oculocephalic, grasp, and feeding reflexes see Chap. 2) associated with some diffuse cerebral dysfunction (dementia). 8. Cerebral cortex: Unilateral disease affecting motor cortex will produce an upper motor neuron pattern of weakness (i.e., hyperactive muscle stretch reflexes and depressed or absent abdominal and cremasteric reflexes) on the contralateral side. Additionally, there may be a Babinski response. ❍

Bilateral disease is associated with the same abnormalities bilaterally, and in addition, there may be "primitive reflexes" due to release of these responses from cortical inhibition (see Chap. 2).

❍

With bilateral damage to the motor cortex (particularly when corticobulbar system is heavily affected), inhibitory control of the complex emotional expression reflexes becomes defective. These individuals cry or laugh with minimal emotional provocation and the patient usually says that they do not understand why they are crying or laughing. These complex emotional reflexes are subserved by the limbic system and are normally under inhibitory modulation by the neocortex. Bilateral damage may release these responses in a pattern that is termed "pseudobulbar" (see Chpt. 5).

References

●

DeJong, R.N.: The Neurologic Examination, ed. 4. New York, Paul B. Hoeber, Inc., 1958.

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Monrad-Krohn, G.H., Refsum S.: The Clinical Examination of the Nervous System, ed. 12, London, H.K. Lewis & Co., 1964.

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Wartenberg, R.: The Examination of Reflexes: a Simplification. Chicago, Year book Medical Publishers, 1945.

Questions Define the following terms:

hyper-reflexia, pathological spread of reflex, clonus, Babinski sign, Hoffmann's sign, myotatic reflex, upper motor neurons, lower motor neurons, reinforcement.

8-1. What is the main effect of descending motor systems on reflexes? 8-2. What are the 7 Deep Tendon Reflex exams (DTRs)? What sensory/motor nerves are they testing? 8-3. What are the superficial reflexes?

8-4. What is the effect of damage to corticospinal fibers on myotatic (deep tendon) reflexes? What is the effect on superficial reflexes? 8-5. What primitive reflexes emerge with diffuse bilateral hemispheric dysfunction? 8-6. What happens to DTRs with lesions in the cerebellum & basal ganglia? 8-7. How are DTRs graded? 8-8. What is the most important consideration in testing reflexes? 8-9. What reflex changes would occur in lesions of muscles? 8-10. What reflex changes would occur in lesions of the neuromuscular junction? 8-11. What reflex changes would occur in lesions of the peripheral nerves? 8-12. What reflex changes would occur in lesions of the nerve root? 8-13. What reflex changes would occur in lesions of the spinal cord and brain stem? 8-14. How can damage to sensory nerve fibers affect reflexes? 8-15. What is the effect of neuropathy on muscle stretch reflexes? 8-16. What are some visceral reflexes that can be tested?

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Chapter 9 - Sensory system evaluation

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Evaluation of sensation is hindered by several difficulties. Sensation belongs

Screening exam

❍

to the patient (i.e., is subjective) and the examiner must therefore depend

Double simultaneous

almost entirely on their cooperation and reliability. A demented or psychotic

stimulation

patient is likely to give only the crudest, if any, picture of their perception of ●

sensory stimuli. An intelligent, stable patient may refine asymmetries of

Patterns of sensory loss

stimulus intensity to such a degree that insignificant differences in sensation ❍

Peripheral

are reported, only confusing the picture. Suggestion can modify a subject's neuropathy

response to a marked degree (e.g., to ask a patient where a stimulus changes ❍

Radiculopathy

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Spinal cord

❍

Brain stem

❍

Thalamus

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Cerebral cortex

suggests that it must change and may therefore create false lines of demarcation in an all too cooperative patient). Obviously the examiner must not waste time and efficiency on detailed sensory testing of the psychotic or demented patient, and must warn even the most cooperative patient that minute differences requiring more than a moment to decipher are probably of ●

References

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Questions

no significance. Additionally, the examiner must avoid any hint of predisposition or suggestion. Nonetheless, even after all precautions are

taken, problems with the sensory exam still arise. Uniformity in testing is almost impossible and there is considerable variability of response in the same patient. Factors that may affect the patient's variability and should be controlled are fatigue and mood. Fatigue

is particularly likely to be induced by a long, detailed, unnecessary, and tedious sensory examination during which the examiner is frequently exhorting the patient's undivided attention. A rapid, efficient exam is the most practical means of diminishing fatigue. Mood is less subject to modification. Use of a pressure transducer, such as VonFrey monofiliments, allows more consistent stimulus intensities and therefore more objectivity in the examination; however, this is impractical at bedside and does not eliminate patient variability. Sensory changes that are unassociated with any other abnormalities (i.e., motor, reflex, cranial, hemispheric dysfunctions) must be considered weak evidence of disease unless a pattern of loss in classical sensory pattern is elicited (for example, in a typical pattern of peripheral nerve or nerve root distribution). Therefore, one of the principle goals of the sensory exam is to identify meaningful patterns of sensory loss (see below). Bizarre patterns of abnormality, loss, or irritation usually indicate hysteria or simulation of disease. However, the examiner must beware of their own personal limitations. Peripheral nerve distributions vary considerably from individual to individual, and even the classic distributions are hard to keep in mind unless one deals with neurologic problems frequently. Therefore, it is advisable for the examiner to carry a booklet on peripheral nerve distribution, sensory and motor (such as: Aids to the Examination of the Peripheral Nervous System, published by the Medical Council of the U.K.).

Screening exam As in all components of the examination, an efficient screening exam must be developed for sensory testing. This should be more detailed when abnormalities are suspected or detected or when sensory complaints predominate. Basic testing should sample the major functional subdivisions of the sensory

systems. The patient's eyes should be closed throughout the sensory examination. The stimuli should routinely be applied lightly and as close to threshold as possible so that minor abnormalities can be detected. Spinothalamic (pain, temperature and light touch), dorsal column (vibration, proprioception, and touch localization), and hemispheric (stereognosis, graphesthesia) sensory functions should be screened. Pain (using a pin or toothpick), vibration (using a C128 tuning fork), and light touch should be compared at distal and proximal sites on the extremities, and the right side should be compared with the left. Proprioception should be tested in the fingers and toes and then at larger joints if losses are detected. Stereognosis, the ability to distinguish objects by feel alone, and graphesthesia, the ability to decipher letters and numbers written on skin by feel alone, should be tested in the hands if deficits in the simpler modalities are minor or absent. However, Significant defects in graphesthesia and stereognosis occur with contralateral hemispheric disease, particularly in the parietal lobe (since this is the somatosensory association area that interprets sensation). However, any significant deficits in the basic sensory modalities cause dysgraphesthesia and stereognostic difficulties whether the lesion or lesions are peripheral or central. Therefore, it is difficult or impossible to test cortical sensory function when there are deficits of the primary sensory functions. It may be surprising that the more basic modalities are usually not greatly affected by cortical lesions. With acute hemispheric insults (e.g., cerebral infarction or hemorrhage), an almost complete contralateral loss of sensation may occur. It is relatively short-lived, however; perception of pin and light touch, as routinely tested, returns to almost normal levels, whereas proprioception and vibration may remain deficient (though considerably improved) in most cases. This lack of a significant long-term deficiency in basic sensation following hemispheric lesions has no completely satisfactory explanation,

although some basic sensations probably have considerable bilateral projection to the hemispheres.

Double simultaneous stimulation Double simultaneous stimulation (DSS) is the presentation of paired sensory stimuli to the two sides simultaneously. This can be visual, aural or tactile. Light touch stimuli presented rapidly, simultaneously, and at minimal intensity to homologous areas on the body (distal and proximal samplings on extremities) may pick up very minor threshold differences in sensation. Additionally, this testing can also detect neglect phenomena due to damage of the association cortex. Neglect may be hard to distinguish from involvement of the primary sensory systems. However, neglect usually can be demonstrated in multiple sensory systems (i.e., visual, auditory, and somesthetic), confirming that this is not simply damage to one sensory system. Association cortex lesions, particularly involvement of the right posterior parietal cortex, may become apparent only on double simultaneous stimulation. The face-hand test is a further modification of DSS. This test takes advantage of the fact that stimuli delivered to the face dominate over stimulation elsewhere in the body. This dominance is best illustrated in children and in demented and therefore regressed patients. Before the age of ten, most strikingly earlier than age five, stimuli presented simultaneously to the face and ipsilateral or contralateral hand are frequently (more than three in ten stimulations) perceived at the face alone. Perception of the hand, and, if tested, other parts of the body is extinguished. In an older child or adult, several initial extinctions of the hand may occur, but very quickly both stimuli are correctly perceived. In the patient with diffuse hemispheric dysfunction, dementia, a regression is frequently seen to consistent bilateral extinction of the hand stimuli.

This test therefore can be doubly useful, first as an indication of diffuse hemispheric function and second by stimulating the face and opposite hand, a means of detecting minor hemisensory defects (e. g., if the patient consistently extinguishes only the right hand and not the left, a sensory threshold elevation due to primary sensory system or association cortex involvement on the left is suspect).

Patterns of sensory loss Since one of the main goals of the sensory exam it is important to consider the principle patterns of sensory loss resulting from disease of the various levels of the sensory system. These patterns of loss are based on the functional anatomy of the various components of the sensory system and we will also briefly review some of these elements.

Peripheral neuropathy (polyneuropathy) Peripheral neuropathy, that is, symmetrical damage to peripheral nerves, is a relatively common disorder that has many causes. Most of these can broadly be classified as toxic, metabolic, inflammatory or infectious. In this country, the most common causes are diabetes mellitus and the malnutrition of alcoholism, although other nutritional deficiencies or toxic exposures (either environmental toxins or certain medicines) are occasionally seen. Infections, such as Lyme disease, syphilis or HIV can cause this pattern and there are inflammatory and autoimmune conditions that can produce this pattern of damage. A more complete discussion can be found in chapter 12. Because this is a systemic attack on peripheral nerves, the condition produces symmetrical symptoms. The initial symptoms are most often sensory and the longest nerves are affected (the ones that are most exposed to the toxic or metabolic insult). The receptors of the feet are considerably farther removed from their cell bodies in the dorsal

root ganglia than are the receptors of the hands. The metabolic demands on these neurons is substantial which accounts for their being the first affected and for the early appearance of sensory loss in the feet in a "stocking" distribution. Later on, as the symptoms reach the mid-calf, the fingers are involved and a full "stocking-glove" loss of sensation develops. Even later, when the trunk begins to be involved, sensory loss is noted first along the anterior midline (Fig. 9-1). Vibration perception is often the earliest affected modality since these are the largest, most heavily myelinated and most metabolically demanding fibers. Usually the loss of pin, temperature, and lighttouch perception follow, and conscious proprioception (joint position sense) is variably affected. Despite the fact that proprioception follows many of the same pathways as vibration it is usually not as noticeably affected because the testing procedure (i.e., moving the toes or fingers up or down), is quite crude and is not likely to pick up early loss. The peripheral deep-tendon reflexes are depressed early in most cases of peripheral neuropathy, particularly the Achilles reflex. This is because the sensory limb of this reflex depends on large myelinated fibers. As a rule, symptomatic motor involvement is late and, when it occurs, it affects the intrinsic muscles of the feet first.

Radiculopathy Radiculopathy (nerve root damage) is the relatively common result of intervertebral disc herniation or pressure from narrowing of the intervertebral foramina due to spondylosis (arthritis of the spine). The most common presentation of this is sharp, shooting pain along the course of the nerve root (Fig. 9-2). Single-root usually does not have any sensory loss because of the striking overlap of dermatomal

sensory distribution (Fig. 9-3). There may be slight loss, often accompanied with paresthesias (tingling or pins and needles) in small areas of the distal limbs where the sensory overlap is not great. Table 9-1 lists some of the common areas of paresthesia or decreased sensation with common nerve root injuries. Herpes zoster, which affects individual dorsal roots, nicely demonstrates dermatomal distribution because, despite the lack of sensory loss (attributable to overlap), vesicles ("shingles") appear at the nerve endings in the skin (see Fig. 9-3). Nerve root damage in the cauda equina often produces a "saddle" distribution of sensory loss by affecting the lower sacral nerve roots. This saddle distribution of sensory loss can also be seen in anterior spinal cord damage (see the next section) and, in either case, must be taken quite seriously due to the potentially serious sequellae of spinal cord and cauda equina damage. Nerve root pain is often quite characteristic. It is often quite sharp and well-localized to the dermatomal distribution and may be brought on by stretching of the nerve root (Fig. 1-5) or by maneuvers that load the intervertebral discs and compress the intervertebral foramina (Fig. 1-4). However, pain can also "refer" (see Chapt. 26). This referred pain is less localized and is often felt in the muscles (myotomal) or skeletal structures (sclerotomal) that are innervated by the nerve root. The person usually complains of a deep aching sensation. Myotomes should not be memorized but can be looked up easily by referring to the motor root innervations of muscles, which are essentially the same as their sensory innervations. Sclerotomal overlap is so great that localization on their basis is impractical.

Spinal cord Spinal cord damage is characterized by both sensory and motor symptoms both at the level of involvement as well as below by affecting the tracts running through the cord. Symptoms referable to

the level of injury appear in the pattern of dermatomes and myotomes and, when present, are very useful for localizing the level of spinal cord damage. The symptoms of damage to the long sensory tracts (the dorsal columns and the spinothalamic tract) are less helpful in localizing the lesion because it is often impossible to determine the precise level of the sensory loss and also because, particularly in the case of the spinothalamic tract, there is considerable dissemination of the signal in the spinal cord before it is relayed up the cord. Similar difficulties make it difficult to localize the level of spinal cord damage by examining for damage to the descending (corticospinal) motor tracts. Therefore, when long tract damage is identified, one can only be certain that the lesion is above the highest level that is demonstrably affected. Compression of the spinal cord from the anterior side first involves the spinothalamic paths from the sacral region, and a "saddle" loss of pin and temperature perception is usually the first symptoms even with lesions high in the spinal cord (Fig. 9-4). In this case, as symptoms progress with greater degrees of compression, symptoms progressively ascend the body up toward the level of the actual cord damage (see Fig. 9-4). Intramedullary lesions of the spinal cord (such as syrinx, ependymoma, or central glioma) may present with a very unusual pattern of "suspended sensory loss". This consists of an isolated loss of pain and temperature perception in the region of the expanding lesion because of damage to the crossing spinothalamic tract fibers (Fig. 9-5). In this pattern of sensory loss due to expanding intramedullary lesions, there is "sacral sparing" of pain and temperature because the more peripheral spinothalamic fibers (the ones from the sacrum) are the last to be involved (see Fig. 9-4). With intramedullary lesions, the dorsal columns are also usually spared until extremely late in the course of expansion, leaving touch, vibration, and proprioception intact. The loss of one or two sensory modalities (such as pain and

temperature sense, in this case) with preservation of others (such as touch, vibration and joint position sense) is termed a "dissociated sensory loss" and is in contrast to the loss of all sensory modalities associated with major nerve or nerve root lesions or with complete spinal cord damage. Complete hemisection of the cord is seen occasionally in clinical practice and is quite illustrative of the course of spinal cord sensory pathways. This lesion results in a characteristic picture of sensorimotor loss (Brown-Sequard syndrome), which is easily recognized due to the loss of dorsal columns sensations (vibration, localized touch, joint position sense) on the ipsilateral side of the body and of spinothalamic sensations (pain and temperature) on the contralateral side (Fig. 9-6).

Brain stem Brain stem involvement, like involvement of the spinal cord, is characterized by long-tract and segmental (cranial nerve) motor and sensory abnormality and is localized by the segmental signs. The picture of ipsilateral cranial nerve abnormality and contralateral long-tract dysfunction is quite consistent (Fig. 9-7). Both the dorsal columns and pyramids decussate at the spinomedullary junction (the spinothalamic system has already decussated in the spinal cord). This accounts for the typical crossed presentation of symptoms in the body. Below the level of the midbrain, the spinothalamic and dorsal column (medial lemniscus) systems remain separate and therefore lesions may involve the pathways separately (i.e., there may be a dissociated sensory loss). For example, an infarction caused by occlusion of the posterior inferior cerebellar artery typically involves only the lateral portion of the medulla. The ipsilateral trigeminal tract and nucleus and the spinothalamic tract are frequently included in the lesion, leaving a loss of pain and temperature perception over the ipsilateral face (see Chap. 5) and the contralateral side of the body from the neck down. The medial lemniscus and its

modalities (i.e., vibration, joint position and well-localized touch) are spared.

Thalamus Thalamic lesions are associated with contralateral hemihypesthesia. Initially, if the lesion is acute, there is considerable loss bordering on anesthesia, but some recovery is expected over time, especially of touch, temperature, and pain perception. Vibration and proprioception remain more severely affected. Unfortunately, episodic paroxysms of contralateral pain may be a striking and not infrequent residual of thalamic destruction (this is one of the "central pain syndromes"). The pain can be controlled occasionally with anticonvulsants. An additional residual that may develop over time is marked contralateral hyperpathia in spite of the presence of diminished overall sensitivity of the skin. Stimulation of a site with a pin causes a very unpleasant, poorly localized and spreading sensation, which is frequently described as burning. This is presumably an irritative phenomenon of the nervous system, although it may also result from loss of normal pain-suppression mechanisms. It is seen most often after thalamic lesions, although it can occur as a residual of lesions in any portion of the central sensory systems. A hypersensitivity to cold sensation frequently accompanies the hyperpathia.

Cerebral cortex As discussed earlier, cortical lesions tend to leave minimal deficits in basic sensation but, especially if the parietal lobe is damaged, there may be striking contralateral deficits in the higher perceptual functions (see Chap. 2). Stereognosis and graphesthesia are abnormal in spite of minor difficulties with vibration and proprioception and even less, if any, difficulty with pain, temperature, and light-touch perception. Of course, if there is significant deficit of primary sensations, it may be impossible to test

for deficits of higher perceptual functions.

References

●

Brodal, A.: Neurological Anatomy in Relation to Clinical Medicine, ed.2, New York, Oxford University Press, 1969.

●

Medical Council of the U.K.: Aids to the Examination of the Peripheral Nervous System. Palo Alto, Calif., Pendragon House, 1978.

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Monrad-Krohn, GH, Refsum, S.: The Clinical Examination of the Nervous System, ed. 12, London, H.K. Lewis & Co., 1964.

●

Wolf, J.: Segmental Neurology, Baltimore, University Park Press, 1981.

Questions Define the following terms:

conscious proprioception, agnosia (sterioagnosia), graphesthesia, dermatome, sclerotome, myotome, radiculopathy, myelopathy, anesthesia/hypoesthesia, hyperpathia, allodynia, hyperesthesia, dysesthesia, paresthesia, polyneuropathy, subjective.

9-1. What are the steps involved in the sensory exam? 9-2. How is it possible to lose some types of sensations and not others? 9-3. What sensations are conveyed by the small-diameter sensory nerve fibers in a peripeheral nerve? 9-4. What sensations are conveyed by large-diameter sensory nerve fibers in a peripeheral nerve? 9-5. What sensations are conveyed by the dorsal columns?

9-6. What sensations are conveyed by the spinothalmic tract? 9-7. What is tested by double simultaneous stimulation? 9-8. Where would the lesion be if the patient was able to detect all modalities of sensation but could not recognize an object placed in the right hand? 9-9. What is the common sensory loss from damage to the spinal cord? 9-10. What would be the expected sensory loss from damage restricted to the left side of the spinal cord? 9-11. What is the characteristic of sensory loss due to damage to peripheral nerves in a limb? 9-12. What is the pattern of sensory loss seen in diffuse damage to peripheral nerves (polyneuropathy?

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Chapter 10- Motor system examination

On this page ●

In this chapter we discuss the evaluation of the motor systems, that is the

Examination of the motor system

systems involved in generation and control of voluntary and reflex

❍

Strength

❍

"Deep tendon"

movements. The motor system can be divided into (1) the peripheral apparatus, which consists of the anterior horn cell and its peripheral axon,

reflexes

the neuromuscular junction, and muscle, and (2) the more complex central ❍

apparatus, which includes the descending tracts involved in control (i.e., the

Superficial reflexes

pyramidal system) and the systems involved in initiating and regulating ❍

Muscle bulk

❍

Coordination

❍

Muscle tone

❍

Abnormal

movement (the basal ganglia and cerebellum). Dysfunction in individual components of the motor system systems results in fairly specific abnormalities that can be evaluated at the bedside. Although multiple components may be involved (particularly with diseases of the movements

central nervous system) isolated involvement of the various components ❍

Station

❍

Gait

commonly occurs. We will consider these components in order to help you establish an orderly approach to motor system evaluation (Table 10-1). Examination for motor dysfunction includes assessment of strength, muscle tone, muscle bulk, coordination, abnormal movements and various reflexes.

●

Disorders of the motor system

Many of these are best detected through simple (but careful) observation.

❍

Muscle disorders

However, a few maneuvers aid in the detection of abnormality. Table 10-2

❍

Neuromuscular

disease

lists the components of a comprehensive and efficient screening examination that will elicit and localize most motor system dysfunctions. If no

❍

Lower motor neuron damage

abnormalities are found, this exam should only take two to three minutes in a cooperative patient. Table 10-3 lists the findings expected with diseases

❍

listed in Table 10-1, and Table 10-4 lists differentiating points between

Upper motor neuron damage

diseases affecting the nerves versus those primarily damaging muscle.

❍

Basal gangliar disease

Elements of the examination ❍

Examination of the motor system can be relatively objective and Tables 10-2

Cerebellar disease

and 10-3 outlines an approach using isolated segments of the motor system ●

References

●

Questions

as models. Mixed-system involvements do occur with variable symptom and sign predominance, depending on such variables as the dominance of the

various motor systems involved and the extent of the lesion(s) in each system. Lack of cooperation caused by patient fatigue, misunderstanding of the tasks demanded, or lack of physician-patient rapport must always be considered. Feigned or hysterical weakness, for example, usually can be distinguished by its bizarre localization, the absence of expected involvement of other systems (i.e., reflex, sensory, cranial), and the irregular ratchet-like giving way of muscles tested. It is always important to consider the implications of your findings and what additional or confirmatory test can be done to clarify and document your conclusions about the patient's motor system abnormality.

Strength Strength is conveniently tested by having the patient resist your force as you attempt to move their body

part against the direction of pull of the muscle that you are evaluating. This is graded on a graded scale of 0-5, with "0" representing absolutely no visible contraction and “5” being normal. A grade of "1" means that there is visible contraction but no movement;"2" is some movement but insufficient to counteract gravity;"3" is barely against gravity (with inability to resist any additional force); and "4" being less than normal (but more than enough to resist gravity). Obviously, there is ample range between 3 and 5, making the determination somewhat subjective. Some examiners expand the 5 point scale into a 9 point scale by the addition of “+” symbols when strength seems to be between numbers. Still others add “-“ symbols when a muscle seems to function just below a level. While there may be merit in having a scale beyond the original 5 points (particularly between 3 and 5) it must be remembered that the scale is quite arbitrary and lacks the precision suggested by the creation of many categories. Additionally, "normal" is a designation that takes into account the patient’s age and level of conditioning. This assessment can be made with greater precision when there is a normal side with which to compare it. In order to test strength at various levels of the nervous system, several muscles must be tested. The more common of these muscles, along with their particular peripheral nerve and nerve root levels, are found in Table 10-5. It is often very efficient to test patients using functional tasks rather than by manually testing each muscle. For example, the patient may be asked to hold the arms horizontally out in front with the palms up and eyes closed. Diffuse weakness of the upper limb often produces a “pronator drift”, i.e., downward drift of the weak limb with the hand pronating (turning in). If the limb drifts straight down, without pronation, this is not suggestive of physiologic weakness and the patient may have a conversion disorder or malingering. Erratic drift of the limb can be seen with proprioceptive sensory loss

(confirmed by testing of proprioception). When testing strength in the legs it is helpful to have the patient attempt to walk on the toes and then heels. Other tests of the legs would include hopping on each foot, standing from a chair (without use of the hands) or climbing a stair. These latter tests examine more proximal muscles. When confronting the patient with weakness, some assessment of effort should be made. Poor effort is usually reflected as good initial contraction, followed by a collapse (often termed "breakaway" or “collapsing” weakness). This is not a pattern seen in true neurologic injury where strength is typically inadequate but relatively constant. It is usually easy to detect the patient with "collapsing" weakness if you apply varying force during the muscle test. With true neurologic weakness, the maximum force that the patient applies does not vary appreciably. "Collapsing weakness" should not be graded. There are several potential causes of collapsing weakness, ranging from pain to the conscious embellishment of symptoms. When this pattern is seen, other more objective elements of the examination (such as reflex testing) become more important. The ultimate goal of strength testing is to decide whether there is true "neurogenic" weakness and to determine which muscles/movements are affected. In correlation with the remainder of the motor exam it should be possible to determine the particular part of the nervous system that is at fault to produce this weakness. Probably the most important decision is whether the weakness is due to damage to upper or lower motor neurons (UMN or LMN). As you may recall from chapter 8, upper motor neuron weakness is due to damage to the descending motor tracts (especially corticospinal) anywhere in its course from the cerebral cortex through the brain stem and spinal cord. UMN weakness is typically associated with increased reflexes and a spastic type of increased tone. On the other hand, LMN weakness is due to damage of the anterior horn cells or their axons (found in the peripheral

nerves and nerve roots). This results in decreased stretch reflexes in the affected muscles and decreased muscle tone. Additionally, atrophy usually becomes prominent after the first week or two, and this atrophy is out of proportion to the amount of disuse produced by the weakness.

"Deep tendon" (myotatic) reflexes The "deep tendon" (myotatic) reflexes are a critical part of the neurologic examination that is discussed in Chapt. 8. Testing reflexes is the most important element of determining whether weakness is of an upper or lower motor neuron type (limited only by the fact that only certain muscles actually have reliably tested stretch reflexes (include the biceps, triceps, brachioradialis (radial periosteal), quadriceps, hamstring and calf muscles). Since the reflex arc includes stretch receptors and sensory fibers, it is not necessary to damage motor axons to abolish reflexes. However, in the setting of the patient with known weakness, reflex testing is a powerful tool to investigate the cause. As you may recall from chapter 8, symmetry of reflexes is the most important consideration in determining normality. Pathological "spread of reflexes" (i.e., contraction of muscles that produce motions other than the one associated with the test muscle) is another objective sign of hyperactivity. You may recall that sustained clonus (repeated muscle contraction when a muscle is passively stretched) is an indicator of hyperactive reflexes. Conditions that damage lower motor neurons decrease muscle stretch reflexes by interrupting the reflex arc (Fig. 8-1). Therefore, a diminished reflex in a weak muscle suggests damage to the lower motor neurons somewhere along the course to the muscle (i.e., anterior horn cells, motor nerve root, or peripheral nerve). Hyperactive reflexes are seen after damage to upper motor neurons (i.e., descending motor tracts). There are other confirmatory findings that may suggest upper or lower motor neuron

disease. These signs include atrophy (LMN), fasciculations (LMN), spasticity (UMN), Babinski sign (UMN) or loss of superficial reflexes (UMN).

Superficial and "pathologic" reflexes Superficial reflexes (abdominal, cremaster and plantar) are discussed in chapter 8. These reflexes are mediated above the spinal cord. Therefore, disruption of the spinal cord or brain stem can abolish these reflexes. Of course, the superficial reflexes can also be abolished if there is extensive damage to sensory nerves or lower motor neurons in the region. The "Babinski response" (upgoing toe) is the classic pathological reflex seen with upper motor neuron damage. This reflex replaces the normal plantar response. The findings upon testing of superficial reflexes should be placed in the context of the remainder of the motor exam when evaluating upper and lower motor neurons.

Muscle Bulk Muscle bulk is primarily assessed by inspection. Symmetry is important, with consideration given to handedness and overall body habitus. Generalized wasting or cachexia should be noted and may reflect systemic disease, including neoplasia. Some areas can be adequately evaluated by inspection alone, such as the thenar and hypothenar regions or the shoulder contour. Some areas, like the thigh, leg, arm and forearm, may be better evaluated by measurement. These measurements can also permit assessment over time. Severe atrophy strongly suggests denervation of a muscle (such as with LMN lesions). This usually begins at least a week after acute injury and gets progressively worse with time (unless reinnervation

takes place). Atrophy due to LMN damage must be distinguished from that which occurs secondary to disuse. However, there is usually a clear substrate for disuse (bedrest, cast, etc.) and there is little overall change in strength. Unfortunately, patients who have limited functional reserve (such a those with prior neural disease or the elderly) can be severely affected by disuse and deconditioning.

Coordination Coordination is tested as a part of a sequence of movements. Typically the patient is asked to hold his/ her hands in front with the palms up, first with the eyes open and then closed (as when examining pronator drift, above). It is usually good form to instruct the patient to prevent movement of his/her hands, and to exert some force either toward the floor or in attempting to push the hands apart. This force can be used to assess the strength of the patient and then should be released suddenly and without warning. After a short excursion, the patient should check this movement, and this checking should be symmetrical. The patient may then be asked to touch his/her nose, and subsequently the examiners finger. This can be repeated a few times to assess the smoothness and accuracy of the movement. Further assessment can be obtained by having the patient perform a rapidly repeated movement such as tapping the thumb and forefinger together, or by having the patient clap his hands. This test can be made somewhat more difficult by having the patient repeatedly strike first the palmar and then the dorsal aspect of one hand against the palm of the other. This, of course, must be done with each hand, and you are evaluating rhythmicity and speed in performance of the movement. Lower extremity coordination can be tested in the supine position by having them attempt to place the heel of one foot on the opposite knee and subsequently tap or slide the heel down the shin to the ankle. This should be done with each leg. Other tests of lower limb coordination include tapping of the foot on

the examiner’s hand, or attempting to draw a number in the air with his/her foot. If the patient can stand and walk, it is usually only necessary to evaluate gait in order to assess lower limb coordination. The patient who can stand on either foot for ten seconds without excessive sway does not need further testing of leg coordination. These maneuvers test several neurologic systems. Strength is required for all of these tests. Excessive rebound (or loss of checking) is suggestive of cerebellar injury on the side of the abnormality. Similarly, difficulty with rapid alternating movements (dysdiadochokinesia) or marked overshoot or undershoot when attempting to hit a target (intention tremor) suggests cerebellar problems on that side. Repetitive over and undershoot during voluntary movement may reflect as "intention tremor". Extreme slowness of movement can be produced by extrapyramidal disease (such as Parkinson’s). Of course, problems with any part of the motor systems may affect coordination. For example, if there is a marked alteration in muscle strength, muscle tone, or if the patient is having abnormal movements this can influence your perception of coordination. Therefore, although tests of coordination are mainly directed toward assessing cerebellar function, you must decide whether other problems in the motor system are affecting these tests.

Muscle Tone Muscle tone may be increased or decreased, with increased tone being much easier to detect. Tone can be assessed by one of two means. The most common method is for the examiner to passively move the patient’s limb (especially at the wrist). The second method involves evaluating arm swing (with the patient standing). Tone is often easily checked by having the patient stand with his/her arms hanging loosely at their side. When the patient’s shoulders are moved back and forth or rotated the arms should

dangle freely. Increased tone is usually reflected as the arms being held stiffly both in the standing position and when walking. The lower limbs can be evaluated with the patient seated with the legs dangling. Movement of the feet should result in gentle swinging of the legs of a brief duration. Increased tone results in abrupt restriction on the excursion of the feet. There are two common patterns of pathologically increased tone, spasticity and rigidity. Spasticity is found with upper motor neuron injuries and manifests as a marked resistance to the initiation of rapid passive movement. This initial resistance gives way and then there is less resistance over the remaining range of motion (clasp-knife phenomenon). Rigidity is an increase in tone that persists throughout the passive range of motion. This has been termed "lead pipe" rigidity and is common with extrapyramidal disease, especially Parkinson’s disease. Many older individuals have paratonia. This is a phenomenon in which the patient is essentially unable to relax during passive movements. You will note that the resistance is irregular and generally greatest when you change the pattern of movement. Of note, most of these individuals have apparently normal tone when you test them in a standing position and move their shoulders about (as described above). Extreme paratonia is common in patients with dementia. Some types of increased tone appear to be prolongations of voluntary muscle contraction. Myotonia is a slowness of relaxation of muscles after a voluntary contraction or a contraction provoked by muscle percussion. This is a disorder of striated muscle and not an abnormality of innervation and may be seen in conditions such as myotonic dystrophy or congenital myotonia (a disorder of ion channels). Occasionally, metabolic diseases of muscle (such as hypothyroidism) can result in myotonic discharges. Myotonia can be easily observed by asking the individual to reverse a muscle action quickly (i.e., trying to rapidly open a tightly clenched fist) or by tapping on a muscle belly (such as the thenar muscles).

Neuromyotonia is a rare condition of irritability of the nerve (possibly autoimmune) where there is persistent contraction. Muscle contractions are not terminated and the patient becomes "stiff" with movement.

Abnormal movements There are a number of types of abnormal movements including tremor, chorea, athetosis, dystonia, hemiballism and fasciculations. Each of these has clinical implications that require discussion. Tremor is the most common abnormal movement seen in practice. Three characteristics are of particular importance. These include the symmetry (or asymmetry) of the tremor, the rate of the tremor (basically, whether it is fast or slow, i.e., greater or less than 7 cycles per second) and the circumstances under which the tremor is present (i.e., whether it is worst at rest, during sustained postures or when moving). Physiological tremor comes in two types. Rapid (>7cps) tremor is characteristic of states with increased sympathetic function (think of the last time you had too much coffee). This is most commonly secondary to anxiety, but may occur with increased adrenaline (such a pheochromocytoma) or thyrotoxicosis. A slower tremor must be classified with regard to the conditions in which it is most evident. If it is present predominantly at rest, and decreases with movement, this suggests extrapyramidal disease such as Parkinson’s disease (PD). In PD, the tremor is frequently asymmetrical and is usually associated with other signs (bradykinesia, rigidity or delayed postural corrections). Tremors which are severe on sustained postures (such as with the hands outstretched), but which may worsen slightly with action are characteristic of essential tremor (this is also seen in “senile” tremor or familial tremor). These tremors are absent at rest and are often worsened by anxiety. They are often asymmetrical and characteristically affect the use of writing and eating implements. Damage to

cerebellar systems (particularly the hemispheres or dentate connections) often produces a tremor that is most pronounced during voluntary actions. The second most common type of abnormal movement that is seen in practice is fasciculation. These are twitches in muscle (actually, contraction of a single motor unit, i.e., all of the muscle fibers attached to a single motor neuron). These can be felt and often seen. These are random and involuntary occurrences and do not result in movement of a joint. Fasciculations may reflect damage to lower motor neurons, either the cell body or the motor axon located in the nerve root or peripheral nerve. Of course, if the fasciculations were due to LMN lesions one would expect some weakness, decreased tone and (after a while) atrophy. Also, one would expect that the fasciculations would remain in a single group of muscles for more than transiently. Fasciculations may also be a finding in muscle overuse, or a sign of local muscle irritation. Also, there are some individuals who have “benign fasciculations” particularly in the calf muscles. Of course, these are not associated with weakness or other motor system abnormalities. There are several other, less common abnormal movements. Chorea is a rapid, fleeting, random and non-stereotyped movement which is worsened by anxiety and which can be suppressed for short periods by conscious effort. They differ from tics since tics are stereotyped and repeat within the same muscle groups. Tics may affect the voice, as well, and consist of repeated throat clearing, sniffing or coughing. Multiple vocal and motor tics are seen in Tourette syndrome. Athetosis is a slow, writhing, snakelike movement of a body part or parts. Dystonia is a sustained twisting of the body, usually the trunk or neck (where it is called torticollis). Hemiballism is a flinging motion of one side of the body, potentially resulting in falls. Involuntary movements are seen in a number of clinical situations. Chorea, athetosis and hemiballism are reflections of basal ganglia disease. This may be congenital (a type of cerebral palsy), post infectious

(Sydenham's chorea), hereditary (Huntington's chorea), metabolic (Wilson's disease) or cerebrovascular.

Station This is the ability to maintain an erect posture. One should be able to stand both with the eyes open and closed with a relatively narrow base of support (the feet close together). You should record excessive sway, falling to one side, or marked worsening in the ability to stand when the eyes are closed. Excessive sway with the eyes open is common with cerebellar or vestibular problems. This may be to one side (and commonly is with vestibular disorders) or may be to both sides (especially with conditions that effect the midline portion of the cerebellum, such as intoxication). You must consider the possibility of other explanation such as the patient not have enough strength to stay upright or severely delayed reactions to destabilization (such as with Parkinson’s disease). Some patients can stand well with the eyes open, but have marked increase in instability with the eyes closed. This is suggestive of a disorder of conscious proprioception (i.e., joint position sense, as may be seen with peripheral neuropathy or dorsal column/medial lemniscus dysfunction). This is termed a Romberg sign. Proprioceptive problems on one side can be brought out with standing on one foot. Of course, there are other tests of conscious proprioception, including evaluation of joint position and vibration sense in the feet. These data must be correlated with the findings on station.

Gait This is an important part of any neurologic exam. It is particularly important to observe the symmetry of the gait, the ability to walk with a narrow base, the length of the stride when walking at a normal

pace, and the ability to turn with a minimum of steps and without loss of equilibrium. When observing a normal person from behind, the medial parts of the feet strike a line and there is no space visible between the legs at the time of heel strike. This is a narrow-based gait and deviation from this can be measured in the amount of distance laterally each foot strikes from the line that their body is following. Tandem walking (the ability to walk on a line) may be used to evaluate for stability of gait, recognizing that many normal elderly patients have trouble with this. Damage to virtually any part of the nervous system may be reflected in gait. An antalgic gait, or the limp caused by pain is familiar to any practitioner. Patients with unilateral weakness may favor one side, and if the weakness is spastic (i.e., from upper motor neuron damage) the patient may hold the lower limb stiffly. S/he will drag the weak limb around the body in a "circumducting" pattern. A staggering or reeling gait (like that of the drunk) is suggestive of cerebellar dysfunction. Generally, the patient with true vertigo will tend to fall to the one side repeatedly (especially with the eyes closed). A patient with foot drop will tend to lift the foot high (steppage gait). Hip girdle weakness often results in a "waddle," with the hips shifting toward the side of weakness when the opposite foot is lifted from the floor (of course if both sides are weak the hips will shift back and forth as they take each step). Patients with Parkinson's disease often have difficulty initiating gait. The steps are usually short though the gait is narrow-based. If severe, the patient may be propulsive (they may even fall). Patients who are "glue footed" (sliding their feet along the ground rather than stepping normally) may be suffering from damage or degeneration of both frontal lobes or the midline portion of the cerebellum. When damage to these areas is severe the patient may be severely retropulsive (tending to fall over backwards repeatedly). Dorsal column injury may result in a gait in which the patient "stamps" his or her feet, and usually also needs to look at the feet in order walk. Patients with painful neuropathy of the feet may

walk as if they are "walking on eggs" and patients with spinal stenosis may walk with a stooped posture (a "simian" posture).

Disorders of the motor systems The reflection of motor system disease depends on the particular part of the motor system that is involved. Here we will discuss the characteristic deficits produced by each level of the motor system.

Muscle disease (see Chapt. 12) Typically, muscle disease (myopathy) has its earliest and greatest effects on proximal musculature. There is little atrophy (until very late) and deep-tendon reflexes are decreased only in proportion to the weakness. Certain metabolic myopathies may result in cramping due to the fact that energy is required to relax muscles and myotonia may also produce difficulty in relaxation. There are no sensory changes in myopathy.

Neuromuscular disease (see Chapt. 12) Myasthenia gravis is the prototypical neuromuscular disease. This condition results from autoimmune damage to acetylcholine receptors, which results in inefficient neuromuscular transmission. Initial contraction is strong but during sustained contraction, depletion of neurotransmitter results in progressive weakness. This can be seen during tonic actions (like simply holding up the eyelids or maintaining the arms out in front) or in actions that require sustained activity (like talking or swallowing a meal). For further information see Chapt. 12.

Lower motor neuron (LMN) disease (see Chapt. 12)

These conditions occur due to damage to the anterior horn cells, the ventral roots or the peripheral nerves anywhere along their course to the muscles. In the majority of cases, the weakness is distal. The best explanation for the predominantly distal weakness in neuronal disease is that longer motor (also sensory) nerve fibers are more exposed and vulnerable to the many processes that damage nerve. An exception to this rule is the diffuse polyneuropathy of Guillain-Barre syndrome (presumed to be an autoimmune process). In this case weakness may begin in the proximal muscles and this is presumable because the primary damage to nerves is occurring quite proximally (near the nerve root level). LMN disease results in weakness in the muscles connected with the affected nerve fibers. Understanding of the distribution of nerves and nerve roots to the individual muscles is essential to correct interpretation (Table 10-5). Additionally, there is atrophy (after the first week or two following an acute injury) that is out of proportion to simple disuse. Furthermore, reflexes are usually affected quite early and severely. This is because most conditions that damage LMNs also damage sensory nerve fibers that represent the afferent limb of the muscle stretch reflex. Finally, when there is damage to LMNs in peripheral nerves, there is often an accompanying sensory loss that can aid in diagnosis of the nerve that is involved.

Upper motor neurons (UMN) Historically, this has been associated with the corticospinal (pyramidal) tract. However, this is not quite accurate since voluntary motor pathways arising in the cerebral cortex can function by activating more primitive descending tracts from the brain stem. It is clear that the direct projections in the corticospinal tract are responsible for highly skilled movements, especially of the hands. In this section we will refer to direct and indirect corticospinal projections to distinguish the corticospinal tract itself

from the indirect activation of other descending motor tracts by cerebral cortical input. Additionally, it must be understood that the motor cortex does not act independently, but rather under the influence of the premotor cortex (involved in planning and initiating movement) as well as "extrapyramidal" systems such as the basal ganglia and cerebellum (see below). The classic picture of acute damage to UMNs includes contralateral paralysis of distal limb movements, while proximal limb movements are severely weakened and trunk movement minimally involved. Muscle tone (measured as passive resistance to manipulation) is depressed in this initial phase. The deep-tendon reflexes are also likely to be absent, recovering over time to normal or hyperactive levels. The superficial reflexes (abdominal and cremasteric) opposite the lesion are depressed or absent. A Babinski response is often present on the weak side. Over weeks to months proximal strength improves to a significant degree, whereas distal movements make only a poor recovery. A rudimentary grasping capability is frequently all that remains in the hand. Extension, opposition, and individual finger movements remain severely affected or lost. Presumably, the recovery of proximal functions relates to some bilaterality of distribution of corticospinal fibers that innervate proximal muscles. The modest recovery of distal movements is suspected to relate to preserved motor pathways from the brain stem (presumably under extrapyramidal control). Damage to the precentral gyrus (primary motor cortex) or isolated damage to the medullary pyramid produces a rather pure corticospinal tract lesion. In these cases, the weakness of distal muscles is severe but there is little appearance of other findings such as spasticity and hyperreflexia that are hallmarks of most UMN lesions. Other UMN lesions also damage indirect descending connections between the cerebral cortex and spinal cord. This happens with lesions of the premotor cortex, corona radiata, internal capsule, cerebral peduncle, basal pons, and lateral columns of the spinal cord. Invariably,

lesions in these areas also involve other cerebrofugal pathways that are intermixed with the direct corticospinal (pyramidal) projection. In all of these cases (in addition to the weakness), there is a decrease in tonic inhibition of reflexes and an increase in resting muscle tone. This is accompanied by hyperactivity of the deep-tendon reflexes and development of what is traditionally called spasticity. Spasticity is elicited during passive manipulation of the muscles. The muscles at rest do not have excessive tone but any brisk stretch of a muscle group (particularly the flexors in the upper extremity and the extensors in the lower extremity) will result in a "catch" at about midlength of the muscle followed by a sudden release of the catch and relaxation of the muscle. The last two components, the catch and release, have been likened to a closing pen knife, which is the origin of the term "clasp-knife" spasticity. Hyperactive deep-tendon reflexes and spasticity have a similar mechanism (overactive muscle stretch reflexes). The giving away or release portion of the clasp-knife phenomenon is presumed to be caused by increased firing of the inhibitory Golgi tendon organs, which produce an overactive reflex to inhibit the muscle. If the lesion extends beyond the confines of the traditional corticospinal path, more descending pathways are involved and a greater degree of spasticity is noted; also there is a poorer recovery from weakness. This is presumably because of loss of more inhibitory influences on the segmental reflex arc and loss of more facilitatory influences on the motor neuron effector systems. After very acute lesions of the descending motor systems there is often initial flacid weakness that is sometimes followed by stereotyped movements and postures (decorticate posture, decerebrate posture or generalized withdrawal reactions)(Fig. 10-1). Acute destructive lesions of the descending motor pathways cause a transient shock state of flaccid, areflexic paralysis. When progressively greater amounts of the descending pathways are involved, a longer period of shock ensues. Acute cortical

destruction may result in only hours to days of shock, whereas acute transection of the spinal cord can cause a shock state that persists for many weeks to months before spastic hyperreflexia and rudimentary spinal reflex behavior return. The precise pathophysiology of spinal shock is not clear, but it may complicate the evaluation of the patient following acute injury. It is always difficult to predict the final extent of the neurological injury in the setting of shock. Chronic or slowly progressive destruction of the descending motor pathways is not associated with a shock state. Presumably this is because compensatory reorganization of the motor function occurs in pace with the losses. Lesions that extensively destroy the cerebral cortex and basal ganglia, and preserve at least some of the diencephalon (like those caused by severe hypoxia) may result in stereotyped motor responses that involve flexion of the upper extremities and extension of the lower extremities. Noxious stimulation is usually necessary to elicit this reflex activity, which has been called decorticate posturing (Fig. 10-1). It has been thought, on the basis of experimental data, that release of the rubrospinal motor system is, at least in part, responsible for decorticate posturing. Transection of the brain stem, for example by stroke, at the level of the midbrain or pons is followed after a period of neuraxis shock by severe spasticity and reflex extension and pronation of the upper extremities with extension of the lower extremities and trunk on noxious stimulation (see Fig. 10-1). This response is called decerebrate posturing and depends on preservation of the vestibular nuclei in the caudal brain stem, with the extension being produced by vestibulospinal pathways. Lesions transecting the lowest portion of the brain stem or the upper spinal cord result in quadriplegia and severe spasticity after a period of shock. In time, reflex flexion movements can be elicited with noxious stimulation (see Fig. 10-1). These probably represent primitive spinal withdrawal responses. As a rule, UMN lesions affect large areas of the body below the level of injury. It is often difficult to

localize the specific level of damage by the pattern of weakness. Associated neurologic findings may clarify the level. For example, cranial nerve involvement or involvement of nerves or nerve roots may indicate a brain stem or spinal cord level of involvement, respectively, while cortical findings such as language difficulties, visual field abnormalities, dyspraxias, or other disorders of higher integrative function suggest cortical damage. In most UMN lesions, the whole side of the body below the lesion is affected (hemiparesis or hemiplegia). However, in the cerebral cortex the motor representation for the arm, face, and trunk lie within the supply of the middle cerebral artery, whereas the leg lies within the distribution of the anterior cerebral artery (Fig. 10-2). Loss of middle cerebral cortical perfusion therefore causes a greater degree of weakness of the upper extremity than of the lower extremity. Occlusion of the anterior cerebral artery, an uncommon event, is associated with greater weakness in the leg than in the arm. Because sensory and motor systems are near one another through the spinal cord, most of the brain stem and the cerebral hemispheres, it is common to have some sensory as well as motor symptoms. The sensory abnormality (see Chapt. 9) may help localize the lesion. Pure involvment of UMNs without any sensory damage is most often seen with small lesions (usually vascular) in the posterior limb of the internal capsule or in the base of the pons.

Basal Ganglia The abnormalities associated with lesions and degenerative processes in the basal ganglia are discussed in some detail in Chapter 18. The findings are generally categorized into "hyperkinesias" and "hypokinesias". The classic picture of parkinsonism (the most common cause being Parkinson disease) includes bradykinesia (slow movements), rigidity, difficulty initiating movements and delayed postural

corrections. These symptoms all fall into the category of "hypokinesia". There may also be a tremor at rest (suppressed by movement), which is a form of hyperkinesia. The rigidity of parkinsonism is present in all ranges of passive manipulation and cannot be abolished by sectioning the dorsal roots. Therefore, it is not due to reflex overactivity (deep tendon reflexes are normal in parkinsonism). It is probably due to tonic overactivity of the descending motor pathways and it can be abolished by cutting descending motor tracts (see Chap. 18). Other types of "hyperkinesia" include chorea, athetosis, hemiballism, tic and dystonia. These are indicative of dysfunction of the basal ganglia (extrapyramidal) system. However, they are not diagnostic of a particular cause (see Chap. 18).

Cerebellum Cerebellar disease produces predominantly motor symptoms. There are three main parts of the cerebellum, which have slightly different functions. The lateral cerebellar hemispheres (the neocerebellum) are involved in controlling distal limb movement of the ipsilateral limbs. The vermis of the cerebellum (midline) is involved in control of axial functions as well as the voice and eye movements. The posteroinferiorly-located vestibulocerebellum (floculonodular lobe; archicerebellum) is involved in vestibular functions and regulation of the vestibulo-ocular reflex (see Chapt. 6). Damage to the neocerebellum produces predominant symptoms of tremor, ataxia, and hypotonia. The tremor is of a particular type, consisting of rhythmic, variably 3-8 per second oscillations that occurs predominantly on voluntary activity and reaches its peak of oscillation toward the end of the movement. It disappears with posturing or at rest. It is noticed dramatically when reaching for objects (such as when performing finger-to-nose testing. The ataxia (incoordination) is manifest in several ways. There is dysmetria (past-pointing) with overshoot and/or undershoot of the target. Also, there may be lack of

checking (excessive rebound). For example, if the patient is asked to hold their hand extended out in front of them while pressure is applied and then suddenly released, there will be excessive movement before the patient "checks" the motion. Additionally, the patient will have difficulty performing a rapidly repeated motions (tapping fingers, patting hands or tapping feet) and this may be even more obvious if there is rapid alternating movements involved in the motion (such as pronation and supination of the hands). Ataxia of the legs is manifest in difficult in walking, often characterized by a broad-based and/or drunken gait. Diosrders affecting the midline cerebellum (vermis) effect axial motor activity. This is likely to be manifest as head and trunk instability as well as speech and eye movement problems. The problems with trunk stability are usually brought out during attempts to stand still or to walk. When there is both instability of the trunk and ataxia of the legs patients will have severe ataxia. After vermal lesions, the speech may sound drunken or inappropriately staccato and eye movements may be erratic and uncoordinated when patients have damage to the vermis. Because it is an important symptom of cerebellar disease, it would be appropriate to say a few more words about ataxia. Cerebellar ataxia is fairly easy to observe in the office and it has at least two origins: (1) intention tremor of the legs, giving a dysmetric gait, and (2) truncal imbalance. If it is advanced, the patient has a wide-based compensatory gait, and if there is lateralized limb involvement, they tend to lean and fall toward the affected side. A sensitive test for ataxia is heel-to-toe tandem walking; this should be part of any neurologic screening examination in a patient with gait or balance complaints because it detects early cerebellar dysfunction. If the trunk alone is involved, as in early alcoholic degeneration or with a tumor of the vermis, there is a tendency to fall to either side, forward or backward. Some persons with midline cerebellar damage may have a stronger tendency to fall

backward. This is called retropulsion and can also be seen in basal ganglia dysfunction (particularly parkinsonism) and in frontal lobe disorders. When retropulsion is due to cerebellar involvement, it frequently has an involuntary tonic character, i.e., the patients actually appear to be actively pushing themselves backward. Even at rest, sitting or standing, there is a tendency to lean or fall backward. With frontal lobe dysfunction and parkinsonism, the retropulsion is usually passive rather than active, i. e., the patient has difficulty recovering from being pushed backward or from a backward-leaning position, but he has no active or forced retropulsion at rest. Damage to the vestibulocerebellum (flocculonodular lobe; archicerebellum) produces vestibular findings, including nystagmus that may be quite severe and in different directions depending on which way the patient is looking ("gaze-shifting nystagmus"). This is often more severe than symptoms due to vestibular damage since vestibulocerebellar damage is more difficult to compensate for. Finally, cerebellar damage can occasionally be reflected in hypotonia. The examiner should check for tone abnormalities by asking the patient to relax and not resist. The limbs are then moved rapidly by the examiner in several ranges. A lack of resistance or a floppiness is noticed with hypotonia. Having the patient sit with his legs swinging free may test the legs. The leg is lifted by the examiner and released. Normally the leg swings back and forth several times and then stops, arrested by inertia and the normal resting muscle tone, which is a manifestation of the sensitivity of the normal muscle stretch reflex. With cerebellar hypotonia, the leg swings freely, unchecked, like a pendulum, arrested mainly by passive limb inertia.

References

●

Brodal, A.: Neurological Anatomy in Relation to Clinical Medicine, ed. 2, New York, Oxford

University Press, 1969. ●

Medical Council of the U.K.: Aids to the Examination of the Peripheral Nervous System, Palo Alto, Calif., Pendragon House, 1978.

●

Monrad-Krohn, G.H., Refsum, S.: The Clinical Examination of the Nervous System, ed. 12, London, H.K. Lewis & Co., 1964.

●

Wolf, J.K.: Segmental Neurology, A Guide to the Examination and Interpretation of Sensory and Motor Function, Baltimore, University Park Press, 1981.

Questions Define the following terms:

spasticity, rigidity, hemiparesis/plegia, bradykinesia, paraparesis/plegia, upper motor neurons, lower motor neurons, internal capsule, chorea, athetosis, dystonia, hemiballism, tic, fasciculation.

10-1. Describe the course of "upper motor neurons". 10-2. Over what functions do the upper motor neurons exert the greatest control (what movements are most effected by damage)? 10-3. Where are sites of potential lesion producing lower motor neurons signs and symptoms? 10-4. What are the features of lower motor neuron damage? 10-5. What is the significance of fasciculations? 10-6. What are the characteristics of peripheral nerve damage? 10-7. What are the characteristics of muscle disease?

10-8. What are the characteristics of basal ganglia disease? 10-9. What are the characteristics of cerebellar disease?

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Chapter 11 - Basic principles in neurologic disease

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Disturbances of the nervous system, both peripheral and central, are manifested in

course and

four basic ways:

1. Ablative or deficiency phenomena associated with destructive (e.g.,

tempo

●

Recovery of function

infarction, tumor, trauma) and depressing processes (e.g., anesthesia). 2. Irritative phenomena as represented by seizures and the pins-and-needles

Disease

●

Reference

or burning paresthesias of peripheral neuropathy, both of which represent excessive neuronal firing secondary to pathologic depolarization. 3. Release phenomena as represented by the hyperactive reflexes and spasticity of corticospinal system involvement, the tremor of Parkinson's disease, the excessive emotional responses following bilateral corticobulbar system loss, sedative withdrawal hyperactivity and the appearances of primitive responses in dementing illnesses (with generalized cerebral cortical degeneration). 4. Compensation phenomena. These may be appropriate or inappropriate compensations. For example, appropriate compensation would include visual-motor compensation for the nystagmus and vertigo of vestibular disease; circumduction of the paretic leg on walking to avoid tripping; a high-stepping gait to avoid tripping with a foot drop; or a broad-based gait to compensate for ataxia. Inappropriate compensations would include tendon contractures, for example.

Combinations of these disturbances are the rule. The person who has cerebral infarction is hemiparetic, develops spasticity, may develop seizures early or late, and compensates for hemiparesis appropriately with a circumducting gait. If physical rehabilitation is not carried out, s/he can develop a functionally inappropriate flexion contracture of the arm.

Disease course and tempo (Fig. 11-1) Momentum of disease is another phenomenon that should be considered. This refers essentially to the rate of involvement of the nervous system. An acute destructive lesion (e.g., infarction) causes an early maximal deficit, whereas a chronic, slowly progressive lesion (e.g., tumor) usually produces considerably less deficit because of compensating mechanisms (such as mechanical adjustment, redundancy of function in other regions) that parallel the destructive forces. For example, we have seen a slow-growing meningioma compressing the frontal lobes reach the size of a lemon over at least 25 years and cause no clear-cut neurologic deficit; the patient was admitted to the hospital for onset of seizures. Malignant glial tumors (glioblastoma) frequently infiltrate neuronal tissue and many neurons lying within the tumor continue to function; this is one reason for the surprisingly small deficit occasionally associated with very large tumors despite their typically rapid growth. It is not surprising, therefore, that removal of these tumors almost invariably leaves the patient with greater neurologic deficits because many functioning neurons are lost. Degenerative processes typically produce slow progression while other conditions (such as multiple sclerosis) can appear as exacerbations or flare-ups. Conditions that produce recurrent injury to the brain (such as repeated strokes) appear as a stepwise progressive dysfunction.

Recovery of function Recuperation of function following the removal of lesions of the nervous system takes three basic forms: resolution, reorganization and compensation. Resolution of the lesion (as seen by the clearing of edema, ischemia, hemorrhage or tumor compression of tissue, and metabolic suppression of neurons, for example, drugs, uremia, hypoxia, etc.) is the main mechanism of recovery in adults and older children with major dysfunction. Reorganization as derived from redundancy and/or multipotentiality of function in the remaining normal neurons is an important mode of recuperation following minor destructive lesions. For example, there is significant resolution of symptoms and recovery of normal function after lesions that damage one vestibular nerve. In young children (five years or younger) this can be the major mode of recuperation following destructive lesions. In adults and older children plasticity or multipotentiality of neuronal function is less able to aid in compensation, whereas in young children it can be very marked for certain major functions. For example, damage to the left hemisphere that would be expected to leave an adult with permanent and severe dysphasia can be well compensated by development of speech in the right hemisphere in young children. Additionally, residual hemiparesis in children following large hemispheric lesion is less than that seen in adults. Redundancy assumes multifocal localization of function. Although it is not the major source of recuperation following large lesions, it is the reason for the lack of dysfunction in some capabilities. For example, well-imprinted memories of past events are very resistant to hemispheric lesions because they are diffusely represented in both cerebral cortices. Compensation is the process of using unaffected neuronal systems to replace the functions of damaged ones. This occurs depending on the degree of damage and the particular system affected. This also depends on conscious awareness of a deficit, which can be a problem in patients with parietal lobe

(particularly nondominant) lesions. Compensation might include using an unaffected limb to replace the function of one that is impaired. It also may include training to check the region of a visual field deficit. Some compensation may be enhanced artificially. For example, prisms can be used to correct double vision or to expand visual field. Various devices have been developed to allow patients with deficits to perform certain functions that would otherwise be impossible.

Reference

●

Monrad-Krohn, G.H. and Refsum, S.: The Clinical Examination of the Nervous System, ed. 12, London, H.K. Lewis & Co., 1964.

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Chapter 12 - Neuromuscular system disorders

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The nervous system can be considered a reflex arc designed for analyzing the

Anatomical neuromuscular

environment through sensation and then modifying the environment through

units

movement. The neuromuscular component of the nervous system is made up of ●

the first and the last components of this reflex. It consists of the first sensory

Functional neuromuscular

element and the last motor element. Table 12-1 lists the parts of this peripheral

units

apparatus. ●

Nerve anatomy

The neuromuscular system has a relatively simple design and a e physiology, and action

and therefore its clinical expression can be limited. From the type and the potentials

distribution of these manifestations, it is possible to achieve a diagnosis and to ●

Diseases of nerves

do the following: ❍

1. Confirm that such manifestations arise in the sensory unit or the motor unit (PNS) as opposed to in the CNS.

neuropathy

❍

2. Determine which part of the system is affected. For example is the weakness caused by defect of nerve fiber, neuromuscular junction (NMJ), or muscle fibers). 3. In the case of nerve fiber disease, it is possible to determine the level of the lesion along the nerves or roots.

Peripheral

Axonal disease

❍

Effects of disease on nerve conduction

4. In disease of the peripheral nerves the type of injury either to myelin or

❍

axons can be determined.

nerve injury on muscle

The specific Neuromuscular diagnosis is made by history, examination and ❍

supported by laboratory studies, neurophysiology and in selected cases muscle

●

Neuromuscular junction disorders

function and clinical manifestations.

❍

Anatomy and Physiology of Peripheral Nerve Fibers ❍

sensory and motor nerve fibers (axons) which pass through nerve roots, plexi

origin in receptive elements that may be in the skin, muscles, joints, bones or even the internal organs. They typically have cell bodies located in the dorsal

Myastheinia gravis

There are several components of the peripheral nervous system. These include

and the peripheral nerves, themselves. Sensory nerve fibers (axons) have their

Myelin disorders

and nerve biopsises and genetic testing. What follows is an integrated picture relating normal and abnormal structure,

Effects of

Myasthenic syndrome

●

Muscle diseases

●

References

●

Questions

root ganglia located close to the spinal cord. Somatic motor nerve fibers (axons) arise from motor neurons in the ventral horn of the spinal cord. These nerve fibers terminate on muscle fibers at the neuromuscular junction or on muscle spindles (setting the sensitivity to muscle stretch). Autonomic motor nerve fibers terminate on glands, organs or smooth muscle fibers. These are unique since there are typically 2 neurons in a sequence (with the postganglionic neuron located in a ganglion). The peripheral nerves not only include the nerve fibers but also several layers of connective tissue (endoneurium, perineurium and epineurium) and blood vessels. Nerve fibers have a high metabolic demand and little reserve of energy stores. Therefore, circulation is

critical for moment-to-moment supply of oxygen and metabolic substrates. Peripheral nerves receive collateral arterial branches from adjacent arteries which anastamose with other arteries entering the nerve, above and below. There is usually sufficient collateral circulation to survive damage to one of the feeding arteries. Individual nerve fibers consist of axons that may be myelinated or unmyelinated. Myelin in the peripheral nervous system derives from Schwann cells, which adhere to nerve cell membranes and create multiple layers or wrapping of the membrane. These are fused layers of Schwann cell membrane, comprising an electrically insulating lipid-rich layer around the nerve fibers. In between these Schwann cells are the nodes of Ranvier, a short segment of the nerve fiber devoid of myelin. At these nodes there is a high density of voltage-gated Na ion channels that facilitate membrane depolarization. The role of myelin is to increase the velocity of nerve conduction with speed being proportional to the distances between adjacent nodes of Ranvier. The use speed of large myelinated fibers is 40-70 meters/ second. The function of nerve fibers can, to some extent, be deduced from the velocity of conduction (see Table 12-2). Most somatic motor axons are large, heavily myelinated fibers. This is also true of the sensory nerve fibers innervating muscle spindle (stretch) and Golgi tendon organ (tension) receptors. Intermediate size fibers convey touch and proprioception , joint position sense. Lightly myelinated fibers convey sharp pain sensation and autonomic preganglionic motor function. Pathologic processes that primarily affect myelin tend to effect functions mediated by the most heavily myelinated nerve fibers and would also profoundly affect the speed of nerve conduction. Unmyelinated nerve fibers conduct very slowly by a continuous mode of propagation of electrical signal (non-saltatory). These fibers convey aching, burning pain and temperature sensation and also include the sympathetic, postganglionic motor nerves. Their speed is approximately 1 meter/second.

Nerves are protected from pressure by connective tissue padding and they are also protected from traction by the connective tissue. Nerve roots are less protected because there is less connective tissue. In order to accurately diagnose disorders affecting peripheral nerves it is important to recall the anatomical distribution of sensory fibers in the nerve roots (Fig. 9-2) and peripheral nerves (Fig. 9-3). Nerve roots have nearly complete overlap, so there is limited sensory loss (usually distally, where there is less overlap) with damage to a single nerve root. Peripheral nerve injuries usually produce more sensory loss. It is important to note that there is significant variability in the precise borders of the peripheral nerve distribution of although the general pattern is quite consistent. It is also important to understand the motor innervation of certain major nerve roots and peripheral nerves (Table 10-5). There may be weakness of shoulder abductors and external rotators with C5 nerve root lesions, weakness of elbow flexors with C6 nerve root lesions, possible weakness of wrist and finger extension with C7 nerve root lesions and some weakness of intrinsic hand muscles with C8 and T1 lesions. In the lower extremity, there may be some weakness of knee extension with L3 or L4 lesions, some difficulty with great toe (and, to a lesser extent, ankle) extension with L5 lesions and weakness of great toe plantar flexion with S1 nerve root damage. It is critical for the survival of nerve fibers that they be able to maintain a stable resting membrane potential by sustaining ion gradients across the axonal membrane. This requires normal integrity of the membrane constituents (lipid layers, membrane proteins and ion channels). It also requires energy, which the neuron uses to create the ion gradients and for transport, moving constituents from the cell body down the axon, and back to the cell body. All of this requires high blood flow to the nerve. Diminished blood flow (ischemia) is poorly tolerated by nerves. Axonal transport is critical to the function of the peripheral nerve. All protein constituents of the nerve

are synthesized in the neuronal cell body. Microtubules within the axon perform the transport function and may extend over distances that can exceed a meter in the longest nerve fibers. Therefore, all structural proteins as well as enzymes that function in the nerve terminal come from the cell body. Even structural components, such as the mitochondria in the nerve terminal, are transported down the axon. There is a class of protein compounds (trophic factors) that travel orthodromically to the periphery or antidromically to the cell body. These factors are critical to the health of the innerved tissues. Additionally, there are trophic factors released by the peripheral tissues, taken up by nerve terminals and transported in a retrograde manner back to the nerve cell bodies. Loss of these trophic factors can result in either the death of neurons or atrophy of peripheral tissues. This is the reason why a muscle whose innervating axon is sectioned undergoes atrophy much more quickly and severely than one where the axon is intact, as in demyelination with conduction block... In both cases, there is complete weakness of the muscle, although only in the former case are trophic factors lost. It is important to note that nerves receive innervation by way of the nervi nervorum. Most of these nerve fibers are either sensory or motor (from the sympathetic nervous system). The density of this innervation is not uniform and varies with the particular nerve in question as well as with the location along the nerve. These fibers may be responsible for some pain with nerve injury.

Motor Units The motor unit is also a physiologic unit. Normally contraction of striated muscle is not possible except through firing of motor neurons that are activated through descending pathways and also through reflex connections. The muscle fibers in a motor unit respond in an all-or-none fashion to excitation by the motor neuron

(both to natural excitation and artificial stimulation, for example, to electric nerve stimulation). The nervous impulse reaches all the muscle fibers in a unit almost at the same time. The result is a brisk twitch. The electric counterpart of this muscle discharge is a motor unit potential. It can be recorded with a needle electrode inserted into the muscle. It is the composite of the summated action potentials of many single muscle fibers. Its amplitude roughly expresses the numbers of muscle fibers activated. Its duration represents the range of terminal conduction times to those activated muscle fibers (temporal dispersion). Repeated activation of the same motor unit produces nearly identical motor unit potentials each time because the times for nerve impulse arrival and neuromuscular transmission are quite constant for any given nerve branch, and because all muscle fibers in the motor unit respond every time. What is the behavior of motor units in effort? At rest there is normally no motor unit activity. With increasing effort, tension increases by, (1) increasing the firing rates of individual units and by, (2) recruiting more units into the effort. These are recruited such that, with full effort, the electrical activity of individual motor units can no longer be recognized. Irritation of motor neurons or motor axons can result in spontaneous discharge of individual motor axons and contraction of the motor unit. These can be seen on the skin surface as random, involuntary twitches that are termed fasciculations. While these are often normal (due to temporary irritation of motor nerve fibers) persistent fasciculations, especially in a muscle that is showing weakness or atrophy, indicates damage to the anterior horn cell or its axons. Muscle fibers that have been denervated for days to weeks become hyperirritable (to the point where they are spontaneously active). The spontaneous contraction of individual muscle fibers is termed a fibrillation but it is not visible from the skin surface. Needle electromyography can detect fibrillations,

which are fairly reliable signs of damage to motor nerve fibers but which may also be seen in muscles diseases (especially those that damage the distal motor axons). Central nervous system disease makes it impossible to achieve high firing rates of the motor units. Conditions that damage some motor units (sparing others) usually result in high firing rates of individual motor units because of the decreased number of units which must maintain the muscular effort.. Weakness with a high firing rate indicates a loss of motor neurons or motor axons.

Composition of Nerves and Nerve Action Potentials Most nerves contain a mixture of myelinated and unmyelinated fibers distributed in three well-defined sizes of populations: large myelinated fibers, small myelinated fibers, and many small unmyelinated fibers. Normally, the largest-diameter fibers conduct the fastest, and fibers of similar diameter conduct at similar velocity. Therefore, following simultaneous stimulation of all fibers in a nerve, the action potentials of individual nerve fibers summate in time, giving rise to compound nerve action potentials (NAP). In the clinic, NAP's are recorded routinely, but we can only record the NAP corresponding to large myelinated fibers. In the clinic we can measure nerve conduction velocity (see this discussion of electrodiagnosis for further explanation).

Disease The following discussion will consider the three basic types of neuromuscular disorders, i.e., damage to the peripheral nerves (including myelin), damage to muscle (myopathy) or damage to the neuromuscular junction.

Peripheral nerve damage (peripheral neuropathy) Peripheral neuropathy generally appears in one of three patterns that can be distinguished clinically. These include involvement of one isolated nerve or root (mononeuropathy), several isolated nerves (mononeuropathy multiplex), or peripheral nerves diffusely (polyneuropathy). In each of these patterns, the primary disorder in each case may involve the neuron (or its neurite) or the Schwann cell. The etiologies of the three patterns of presentation are rather distinct and, therefore, recognition of the pattern is clinically important. The particular nerve or nerves that are affected can be determined by the symptoms. Symptoms may be "positive" (including pain and dysesthesia), may be negative (including loss of sensation, weakness or loss of reflexes), or may be irritative (such as fasciculations or paresthesias).

Mononeuropathy Mononeuropathy and radiculopathy is most often traumatic. This may be acute (such as wounds or blows to the nerve) or chronic (by chronic pressure in vulnerable sites). The neuropathy in these cases is recognized by the distribution of symptoms. Also, nerves that are in the process of trying to recover from damage can have a Tinel's sign at the site of this process. This is an "electrical" type of sensation in the distal distribution of the irritated nerve elicted by tapping the nerve at this site. For example in carpal tunnel syndrome the Tinel’s sign is present at the wrist.. Both negative (loss of sensation, weakness, atrophy) and positive (paresthesia, pain) may be present in mononeuropathy. Anything that damages peripheral nerves in general (see the section on polyneuropathy) promotes entrapment neuropathy by lowering the resistance of the nerve to damage.

The most common of the mononeuropathies is carpal tunnel syndrome (CTS), which is a condition of chronic damage to the median nerve at the wrist. Anything that compromises the volume of the carpal tunnel (congenitally small carpal tunnel; thickening of the ligaments; disruption or swelling of the joint; inflammation of the synovium) can promote CTS. A controversial subject is how much occupational activities (such as typing) contribute to symptoms. The symptoms of CTS include decreased sensation in the radial digits (sparing the palm) along with potential dysesthesias provoked by wrist position (including at night). There may be weakness in thumb abduction and opposition (often with some clumsiness) and atrophy. Pain is common, but is less predictable and the distribution may be well beyond the distribution of the median nerve, especially the wrist and even up the forearm to the elbow or even the shoulder. Other common nerve entrapments in the upper extremity include the ulnar nerve at the elbow. Damage can be due to bone and joint problems at the elbow but is also promoted by chronic pressure on the elbow and full elbow flexion. Weakness and atrophy of the intrinsic hand muscles is common. There may be sensory loss over the small digits and the ulnar side of the hand on the palmar and dorsal side. Damage to the ulnar nerve can occur at the wrist, usually due to chronic pressure (such as hand position in bicycle riding, for example). In this case, any sensory symptoms would be minimal. The radial nerve may be damaged by lesions (such as fractures) of the humerus, since the radial nerve has a course in close proximity to the humeral shaft. It is also somewhat prone to trauma at the lateral elbow. When the main part of the radial nerve is injured, there is weakenss of wrist extension (wrist drop) and diminished sensation on the dorsum of the hand (not to the finger tips). The radial nerve divides into a superficial (cutaneous) branch and a deep (muscular) branch at the elbow. The superficial branch can be damaged by trauma or direct pressure over the distal radius (e.g., handcuffs), producing

sensory loss and dysesthesia/paresthesia on the dorsum of the hand. The deep branch can be compressed in the tunnel that it makes through and under the supinator muscle. This can weaken many of the extensors (such as for the fingers) while sparing the brachioradialis muscle and the extensors of the radial side of the wrist. Thoracic outlet syndrome is actually a heterogeneous group of disorders that include obstructions to the lower brachial plexus or axillary vessels in the areas of the thoracic outlet (the region around the first rib and the scalene muscles that attach to it). Sometimes there is a cervical rib or band of connective tissue connecting from the cervical spine to the first rib. There are other areas of vascular compression between the clavicle and the upper ribs. Sustained depression of the shoulders, abduction and external rotation of the arm or rotation of the neck can provoke symptoms. If these maneuvers reproduce the patients complaints, some consideration should be given to possible TOS. If TOS affects nerves, the symptoms should be in the distribution of the ulnar nerve (that arises from the lower brachial plexus). However, there are likely to be symptoms in the ulnar aspect of the forearm as well. In the lower extremity, the most common entrapments neuropathies include damage to the lateral femoral nerve, the fibular (peroneal) nerve, the posterior tibial nerve and the interdigital nerves. The lateral femoral cutaneous nerve can be entrapped where it goes under the lateral part of the inguinal ligament. It can result from weight gain, tight belts or pregnancy and produces decreased sensation and dysesthesia in the lateral thigh. Fibular (peroneal) nerve damage usually occurs at the fibular head due to direct trauma or pressure. This may produce "numbness" on the dorsum of the foot and weakness of foot and toe dorsiflexion and eversion. Inversion should be unaffected. tibial nerve entrapment at the medial aspect of the ankle has been termed "tarsal tunnel syndrome". This is rare, occurring after severe ankle trauama or with connective tissue disorders such as rheumatoid arthritis. Interdigital

neuromas are common and result from pinching the common digital nerves between metatarsal heads. This results in paresthesia and dysesthesia on the sides of adjacent toes (particularly after walking).

Radiculopathy Radiculopathy indicates damage to nerve root(s). This occurs with several spinal diseases. In younger individuals this is usually due to intervertebral disc herniation. In older individuals, this is more often due to degenerative changes in the disc, bones and joints, which results in thickening of the tissues. Thinning of the discs can result in narrowing of intervertebral foramina, which can also result in nerve compression. These problems tend to occur in the lower lumbar region and the mid- to lower cervical area (which are the levels of the most commonly damage nerve roots). Nerve root entrapment most often occurs in the cervical and lumbar areas, but should be considered when symptoms follow a well-defined nerve root distribution and whenever distal symptoms are coupled with pain in the back or neck. The symptoms often include pain projected along the distribution of the nerve root along with provocation when the nerve root is stretched (such as by straight leg raising or lateral flexion of the neck) or pinched (such as by arching the back or compression of the neck). Coughing, sneezing and straining also often worsen symptoms. There may also be a more constant, deeper, aching pain ("like a toothache") although this is less specific and can result from many painful processes. There is usually not much sensory loss because of overlap of nerve roots although there are a few areas of the distal limbs (called "autonomous zones") where there is little overlap between roots (see Table 123). Other signs of radiculopathy include weakness (of a "lower motor neuron" type) and reflex loss. The most common symptoms of radiculopathy are noted in Table 12-3.

Polyneuropathy Polyneuropathy is a common condition. It is not always easy to determine it’s cause.. In this condition the longest peripheral nerve fibers are usually first. Peripheral neuropathy can affect either the axon, or myelin sheaths (demyelinating), or both. This syndrome is usually symmetrical. Patients with polyneuropathy are more susceptible to compression neuropathy. Since the nerves to the lower limbs are the longest they are the most dependent on a good supply of metabolic substrates, and also have the greatest exposure to toxins or conditions damaging myelin. Therefore, symptoms and signs are most prominent in the feet. Loss of sensation ("numbness") is the most common finding but paresthesias or dysesthesias (prickling, tingling, burning, etc) are also common. When large diameter nerve fibers are affected vibration and joint position sense are impaired. Many patients with large-fiber damage in the feet complain about balance trouble (and have Romberg sign). Such patients may have difficulty walking in the dark or on irregular surfaces because of proprioceptive problems with the feet. Polyneuropathy may also result in distal weakness and atrophy if there is actual loss of motor axons. Ankle jerk reflexes are most often lost. Small nerve fibers can be affected first (with decreased sensitivity to pain and temperature). Such patients often injure themselves without awareness (which can result in tissue loss, including amputation). In around 2/3 of cases of polyneuropathy has an identifiable cause. The most common single cause is diabetes mellitus, which can damage axons as well as myelin. High alcohol intake can result in peripheral nerve damage but this is most likely due to nutritional deficiencies. Especially B vitamins can be associated with peripheral neuropathy.). In the United States, the most common deficiency is in

vitamin B12 (secondary to poor absorption of Vitamin B12). Usually B-12 deficiency causes more of a myelopathic picture then a polyneuropathy. Paradoxically, excesses of pyridoxine can also result in a polyneuropathy. Toxins such as heavy metals, certain organic solvents and industrial exposures (such as carbon disulfide) may result in peripheral neuropathy. Usually there is some history of significant exposure although testing may be necessary. A variety of medications, especially some chemotherapeutic agents and some drugs used to treat seizures or HIV infection (HAART therapy), can be neurotoxic. Certain systemic inflammatory conditions such as systemic lupus erythymatosis, Sjogren’s Syndrome, Wegner’s, and polyarteritis nodosa are associated with neuropthy but most of the time it is in the pattern of mononeuropathy multiplex (see below). Certain chronic infectious conditions such as tertiary syphilis, Lyme disease and HIV) may result in polyneuropathy and should be evaluated in the appropriate clinical setting; although again the pattern may be a pattern of mononeuropathy multiplex. Leprosy causes a patchy sensory neuropathy; which can result in mutilation of the patient’s digits.. There are some other metabolic conditions that can cause neuropathy, including severe sprue and porphyria. Abnormal proteins in the blood may result in deposition a polyneuropathy associated with monoclonal gammopathies or amyloid. A special note should be made of immune demyelinating conditions that can present either acutely or chronically. The acute form is termed Guillain-Barre syndrome or AIDP (acute demyelinating polyradiculoneuropathy). It is markedly different then the other causes of neuropathy in its rapid course and severe weakness produced by demyelination. It is critical to recognize this condition since it can progress rapidly to respiratory paralysis and life-threatening autonomic instability. A chronic, immune mediated neuropathy may result in relapsing or progressive polyneuropathy with most commonly asymmetric weakness and sensory loss. This condition is associated with high cerebrospinal

fluid protein levels; it is called chronic inflammatory demyelinating polyradiculoneuropathy - CIDP. Because both of these conditions (AIDP and CIDP) are demyelinating, affecting the largest nerves, reflexes are lost early in the condition. Both AIDP and CIDP can be treated with immune modulating therapies. Finally, there are a large number of peripheral neuropathies that may be familial. Some of these have very clear pattern of inheritance, such as Charcot-Marie-Tooth Disease or hereditary motor sensory neuropathy (HMSN). Sometimes the hereditary peripheral neuropathies may not have a clear pattern of inheritance. It is always necessary to examine many of the patient's relatives in order to make a diagnosis. EMG/NCS are performed to characterize the peripheral neuropathy in the patient. It may also be performed on relatives to gain more information. Most familial neuropathies do not have a rapidly progressive course. Weakness is usually prominent and there may be marked sensory loss. In HMSN pain was thought to be rare but this may not be the case. Finally genetic testing may be done to help with confirmation of the diagnosis. In HMSN type I the demyelinative form testing is most useful. It is available bit less helpful in the axonal forms HMSN II. Many patients (at least 25 maybe as high as 40% with polyneuropathy have no identifiable cause of their condition. Therefore, it is often somewhat difficult to determine how much investigation is required. Most patients with idiopathic neuropathy have relatively mild sensory symptoms and are older. Additionally, their symptoms are generally quite slowly progressive. Therefore, when a patient is identified with polyneuropathy, initial consideration must be given to the identifiable causes listed above, recognizing that the findings may be negative. These patients do require a good history of the timing of symptoms and of possible risk factors and exposures to medications and toxins. NCS/EMG are routinely done to confirm diagnosis and to characterize the peripheral neuropathy. If symptoms are acute, then urgent consideration must be given to inflammatory conditions (such as Guillain-Barre),

severe metabolic abnormalities or to toxic exposures. Most patients with polyneuropathy should have certain basic metabolic tests performed, including a CBC, glucose level, HgbA1C, TSH, serum protein electrophoresis, and sedimentation rate. In selected cases, an RPR, HIV, Lyme titer, ANA, rheumatoid factor, antineutrophil cytoplasmic antibody titer, and screen for heavy metals and porphyrins may be indicated. If these tests are negative, a follow-up examination after a number of months (or sooner if symptoms suggest rapid progression) is imperative. In younger patients and those with acute or subacute progression, specialty referral for more sophisticated testing such as sural nerve biopsy or skin biopsy looking for unmyelinated fiber loss is necessary. Some investigators feel that abnormal glucose tolerance in the absence of diabetes can cause a painful small fiber neuropathy. Any hope of arresting the polyneuropathy requires an identification of the cause. In some cases, removing the causative agent will improve the polyneuropathy . Patients who have lost sensitivity to pain are at risk of damaging their feet (resulting in ulcers or Charcot joints). Particular attention must be given to proper footwear and foot mechanics. Significant proprioceptive loss produces instability, especially when walking on irregular surfaces or when vision is obscured. These individuals will typically have a Romberg sign that improves dramatically when touching stationary object with one finger. These patients improve with use of a cane.

Mononeuritis Multiplex "Mononeuritis multiplex" is a relatively rare presentation of certain disorders that damage nerves primarily by interfering with blood flow to nerves or plexi or due to an autoimmune process damaging either the myelin or axon.. This results in an unpredictable and patchy nerve damage. If this is produced by interruption of circulation, the symptoms can occur

abruptly. The most common cause of mononeuritis multiplex is diabetes mellitus. This may occur along with or independent of diabetic polyneuropathy. Other potential causes of mononeuritis multiplex include any condition that results in systemic vasculitis (such as the autoimmune conditions like systemic lupus erythematosis or polyarteritis nodosa) or infectious vasculitis (such as with Lyme disease). If the etiology of the condition is not clear, specialty evaluation is necessary since a cause should be identified that will likely have treatment implications. Other potential causes of mononeuritis multiplex include any condition that results in systemic vasculitis (such as the autoimmune conditions like systemic lupus erythematosis or polyarteritis nodosa) or infectious vasculitis (such as with Lyme disease). If the etiology of the condition is not clear, specialty evaluation is necessary since a cause should be identified that will likely have treatment implications. In diabetes, an inflammatory disorder of the lumbar plexus or rarely the brachial plexus can occur. This is heralded by severe pain in the hip or shoulder with prominent weakness of the ilipsosas, thigh adductors, and quadriceps muscles; when the lumbosacral plexus is affected. Usually the patient has poor control of their diabetes and systemic symptoms such as weight loss and fatigue. The diagnosis is aided by NCS/EMG. Treatment is focused on control of diabetes and the judicious use of IVIG or IV pulse steroids (with very careful monitoring of blood glucose levels). This usually affects the femoral nerve, with prominent weakness of the quadriceps muscle and loss of patellar reflex (termed diabetic amyotrophy). The condition typically shows slow and variable recovery over months. There are rare idiopathic cases of mononeurities multiplex that are particularly common in the brachial plexus distribution. This is most common in middle-aged men and has been termed neuralgic

amyotrophy (also known as idiopathic brachial neuralgia or Parsonage-Turner syndrome) due to the fact that it is usually painful at the outset, with subsequent appearance of atrophy and weakness. The typical course is very slow improvement. In this condition early judicious use of IVIG and pulse IV steroids may be helpful. There are more minor and quite focal varieties of this syndrome, which can complicate diagnosis.

End-plate (neuromuscular junction) With few exceptions each muscle fiber has one (and only one) end-plate; this is the plug for a nerve terminal branch. It was thought initially that end-plates were electric synapses, that the electric nerve impulse propagated directly from nerve to muscle. Instead there is anatomical discontinuity, a neuromuscular (N-M) cleft, which is a chemical synapse. There is also a chemical transmitter, acetylcholine. Therefore, some time is wasted in N-M transmission (N-M delay). It was discovered that at rest there are normally intermittent discharges at the end-plate region of fairly constant amplitude and duration (miniature end-plate potentials). These are not capable of triggering muscle action potentials. Subsequently, electron microscopists discovered the synaptic vesicles which contain acetylcholine (ACh). It was known that ACh is capable of depolarizing the postsynaptic membrane and, in view of the regular size of such synaptic vesicles and the morphologic evidence that vesicles may open to the synaptic cleft, it became obvious that each miniature end-plate potential is the result of spontaneous emptying of a fairly constant number (quantum) of molecules of ACh from a vesicle. Acetylcholinesterase in the end-plate destroys the ACh molecule and the fragments are recycled. Anticholinesterase drugs facilitate the depolarizing effect of ACh, but excess ACh eventually may block neuromuscular transmission (i.e., cholinergic block).

Arrival of a nervous impulse at the presynaptic terminal causes release of many quanta, and this is normally sufficient to fire an end-plate potential, which spreads at 4 m/second along the whole muscle fiber membrane as the muscle fiber action potential. From the membrane the potential propagates into the depth of the muscle fiber to trigger myofilaments to slide and shorten the fiber. The neuromuscular junction is vulnerable at many points to pharmacologic agents. There are many examples of N-M block caused by toxins such as botulinum and curare but the most common disorder is myasthenia gravis.

Myasthenia gravis.

In myasthenia gravis there is a reduction in the size of the miniature end-plate potentials caused by a decrease in the number of ACh receptors on the postsynaptic side. Its consequence is a reduced safety factor for neuromuscular transmission; successful conduction of a nerve impulse is not followed by efficient transmission to a muscle fiber. There are degrees of neuromuscular block (as there are of nerve conduction block). The mildest form consists of only increased N-M delay in some junctions of motor units. In severe forms, many endplates are blocked, but the functional state of a given end-plate varies with time and use. During highfrequency activations (as in exercise) more end-plates fail to activate the muscle due to insufficient release of acetylcholine. So, in myasthenia gravis motor units contract without their full number of muscle fibers; sometimes all contract, sometimes a few, and sometimes none. A cardinal feature of myasthenia gravis is that repetition makes things worse in the end-plate. This explains why weakness fluctuates in connection with exercise and rest, that is, fatigability. A routine electrophysiologic test that demonstrates this phenomenon is repetitive nerve stimulation and

recording of the amplitude of the compound muscle action potential (summation of all muscle fiber potentials from all excitable motor units in the muscle). Normally there is little variation in successive firings. In myasthenia gravis there may be an abnormal decrement due to N-M block (or fatigue). This may be followed by post-tetanic facilitation (Fig. 12-2). Acetylcholine or cholinergic substances or anticholinesterases improve this N-M transmission defect (before leading to cholinergic block). However, myasthenia gravis is more than just a functional endplate disorder. It may lead to muscle fiber atrophy and fixed weakness. Indeed, often there is evidence of neurogenic atrophy of muscle and also selective type II fiber atrophy. The thymus gland and immune mechanisms (autoimmunity against ACh receptor) have a great deal to do with myasthenia gravis, although their exact roles are not totally clear. In practice, thymectomy, corticosteroids, immunosuppressive drugs, human immunoglobulin and removal of antibodies by plasma exchange may be useful in treatment.

Myasthenic syndrome.

There is another interesting and uncommon disorder of neuromuscular transmission -- the myasthenic syndrome or Lambert Eaton Syndrome (LEMS). It may be associated with carcinoma. LEMS may improve after removal of the tumor (usually bronchogenic small-cell carcinoma). The defect in neuromuscular transmission is caused by reduced numbers of quanta released from nerve terminals in response to a nerve impulse. This is due to defective calcium channel function in the presynaptic membrane. It causes weakness that tends to improve with exercise; repetitive stimulation causes facilitation rather than the fatigue seen with myasthenia gravis (see Fig. 12-2). The defect can be demonstrated also in vitro in nerve/muscle biopsies from other patients. Acetylcholine-releasing agents

such as 4-aminopyridine may help correct the transmission defect. Another well-known and fortunately rare disorder of transmitter-release blockade is botulism.

Muscle

There are many things that can go wrong in muscles; failure to propagate a muscle action potential to invade the T-system, failure of electromechanical coupling, failure in the physical mechanism of sliding filaments and failure of the normal energy production mechanisms. In recent years there has been an overwhelming number of "new" muscle diseases based on very specific failures in the system. However, most of these conditions present in a rather stereotyped method and clarification of the precise etiology may require very elaborate procedures. We will discuss a practical approach to the recognition of muscle disease, while electron microscopic, metabolic and genetic testing may be required for precise diagnosis.. Recognition of a myopathy usually begins with recognition of a symmetrical, proximal muscle weakness, although cramping of muscles (particularly with exercise) or, in rare cases, symmetrical aching discomfort in muscles may be the initial findings (especially in inflammatory myopathies). Muscle enzymes (particularly CK levels), may be helpful in clarifying that there is actual muscle disease and electromyography can establish that the disorder lies in muscle as opposed to the neuron or nerve fiber. On EMG examination the motor unit action potentials are small, brief and polyphasic (myopathic) (see Fig. 12-1). Muscle biopsy may help confirm and classify the myopathy but special staining of the muscle biopsy and genetic testing may be necessary. Unfortunately, few muscle diseases are effectively treated.

The following is a very oversimplified but practical review. Two major groups of muscle disease can be distinguished. The first group includes disorders of muscle that cause destruction of muscle fibers, leading to (usually progressive) muscle weakness and wasting. The second main group includes diseases that cause more of a functional defect than structural fiber degeneration (little wasting). Most of these are "channelopathies" that cause altered muscle function without a lot of fiber death. Within each of these groups of conditions, there are subtypes that we will briefly discuss. Diseases that actually progressively destroy muscle fibers, themselves, fall into three main types: the dystrophies, the metabolic myopathies and the inflammatory myopathies.

1. Muscular dystrophies: These conditions are genetically determined, not effectively curable, and progressive. The types of muscular dystrophy are usually classified according to inheritance and distribution of weakness. The earliest (and most devastating) is Duchenne dystrophy. This is an X-linked disorder due to mutation of the gene for a normal protein (inappropriately named "dystrophin") that attaches the contractile elements to the muscle membrane. Early in life, another protein performs this function, so symptoms usually don't start until after the child is standing and beginning to walk. The child experiences a progressive decline in muscle strength (wheelchair in late childhood and usually death from cardiac involvement in the early 20s). A less severe mutation in the same gene causes a somewhat later onset condition (Becker dystrophy). There are other dystrophies (most with onset in late childhood or early adolescence) including: facioscapulohumoral dystrophy, limb girdle dystrophy and oculopharyngeal dystrophy. Each of these has its own hereditary pattern. The names describe the predominant muscle groups involved. Myotonic dystrophy is unique in that it tends to affect distal muscles and causes

noticeable myotonia. It is more severe in children of affected mothers and the severity of symptoms is based on the number of repeats found in a specific part of the genome. 2. Metabolic myopathies: Within this category are acquired and genetic disorders. The prototypical acquired disorder is thyroid disease. Both hyper- and hypothyroidism can result in myopathy due to interference with the normal metabolic activity of muscles. Certain medications and toxins can affect the metabolic machinery of muscles, causing myopathy. There are genetic disorders that interfere with metabolism of carbohydrates or fats, resulting in myopathy and, often, accumulation of intracellular inclusions (usually due to buildup of metabolic products). Some of these conditions result in exercise intolerance, occasionally with myoglobinuria and some result in exercise-induced cramping (due to insufficient energy production needed for muscle relaxation). Some, more poorly defined conditions result in intracellular inclusions seen on electron microscopy (nemaline myopathy, myotubular myopathy). The mitochondrial myopathies are a heterogeneous group of muscle diseases associated with excessive replication of somewhat defective mitochondria. They accumulate in cells. Not surprisingly, muscles are commonly affected (since they are major consumers of energy), but many other areas (including the brain) are also affected. 3. Inflammatory myopathy: There are inflammatory myopathies may be acquired or autoimmune. The acquired inflammations include sarcoidosis and certain infectious conditions (such as trichinosis). The autoimmune myopathies include polymositis and dermatomyositis, as well as inclusion body myositis. The former two may be triggered by underlying neoplasm and may respond to immune suppression. Inclusion body myositis is more insidious and often occurs in older individuals. Unfortunately, this does not usually respond to immunosuppression. The finding of inflammatory cells on biopsy is usually diagnostic and the identification of

inflammatory myopathy is important since most are treatable by immune modulating therapy.

The second main group of disorders affecting muscles includes diseases that cause more of a functional defect than structural fiber degeneration (little wasting). These conditions are ion channelopathies.

1. Myotonic disorders: Myotonic disorders: Here we have congenital myotonia and paramyotonia congenita. In the former condition (due to chloride transport abnormality) the symptoms improve with exercise, while the latter condition (due to sodium channelopathy) worsens with exercise and with cold. Needle insertion into muscles usually easily identifies myotonic potentials. 2. Periodic paralysis: These are thyrotoxic periodic paralysis and familial periodic paralysis (hypo-, hyper-, or normokalemic and Andersen syndrome). These often produce generalized and temporary weakness after large meals or exercise. Diagnosis can be made by provoking the weakness by a glucose load and exercise.

Myotonias and periodic paralyses are rare and are recognized clinically. Electromyography may show typical myotonic discharges. Treatment of symptoms and avoidance of precipitating factors may be helpful in both groups.

References

●

Brooke, M.H.: A Clinician's View of Neuromuscular Diseases. Baltimore, Williams & Wilkins Co., 1977.

●

Dyck, P.J., Thomas, P.K., Lambert, E.H.: Peripheral Neuropathy, Philadelphia, W.B. Saunders

Co., 1975. ●

Engle, E.J., Banker, B.Q.: Myology. New York, McGraw-Hill, 1986.

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Walton J.N.: Disorders of Voluntary Muscle, ed. 4, New York, Churchill Livingston, 1981.

Questions Define the following terms:

neuropathy, myopathy, neuromuscular junction/myoneural disease, "dying back", demyelinative, Wallerian degeneration, epineurium, perineurium, endoneurium, Schwann cells, myelin, entrapment neuropathy, carpal tunnel, lateral femoral cutaneous neuropathy/ meralgia paresthetica, polyneuropathy, Charcot-Marie Tooth, Lambert-Eaton myasthenic syndrome, paraneoplastic syndrome, myasthenia gravis, nerve conduction study, electromyography.

12-1. What modalities are conveyed by large, myelinated nerve fibers? 12-2. What do small-diameter sensory nerve fibers convey. 12-3. What is entrapment neuropathy? 12-4. What are symptoms of polyneuropathy? 12-5. What are the causes of polyneuropathy? 12-6. What are the potential causes of myopathy? 12-7. What are the common symptoms of myopathy? 12-8. What effect do myopathies have on reflexes? 12-9. What additiional test would point to myopathy as a cause of weakness?

12-10. What is the most common neuromuscular/myoneural junction disease? 12-11. Who is most often affected by myasthenia gravis? 12-12. What are the symptoms of myasthenia gravis? 12-13. What blood test may be helpful in diagnosis 12-14. What is the common distribution of symptoms in the body? 12-15. What is the treatment for myasthenia gravis? 12-16. What is Lambert-Eaton myasthenic syndrome? 12-17. What is the function of nerve conduction studies? 12-18. What does electromyography evaluate?

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Disorders of the Nervous system - Reeves & Swenson Table of Contents

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Chapter 13. Epilepsy

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Epilepsy is "an occasional, an excessive and a disorderly discharge of nervous

Generalized seizures

❍

tissue" (John Hughlings Jackson, 1889) induced by any process involving the

Grand mal seizures

cerebral cortex that pathologically increases the likelihood of depolarization ❍

and synchronized firing of groups of neurons. There are many potential

Petit mal seizures

underlying causes including metabolic disorders of nerve cells or virtually ●

Partial seizures

any disorder that damages cortical tissue including trauma, hemorrhage, ❍

Simple partial

ischemia, anoxia, infection, or hyperthermia, as well as the presence of scar seizures

tissue relating to prior injury. ❍

Simple motor

All neurons in the nervous system are capable of excessive firing when seizures

damaged; however, the threshold for this abnormality varies considerably in ❍

Simple

different areas. The cerebral cortex is the only area from which epileptiform somatosensory

activity arises with any frequency. Not all areas of the cerebral cortex have seizures

the same tendency to epileptic activity: most of the neocortex is relatively ❍

resistant, while the temporal lobes and frontal lobes (particularly the limbic

seizures

areas) are highly susceptible. Electrodes applied to the scalp (the electroencephalogram; EEG) are often

❍

Simple visual seizures

able to detect abnormal activity of a seizure. The excessive electroencephalographic discharge recorded can be useful in localizing the

Simple auditory

❍

Simple olfactory

seizures

source of the seizure activity and occasionally by its pattern can delineate the type of seizure disorder. It is unusual to have the opportunity to record an

●

Complex partial seizures

EEG during the actual clinical seizure. However, up to 2/3 of patients have abnormal electrical discharges that can be recorded between clinical events.

●

Status epilepticus

A normal EEG in a person suspected of having epilepsy does not rule out the

●

Therapy

possibility since inter-seizure (interictal) electric activity is frequently normal.

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References

It is important to note the distinction between seizures and "epilepsy" (often

●

Questions

called a "seizure disorder"). A seizure is an event. All human cerebral cortices have the potential to generate seizures given enough of a stimulus. In fact, nearly 10 percent of people will have one at some time in their life. However, the term epilepsy implies an abnormally heightened tendency to have seizures such that the person is likely to have them in the course of normal life from time-to-time. This can range from one a decade to many in a day. There are several types of seizures. Broadly, they can be divided into primary generalized seizures and focal onset (localization-related) seizures. In primary generalized seizures, the seizure involves all of the cerebral cortex simultaneously. In focal onset seizures, it involves a localized cluster of neurons having epileptiform activity. Table 13-1 presents a simplified functional-anatomical categorization of seizure types. It is not exhaustive but it does give the spectrum of major seizure categories. While most seizures present with motor correlates, some can present with mainly inhibitory phenomena. The blank, staring episodes of petit mal, the common childhood seizure disorder, are a good example. Seizures are not only recognized by the activity during the main portion of the seizure but also by phenomena that lead up to the clinical seizure (often termed an "aura"), and the condition of the patient after the event (the "post-ictal" state).

Seizures of Generalized Onset

Grand mal (generalized motor) Generalized seizures involve abnormal electrical activity in all of the cerebral cortex simultaneously. Therefore, it is presumed that the triggers and signals for these seizures are arising outside of the cortex (reticular formation of the upper brain stem or thalamus). In any event, some signal recruits all of the cerebral cortex to depolarize synchronously and, therefore, results in sudden loss of consciousness and massive synchronous motor activity. This is manifested initially by tonic contraction of all muscles of the body. The individual assumes a rigid extended posture due to extensor muscles overpowering the flexors. Respiration is arrested and air is expelled from the lungs through a closed glottis (resulting in a guttural "cry"). This is followed in seconds (up to one minute) by synchronous intermittent contraction and relaxation (clonic activity) of the limbs and trunk, and then complete relaxation as the electrical seizure dies (Fig. 13-1). The clonic phase and the postictal phase probably result from massive activation of inhibitory neurons in the brain. Usually the seizure is exhausted within several minutes but rarely may continue for hours or days as "status epilepticus". Autonomic motor overflow frequently occurs simultaneously, manifested clinically by emptying of the bladder and, less often, the bowel. The pupils are large during the ictal phase and blood pressure and pulse are erratic (usually elevated), A variable postseizure (postictal) period of depressed consciousness and confusion ensues. The length of this period probably depends on the length of the seizure and to some degree the general health of the brain. For example, it is likely to be much longer in the elderly and in those with a background of diffuse brain dysfunction.

"Spike-wave" electric activity is seen 0n the EEG during the clonic phase of generalize-motor seizures. The spike, which represents massive and synchronous depolarization, manifests itself clinically as the clonic, flexion motor jerk followed by a phase of relaxation, which electrically is seen as the wave, massive inhibition. Grand mal seizures were considered the most prevalent type of adult seizure until recently when it was realized that many seizure types were being overlooked. Many patients with localization-related (focal) epilepsy have the event culminate in what has been termed a "secondarily generalized seizure". This secondary generalization either occurs through activation of the upper brain stem or by direct corticocortical spread through the commissures (corpus callosum, hippocampal commissure or anterior commissure). Clues to the fact that this seizure is not a primary generalized seizure may be found either in a premonitory "aura" (usually visceral or emotional symptoms leading up to the seizure) or reports from observers of unusual motor events (such as blinking, twitching, sniffing, picking at the clothes or lip smacking) immediately prior to losing consciousness. These symptoms are the result of electrical activity in the focal area prior to generalization. Most individuals with primary generalized epilepsy begin with seizures in childhood and they are often the result of abnormal sensitivity of neurons (some conditions have clear abnormalities in ion channels and a definite inheritance). However, these are relatively rare conditions. On the other hand many metabolically induced seizures may well fit the grand mal category. Ionic abnormalities (Na, K, Ca, Mg, BUN, pH, etc.), sedative withdrawal in addicts (alcohol, barbiturates, benzodiazepines), hypoglycemia, hypoxia, and hyperthermia (especially in children), are the major metabolic categories. There are some uncommon toxins that can also generate seizures. Remember, seizures of this type do not necessarily indicate epilepsy unless there is an abnormal tendency to have seizures without the severe metabolic

insult.

Petit mal (absence) These are generally seizures of childhood that are thought also to originate in the upper brain stem. Clinically, patients show many short episodes (a few seconds) of blank staring (absence) for which the patient has no memory. The EEG is highly specific (showing 3 per second spike/wave activity that can almost always be brought on by hyperventilation) (Fig. 13-2). The pathophysiology of absence is not certain. This pattern of spike and wave activity may be a nonspecific response of the immature cortex to a seizure focus in any cortical location. Some evidence for this is observed in long-term follow-up of children with petit mal seizures. A significant proportion goes on to develop focal seizures, particularly those of limbic (frontal or temporal) origin. Presumably the limbic cortical focus spreads its abnormal and excessive discharges centrally to the reticular formation, where they are generalized to the remainder of the hemispheres as recorded on EEG. Some reflection of this suspected focal onset in many cases of petit mal epilepsy is the presence of eye movements, eyelid flickering, chewing movements, and salivation - positive phenomena in an otherwise negative or inhibitory seizure. These are probably behavioral manifestations of limbic or other focal cortical discharge. You might ask why the petit mal seizure is predominantly a negative (absence) phenomenon when there appears to be diffuse hemisphere electrical synchronization. Several reasons for this are suggested, and one of these is reflected in the spike-wave electroencephalographic pattern. The spike represents diffuse hemispheric depolarization excitation, whereas the wave is considered to represent diffuse hemispheric inhibition (hyperpolarization). This postexcitatory inhibition is presumably adequate to prevent

positive behavioral manifestations (e.g., convulsions) from being initiated by the massive depolarization. Another reason for lack of positive manifestation is that the immature motor cortex of children may be more resistant to excitatory recruitment. Children with petit mal usually maintain their posture during the short (seconds) absence attacks. This is presumed to be because the seizure activity does not spread to involve more resistant brain stem postural mechanisms. Approximately one third to one half of children with petit mal epilepsy have spontaneous remission from their seizures later in childhood or during adolescence. Neuronal maturation presumably increases the capability of the hemisphere for spontaneously inhibiting excessive synchronous activity. Of the remaining children who continue to have seizures one group has generalized motor seizures with no evidence of focal onset. The remainder, who have persistent epilepsy, develop seizures of clinical focal character, more often limbic, with or without secondary spread to diffuse hemispheric synchronization associated with generalized motor clinical manifestation.

Seizures of Focal Nature (Partial Seizures) With or Without Secondary Spread to Generalized Motor Manifestation Partial (focal) seizures begin in a particular part of the cerebral cortex. They are categorized by their initial manifestations and whether they result in a secondary generalized convulsion. The initial manifestations of these seizures is based on the function of the tissue in which the epileptiform activity begins. These seizures have either a rather simple presentation if the cortex in which they begin has a well-defined sensory or motor function. When this involves sensory cortex there is usually a positive phenomenon (i.e., a presence of the sensation) rather than initial loss of sensation. For example, paresthesias, flashing lights or smells may be perceived if the postcentral gyrus, calcarine cortex or

uncus regions are involved in the seizure activity. If the primary motor cortex is involved, local tonic and/or clonic motor phenomena may be seen. So-called "complex partial seizures" involve the association cortices of the frontal, temporal or parietal lobes. These are characterized by more complicated emotions, feelings or perceptions, along with a "clouding of consciousness". The patient is not fully in tune with their environment and responds to internal cues. Memory for the event is usually partial, at best. A good history of the symptoms right at the onset of the seizure may give important clues as to the origin. If the seizure is not contained by normal inhibitory processes in the brain, it can spread to involve both hemispheres via the corpus callosum and/or the reticular formation of the mesodiencephalon and a generalized motor clinical seizure results. This may be tonic, tonic-clonic or just clonic in nature and is termed a "secondarily generalized seizure".

Simple partial seizures (elementary or primary cortex involved)

Motor cortex

Seizures arising in or adjacent to the motor cortex appear simply as clonic jerking of the motor structures (muscle groups) innervated by the cortex involved (on the contralateral side). If the seizure spreads from the focus, the clinical seizure progresses to involve contiguous areas of the body (Fig. 133). The progression appears as a march of activity over the body (and over the cortex; Jacksonian march) from the upper extremity to the face, trunk, and lower limb. As with any partial seizure, it may subsequently generalize either via the corpus callosum or the rostral brain stem.

Somatosensory cortex

Seizures arising in the somatosensory cortex produce paresthesia on the contralateral side that can spread (in a manner similar to the "march" of motor symptoms) over the body. After the focal seizure there may be diminished sensations in the region. The patient with rapid onset of transient sensory symptoms can represent a particular diagnostic difficulty. The differential diagnostic possibilities for this presentation include transient ischemic attacks (TIA), migraine transient dysfunction, and simple partial seizures of a sensory sensory type. There are some factors that would favor a diagnosis of TIA. Older age, clinically evident cervical vessel stenotic disease, lack of a "march" (see above), previous history of cerebrovascular disease, changes in the retinal blood vessels (e.g., residual cholesterol emboli) and additional involvement of motor systems would all suggest episodes of TIA (see, Chap. 19). Migraine would be suspected if the sensory symptoms were followed by headache, usually unilateral (see Chap. 21). However, it must be kept in mind that headache may be a rare manifestation of seizure (usually during the postictal period), and may also be seen with transient ischemic attacks on occasion. It is helpful to note that the sensory symptoms of migraine spread ("march") over the body in a period of minutes, while those of seizure usually march over seconds. On the other hand, symptoms of transient ischemia appear suddenly. Of course, if the focal seizure is followed by a secondarily generalized seizure, the diagnosis of seizure disorder is almost assured. It is very rare that transient ischemia initiates a focal seizure.

Auditory-vestibular

Auditory-vestibular cortex involvement appears as a hallucination of sound (tinnitus) and vertigo with or without generalization. This may be mistaken for inner ear disease (such as Meniere syndrome) if a

generalized convulsion does not occur. Audiometric tests are very useful and will almost always show abnormality in Meniere syndrome but not in simple partial seizures. Of course, an EEG may be helpful by showing focal abnormality in the posterior temporal region. However, the EEG is frequently normal between seizures.

Visual cortex

Visual cortex involvement is manifested as hallucinations in the contralateral visual field. Foci in the primary visual cortex (calcarine cortex) appear as unformed flashes, spots, and zig-zags of light, colored or white, whereas foci in the visual association cortex cause more formed hallucinations such as floating balloons, stars, and polygons. Yet more anterior in the visual association areas (in posterior temporal or parietal lobes) more complex sensory hallucinations may occur (e.g., people talking, occasionally described as something like a flashback).

Olfactory-gustatory cortex

Focal seizures arising in the olfactory cortex (near the uncus of the rostral medial temporal lobe) foci may give rise to hallucinations of smell and taste, most often described as acrid and unpleasant. Spread to adjacent cortex is common, and complex partial seizure results.

Complex partial seizures Complex focal (partial) seizures result from partial seizures beginning in the frontal, temporal or (less often) parietal association cortex. These manifest with behavioral, visceral and affective (emotional) phenomena. The limbic cortex has the lowest cortical threshold for initiating and sustaining seizure

activity. Additionally, the limbic cortex, which includes the hippocampus, parahippocampal temporal cortex, retro-splenial-cingulate-subcallosal cortex, orbito-frontal cortex, and insula - is the cortex most susceptible to metabolic injury. This is particularly true of the hippocampus. It is not surprising then that complex partial epilepsy is quite common - probably the most common form of seizure disorder. If this seizure does not generalize rapidly, it can remain as a partial seizure for a prolonged period. The visceral and affective (psychomotor) components of the seizure dominate the clinical picture. Simple and/or complex visceral, sensory and emotional phenomena dominate the picture. There may be peculiar and unpleasant smells and tastes, bizarre abdominal sensations, fear, anxiety, rarely rage, and excessive sexual appetite. These may be combined with some visceral and behavioral phenomena such as sniffing, chewing, lip smacking, salivation, excessive bowel sounds, belching, penile erection, feeding, running, rarely rage, and sexual behavior. Rarely, a seizure completely isolates the limbic system from the neocortex and reticular formation, which continue to function normally. The patient may carry out complex functions (e.g., drive a car), and because the memory functions of the hippocampus are not functioning normally, they may have no idea of what transpired. This type of behavior, associated with amnesia, is more often caused by transient ischemia, head trauma or migraine phenomena involving the hippocampal regions than by seizure activity. You may wonder why focal cortical seizures do not all generalize and why focal epileptiform activity seen on the EEG is not always manifested as a clinical seizure. It appears that this results from collateral inhibition that is present in normal brain to prevent just such excessive excitation. Of course, this can be overcome if the region of brain that is involved is too great, if inhibition is exhausted or if the excitatory activity overwhelms the inhibition.

Continuous Seizures (Status epilepticus and Epilepsia Partialis Continua) Generalized and focal seizures may on occasion become continuous with very little or no interictal period. The usual definition is continuous or recurrent seizures over a 30-minute period without return to normal over the period. Presumably, in status, the normal brain inhibitory mechanisms for terminating seizures are not sufficient to stop the activity. Circumstances that predispose to status epilepticus are similar to those that result in recurrence of single or multiple seizures in individuals who are otherwise medically or physiologically well controlled. An example is acute termination of anticonvulsant medication, which results in temporarily heightened seizure susceptibility. This appears to result in rebound hyperexcitability similar to that seen in patients who are dependent on sedative medications or alcohol. Although withdrawal of medication is the most common cause of status epilepticus, any circumstance that increases central nervous system excitability may lead to seizure recurrence or less commonly status epilepticus. Emotional excess (e.g., fright or anger), fever, or other hypermetabolic states, hypoglycemia, hypocalcemia, hypomagnesemia, hypoxemia, and toxic states (e.g., tetanus, uremia, exogenous, excitatory agents such as amphetamine, aminophyline, lidocaine, penicillin) are a few examples. Continuous generalized motor seizures (status epilepticus) are a medical emergency. If they are not terminated, the chance of dying is very high and many survivors are left with brain damage. The massive muscle activity of the seizures leads to hyperthermia with temperatures as high as 106 degrees Fahrenheit or more, which if sustained, causes irreversible damage to neurons. Hypoxia from inadequate pulmonary ventilation also causes brain damage. Severe lactic acidosis from shock and tissue hypoxia, amplified by excessive muscle activity, probably contributes to neuron deterioration. Death usually is not from brain dysfunction directly, but from overtaxation of cardiopulmonary reserve

by the combination of massive continuous exercise, hypoxia, lactic acidosis, shock, and possibly also hyperthermia. Additionally, massive autonomic activity can result in severe blood pressure changes and arrhythmia. Though somewhat controversial, it is possible that brain damage can also be caused by continued seizure activity alone. Therefore, even the person who is paralyzed by a neuromuscular blocking agent (curariform drug), intubated and mechanically ventilated, and whose blood pressure and temperature are controlled within normal range needs to have their seizure activity terminated as soon as possible. Continuous partial (focal) seizure activity (epilepsia partialis continua) is less life threatening but may, if prolonged, lead to focal neuronal damage. Its tendency to generalize into major motor status epilepticus also makes it important to terminate the seizures as soon as possible. The etiologic factors are similar to those initiating seizure recurrence and status epilepticus. Occasionally epilepsia partialis continua is the presenting manifestation of a seizure focus. This is most common in adults, and neoplasm or ischemia-infarction of the brain is the most frequent cause followed by less common causes such as stimulant toxicity and hyperglycemia.

Therapy Initial treatment of epilepsy is based on medical suppression of the excitable focus. Much has been learned about the pharmacologic effects of antiepileptic drugs, but their exact modes of action remain unclear. Seizures that are symptomatic of systemic or localized central nervous system metabolic disorders, such as infection, disorders of fluid and electrolyte balance, exogenous and endogenous toxicities, and renal failure, are best treated by ameliorating the underlying condition, if possible, and the concomitant use

of anticonvulsant medications where indicated. Some anticonvulsant drugs suppress neuronal membrane excitability, probably by hyperpolarization, which possibly reflects a decreased intracellular sodium or calcium concentration. Some appear to depress excitatory synaptic transmission or increase inhibitory neurotransmission. Many anticonvulsants affect the activity of ion channels (particularly fast sodium channels) that are important in seizure generation and propagation. All these mechanisms could increase neuronal resistance to excessive discharge or protect normal neurons from recruitment by neighboring excessive discharge. An ideal anticonvulsant decreases abnormal excitability, has a minimal sedating effect, and is free of other significant and deleterious side effects. No medication achieves these goals. Fortunately, phenytoin, carbamazepine, valproic acid and phenobarbital, mainstays of epilepsy therapy, approach these criteria while a host of newer agents (e.g., gabapentin, lamotrigine, topiramate, etc.) may have fewer side effects and be at least as effective for some seizure types. Some drugs have effectiveness against only one seizure type (ethosuximide for absence seizures) while most have a variable effect on generalized versus partial seizures. A special case is the emergent treatment of status epilepticus, where is it an urgent matter to stop the seizure in the minimum amount of time, using parenteral medications even at the expense of sedation. In this situation, intravenous benzodiazepines (such as diazepam or lorazepam), phenytoin and phenobarbital are the drugs of choice. Of course, intubation and even general anesthesia may be necessary while exploring the reason for the status epilepticus. Medical therapy is successful in decreasing seizures in almost 80% of epileptics. 50% have their seizures reduced to a negligible level. Approximately 30% gain complete arrest of their seizures. If one anticonvulsant is not successful, a second it attempted. If two have been tried unsuccessfully, the

likelihood of successful medical control of seizures declines substantially (even if multiple anticonvulsants are used simultaneously). If medical therapy does not adequately control the seizures, surgical removal or isolation of the seizure focus can be considered. The focus must be localized by imaging and/or electrodiagnostic study, and, if localized, must be surgically approachable. The most common operations carried out today are temporal lobectomy and, less often, local corticectomy. Surgical isolation of seizure foci in one hemisphere by corpus callosum section is successful in some resistant cases; the major aim of this type of surgery is to decrease the seizure generalization. Seizures that spread via the brain stem would be unlikely to be affected by corpus callosum section. Fortunately, this appears to be a more resistant and less common path of generalization. Of course, if seizures are symptomatic of a treatable medical condition, that condition must be addressed, where possible. Approximately 10% of persons with focal epilepsy have a tumor, for example. The older the patient, the more likely that seizures are to be the result of tumor or scarring from prior cerebrovascular disease. This agrees with the age-incidence spectrum of neoplasm and stroke. Therefore, patients with clearly focal seizures merit more extensive neurologic evaluation, including magnetic resonance imaging (see Chap. 23). MRI is preferred to CT scanning since it provides a much better view of the inferior frontal lobes and the anteromedial temporal lobes that are often obscured by bone in the CT scan. It is preferred that the imaging be performed without and then with contrast media due to the fact that some small tumors may be overlooked unless their tendency to enhance with contrast is recognized.

References

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Gastaut, H. Broughton, R.: Epileptic Seizures. Springfield, IL, Charles C. Thomas, Publisher. 1972.

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Laidlaw, J., Richens, A.: A Textbook of Epilepsy. Edinburgh, Churchill and Livingston. 1976.

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Schmidt, R.P., Wilder, B.J.: Epilepsy. Philadelphia, F.A. Davis Co., 1968.

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Sutherland, J.M., Eadie, M.J.: The Epilepsies. London, Churchill Livingstone, 1980.

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Woodbury, D.M., Penry, J.K., Pippenger, C.E. (Eds): Antiepileptic Drugs. 2nd Ed., New York, Raven Press, 1982.

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Reeves, A.G.: Epilepsy and the Corpus Callosum. New York, Plenum Press, 1995.

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Engel, J.: Surgical Treatment of Epilepsy. New York, Raven Press, 1987.

Questions Define the following terms:

epilepsy, primary generalized seizure, complex partial seizure, myoclonic seizure, petit mal seizure, simple partial seizure, focal seizure, secondary generalization, status epilepticus, postictal period, interictal, Todd's paralysis, hippocampal sclerosis, temporal lobe epilepsy, seizure focus.

13-1. What is epilepsy? 13-2. What are primarily generalized seizures? 13-3. What are potential causes of primary generalized seizures? 13-4. Does epilepsy last a lifetime? 13-5. What is the usual description of a generalized seizure? 13-6. What is a petit mal (absence) seizure?

13-7. What is a myoclonic seizure? 13-8. What are partial seizures? 13-9. What is a simple partial seizure? 13-10. What is a complex partial seizure? 13-11. What are common auras of complex partial seizures arising in the temporal lobes? 13-12. What is secondary generalization? 13-13. What is status epilepticus? 13-14. What are common causes of status epilepticus? 13-15. Why is status epilepticus an emergency? 13-16. What can be done in order to evaluate epilepsy? 13-17. What are "non-epileptic" seizures? 13-18. What are the available therapies for epilepsy?

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Disorders of the Nervous system - Reeves & Swenson Table of Contents

Chapter 14 - Demyelinating diseases of the nervous system Introduction

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Introduction

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Guillain-Barre syndrome

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Chronic inflammatory

This group of diseases (see Table 14-1) is characterized by lesions that are

demyelinating

associated with loss of myelin with relative sparing of axons. There are

polyradiculoneuropathy

many type of disease that damage myelin in concert with the destruction

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of axons. However, these conditions are not considered "demyelinating" due to their nonspecific and secondary effects on myelin. Additionally, there are metabolic disorders of myelination characterized by the

Multiple sclerosis

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Clinical features

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Diagnosis of MS

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Etiology of MS

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Prognosis of MS

accumulation of abnormal breakdown products. These are considered to be "dysmyelinative" disorders, or leukodystrophies (i.e., metachromatic ●

leukodystrophy, Krabbe's disease) and not demyelinative even though

Allergic diseases of myelin

both conditions tend to strike white matter pathways. ●

References

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Questions

Central nervous system myelin and peripheral nervous system myelin are antigenically different (as befits the fact that CNS myelin derives from oligodendroglia and PNS myelin comes from Schwann cells). Therefore, some demyelinating disorders attack the central nervous system (the prototype is multiple sclerosis), while others affect the peripheral nervous system (the prototype being Guillain-Barre syndrome).

Peripheral Nervous System (PNS)

Guillain-Barre Syndrome There is evidence that the Guillain-Barre Syndrome (GBS) is mediated by immune attack on peripheral nerve myelin. In this condition, peripheral nerves (actually, usually at the level of the proximal nerve roots) show inflammatory infiltrates with cells involved in cell-mediated immunity. Because cell mediated immunity is involved, the condition appears to depend more on local cytokine production than the development of circulating antibodies. Nonetheless, plasmapheresis (which removes significant amounts of circulating antibodies) and human immune globulin infusions (which modulate the immune system by unclear mechanisms) are capable of limiting the acute damage in the condition (these help only if done early in the clinical course). The major pathologic changes, as would be expected with an autoimmune disease) include perivascular inflammatory infiltrate, along with demyelination in the affected nerve roots and nerves. There is usually relatively little damage to underlying axons unless the inflammatory reaction is dramatic. GBS is a dramatic acute demyelinating neuropathy with rapid onset (hours to days). This usually produces weakness of the extremities and axial musculature, which can evolve to respiratory motor failure and asphyxiation if support is not available. Prior to availability of artificial respiratory support, the mortality rate was 60%. Involvement of the autonomic nervous system also may occur indicating an axonal involvement and, indeed, there is a form of GBS in which axonal involvement predominates (particularly in the Orient). Autonomic involvement may lead to threatening blood pressure irregularities and cardiac arrhythmias. This condition often involves the largest sensory nerve fibers as well. Because the largest, most heavily myelinated sensory fibers are the muscle stretch fibers, and since

these fibers and the motor axons are direct parts of the reflex arc, deep tendon reflexes are almost always lost very early in the course of the condition, even in muscles that are not yet clinically weak. As the condition progresses, there can be sensory change, as well (usually numbness and tingling), but the picture is usually dominated by flaccid weakness. Although the most common presentation is with an ascending paralysis, rarely, it can begin by affecting cranial muscles. Diagnosis can be aided by CSF evaluation, which shows high protein levels, with very few actual inflammatory cells (usually not above the upper limit of normal). This has been termed "cytoalbuminologic dissociation" There is an experimental model for this condition (experimental allergic neuritis). A prior, usually upper respiratory, infection with one of a variety of agents was the original reason for implicating an immune mechanism. More recently, it has been recognized that preceding diarrheal illness due to camphylobacter infection can also trigger it. The putative mechanism for the condition is "molecular mimicry" with either the microbe itself or the changes in body cells produced by infectious agents producing an immune reaction that finds similar epitopes expressed on the Schwann cell. Typically, after a period of progression that can last a week or two, the condition stabilizes and then spontaneously improves (with proliferation of the Schwann cells and reconstitution of the myelin sheath). This improvement occurs over weeks to months and many patients, even those who are severely affected, recover completely. The more severe the symptoms and the older the patient, the more likely there is to be residual damage. The more severe the actual damage to underlying axons (as a byproduct of a severe immune attack on the myelin sheath) the more likely there is to be residual. Electromyography is able to determine how much axonal damage there has been.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

This condition is due to a chronic immune attack on the peripheral myelin. It is usually more insidious than Guillain-Barre syndrome and it also responds better to immune modulating treatments. Not only does it get better with plasmapheresis and human immune globulin infusions, but also responds to immunosuppressant medications, including Prednisone. However, in distinction to GBS, the condition relapses off of immunosuppressants and also can have some spontaneous waxing and waning of symptoms. The diagnosis of the condition can be tricky especially at the onset. As with GBS (and for the same reason) it often abolishes reflexes even in clinically unaffected muscles). Also, CSF shows very high protein (often higher than with GBS) with few actual inflammatory cells.

Central Nervous System (CNS)

Multiple sclerosis Multiple sclerosis has been defined as "multiple white matter lesions separated in space and time". The lesions of multiple sclerosis (MS) the lesions are scattered in the white matter, but often clustering near the ventricles. They are variable-sized, well-circumscribed plaques of demyelination. They may occur anywhere within the white matter of the central nervous system. Peripheral nerves are not involved. Lesions of the optic nerves are common (remember that the optic "nerve" is really an extension of the CNS and not a peripheral nerve). The demyelinative lesions are typically associated with perivascular mononuclear cell infiltration, but the pathologic picture, as well as the time course of the illness, differs from that seen in experimental allergic encephalomyelitis (see below). Clinical findings: MS is uncommon in children under the age of ten, and it usually presents before the age of 55. It is slightly more prevalent in women than men. The clinical pattern appears in three

main types: relapsing-remitting multiple sclerosis (RRMS); secondary progressive MS (SPMS); and primary progressive MS (PPMS). The most common of these types is RRMS in which symptoms typically develop subacutely (over hours to days), with subsequent stabilization and gradual improvement over weeks to months. Patients may return to normal or may be left with a residual. Imaging may show new lesions or reactivated lesions (by the presence of contrast enhancement on MR scanning) during the exacerbation, although it is rare that you are able to visualize that actual lesion causing the symptoms. Although the substrate for demyelination is an immune attack on the oligodendroglia (with a block of nerve conduction due to the loss of myelin), presumably the main substrate for remission is the ability of these glia to remyelinate the axons if they are not too severely damaged. There may be some recovery on the basis of compensation as well as the ability of surviving axons to assume the lost functions. Unfortunately, all of these recovery mechanisms have severe limitations and residual dysfunction results from inadequate recovery. As lesions accumulate, remissions are less complete. Eventually there are so many lesions that new ones are not apparent clinically as discrete events. The disease's course is then steadily progressive in the "secondarily progressive" form. Rarely, the disease progresses relentlessly right from the start (with no exacerbations/attacks). This condition may actually be pathophysiologically distinct from RRMS and SPMS since it does not appear to respond to treatments that do affect these patterns of disease. This remains to be clarified. The nature of the deficit depends on the location and size of the demyelinating plaque. Certain locations are especially common. Lesions in the optic nerve produce optic neuritis. If the plaque involves the optic disk, edema is seen on funduscopic examination (optic papillitis); if it involves the nerve behind the disk, there are no acute changes on funduscopic examination (retrobulbar neuritis). In either case,

optic atrophy often develops with time, though it is not apparent before about two weeks after the symptomatic onset. Acute optic neuritis is usually associated with pain on eye movements (due to irritation of the optic nerve), and there is some visual field defect (usually a central or paracentral scotoma). Although 40% of persons with MS have optic neuritis, up to 40% of patients with optic neuritis do not go on to develop MS (some of these may actually have ischemic optic nerve disorders, while others have what has been termed a "clinically isolated syndrome", where symptoms remain in one location). The medial longitudinal fasciculus is a tract that is occasionally involved by demyelinating plaque, producing unilateral or bilateral internuclear ophthalmoplegia (see Chap. 4). During attempted lateral gaze there is paresis of the medial rectus (insufficient adduction) and nystagmus of the abducting eye. However, convergence movement of the medial rectus is usually spared. Internuclear ophthalmoplegia is almost always due to demyelination but it can rarely be seen in persons with vascular disease (especially the elderly) and very rarely results from tumor in the fourth ventricle or other inflammatory condition. Damage to spinal cord pathways (myelopathy) is yet another common presentation. This can include damage to descending motor pathways, producing spastic hemiparesis or damage to sensory tracts (usually the dorsal columns). In the latter case, paresthesias may be very distressing. The cerebellar connections can be affected with incoordination of the limbs, ataxia and dysarthria (scanning speech or "drunken speech). Tic douloureux (trigeminal neuralgia) sometimes occurs and MS must be a consideration in a young patient with trigeminal neuralgia. Lhermitte's symptom, an electric or tingling sensation referred to the trunk and limbs during neck flexion (chin on chest), was first described in association with multiple sclerosis. It is presumed to be caused by stretch of damaged dorsal columns, depolarizing axons (see Chap. 1). Although this can appear with other intrinsic and occasionally

extrinsic spinal cord lesions, it is most commonly seen with multiple sclerosis. The vestibular system may result in imbalance, but usually vertigo (if present) is mild, while nystagmus can be severe and bizzare. Certain nonspecific symptoms are quite common, including fatigue. However, it is important to consider alternative explanations for this before ascribing symptoms to this mechanism. There are some symptoms that rarely occur with MS. For example, hearing is unaffected by MS. Lower motor neurons are very rarely affected (and then only in advanced MS). Aphasia is also quite rare. Patients with MS usually have intact intellect at the beginning, but progressive and severe subcortical hemispheric white matter lesions may result in dementia late in the course. Diagnosis: The diagnosis of MS is strongly suggested when a person in the appropriate age range has evidence of lesions of white matter separated in space and time. There are several conditions that should at least be considered before making the diagnosis. Multiple emboli and vasculitis can result in small infarcts that can appear as white matter damage. Central nervous system sarcoidosis (an idiopathic, steroid-responsive inflammatory condition) can produce reversible optic neuritis and other CNS signs. Whipple disease also has a tendency to result in inflammatory lesions, along with unusual eye movements due to midbrain involvement. Vitamin B12 deficiency is suggested by dementia, spasticity, and posterior column findings. Meningovascular syphilis, a rare but reemerging entity that can give rise to multifocal CNS damage due to multifocal meningeal vascular inflammation. CNS Lyme disease can also produce multifocal disease, probably due to vasculitis. An additional concern is that single lesions (by definition, not MS) can affect several different neurological systems. For example, a patient may have cerebellar ataxia and spastic paraparesis that could both result from a single lesion compressing the rostral spinal cord and the cerebellum at the level of the foramen magnum. Fortunately, magnetic resonance imaging (MRI) (see Chap. 23) is particularly good at detecting such

lesions (although they were difficult to see with older technology, such as the CT scan). On the other hand, if that person also had optic neuritis or hemiparesis involving the face, one lesion could no longer explain the findings. A history of remissions and exacerbations also helps in the diagnosis of MS, but it must be remembered that the symptoms of neoplasms commonly fluctuate to some degree. To evaluate for the potential for other conditions, it would be appropriate to consider several blood tests in the initial evaluation of the patient with suspected MS. These tests include complete blood count (CBC), antinuclear antibodies (ANA), serum test for syphilis (RPR, VDRL, etc.), fluorescent treponemal antibody test (FTA), Lyme titer, ESR and, possibly, angiotensin converting enzyme level (a test for sarcoidosis). Imaging (MRI if at all possible) should be performed to rule out alternative diagnoses and because MRI can provide information about dissemination of disease. Over 90% of patients with MS have abnormalities on the MRI scan. Multifocal white matter disease of MS are easily observed but not easily differentiated from vascular lesions, gliotic scars or other forms of inflammation (see Chap. 23). As yet, there are no entirely pathognomonic criteria for MS on an MRI scan, but McDonald criteria are used in research studies. Spinal fluid examination may show evidence of immunologic activity in the CNS: slight elevation of mononuclear white blood cells (pleocytosis) are often found, and CSF oligoclonal IgG bands and increased globulin to albumin ratio can be found in 90% of cases. There may also be an increase in CSF myelin basic protein levels, which is evidence of actual damage to myelin. Evidence of subclinical demyelinated lesions can be provided by MRI, visual, somatosensory, or brain stem auditory evoked responses. The "hot bath test" is an historically interesting test. A hot bath often amplifies symptoms and worsens deficits by raising body temperature (which slows conduction in demyelinated plaques). Etiology: Autoimmune and infectious mechanisms have received the greatest amount of attention

recently. Genetic susceptibility to MS is suggested by finding certain histocompatibility antigens overrepresented in patients with MS. This appears to convey risk rather than be causative, however. The spinal fluid changes noted above indicate production of immunoglobulins in the CNS. Recent studies have demonstrated reduction in the number of suppressor cells (that normally inhibit immune responses) immediately prior to exacerbations of MS. An infectious etiology has been suggested by the following evidence:

1. The distribution of MS is very non-uniform. Temperate climates have a higher incidence than warm climates, but the disease is uncommon in Japan. In the Orkney and Shetland islands, north of Scotland, the incidence is extremely high: 1 in 300 persons are affected. Not far away, however, in the Faroe Islands, the disease was unknown until British troops arrived during World War II. 2. Epidemiologic studies suggest that MS is often acquired in childhood or adolescence. Moving from a high-risk to a low-risk area after the age of 15 does not appear to reduce one's chances of developing MS. 3. There is an increased incidence of measles antibody titers in persons with MS. 4. However, there have been extensive and, to date, unsuccessful investigations to attempt to detect active infection.

These findings strongly implicate an environmental factor, probably infectious; however, the identity of the factor is presently unknown. Additionally, it appears that whatever triggers the immune reaction that is active during MS does not appear to be present at the time of diagnosis. It is likely that both infectious and immune mechanisms contribute to the pathogenesis of MS. A viral infection may trigger an inappropriate immune response with antibodies to a common virus-myelin antigen.

Prognosis: The course varies from a few months ("acute MS") to more than 50 years, with the average survival after diagnosis being 15 to 20 years. Death is usually from superimposed infection and not due to the effects of the disease itself.

Demyelinating on an allergic basis Experimental allergic encephalomyelitis (EAE) is the model for this group of demyelinative disorders. This is a rare disease, clinically, but it is a commonly used experimental model for investigation of demyelination and illustrates the results of immune attack on neural tissue. EAE develops several days after an animal is inoculated with central nervous system (CNS) myelin basic protein accompanied by Freund's adjuvant. The CNS becomes peppered with lesions consisting of perivenous lymphocytic infiltration and demyelination. These lesions are similar pathologically to these seen in a naturally occurring (rare) human disease, acute disseminated encephalomyelitis (ADEM). This disease may occur following various viral infections or following vaccinations (and hence is also called postinfectious or postvaccinal encephalomyelitis). In some instances, this disease can be shown to relate to hypersensitivity to CNS myelin. Acute hemorrhagic encephalomyelitis is currently thought to be merely a more fulminant variety of ADEM, in which necrosis of vessels leads to superimposed hemorrhage.

Reference

●

McAlpine, D., Lamsden, C.E., Acheson, E.D.: Multiple Sclerosis - A Reappraisal, ed. 2, Edinburgh, Churchill and Livingstone, 1972.

Questions

Define the following terms:

demyelination, Guillain-Barre syndrome, multiple sclerosis, Schwann cell, oligodendrocyte, cytoalbuminologic dissociation.

14-1. What is a good working definition of multiple sclerosis? 14-2. What causes multiple sclerosis? 14-3. Can a patient with a single episode of demyelination be diagnosed with MS? 14-4. What are the patterns of presentation for MS? 14-5. What are common symptoms of MS? 14-6. Are certain portions of the nervous system not affected by MS? 14-7. What supportive tests are there for the diagnosis of MS? 14-8. What other conditions can produce symptoms similar to MS? 14-9. What is Guillain Barre syndrome (acute inflammatory demyelinating polyradiculoneuropathy AIDP)? 14-10. What causes Guillain-Barre syndrome? 14-11. What laboratory findings are supportive of the diagnosis of Guillain-Barre syndrome? 14-12. What is the usual clinical picture for Guillain-Barre syndrome? 14-13. What treatments help in Guillain-Barre syndrome? 14-14. What is chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

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Chapter 15 - Degenerative diseases of the nervous system

On this page ●

Introduction

●

Amyotrophic

Introduction In this chapter we will discuss conditions that have historically been classified as

lateral sclerosis

●

degenerative. These disorders generally are characterized by the loss of neurons

Spinocereballar atrophy

and secondary gliosis (scarring) without evidence of major inflammation or

●

Alzheimer's disease

necrosis of tissue. Many diseases previously classified as degenerative are now

●

Pick's disease

●

Muscular dystrophy

known to be associated with specific metabolic deficiencies or have other definite cause (Table 15-1). Others are transmitted by infectious agents (see

❍

Chap. 22). However, we are still left with a large number of progressive diseases

Duchenne's dystrophy

of unknown etiology, and their classification is based on pathologic and clinical ❍

findings. This is true of many of the disorders of the basal ganglia and the rest of

Limb girdle dystrophy

the extrapyramidal system. However these disorders will be discussed in ❍

Myotonic

chapter 18. As time passes, it is quite likely that the specific biochemical and dystrophy

pathophysiological processes underpinning many of these diseases will be ●

Prion diseases

●

References

elucidated and their classifications will change. In this chapter we discuss the more common of these conditions (designated by asterisks in Tables 15-2). They range from extremely common (Alzheimer disease) to quite rare (the

spinocerebellar degenerations). Many are devastating conditions that often affect people in the prime of life. Certainly these are important to discuss in any course on neurology.

Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS) is one of a number of degenerative conditions that selectively involve the motor system, collectively termed "motor neuron disease". There are two inherited conditions (Werdnig-Hoffmann disease in infants and Kugelberg-Welander disease in children and young adults) that are characterized by anterior horn cell degeneration only. In ALS, which affects mainly adults 40-60 years of age, there is degeneration not only of the anterior horn cells and some of the cranial nerve motor nuclei, but also of the corticobulbar and corticospinal tracts. Clinically, therefore, one sees a combination of lower motor neuron findings (atrophy, and fasciculations) along with upper motor neuron findings (spasticity and hyperactive reflexes). Therefore, although weakness without sensory change is the hallmark, this weakness is of two types and may express quite differently in the arms and in the legs of a single patient. The disease may start asymmetrically, but usually within months it involves many muscle groups on both sides of the body. The average patient survives three years with death resulting from weakness of the bulbar and respiratory musculature and resultant superimposed infection. There are some variants of the condition that selectively involve either upper motor neurons or the lower motor neurons. In primary lateral sclerosis, the upper motor neuron signs predominate, but eventually there is some evidence of lower motor neuron involvement, so that this entity is no longer felt to be distinct from ALS. The course tends to be longer than in the usual variety of ALS, with some persons surviving ten years or longer. There is also a variant that involves only lower motor neurons and one that selectively involves the cranial musculature (termed progressive bulbar palsy). Again, with

time these variants often show signs of evolution to a more typical ALS pattern. Motor neuron disease is a very active field of research. There has been great interest in the possible contribution of environmental toxins to the condition. This has partially been based on identified clusters of ALS and a very clear example of toxin-induced motor neuron disease (ALS-dementia complex of Guam). The finding of certain families of patients with clearly hereditary ALS stimulated research identifying neuronal deficit of the antioxidant superoxide dismutase as a cause. This has lead to research into free-radical destruction of motor neurons. There is also some research suggesting the involvement of inflammatory cytokines in the condition (despite the absence of major inflammation in most cases). Despite these preliminary findings, extensive research has yet to lead to any effective therapy.

Spinocerebellar ataxia (degeneration) Spinocerebellar ataxias (SCAs) large and growing number of rare conditions that share the characteristics of being hereditary, of being progressive and of producing ataxia as a dominant symptom. A full treatment of these conditions is beyond the scope of this text. Friedreich ataxia is by far the most common of these conditions and we will consider it as a prototype of this group of conditions. This disease is an autosomal recessive condition that usually begins in late childhood, but whose onset can be delayed until early adulthood. Several spinal cord pathways are progressively damaged including the dorsal columns and the lateral columns (upper motor neurons) as well as cerebellar pathways. After a reasonably normal early childhood, progressive clumsiness of gait and skeletal deformity (such as scoliosis) is noted, typically with progression to a wheelchair after about 10 years of symptoms. Ultimately, in 1996, this condition was shown to result from a defective gene producing a mitochondrial

protein, frataxin. The other SCAs have different genetic abnormalities (not all of which are known). This leads to iron deposition in the mitochondria and cell damage and patients die from cardiomyopathy, typically 30-40 years after onset of symptoms. This disease has its onset in childhood or adolescence, with ataxia that is due to proprioceptive loss and cerebellar ataxia. There is atrophy of the small muscles of the feet, indicating a peripheral neuropathy. Mild spastic weakness and upgoing toes may be seen later. Severe disability and death usually occur by the third or fourth decades; however, mild forms, or formes frustes, of the disease are not infrequent. Extraneurologic signs include pes cavus, kyphoscoliosis, and cardiomyopathy, which may result in terminal congestive heart failure. The lesions in Friedreich's ataxia involve the dorsal root ganglia, with secondary lesions in the peripheral nerves and dorsal columns. In addition, lesions are present in Clarke's column and in the lateral columns and the cerebellum. Most of the other spinocerebellar ataxias begin in adulthood. The best known of these are the autosomal dominant SCAs, where specific gene and, for many, gene products are known. This list is growing and there are also autosomal recessive SCAs to add to the list but the taxonomy is complicated and evolving as more becomes known about the specific dysfunctional genes. These conditions enter into the differential diagnosis of a slowly progressive neurologic disorder presenting with severe ataxic symptoms.

Alzheimer disease Alzheimer described a presenile dementing illness characterized pathologically by neurofibrillary accumulation in the neurons as well as senile plaques containing substantial amounts of beta amyloid configured proteins. Since the pathologic changes are identical in most cases of old-age dementia

(occurring over the age of 65), we use the term Alzheimer disease to include this common form of dementia, which affects approximately 5-10% of adults over 65 and possibly as many as 40% of individuals over 85. There is early loss of cholinergic neurons in the nucleus basalis (of Meynert) and drugs that inhibit central nervous system acetylcholinesterase (increasing the amount of acetylcholine available in the brain) improve symptoms of the condition modestly. The disease has a familial tendency in some families and is associated with mutations in the beta amyloid gene. Also, risk of Alzheimer disease is higher in individuals with the episolon 4 version of apolipoprotein. This risk is particularly high in individuals who are homozygos for this. The pathologic changes in persons with Alzheimer's disease are most severe in the hippocampi. This is the reason that loss of recent memory (i.e., learning new material) is an early clinical feature. The posterior temporo-parietal association area is often affected early, as well. Therefore, mild anomia (trouble finding nouns) and constructional apraxia are also common early signs. As the illness progresses, more severe cognitive loss and eventually frontal lobe disturbances become prominent, but paresis, sensory loss, or visual field defects are not seen. Despite trouble finding the right words, repetition of even complex phrases is preserved. Alzheimer disease is the most common cause of dementia of age. Older persons with dementia are often diagnosed as having "cerebral arteriosclerosis" when, in fact, they have Alzheimer disease. Vascular dementia does occur in association with Alzheimer's disease but is frequently associated with clear findings indicative of prior strokes (spasticity, paresis, pseudobulbar palsies, aphasia, etc). Amyloid also collects in arterial walls in Alzheimer disease patients and may contribute to a coexisting vascular dementia (amyloid angiopathy). Unfortunately, there is no definitive diagnostic test for Alzheimer disease. Pathologic diagnosis is still

the only way to definitively diagnose the condition. Imaging is insensative (although is often useful to rule out other conditions that can cause dementia). Some functional imaging studies have shown promise at defining abnormalities in function of the temporal and posterior parietal lobes, however this has not been widely applied in clinical practice. Investigators have been looking at certain components in the CSF (particularly tau proteins and beta amyloid) as a possible diagnostic test. However there are still many questions about the utility of these tools. Obviously, methods for definitive diagnosis will be more important if a specific therapy is proven effective. Recent data suggest that accumulation of amyloid deposits in the characteristic Alzheimer's plaques is the active pathology of the disease. There are animal models of the condition that are improved by vaccination against amyloid in an attempt to stimulate the immune system to help clear away amyloid. However, this approach has yet to produced an effective human treatment. Epidemiologic and a few prospective studies suggest that there may be some element of inflammation in the condition and some have suggested excess oxidation as a contributing factor. Despite some limited therapeutic trials, there are no proven methods for arresting the progression of the condition.

Pick's disease Pick's disease (also known as frontotemporal dementia) is a rare condition that can run in families and results in degeneration of the frontal and temporal lobes of the brain. This can be severe in some cases permitting reasonably accurate diagnosis on the basis of imaging. However, most cases are not so easy to diagnose, especially at the onset. This condition tends to present in one of two ways. Firstly, it may present as disordered behavior (usually either with disinhibited behavior or with apathy). The disinhibited behaviors include agitation, socially inappropriate behavior or impulsivity. There is usually

a lack on insight into their condition and a lack of empathy. The second presentation is dominated by language problems, usually accompanied by behavioral problems. Despite these deficits, memory and spatial skills remain intact. Pathology does not show the changes of Alzheimer disease, but rather shows the presence of intraneuronal "Pick bodies". There is no effective therapy for Pick's disease other than, perhaps, psychotropic medications and behavior modification to control the worst of the behavioral issues. This condition tends to be more aggressive than Alzheimer disease, usually resulting in death in 2-10 years.

Muscular dystrophies Collectively, these conditions result in non-inflammatory degeneration of muscles

Duchenne muscular dystrophy This is the most common type and is a sex-linked recessive trait. It affects young boys, in whom pseudohypertrophy of the calves and weakness of the hip and shoulder girdles progress from early childhood. Levels of serum muscle enzymes (CPK and aldolase) are extremely high. The children are usually confined to a wheelchair by the age of 10, and they usually die in the second to third decade. It is due to a mutation in the gene for an inappropirately-named normal protein named dystrophin. A less severe mutation in this same gene is responsible for a somewhat later onset dystophy, Becker dystrophy. No effective therapy is known although steroids may slightly prolong the course.

Limb-girdle muscular dystrophy This is a heterogeneous group of conditions that usually appear in adolescence or adult life with

proximal limb weakness. The weakness usually progresses slowly, but it may arrest spontaneously. There are at least 15 different mutations that contribute to this presentation and some are passed on recessively while others have dominant inheritance.

Facioscapulohumeral muscular dystrophy This condition also can be recessive or dominant and appears to have at least several different genetic abnormalities producing this phenotypically distinct pattern of weakness and wasting. Symptoms usually appear in adolescence or very early adult life with weakness of face muscles and of muscles attached to the scapula and proximal upper limb. The weakness usually progresses slowly and life expectancy is normal. Mental retardation is common and there may be abnormalities of cardiac rhythm.

Myotonic dystrophy In this disease myotonia (delayed relaxation of muscles) is combined with dystrophy (muscle atrophy not secondary to peripheral nerve or anterior horn cell involvement). The disease, which is transmitted as an autosomal dominant condition, usually begins in childhood or young adult life (possibly infancy with maternal transmission). There are cases where it has been unrecognized until advanced ages, however. It is due to repeats in the sequence of the myotonic protein kinase gene. These repeats often get longer in sequential generations, with earlier onset of symptoms. Myotonic dystrophy, as opposed to most forms of myopathy, is distal, affecting the muscles of the hands before more proximal musculature. In addition, facial and neck musculature are involved early. Evidence points to an abnormality of membranes that is not restricted to muscle. Numerous nonneurologic problems are found: frontal balding, testicular atrophy, diabetes, cardiac arrhythmias, and others. It progresses slowly. Many victims succumb to respiratory failure and superimposed infection

by the fifth decade.

Prion diseases of the nervous system These conditions are discussed in Chapter 22 on infectious diseases. The group of diseases caused by abnormal proteins (scrapie, kuru, Creutzfeldt-Jakob disease, bovine spongiform encephalopathy) and the primary pathologic change is neuronal degeneration and reactive gliosis. These conditions are transmissible, but the "infectious agent" in these cases appears to be an abnormal protein rather than a virus, bacteria or parasite. It appears that some cases can be sporadic due to de-novo configurational changes in proteins.

References

●

Walton, J.N.: Disorders of Voluntary Muscle, ed. 3. Edinburgh, Churchill and Livingstone, 1974.

●

Engel, A.G. and Banker, B.Q.: Myology. New York, McGraw-Hill, Inc., 1986.

●

Whitehouse, P.J..: Dementia, Philadelphia, F.A. Davis Co., 1993.

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Chapter 16 - Dementia

On this page ●

Dementia refers to a loss of higher intellectual (cognitive) and emotional function. Studies indicate that up to 20% or more of persons who have

Is the patient demented?

●

Types of dementia

symptoms suggestive of dementia turn out to have treatable illness. About half ❍

Memory loss

❍

Frontal lobe

of them will have psychiatric problems, but the remainder will have treatable organic disease. The proportion of treatable cases is lower the older the

dementia

population and the more chronic the dementia. However, even in this group a ❍

Cortical

significant number of persons may be helped. Dementia is a very common dementia

problem and it may go unrecognized for quite some time. The clinical ❍

Subcortical

importance of this subject can hardly be exaggerated. Over the age of 65, 5-10% dementia

of the population has significant cognitive problems. Over the age of 80 this ●

Confusional states

●

Organic psychosis

●

Evaluation of the

proportion rises to 15-20%, rising to nearly 40% by age 85. The incidence of dementia is fairly steady from 65 on, but the percentage of individuals with dementia climbs steadily with age due to accumulation. Recent data suggests

demented patient

that here is a possible decline in the incidence of dementia after one reaches the ninth decade. The importance of these statistics becomes immense considering

●

hydrocephaly

the generally aging population. There were approximately 20 million over 65 in the late 1980's. By 2030, it is estimated that 60-70 million Americans will be over 65. The socio-economic consequences of having 5-10% of this population

Normal pressure

●

Multi-infarct dementia

demented are staggering particularly given the burden that dementia places on

●

Alcohol

the individual, their families and society.

●

References

●

Questions

Is the Patient Demented? Several problems often arise in trying to decide whether or not a patient is actually demented.

1. Senescence: Mild defects in memory and other higher cortical functions occur normally with age. One may complain of these, but may be able to perform normally on clinical mental status testing and on formal psychological tests that take this normal deterioration into account. This has been described as mild cognitive impairment (MCI) and, although such patients are at increased risk of full-blown dementia, we have yet to develop a foolproof method for determining who will undergo such progression. 2. Mental retardation: Because dementia is defined as a loss of function, the history should be adequate to document that the person was once capable of better performance. Educational and occupational histories are valuable in this regard. The patient should be asked at what age they achieved their highest educational grade, to ascertain whether they progressed normally through school. 3. Psychiatric illness: Mistakes can be made in both directions. Organic illness can mimic many symptoms of psychiatric disease, especially the psychoses; and some psychiatric illness may prevent adequate evaluation of a patient's intellectual functioning. A few rules are useful: ❍

(a) With the exception of depression, the functional psychoses rarely arise after the age of 40. A 50year-old person with their first "schizophrenic break" should therefore be suspected of having organic

disease; ❍

(b) Depression may accompany mild dementia, but contrary to what is commonly stated, depression is not the first sign of the usual form of dementia of old age. In fact, depressed elderly persons with normal mental status do not have an increased incidence of subsequent organic dementia. Furthermore, when dementia is moderately severe, a person cannot sustain a deep depression although they may be querulous and at times sad. Severe depression, therefore, is rarely a symptom of organic disease;

❍

(c) Although loss of recent memory (learning capacity) is not a necessary accompaniment of organic dementia, it is not seen in functional states. If adequate testing can be done, the finding of a definite recent memory deficit strongly militates against a diagnosis of functional disease. The two major exceptions are depressive pseudodementia and malingering. It is rare for the malingering person to mimic convincingly the type of memory loss seen in those with organic disease. The malingerer is more likely to forget everything, including items of remote memory usually retained by truly amnesic persons;

❍

(d) Regressive reflexes (see Chap. 10) are indicative of organic disease; and

❍

(e) Urinary incontinence is rarely seen in adults with functional disease.

❍

(f) Depressive pseudodementia presents a difficult clinical problem. These patients, usually elderly, have decreased activity and speech and deficits in intellectual functioning. Depressive symptoms may not be prominent. When there is doubt and the preliminary medical evaluation for dementia is negative, it is sometimes worthwhile to treat these patients for depression (with drugs or, in some intractable cases, electroconvulsive therapy). Patients with pseudodementia usually respond, and their intellectual functioning returns to normal.

Types of Dementia Dementia is not a unitary condition. Findings differ greatly among patients, reflecting to a large extent, the regions of the brain involved or the nature of the biochemical insult. Localization of hemispheric function was discussed in Chapter 2.

Loss of recent memory Loss of recent memory (as tested by a person's ability to remember three items after five minutes of distraction) in the absence of defects of attention (as tested, for example, by the digit span - the ability to repeat 7 numbers forward and 5 numbers backward) is indicative of bilateral lesions in the hippocampi or related structures (fornices, mamillary bodies, dorsomedial thalamus). A limited number of pathologic states, therefore, underlie this type of problem (Table 16-1). Unilateral damage to the hippocampal and adjacent neocortical regions may cause verbal memory defects if the lesion is in the dominant hemisphere. Difficulties learning visuospatial tasks have been seen in persons with damage or removal of the right temporal lobe. The defects with unilateral disease tend to be mild and patients often improve over time, whereas bilateral hippocampal-temporal lobe damage leaves devastating recent memory problems. Difficulties with remembering ("absent mindedness") are a common complaint over the age of 60 and may represent an age related loss of hippocampal-temporal lobe function. As a rule, this mild and "benign" memory difficulty can be differentiated from pathologic loss of learning capacity. The patient with benign forgetfulness brings him- or herself to see the physician. They can "remember that they cannot remember" (i.e., insight is preserved). The patient with pathological or "malignant" memory loss

is unable as a rule to imprint new memories and has little insight or concern about the problem (unless very mild). The patient is typically brought to the physician by a concerned family member and is found to have general intellectual deficits in addition to memory problems.

Frontal lobe dementia Persons with frontal lobe lesions may have significant dementia with no abnormality of recent memory. Often intellectual function is intact on routine testing, but the patient's behavior is inappropriate, frequently disinhibited (see Chap. 2). Later, tests of manipulation of knowledge (calculations, proverbs, similarities) are poorly done. Regressive reflexes are commonly seen at this stage.

"Cortical" dementia Cognitive functions such as language, praxis (the ability to synthesize and sequence motor tasks), and visuospatial functions can be impaired by diseases that affect the cortex, e.g., stroke, Alzheimer disease, frontotemporal dementia, diffuse Lewy body disease and Creutzfeldt-Jacob disease. Often these diseases affect other aspects of hemispheric function, such as memory (temporal lobe) and motivation (frontal lobes).

Subcortical dementia Dementia can result from diseases that affect mainly subcortical structures. Some clues to this are the presence of severe motor abnormalities, significant difficulties with attention and concentration or improvement of memory with prompting (which usually doesn't happen with cortical disease such as Alzheimer disease). For example, patients with progressive supranuclear palsy (Steele-Richardson-

Olchewsky disease, an uncommon disease affecting the midbrain and other subcortical structures) may show a remarkable slowness in performance; tests are performed well only if the patient is given a great deal of time. Often persons with subcortical disease (such as Parkinson's disease) have dementias that resemble frontal lobe dementias. Some preliminary studies have shown that patients with Parkinson's who have dementia, may have a slowed central reaction time. That is, the time between receiving a command for performance and the motor onset of that performance at the cortical level is delayed even though the performance is ultimately carried out correctly. In some patients with Parkinson disease, however, there is, in fact, diffuse loss of cortical neurons which best explains their more typical diffuse cognitive fall-off. Cortical and subcortical dementias can coexist.

Confusional states Deficits in maintaining attention may markedly reduce intellectual functioning. Many metabolic dementias (such as hepatic encephalopathy, delirium tremens, and cognitive deficits produced by many drugs) are manifested principally by the inability to attend to important stimuli. Lesions affecting the brain stem or thalamic reticular formation, if insufficient to produce stupor or coma, result in an attentional deficit. In general, these are referred to as confusional states or "encephalopathy."

Organic psychoses Diseases affecting the limbic system or related structures may produce a wide variety of psychiatric findings. Persons with temporal lobe epilepsy commonly have behavioral disturbances, with hyposexuality, hyper religiosity, and even paranoid psychosis being described as possible interictal phenomena. Temporal lobe lesions or damage to the medial hypothalamus may trigger aggressive behavior, potentially accompanied by changes in appetite for food and sex. Damage to the left frontal

lobe often produces depression, while the right frontal lobe can trigger mania. Orbital and medial frontal cortex lesions can markedly alter personality, potentially producing apathy on the one hand, or disinhibition (with socially inappropriate behavior) on the other. Persons with Huntington disease may experience episodes that are indistinguishable from acute paranoid schizophrenia or manic-depressive illness. Diffuse Lewy body disease usually results in vivid hallucinations to go along with dementia. Obviously, the distinction between functional and organic disease can be difficult. It is, therefore, important to look for other indications of organic disease in these persons (for example, fever, incontinence, seizures, focal neurologic signs, regressive reflexes, movement disorders) before referring them for psychiatric care.

Evaluation of the Demented Patient After having decided that a person is demented, certain features of the history and examination help determine the subsequent evaluation. The following questions are helpful to keep in mind:

1. Do the mental changes themselves localize the lesions(s)? The important diagnostic points were reviewed earlier in this chapter and in Chapter 2. 2. Are there associated focal neurologic deficits such as hemiparesis, visual field defects, or sensory changes to suggest focal brain injury? 3. Are there neurologic deficits suggestive of systems degeneration, for example, chorea, parkinsonism, or cerebellar abnormalities? These might suggest a particular type of degenerative disease (such as Huntington disease, parkinsonism, or spinocerebellar degeneration), or less often, a metabolic problem (such as Wilson's disease or chronic hepatic encephalopathy).

4. Is there evidence of increased intracranial pressure? 5. Is confusion or inattention a major part of the picture? Certain findings on the neurologic examination strongly suggest a metabolic deficit. A prominent confusional state is one. Multifocal myoclonus and asterixis (see Chap. 24) are others often associated with uremic or hepatic encephalopathy. 6. Are there associated symptoms or signs indicative of a systemic disease, such as a thyroid disorder, Cushing's disease, collagen vascular disease, malignancy, or infection? 7. Is the patient taking medications that can affect mentation (e.g., antihypertensives, sedatives, neuroleptics, antidepressants, anti-convulsants, etc.)? 8. Is the course acute or chronic? Most (but not all) irreversible degenerative diseases are chronic. As mentioned, although the chance of finding a reversible etiology are less with the chronic dementias, remediable causes are found in enough patients to merit a complete evaluation. 9. Are there major fluctuations in performance? While patients with the progressive dementing disorders do have their ups and downs, marked fluctuations in performance suggest the presence of an encephalopathy and increase the chances of finding some treatable factor that will improve performance.

The answers to these general questions determine the sort of evaluation required. If the examination indicates a focal brain lesion, the evaluation should aim to document the lesion (e.g., tumor, stroke, subdural hematoma) and to determine its nature (computerized tomography, magnetic resonance imaging, and if necessary, arteriography). If the examination suggests a metabolic problem (confusion without focal neurologic signs), an intensive search for metabolic derangements should be made before

looking for focal lesions or bilateral degenerative disease. This evaluation includes numerous blood studies and a lumbar puncture (to exclude subarachnoid hemorrhage or infection). In the patient in whom there is no obvious clue to the nature of the underlying disease, the screening evaluation outlined in Table 16-2 as indicated. Most of the treatable causes of dementia (listed in Table 16-3) would be excluded on the basis of this evaluation combined with a careful history and physical examination. Following this evaluation, treatable causes of dementia should have been ruled out; however, there are still a large number of persons for whom a diagnosis has not been made. The vast majority of such patients will have degenerative disease, the most common by far being Alzheimer disease.

Normal-Pressure Hydrocephalus Although there is little question that this entity exists, its exact pathogenesis is disputed, and there is no agreement about how to select patients for treatment. The entity consists of progressive hydrocephalus, with normal CSF pressure (as determined by lumbar puncture), producing gait disorder, and urinary incontinence and, usually later, dementia. The gait disorder is usually a broad-based gait with a tendency to fall backward. These patients tend to slide their feet along the floor(sometimes described as "robotoic", "glue-footed", or "magnetic") rather than picking them up and going through the normal heel-to-toe gait cycle (gait apraxia). The incontinence is also usually somewhat unusual in that it results in the loss of large volumes of urine without any warning. Reducing the hydrocephalus with ventriculoatrial or ventriculoperitoneal shunts improves the clinical picture. However, since this procedure has significant morbidity in the elderly, selection of patients for this procedure is probematic. About half of patients with NPH have a history of subarachnoid hemorrhage, trauma or meningeal infection. In these cases, presumably blood or proteinaceous fluid has blocked the normal flow of CSF. In the rest of cases, no such predisposition is historically apparent. The normal CSF pressure is difficult

to explain. In some patients, the CSF pressure fluctuates; although a single lumbar puncture may show normal pressure, 24-hour monitoring demonstrates abnormally high-pressures some of the time, or persistently high normal pressures. According to Poiseuille's Law, pressure should actually be low in patients with large ventricles. Therefore, it is possible that the pressure it too high for the size of the ventricles. To make the diagnosis, the examiner should be able to document the presence of hydrocephalus, the absence of severe cortical atrophy, and inadequate reabsorption of spinal fluid. Computerized tomography (CT) or magnetic resonance imaging (MRI), will adequately assess ventricular size and cortical atrophy. Two tests are available to assess CSF flow: cisternography and the CSF infusion test. These are described in Chapter 23. Withdrawing 40-50 cc of spinal fluid has been shown to acutely and temporarily improve gait, continence and sometimes mentation in some. Such a finding would confirm the diagnosis and predict a positive response to a permanent shunt. However, these tests are not terribly sensitive and, therefore, there are no absolute guidelines are available for patient selection. The appearance of the patient (i.e., a typical picture of gait apraxia, incontinence and mild dementia), the tempo of the illness, the history of predisposing causes, and the results of these tests must all be considered and weighed against the possible complications of shunting (infection, embolization, shunt failure, subdural hematoma, and effusion).

Multi-infarct dementia Approximately 20% of patients with dementia will ultimately be shown to have multi-infarct dementia, the result of multifocal small artery occlusive disease. A history of acute episodes of focal dysfunction superimposed on progressive dementia in a person with appropriate risk factors for vascular disease

(hypertension, smoking history, diabetes mellitus, hyperlipidemia, obesity, etc.) and the presence of focal dysfunction(s) on examination are strong support for the diagnosis. Magnetic resonance imaging (MRI) will show the typical bilateral multifocal small areas of attenuation deep in the hemispheres. Treatment consists of attending to the risk factors when possible. Anticoagulation with antiplatelet agents such as aspirin may be useful prophylaxis. The use of antithrombic agents (such as Coumadin) have not been proven effective outside of the setting of cardioembolism and may be too risky in a demented patient (due to increased chance of falling and hemorrhage). In the special case of the quite rare cerebral vasculitis, treatment may be able to arrest the underlying condition. Of course, preventing more strokes does not result in resolution of the dementia (although there may be some improvement due to compensation).

Alcohol Surprisingly, chronic alcoholism and its associated nutritional deficiencies plus a probable direct toxic effect of alcohol upon neurons is not frequently recognized as a common cause of dementia in our society. Chronic alcoholics, of which there are approximately ten to eleven million in the United States, show deficits in frontal lobe function when carefully tested. This is in the absence of significant blood alcohol levels which, when present, markedly amplify the defects. This is a preventable and treatable dysfunction although reversibility of the chronic state is likely to only be partial. The end stage Wernicke-Korsakoff Syndrome (see Table 16-3) or, for that matter, acute alcoholic cerebellar degeneration are only partially and inadequately reversible in most cases.

Reference

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Whitehouse, P.J.: Dementia. Philadelphia, F.A. Davis Co., 1993.

Questions Define the following terms:

dementia, Alzheimer's disease, amnesia, Creutzfeldt-Jacob disease, Huntington's disease, transcortical aphasia, dysinhibition, paratonia, gait apraxia, palmomental reflex, grasp reflex.

16-1. How can you define dementia? 16-2. How can you test for the presence of dementia? 16-3. Are there any physical exam findings in demetia? 16-4. What are the two basic types of dementia? 16-5. What is the most common cause of dementia? 16-6. What is the second most common cause of dementia? 16-7. What is the pathology of AlzheimerÕs disease? 16-8. What language problems are found in Alzheimer's disease? 16-9. What are the characteristics of multi-infarct dementia? 16-10. What are the characteristics of Creutzfeldt-Jacob disease? 16-11. What diagnostic tests are there for Creutzfeldt-Jacob disease? 16-12. What is Huntington's disease? 16-13. What is normal pressure hydrocephalus (NPH)? 16-14. How can you diagnose normal pressure hydrocephalus (NPH)? 16-15. What are some treatable causes of diffuse cortical dysfunction (dementia)?

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Chapter 17 - Infectious diseases of the central nervous system

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Meningitis

❍

Infection of the nervous system can involve themeninges (meningitis) or of

Bacterial meningitis

the brain substance, itself (encephalitis) or both (meningoencephalitis). ❍

Viral meningitis

❍

Granulomatous

Additionally, infections can be acute or chronic. The organisms that are involved in infection are bacterial, parasitic or viral. Additionally, there is an

meningitis

unusual class of infectious agent that can damage the brain (prions). We will ❍

Tuberculous

discuss each of these scenarios and consider the differential diagnosis. meningitis

❍

Meningitis

Cryptococcal meningitis

Acute bacterial meningitis (purulent meningitis) Bacteria reach the subarachnoid space via the bloodstream or, less often, by

❍

●

extension from contiguous structures such as the sinuses or ears. The

Sarcoidosis

Viral encephalitis

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infection is usually confined to the subarachnoid space, but toxins (from

Herpes simplex encephalitis

bacteria or leukocytes) can result in edema and also can damage blood

❍

Rabies

vessels, causing additional damage. Patients with bacterial meningitis

❍

Poliomyelitis

therefore present with changes in alertness (sensorium) in addition to headache, fever, and stiff neck. Intracranial pressure is increased because of

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Brain abscess

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Empyema

cerebral edema and due to interference with the normal circulation and

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resorption of cerebrospinal fluid (CSF) by the inflammatory process.

Miscellaneous bacterial infections

The lumbar puncture is diagnostic. The CSF is usually under increased ❍

Syphilis

❍

Lyme disease

❍

Leprosy

pressure. There are often more than 1,000 WBCs/cu mm, particularly neutrophils (PMNs). However, very early in the course (especially of meningococcal meningitis) there may be few or no cells or the cells may be ●

Ricketsial infections

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Fungal infections

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Protozoal infections

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Helminth infestations

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Prion disease

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Atypical viral

mainly lymphocytes. The amount of protein is usually elevated and the amount of glucose low. The fluid should be gram stained (even if there are no cells); often the organism can be accurately identified. Both aerobic and anaerobic cultures should be obtained and bacterial antigens can be rapidly tested, often determining the particular organism responsible. The lumbar puncture is usually accurate up to several hours after antibiotics are started. infections

Therefore, if there will be delay in performing the lumbar puncture, ●

antibiotics can be started since this is, indeed, an emergency.

infection

Prompt treatment (without waiting for the results of culture) is essential. The choice of antibiotic may be guided by the appearance of the organism on the gram stain or, if identification is not certain, by the clinical picture. In

CSF findings in

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References

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Questions

neonates, group B beta-hemolytic streptococci and enteric gram-negative bacilli are the most common pathogens, accounting for 60-70% of the cases of meningitis. From the age of two months to ten years, more than 90% of the cases of meningitis are caused by Hemophilus influenzae, meningococci, or pneumococci. Hemophilus meningitis is rare after the age of ten. Although other organisms, such as Listeria or Streptococcus, occasionally cause meningitis in otherwise healthy

individuals, the occurrence of unusual organisms should raise the suspicion of an immune deficiency or an unusual source of infection. Table 17-1 summarizes the common intracranial bacterial infections and the recommended initial therapy. The complications of acute bacterial meningitis are listed in Table 17-2. Cerebral edema may at times be severe and may lead to transtentorial or foramen magnum herniation and death early in the course of meningitis. The inflammatory process causes a vasculitis that affects the smaller arteries and veins. Usually this does not produce focal neurologic signs; but in more severe cases of meningitis, focal signs of ischemia or stroke may develop, often during the second or third week. Arterial occlusion may occur. Cortical vein thrombosis produces hemorrhagic infarction of the cortex, with resultant focal signs and (often) seizures. The thrombophlebitis may spread to involve the venous sinuses, resulting in diminished absorption of CSF and raised intracranial pressure. Raised intracranial pressure may also result from damage to the arachnoid granulations (the sites of resorption of CSF), with resultant communicating hydrocephalus. This may occur after the meningitis has been cured and may require shunting of CSF. In infants, increased intracranial pressure and continued fever may result from a subdural effusion. These are usually sterile but may be infected (empyema). If subdural effusions are symptomatic, repeated subdural taps via the anterior fontanelle are necessary in this rare condition. There are various systemic complications of meningitis. Inappropriate antidiuretic hormone (ADH) secretion may result in hyponatremia from water excess and salt loss. Water restriction is usually effective in treating this transient complication. A more serious complication is disseminated intravascular coagulation, which occurs with purpura, cyanosis, pain, fever, and hypotension. This is due to vasculitis with intravascular deposition of fibrin. Adrenal hemorrhage may accompany this, but the symptoms are thought not to be secondary to adrenal insufficiency. Treatment of the underlying

condition is probably the only effective therapy, although steroids (particularly in children) and heparin have been advocated. Lactic acidosis also occurs and frequently requires therapy with bicarbonate. Following recovery from purulent meningitis, residual brain damage may be evidenced by cranial nerve palsies, mental retardation, or seizures. The incidence of brain damage varies with the severity of the meningitis and the organism, and tends to be high in neonatal meningitis. An unusual bacterial meningitis may accompany early Lyme disease, with meningitis presenting several weeks after infection (often while the rash of erythema migrans is still present). This can occur along with damage to the facial nerve.

Viral meningitis Although pathologically some cerebral involvement is seen in most cases of viral meningitides, the clinical picture is more often one of pure meningitis: headache, fever, stiff neck, and sometimes lethargy, but with no focal neurologic signs or seizures. When there are signs of cerebral involvement, the process is called meningoencephalitis. The CSF is usually under normal pressure and there is a moderate number of WBCs (usually fewer than 500/cu mm). Initially, these cells are often polys, but after a day or two lymphocytes begin to predominate. The amount of protein in the CSF is normal (or slightly elevated); the level of sugar is normal. The illness is self-limited and sequelae are unusual. The term "aseptic meningitis" has been used for this and some of the chronic meningitis problems, since there are no bacteria grown on cultures. Lymphocytic choriomeningitis infections are atypical in that the CSF pleocytosis is more marked (often several thousand cells, with a marked lymphocytic preponderance) and the pleocytosis may take several

weeks to disappear. In other respects, they resemble other varieties of viral meningitis, with recovery being the rule. HIV can result in a meningitis usually early on, at the time of initial seroconversion.

Chronic (granulomatous) meningitis There is a clinical picture of more slowly-evolving meningitis. There are fewer signs of meningeal inflammation (headache, neck stiffness, etc), and more findings of focal neurologic damage (cranial nerves, focal sensorimotor deficit, cognitive deterioration, etc). There are infectious and non-infectious forms of chronic meningitis. The most common infectious types are tuberculous and cryptococcal meningitis. Atypical bacteria, such as brucella, spirochetes (syphilis and Lyme) may produce subacute or chronic infections and uncommon parasites such as ehrlichia can invade the meninges. Noninfecti0us types include carcinomatous meningitis and some other granulomatous forms, like sarcoid. With the diversity of causes and the nonspecificity of presentation, it is no wonder that diagnosis may be extremely difficult. We will consider some of the more common causes. Tuberculous meningitis. This occurs most often in children and debilitated and immune incompetent adults. The meningitis results from seeding from a tuberculoma in the brain or meninges. The tuberculoma, in turn, arises from the hematogenous spread from a primary focus (usually in the lung). The patients present with headache, malaise, and fever. Weight loss may be prominent. A physical examination may show normal results, or nuchal rigidity may be present. The thick basilar meningitis may produce hydrocephalus, cranial nerve palsies, or an arteritis of the small penetrating arteries of the brain stem. The CSF shows a moderate pleocytosis (usually fewer than 300 WBCs/cu mm), mostly lymphocytes. The level of protein is high, and the amount of sugar low (these changes may

be mild early in the course). The organism is occasionally demonstrable by acid-fast bacillus (AFB) strains of the CSF sediment, but often it is not. Routine cultures are negative, but specialized cultures may take 4 to 8 weeks to grow. The chest x-ray and tuberculin skin test may be helpful, but both can show normal results (the latter is the result of anergy). Polymerase chain reaction testing is rapid and fairly accurate. However, there can be false negative findings if there are few organisms. If the diagnosis of tuberculous meningitis is suspected on clinical grounds, treatment should be instituted. Isoniazide (INH), streptomycin, rifampin and pyrazinamide are used in combination. Ethambutol may be useful if given in high doses. Treatment is continued for at least 6-9 months. Corticosteroids may be helpful in reducing the inflammatory response, which itself can contribute to the patient's symptoms. Sequelae are common. Cryptococcal meningitis. Cryptococcus neoformans (Torula) often produces an indolent infection; its symptoms occasionally may extend back months or even years before the diagnosis is made. A debilitated state, immune incompetence or suppression, and diabetes mellitus are frequently associated conditions. Headache is the most common symptom, and mental deterioration may occur. Cranial nerve palsies and focal brain stem dysfunction secondary to arteritis can be prominent. The CSF is similar to that seen in persons with tuberculous meningitis. The fungus may be seen on India ink preparations and may grow in culture. It is not rare, however, for the organism not to show itself. Cryptococcal antigen can often be detected in the CSF, providing a valuable aid to the diagnosis. Treatment is with systemic and intrathecal amphotericin B and 5-fluorcytosine. Rarely, other fungal infections (such as Coccidioides, Mucor, Candida, Actinomyces, Histoplasma, or Aspergillus) can present with chronic meningitis (usually in an immunocompromised host). Other forms of chronic meningitis. Sarcoidosis is a rare granulomatous condition of uncertain

etiology. The symptoms may be nonspecific (headache, nuchal rigidity), and the CSF may be identical to that in persons with tuberculous or fungal meningitis. Transient cranial nerve signs as well as evidence of CNS dysfunction can occur. The diagnosis may be suspected if there is evidence of systemic sarcoidosis, but this is not always the case. Direct involvement of brain parenchyma can occur even in the absence of meningeal involvement. Multifocal lesions in the periventricular region sometimes also involving the optic nerves may masquerade as multiple sclerosis. Treatment with immune suppressing drugs and corticosteroids has proven effective in most patients. Carcinomatous meningitis is a condition of infiltration of the meninges by cancer cells. This usually occurs as a complication of advanced metastatic disease. However, particularly with lymphoma, it may occur without other evidence of systemic disease. Patients are usually very ill and many of the symptoms are due to hydrocephaly or damage to exiting cranial nerves or nerve roots. CSF protein is very high and centrifugation of large volumes of spinal fluid may yield cancerous cells. Flow cytometry can demonstrate the monoclonal nature of lymphocytes when the condition is due to lymphoma. Rarely, biopsy of the inflamed meninges may be necessary to definitively diagnose the condition. There are some other, rare, infections that can be chronic. Brucellosis can produce waxing/waning meningitis. Spirochetes, such as neurosyphilis and Lyme can produce chronic inflammation and certain parasites (such as Erlichia) can also present this way. Certain drugs can inflame the meniges in a rare, idiosynchratic reaction, when taken orally (such as NSAIDs or sulfa drugs). Many drugs can irritate when delivered to the spinal fluid (i.e., chemotherapy, antiviral/antifungal agents, contrast agents).

Viral Encephalitis

Meningeal involvement is present in most forms of encephalitis; however, the clinical picture is dominated by evidence of brain dysfunction. In addition to headache and fever, patients often have strikingly depressed levels of consciousness, and seizures are common. Behavioral changes and focal neurologic signs are sometimes present. The CSF contains a moderate number of cells. The level of protein is normal or high, and the amount of sugar is usually normal. The major causes of viral encephalitis are listed in Table 17-3. The arbovirus encephalitides are usually epidemic; the others are usually sporadic. Because the clinical findings are similar in most cases of encephalitis, the diagnosis of the offending agent must rest on laboratory investigations (polymerized chain reaction, antigen detection, growing the virus or detecting increasing levels of antibody titers). We briefly discuss three varieties that can be distinctive.

Herpes simplex encephalitis (HSE) This is the most common sporadic (nonepidemic) form of encephalitis. Although many encephalitides are seasonal in their appearance, especially prominent in the summer, herpes simplex occurs any time of the year. It is caused by the type I herpes simplex virus, normally present in cold sores. The portal of entry in many is presumed to be through the nasal mucosa or by direct extension from the adjacent trigeminal ganglion (in whose cells the virus is dormant). This portal of entry presumably accounts for the localization of the disease to the orbitofrontal and anteromedial temporal cortices. The pathologic reaction is unusually severe, with inflammation, edema, necrosis, and hemorrhage. Clinically, patients often have personality changes (secondary to the involvement of the limbic system). They have difficulty with memory (imprinting) because of involvement of the mesial temporal lobe (hippocampi), and a decreased or lost sense of smell (anosmia) because of involvement of the olfactory bulbs.

Olfactory hallucinations are not uncommon, caused by both irritation of the olfactory bulbs and the olfactory cortex. Headache, fever and somnolence are the usual complaints. If edema is severe, papilledema can be seen and seizure may result from irritation of the cortex. If the involvement is asymmetric, hemiparesis or aphasia may be present, leading to suspicion of stroke or mass lesion and complicating the assessment. The CT scan may show focal abnormality (including hemorrhage) in one or both temporal lobes. Magnetic resonance imaging can show changes sooner, but the changes are not specific for HSE. The polymerase chain reaction in the CSF is the most effective diagnostic tool and can be run fairly rapidly in most major medical centers. However, since it does take time for results of this test to return, it may be necessary to treat the patient while awaiting results. The electroencephalogram (EEG) usually shows bitemporal slowing and sharp activity and is frequently the first laboratory abnormality to be positive. Occasionally it may be difficult to differentiate encephalitis from a temporal lobe abscess without surgical exploration and biopsy. Treatment with an antiviral agent (acyclovir) has been shown to be effective. Combating the host inflammatory response with steroids has been considered by some an effective supplementary therapy, despite the theoretical risk of exacerbating the infection and the lack of concrete evidence of efficacy. Survivors may show severe cognitive changes; not uncommonly, there is a specific deficit in recent memory (imprinting) because of bilateral hippocampal destruction. Acyclovir is a relatively benign medication and, therefore, when herpes simplex encephalitis is suspect, acyclovir should be started immediately, even prior to beginning diagnostic tests because the morbidity and mortality due to this destructive encephalitis poses a much greater risk than the therapy. It is advisable to also cover for possible bacterial cerebritis until the issue is clarified.

Arbovirus Arboviruses are the leading cause of epidemic encpehalitis. The most common forms in the US are eastern and western equine encephalitis, St Louis encephalitis, California encephalities and, most recently, West Nile virus. The infections range from very mild to fatal. The usual incubation period is 218 days after mosquito bite and the incidence is highest in late summer and early autumn, until the first hard frost does away with the mosquito population for that year. Birds and other animals (such as horses) are the usual reservoir for the infection, and they are involved in its spread. Initial viral symptoms may give way to high fever and neck stiffness (meningeal signs). However, as with most forms of encephalitis, it is the confusion and depressed levels of consciousness (stupor) that mark the infection as being of the brain (encephalitis) and not just the meninges.

Rabies The incubation period after the bite of a rabid animal may be prolonged (as long as one year). The further from the CNS that the infection is introduced to the body, the longer the incubation period. The infection appears to gain access to the nervous system through retrograde transmission and it attacks neurons in specific areas, particularly the limbic system, hypothalamic area, and brain stem nuclei. There may be little or no meningeal inflammation (i.e., the CSF may be normal). Behavioral changes (particularly an agitated delerium), seizures, and painful spasms of the throat musculature are prominent, particularly precipitated by swallowing food or liquids. This latter feature is the source of the ancient name for rabies "hydrophobia." If bitten by or exposed to the saliva of a suspected rabid animal, effective immune therapy is available and should be initiated while waiting for proof of the suspect animal's disease since there is no effective therapy once neurologic symptoms

develop.

Poliomyelitis Encephalitis is usually a minor aspect of this infection, which has a predilection for anterior horn cells and the cells of the brain stem motor nuclei. A prodromal gastrointestinal illness and a nonspecific viral meningitis usually precedes the development of lower motor neuron signs (spotty asymmetric weakness, reflex loss, and fasciculations). The success of the polio vaccines (Salk and Sabin) have made polio a rare infection in the western world. It has always been unusual in the third world because of poor sanitation which causes infection early in life when susceptibility to nervous system invasion by the poliovirus is low.

Brain Abscess Bacterial brain abscesses can arise either from direct extension from a parameningeal focus of infection (ear and sinus infections) or by hematogenous spread. Pulmonary pathology (especially bronchiectasis) is the most common source of the hematogenous spread. Persons with cyanotic congenital heart disease and pulmonary arteriovenous malformations are prone to develop abscesses. This is because bacteria originating in the bowel and reaching the vena cava and the right side of the heart via the portal system, liver, and hepatic veins are short-circuited to the left side of the heart and systemic circulation. Thus they miss filtration by the pulmonary macrophage system. Although subacute and acute bacterial endocarditis may be associated with mycotic aneurysms and meningoencephalitis, it is infrequently the cause of brain abscess. This may be because the bacteria that usually cause endocarditis are aerophilic and therefore unlikely to propagate within an infarct or ischemic zone; the arterial wall is more prone to

involvement because of its high oxygen saturation. The pia-arachnoid surface is also highly vascularized and a favorable site for aerobe propagation. In hematogenously spread abscesses, they are most likely to occur in areas of ischemic injury to the brain and most likely to include anaerobic or microaerophilic organisms (such as come from the bowel). On the other hand, aerobic bacteria are frequently cultured from abscesses that have sinus tracts connecting them to the exterior, i.e., sinus infections, middle-ear infections, and skull fractures. Abscesses secondary to ear infections are usually in the middle third of the temporal lobe, or less often, in the cerebellum. Abscesses secondary to spread from the paranasal sinuses or from dental infections are more often in the frontal lobes. Hematogenous spread can result in an abscess in any location, and multiple abscesses are not uncommon. There are two stages in the development of a bacterial brain abscess. In the first stage, the primary infection is often active, and the brain infection is a cerebritis - an inflammatory response with some tissue breakdown. The patient is usually febrile and may complain of headache. The intracranial pressure is usually raised. There may be focal signs, but lesions in the temporal lobes, frontal lobes, or cerebellum can be distressingly silent. The CT scan or MRI is usually abnormal and the EEG is usually focally abnormal. Arteriography does not show any well-defined mass. The spinal fluid may show a pleocytosis, with a raised level of protein and a normal amount of glucose, but it can be entirely normal. Of course, spinal tap in a patient with potentially elevated intracranial pressure should only be done after scanning to ascertain the risk of potential herniation. Treatment with antibiotics alone at this stage may produce complete resolution and surgery is not recommended due to the lack of clear margins or a defined wall to the infection. In the second stage, the region of the cerebritis becomes organized and walled off, and a true abscess

forms. Fever often subsides. There may be signs of an expanding mass. The CSF and EEG and brain scan are as before. A mass is seen on CT scan or MRI. Treatment with antibiotics alone may not be effective because the abscess is walled off; surgical drainage may be necessary. Untreated, the brain abscess may cause cerebral herniation or rupture into the ventricles, causing severe (and often fatal) meningitis. The WBC count in the CSF in the latter instance is often more than 10,000/cu mm.

Empyema Infection may form in the epidural or subdural spaces; it is usually the result of spread from an adjacent infection (in the bone, skin, or sinuses), but sometimes it arises from hematogenous spread. The diagnosis of cerebral subdural or epidural empyema can be difficult unless there is a high index of suspicion. The symptoms of spinal epidural empyema are somewhat more uniform, but the diagnosis is still often missed. The presenting complaint is usually pain over the infected region, and there is usually fever. The patient then experiences pain in the distribution of the spinal nerve roots in the area. Finally, symptoms referable to the spinal cord occur as a result of compression or infarction secondary to thrombophlebitis. If treatment (surgical drainage and antibiotics) can be instituted before the spinal cord is affected, the outcome should be good; otherwise irreversible cord damage and paralysis can result.

Miscellaneous Infections

Bacterial Numerous bacterial infections may be manifested by processes other than acute purulent meningitis or

brain abscess. Tuberculous meningitis has been mentioned. Encephalitis symptoms may be present with pertussis, tularemia, typhoid, and other acute infections. Brucellosis may appear as chronic meningitis. Neurosyphilis, uncommonly seen in this country today, is nevertheless important.

Syphilis

Syphilis produces an amazing array of CNS disorders, which can mimic infectious, vascular, neoplastic, or degenerative disease. Meningitis (rarely of clinical significance) may occur within five years of a person contracting the infection. From seven to 15 years after contact, an inflammatory vasculitis (meningovascular syphilis) can produce infarction in virtually any area of the CNS. Tertiary syphilis (1520 years after contact) has two classic presentations: tabes dorsalis and paretic neurosyphilis (general paresis of the insane). Tabes is an inflammatory process that affects the dorsal root ganglia, producing loss of position and vibration sensation, loss of deep-tendon reflexes, and severe "lightning" pains in the abdomen and legs. Periodic attacks of abdominal cramps and vomiting are common. The ArgyllRobertson pupil (small and irregular with light reaction lost and accommodation preserved) is usually present, and bladder dysfunction is common. General paresis consists of an infection of the cerebral cortex, particularly in the frontal lobes, producing a progressive frontal lobe dementia. Pupillary changes, myoclonic jerks, and tremor are also frequently present. Neurosyphilis may be diagnosed serologically using nonspecific (reagin) tests such as rapid plasma reagin (RPR) or Venereal Disease Research Lab test (VDRL) or specific treponemal antibody tests such as the fluorescent treponemal antibody test (FTA). The former may have normal results in the serum in tertiary syphilis, and therefore an FTA must always be ordered when this form of the disease is being

considered. The CSF VDRL is diagnostic of neurosyphilis because false positives occur only when falsepositive blood is inadvertently introduced into the CSF by a traumatic lumbar puncture (see Chap. 13). Occasionally all these tests are negative. If symptoms and signs are compatible with CNS syphilis, and if CSF pleocytosis or increased concentrations of CSF protein suggest active disease, treatment should be instituted. Prolonged treatment with penicillin is the treatment of choice.

Lyme disease

This is another spirochaetal disorder with both acute and chronic phases and multisystems involvement. The spirochete (Borelia burgdorferi) is blood borne and transmitted by ticks. The disease usually first manifests itself as an enlarging circiform rash (erythema chronicum migrans) which may then be followed by a migrating arthritis which has been misdiagnosed as atypical rheumatoid arthritis in the past. Later, the meninges may be involved with cranial neuropathies prominent. The seventh nerve appears to be involved most frequently. This may be followed, in some patient, by a condition with multifocal parenchymal lesions occur in some with a fluctuating course giving rise to misdiagnoses of multiple sclerosis. Diagnosis is suspected when the course is typical and can usually be confirmed by serological testing. The treatment of choice is doxycyclin or amoxicillin and is successful early in the course but less so in chronic, late stage illness. When there is involvement of the brain parenchyma or heart, certain other intravenous antibiotics may be necessary.

Leprosy

Because the leprosy bacillus can multiply only at temperatures a few degrees below core body temperature, CNS leprosy is rare if it exists at all. Leprosy produces a peripheral neuropathy, which is

characterized by the involvement of nerves only in the cooler parts of the body. In persons with tuberculoid leprosy, nerve trunks are involved; the nerves situated immediately subcutaneously are affected (for example, the ulnar nerve at the elbow). In lepromatous leprosy, terminal nerve endings are involved, producing a patchy sensory loss; the cooler areas of the skin (ears, back of the hands) are affected first. Leprosy is rare in the United States, but worldwide it is one of the most important causes of peripheral neuropathy. An influx of new cases appeared in the U.S. when veterans who contracted the disease in southeast Asia returned home.

Rickettsial infections The various rickettsial diseases may be accompanied by nonspecific meningoencephalitis. In this country, Rocky Mountain spotted fever is the most common of these conditions and may occur in almost any location. The initial symptoms are often neurologic (headache, stiff neck, lethargy). The diagnosis is suggested by a history of a tick bite and the characteristic rash. Treatment with antibiotics (tetracycline or chloramphenicol) is effective and may be lifesaving.

Fungal infections Most often fungal infections occur in persons who have altered immune mechanisms: the debilitated, those with advanced diabetes or receiving immunosuppressant therapy. Aspergillosis and candidiasis are not uncommon in these persons. Mucormycosis is usually seen in diabetics, and is often associated with ketoacidosis. CNS involvement is usually secondary to spread from the nasal sinuses to the orbit (causing proptosis and ophthalmoplegia) through the cribriform plate into the brain. Coccidioidomycosis and cryptococcosis may occur in the normal host. Granulomatous meningitis is the

usual presentation. Various fungi can produce cerebral granulomata or abscesses. Treatment of fungal infections is generally less satisfactory than treatment of bacterial or rickettsial infections, but some improvement is often obtained with intrathecal amphotericin B or 5-fluorocytosine.

Protozoal infections Amoeba, trypanosomes, malaria, toxoplasma, and other protozoa may affect the CNS. Toxoplasmosis, a ubiquitous organism, may cause infection in utero producing underdevelopment of the cerebrum and resulting in microcephaly and mental retardation. Retinal involvement and intracerebral calcifications (seen on skull x-rays) may aid in making the diagnosis. This infection is also becoming more common in immunosuppressed persons. The syndrome presents as destructive meningoencephalitis, usually with multiple small abscesses in the basal ganglia region and particularly in the patient with the acquired immune deficiency syndrome (AIDS), caused by systemic retrovirus infection (see below). This infection is common enough in this group of patients that multiple small abscesses (ringenhancing lesions), when found in an AIDS patient, are treated presumptively for toxoplasma before considering other diagnoses.

Helminth infestations Helminth infestations may produce various CNS findings, including meningoencephalitis (trichinosis), vasculitis (filariasis, schistosomiasis), or focal granulomata (cysticercosis). The patient may have a meningitis or encephalitis picture, or the process may be manifested as a mass lesion or seizure disorder. Cerebral cysticercosis is the most common cause of focal onset epilepsy in Central and South American.

Prion diseases (Table 17-4) This fascinating group of uncommon diseases is pathologically similar and has the following characteristics:

1. They are transmissible experimentally. 2. They have a long latent period (up to many years). 3. Pathologically they resemble degenerative diseases; there is neuronal degeneration with astrocytic reaction but no evidence of inflammation. 4. Clinically they produce a chronic or subacute illness, which is steadily progressive. 5. The nature of the infectious agent is elusive but is probably an abnormally folded protein.

These diseases therefore provide possible models for degenerative diseases of the nervous system (such as amyotrophic lateral sclerosis and spinocerebellar degenerations). Because Creutzfeldt-Jakob disease (a progressive dementia with myoclonus, extrapyramidal signs, and sometimes cerebellar and anterior horn involvement) has been transmitted experimentally, this model may also apply to other degenerative diseases of the CNS. As yet, however, efforts to transmit other degenerative diseases have not been successful.

Atypical conventional virus infections (Table 17-4) In persons with these conditions, virus particles can be identified pathologically, immunologically, and by culture. Inflammatory reactions can be seen, and inclusion bodies may be present. As opposed to most acute viral infections, they cause a subacute or chronic disease, usually after a long latent period.

Subacute sclerosing panencephalitis (SSPE) is a disease that affects children or adolescents; it presents with progressive mental deterioration, myoclonic jerks, and then progressive pyramidal and extrapyramidal involvement, which leads to death within a few years. The CSF may be normal except for a high level of gamma globulin and high measles antibody titers. A measles-like virus can be grown from infected brain tissue. Some of these children have defective immune responses. The disease may result from infection at an early age with a form of measles virus, but the exact pathogenesis is still unknown. Progressive multifocal leukoencephalopathy (PML) is a disease that occurs almost exclusively in debilitated persons (most often patients with lymphoma and more recently in patients with AIDS). Pathologically there are small areas of demyelination, and inclusion bodies are seen in oligodendroglia (the cells of the CNS that elaborate myelin). Clinically patients have focal cortical signs, and as lesions become more numerous, the clinical course becomes one of progressive deterioration. Death usually occurs within one to two years. Two different papovaviruses have been isolated: One of them (the JC virus) is a virus with which most adults have had contact. The acquired immune deficiency syndrome (AIDS) is a disease caused by a retrovirus, which has the capacity to elude and destroy the body's various immune defenses. The virus has relatively low infectivity and is passed by repeated sexual contact, blood and blood products and direct introduction into tissue or the blood stream by infected needles, surgical instruments, etc. In this country, the major victims have been promiscuous homosexuals, drug addicts, prostitutes and hemophiliacs although worldwide this appears to be mainly passed by heterosexual contact. The virus causes direct problems by tissue invasion (the central nervous system is a prominent target) and indirect problems as a result of the immune deficiency state. Slowly progressive encephalitis is caused by direct involvement that is, however, usually overshadowed by the appearance of the various infections of immune compromise.

The most prominent co-infections are toxoplasmosis in its various parenchymal and meningeal forms, cytomegalic virus encepahalitis, cryptococcal meningitis, progressive multifocal leukoencephalopathy, tuberculous meningitis or granuloma and syphilis. In the absence of immune surveillance various malignancies are also predisposed (lymphomas appear most common). A Guillain-Barre-like polyneuropathy, believed to be caused by autoimmune attack against viral involved myelin or Schwann cells may be an early and reversible involvement before the retrovirus destroys the body's capacity to have an autoimmune reaction. There are therapies for many of the secondary phenomena. A variety of antiretroviral therapies are now available which effectively slow the progression of the disease but no curative agent is available yet. Prophylactic measures have begun to decrease the incidence in the sexual and transfusion population. Drug addicts and their sexual partners remain a significant reservoir and attitudes (both ignorance of risk and fatalistic acceptance) are barriers to prevention. There is growing risk of individuals misinterpreting successful treatment with cure and therefore not recognizing the seriousness of the condition. Poor education, cultural barriers and the limited availability of treatments remain a major barrier to progress in the third world, where AIDS remains a major cause of mortality.

Cerebrospinal Fluid in Infectious Disease and Related Conditions The CSF findings in persons with the three major varieties of meningitis have been discussed and are summarized in Table 17-5. Although the differences noted are helpful, it is important to realize that there are exceptions to these rules. Patients with viral meningitis may have more than 1,000 WBCs/cu mm. Acute bacterial meningitis may present with few WBCs for a variety of reasons: (1) the patients immune response may be inadequate, (2) the leukocyte response may be suppressed by the presence of

alcohol in the blood and tissues, (3) the meningitis may have been partially treated, and (4) the tap may have been done early in the course of the disease before cells appeared. In the second and last instances, a repeat tap in two to six hours usually reveals a brisk pleocytosis. Many conditions other than viral infections can produce a modest pleocytosis, normal or elevated levels of protein, and normal (or low) amounts of sugar. These are listed in Table 17-6. Finally, a low level of glucose in the CSF is not pathognomonic of infection. Several mechanisms are invoked to explain the low level of CSF glucose in persons with meningitis: The glucose may be metabolized by organisms, by phagocytes, or by the inflamed meninges and brain. In addition, transport of glucose into the CSF is often blocked in cases of meningitis. Some of these mechanisms may also explain the low level of CSF glucose found in persons with other conditions (Table 17-7). It should be clear, therefore, that although the CSF findings provide important clues to the diagnosis of CNS infections, the definitive diagnosis rests on identifying the causative organism microscopically or by culture. Serologic methods may be useful, but, in general, evidence of rising titers of antibodies to an infectious agent appears after the illness is over. Recent studies indicate that counter imunoelectrophoresis and polymerized chain reaction may be capable of detecting minute amounts of bacterial antigens in the CSF rapidly and thereby enable the rapid and specific diagnosis of meningitis.

References

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Baker, A.B., Baker, L.H.: Clinical Neurology. New York, Harper & Row, 1974, Chaps. 14-19.

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Dodge, P.R., Swartz, M.N.: Bacterial meningitis - A review of selected aspects. N. Engl. J. Med. 272:954, 1965.

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Thompson, R.A., Green, J.R. (eds): Infectious Diseases of the Central Nervous System, in: Advances in Neurology, Vol. 16, New York, Raven Press, 1974.

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Mandell, L.A., Ralph, E.D. (eds): Essentials of Infectious Diseases, Boston, Blackwell, 1985.

Questions Define the following terms:

meningitis, encephalitis, hydrocephaly (communicating and internal), meningismus, Kernig's sign, pleocytosis, Brudzinski's sign, parameningeal.

17-1. What broad classes of meningitis are there (name 4)? 17-2. What are the most common causes of acute meningitis? 17-3. What are the most common causes of acute bactieral meningitis? 17-4. Which bacterial would you suspect in adults? In older children/adolescents? In young children? In infants? In the elderly? 17-5. What are the signs and symptoms of acute bacterial meningitis? 17-6. What are some potential complications of meningitis? 17-7. What is the most critical diagnostic test for diagnosis? 17-8. What are the findings in the CSF in acute bacterial meningitis? 17-9. What are the priciples of treatment of acute meningitis? 17-10. What is the most common cause of aseptic meningitis. 17-11. What are the symptoms of aseptic meningitis? 17-12. What are the CSF findings in aseptic meningitis? 17-13. What are causes of chronic meningitis?

17-14. What are the signs and symptoms of chronic meningitis? 17-15. What is the key to diagnosis of chronic meningitis? 17-16. What are parameningeal infections? 17-17. What are the features of acute viral encephalitis? 17-18. What are the potential complications of acute viral encephalitis? 17-19. What are the potential causes of acute viral encephalitis? 17-20. What are the potential causes of chronic encephalitis? 17-21. What are the causes of brain abscesses? 17-22. What are the symptoms of brain abscess? 17-23. What are the most common organisms in brain abscess? 17-24. What is the treatment for brain abscesses? 17-25. What about lumbar puncture in brain abscesses?

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Chapter 18 - Disorders of basal ganglia function

On this page ●

There is no definitive list of structures that are included in the extrapyramidal

Parkinsonian syndromes

system, but all lists would include the basal ganglia (caudate, putamen, and

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Clinical features

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Rigidity

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Bradykinesia

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Tremor

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Postural deficits

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Parkinson's

globus pallidus), and the subthalamic nucleus. The substantia nigra is an associated structure with important basal ganglia interconnections. The cerebellum and perhaps also the red nucleus play an important role in some abnormalities associated with basal ganglia disorders. Important interconnections of the basal ganglia are the nigrostriatal pathway, and the ansa and fasciculus lenticularis, and the fasciculus thalamicus, which

disease

interconnect the globus pallidus and the ventral lateral and ventral anterior ❍

Parkinson's plus

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"Parkinsonism"

(VL-VA) nuclei of the thalamus, and the VL-VA thalamocortical fibers, the subthalamopallidal pathway, striatopallidal fibers, and cerebellothalamic ●

Chorea

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Hemiballism

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Athetosis

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Dystonia

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Tardive Dyskinesia

movement disorders. For the most part, these clinical understandings have

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References

been supported and expanded by basic science investigations, although it is

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Questions

interconnections (Fig. 18-1). The normal functions of the human basal ganglia have largely been deduced from study of functional problems associated with destructive or irritative lesions. To a large degree, the deficits are in motor function and , therefore, the extrapyramidal system and basal ganglia have been associated with

becoming increasingly evident that these brain regions are involved in a greater array of functions than heretofore obvious. Although far from complete, this understanding has permitted development of some effective therapies for movement disorders. In lower vertebrates the basal ganglia are a major motor control system. With progressive evolution of the brain in higher vertebrates, culminating in humans, the pyramidal system and the neocerebellar cortices have assumed a greater level of importance in motor control. However, as is true in many brain functions, the "more primitive" portions of the brain have not been discarded, but rather remain in control of some of the more primitive functions of the nervous system. In primates and other neomammalian species, the basal ganglia appear to be important in the process of initiation of movement and the automatic maintenance of movements once they are initiated. Postural control, resting muscle tone, automatic associated movements (e.g., swinging the arms while walking), and possibly emotional motor expression (e.g., smiling, frowning, laughing, crying, etc.) appear to be important functions of the basal ganglia. Some deficits observed with basal ganglia disease reflect loss of the preceding functions. However, other manifestations fit less easily into a scheme of lost normal function. One can only conclude that they reflect how the remaining normal brain functions when components of the basal ganglia are missing. There are two major disorder complexes associated with disease of the basal ganglia and related structures: the parkinsonian syndrome and the choreas. Athetosis and the dystonias, also basal ganglia disorders, are much less common, with the exception of spasmodic torticollis and dystonias produced by certain neuroleptic drugs.

Parkinsonian Symptoms

"Parkinsonism" is a relatively common complex of neurologic symptoms that can be seen with many types of extrapyramidal disease. This constellation of symptoms appear as the end product of many degenerative disorders of the brain, although some produce the symptoms much earlier in the course than others. For example, most patients with a generalized dementing condition of the brain will eventually develop symptoms of parkinsonism. However, this occurs quite late in the course of the disease for most of these conditions. Cerebrovascular disease can also target the extrapyramidal system (especially when diffuse), leading to parkinsonian symptoms. On the other hand, symptoms occur relatively early in conditions that selectively target the basal ganglia and related structures. Examples include progressive supranuclear palsy, cortico-basal ganglionic degeneration, striatonigral degeneration, multi system atrophy and diffuse Lewy body disease. In the case of idiopathic Parkinson's disease, the constellation has been related specifically to deficient function of the nigrostriatal dopaminergic systems. In this case, the major underlying pathologic abnormality is either a degeneration of neurons of the substantia nigra pars compacta (which are the source of the dopamine in the striate nuclei), or a drug-induced suppression of dopamine effectiveness. The latter is a common cause of the parkinsonian syndrome because of the widespread use of certain neuroleptic (tranquilizing) drugs (phenothiazines, butyrophenones, and reserpine) and it can be easily reversed by discontinuation of the drug. A rare cause of acute and irreversible parkinsonism is poisoning with the "designer drug" MPTP, a derivative of the narcotic analgesic meperidine. The free radical breakdown product of MPTP, MPP+ appears to be the toxic molecule, which destroys the pigmented dopaminergic cells in the substantia nigra. From this tragic discovery has arisen a major experimental model (monkeys and other mammals also develop the parkinsonian syndrome when exposed to this toxin). The toxicity can be blocked by

antioxidant therapy (Vitamin E, etc.) and a monoamine inhibitor, deprenyl. This has led to speculation concerning the etiology of parkinsonism and to clinical trials of both entities to determine a possible prophylactic effect in idiopathic parkinsonism. Ameliorative but not curative medical therapy is now available for Parkinson's patients, mainly in the form of dopamine repletion or deep brain stimulation.

Clinical features Parkinsonism is characterized by varying degrees of: (1) rigidity, (2) bradykinesia, (3) tremor, and (4) postural defects. Dementia, usually appearing late and less severe than the other abnormalities, is also relatively common (approximately 20%) and considered secondary to degeneration of cerebral cortical neurons which can be involved in a more diffuse degenerative process (diffuse Lewy body disease). Parkinsonism may also be part of a more prominent dementing process such as Alzheimer's Disease, presumably because the degenerative process also affects the basal ganglia. Rigidity is plastic in nature and present in all ranges of passive manipulation and active movement. This appears to be due to overactivity in descending motor pathways from the brain stem. The gamma motor system probably is not involved because cutting the dorsal roots does not modify the rigidity. The rigidity has a superimposed cogwheel halting character if tremor is part of the syndrome. Bradykinesia is actually not a slowness of movement so much as an inability to initiate or carry out movements despite the presence of adequate strength. An illustration of this presumed dyspraxia is seen in the parkinsonian patient who, frozen with bradykinesia, leaps from their wheelchair and runs with full coordination from a burning house and then safe, settles back to an inability to initiate volitional locomotion. The capability for catastrophe motivated, well-learned, and relatively automatic

behavior is present, but volitional behavior is defective. Once movement is initiated, it can often be continued with reasonable speed. Bradykinesia and rigidity are additive in hindering movement and are usually present together. Bradykinesia is, however, not dependent on or necessarily proportional to rigidity, and vice versa. There is a small population of patients who have pure bradykinesia without other characteristic parkinsonian deficits. They have been described as having a pure "ignition" syndrome. Also included by many under bradykinesia is the characteristic depression or loss of associated movements, such as arm swinging while walking and emotional expression --e.g., an immobile face when the patient is happy or sad despite the ability to grimace voluntarily. Facial muscle rigidity can also partly or completely account for the "masked facies." The tremor of parkinsonism is a rhythmic (four to eight per second) oscillation of opposing muscle groups, which is particularly prominent in the distal portions of the extremities. The upper extremities are affected earlier than the lower extremities. The neck and cranial muscles may also be involved. Early in parkinsonism the tremor may begin in one extremity, as may rigidity and bradykinesia as well. In the absence of tremor the presentation may be erroneously diagnosed as hemiparesis. The absence of true weakness, the character of rigidity (full range instead of clasp knife) and the decrease in associated movements help to differentiate the two. Generalization to both sides of the body ultimately occurs in most. The tremor has been erroneously considered a tremor at rest, but actually it is a tremor of postural or resting muscle tension. When the patient is completely at rest and relaxed (which is nearly impossible for most patients with Parkinson's disease), the tremor disappears. It is most characteristic that a parkinsonian tremor may be seen with the hands folded in the lap or when walking with the hands hanging by the sides.

The postural (e.g., arm held in position demanding muscle tone) or resting muscle tension tremor of parkinsonism is to be differentiated from the tremor of cerebellar damage, which is not present until the patient directs their limbs into purposeful activity (i.e., intention tremor). The tremor of Parkinson's disease is suppressed by the initiation of voluntary movement. There is a story, at least partly true, of a skilled surgeon who developed a parkinsonian tremor and continued to operate successfully for some time. As the disease progresses, however, many patients may begin to develop a coexistent intention tremor, which supports a hypothesis that involvement of the cerebellar system is important in the pathogenesis of parkinsonian tremor. All forms of tremor, and indeed most adventitious movement abnormalities, are increased by anxiety or any other stress that increases muscle tension; therefore they are reduced to varying degrees by natural or sedative-induced relaxation. Postural deficits are less well studied and understood. However, it is characteristic for a person with parkinsonism to have difficulty adjusting to postural change. This can be demonstrated by seating the patient on the edge of a tilt table. When the table is tilted, the normal response is to lean uphill, thus preserving one's balance. The parkinsonian patient tilts with the table without adjusting and topples over (Fig. 18-2). If the patient is given a good shove backward, instead of normally catching their balance s/he tends to fall back like a tree. In some patients this retropulsion can be initiated by simply having the patient attempt to look up or back up. Patients with moderately advanced parkinsonism frequently have a flexed (stooped) posture, which may well be a compensation for the postural imbalance that causes retropulsion. Falling is a common problem for parkinsonian patients because of the combination of their rigid/bradykinetic shuffling gait and the postural adjustment deficit. They are unable to make the appropriate kinetic-postural adjustment necessary to prevent them from falling. A bizarre but typically parkinsonian fall occurs when the patient is unable to initiate stepping movement

with their feet although s/he has already initiated forward movement of the trunk. To avoid falling on their face, s/he usually drops to the knees.

Parkinson's Disease Parkinson’s disease (PD) is the single most common (and most treatable) condition that produces parkinsonism. Most cases are sporadic, although there are some clearly defined families with autosomal dominant inheritance patterns. Most of these families are containing defective genes for one of several intracellular proteins. The ultimate pathology in PD is the presence of Lewy bodies (ubiquitincontaining granules) in the cytoplasm of neurons in the degenerating substantia nigra, pars compacta (the region of dopaminergic neurons projecting to the substantia nigra). Because there are some small clusters of Parkinson’s disease and because poisoning with MPTP (a byproduct of amateur attempts at synthesis of Demerol), there are some suspicions of environmental factors in the genesis of the disease. It appears that compounds that generate free radicals when oxidatively metabolized have a particular predilection for damaging the substantia nigra (due to the high oxidative functions of these neurons). Although PD can occur at any age, it is rare before the 30s, and increases in frequency with advancing age. This can be explained by gradual, age-related loss of neurons in the substantia nigra. Most often the symptoms begin asymmetrically. There is a variable constellation of tremor, bradykinesia, rigidity, difficulty initiating movements and delayed postural corrections. The condition can present with tremor or with rigidity. Rarely, it can primarily present with balance issue in the absence of other symptoms. These cases are particularly difficult to diagnose. The fundamental pathology in pure cases of PD is a deficiency of dopamine in the striatum of the basal ganglia (the caudate and putamen). Dopamine has the effect of stimulating the direct circuit through

the basal ganglion and inhibiting the indirect pathway through the basal ganglia. Ultimately, since the direct pathway is facilitatory to movement and the indirect pathway is inhibitory, the net effect of dopamine is to increase the excitability of the motor areas of the cerebral cortex and increase movement (see this discussion of functional anatomy if you desire further elucidation). Therefore, when the tonic activity of dopamine is lost, the motor and premotor cortex is less excitable and the patient is less mobile, with shower responses and less spontaneous movement. As our understanding has progressed, it has become apparent that some patients have pure dopamine deficiency. These patients have near-complete resolution of their symptoms when dopamine is replaced. However, there are also patients with additional degeneration of the extrapyramidal system. These patients usually have incomplete resolution of symptoms, with improvement based on how much additional damage has been done. Treatment of PD is often initiated with the combination of levodopa (a dopamine precursor that crosses the blood-brain barrier) and carbidopa (and inhibitor of dopa decarboxylase that does not cross the BBB). This latter medication prevents conversion of levodopa to dopamine outside the brain, thereby minimizing dopaminergic side effects and assuring as much delivery of dopamine as possible to the brain. The entry of dopamine to the brain can be diminished by competition with other amino acids, and some patients have their response to levodopa blocked by a protein meal. Levodopa is easily converted to dopamine in the brain and results in an increased concentration and storage of dopamine in dopaminergic neurons. Although the levodopa is typically quite short-lived in the peripheral circulation, the fact that it boosts dopamine storage in the brain can result in improvement of symptoms lasting many hours. However, as the condition progresses, the capacity to store dopamine declines and the duration of action becomes shorter (sometimes only persisting for the

hour or two of high blood levels). This progressive decline in dopamine storage results in “wearing off” that can occur at progressively shorter intervals and, eventually, severely fluctuating symptoms, with “on-off” periods being prominent. The patient can even freeze in place unpredictably. After long-term administration of levodopa, over-responsiveness to dopamine may develop. Striatal neurons appear to become particularly sensitive to dopamine after years of exposure to levodopa (and, to a lesser extent, other Parkinson’s treatments) due to proliferation of dopamine receptors. This can result in “peak-dose dyskinesia” that is seen as choreoathetosis (see below). Other complications of Parkinson’s treatment include nausea (due to stimulation of peripheral dopamine receptors), hypotension (which can also occur due to PD, itself) and hallucinations/ nightmares. These latter are typically visual in nature. Other treatments for PD include anticholinergic medications (these have limited effect and many sideeffects), direct dopamine agonists (these stimulated the dopamine receptors directly) and medications that slow the breakdown of dopamine (either by locking centrally-acting monoamine oxidase or catechol-O-methyl transferase). Other methods of delivery of levodopa are being explored and, if medications are producing excessively variable responses, neurosurgical procedures (mostly either destruction of the medial glolbus pallidus or stimulator implantation into the subthalamic nucleus) are often used (see Fig. 18-1 for the anatomical relationships of these structures). Symptoms are invariably progressive, although there has been great interest (and slight evidence) for neuroprotective approaches to prevent this progression. Eventually, most patients develop less response to medication, coupled with increased side-effects. This probably occurs due to degeneration extending to other neuronal cell populations as well as proliferation of dopamine receptors on remaining neurons.

Parkinson’s plus There are some conditions characterized by symptoms of Parkinson’s disease plus areas of degeneration. Multiple system atrophy (MSA) commonly has additional pyramidal signs (spasticity and upgoing toes), autonomic dysfunction (bladder and blood pressure control) and cerebellar findings along with symptoms of Parkinson’s disease. This is associated with a very specific pathology, the presence of glial cytoplasmic inclusions, in many brain regions (accounting for diffuse symptoms. There are 3 main variants of this condition, all with similar neuronal pathology, simply targeting different areas predominantly. When the extrapyramidal system is mostly affected this is termed “striatonigral degeneration”, when the cerebellar systems are mostly affected, the diagnosis is “olivopontocerebellar atrophy” and when the autonomic preganglionic neurons are targeted, the condition has been called Shy-Drager syndrome. This latter condition produces profound orthostasis and bladder dysfunction as early symptoms. With progression of any of these variants, elements of the other conditions may come out. None of these conditions are as responsive to treatment as is Parkinson’s disease (and side-effects to medications are typically greater).

“Parkinsonism” As we described previously, any condition that results in sufficient degeneration of the extrapyramidal system can result in "parkinsonism". However, there are several specific causes of parkinsonism that deserve a little more discussion. These are all characterized by some appearance of the above-described symptoms of parkinsonism, especially rigidity and bradykinesia. Progressive supranuclear palsy (PSP) is a condition of degeneration, with prominent accumulation of

neurons containing tau proteins in many areas including the rostral midbrain. Symptoms usually start in the 50s or 60s. Most of these patients have early gait difficulty and there is often a significant dysarthria early in the course. Vertical gaze is affected early in the course. The patient has trouble looking up and down although the eyes can be moved much further by oculocephalic tests. Many patients eventually develop retrocollis (a dystonic extension of the neck) and they often develop severe swallowing troubles (that can lead to pneumonia). Emotional lability, personality change and cognitive problems usually occur a little later. This condition progresses more rapidly than does Parkinson’s disease and death is due to pneumonia or the effects of debility. There is little response to Parkinson’s medications. Cortical basal ganglionic degeneration (CBD) is a rare, degenerative condition that results in degeneration of both the fronto-parietal region of the cerebral cortex and various structures of the extrapyramidal system. There may be large, ballooned neurons and other neurons containing neurofibrillary tangles. This condition usually begins in the 50s and 60s and presents asymmetrical motor difficulties that can include prominent apraxia of a limb (“I just can’t make it do what I want to”). Sometimes this is so severe that it has been termed “alien hand.” Dystonia of one limb is a common symptom. Patients usually don’t have significant memory loss but may have “executive” function problems (i.e., distractible, trouble planning movements, deficient judgment, etc). Patients may also have trouble with graphesthesia despite intact sensations. There is no effective treatment other than palliation. Diffuse Lewy body disease (DLBD) is a condition where neurons in the cerebral cortex and extrapyramidal system are undergoing degeneration with prominent ubiquitin-containing inclusions (Lewy bodies). This condition is most remarkable for vivid and severe hallucinations early in the

condition, along with confusion, a progressive dementia and parkinsonian features. These patients are very sensitive to the older antipsychotic medications to which they are often exposed because of hallucinations, often with paranoid delusions. Some of the newer antipsychotics are significantly better in this regard (such as quetiapine and clozapine). Some of the anticholinergic treatments (as used for Alzheimer’s disease) may be helpful, but only for a short period.

Chorea Chorea is the term for a type of involuntary movement disorder characterized by irregular and fleeting movements of the limbs and/or axial musculature including also the muscles of the face, jaw and tongue. The intensity of movement varies from very minimal buccolingual chorea characteristic of longterm neuroleptic toxicity to the wild and exhausting limb-flailing chorea called hemiballism. Limb tone in persons with chorea is neither rigid nor spastic; it is usually hypotonic or normal. Degenerative and destructive processes in the striatum and subthalamic nuclei and striatal suppression related to certain classes of drugs are the major pathologic substrates of chorea. Superficially it appears paradoxical that the most common causes of choreiform movement disorders are the same neuroleptic drugs (phenothiazines, butyrophenones, and reserpine) that are the most common cause of parkinsonian disability. Unfortunately the choreiform abnormalities are not so easily reversible and may be permanent in some cases. The model for choreiform disorders is Huntington's chorea. This condition is a rare, inherited (autosomal dominant), degenerative process involving the striatum, particularly the small-cell population (the large-cell neurons are relatively spared), and also the cerebral cortex, giving rise to a combination of progressive limb and axial chorea and dementia. Sometimes early in the disease a parkinsonian syndrome with rigidity and bradykinesia precedes the chorea, presumably because of

involvement of the dopamine system of the striatum. This changes to chorea with progression. When this unfortunate process is recognized in a family, genetic counseling becomes paramount as an exercise in prevention, the aim of which is to discontinue the abnormal gene pool. Sydenham's or rheumatic chorea is a mild, self-limited limb and axial disorder associated with rheumatic fever in children. The decreasing incidence of rheumatic fever may soon make Sydenham's chorea an historical curiosity. It is occasionally exacerbated or uncovered in adult women who are pregnant (chorea gravidarum) or taking birth control pills. Because it is reversible and not progressive or fatal, very little is known of the pathophysiology. However, it is presumed that the substrate is striatal dysfunction because the same drugs that to some degree ameliorate Huntington's chorea are also effective against Sydenham's chorea. A variety of metabolic conditions are associated with choreiform movements. Among these are hyperthyroidism, lupus erythematosus (presumably the vasculitis affects the arteries supplying the striatum), atropine poisoning, anticonvulsant toxicity (e.g., phenytoin, carbamazepine, and phenobarbital), and L-dopa therapy for parkinsonism. Relief coincides with clearing of the metabolic derangement.

Hemiballism Hemiballism is a violent, flailing chorea of the limbs opposite a lesion in the subthalamic nucleus or, rarely, the striatum. With few exceptions the pathogenesis is infarction, less often hemorrhage, and rarely tumor. Fortunately, in most cases the disease is self-limited because the process (e.g., ischemia) resolves or because the lesion enlarges to involve either the cerebral peduncle or the internal capsule, causing weakness from involvement of the pyramidal system; the chorea, which is expressed through an

intact pyramidal system, disappears.

Athetosis Athetosis is a rare movement disorder characterized by involuntary, slow, twisting, writhing movements of the trunk and limbs. It frequently has associated erratic choreiform components. Striatal injury, particularly prominent in the putamen, has been considered the pathophysiologic substrate; however, widespread brain damage is usually present and confounds any clear analysis. The most common causes are perinatal hyperbilirubinemia, which involves the brain (kernicterus) and prematurity (which can result in damage to developing forebrain often with periventricular hemorrhage). These leave the infant with cortical and prominent basal ganglia damage, with subsequent choreoathetosis and, usually, mental retardation.

Dystonias With one exception the dystonias are uncommon disorders. They are characterized by torsion spasms of the limbs, trunk, and neck. They may be progressive or static and are related to past encephalitis in a few cases but are usually idiopathic. In a few individuals who were well studied post mortem, either no pathology or various combinations of basal ganglia lesions were seen. Spasmodic torticollis is the most common idiopathic form and is characterized by intermittent excessive and involuntary contractions of the sternomastoid muscle on one side (rarely bilateral giving retrocollis). Interestingly, the head can be guided back to a neutral position with very gentle pressure on the side of the face. The head drifts back to its distorted position when the pressure is released. Therapy with anticholinergic medications has had a minimal positive effect on dystonic disorders. Recently, intramuscular injections of weak

solutions of botulinum toxin, a powerful neuromuscular transmission blocking agent, have been shown to be useful in relieving dystonia for periods up to four to six months. The one frequently seen dystonia is related to an overdose of neuroleptic drugs and is always reversible when the drug is withdrawn or counteracted by anticholinergic drugs. Involuntary and occasionally severe tonic contraction of axial muscles is most common, ranging from jaw clenching similar to the trismus (lockjaw) of tetanus to severe opisthotonic posturing similar to that seen in decerebration. Recognition of this easily reversible cause of these otherwise ominous signs is obviously important. A good history can usually clarify the situation, and reversal of the dysfunction with anticholinergic medication confirms the diagnosis.

Tardive dyskinesia Tardive dyskinesia is the term given to the iatrogenic axial chorea seen most often in women exposed to long-term neuroleptic use. The neuroleptic drugs (phenothiazines and butyrophenones), among many other effects, block both dopamine and to a lesser degree acetylcholine systems and usually cause parkinsonian side effects; dystonia is caused by acute overdose. On withdrawing the drugs or decreasing the dose, these difficulties usually clear. In its mildest form, constant mouthing with protrusion of the lips, mandible and tongue is seen, not unlike the movements of some very elderly persons and individuals who continually adjust loose upper dental plates. In more advanced stages the trunk muscles are involved and there is a characteristic irregular, incessant pelvic thrusting, which can cause the patient to become a recluse. Unfortunately, after chronic use, axial and to a lesser degree limb choreiform movements are uncovered in some cases and persist. Treating these patients with the same dopamine-blocking neuroleptics is usually successful in improving symptoms for a while, presumably

on the basis of production of parkinsonian side effects. Unfortunately, the choreiform-causing changes continue to occur and finally break through the parkinsonian effects so that the dose of the drug must continually be increased. Withdrawing the drug leaves a worse choreiform problem. The mechanism of tardive dyskinesia appears to be due to a compensatory increase in the number of dopamine receptor sites following long-term administration of neuroleptic drugs, producing hypersensitivity. When the drugs are withdrawn, uncovering blocked dopamine receptor sites or increasing dopamine levels toward normal, the total number of active sites may have become so great that there is an excessive dopaminergic response (chorea) to normal levels of dopamine elaboration in the striatum. Some of the newer "atypical neuroleptic" drugs are less likely to do this but most still can result in dyskinesia. Antioxidant prophylaxis and therapy has recently shown some promise in preventing and, to a lesser degree, reversing tardive dyskinesia. However, this may not be as effective as was first suspected. Nonetheless, it might be prudent to include antioxidants concomitantly with chronic neuroleptic therapy.

References

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Calne, D., Chas, J.N., Barbeau, A. (eds).: Dopaminergic Mechanisms. Advances in Neurology, vol 9., New York,, Raven Press, 1975.

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Carpenter, M.B.: Brain stem and infratentorial neuraxis in experimental dyskinesia. Arch. Neurol. 5:504, 1961.

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Coleman, J.H., Hayes, P.E.: Drug-induced extrapyramidal effects - A review. Dis. Ner. Syst. 36:591, 1975.

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Marsden, C.D., Fahn, S. (eds.): Movement Disorders 3. Oxford, Butterworth Heinman, 1994.

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Diploc, A.T., et al. (eds.): Vitamin E, Biochemistry and Health Implications. Annals of the N.Y. Academy of Medicine, Vol. 570, 1989.

Questions Define the following terms:

extrapyramidal, oxidative stress, parkinsonism, Parkinson's disease, bradykinesia, delayed postural reflexes, resting tremor, cogwheel, festination, chorea, athetosis, hemiballismus, dystonia, "wearing off", "on-off", hypophonia.

18-1. What are the functions of the extrapyramidal system? 18-2. What is the cause of Parkinson's disease? 18-3. What are the symptoms of Parkinson's disease? 18-4. What is the pathology of Parkinson's disease? 18-5. What are the treatments for Parkinson's disease? 18-6. What problems complicate treatment of Parkinson's patients? 18-7. What surgical treatments are available for Parkinson's disease? 18-8. What is essential tremor? 18-9. How do you recognize essential tremor? 18-10. What are the available treatments for essential tremor? 18-11. What are potential causes of chorea and athetosis?

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Disorders of the Nervous system - Reeves & Swenson Table of Contents

Chapter 19 - Cerebrovascular disorders Each year approximately 700,000 adults in this country have a stroke.

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On this page ●

Occlusive disease

●

Diagnostic and

Cerebrovascular dysfunction, occlusive and hemorrhagic, is the third most

therapeutic

common cause of death in this country and is very high on the list of

considerations

disorders causing morbidity. Approximately 2 million people are now ●

disabled from the effects of one or more cerebrovascular events. A great

Transient ischemic attack (TIA)

number of these individuals are in the working-age population. ❍

Carotid syndromes

❍

Vertebrobasilar

Approximately 80% of all strokes are ischemic (due to occlusion of a vessel). Atherothrombotic occlusion, embolic occlusion and small vessel syndromes

occlusion are the three major categories. While the pathophysiology of ❍

Differential

atherothrombosis is similar to the pathophysiology of occlusion in many diagnosis of TIA

other vascular beds, the small vessels of the brain appear to be particularly ❍

Medical therapy for

susceptible to the effects of aging, complicated by hypertension and TIA

diabetes. These vessel walls can undergo a change known as ❍

"lipohyalinosis" that can damage the wall and compromise the lumen.

Surgical therapy for TIA

Also, tiny cerebral vessels can be damaged by accumulation of abnormal ●

Stroke in evolution

resulting from progressive accumulation of amyloid on the walls of small

●

Completed stroke

arteries and arterioles over the surface of the cerebral hemispheres. It

●

Stroke prophylaxis

proteins in a condition called "amyloid angiopathy." This is a disorder

occurs with increasing frequency after age 65 and progressive arterial

●

stroke

narrowing results in ischemic lesions. The affected vessels are fragile and may also give rise to intracerebral hemorrhage. The condition is frequently

Uncommon causes of

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associated with Alzheimer's disease, adding an ischemic component to that

Intracranial hemorrhage

❍

disease's degenerative process. A small number of occlusive strokes are

Intraparenchymal hemorrhage

caused by inflammatory involvement or spasm of arteries. Also, trauma

❍

Prognosis of

can result in the accumulation of blood in the wall of the artery, a

intraparenchymal

condition called "dissection" because it separates ("dissects") the intima

bleeding

from the adventitia. This can compromise the lumen and even result in

❍

local thrombus and thromboembolus from the damaged area of blood

Subarachnoid hemorrhage

vessel. In some patients with weak connective tissue this can happen

❍

spontaneously and can be a cause of stroke in young patients.

Prognosis of subarachnoid

Although there are no clear-cut data on this point, there is increasing

hemorrhage

evidence that a major percentage of occlusive strokes are caused by ●

References

●

Questions

embolism of clot or atheromatous material from cervical carotid or vertebrobasilar atherosclerotic plaques to the intracranial vessels.

Complete occlusion of the cervical portion of the internal carotid or vertebral arteries is probably not, as once thought, the most common cause of cerebral infarction, although primary intracranial branch occlusion is still considered a relatively frequent cause of stroke. The symptoms of ischemic stroke are typically the sudden, usually unprovoked onset of a neurological deficit referable to damage to brain in the distribution of a specific artery. There are individual differences in presentation based on the particular blood vessels affected (see below) and the particular

pathophysiology. For example, embolic strokes typically reach maximum deficit within the first several minutes, while atherothrombotic strokes may present as transient deficits or the stuttering evolution of symptoms. Not all ischemic strokes are due to occlusion of arteries. Cerebral vein occlusion can cause ischemia, although less commonly. This typically occurs in hyperviscosity conditions (such as dehydration or other hyperviscosity states, such as with high red or white blood cell counts or thrombocytosis), hypercoagulability and, occasionally, in otherwise healthy young women due to the effects of estrogen on coagulation. These strokes are more likely to present with headache, confusion and seizure, along with evidence of some intraparenchymal hemorrhage on scans. Intracranial hemorrhage, excluding traumatic causes, accounts for approximately 20% of all strokes. Primary intracerebral hemorrhage in hypertensive individuals and subarachnoid hemorrhage from weak blood vessels (congenital or acquired arterial aneurysms or arteriovenous malformations, mostly) are the major categories. Amyloid angiopathy may be a major etiology in individuals over 65.

Occlusive disease The brain, in contrast with other organs, localizes specific functions to particular regions. Therefore, occlusion of an artery supplying a small area of the brain has a profound and specific effect. Although regeneration or at least functional compensation by the remaining tissue is the rule with most organs, significant regeneration does not occur in the brain. Functional compensation does occur, but the margin of safety is not nearly so great as in the kidney or other organs. Therefore, vascular occlusion and focal injury is significantly more serious in the brain. The brain makes up only 2% of total body weight but uses more than 10% of the oxygen metabolized by

the body, uses almost 20% of the glucose, and receives almost 20% of the cardiac output. This amounts to about 50-80cc of blood per 100 grams of brain tissue per minute in gray matter and a third to a half of this in white matter. If blood flow falls below about 15cc per 100 grams per minute, dysfunction of neurons begins, and the longer the brain is ischemic the more likely there is to be cell death and necrosis. Neurons respire only aerobically and therefore are dependent on an uninterrupted supply of metabolic substrates. An illustration of this is that only three to eight minutes of cardiac arrest result in irreversible brain damage, emphasizing the striking dependency of the brain on an adequate blood supply for proper functioning. There are well-developed safety factors that help to protect the brain when its blood supply is threatened. The brain vasculature is able to adjust its arterial perfusion over wide changes of blood pressure to keep a relatively constant and adequate blood supply. This self-adjustment or autoregulation causes cerebral vasodilatation when the mean blood pressure drops below normal levels and maintains an adequate blood supply until the mean arterial pressure reaches approximately half the normal levels (50-60 mm Hg); lower pressures are associated with focal and diffuse cerebral dysfunction. This safety factor can be of great importance during systemic hypotension and also at a local level can protect against flow changes caused by increased intracranial pressure or progressive atherosclerotic narrowing of cortical or cerebral arteries. The cerebral arterial system, through a direct myogenic reflex contraction, responds to increasing blood pressure by constriction, thus keeping perfusion within normal ranges and avoiding the possible hemorrhagic consequence of excessive pressures. When mean arterial pressure rises above approximately 150 mm Hg for prolonged periods, however, autoregulation may break down. Segments of cerebral arterioles may dilate to an excessive degree, breaking down internal integrity and the blood-

brain barrier allowing focal cerebral edema and dysfunction. This condition has been appropriately labeled hypertensive encephalopathy and occurs rarely, probably because extended periods of hypertension of such great degree are unusual. During systemic hypoxia, the brain is able to extract oxygen from the blood in increasing amounts and thus compensate for arterial hypoxia down to a tension of 50 mm Hg. Beyond this, some vasodilatation probably occurs, possibly on the basis of tissue hypoxia and associated local tissue acidosis, which is a strong stimulant of cerebral arteriolar and capillary dilatation. Small changes in the arterial CO2 partial pressure cause marked changes in cerebral blood flow, presumably by changing the perivascular hydrogen ion concentration. High CO2 tensions such as occur with pulmonary disease result in a lower pH in tissue and cerebral vasodilatation, which is an indirect protection against the associated hypoxia to which the brain vasculature is less reactive. Low CO2 partial pressures, such as occur with hyperventilation, cause a decrease in the perivascular hydrogen ion concentration and subsequent vasoconstriction. This decreases the cerebral vascular bed and may decrease intracranial volume by as much as 2-3%. During central neurogenic hyperventilation caused by midbrain or pontine dysfunction (see Chap. 24), this decrease in volume may have some protective effect against progressive rostrocaudal deterioration though hyperventillation in an otherwise normal individual often produces light-headedness due to diminished cerebral blood flow. Collateral circulation is the major safety factor that helps protect the brain from damage caused by occlusion of one or more of its major arterial inputs. In the human there are many potential channels for collateral circulation, but only a few are significant following cerebrovascular occlusion. The circle of Willis (Fig. 19-1) is the most important channel for collateral circulation following occlusion of either the internal carotid system or the basilar system. It is occasionally developmentally incomplete, and

even when complete is often an unsuccessful collateral channel unless vessel occlusion occurs gradually, which gives an opportunity for increased compensatory flow through the usually small posterior and/or anterior communicating arteries. Fortunately, a common cause of narrowing in the major cerebral vessels is gradual atherosclerotic thrombotic occlusion, which often allows time for adequate development of collateral flow to the distribution of the affected vessel. The most frequently occluded major vessel is the internal carotid artery in the cervical region just above the bifurcation of the common carotid artery. Following occlusion and despite frequent anomalous variations in the circle of Willis, collateral flow is possible in approximately 90% of the population from the opposite carotid system via a patent anterior communicating artery or from the vertebrobasilar system through a patent ipsilateral posterior communicating artery, or from both sources. This rather optimistic view of the compensatory potential of the circle of Willis is somewhat dampened by the realization that age and associated cerebral atherosclerosis can also affect these potential collateral channels. Also, if atherosclerosis predisposes to thrombus formation and subsequent embolus, and if the emboli lodge beyond the circle of Willis (such as in the middle cerebral artery or its branches), then the circle proves useless as a collateral supply. The rapidity of occlusion with embolism also tends to preclude a useful development of collateral from other sources. There is some anastomosis between the distributions of the main cerebral arteries and the main cerebellar arteries. These anastomoses largely occur at the arteriolar level in the pia over the respective hemispheres. These channels are variable and also limited by the same factors that limit the effectiveness of the circle of Willis, i.e., anatomical variability, difficulty responding to rapid occlusion, and the condition of the vessels. The penetrating arterial branches that reach the deeper structures of the brain anastomose to some degree at a capillary level with neighboring arterial branches, but this

collateral circulation by itself is rarely of functional significance following an occlusion and the penetrating vessels therefore act essentially as end arteries. Based on this anatomy of anastomosis, there is an area of overlapping blood supply in the regions between major blood vessels. This becomes clear to you if you review the areas of blood supply, especially of the brain stem and deeper structures of the cerebral hemispheres. With ischemia in the distribution of a single-vessel system (e.g., the middle cerebral, Fig. 19-2), these areas of overlap are often able to avoid major damage. However, if blood flow is affected diffusely (such as with severe systemic hypotension/shock), these areas, somewhat inappropriately called watershed areas, become the regions of the greatest damage. This is because they are at the farthest reaches of blood supply and therefore are the first to develop decreased flow with low systemic perfusion pressure. A third group of potential collateral circulation channels consist of connections between the external and internal carotid arteries (e.g., external maxillary-ophthalmic-internal carotid). These potential channels are rarely significant as a sole source of collateral circulation in persons with acute stroke. However, they may give major collateral support and decrease the severity of or prevent ischemia with slowly progressive occlusions of major vessels. Individuals have been described who have minimal symptoms or signs of cerebral ischemia but have complete occlusion of three and even all four major cervical vessels (both internal carotids and vertebral arteries). In such patients, arteriograms reveal large collateral channels from the external carotid system that anastomose with the intracranial arterial systems through the orbit and/or foramen magnum. Very gradual and probably staggered carotid and vertebral occlusion allows these compensatory channels to enlarge and prevent major ischemia. Almost 50% of persons who suffer a complete ischemic stroke have stenotic or occlusive disease in the cervical vessels. Also, approximately half of patients with completed ischemic stroke have a history of

prodromal symptoms and signs referable to ischemia in the areas supplied by the involved vessels. These episodic signs and symptoms take the form of transient neurologic deficits (transient ischemic attacks, TIAs).

Diagnostic and Therapeutic Considerations For therapeutic convenience and with some arbitrary delineation, the degree of cerebral arterial occlusive disease can be divided into (1) covert disease (i.e., asymptomatic with risk factors for disease), and (2) overt disease (i.e., symptomatic). In the latter case, symptoms may appear in three patterns: a. transient ischemic attack, b. stroke-in-evolution, and c. completed stroke.

Covert disease

It is critical to identify patients who are at risk for stroke and, where possible, institute programs to prevent them. There are different risk factors for different types of stroke. For example, small vessel damage is promoted by hypertension and diabetes mellitus. Hypertension is also a major risk factor for intracerebral hemorrhage. There are multiple risk factors for arteriosclerosis, a major predisposition for stroke due to large vessel occlusions. Embolic disease usually results from some cardiac abnormality (such as atrial fibrillation, cardiac valvular disease or large right to left shunts. Most of the above conditions are, to some extent, treatable in a manner that can decrease risk for stroke. Unfortunately, many of these interventions provide imperfect prophylaxis and some major risk factors for stroke are not modifiable, such as advancing age. Hypertension is the major prospectively proven and modifiable predisposition to both ischemic and hemorrhagic stroke. The pulsatile trauma to arteries and turbulent flow caused by systemic

hypertension presumably initiates the atherosclerotic process and also causes microscopic arterial wall trauma and aneurysmal ballooning in small penetrating vessels (a process called lipohyalinosis). The thickening of the wall due to this process presumably is the reason for most small vessel occlusions, and the fact that this process results in weakening and microaneurysmal dilations of the wall makes hypertension the source of most intracerebral hemorrhages. Most authorities now feel that treatment of even mild hypertension is useful prophylaxis against stroke. In the last 25 years the incidence of ischemic stroke, intracerebral hemorrhage and, to a lesser degree, heart attack have decreased (recent data suggest that a plateau has been reached). The major reason for this decrease appears to be the aggressive treatment of hypertension. Dietary modification (e.g., eating less red meat, less dairy products, and more fish and fowl, whole grains, vegetables and fruits) and decreased smoking have probably contributed to the decline, as well. There are many factors, in addition to hypertension, that contribute to atherosclerosis. Obesity, hyperlipidemia, sedentary lifestyle, and cigarette smoking, are major factors (they are also implicated as causes of coronary atherosclerosis and insufficiency). Homocysteine, an amino acid by-product of the metabolism of methionine, an essential amino acid derived mostly from red meat, has been linked to the atherosclerotic process. It may interact with the "bad" form of cholesterol (low density lipoprotein: LDL) in the pathological process. If inadequate amounts of folic acid, Vitamins B12 or B6 are present in the diet, homocysteine accumulates and may be damaging. High red meat intake and low vegetable intake are prevalent in the western world, especially North America resulting in a folic acid deficiency in a significant portion of the population. Despite recognition of this risk factor, recent studies using folic acid (also B6 and B12) to try to prevent cardiovascular, cerebrovascular, and peripheral vascular events have had disappointing results. Nonetheless, epidemiological studies have clearly shown an association

between low prevalence of atherosclerosis and vascular events in populations eating more whole grains, vegetables, and fruit. However, it not clear what specific ingredient or ingredients are involved or whether the effect is actually due to lower intake of animal products in this type of diet. Low-density lipoproteins (LDL) appear to be critical to the process (they are the major lipid component of the "plaque"). Treatments that lower LDL with newer drugs (statins, which decrease cholesterol production by the liver) are associated with a decreased incidence of vascular events, including stroke and myocardial infarction. However, it is not clear that this effect is directly due to the lipid lowering function and the statins may work by anti-inflammatory, antioxidant, or other means to lower stroke risk. This is an active area of research. It is clear that oxidation of LDL is a part of the process of atherogenesis, although prospective studies of antioxidant administration (e.g., Vitamins E, C, and beta carotene) have yielded disappointing results. Elevated high-density lipoproteins (HDLs) are inversely proportional to the risk of atherosclerosis. However, it is harder to elevate HDLs than to lower LDL and drug development and study is in its infancy. Persons with diabetes mellitus are predisposed to atherosclerosis and occlusive stroke. It is suspected but not definitively proven that fastidious treatment of the glucose intolerance is useful prophylaxis against generalized atherosclerosis. It appears that the prime mechanism of damage is due to osmotic effects of glucose and its breakdown products on endothelial health so glucose control would be predicted to help. For persons at risk for embolization from cardiac valves, fibrillating atria, or ischemic endocardium, chronic anticoagulation with antithrombin agents is considered the treatment of choice. Some antiplatelet agents appear also to be of use in persons with artificial heart valves. Of course, full anticoagulation conveys some risk of both intrapaenchymal hemorrhage as well as hemorrhage around

the coverings of the brain. However, in the above situations, this risk appears less than the risk from well-regulated anticoagulation in these patients with risk for repeated systemic embolizations. It is less clear what to do about patients with right to left shunts (such as a patent foramen ovale). These can be closed via transcutaneous catheter placement of an "umbrella", however, the precise criteria for considering such closure are not well-established.

Overt disease

1. Transient Ischemic Attack

A transient ischemic attack (TIA) is defined as a reversible episode of neurologic deficit caused by vascular insufficiency usually lasting no 5 to 30 minutes but occasionally persisting for 24 hours and rarely several days (the longer the TIA the more likely there is to be some actual tissue destruction seen by sensitive tests, such as MRI). The syndrome of TIA is defined by complete clinical recovery, despite the fact that there may be evidence of damage on MRI. Approximately half of all patients who develop completed ischemic destruction (infarction) of brain tissue have had premonitory transient ischemic attacks. This underscores the importance of recognizing the TIA, since this defines a patient who is at risk for stroke. In many instances, the risk of going on to have stroke is modifiable and identification of the TIA affords an opportunity to institute such treatment. From 20-40% of patients with TIAs progress to ultimately develop a cerebral infarction. The prognosis for vertebrobasilar distribution attacks is somewhat better than that for carotid attacks, with approximately 20% and 40%, respectively, developing infarction on long-term follow-up, if untreated. Most of what we will present in the following discussion of TIA will be relevant to later discussion of

ischemic stroke, its symptoms and presentation. Therefore, we will address these issued in some detail before going on to consider the issue of stroke. First, we will discuss the symptoms of ischemia in several vascular distributions. Although these symptoms are transient in the syndrome of TIA, completed stroke in the particular vascular distribution will result in similar (albeit permanent) symptoms. Then we will consider the management of the patient presenting with TIA before continuing with discussion of stroke.

Syndromes of the carotid system

Disease in the carotid circulation results in one of several symptoms patterns. One classic pattern is transient monocular visual obscuration (amaurosis fugax) that is due to retinal ischemia. Amaurosis fugax usually results from internal carotid stenotic or ulcerative disease. Symptoms of damage to the cerebral hemisphere classically present as contralateral hemimotor, hemisensory, and hemivisual deficits, while dysphasia may be present if the dominant hemisphere is involved. Cerebral symptoms alone may be caused by either cervical carotid disease, hemispheric small-vessel disease or embolization from the heart (atrial fibrillation, valvular disease or ischemic wall) or aortic arch. A palpably depressed carotid pulsation suggests carotid stenotic or occlusive disease, although this is often not detected due to preserved pulsation in the patent overlying external carotid. The presence of an ipsilateral carotid bruit (usually in early systole and high-pitched) not referred from aortic valvular disease is strong evidence of carotid stenosis; however, almost 75% of patients with radiologically proved carotid stenosis do not have a bruit audible at the bedside. Remember, complete occlusion of the carotid artery will not have a bruit. Also, be aware that approximately 10% of adults who have a carotid bruit on routine examination with no history of ischemic disease have normal carotids on angiographic

investigation. Therefore, when a localized bruit is heard over the carotids, atherosclerotic disease is present in 90% of cases, although the clinical significance of this bruit is not predictable. When is a carotid lesion significant? Before blood flow is hemodynamically disrupted to a significant degree, a carotid stenosis must be at least two-thirds complete; the diameter of the lumen as demonstrated angiographically is usually 1 mm or smaller. As mentioned, approximately 90% of the population can, because of collateral circulation through the circle of Willis, withstand complete occlusion of a single carotid or vertebral artery without ischemic symptoms, barring the presence of other occlusive disease beyond the circle of Willis. Rapid occlusion by trauma or thrombus in an otherwise normal carotid is more likely to be associated with cerebral symptoms because of lack of time for development of effective collateral circulation. In patients with a borderline-significant stenosis, significant drops in mean arterial blood pressure may cause focal symptoms of transient ischemia. However, the fall in blood pressure would have to be quite large and this is a rare mechanism of TIA. A higher proportion of transient ischemic episodes are due to microemboli arising from atherosclerotic plaques (particularly those with ulcers) in the cervical vessels. The emboli from ulcerated plaques may consist of platelet aggregates, small thrombi or atherosclerotic ulcer debris. Emboli typically are broken up rapidly on meeting the small vessels of the retina and brain and then pass distally with subsequent alleviation of ischemic symptoms and signs. These small emboli can sometimes be viewed by transcranial doppler assessment providing evidence for this mechanism.

Syndromes of the vertebrobasilar system

Transient ischemic symptoms referable to the posterior vascular systems are quite variable, which is consonant with the many functional systems packed into the relatively small structure of the brain stem

and posterior portions of the hemispheres. Alone or in various combinations, vertigo, bilateral blurring or loss of vision, ataxia, diplopia, bilateral or unilateral (occasionally alternating) sensory and motor deficits, and syncope are common manifestations of vertebrobasilar insufficiency. Transient vertigo or ill-defined dizziness is a very common complaint in persons past age 60 and is not necessarily related to ischemia. Indeed the most common cause is benign positional vertigo, a disorder of aging related to otolith displacement into the posterior semicircular canals and occasionally cervical spondylosis (see Chap. 6). The associated symptoms noted earlier must therefore be present before a clinical diagnosis of transient vertebrobasilar ischemia can be entertained. Evidences of vertebral insufficiency at the bedside are: (1) depression of blood pressure in either arm, suggesting the possibility of subclavian or brachiocephalic (innominate) artery occlusion with reverse flow in the ipsilateral vertebral artery; (2) bruits over the supraclavicular regions in the absence of aortic ejection murmur, suggesting either subclavian or vertebral narrowing; (3) bruits over the posterior triangle of the neck, which may be changed on turning the head, suggesting vertebral narrowing; and (4) production of vertebrobasilar ischemia symptoms and signs by flexing, extending, or rotating the neck, suggesting osteoarthritic compression of the vertebral artery in the transverse vertebral foramina.

Differential diagnosis

Transient neurological symptoms in individuals >45 years old are most commonly due to cerebrovascular events (TIA). However, there are a several other possibilities that should be considered. Migraine equivalent, focal seizures, benign positional vertigo, Meniere's disease, and demyelinating disease are the most commonly encountered categories of disease that can be mistaken for TIAs.

Historical information is usually sufficient to eliminate or implicate these possibilities. Cranial arteritis (temporal arteritis) must be considered in the patient over 50 who has transient amaurosis usually with but occasionally without temporal headache. Such persons almost invariably have an elevated sedimentation rate (usually higher than 55 mm/hour) and may also have an associated proximal limb condition called polymyalgia rheumatica (chronic aching in the proximal limbs and pelvic and shoulder girdles associated with malaise). These patients usually have a positive temporal artery biopsy, and respond dramatically to corticosteroid therapy. Occasionally persons with cranial arteritis have a stroke caused by inflammatory occlusion of major cervical (most often the vertebral artery) or cerebral vessels. Therefore, a test of sedimentation rate should be ordered routinely in all stroke patients over the age of 50. Hypoglycemia is also a consideration, although such patients usually show evidence of diffuse bilateral cerebral dysfunction. Occasionally the low blood glucose level presents as focal and lateralized difficulty. It is reasonable therefore to check the blood glucose level early in all apparent stroke patients (this should also be done due to the fact that stroke victims with elevated sugar have a poorer prognosis and may require acute therapy). Treatment with glucose of the rare patient with hypoglycemic "stroke" may give dramatic results. Some patients with focal lesions (tumors or AVMs) may present with transient symptoms (probably due to ischemia in adjacent brain tissue by poorly regulated shunting of blood into the lesion).

Medical therapy

Treatment of the patient after a TIA is dependent upon recognizing that this places them at higher risk for ischemic stroke and that many of the risks are modifiable. To some extent, the selection of therapy is based on recognition of the specific etiology of the TIA, while some other recommendations are generic

and appropriate for all such patients. For example, modification of stroke risk factors (smoking, hypertension, obesity, hypercholesterolemia, poor glucose regulation) are generic recommendations. Also, platelet antagonists generically decrease stroke risk after TIA (assuming that these medications are tolerated). They appear to work by decreasing platelet aggregation and the initiation of intravascular coagulation, a step in the genesis of stroke of many types. Antiplatelet medications have been clearly shown to prevent cerebral infarction by a number of multiple-institution studies. In particular, persons with TIAs appear to have approximately 20-30% less chance of going on to have a completed stroke if they take acetylsalicylic acid than if they do not. More recently, statin drugs have been shown to decrease the risk of stroke in patients with cerebrovascular disease. Interestingly, it is not clear whether this effect is actually due to the lipid-lowering effects of the medication. In any event, these medications should be considered earlier in the management of patients with cerebrovascular disease than would be warranted on the basis of their lipid profile alone. Although these generic recommendations may be all that can be done to decrease the potential for stroke in the patient with small vessel disease, there are two specific scenarios that would call for additional or different therapy. These scenarios include the patient with severe atherosclerotic disease of the large vessels and the patient with significant risk for cerebral embolization from cardiac sources. In the former case, surgical intervention may be necessary (see below) while, in the latter case, anticoagulation is often appropriate. Persons with clinical evidence of embolization from sources other than the cervical vessels (e.g., atrial fibrillation, diseased or prosthetic cardiac valves, and infarcted cardiac walls or aorta) may benefit from anticoagulation. It has now been shown that patients with chronic and intermittent atrial fibrillation, whether caused by rheumatic disease or atherosclerosis, should be on long-term, low-level

anticoagulation with warfarin (Coumadin) (INR between 2 and 3). Patients with mechanical heart valves require even higher levels of anticoagulation. There are some special cases that should be discussed. Individuals who have atrial fibrillation (AF), are under the age of 65, and who have no other evident cardiac disease on echocardiography (i.e., idiopathic AF) may not need warfarin. The incidence of complicating hemorrhage from the anticoagulant is higher than the incidence of embolic stroke in these patients. They may be treated with platelet inhibitors (aspirin, others), which have a small but significant prophylactic effect and fewer hemorrhagic side effects. However, other patients with atrial fibrillation should be maintained on warfarin unless their risk of bleeding with the anticoagulant exceeds their risk of stroke. This may occur in the patient who is at very high risk of falling, for example. Aspirin, alone, may provide these patients some prophylaxis with minimal risk of life-threatening hemorrhage (assuming that they do not develop gastritis or bleeding ulcers). Another special case relative to embolization is the individual with a right-to-left shunt (either through the heart or lungs). Although selection criteria are not entirely established, most patients who have had a documented stroke or TIA due to such a shunt should be considered for closure. These days, there are an increasing number of methods for minimally invasive closure of shunts.

Surgical therapy

Carotid stenosis on the side of transient symptoms is the clearest reason for vascular surgery today. When stenosis exceeds 70% and in some cases of lower level stenosis when the plaque shows signs of irregularity, surgical treatment should be considered. At lower levels of stenosis, surgical treatments are no better than medical (platelet antagonists) and, of course, with low-level stenosis (<50%) surgical

treatment is not as good as medical. There is more controversy about what to do in the case of highlevel asymptomatic stenosis. Probably, platelet antagonists are most appropriate until stenosis is very high (>90%). Future studies will be needed to clarify this issue. The surgical treatment of choice has been carotid endarterectomy, a procedure in which the carotid artery is opened and the diseased tissue is removed from the inside before the artery is closed up again. This procedure is associated with some stroke risk, but this perioperative stroke risk should be below 3% within the first month (with an overall complication rate of <5%, otherwise, it should not be performed due to superiority of medical management.). Completely occluded carotids are rarely operated on now because of the high risk of hemorrhagic complications and surgical failure as well as temporarily heightened stroke risk. There are recent attempts to determine whether endovascular procedures might yield better results. One difficulty with angioplasty or stent placement is that the procedure may result in distal embolization due to disrupted plaque. Therefore, the most recent procedures have deployed a protective device downstream of the procedure. Although there have been some promising results, this remains under investigation. It should be noted that this procedure does have the potential for treating athersclerosis at other levels of the cerebral circulation (endarterectomy is only possible in a limited area of the extracranial carotid artery system). Vertebrobasilar ischemic disease is rarely surgically approachable. The exceptions might include proximal subclavian or brachiocephalic stenosis, proximal vertebral stenosis, and vertebral impingement in the transverse cervical foramina by osteoarthritic spurs, and a variety of procedures have proved successful. In some cases of osteoarthritis, moderate immobilization of the neck with a soft orthopedic collar is often adequate to enable the person to avoid surgery.

In all patients going to surgery in most institutions, especially those with carotid disease, antiplatelet anticoagulation (where not medically contraindicated) is begun prior to surgery to decrease the incidence of operative embolization and is continued indefinitely after surgery.

2. Stroke-in-Evolution

Approximately 20% of persons who progress to cerebral infarction and approximately 10% of those who suffer a cerebral hemorrhage have a history of evolution of deficit over several hours to several days (and, rarely, longer). Anticoagulation with heparin has been commonly used and many consider it worthwhile, however, it is unproven therapy for patients with ischemic infarction-in-evolution. Of course, patient selection must be made with care because anticoagulation is contraindicated for persons with cerebral hemorrhage and also for those with severe hypertension. In Table 19-1 are listed some useful points to distinguish hemorrhage from ischemic infarction. However, there are many cases that cannot be clinically differentiated. The CT scan is considered the "gold standard" in this determination (since recently extravasated blood is very white on scans). Clearly this technique, which is rapid and noninvasive (and therefore not subject to the potential complications of invasive tests like lumbar puncture and arteriography), has revolutionized the emergency diagnosis of intracranial catastrophe (see Chap. 23). In patients with clear-cut and substantial neurologic symptoms of very recent onset (less than 3 hours), urgent consideration should be given to possible thrombolysis (with tissue plasminogen activator TPA). It is critical to know the precise moment at which the stroke began. Otherwise, it must be assumed that the stroke began immediately after the patient was last known to be well. The reason that this treatment should not be initiated after 3 hours from the onset of symptoms is that TPA performed

later than this significantly increases the risk of bleeding as the injured brain tissue is reperfused. This treatment should only be initiated after a CT scan is performed, demonstrating that the stroke does not have a hemorrhagic component. Also, it should not be given in a patient with extremely high blood pressure (due to potential for hemorrhage). There have been ongoing studies to determine whether some more focused thrombolysis (through an endovascular catheter) might be beneficial when performed after this 3-hour window (without producing intolerably high bleeding complications). Additionally, a recently approved device (the Merci retrieval system) has been approved for human use, for the mechanical extraction of emboli in cerebral vessels. It must be remembered, however, that approval of a device does not mean that adequate investigation has been done in order to prove its utility, which remains under investigation. While systemic thrombolysis (with TPA) represents an important intervention, the technique is applicable to a limited subset of the stroke patient population. The need for rigorous demonstration of a focal clinical deficit, for a precise time of onset of symptoms (<3 hours from treatment), and for a CT scan free from intraparenchymal hemorrhage prior to treatment, can only be met in a small group of the larger stroke population. Because of the severe time limits for intervention, a public education campaign has been launched throughout the country to establish stroke as a "911" emergency in hopes that patients will go to the hospital soon enough to make some of these acute therapies practical. Because of limitations in this approach we are looking for other ways to improve outcomes in the immediate post-stroke period. Other modes of therapy, which have some rationale, but are unproved in efficacy, aim at relatively or absolutely increasing the collateral blood supply or the amount of tissue oxygen to regions of progressing ischemia. Oxygenation of an ischemic brain can be increased in the hyperbaric chamber

and stroke dysfunction can be alleviated in some cases by this means. Unfortunately the deficits return when the patient is removed from the chamber. Standard means of oxygenation (e.g., nasal mask or catheter) have not proved useful unless they alleviate a systemic respiratory hypoxia. Hyperbaric oxygen has not, to date, been shown to improve long-term outcomes. There has been substantial interest in the potential for protection of ischemic neurons, "cytoprotection". This remains an ongoing area of active research since several approaches have shown promise in experimental models. Unfortunately, to date, none of these approaches have proven to be of clinical utility. The two fundamental approaches that have been investigated are to decrease metabolic need in the ischemic area, or to interfere with processes that occur in the ischemic brain tissue that result in sustained damage to cells. The cerebral need for oxygen can be decreased by hypothermia and some depressant drugs (e.g., barbiturates). Experimental evidence in animals with vascular occlusions supports the hypothesis that this might preserve some ischemic neurons from destruction while collateral circulation develops. Little clinical data are available to support or refute these findings. In recent years, some very promising approaches to the preservation of neuronal tissue from ischemic damage have evolved. Excitatory neurotransmitters such as glutamate have been shown to be released in pathologically high concentrations during ischemia and flood the ischemic zone causing excessive opening of calcium channels. This results in a calcium flood into the neuron, which is toxic to the mitochondria and causes death of the neuron. Glutamate receptor blockers and also calcium channel blockers have been shown to decrease the extent of ischemic damage in experimental animals and continue to be investigated in early clinical studies. The prevention of peroxide and free radical formation, which occurs in ischemic tissue especially when reflow occurs, has also been shown to be useful in decreasing the extent of experimental ischemic damage. From animal studies it is clear that

any of these protective agents, if they are to be successful, be given within hours of the onset of ischemia and infarction, with the rule being "the sooner the better". In most institutions surgery is not considered a useful approach to the occlusive stroke-in-evolution. However, just as with thrombolytic agents, if the patient is seen early enough (within one to two hours of onset of symptoms) and found to have an occluding internal carotid artery in the neck, endarterectomy could prove to be effective. Of course, if the stroke process stabilizes spontaneously or by conservative therapy and little neurologic deficit remains, the patient should be considered for evaluation for prophylactic cervical vessel surgery if significant stenosis is identified (see below).

3. Completed Stroke

The completed cerebral infarction is defined in two ways, temporal and anatomical. Temporal completion is a fixed, neurologic deficit lasting more than several days. Any recovery that occurs thereafter is related to dissipation of edema, vascular collateralization of surviving but functionally depressed tissue, and functional reorganization of surviving brain. The last, though formerly believed of great importance, has the least significance in recovery except in children. As time progresses, patients may develop compensatory strategies, and this can be encouraged through physical and occupational therapy. Restriction of use of the good limb (forcing use of the affected limb) appears to improve outcome, possibly by encouraging plasticity of central pathways. Alternative communication strategies may also be enhanced by speech therapy. Anatomical completion refers to infarction of the entire region of supply of a major cerebral vessel (e.g., the middle cerebral artery). In this sense, infarction in the distribution of one branch of the middle cerebral artery, producing for example an isolated expressive aphasia or monoparesis, is considered incomplete.

No proved therapy exists for reversing the temporally completed infarction, whether anatomically complete or not. One approach, however, aims at preventing or suppressing the significant cerebral edema, which almost invariably follows infarction and may be clinically significant from eight hours to seven days following the primary insult. This edema, by compressing contiguous vessels, may increase the area of destruction and also can cause secondary brain stem compression by the various routes of herniation of brain substance (e.g., tentorial and foramen magnum herniation; see Chap. 24 on stupor and coma). Herniation with brain stem compression is the most common cause of death occurring during the acute phase of infarction and hemorrhage. Various measures have been tried to prevent or lessen the edema to decrease both morbidity (size of stroke) and mortality. Corticosteroids, are not effective in decreasing the edema of cerebral ischemia, termed "cytotoxic edema." It is a common misperception that steroids are useful due to the fact that they are useful in decreasing the cerebral edema caused by neoplasms and inflammatory lesions. Hyperosmotic agents (e.g., urea, mannitol, glycerol), which dehydrate normal brain tissue, probably do not affect the edema in an ischemic or infarcted area that does not have access to the agents. They have not been clearly shown to decrease the morbidity of infarction. A drawback of hyperosmotic dehydration is that it increases blood viscosity and, therefore, could decrease blood flow into areas already compromised. If a patient is dehydrated early in the course of a stroke, careful hydration may, in fact, increase blood flow to the brain ischemic zones. Craniectomy in patients who are showing signs of herniation may be a better way to decompress the swollen brain and is being studied. Hyperthermia is not uncommonly present in patients admitted with ischemic stroke because of infection, dehydration, or central hypothalamic thermal dysregulation. It is associated with increased ischemic damage because of increased metabolic demand of hyperthermic brain tissue or for other

reasons. It should be treated quickly with temperature-lowering agents or procedures. Hyperglycemia is also a frequent temporary manifestation of stroke. Adrenalin outpouring and also increased cortisol production in the stressful circumstance of acute stroke (in an elderly patient with poor insulin reserve) is the likely etiology. Hyperglycemia likely reflects inadequate cellular glucose supply and should be remedied by careful lowering of blood glucose with insulin in the acute period. Hyperglycemia within the first 24 hours of stroke onset has been associated with increased stroke size. Carotid surgical therapy in persons with an anatomically incomplete infarction is considered useful prophylaxis against complete infarction for those with milder deficits who have approachable ipsilateral cervical carotid stenotic disease which is 70% or greater in degree. Presently, most centers wait four to six weeks before carrying out the surgery in order to avoid possible hemorrhage into the necrotic infarcted zone when normal flow and pressure are re-established.

Prophylaxis Of course, a major indication of high risk for stroke is the history of stroke. Therefore, careful consideration of modification of the various risk factors for stroke (see above) is critical.

Some Uncommon Causes of Occlusive Stroke Arteritis is an unusual cause of cerebrovascular occlusive or hemorrhagic disease and probably accounts for less than 1% of strokes in adults. The two major causes of inflammation and occlusion of the cerebral arteries are diffuse or focal autoimmune arteritis (e.g., polyarteritis nodosum, lupus erythematosus, giant cell and other cranial arthritides, and Takayasu's giant cell arteritis of the aortic arch vessels) and septic or infectious arteritis, which may be associated with purulent meningitis or

direct involvement of arterial walls by fungi (mucormycosis and aspergillosis in debilitated, immune deficient, or diabetic individuals) or bacteria seeded to arteries from septic emboli of cardiac origin. Meningovascular syphilis is a rare cause of stroke today. Thrombotic occlusion of or intracranial hemorrhage from diseased and weakened arterial walls may occur with either autoimmune or septic arteritis. Hemorrhage is most commonly seen with fungal and bacterial involvement where the arterial walls may be weakened and balloon out to form aneurysms, which are prone to rupture. Treatment of arteritic stroke is aimed at the primary process (i.e., corticosteroids for autoimmune disease, antibiotics for infectious disease, surgery where possible for aneurysms) and supportive care. Occlusive strokes in children may follow viral illness and are therefore presumed by many to be caused by focal autoimmune inflammatory processes or direct viral involvement. Migraine may rarely be associated with ischemic stroke, presumably on the basis of prolonged vasospasm or arterial edema. Women taking birth control medications are slightly more susceptible to cerebral arterial occlusion, and this susceptibility is increased if there is a history of migraine and if they smoke. Carotid or vertebral artery dissection is an unusual but increasingly recognized cause of ischemic infarction. Blood enters the wall of the blood vessel and accumulates between the intimal (endothelial) and media of the carotid or vertebral vessels. This may occur due to disruption of the endothelium, with a flap forming, or due to rupture of a small blood vessel in the wall of the artery (the vasa vasorum). This is often traumatic, although the trauma may be trivial (turning or extending the head, for example). Recently, it has been found that many patients with dissection have abnormally weakened connective tissue, sometimes associated with very clear connective tissue disorders (such as Marfan's syndrome or Ehrlers-Danlos' syndrome) and sometimes only observable at the ultrastructural or

biochemical level. The blood in the artery wall enlarges the wall, narrowing or occluding the main flow. If adequate collateral circulation is not available, symptomatic ischemia may lead to infarction and permanent deficits. Further, clot may form above the constriction and release emboli upstream to cause ischemic lesions. Clot may be released from the subintimal column of relatively static blood if the dissection reenters the vessel lumen upstream and the thickened wall may obstruct arterial branches. Dissection is usually associated with acute pain in carotid and vertebral referral areas: the lateral aspect of the neck and the ears and mastoid region, and behind the eye for the carotid, and the posterior lateral neck and occipital region for the vertebral. Involvement of the carotid sympathetic plexus frequently results in an ipsilateral Homer's syndrome, a distinct diagnostic marker. Diagnosis is clinical and by imaging with invasive angiography, CT angiography or less sensitive magnetic resonance angiography. Treatment is controversial but the use of anticoagulation with heparin and then warfarin (to avoid embolic complications) is espoused by some. Surgery is not considered useful at this time. The prognosis tends to be good with or without therapy with spontaneous resolution of the dissection over weeks to months. Most asymptomatic dissections are probably misdiagnosed as atypical headaches. Vasospasm occurs in a significant number of persons with subarachnoid hemorrhage and can be severe enough to cause ischemia and infarction. The spasm is thought to be related to release of vasoactive substances (e.g., serotonin) into the subarachnoid space from extravasated platelets and possibly also basophils. Prophylactic treatment with centrally active calcium channel blockers, which may either decrease vasospasm or ischemic damage, or both, has shown some promise. Hyperviscosity and hypercoagulable states predispose to arterial occlusive disease, and the risk is greatly amplified if arteriosclerotic vessel changes are already present. Hyperviscosity that causes a sluggish blood flow and a predisposition to coagulation is associated with dehydration,

hyperproteinemias, and dysproteinemias (e.g., macroglobulinemias, cold agglutinins), polycythemia, leukemia, and sickle cell disease. Thrombocythemia (excessive platelets), thrombotic thrombocytopenia purpura (abnormal platelets), and rare cancer-associated coagulopathies are examples of excessive clotting capacity that predisposes to arterial occlusion. Antiphospholipid antibodies are a cause of vascular occlusive disease being given more attention. Some individuals who have had stroke have been shown to have high titers of antiphospholipid antibodies, in particular, some patients with malignancy or connective tissue diseases; and some medications have also been implicated. These antibodies (e.g., anticardiolipin antibody and lupus anticoagulant) are associated with thrombotic disease and a number of other conditions such as spontaneous abortions and presently are not well understood. Prophylactic therapy with antiplatelet agents and/or antithrombin agents is being used empirically.

Venous occlusion Symptomatic cerebral vein or venous sinus occlusion is rare. This may be explained in part by the rich interconnections in the cerebral venous system and the lack of valves in the major sinuses. Both contribute to create a collateral circulation safety factor when focal portions of the venous system are obstructed. When major channels are occluded, such as the posterior portions of the sagittal sinus, a lateral sinus, or the internal cerebral veins, collateral circulation is frequently inadequate and edema and hemorrhagic infarction may occur and cause a stroke-like picture with headache, focal and diffuse deficits and focal and generalized seizures. Edema may appear rapidly and massively and lead to rostrocaudal deterioration (herniation) and death (see Chap. 24). Some predisposing elements in venous occlusion are severe dehydration (causing hyperviscosity of

blood flow and increased coagulability), other causes of hypercoagulable states (discussed earlier), and infection of the meninges or neighboring structures involving vein and sinus walls (purulent meningitis, chronic otitis media, and chronic sinusitis). The risk of cerebral sinus thrombosis is higher during the postpartum period either because of dehydration or for other reasons. Therapy is aimed at treating the primary process when possible, decreasing edema and suppressing seizures. If the patient survives the acute period, recanalization of the veins often occurs and considerable function may return to the involved cerebral tissue, which has not lost its arterial supply.

Hemorrhagic cerebrovascular disease Intracranial hemorrhage falls into two major categories: (1) spontaneous hemorrhage (associated with hypertension and with congenital or other arterial aneurysms and arteriovenous malformations); and (2) traumatic hemorrhages into the epidural, subdural, and subarachnoid spaces or parenchyma of the central nervous system. Traumatic hemorrhage is discussed in Chapter 22. Spontaneous intracranial hemorrhage accounts for approximately 20% of all strokes. The primary hemorrhage may be into the parenchyma of the central nervous system or into the subarachnoid space. Parenchymal hemorrhages often rupture into the ventricular system or into the subarachnoid space, whereas primary subarachnoid hemorrhages frequently dissect into the cerebral parenchyma.

Intraparenchymal hemorrhage

Intraparenchymal hemorrhages are almost invariably associated with hypertension and are presumed by many to be the result of weakening of arterial walls by the trauma of an excessive pulse pressure. The most common sites of involvement are: (1) the region of the putamen-external capsule in the

distribution of the lenticulostriate branches of the middle cerebral artery (50%); (2) the thalamus in the distribution of the small penetrating vessels from the posterior cerebral and posterior communicating arteries (10%); (3) the cerebellum in the distribution of the deep penetrating branches of the superior cerebellar artery (10%); and (4) the pons in the distribution of the paramedian branches of the basilar artery (10%). The remaining 20% occur into the white matter of various lobes of the cerebral hemispheres. Another etiology for the lobar hemorrhage has recently been described. In aging individuals, and especially in those with Alzheimer's Disease, amyloid deposition may occur in the penetrating cortical vessels, making the vessels more friable and subject to hemorrhage. Typically, the hemorrhage is lobar (i.e., immediately subcortical) and the likelihood that amyloid angiopathy is the etiology of the hemorrhage is increased if there is no past history of hypertension. There are other, less common conditions that can result in primary intraparenchymal hemorrhage. For example, they can occur with bleeding diatheses such as thrombocytopenia, leukemia, and anticoagulant therapy. They are a feared complication of the use of TPA either for heart attack or stroke. Intraparenchymal hemorrhage can occur due to arteriovenous and capillary malformations and can also occur due to bleeding into a necrotic area of brain due to a large stroke (often called "hemorrhagic conversion). Massive hemorrhage may also occur into rapidly growing malignant neoplasms, which outstrip their blood supply and develop central necrosis. It is frequently difficult to clinically differentiate the patient with intraparenchymal hemorrhage from one with massive ischemic infarction. Of course, a CT scan is the "gold standard" for this differentiation in the ED. However, there are certain aspects of the history and observations are suggestive of hemorrhage (see Table 19-1). A history of poorly controlled hypertension, acute headache, and vomiting at the onset of stroke are common in hemorrhage. Additionally, hemorrhage often produces signs of

rapidly expanding unilateral intracranial mass (e.g., evidence of secondary compression of the brain stem leading to decreasing awareness and coma, progressive pupillary dilation, paralysis of eye movements, abnormal respiratory patterns of neurogenic origin [see Chapter 24], papilledema, and hemorrhages on ophthalmoscopic examination). It is critical to recognize cerebellar hemorrhage as early as possible. If nausea and vomiting with associated occipital headache and ataxia precede cranial nerve dysfunction and depression of consciousness in a hypertensive patient, it is important to consider cerebellar hemorrhage because it may be surgically remediable. Unfortunately, thalamic, pontine, and putamenal hemorrhages usually are not surgically approachable without producing intolerable surgical morbidity. If available, as mentioned earlier, computerized axial tomographic radiography (CT scanning) quickly determines the presence and location of intracranial hemorrhage (see Chap. 23).

Prognosis

Intraparenchymal hemorrhage causes death in almost two thirds of an unselected series of patients, with the exception of cerebellar hemorrhage, which, when treated by aspiration, may have a mortality of less than 50%. Lobar hemorrhage may have a mortality of less than 50% with or without surgical treatment. The comatose patient with intraparenchymal hemorrhage at any site rarely survives; the alert and stable patient has a much better prognosis. CT scanning has recognized many small intraparenchymal self-limited hemorrhages that in the past were evident only as rapid-onset clinical deficits of a focal nature and presumed to be ischemic strokes. Adding these cases to the total population of persons with hemorrhage has progressively decreased the mortality statistics. Nevertheless, for the clinically catastrophic presentation, the prognosis for survival still remains very poor.

Subarachnoid hemorrhage

Ninety percent of primary subarachnoid hemorrhages arise from congenitally derived arterial outpouchings (berry aneurysms) that lie at bifurcations of the major components of the circle of Willis. The most common sites are the carotid-posterior communicating and the anterior cerebral-anterior communicating artery junctions. Defects in the elastic membrane and media of the arteries are considered the basis for berry aneurysm formation. It is possible that these defects are congenital, although it is clear that the actual aneurysmal outpouchings develop over the course of time. They rupture most often in early to late middle life, rarely in childhood, presumably after years of pulsatile trauma have caused them to balloon into a thin-walled sac. The presence of hypertension predisposes to earlier ruptures. Approximately 1-2% of the population has berry aneurysms as determined in general autopsy series. Much less than 1-2% of the population develops subarachnoid hemorrhage so the incidence of hemorrhage of an unruptured aneurysm must be small. Aneurysms 10 mm or larger in diameter are considered to be the most likely to rupture. Of those who have aneurysms, approximately 15% have more than one. Rarely, aneurysms can develop from bacterial or fungal inflammation and necrosis of arterial walls (as described in the earlier section on occlusive disease). Aneurysms associated with bacteria occur most frequently in small arterial branches over the surface of the cerebral or cerebellar hemispheres. With fungal involvement, major arteries at the base of the brain are the most common target. Approximately 10% of subarachnoid hemorrhages originate from congenital arteriovenous malformations, which reach the surface of the cerebral hemispheres or ventricular system. The clinical presentation of subarachnoid hemorrhage is classically associated with sudden onset of a

severe headache occasionally initiated by a "popping" or "bursting" sensation. The breakdown products of blood cause a chemical meningitis within several hours following the hemorrhage, which is manifested as nuchal rigidity and frequently a low-grade fever. Platelet or basophil lysis or just the mechanical trauma of tearing of the aneurysm wall may cause some vasospasm and ischemia-infarction with focal or diffuse neurologic deficit. Large amounts of subarachnoid blood frequently block egress of cerebrospinal fluid (CSF) from the subarachnoid space by plugging the arachnoid villi or obstructing CSF flow from the basal cisternae over the hemispheres or by both processes. This results in an acute communicating hydrocephalus with diffuse cerebral dysfunction. With partial blocks or the development of a chronic inflammatory response to the presence of blood, a slowly progressive communicating hydrocephalus may develop and appear as progressive dementia with gait abnormality and incontinence (see Chap. 16). This may become manifest after the patient has been improving from the acute hemorrhagic event. Focal signs may also be caused by dissection of the subarachnoid hemorrhage into the parenchyma of the brain. This occurs most commonly with anterior communicating aneurysms, which are tightly enclosed between the frontal lobes, and middle cerebral aneurysms, which are tightly enclosed between the operculum and the insula. In the absence of focal signs, the CSF must be examined by lumbar puncture to determine whether subarachnoid hemorrhage is present. If there are focal signs the diagnostic procedures of choice are CT scanning to determine the presence or absence of hemorrhage and radiographic opacification of the cerebral arteries (angiography) to find the aneurysm or arteriovenous malformation if surgery is being considered. Lumbar puncture is somewhat risky because it may lead to further hemispheric shift and secondary brain stem compression if there is an expanding hemorrhagic mass (see Chap. 23 and

Chap.24). A negative CT scan in a patient suspected of subarachnoid hemorrhage does not rule out subarachnoid hemorrhage. Therefore, a subsequent lumbar puncture is necessary. Aneurysm surgery in the hands of a skilled surgeon is successful in selected cases. Clipping the neck of the aneurysm is generally the procedure of choice. Arteriovenous malformations may be suspected before hemorrhage occurs because they may give rise to unilateral vascular headaches, sometimes focal seizures, and/or sensorimotor deficits. Some have an audible bruit that can be heard by listening over the skull.

Prognosis

The mortality from untreated subarachnoid hemorrhage is approximately 50%, although this refers mainly to hemorrhage from aneurysm (coma in the early phase of subarachnoid hemorrhage being an indicator of very poor prognosis). Arteriovenous hemorrhages tend to occur in a lower pressure system and cause less tissue destruction. They are more likely to arrest spontaneously. The mortality from arteriovenous malformation hemorrhage is approximately 10%. Rebleeding from a ruptured aneurysm, which is likely to occur in the first two weeks after the initial hemorrhage, is the major cause of death after surviving the primary hemorrhage.

References

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Marshall, J.: The Management of Cerebrovascular Disease, Ed. 3. Oxford, Blackwell Scientific Publications, 1976.

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Caplan, L.R. and Stein, R.W.: Stroke. Butterworths, Boston, 1986.

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Millikin, C.H., McDowell, F., and Easton, J.D.: Stroke. Lea & Febiger, Philadelphia, 1987.

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Barnett HIM et al: Stroke: Pathophysiology, Diagnosis and Management, ed. 3. WB Saunders, 1998.

Questions Define the following terms:

amaurosis fugax, homocystinemia, transient ischemic attack, large vessel disease, small vessel disease, hypercoagulability, emboli, ischemic penumbra, stroke in evolution, completed stroke.

19-1. How common is stroke (cerebrovascual accident - CVA)? 19-2. Approximately what percentage of strokes are ischemic? 19-3. What is the pathology of atherosclerotic-thrombotic strokes? 19-4. What are potential sites of emboli to the cerebral circulation? 19-5. What is vasculitis and what causes it? 19-6. What are the symptoms of stroke? 19-7. What is a transient ischemic attack (TIA) 19-8. What are risk factors for small vessel disease? 19-9. What is the treatment for small vessel ischemic disease? 19-10. What are risk factors for large vessel disease? 19-11. What is the treatment for large vessel cerebrovascular disease? 19-12. What are risk factors for embolic CVA? 19-13. What is the treatment for emboic stokes?

19-14. What are some causes of stroke due to increased viscosity of the blood? 19-15. List major risk factors for stroke. 19-16. What are the general preventative measures for stroke? 19-17. What is the treatment for a transient ischemic attack? 19-18. What major factors prevent the development of stroke with occlusion of cerebral blood vessels? 19-19. What are the potential causes of stroke in young individuals? 19-20. Outside of risk factor modification, what are the roles for the different treatment options for stroke prevention? 19-21. What are the therapeutic options for a stroke in progress? 19-22. How can ischemic stroke result in death? 19-23. What are the stages of recovery from stroke? 19-24. What are the types of intracranial hemorrhage? 19-25. What are some causes of intracranial hemorrhage? 19-26. What are the potential complications of subarachnoid hemorrhage?

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Disorders of the Nervous system - Reeves & Swenson Table of Contents

Chapter 20 - Mass lesions - Neoplasm When an intracranial mass lesion is observed on imaging studies there are

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On this page ●

Neoplasms

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Symptoms

several potential causes to consider in the differential diagnosis. Frequently

❍

symptoms are non-specific to the cause of the mass as they are simply the

Increased intracranial

manifestation of tissue dysfunction and pressure exerted by the mass on

pressure

normal structures. In some instances, however, the symptoms are specific ❍

Headache

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False localizing

to the etiology. Hemorrhage, which can be parenchymal or extra-axial is the most common cause of intracranial mass lesions and is discussed in

signs

chapter 19. Tumors, both malignant and benign, are the most common ❍

Seizures

mass lesions affecting the intracranial and intraspinal contents. Less ●

Tumor Types

common mass lesions include inflammatory masses (i.e., granuloma, ❍

Meningiomas

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Gliomas

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Primitive

abscess, and rarely, localized hemorrhagic viral encephalitis) and on occasion demyelinating plaqes of multiple sclerosis (tumefactive plaque). They are expanding mass lesions and therefore their clinical presentation is

neuroectodermal

much the same as that of neoplasms, except that the inflammatory lesions ❍

Metastasis

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Spinal tumors

improved spontaneously in the case of multiple sclerosis.

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Cerebellar tumors

We will consider neoplasms as our model in this chapter since many of the

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Pituitary tumors

are frequently associated with some systemic manifestations of infection or there is a history of a previous episode of neurologic dysfunction that

principles concerning their effects also hold for other categories of mass

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Clinical course

lesions. The specific causes and effects of abscesses are considered further

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Diagnostic testing

in chapter 17, the causes and clinical presentation of hemorrhage are

❍

Imaging

discussed in chapter 19 and the traumatic hematomas are considered in

❍

Lumbar puncture

chapter 22.

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Spine imaging

Neoplasms Intracranial tumors or neoplasms are classified according to the cell of

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Treatment

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References

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Questions

origin. Table 20-1 lists the types that most commonly affect the brain and spinal cord. Central nervous system (CNS) neoplasms are seen in all age groups, but the frequency of specific types varies with age. Posterior cranial fossa and spinal cord neoplasms predominate in children, whereas middle and anterior cranial fossa tumors are most common in adults. Metastatic neoplasms are common in adults and unusual in children. Breast and lung carcinomas are the most common systemic cancers in adults that metastasize to the CNS and they do so in about one quarter of patients who have these malignancies. The most frequent primary intracranial tumors are gliomas, and the most aggressive astrocytoma (glioblastoma multiforme) leads the list. Meningiomas, extra-axial tumors of the meninges, follow in frequency. The cause of brain tumors is unknown although there are hereditary syndromes in which a predisposition to develop CNS neoplasms has been observed. For example, individuals with neurofibromatosis have a relatively high incidence of acoustic and other cranial nerve neurilemomas, glial neoplasms, and meningiomas. A similar predisposition is seen in persons with tuberous sclerosis and several other rare conditions. In addition, children who received radiation therapy for a fungal

infection of the scalp (tinea capitis) also have a higher incidence of brain tumors as adults.Table lists the types of neoplasms that most commonly affect the brain and spinal cord. Central nervous system neoplasms are seen in all age groups, however, the specific types of neoplasms vary with age. Posterior cranial fossa and spinal cord neoplasms predominate in children, whereas middle and anterior cranial fossa tumors are most common in adults. Metastatic neoplasms are common in adults and unusual in children. Breast and lung carcinomas are the most common neoplasms in adults to metastasize to the CNS and they do so in about one quarter of persons who have these malignancies. The most common primary neoplasms are gliomas, and malignant astrocytoma (glioblastoma multiforme) leads the list.

Symptoms The manifestations of CNS neoplasms depend on a variety of factors, The most relevant of these factors are location, growth rate, amount of edema and intratumoral bleeding. To some extent, the dysfunction of the surrounding brain tissue depends on the rate of development of pressure and, therefore, on the rate of tumor growth. Slow-growing neoplasms such as meningiomas and neurilemmomas cause relatively little dysfunction until very late in the course of the disease because of the ability of the brain (and to lesser degree the spinal cord) to accommodate and compensate in pace with the expanding, compressive process. Rapidly enlarging neoplasms such as metastatic tumors and glioblastomas cause progressive loss of function over a short interval of time (weeks to months). Occasionally, a rapidly growing neoplasm causes sudden loss of function clinically suggestive of a stroke. This is usually the result of hemorrhage or infarction in the core of the neoplasm, which may become necrotic due to outstripping its blood supply. Also, edema may appear in and around certain neoplasms (most notably metastatic tumors) and cause the rapid appearance of symptoms and signs. Though dysfunction

appears rapidly with glioblastomas, it is frequently less than the tumor size would predict because the tumor infiltrates nervous tissue and leaves many neurons functional. Therefore surgical removal of gliomas may increase a patient's neurologic impairment, although usually the deterioration is transitory. The intracranial space is a closed chamber, with one outlet (the foramen magnum) and stiff dural membranes (the falx cerebri and the tentorium cerebelli) that divide the space into compartments. Depending on where they are located (supratentorial or infratentorial), expanding masses create vectors of force that are directed toward the paths that connect these intracranial compartments (for example, the subfalcine passage that connects one hemisphere region to the other, the tentorial notch that connects the supratentorial and infratentorial compartments and the foramen magnum that connects with the vertebral canal). This gives rise to a potentially lethal complication of mass lesions, herniation of brain tissue into another compartment. As herniation progresses there is a pattern of rostro-caudal deterioration of neural functions, which is discussed further in the chapter on stupor and coma (Chapter 24). Infants whose cranial sutures are not closed do not show rostro-caudal deterioration until quite late because the cranial cavity can enlarge progressively with widening of the sutures. Papilledema, swelling of the optic nerve head caused by increased intracranial pressure, is also late in developing or absent in infants with expansion of the intracranial contents for the same reasons. The tumor's location can often predict the severity of symptoms and degree of loss of function. Brain regions having redundant functions are less likely to be recognized early in the course. For example, frontal-pole tumors produce few, if any, deficits until they are very large (we have on record a frontalpole meningioma that was the size of an orange and produced no noticeable loss of function). At the other extreme, even very small tumors involving the primary motor or sensory cortex, the brain stem or the spinal cord may cause early severe impairment. In addition to producing dysfunction by direct

pressure, intracranial tumors can produce focal defects by edema within nervous tissue in and around the mass (which on occasion can be massive), and by ischemia caused by compressing of blood vessels supplying the surrounding brain. Some rapidly growing and very vascular neoplasms may cause ischemic injury by stealing the blood flow from adjacent normal brain tissue. The symptoms and signs resulting from intracranial neoplasms can be divided into non-localizing, localizing, and seizures.

Non-localizing clinical manifestations

Increased intracranial pressure

Increased intracranial pressure is characteristic of many intracranial masses and it is related to tumor size, edema, rapidity of growth, ventricular system obstruction (i.e., hydrocephalus), rate of cerebrospinal fluid absorption relative to production, venous obstruction, presence or absence of closed cranial sutures, and other unknown factors. Headache is the most common symptom associated with increased intracranial pressure, occurs in a high proportion of persons with rapidly expanding masses, less often with slow-growing tumors. Strictly speaking, however, increased intracranial pressure alone does not necessarily cause headache. It is usually the process that has caused the increased pressure that also causes the headache by involving or displacing pain-sensitive intracranial structures such as superficial cerebral blood vessels, meninges, and some cranial and upper spinal nerves (see Chapter 21). The pain location is not usually useful for location of the tumor since the pain can be referred. The headache is frequently worse in the mornings after the subject has been horizontal through the night,

which presumably is the result of increased pressure-induced peri- and intratumor edema with accentuation of the tumor's size and traction effects. Nausea and vomiting are also relatively common and considered secondary to traction on lower brain stem emetic centers or a reflection of increased autonomic afferent bombardment of the brain stem caused by traction of blood vessels and meningeal structures. The most easily observed and most telling sign of increased intracranial pressure on examination is papilledema, swelling of the optic nerve head, which is associated with a loss of retinal venous pulsations and enlargement of the blind spot on visual field testing (see the section on papilledema in Chap. 1). As mentioned, papilledema may not be manifested in infants whose cranial sutures have not yet closed. Also, older patients who have increased intraocular pressure (glaucoma) do not readily develop papilledema. A rising or, less commonly, a slowed pulse rate and elevation of blood pressure are occasional and ominous signs of increasing intracranial pressure and imminent or ongoing rostrocaudal deterioration. It is hypothesized by some that rising pulse rate and blood pressure are compensatory autoregulating responses to the decreased cerebral blood flow caused by the raised intracranial pressure. The slowed pulse, when it occurs, appears to be a vagal excitation or release phenomenon. It may be a response of the carotid sinus to the acute rise in blood pressure or a release of the medulla and vagal outflow from diencephalic sympathetic counter forces.

Other non-localizing manifestations

Other non-localizing, also called false localizing, manifestations are abnormalities found on neurologic examination that are distant from the tumor locations and frequently misleading secondary effects of

tumor enlargement. The most common are related to expanding supratentorial masses and are: (1) unilateral or bilateral sixth-nerve palsies caused by rostrocaudal displacement of the brain stem with stretching of the already taut abducens nerves; (2) third-nerve dysfunction from compression by herniating temporal lobe where the nerve passes forward at the edge of the tentorium; (3) compression of the contralateral cerebral peduncle against the edge of the tentorium, causing an ipsilateral to mass hemiparesis; (4) posterior cerebral artery compression against the edge of the ipsilateral to mass tentorium, causing ischemia-infarction of the occipital cortex and a contralateral homonymous hemianopsia; and (5) hydrocephalus secondary to tumor compression and occlusion of fourth ventricle, aqueduct of Sylvius, third ventricle, or foramen of Monro, which causes diffuse hemispheric dysfunction (i.e., dementia) that may obscure the local compressive and destructive signs of the mass itself. Isolated personality and behavioral changes may be the initial manifestations of an intracranial mass, although usually by the time of presentation there are other associated signs and symptoms. A gait disorder is another non-localizing syndrome that may result from a brain tumor.

Localizing clinical manifestations Focal neurological symptoms and findings caused by cortical tumors correlate with the location of the mass and the surrounding edema. If the lesion affects the motor frontal cortex there is going to be a contralateral hemiparesis. Likewise tumors in the speech area will result in aphasia. Pattern of visual field defect found on examination will help in localizing where the tumor is affecting the visual pathway (i.e. bitemporal hemianopia from a suprasellar mass compressing the chiasm).

Seizures

Seizures are the initial manifestation of approximately one quarter of adults with neoplasms and localize the tumor to the cerebral hemispheres. If focal, the seizures may localize the tumor precisely. Any adult who has a recent onset of seizures, particularly focal seizures, is considered a tumor suspect until adequate neurologic workup proves otherwise.

Specific Tumor Types There are many types of tumors that develop intracranially. Primary tumors of the brain can derive from any of the common tissue types that are normally present (see Table 20-1). Additionally, most tumors that metastasize can spread to the brain (although some common tumors, such as prostate and colon cancer, are less likely to). Finally, the nervous system can be affected by invasion from tumors in adjacent regions such as the skull and spinal cord.

Meningiomas

Meningiomas are almost always benign and very slowly growing tumors. They may be very large because their slow growth allows the brain to adapt. Most meningiomas these days are found on scans done for other reasons and are asymptomatic. These are tumors that develop from the dura and have some attachment to the dura. They are typically quite hard and may calcify. The damage that is done is due to pressure. Meningiomas in very delicate areas (such as where there are many cranial nerves, for example, the sphenoid wing), may produce severe symptoms. However, when they occur over the hemispheres they can be large without any symptoms at all. Meningiomas may irritate surrounding tissue and result in seizures.

There are some classic presentations for meningioma. Large meningiomas may develop inferior to the frontal lobe ("olfactory groove" meningiomas). By pushing up on the frontal lobes there may be personality changes (usually with loss of the sense of smell). Sphenoid wing meningioms often damage the optic nerve or the extraocular nerves. Meningiomas at the foramen magnum may produce a very high cervical myelopathy. Unfortunately, CT scans are often not very good at the base of the skull (due to artifact) and, therefore, these may be overlooked even if the head is imaged with CT. Most meningiomas are surgically resectable if they are producing symptoms. They may shrink slightly with radiation therapy. Most often these tumors can be watched since they are very slowly growing and since they very rarely undergo malignant transformation.

Glioma

The support cells of the nervous system are called glia (oliogodendroglia, astroglia and ependymal cells). Gliomas are tumors that derive from these supportive cells. These are the most common intraaxial primary brain tumors. Astrocytomas are more common than oligodendrogliomas. Astrocytomas are tumors of the astrocytes. They invade adjacent normal brain tissue and, invariably, the tumor is much larger than is visible by imaging. Also, it usually produces fewer symptoms than would be anticipated by size because it invades brain tissue and coexists with normally functioning neurons. This makes it very difficult to remove these tumors completely. Astrocytomas are tumors of the astrocytes. They invade adjacent normal brain tissue and, invariably, the tumor is much larger than is visible by imaging. Also, it usually produces fewer symptoms than would be anticipated by size because it invades brain tissue and coexists with normally functioning neurons. This makes it very difficult to remove these tumors completely.

There are several grades of gliomas. The most malignant (and most common) is the glioblastoma multiforme, where there are pathologic features of necrosis (due to outgrowing blood supply), pseudopalisading of cells and proliferation of endothelial cells. While most of the primary nervous system tumors don't metastasize, this one can (usually by spreading in the CSF). Lower grade gliomas tend to grow quite slowly, though they can degenerate into glioblastoma multiforme. Oligodendrogliomas are typically somewhat less aggressive. They often present with seizures rather than specifically with mass effect. As with many slowly growing tumors, they can calcify. These have a somewhat better prognosis with chemotherapy and radiation therapy. However, they are often not completely curable. Unfortunately, there is rarely a definitive cure for glial tumors. They tend to infiltrate into surrounding normal brain, and therefore usually are not totally respectable unless they are very small and in areas of brain where very large resections can be made. Occasionally, a very low-grade glioma can be cured by less radical resections. Radiation therapy can decrease growth (and can cause some regression in size), but is also not curative. There are newer forms of chemotherapy that are being developed that are somewhat better than older versions. However, cures are quite rare with this kind of tumor.

Neurolemoma

Neurolemomas derived from the coverings of nerves. By far the most common of these tumors is an acoustic neuroma. This is a bit of a misnomer since usually this tumor arises from the vestibular nerve. The slow growth of this tumor often impinges upon the acoustic nerve with gradual hearing loss. It may affect the facial nerve as well with facial weakness. It is quite rare that actually produces vertigo because the slow growth permits ample time for compensation. These tumors are resectable, though larger

tumors may leave residual deficit.

Ependymoma

Ependymomas derive from the lining tissue of the ventricles and the central canal of the spinal cord. These have a tendency to be seen in younger individuals and often focus on the fourth ventricle or spinal cord region. These tumors can exceed the ventricular system and even subarachnoid space and so-called drop metastases are possible. Some of these tumors are completely resectable blood most require adjuvant treatment. Deficits may result from pressure and local invasion or from the effects of treatment. These tumors often recur after attempted treatment, however.

Primitive neuroectodermal tumors

Primitive neuroectodermal tumors are most often seen in children and young adults. They are often midline tumors and are particularly common in the posterior fossa (especially in the area of the cerebellum/fourth ventricle and the area of the tectum. These cells these tumors are often called "small blue tumors", because they have a heavy concentration of nuclei on pathologic specimens, giving a strong basophilic appearance of a sea of blue dots. They are sensitive to chemotherapy and radiation but are not completely curable in most cases. These tumors can also spread to other areas of the brain and spinal cord through the spinal fluid. Some of the particular types of tumors in this category include pineal tumors and medulloblastomas.

Metastasis

There are many tumors that metastasize to the brain and spine. Most of these represent the common tumor types seen in adults. These include lung cancer, breast cancer and colon cancer. Some uncommon tumor types have a tendency to metastasize to the brain disproportionately, including renal cancer, while some common tumors rarely metastasize to the brain (such as prostate cancer). Ovarian cancer and melanoma also commonly metastasize to the brain. Although solitary brain metastases may be surgically removed with improvement in outcome, multiple metastases represent a more difficult issue. Newer stereotactic radiation procedures may be quite helpful but are usually only palliative. Of course, the prognosis of the condition is heavily influenced by the primary tumor. Nonetheless, metastasis to the brain or spinal cord may represent an important source of morbidity. Lymphoma is a form of cancer that can either develop in the brain (primary) or spread to the brain. Patients with severe immunosuppression, such as with HIV, are at particular risk for primary CNS lymphoma and this can often mimic other neurologic conditions, such as demyelinating disease. In the case of secondary spread of lymphoma to the nervous system, involvement of nerve roots and the meninges (carcinomatous meningitis) is a common presentation.

Spinal

There are many tumors that affect the spine and spinal cord. Most are metastatic (see above), however, there are some primary tumors as well. Some of these primary tumors affect the vertebra (such as multiple myeloma). Spinal tumors often result in expanding extradural masses, which can compress the cord or nerve roots. There are intradural but extramedullary tumors, such as neurofibromas, meningiomas or Schwanomas, and there are intramedullary spinal cord tumors such as gliomas or

ependymomas. Additionally, these latter two tumors can metastasize in the spinal fluid and result in extra-axial masses. The key to diagnosis of spinal tumors is recognizing unusual types and locations of radicular pain as well as properly investigating progressive myelopathy. A particular concern is spinal epidural metastasis with resultant spinal cord compression. Such a condition can produce major morbidity. The earliest symptom in most cases is back pain. This makes diagnosis difficult since back pain is common in the general population. However, back pain in a patient with a history of cancer, a new type of back pain in an older individual, back pain that does not seem responsive to specific positions or motions, back pain that awakens the patient from a sound sleep or back pain that is unresponsive to normal treatments should be viewed with high suspicion. When a patient is identified with epidural spinal cord compression, rapid administration of steroids and treatment with surgery or radiation may has a high potential for preserving function (though outcomes are highly dependent on the degree of disability at the time of initiating therapy).

Cerebellar tumors

Cerebellar tumors in children represent a particularly important clinical phenomena. Children have a higher predilection for posterior fossa tumors than adults (where tumors tend to be supratentorial). The most common of these is cerebellar astrocytoma. As opposed to adult astrocytomas, these are often surgically curable. Children may develop similar astrocytomas in the pons. However, in this location they are not curable due to the fact that large surgical procedures in the pons usually produce intolerable deficits. In addition to astrocytomas, medulloblastoma (as described above) can represent a severe and devastating form of cancer that usually develops in the cerebellar region of children. This may occasionally respond to chemotherapy and radiation, but is typically progressive and fatal.

Cerebellar tumors are relatively rare in adults. However, hemangioblastoma represents one type of tumor that may be seen (usually as a cystic mass) in the cerebellum of adults.

Pituitary tumors

Neoplasms involving the pituitary gland, hypothalamus, or both most commonly give rise to loss of function, often with systemic metabolic or endocrinologic effects. Combinations of loss of posterior pituitary function (diabetes insipidus) and anterior pituitary function (hypogonadism, hypoadrenalism, hypothyroidism, and insufficient growth) may be seen. Hypothalamic involvement may also cause changes in behavior (hypophagia, hyperphagia, placidity, sedation, low threshold for rage reactions) and autonomic function disorders (Horner's syndrome, disordered temperature regulation with hypothermia from posterior involvement or hyperthermia from anterior involvement). Encroachment on the neighboring optic chiasm leads to visual field defects, classically bitemporal hemianopia (see Chap. 3). This can also be seen with craniopharyngioma, a benign, cystic tumor that derives from remnants of Rathke's pouch. Anterior pituitary tumors may produce positive humoral effects via increased secretion of pituitary hormones. Eosinophilic adenomas secreting growth hormone are associated with gigantism in children or acromegaly in adults, whereas basophilic adenomas are associated with Cushing's hyperadrenal syndrome. Anterior pituitary adenomas are frequently associated with excess prolactin production and galactorrhea (often accompanies by amenorrhea and infertility). A more bizarre positive humoral affect is seen with some hemangioblastomas of the cerebellum. An erythroprotein-like substance is secreted, causing polycythemia.

Clinical course It is typical for a person with a neoplasm to have a downhill course interrupted by periods of some improvement. There is no proven explanation for these periods of improvement; however, it is speculated that changing levels of edema and vascular integrity around the tumor are important and that circadian changes in circulating cortisol levels may bring about these changes. Variations in absorption and production of cerebrospinal fluid in response to the mass and increased intracranial pressure may also play a role. In summary, the typical patient afflicted with a rapidly growing brain tumor has a progressive focal loss of neurologic function, with or without seizure activity. S/he complains of headache, which is frequently worse in the morning and associated with nausea, less often vomiting, and may be generalized or focal. On examination, early or well-developed papilledema may be present and focal signs of neurologic dysfunction are elicited. In contrast, the person with a slowly growing neoplasm (e.g., meningioma) may develop very little abnormality until the tumor has become very large (may take many years) and accommodation is no longer possible, at which time a relatively acute decompensation may occur. With spinal cord neoplasm, extrinsic or intrinsic, progressive segmental and long-tract motor and sensory deficits are typical. Focal back, neck, or limb pain is most common, with extramedullary masses affecting spinal roots and the bony encasement.

Diagnostic testing A thorough neurologic examination utilizing the patient's story to assess the problem usually localizes the neoplasm. This may be supplemented by specialized imaging techniques.

Imaging

CT scan or MRI are routine diagnostic procedures to be carried out on all persons suspected of having an intracranial tumor. By CT scan intracranial lesions that are of different density from the brain can be delineated. Where density differences are too small for visualization, enhancement procedures may be effective. Magnetic resonance imaging (MRI) essentially detects hydrogen and therefore water, in differential concentrations. Neoplasms, hemorrhages, infarctions, demyelinated plaque, and other structural abnormalities are readily visible (see Chap. 23). The injection of intravascular contrast often helps to clarify the lesion since many tumors have blood vessels that do not have normal blood-brain barrier. Therefore, while the contrast is excluded from normal brain, it often "enhances" the appearance of the tumor. Magnetic resonance spectroscopy, which can evaluate the chemical constituents of a mass, may be used to distinguish tumors from other enhancing masses, such as abscesses. Further, positron emissions tomography may be used to show the relatively high metabolic activity in the tumor. Opacification of the cerebral arteries and veins (angiography) may define the arterial supply of the tumor and aid resection (and, occasionally, diagnosis). Abnormal tumor vessels can be delineated with arteriography in some neoplasms. Arteriovenous malformations and giant aneurysms may present clinically as mass lesions and are best delineated by angiography.

Lumbar puncture

Lumbar puncture is carried out to study the cerebrospinal fluid after results of the routine diagnostic procedures have proved negative. If preliminary observations indicate a mass lesion or suggest

increased intracranial pressure, a lumbar puncture should not be done because of the chance of precipitating rostrocaudal deterioration by the rapid and possibly differential lowering of the CSF pressure in the lumbar subarachnoid space. A lumbar puncture is carried out as a preliminary examination only when (1) CNS infection (in particular, meningitis) is suspected, and (2) a patient has severe acute headache or other symptoms or a history that suggests subarachnoid hemorrhage in the absence of focal neurologic deficit and a CT scan is negative. CT scans can miss small subarachnoid hemorrhages. If this is a focal deficit, hospital admission is necessary for comprehensive study including CT scan or MRI and arteriography prior to considering lumbar puncture. With neoplasm, elevation of the level of protein in the CSF is the major finding sought, and it is nonspecific ally elevated in a majority of persons. Occasionally neoplastic cells are shed into the CSF and can be identified by cytologic techniques; tumor typing may also be possible. Both metastatic and primary malignant neoplasms are likely to shed malignant cells into the CSF, particularly those tumors located near the subarachnoid or ventricular surface of the brain. Rarely, a meningeal inflammatory response occurs with superficial and especially necrotic tumors. The CSF is infiltrated with predominantly mononuclear white cells. A polymorphonuclear cell predominance may occur, and there may be an acute, full-blown clinical picture of meningitis. Seeding of the meninges by metastatic tumor cells in the absence of any metastatic CNS mass lesions may occur and present as a chronic meningitis. As a rule, CSF cytology readily diagnoses leukemic infiltration while multiple CSF samples may be needed to determine the presence of carcinoma cells.

Spine imaging

Spine films are routine for persons suspected of harboring spinal neoplasm. Progressive para- or

quadriparesis is characteristic of spinal tumor and is a major neurologic emergency. MRI with and without enhancement is the procedure of choice in the emergency situation. If MRI is unavailable, a CT scan or CT-myelogram should be carried out (see Chap. 23).

Treatment Treatment of CNS neoplasms is either palliative (surgical decompression, chemotherapy and radiotherapy, and corticosteroid and hyperosmotic agent decrease of edema) or curative (surgical removal, occasionally radiotherapy and rarely chemotherapy). Palliative therapy is used most for malignant tumors or tumors that are not removable because of proximity to or presence within vital centers. Curative therapy is most often for benign, accessible tumors and occasionally for isolated, single metastases.

References

●

Jennett, W.B. and Lindsay, K.: An Introduction to Neurosurgery, ed. 5. Oxford, ButterworthHeinemann, 1994.

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Rubinstein, L.J.: Tumors of the Central Nervous System, Atlas of Tumor Pathology 2d Series, fasc. 6. Washington, DC, Armed Forces Institute of Pathology, 1972.

Questions Define the following terms:

metastasis, primary brain tumor, meningioma, glioma, oligodendroglioma, astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, medulloblastoma, ependymoma, drop

metastasis, sensory level, myelopathy, radiculopathy, non-metastatic complications of cancer, paraneoplastic syndrome.

20-1. How are tumors localized? 20-2. What are the signs that localize tumors? 20-3. What are some irritative signs of tumors of the nervous system? 20-4. What are the signs and symptoms of increased intracranial pressure that can be found in brain tumors? 20-5. What signs and symptoms are common in tumors of the pituitary region? 20-6. What signs and symptoms are common in tumors of the pineal region? 20-7. Why do symptoms of brain tumors often respond to steroids? 20-8. What are the types of primary brain tumors? 20-9. Why is it usually impossible to cure a glioma? 20-10. What glioma is usually resectible? 20-11. What tumors are primarily localized to the posterior fossa? 20-12. What are the treatments for brain tumors? 20-13. What are non-metastatic complications to systemic cancers? 20-14. What is the most common cause of tumors of the spine? 20-15. What are the common signs and symptoms of metastatic tumors of the spine? 20-16. Why is it critical to identify malignant spinal cord compression early? 20-17. What is the standard therapy for spinal cord metastatic disease? 20-18. What are the primary tumors of the spine?

20-19. How can you evaluate possible metastatic disease affecting the nervous system?

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Disorders of the Nervous system - Reeves & Swenson Table of Contents

Chapter 21 - Headaches

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Causes of head pain

Causes of head pain

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Distorsion

Intracranial disease can produce pain in only a limited number of ways.

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Vascular distension

With rare exception, stimulation or destruction of the brain itself does not produce pain. The following intracranial structures are pain-sensitive:

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Inflammation

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Pain referral

1. Meningeal arteries ●

Headache classification

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Potentially dangerous

2. Proximal portions of the cerebral arteries 3. Dura at the base of the brain HA

4. Venous sinuses ❍

5. Cranial nerves 5, 7, 9, and 10, and cervical nerves 1, 2, and 3

Subarachnoid hemorrhage

Distortion or traction Increased intracranial pressure, when it does not result in traction on painsensitive structures, does not cause headache. You may raise your own

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Meningitis

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Intracranial mass

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Intracerebral hemorrhage

intracranial pressure to abnormally high values transiently by the Valsalva maneuver; this does not cause pain. Conversely, an intracranial mass that

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Abscess

distorts the dura or the arteries at the base of the brain causes headache

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Acute

even if the intracranial pressure is normal.

hydrocephalus

Drainage of spinal fluid with the patient in erect posture causes headache,

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presumably secondary to traction on the venous sinuses when the brain

Pseudotumor cerebri

sinks toward the tentorium, as it loses CSF flotation. This is thought to be the mechanism of headache following lumbar puncture, which is relieved when the person lies down. A more general term for this headache is "low

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Vascular HA

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Temporal arteritis

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Hypertensive

pressure headache" because it can also result from any cause of CSF leakage.

encephalopathy

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vascular

Distensions of a vessel malformations

Distension of extracranial and occasionally intracranial arteries is thought ❍

Cervical fractures

to be the cause of pain in migraine. Increased flow through collateral & dislocation

circulation may produce the headache that sometimes accompanies large❍

Metabolic causes

vessel occlusion. This appears to activate the trigeminal nerve terminals in of HA

the vessel wall. ❍

Inflammation

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Glaucoma

Evaluation of dangerous HA

Inflammation in the subarachnoid space, whether caused by infection, hemorrhage, or chemical irritation, results in headache. Some inflammation

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Extracranial lesions

may me intrinsic to the blood vessel walls. This may occur with autoimmune

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Specific HA syndromes

diseases (see giant cell arteritis, below), or may accompany activation of

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Migraine

certain nerves in the blood vessel wall. A leading theory of migraine pain is inflammation around blood vessels due to release of pro-inflammatory neurotransmitters from nerve terminals in the blood vessels around the

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Migraine aura

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Migraine treatment

brain.

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Cluster HA

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Tension-type HA

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Indomethacin-

Referral of pain Referred pain refers to the phenomenon of feeling pain in a region that is

responsive HA

not actually toe source of the pain. This occurs because pain from many ●

Neuralgias

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Other causes of HA

sources converge on single "wide dynamic range" pain transmission neurons. Therefore, when the pain signal is relayed, its location requires

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interpretation. In the case of pain from the head and upper neck region,

"Psychiatric" causes of HA

there is a high degree of convergence on neurons of the spinal nucleus of the ❍

"Analgesic

trigeminal nerve (which extends several segments down in the neck region. rebound HA

In general, lesions above the tentorium produce pain that is referred to the ●

References

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Questions

trigeminal distribution (the forehead or behind the eye), because the dura in this region is supplied by the trigeminal nerve. Lesions in the posterior fossa most often produce pain in the ear and the back of the head (this part of the dura is supplied by cranial nerves 9 and 10 and the upper three cervical roots). When the first cervical segment has a dorsal root (as in about 50% of individuals) it may, in addition to receiving afferents from the posterior fossa, which refer pain to the occiput and ear, refer pain to the orbit. This probably relates to the termination of orbital (ophthalmic division) pain nerve fibers in the lowest part of the spinal nucleus of the trigeminal nerve, which also receive termination of the upper cervical pain afferent nerve fibers. Irritation of cranial nerves 7, 9, and 10 may be referred to the ear, because the ear has cutaneous supply from each of these nerves as well as cranial nerve 5. Although the location of pain may at times be misleading, in general, pain lateralization accurately

predicts the side of the lesion.

Classification of Headaches Table 21-1 presents a clinically useful classification of headaches. The clinical evaluation of the person who has headaches should be designed to define an underlying cause for headache when possible (categories A and B) and thereby rule out disease that might endanger the patient. When this is not possible, the evaluation should suggest a classification of the headache based on the characteristic symptoms (categories C and D).

Dangerous headaches These represent a small minority of headaches. Fortunately, with a little thought, it is quite easy to rule out most of these conditions on the basis of the history and examination alone. Most of these conditions are discussed elsewhere in this book. The following comments apply to the patient whose chief complaint is headache (i.e., the patient is not comatose or hemiplegic, etc.). This does not imply that isolated headache is the typical presentation for these conditions, but the person who has a hemiparesis or seizure or coma from a tumor or intracranial hemorrhage does not present a problem in the differential diagnosis of headache.

Meningeal irritation. These include subarachnoid hemorrhage and meningitis. Most of these cases present with meningismus (severe neck stiffness particularly with neck flexion, i.e., nuchal rigidity), although this sign can be lost with deepening coma.

Subarachnoid hemorrhage

Arterial bleeding in the subarachnoid space from a ruptured aneurysm is almost invariably accompanied by the sudden (instantaneous) onset of severe pain and, frequently, vomiting. The pain persists and the patient usually looks very ill or uncomfortable. Nuchal rigidity is often (but not always) found. The remainder of the neurologic examination can be normal. The history of sudden onset of a severe headache that persists, therefore, indicates subarachnoid hemorrhage until proved otherwise. CT scan and (if the scan is negative) lumbar puncture are indicated in the absence of neurologic signs other than those of meningeal irritation.

Meningitis

This diagnosis should not prove difficult because the patient looks ill, and fever and nuchal rigidity are usually present. Remember that in the elderly or debilitated person and in the young child, nuchal rigidity may not be present (see Chap. 17). Lumbar puncture is diagnostic.

Intracranial mass lesions

This category contains neoplasms, intracerebral hemorrhage, subdural or epidural hemorrhage, abscess, and hydrocephalus. Neoplasms. Persons often seek medical advice about their headaches because they are afraid they have a brain tumor. Fortunately, although many persons with a brain tumor have headache, the vast majority of patients with headache do not have a brain tumor. The headache of brain tumor is often mild and nonspecific; it may be worse in the morning; and on examination, vigorous head shaking may

elicit focal pain. If focal symptoms, seizures, focal neurologic signs, or evidence of increased intracranial pressure are present, a full evaluation must be undertaken. In the absence of any of these findings, brain tumor may practically be dismissed as a diagnosis.

Intracerebral hemorrhage This is nearly always accompanied by focal neurologic signs or symptoms. Hypertension, trauma or defects in coagulation are the usual antecedents (see Chap. 19). Subdural or epidural hemorrhage. Epidural and acute subdural hemorrhage occurs in the context of acute head trauma (see Chapter 22). Chronic subdural hematoma may manifest itself weeks or months after an injury, and headache may be the most prominent symptom. This headache must be differentiated from the common postconcussion headache. The latter may persist for weeks or months after an injury and may be accompanied by dizziness or vertigo and mild mental changes. All these symptoms gradually subside. When symptoms increase or when there are lateralizing neurologic findings, subdural hematoma must be suspected.

Abscess (see Chap. 17) Focal signs or mental changes are often present. There may be evidence of increased intracranial pressure. The history often suggests some source of infection (ear infection, bronchiectasis, etc.) or a reason to be susceptible to infection (cyanotic congenital heart disease, immunosuppressant therapy).

Acute hydrocephalus This may be caused by obstructing CSF pathways (such as by inflammation, blood or tumor). Acute

hydrocephalus is accompanied by evidence of brain dysfunction: confusion, lethargy, ataxia, incontinence, and others. Of course, with rapid or severe elevations of intracranial pressure, the fundi may show evidence of increased intracranial pressure.

"Intracranial hypertension" "Idiopathic intracranial hypertension" (what has been called "benign intracranial hypertension" or "pseudotumor cerebri" in the past) is a somewhat more insidious cause of headache and increased intracranial pressure. This is believed to result from diminished resorption of cerebrospinal fluid, with pressure buildup. It is most often recognized by a finding of papilledema, but scanning does not reveal an associated mass (there may be small ventricles, but the image is otherwise normal). Rarely, there may be idiopathic intracranial hypertension without papilledema and, in this case, the condition can only be determined by actual CSF pressure measurements. The prototypical patient is an overweight young woman, possibly with polycystic ovarian disease. This is because high estrogen is believed to predispose tot he condition. Exogenous estrogen is also a predisposition, as is excess vitamin A (or some acne medications) or outdated tetracycline. Venous sinus thrombosis (see below) should be considered before labeling the condition as " idiopathic intracranial hypertension". Although this condition may be termed benign, it can chronically damage the optic nerves, first increasing the physiologic blind spot and later resulting in constriction of the visual fields and even producing retinal hemorrhage. Sometimes serial lumbar punctures are therapeutic as well as diagnostic. Carbonic anhydrase inhibitors may lower pressure a little. Weight loss can also be useful. However, shunting (ventriculoperitoneal or lumboperitoneal) may be necessary in some cases and optic nerve sheath fenestration may prevent damage to the optic nerves.

Vascular headaches These headaches include giant cell (temporal) arteritis, hypertensive encephalopathy, and vascular malformations. Giant cell (temporal) arteritis. This is a systemic vasculitis with a predilection for the cranial vessels, which rarely occurs in persons less than 50 years old. The clinical picture may include: (1) polymyalgia rheumatica - malaise, loss of energy, proximal joint pains, and myalgias; (2) nonspecific headaches, sometimes associated with tenderness and swelling over the temporal or occipital arteries; and (3) evidence of arterial insufficiency in the distribution of branches of the cranial vessels. The latter may involve the external carotid circulation, producing the unique symptoms of jaw claudication (painful jaw muscles provoked by chewing) or infarction of the tongue or scalp; or it may involve the internal carotid circulation, producing retinal ischemia and blindness or, less commonly, stroke. Of the main trunks of the major cerebral vessels, the vertebral arteries are more likely to be involved than the carotids, although involvement of the main portions of these vessels is uncommon. When the vertebrals are involved, ischemic infarction in the brainstem, cerebellum and occipital lobes may result. In giant cell arteritis, the sedimentation rate is usually very high. The disease can be dramatically reversed with steroids. In the person over 50, the ESR should be checked if the history is suggestive of temporal arteritis or polymyalgia rheumatica. If the ESR is high, temporal artery biopsy often confirms the diagnosis, and treatment can be started without delay. Because lesions may skip segments, bilateral biopsy of sufficiently long (one inch) aterial segments should be examined with thorough serial sectioning before discounting the diagnosis. At times, the clinical picture may be sufficiently suggestive so that a trial of therapy is indicated despite normal test results. If the patient is sufficiently

symptomatic, a trial of steroids should produce remarkable improvement in symptoms. There are other conditions that can inflame cerebral blood vessels (such as lupus), however, these are almost invariably accompanied by systemic symptoms. Hypertensive encephalopathy. Cerebral vasoconstriction occurs in response to systemic hypertension to preserve a constant cerebral blood flow. This process is termed "autoregulation". It is thought that in persons with hypertensive encephalopathy cerebral autoregulation fails and segments of arteries dilate despite severe hypertension. This results in edema and hemorrhage. The diagnosis should be considered in patients with severe hypertension (diastolic pressure more than 120 mm Hg) or in previously normotensive patients who suddenly develop less severe hypertension. Retinal changes (hemorrhages and papilledema) and renal disease are frequent accompaniments. Milder degrees of hypertension are generally not associated with headache. Paroxysmal elevations of blood pressure, such as occur with pheochromocytoma or with tyramine reaction with MAOI (monoamine oxidase inhibitors) can produce headache. Vascular malformations. Headache from vascular malformations is discussed later in relation to migraine headache since it may result in a headache with features of migraine. Venous sinus thrombosis. In the case of sinus thrombosis, headache probably results from stretching of the pain sensitive veins that drain into the sinuses, although elevated intracranial pressure may also play a role. In addition to headache, clouding of consciousness and seizures are common and there may be petechial intraparenchymal hemorrhages. Hypercoagulibility and increased osmolarity appear to be the main predisposing factors. High estrogen states can provoke this and dehydration is also a risk factor.

Cervical headaches Pain from the cervical region (arising from periosteum, ligaments, nerve irritation, or reflex muscle spasm) is usually felt over the neck and occiput, but can be referred around the temples and even into the frontal region. In a person with a history of neck trauma or with symptoms or signs of cervical root or cord compression, cervical imaging with MR or a CT scan must be obtained to rule out a condition that might result in cord compression, such as fracture or dislocation. Cervical spine x-rays with lateral views in flexion and extension are useful to detect excessive mobility of the spine. Occipital neuralgia. Some individuals may have irritation or entrapment of the greater occipital nerve in its course through tissues between C1 and C2 and then through the cervical musculature. At times this may be traumatic or related to structural abnormalities in the area. The diagnosis may be clear when there is unilateral shooting pain in the occiput provoked by upper neck movement and associated with hypesthesia or paresthesia in the area. Other cases may be bilateral, more constant or more subtle. A trial of occipital nerve block may provide a diagnosis. Arterial dissection. Dissection of the arteries of the neck can result in an acute neck pain sometimes accompanied by ischemic symptoms. This may be traumatic and usually results in pain over the involved vessel. This occurs due to entry of blood into the wall of the major cervical (carotid or vertebral) artery, usually through a small tear in the intima of the vessel. It may be difficult to diagnose, especially if it was not caused by trauma. However, a completely new type of acute, localized neck pain (often with radiation to the head) that does not improve with rest should be regarded with suspicion.

Metabolic headaches Headache is often associated with hypoxemia, hypercapnea, and anemia, possibly related to the

cerebral vasodilatation that may accompany these conditions. Chronic carbon monoxide exposure may also produce headache.

Glaucoma Headache may accompany glaucoma, usually the acute, narrow-angle type. Pain is localized in the eye or behind the eye.

Evaluation of dangerous headaches From the preceding discussion, a physician can be fairly sure of excluding "dangerous" headaches by the following:

1. There should be no history of serious head or neck injury, of seizures or focal neurologic symptoms, or of infections that may predispose to meningitis or brain abscess. 2. The patient should be afebrile. 3. The diastolic blood pressure should not be greater than 120. 4. The fundi should be normal. 5. The neck should be supple. 6. There should be no cranial bruits. 7. The neurologic examination should be normal; the patient should not be lethargic or confused. 8. In appropriate cases, complete blood cell count, ESR, cranial imaging or neck x-rays should be obtained and be normal.

The duration of the headache is also significant: headache arising recently in a patient who is not prone

to them arouses more suspicions than headache that has been recurrent for years. In addition, the patient's complaints often suggest an alternative diagnosis. Ancillary symptoms that are not classically associated with migraine (nausea, light and sound sensitivity, classic visual symptoms) should be treated with suspicion. A patient with a headache that is always in the same location (most migraines, for example, tend to move around or switch sides from time to time) or one who does not return to normal in between headaches, should also be evaluated carefully. Those patients who have typical migraine only require a good history and physical exam before instituting treatment.

Headaches from extracranial lesions These are listed in part in Table 21-1. The location of the pain often suggests the site of pathology. Other symptoms may accompany the condition: postnasal drip may accompany sinusitis, and on examination there may be tenderness over the affected sinus. Pain increased by chewing points to dental or temporomandibular joint pathology. Uveitis or glaucoma should not be missed. Errors of refraction do not commonly cause headache (despite the popular belief to the contrary). The headaches that accompany cervical spine disease may resemble "tension" headaches, in that both produce excessive contraction of neck musculature.

Specific headache syndromes

Migraine A migraine attack may consist of an aura and a headache, or either alone. In the absence of the aura, it may be difficult to diagnose the migraine with certainty. Research criteria for the diagnosis of migraine are listed in table 21-2. The following are useful diagnostic features (the most helpful are shown by

asterisks):

1. *The headache is episodic; persons can usually tell exactly when a migraine is beginning (and there may be a prodrome). The end of the headache may be less well defined, but it is unusual for a migraine to last more than 3 days (status migrainosus). 2. Onset is often in childhood or adolescence, although it can arise at any age. 3. The headache is often unilateral (but may be bilateral). 4. *The headache can be severe, throbbing (but may be steady), and often accompanied by anorexia, nausea, and sometimes by vomiting, diarrhea, and other symptoms. 5. The headache lasts from several hours to several days, rarely for a week or more. 6. Patients often feel like going to bed with the lights out, and sleep may terminate an attack. 7. There is frequently a family history of migraine. 8. It can sometimes be relieved by taking ergotamine or triptans early in the course. 9. Photophobia and an intolerance of loud sounds and strong smells are common complaints during the headache. 10. There may be a history in childhood of motion sickness or cyclic vomiting (episodic vomiting without other accompanying symptoms or signs).

Physiologically, the headache of migraine is accompanied by vasodilatation of the extracranial arteries, and compression of the carotid or temporal artery on the side of the headache may relieve the pain. Treatment with vasoconstrictors (chiefly ergotamine) may abort a headache but it would be a mistake to consider this to be primarily a pain due to blood vessel dilation. The pain does appear to result from

activation of nerves in the blood vessels that contribute to a sterile inflammatory reaction, both sensitizing and dilating the vessels. There are many precipitants for migraine that vary somewhat between migraineurs. These include psychological stress, allergies, different food substances (e.g., alcoholic beverages, cheese, chocolate, nitrate-containing foods such as hotdogs, and a number of other substances), the menstrual period, birth control pills, disrupted schedules, lack of sleep, poor eating habits, especially missed meals, strong smells, glare, flickering lights (such as fluorescent lights or CRTs) and many others. Some of these have known mechanisms of action, while the reason fro provocation remains obscure for many of these triggers.

Aura

The aura of a migraine is much more specific than the headache, and a diagnosis of migraine may be made on the basis of the nature of the aura alone. As mentioned, the aura is not always present; in fact, migraine without aura (formerly called "common migraine") is much more common than migraine with aura (formerly called "classic migraine"). Being able to define the aura, however, is important not only in diagnosing migraine but also in differentiating this from more serious conditions (seizures or TIAs). The aura of migraine is associated with, but probably not caused by intracranial vasoconstriction. The most prominent theory of causation is a slowly spreading wave of initial neuronal excitation, followed by depression that spreads over the cortex. This phenomenon, termed "spreading depression" progresses over the cortex at the rate of about 3mm per minute. This does appear to correlate with the spread of sensory aura symptoms when they can be localized to a specific part of the brain. Rarely, an aura may persist permanently, most often in elderly individuals, and indicates infarction of the brain.

The most common symptoms involve visual, somatosensory, and language functions (dysphasia). The visual aura is variable: scintillating scotomata are characteristic (an enlarging blind spot with a shimmering edge), but negative scotomata, or blurring of the visual field, may also be seen. There may be bright spots (often colored, called "photopsia"), jagged lines ("fortification spectra") or wavy lines (like heat lines). The symptoms are often homonymous (from cortical involvement), but symptoms referable to retinal ischemia (visual loss in one eye only) may also exist. The onset is gradual, and the symptoms usually last from 10 to 60 minutes. they may progress in a characteristic slow march over the visual field or, if tingling, the body. The somatosensory march of migraine is characteristic and can be differentiated from sensory seizures or from the usual form of TIA by the following:

1. The onset is gradual. 2. The march (spread of symptoms) is slow; if it arises in the hand, it may take several minutes to reach the elbow and then the face. This slow spread differentiates it from sensory seizures, which are more rapid. TIAs or strokes usually encompass large somatotopic areas at once (e.g., whole limb or half body). 3. Symptoms need not be restricted to the distribution of a single blood vessel as they are in TIA, since cortical spreading depression spreads over adjacent areas of sensory cortex rather than along a blood vessel. 4. It usually clears first in the area that was first involved; that is, if it marched from most involved. 5. The symptoms are almost always positive (i.e., pins and needles paresthesias) initially. The symptoms of TIAs are usually negative or ablative (i.e., numbness, heaviness).

Aphasia is the third most common feature of the migrainous aura. When all three symptoms appear as part of the same aura, it is characteristic for them to appear successively (e.g., visual, then sensory, then speech) rather than concomitantly (although this can also occur). The slow march of symptoms appears to correlate with the rate of "cortical spreading depression" (a wave of depolarization which is excitatory on its advanced margin, followed by depolarization inhibition then repolarization). However, despite many lines of evidence, this remains only a theory of what is happening (although it is the best one). Other symptoms sometimes associated with the aura (but seen much less often) are true motor weakness, emotional changes, micropsia or macropsia, olfactory hallucinations, and symptoms of basilar artery ischemia (diplopia, coma, vertigo). Ophthalmoplegic migraine is a variant that appears clinically quite distinct. Most commonly, the oculomotor nerve is involved; less often, the abducens nerve. Often the oculomotor or abducens paresis lasts for many weeks after the onset at the height of the headache. One possible mechanism is that dilation of the internal carotid artery occurs and compresses either the third or sixth nerve in the cavernous sinus to cause paresis or paralysis. With compression damage, one would expect a prolonged recovery period. These rarer manifestations of headache are often perplexing even to the experienced clinician. Some do not even consider these attacks of headache to be migraine, but instead a cranial neuropathy. Familial hemiplegic migraine (FHM) is another and dramatic variant. As with ophthalmoplegic migraine, onset early in childhood and a strong family history are common. There are at least three known genetic mutations accounting for the familial variety (on chromosomes 19, 1, and 2 respectively). FHM type 1 involves the CACNA1A gene (P/Q calcium channel), FHM type 2 involves the sodiumpotassium ATPase pump ATP1A2), and FHM type 3 involves neuronal voltage-gated sodium channels

(SCN1A). Individuals with these abnormalities seem to have a lowered threshold for the initiation of cortical spreading depression. This finding, and the fact that most individuals with migraine have other afflicted family members has led to much speculation about some genetic predilection for many cases of migraine. However, this remains to be proven. In FHM, typically the headache appears first and symptoms and signs of weakness and sensory loss occur later when the headache is most severe. The neurological signs frequently outlast the headache by hours or days and occasionally may be permanent. When the latter is true a CT scan or MRI will usually evidence an area of presumed infarction. Arteriograms carried out during the phase of neurological signs have shown temporary arterial spasm. Hemiplegic migraine may also occur on a sporadic basis. The migrainous aura usually precedes the headache, but it may accompany it or follow it or occur on its own. The latter is particularly true in elderly persons who have a long history of migraine. These migraine aura symptoms without the headache have been termed a "migraine equivalent," "aura without migraine" or acephalgic migraine. In these individuals, it may be quite difficult to determine that symptoms are due to a migraine mechanism.

Treatment of migraine

There are three basic approaches to treatment of migraine. The first is avoidance of trigger factors. However, this is often not practical and typically does not produce adequate control. The second mechanism is the use of medications during the headache. Some of these are nonspecific analgesics and antiinflammatory medications. Recent years have seen the development of a couple of classes of medications that activate serotonin receptors (ergotamine derivatives and the triptans). These receptors appear to be capable of affecting the trigeminal nerve endings on blood vessels, decreasing the release

of inflammatory neuropeptides such as CGRP and substance P, and also constricting blood vessels. The two primary difficulties with the use of short-acting analgesics in migraine treatment are, first of all, that they become less effective once the migraine is well-established and, secondly, that frequent use of short-acting medications results in a gradual decrease in response to these medicines. In some cases this can reach the point that patients develop headache due to discontinuation of the medication, socalled "analgesic rebound headache" or" transformed migraine". This can also occur with regular caffeine use, such that patients may develop headache due to withdrawal from caffeine. With this in mind, however, even patients with occasional severe migraine can be managed with these serotonin agonists (often with the addition of an antiemetic medication). However, frequent migraines may require an alternative approach. The third way of managing migraine is the use of preventative (prophylactic) medications. There are four classes of medications that have been shown to have preventative capability, and each of these classes have several representatives. Most of these have been shown empirically to be effective, although the specific properties of the drugs that result in prophylaxis are not known. Generally, the medications with prophylactic functions fall into one of the following classes of drugs: beta blockers; calcium channel blockers; heterocyclic antidepressants; or anticonvulsants. It must be emphasized that not all members of each of these classes of drugs have similar (or any) prophylactic potential. However, prophylactic medications should be considered in patients with frequent, severe and incapacitating migraines. Of course, some reassurance of the patient that their headache "is not a tumor" may be a wonderful therapeutic intervention in the migraine sufferer. The physician should be familiar with the clinical picture of migraine since it is common and can usually be diagnosed with a good history and physical exam. Rarely, arteriovenous malformation

(AVM) may cause recurrent unilateral migrainous headaches without bleeding. Some consideration should be given to imaging migraine sufferers with strictly unilateral headaches. It is reassuring for the patient with migraine to have had some headaches on the other side or to have the headache ipsilateral to the aura, because this would not be likely with a structural lesion.

Cluster headaches Cluster headaches are uncommon but very severe headaches. They are associated with a variety of autonomic signs and symptoms. This headache syndrome is characterized as follows (research criteria are found in table 21-2):

1. The headache is brief (15 minutes to 3 hours). 2. It usually occurs once or twice daily (or more), often at the same time and often at night. 3. The headache is very severe; persons with the headache are usually agitated and prefer to pace the floor as opposed to the patient with migraine who prefers to remain very still. 4. It is often accompanied by lacrimation and nasal congestion on the same side as the headache. An ipsilateral Horner's syndrome may be present during the headache, and miosis may persist after the headache. 5. The headaches occur in clusters; they may occur daily for several weeks or months and then disappear entirely for months or years, only to recur later. Chronic cluster headache is when a cluster episode does not abate. 6. Men are much more commonly affected than women.

These headaches are clinically distinct from common or classic migraine. There is also a chemical

difference: Persons with migraine have an increase in the level of blood serotonin at the onset of their headache and later, a depletion; persons with cluster headache have no change in serotonin levels but have an increase in blood histamine concentration coincident with their headache. In neither instance is the pathogenesis of the headache understood although recent evidence indicates overactivity in the caudal hypothalamus during the attack. Despite these differences, cluster headaches may be helped by certain prophylactic medications effective for migraine prophylaxis (especially calcium channel blockers and some anticonvulsants). Also, the acute attack may be helped by some of the rapidly acting medications used to abort a migraine attack (such as ergot derivatives and parenteral triptans). Interestingly, breathing 100% oxygen can often abort an attack very rapidly, for unclear reasons. Cluster headaches are usually not preceded or accompanied by an aura.

Tension-type headaches Most people, when under sufficient pressure, get a mild cervical or bifrontal headache which is classified as "tension-type" (research criteria are found in table 21-2). EMG of the frontalis muscle or of the cervical musculature reveals hyperactivity (although increased activity in these muscles is seen in all headache types), and measures directed at relaxing these muscles (benzodiazapines, biofeedback therapy, massage) often relieve the headache. At times tension headaches are quite severe, but generally people are able to continue working with them (unlike many migraines or the usual cluster headache) and rarely are they ill enough to seek a physician's aid. These headaches are rarely pounding, usually don't result in nausea or light/sound sensitivity and usually don't worsen with exertion. The headache may be more prominent when the patient thinks s/he is more relaxed (in the evening or on weekends). Not infrequently, a prolonged tension headache will progress to migraine or the reverse, a migraine

may develop the muscle contraction features of tension headache in addition to the typical migraine symptoms. It has been presumed that the stress from one type of headache triggers the other although it must be noted that there are similarities in the treatment and pathophysiology of migraine and tension-type headaches, at least in migraineurs. This has lead some authors to consider these two headache types as the manifestations of a single pathophysiologic entity in different individuals (or at different ages in the same individual). In migraineurs, both migraine and tension-type headaches respond to the same medications described above for migraine although, because they are less intense and disabling, many of the potential side-effects of some of the specific migraine medications would not be warranted. Migraine prophylactic medications often work for tension-type headaches, but would be reserved for the more severe cases. However, since tension-type headaches are more likely to be chronic and more likely to result in very frequent analgesic intake, it must be considered that analgesic rebound headache (see below) may be a common problem in such patients. Daily intake of analgesics for headache run a high risk of developing resistent headaches in the long-run and should be discouraged in favor of lifestyle and risk modification and even prophylactic medications.

Indomethacin-responsive headache syndromes There is a group of headache syndromes that share the characteristic of being highly responsive to indomethacin (as opposed to resistance to other non-steroidal antiinflammatory medications). These fall into several categories, including: trigeminal-autonomic cephalgias, which result in unilateral headache accompanied by a variety of autonomic symptoms in the head; headaches induced by Valsalva maneuver (lifting, straining, etc); and headaches that have a primary stabbing quality (sometimes called ice-pick headache or jabs and jolts syndrome). Many of these headache syndromes have sharp

and localized pain which are often shorter duration than migraine. A prototypical example of the trigeminal-autonomic cephalgias is SUNCT (short-lasting, unilateral, neuralgiform headache with conjunctival injection and tearing). This usually occurs in middle-age, more commonly in men. The name gives the main features of this headache. The headaches recur frequently, but each one only lasts for seconds to a few minutes. Because of the autonomic symptoms, these headaches may be confused with cluster, but they generally respond to indomethacin. There are other preventative medicines or nerve blocks that may help, as well. Paroxysmal hemicrania has many similar features, although pain is usually longer (2-45 minutes).This is more common in women. There are some more chronic conditions (hemicrania continua), in which pain waxes and wanes with flare ups several times most days (sometimes provoked by activity). Occasionally, there may be autonomic symptoms as well. The headaches may go away after many months, but can return months or years later. Many of these syndromes are only finally identified by their dramatic response to indomethacin, justifying a trial in patient who tolerate this medication.

Neuralgias Neuralgic pain is characteristic; it is very sharp, severe, and brief. There is commonly a "trigger point" an area of skin or mucosa that, when touched, provokes the pain. There is usually a "refractory period" after the jolt of pain, where the trigger zone may be touched without provoking pain. Tic douloureux (trigeminal neuralgia) usually occurs in the elderly and usually involves the second and third divisions of the trigeminal nerve. It should not be accompanied by sensory loss. If there is sensory loss, a structural lesion must be suspected. Neuralgic pain must be distinguished from dental pain,

particularly malocclusions. When present in the young adult, it may be symptomatic of multiple sclerosis and thought to be secondary to a demyelinating plaque in the spinal tract or root entry zone of the trigeminal nerve. Treatment with the anticonvulsants such as carbamazepine is often effective. In persons who do not respond to medical treatment, partial transection of the trigeminal sensory root or other trigeminal manipulative procedures may be necessary. In many of these patients there is an abnormal loop of blood vessel surrounding the trigeminal nerve, producing irritation. Surgical decompression of the nerve may provide lasting relief. Glossopharyngeal neuralgia is much less common. In this condition, neuralgic pain is felt in the throat, ear and neck and may be triggered by swallowing.

Other varieties of headache There are a couple of other headache types that don't fall neatly into one of the types described in the earlier sections.

"Psychiatric" headaches

A small number of persons complain of intractable, constant, severe, disabling headache for which no cause can be found. As a rule, these persons are severely depressed or have other serious psychopathology. Their headaches may respond to the same medications as common tension headaches, but often they are resistant to all treatment, even narcotic analgesics. This assessment is complicated by the fact that psychological stressors may provoke identifiable headaches (like migraine). Also, patients with intractable headaches have a high incidence of having been abused in childhood.

Psychiatric treatment or psychotrophic drugs (such as antidepressants) are sometimes effective.

"Analgesic rebound" headaches (medication overuse headache)

A small but significant population of individuals with debilitating migraine and/or tension headache may become physiologically dependent daily analgesic therapy and develop bifrontal headaches when they attempt to withdraw the medication, which will only respond by taking more of the habitual analgesic. These have been called analgesic rebound headaches and are often noted on awakening in the morning because no medications have been taken during the night time sleep period, thus allowing an adequate period for withdrawal symptoms to appear. This type of withdrawal headache, typically bifrontal in location, can be seen in individuals with chronic daily use of narcotic analgesics, sedatives such as barbiturates and benzodiazepenes, large amounts of caffeine, or with the frequent use of any short-acting headache medication (including over-the-counter medications). Treatment consists of education and withdrawal of the offending agents. Several weeks may be necessary before all symptoms of withdrawal dissipate and hospitalization is sometimes necessary to medically support the acute phase of withdrawal.

References

●

Sacks, D.W.: Migraine: Evolution of a Common Disorder. Berkeley/Los Angeles, University of California Press, 1970.

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Saper, J.R.: Headache Disorders. Boston, John Wright, 1983.

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Lance, J.W.: Mechanism and Management of Headache, 5th ed., London, ButterworthHeinemann, Ltd., 1993.

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Dalessio, D.J., ed.: Wolff's Headache and Other Head Pain, New York, Oxford University Press, 1987.

Questions Define the following terms:

subarachnoid hemorrhage, migraine, photophobia, phonophobia, tension-type headache, cluster headache, temporal arteritis, paresthesia, aura.

21-1. What are bad signs/symptoms in the headache patient (and what might it signify)? 21-2. What does subarachnoid hemorrhage indicate and how can you rule it out? 21-3. How can you rule out intracerebral hemorrhage? 21-4. How can you test for giant cell (temporal) arteritis? 21-5. How can you examine for intracranial pressure? 21-6. What are possible causes of increased intracranial pressure? 21-7. What are the symptoms of common migraine? 21-8. How do you recognize classic migraine? 21-9. How do you recognize tension-type headache? 21-10. How do you recognize cluster headache? 21-11. What is analgesic rebound headache? 21-12.What medical conditions can produce headaches?

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Chapter 22 - Cranial and spinal trauma

On this page ●

Cranial trauma

Cranial Trauma

❍

Concussion

Head trauma is a common cause of disability in this country, with vehicular

❍

Contusion

accidents representing the major cause. Of those who die from vehicular

❍

Laceration

accidents, 75% die from the primary and secondary effects of trauma on the

●

vital centers of the central nervous system. Of those who survive major head trauma, defects in CNS functioning (due to tissue damage) or irritative

cranial trauma

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phenomena (such as seizures) may result. There can be residual symptoms of more minor head injury (such as concussion), although generally good

Intracranial hemorrhage

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prognosis is the rule. Furthermore, surprisingly good recovery is possible even from severe head injury if the person survives the days and weeks after

Secondary effects of

Seizures in cranial trauma

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trauma.

General evaluation in cranial trauma

This chapter deals mainly with evaluation of the person with suspected or ●

proven head injury. As a preamble, some basic principles and definitions

Clinical evaluation in cranial trauma

should be discussed. ●

Evaluation of the

The major effects of trauma on the brain can be divided into two categories: brain stem

primary and secondary (or late) effects. The primary effects are those that are ●

Evaluation of the

caused directly by the head trauma and include concussion, contusion, and cerebral hemispheres

laceration of the central nervous system.

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Neck injury in cranial trauma

Concussion ●

Pre-existing disease

Concussion is a reversible state of diffuse cerebral dysfunction associated with complicating head

a transient alteration in consciousness. Most often there is a brief period of injury

loss of consciousness. However, patients may be only severely stunned or ●

Neurologic signs in

dazed. Typically, there is loss of memory for recent events (retrograde head trauma

amnesia), and this may extend for some seconds or minutes prior to the injury ●

Radiographic

and, rarely, with more severe impact, for days or more. A variable period of evaluation

inability to learn new material (anterograde amnesia) typically follows ●

Case 1

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Case 2

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Other diagnostic

recovery of consciousness and may be dense enough to leave the patient with no memory of early post injury events. Rarely, some patients tell of being "unconscious" for weeks to as long as several months following head injury. In

procedures

fact, they were not unconscious but were unable to remember ongoing events. The retrograde amnesia is presumed to be caused by a mechanical distortion

●

Spinal Cord Trauma

of neurons, probably in the temporal lobes, which consolidate the memory

●

References

trace. The anterograde amnesia is presumed to be the result of distortion of the mesial temporal-limbic circuits known to be necessary for learning. The underlying pathophysiology of concussion appears to be a shearing effect. Rapid displacement of the head, in either acceleration or deceleration injury, causes a swirling of the cerebrum within the cranium, and shearing forces play most markedly at the junctions between brain tissues of different density. Rotational injuries may be particularly damaging, since the brain stem torques quite easily

while there is a lot of inertia against the rotation of the cerebral cortex. This results in torsion of the nerve fibers in the core of the brain (i.e., the reticular activating system). Another major zone of diffuse axonal injury is the interface between gray and white matter. It is here and in the core of the rostral brain stem that microscopic evidence of ruptured axons can be found pathologically. It is not surprising that the patient's resistance to future concussion tends to decline with repeated concussions or that repeated concussion, such as boxers experience, may lead to dementia. Penetrating injuries of the cranium, such as bullet wounds, frequently cause only focal cerebral dysfunction without loss of consciousness because no cranial displacement and brain shearing occur.

Contusions Contusions of the brain are bruises usually associated with more severe trauma than necessary for concussion. They are most prominent at the summits of gyri, the cerebral poles (particularly the frontal poles and the anterior temporal lobe), and portions of the brain stem. All these regions lie close to the bony and dural surfaces of the cranial cavity. They may directly underlie the site of the blow to the cranium or may be opposite the site of impact (contrecoup). The contusions can usually be seen acutely on CT scan (which shows extravasated blood) as small petechiae in the brain parenchyma. The breakdown products of this blood may be seen for years on MRI scanning.

Laceration Laceration of the brain usually follows cranial trauma severe enough to cause fracture of the skull and penetrating injury to the brain by skull fragments or foreign objects. However, fracture of the skull need not be associated with laceration or contusion or major concussion. On the other hand, laceration may

on occasion occur with severe shearing forces unassociated with fracture. Usually some form of hemorrhage (intracerebral, subdural, epidural) is associated with laceration.

Secondary effects The secondary effects of cranial trauma that may further compromise brain function are edema, hypoxia, hemorrhage, infection and epilepsy. Edema may be the result of diffuse shearing of capillary, glial, and neuronal membranes or may be secondary to local contusion or laceration. Edema can generate local pressure that can compromise both arterial and venous cerebral blood flow, causing ischemia and more edema. This may precipitate a vicious cycle sometimes impossible to reverse. The mass effect of edema, focal or diffuse, can cause rostrocaudal brain stem deterioration (possibly with herniation), a major cause of delayed death from head trauma (see Chap. 24). Brain dysfunction and destruction are aggravated by hypoxia, the result of compromised respiratory function caused by the following: (1) injury to the chest, (2) aspiration pneumonia in the unconscious patient, (3) respiratory center depression from rostrocaudal deterioration or direct damage to the medulla, (4) pulmonary edema secondary to hypothalamic-septal damage, or (5) status epilepticus. Blood loss from multiple injuries and, as mentioned, brain edema further compromise delivery of oxygen to the brain. Increased intracranial pressure ICP), mostly due to edema but added to by any intracranial bleeding, is a major cause of secondary injury. High pressure decreases the perfusion pressure in brain blood vessels (since the perfusion pressure is the mean arterial pressure minus the intracranial pressure). If this is too low, there will be further damage to neural tissue due to ischemia, which will result in further edema and an even greater increase in pressure. The treatment of this increase in ICP can be by lowering intracranial pressure. Evacuation of cerebrospinal fluid (via an intraventricular catheter), or

dehydration of the brain (via diuretics and hyperosmotic agents) can lower pressure. Hyperventilation, which constricts intracranial arteries, can lower pressure, but will decrease blood flow. This has been shown to be detrimental. Recently, it has been shown that raising arterial pressure can improve outcome, presumably by increasing perfusion pressure.

Intracranial hemorrhage

Intracranial hemorrhage, arterial or venous, intra- or extracerebral, is a frequent sequela of cranial trauma and may be great enough to cause rostrocaudal deterioration of neural function and death if not recognized and attended to immediately. Rostrocaudal deterioration, if rapid, may itself cause hemorrhage by downward stretching and tearing of the paramedian penetrating arteries of the midbrain and pons. These so-called Duret hemorrhages usually occur when the clinical course of deterioration has reached the midbrain and upper pons (see Chap. 24). It is imperative to terminate rostrocaudal changes at the diencephalic or early midbrain level because Duret hemorrhages in most cases herald irreversible deterioration and death or, at the least, severe permanent brain disability. Subdural and epidural hematomas deserve some comment because both can be treated via surgical intervention, which can be curative if undertaken prior to irreversible brain damage. Both epidural and subdural hematoma are extracerebral. For this reason, and because they are soft masses, there tends to be relatively little effect on the underlying and compressed cerebral hemispheres. However, due to distortion of the brain itself, secondary rostrocaudal distortion of the brain stem is the process that usually gives rise to the major clinical signs (Fig. 22-1): depression of consciousness (reticular formation), hemiparesis (cerebral peduncles), eye signs (third and sixth nerves), and respiratory pattern abnormalities. The process of deterioration often goes through defined stages, which are

discussed in Chap. 24. Herniation, the process of squeezing brain tissue from one intracranial compartment into another, is often the terminal event since this produces permanent damage in the region of herniation. Epidural hematomas are most often arterial. They are usually the result of transection of the middle meningeal artery by a skull fracture that passes through the middle meningeal groove. It must be emphasized, however, that fracture is not necessary since the skull has elasticity that may permit the blow to rupture the artery which is pinned between the dura matter and the skull. Because of the location of the middle meningeal artery, the clots typically lie over the lateral hemisphere (temporal and/or parietal lobes). Since the epidural hematoma is under arterial pressure, it typically continues to grow unless evacuated. However, because the dura is adhered to the inside of the skull, and since the clot is between these layers, the growth of the clot is over hours. The typical middle meningeal artery epidural hematoma is associated with a syndrome that appears within hours of the injury. Classically, trauma is associated with a concussive loss of consciousness. The patient may awaken from this to achieve a good level of consciousness (lucid interval) only to lose consciousness again from brain stem distortion caused by the clot growth. If the bleeding is very severe there is no lucid interval. The patient does not have time to awaken from the concussion before compressive brain stem deterioration begins. Surgical evacuation is critical. Less often epidural collections may be the results of tears in the venous sinuses or leakage from the diploic veins. These hemorrhages may occur over any portion of the hemispheres or in the posterior fossa and are much slower. Subdural hematomas are typically due to disruption of veins that are bridging from the brain to the venous dural sinuses. The hemorrhage is presumed to arise from angular forces that cause the dura to move (along with the skull to which it is tightly adhered) in relationship to the cerebral hemispheres

which tend to lag behind in such rotational injuries. The bridging veins tend to shear where they enter the dura after passing through the thin subdural space between the dura and arachnoid. Subdural hemorrhage is more likely to occur in older individuals presumably because the veins bridging the enlarged subdural space are stretched. Because the blood is under very low pressure (being from veins) the hematoma tends to collect slowly, causing signs and symptoms that develop over days to months. Head trauma that can be so minor that it is not remembered may result in a subdural hematoma under these circumstances. Therapeutic anticoagulation predisposes to subdural hematoma and also intracerebral hemorrhage. Because subdural venous bleeding is slow to accumulate, gradual shifting of the brain occurs and brain stem distortion can be better accommodated in contrast to the acute brain stem distortions and severe dysfunction caused by epidural and acute subdural hemorrhages. Mild depression of consciousness, difficulty with cognitive function, and chronic headache (from meningeal stretching and increased intracranial pressure) may be the presenting picture. Acute deterioration may occur when the capacity to adapt for the expanding mass is exceeded. In this case there may be a picture of rostrocaudal deterioration of brain function that is superimposed on chronic complaints. The acute deterioration may be caused by fresh bleeding into the subdural hematoma from friable vessels that formed on the surface of the hematoma during the process of organized encapsulation of the clot. In many patients the symptoms of subdural hematoma wax and wane over hours or days. These symptoms may include headache, depression of consciousness, confusion and signs of focal cortical dysfunction (based on the region that is affected). The blood products in close proximity to the brain may also result in seizures. Acute subdural hematomas are seen less frequently. They are usually associated with head trauma severe enough to cause skull fracture and cerebral contusion or laceration. Epidural hematoma and

intracerebral hematoma are frequently associated. The mortality is extremely high and the residual dysfunction of survivors is severe. Arterial dissection may affect the carotid or vertebral arteries. This is usually associated with a tear in the intimal lining of the artery and an accumulation of blood in the media. Stroke may result from blockage of the artery or its branches or from artery-to-artery emboli arising from the site of vessel damage. The weakened artery may also rupture (often into the subarachnoid space) with potentially catastrophic results.

Intracranial infection

Open injuries of the skull may result in intracranial infection and may take the form of diffuse sepsis of the brain coverings (meningitis) or local collections of purulence (cerebral, subdural, and epidural abscess, see Chap. 17). Infection of dural sinuses may lead to stasis, occlusion, and infarction (see Chap. 19). The early recognition of posttraumatic meningitis or its prophylaxis in situations with which it is highly associated is critical. Unrecognized and untreated meningitis is a likely cause of death. This is most likely to occur in the unconscious patient. Depressed fractures that tear the dura and lie under or near scalp laceration are particularly prone to infection. Fractures through sinuses (sphenoid, ethmoid, and frontal sinuses) are frequently associated with dural tears and subsequent meningitis or intracerebral abscess. If such fractures lack dural tear, they may be associated with extradural buildup of purulence (epidural abscess). Fracture of the cribriform plate or petrous bone may tear the dura and create a communication between the subarachnoid space and the nasal cavity or external auditory cavities. The former may be recognized by leakage of CSF through the nose (rhinorrhea) and the latter by leakage

from the ear (otorrhea). This leakage is a potential direct passage for bacteria to travel from the exterior to the subarachnoid space. Any fluid collected from the nose can be tested for the presence of glucose (which is high in CSF but not in nasal secretions). These leaks may persist long after recovery from trauma because CSF pressure presumably keeps them open and may cause recurrent meningitis if not repaired.

Epilepsy in head trauma

Epilepsy may be a sequela of head injury. Seizures, frequently focal motor or focal with secondary generalization, occur in the first week after nonmissile trauma in approximately 5% of patients, but they herald chronic epilepsy in only about 25% of those so involved. Seizures appearing weeks to years following injury are much more likely to represent a chronic and recurring disorder. Approximately 5% of persons with nonmissile injuries develop seizures after one week, and the presence of more than 24 hours of anterograde amnesia, a dural tear, or seizures within the first week following injury increases the likelihood that these late seizures will be recurrent. Seizures are also more frequent following penetrating injuries or those patients with cortical laceration. Current evidence suggests that the use of anticonvulsants, which are often given in the initial post-injury period, does not alter the risk of later development of epilepsy. Therefore, most authorities recommend against long term anticonvulsants unless the patient proves to have later onset seizures. These "late onset" seizures appear to correlate with glial scarring and the presence of blood products in the brain. The most common time to develop them is 6-18 months after the trauma and patients are likely to require long-term anticonvulsants.

General Evaluation

Before any useful or reliable neurologic examination can be performed on a patient with acute head injury, the following other essential systems must be evaluated.

1. An adequate airway and adequate oxygenation must be assured. This can usually be tested by a brief physical examination and/or chest x-ray and by arterial blood gas measurements. Hypoxia is commonly associated with head injury in the immediate post-trauma period because of the frequency of lung contusion and/or emesis with aspiration of gastric contents. The hypoxic patient's neurologic status can often be dramatically improved by establishing adequate oxygenation. 2. Blood pressure and pulse should be noted. Adequate blood volume and pressure are also necessary for adequate cerebral oxygenation. Beware - shock is not due to reversible cerebral injury. Shock must be assumed to be from noncerebral causes such as hypovolemia (i.e., from a hidden site of hemorrhage), cardiac failure, or sepsis. Shock that can be produced by cerebral injury is manifest by a loss of peripheral vasomotor tone that is mediated by the medulla. Shock from medullary failure is seldom seen even in the agonal patient. 3. Body core temperature should be noted. Hypothermia secondary to exposure can cause marked neurologic changes. Hypothermia decreases CNS metabolism and tends to decrease the level of consciousness, reflexes, and nearly all motor responses. 4. Baseline blood studies should be done (blood count, electrolytes, and glucose) when the patient is first seen. If the patient is unconscious and a known diabetic, a bolus of intravenous 50% glucose (after 100 mg of thiamine) should be administered after the blood glucose is drawn. Immediate treatment of hypoglycemia (quite possible in the diabetic who is unable to eat because of trauma)

is necessary to minimize brain damage.

Along with assuring an adequate airway, oxygenation, perfusion, and a normal body temperature, a brief history of the trauma can be extremely helpful. Progression or nonprogression of the patient's level of consciousness from the time of trauma to the time s/he is being seen by the examiner should be documented if possible. Was the patient immediately unconscious? For how long? Was s/he awake and talking or walking after the trauma? this is a story often seen in expanding hematomas (especially epidural). Did any witnesses observe seizure activity? Did the patient strike their head and then become unconscious, or did s/he first become unconscious and then strike their head? If available, a brief history may also be important. Was the patient taking any medication, alcohol, or other drugs? Did the patient have a preexisting illness, seizure disorder, or history of syncope?

Clinical Neurologic Evaluation

Brain stem evaluation of the patient with head trauma

The most sensitive and reliable clinical parameter of brain function is the patient's level of consciousness (mediated primarily by the ascending reticular formation of the brain stem, see Chap. 24). On the initial and all subsequent examinations, the level of consciousness should be clearly described and recorded. Confusing and ambiguous terms such as "stupor", "lethargy", and "coma" should be avoided unless defined. Decreasing levels of consciousness often follow a logical progression and can be documented in a stepwise pattern (Table 22-1). The "Glasgow coma score" is a rapid and reproducible tool that may allow comparison of function over time and different observers. After early childhood, the skull is a nonexpanding bony encasement for the brain. The only direction in

which an expanding supratentorial mass can force the brain is through the tentorial opening into the posterior fossa. The midbrain with its segment of reticular activating system normally occupies this tentorial opening. As a supratentorial mass enlarges, it causes transtentorial herniation of the mesial portion of the ipsilateral temporal lobe with compression of the brain stem and reticular activating system (Fig. 22-1). A decrease in the level of consciousness may be the first sign that this is happening. Posterior fossa masses usually expand toward the foramen magnum. They can produce foramen magnum impaction by forcing the cerebellar tonsils into the upper cervical spinal canal. This may produce compression of the medulla with sudden apnea and death from asphyxiation. Direct involvement of the brain stem may occur at several levels. In trauma to the back of the head, the midbrain may be concussed by the rigid leading edge of the tentorium. With a severe linear occipital trauma, especially if a fracture occurs, vertebral arterial compromise may occur with subsequent pontomedullary dysfunction. Either of these can be fatal. The examination should focus on determining brain stem function and should include evaluation of respiration, pupillary response, vestibulo-ocular response and motor response (see also Chap. 24).

1. Respiratory pattern. Normal breathing progresses to hyperventilation ("central neurogenic hyperventilation") as the midbrain is compressed, and then to an irregular respiratory pattern or apnea as the medulla is compressed (see Chap. 1). 2. Pupillary response. Equally responsive pupils progress to midposition without response to light as the upper midbrain (the region of the third cranial nerve nucleus and descending sympathetic pathway) is compressed. No further change is seen even with increased transtentorial herniation and descending brain stem compression (see Chap. 4).

3. Oculocephalic reflex. This reflex should normally be inhibited in the conscious person and disinhibited in the person with depressed consciousness. It can be elicited by briskly turning the patient's head. Of course, if there is a possibility of neck trauma, this should be avoided (caloric testing can be done without neck movement). A disinhibited response is common in patients who are unconscious but whose brain stem is functioning. In this case, the patient's eyes appear to be fixed on an imaginary point as the head is turned (i.e., they move opposite to head movement). If the reflex is absent, the eyes do not move in the head, staying fixed in place. The movements of adduction first disappear with upper midbrain (third-nerve) compression, and the movements of abduction disappear when the compression progresses to involve the pons (sixth nerve). With downward movement of the brain stem caused by expansion of the supratentorial contents, loss of abduction (lateral rectus function) may occur before parenchymal involvement of the pons. This is caused by stretching of the sixth nerve against the edge of the petrous bone (see Chap. 4). 4. Motor response. Normal motor strength and tone progress to intermittent decorticate or decerebrate posturing as the midbrain is compressed. The progression is then to flaccid areflexia as the pons and medulla are compressed. Decerebrate posturing is manifested by leg extension along with arm extension and internal rotation that can occur spontaneously or following any noxious stimulation (such as tickling the nose). Since this is a reflex that is generated in the caudal brain stem (particularly by the vestibular nuclei), the finding of decerebrate posturing suggests that the rostral brain stem is being compromised. Decorticate posturing is similar but leg extension is accompanied by arm flexion and internal rotation. To produce this type of posturing, descending cortical motor impulses must be interrupted. This interruption must be above the level of the midbrain, leaving the rubrospinal and vestibulospinal motor systems intact and facilitated (see Chap. 8).

Cerebral hemisphere functional evaluation

Cerebral hemisphere dysfunction after head trauma, unlike brain stem dysfunction, is not clearly correlated with changes in the level of consciousness. Large cerebral hemisphere lesions can be found in persons who are alert, particularly if the trauma did not cause direct brain stem damage and the lesion does not act as an expanding mass and cause transtentorial herniation. In trauma, two basic mechanisms are responsible for focal cerebral hemisphere deficits:

1. Direct compression of the brain by a mass lesion (hematoma, edematous brain tissue) or by cortical or subcortical brain contusion. Common findings associated with compression or contusion are: ❍

a. Contralateral motor weakness with frontal lesions

❍

b. Receptive aphasia of varying degree with left temporoparietal lesions

❍

c. Contralateral loss of sensation with parietal lesions

❍

d. Contralateral visual field deficits with temporal, parietal, or occipital lesions

2. Uncal (mesial temporal lobe) herniation secondary to a lateral supratentorial mass lesion. The associated findings are: ❍

a. Progressive ipsilateral third cranial nerve dysfunction (Fig. 22-1). This is caused by direct peripheral third-nerve compression by the herniated uncus at the tentorial incisure. The pupil fully dilates and the extraocular muscle movements of the eye controlled by the third nerve become paralyzed on that side.

❍

b. Hemiparesis is also seen with the third cranial nerve deficit. If the paresis is ipsilateral to the

pupillary dilatation, it is caused by a shifting of the brain and brain stem away from the extracerebral lesion (usually hemorrhage) with pressure of the contralateral cerebral peduncle against the rigid tentorial edge (Kernohan's notch - Fig. 22-2). If the paresis is contralateral, it is caused by direct compression or destruction of the cerebral hemisphere and descending fiber tract.

Lesions that produce cerebral hemisphere deficits also act as expanding masses and produce transtentorial herniation. Persons with head trauma who show signs of cerebral hemisphere dysfunction usually have alterations in their level of consciousness that frequently are the result of herniation compression of the brain stem. However, direct traumatic injury to the brain stem may also cause depression of consciousness, particularly following severe trauma. Cranial nerve dysfunction usually belies the presence of direct brain stem involvement, whereas depression of consciousness usually precedes cranial dysfunction with supratentorial expanding lesions. The exception is low temporal lesions, where the third nerve may be involved early (see also Chap. 24).

Neck Injury in the Unconscious Patient An assumption that should be made in the initial evaluation of an unconscious trauma patient is that s/ he has an unstable neck fracture until proved otherwise by x-ray. Head and neck movements should be minimized during the examination. If moved or turned, the head and body should remain as a unit, en bloc. The initial evaluation of a person with head trauma to this point has included checking the following:

1. Respiratory airway patency, oxygenation (arterial blood gases) and perfusion (blood pressure and pulse), and body temperature.

2. Brain stem function. - The level of consciousness is the most important 3. Cerebral hemisphere function. 4. Cervical spinal stability. - A lateral cervical spine x-ray showing all seven cervical vertebrae is necessary for identification of cervical spine fracture and/or instability.

Pre-existing Disease Complicating Head Trauma In the evaluation of an unconscious person, a history of minor head trauma with a disproportionate loss of consciousness should alert the examiner to the possibility of a pre-existing reason for the clinical findings. Other possible causes are:

1. Metabolic: endogenous or exogenous, such as hypoxia, hypoglycemia, sepsis, hepatic or renal failure, and medication overdose (see Chap. 25). 2. A pre-existing seizure disorder, with coma appearing due to a postictal state. 3. Other neurologic disease: subarachnoid hemorrhage, vascular occlusive disease, brain tumor, or chronic subdural hematoma.

If a history strongly suggests any of these, the head trauma may be only an incidental factor in producing the neurologic picture.

Commonly Described Neurologic Signs of Head Trauma Papilledema is evidence for increased intracranial pressure. Thirty minutes to several hours of increased pressure are required before papilledema becomes clinically apparent. Papilledema as viewed through the ophthalmoscope may have several causes, however, the principal

one is impedance of normal venous return. The central retinal veins drain through the optic disk and optic nerve before communicating with the ophthalmic veins that drain into the cavernous sinus, located inside the cranium. The optic nerve is surrounded by a sleeve of dura, which is continuous with the sclera. Between this sleeve and the optic nerve is a space that communicates with the subarachnoid space. Increased intracranial pressure, which is reflected in the subarachnoid space, is therefore communicated into the optic nerve sleeve, compressing the optic nerve and thus impeding normal venous drainage. The secondary vascular stasis in the retinal veins would be expected to produce capillary leakage around the optic disk, which is probably the major cause of visible papilledema. Additionally, high pressure inside the head may be directly transmitted to the ophthalmic veins, although this pressure would be expected to result in flow into other anastomotic pathways. Some patients do not develop papilledema even with marked elevations of their intracranial pressure. A lack of normal spinal fluid (subarachnoid space) communication along the optic nerve may explain this apparent anomaly. Elevated intraocular pressure (glaucoma) may also prevent papilledema. Battle's sign is an ecchymotic discoloration over the mastoid bone behind the ear without local skin or scalp contusion. It indicates periosteal bleeding, which drains toward the exterior from a basilar fracture and usually does not develop for several hours following the trauma. Hematotympanum is blood seen through the tympanic membrane in the middle ear. This finding as well as blood draining from the external ear indicates either a skull fracture across the temporal bone (basilar fracture) or severe shearing of the contents of the middle ear. A conductive or sensorineural hearing loss may be associated. The facial nerve (VII) passes through the temporal bone next to the middle ear and therefore if hematotympanum is noted, facial nerve function should be carefully tested. Peripheral facial nerve

contusion or transection at the fracture line causes facial paralysis, which may develop many hours or days after the trauma. Cerebrospinal fluid leakage may be noted from the nose or ears (as described earlier). This is not necessarily a bad prognostic sign for neurologic recovery but it does indicate a skull fracture. It should alert the examiner to the possible development of meningitis from retrograde passage of bacteria along the leakage tract. The Cushing reflex is a dramatic elevation in blood pressure associated with bradycardia. It is seen with increased intracranial pressure or an expanding mass lesion in the posterior fossa. When pressure is placed on the lower brain stem, peripheral vasoconstriction ensues with an increase in blood pressure. This is presumed by some to be a homeostatic compensation for the decreased cerebral blood flow caused by increased intracranial pressure. The carotid sinus in turn causes reflex cardiac slowing by increasing vagal tone. More often than not, however, the carotid sinus reflex is inadequate to overcome the tachycardia that accompanies the central vasomotor response.

Other diagnostic procedures Computerized tomography (CT scan) has revolutionized the care of head-injured patients (see Chap. 23). Fractures, hemorrhage, and edema are revealed with facility, and surgical intervention is more rationally decided. Additionally, CT techniques can be used to investigate the possibility of arterial trauma, eliminating the need for more hazardous angiography, in most instances. MRI techniques are not usually used in acute trauma because of the slowness of the procedure and the susceptibility to movement and other artifact. It may be applicable to cases of chronic injury (see Chap. 23). Spinal tap is indicated only if there is a serious suspicion of bacterial meningitis. Helpful information is

seldom obtained from the spinal tap in the evaluation of acute head trauma and it may be hazardous. Transtentorial or foramen magnum herniation can be precipitated or accelerated by a lumbar spinal tap in the setting of an expanding intracranial mass. Almost all patients with significant head injury need to have an x-ray of their cervical spine to determine the presence or absence of bony fracture or displacement prior to any significant manipulation of the neck. This must include the cervicothoracic junction.

Spinal Cord Trauma The spinal cord lies protected within the vertebral spinal canal, a channel lined by bone (vertebral bodies and laminae) and ligamentous structures (e.g., posterior longitudinal ligament and ligamentum flavum). The vertebral body laminae and facet fibrous attachments acting together with the preceding two ligaments form a semiflexible tubular structure that subserves maintenance of erect posture and protection of the spinal cord. Direct and indirect forces applied to the spine may cause injury to the spinal cord. Direct injuries that distort, fracture or crush the vertebral column may contuse or lacerate the spinal cord, which lies within the narrow spinal vertebral canal. Stab wounds entering through the interlaminar space may sever the spinal cord without bony injury. Indirect distortion of the vertebral column is by far the most common cause of spinal cord injury. Acceleration-deceleration forces applied to the head or trunk cause distortion of the vertebral column and its contents. Not surprisingly, the most mobile portions of the vertebral column are the most prone to damaging distortion. These are the lower cervical and thoracolumbar junction regions. The rib cage of the thoracic spine makes it the least mobile and therefore the least likely to be distorted by indirect forces.

Flexion and extension distortions of the cervical spine are the most common cause of spinal cord injury. The vertebral bodies may be displaced anteriorly or posteriorly on themselves (listhesis) with or without ligamentous tears causing concussion, contusion, or laceration of the spinal cord. Severe flexion may stretch the spinal cord upward which in conjunction with the bony displacement mentioned earlier adds further injury. If the forces are great enough, or if there is a predisposing fragility of the spine as in the aged with cervical osteoarthritis, fractures may occur and bony fragments contribute to cord damage. Acceleration and deceleration vehicular accidents are the most common causes of cervical and thoracolumbar spinal column distortion. Swimming pool diving accidents, associated with flexion or extension deceleration distortion of the cervical spine, are also frequent causes of spinal cord injury. The spinal cord may be damaged by direct compression or disruption (bone displacement or fracture, hematoma, extruded disk material, and ligamentous distortion), stretching, secondary edema following concussion, or secondary vascular occlusive and hemorrhagic phenomena. All degrees of cord dysfunction may result, from complete disruption with crush or lacerating injuries to minor symptoms with no objective losses from minor concussing forces. A typical crush or contusing lesion typically damages the more fragile central gray matter of the cord with early preservation of the surrounding white matter and long-tract motor and sensory systems. This pattern may persist and, if the gray matter is the primary area of damage, functions below the injury may be preserved while there may be persistent problems at the level of injury ("central cord syndrome"). However, over a relatively short period of time the white matter pathways my be involved, possibly by edema or ischemia and by release of neurotoxic substances at the site of injury. Attempts are being made to determine ways to prevent the ensuing white-matter injury. Surgical decompression

of the segments may be indicated in rare cases. Cooling of the spinal-cord cooling may decrease metabolic demands. Various drugs (antioxidants, vasodilators, etc) have at least some experimental support, but most have not been proven effective in humans. One possible exception is massive doses of corticosteroids, which were reported to make a tiny difference in outcome. However, reassessment of the data from this trial suggests minimal, if any benefit. Any therapeutic approach in the acute event may be limited by the delay in getting the patient to an appropriate spinal cord trauma center. Prevention of further injury by immobilizing the spine at the site of the accident is important and may be the most effective acute treatment. When paraplegia is established as a permanent baseline, rehabilitative efforts become of major importance. The average paraplegic can be rehabilitated to become an independent and productive member of society. The prognosis for the quadriplegic patient, if s/he survives for any length of time, is poor.

References

●

Jennett, B. and Lindsay, K.: An Introduction to Neurosurgery, ed. 5. Oxford, ButterworthHeinemann, 1994.

●

Lindsay, K.W., Bone, I., Callander, R.: Neurology and Neurosurgery Illustrated, 2nd ed. New York, Churchill Livingstone, 1991.

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Disorders of the Nervous system - Reeves & Swenson Table of Contents

Chapter 23 - Neurologic Tests

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On this page ●

Many tests are used specifically for the evaluation of neurologic illnesses (Table 23-1). The general physician should be familiar with

Lumbar puncture

❍

Technique of LP

❍

Interpretation of LP

the diagnostic capabilities of all these tests and should be able to

findings

interpret the results of the lumbar puncture. ❍

Indications for LP

❍

Complications of

Lumbar Puncture

LPContraindication of LPIndications for LP

Technique The technique of lumbar puncture is learned in the ward, so only a

●

Cisternal puncture

few points are made here. Spinal taps should not be done above the

●

Imaging modalities

L2-3 interspace because the spinal cord may be present above this

❍

Skull radiographs

level. If the flow of spinal fluid is not brisk, the following check is

❍

Spine radiographs

simple (Fig. 23-1): The manometer is tilted horizontally to increase

❍

Radioisotope scans

the flow and then brought back to the vertical position so that the

❍

Duplex ultrasound

fluid falls to the true spinal fluid pressure. If this maneuver fails to

examination

increase the flow, the needle is not properly placed or a nerve root has

❍

Cisternography

blocked the needle. Fluid should not be aspirated because this may

❍

Myelography

trap and damage nerve roots. If the initial CSF pressure is high (more

❍

Angiography

Go!

than 180 mm H2O), the physician should try to let it fall without removing fluid; the patient should be encouraged to relax, and their

❍

Indications for angiograms

❍

Angiographic

neck and legs should, if necessary, be unflexed (thus reducing venous

complications

pressure). S/he should not be asked to hyperventilate (this causes ❍

Computerized tomography

❍

Technique of CT

❍

Limitations of CT

❍

Magnetic resonance

cerebral vasoconstriction and lowers even truly high CSF pressures). S/he should be reassured, made comfortable, and allowed to rest for one minute (not much more). Even if the pressure is high, enough CSF should be removed for the performance of routine tests (about 6-

imaging

9 cc; 2-3 cc in each tube).

Examination of the fluid Cell counts should be made in the first and last tubes. The fluid is

●

❍

MRI technique

❍

MRI indications

Electrodiagnostic testing

❍

Electroencephalography

white background) and then analyzed for protein and sugar. The

❍

Evoked potentials

whole CSF or the sediment can be stained for microorganisms (in

❍

Electrodiagnosis of

then examined for color (compare with a tube of water against a

peripheral nervous system

appropriate cases). Analysis for bacterial or fungal antigens or polymerase chain reaction for viruses or tuberculous bacilli should be

❍

Nerve conduction studies

employed depending on the clinical situation. A separate tube

❍

Electromyography

(usually tube 2) should be sent for cultures. Fungal and AFB cultures

❍

EMG in neuropathy

should be requested when indicated. CSF protein electrophoresis and

❍

EMG in myopathy

❍

Neuromuscular junction

measurement of IgG synthesis (which requires comparison of spinal fluid with a blood sample) can give hints to the presence of an

immune/inflammatory condition. Myelin basic protein concentration can confirm damage to CNS myelin.

Interpretation

CSF pressure

Although elevated CSF pressure should raise the question of an intracranial mass lesion, intracranial pressure may also increase when there is an obstruction to the flow of CSF or when the intracranial venous pressure rises (Table 23-2). Reduced CSF pressure can be artifactual (needle not properly placed, or blocked by a nerve root - check flow) or caused by CSF block (as by a spinal tumor or cerebellar herniation through the foramen magnum), general dehydration, prior lumbar punctures (the result of CSF leakage through puncture holes in the arachnoid and dura), or a posttraumatic or spontaneous CSF leak.

Xanthochromia

This is a yellowish discoloration of the fluid that is usually the result of hemolyzed blood and takes two to six hours to develop after bleeding into the CSF. Initially, the supernatant looks pink; the hemoglobin pigments are then transformed into bilirubin, so that after a day the supernatant looks yellow. The supernatant from a traumatic tap should be clear and colorless if centrifuged (since the red cells have not broken down). Other causes of xanthochromia are given in Table 23-3.

Cells (Table 23-4)

Traumatic taps are common, and it is very important to be able to identify them the first time (i.e., without having to repeat the lumbar puncture). The criteria given in Table 23-5 are used. The presence of red blood cells (that are not due to a traumatic tap) indicates bleeding into the CSF due to subarachnoid hemorrhage or extension of cerebral hemorrhage to the subarachnoid space. White cells are the result of inflammatory or infectious processes. High PMNs are usually indicative of bacterial infections (although they can be seen in early, acute viral processes). High lymphocytes are usually a sign of viral or chronic processes, although lymphoma should be considered.

Protein

An elevated level of protein in the CSF is non-specific and has many causes (Table 23-6). Protein electrophoresis may reveal other abnormalities; increased proportions of gamma globulins may be seen in persons with multiple sclerosis, SSPE, or neurosyphilis. The CSF IgG: albumin ratio (using an electroimmunodiffusion method) and the demonstration of oligoclonal IgG bands (using agarose electrophoresis of concentrated CSF) provide evidence of antibody production within the CNS, and are helpful in the diagnosis of multiple sclerosis (but are also positive in chronic CNS infection and other chronic inflammatory disease). The presence of myelin basic protein in the spinal fluid is supportive evidence for the diagnosis of multiple sclerosis and other demyelinating diseases (although it is a nonspecific finding in other causes of damage to CNS myelin).

Glucose

The CSF glucose is normally one half to two thirds of the serum value. For this to hold, ideally the spinal

tap should be done under fasting conditions. Changes in CSF glucose lag from 30 minutes to two hours behind changes in the serum glucose. The causes of low CSF glucose are reviewed in Chapter 17. Infectious (particularly bacterial), or neoplastic conditions are the most common cause of low values. Chronic bacterial or fungal infections give rise to the lowest values. Severe inflammation of the meningies can also decrease the level.

Stains for microorganisms and antigens

When infection is suspected, stains for acid-fast bacilli and gram stains should be obtained on the spun down sediment, even if there are no WBC's in the CSF (e.g., alcohol, when present, will suppress white cell migration and the CSF may have bacteria on staining and no white cells until the alcohol is metabolized by the liver). There are rapid antigen tests for several common bacteria and fungi (particularly cryptococcus).

Polymerase chain reaction (PCR)

This is a rapid test for the presence of DNA. It is particularly useful for viral infections (Herpes simplex is the classic example) and for mycobacterium tuberculosis.

Cultures

While most conventional bacteria will show growth in 1-3 days, note that tubercle bacilli and fungal cultures may take four to eight weeks to grow out.

Other

Viral cultures may be appropriate in some cases. Cytology on the cells can be used to detect neoplastic cells. However, if there is a suspicion of neoplasia, a large volume of fluid should be collected. There are also some chemical markers (for certain types of tumors) that can be measured in the CSF in neoplasia. Flow cytometry can be used to determine whether lymphocytes are monoclonal (such as occurs in lymphoma).

Indications A lumbar puncture must be done if a treatable infection is suspected. Not only can it determine the presence of infection but also provides information on the nature of the infection and how to treat it. Furthermore, since there are other conditions that can present similarly to infection, LP can narrow the differential. LP can be hazardous in the setting of a mass lesion (such as abscess). The process of draining fluid below such a lesion may result in shift of the brain. Therefore, if a CT scanner is available, imaging should be done prior to the LP. If there will be any significant delay in obtaining the scan, empiric antibiotics can be given up to several hours prior to performance of the LP without seriously compromising the diagnostic value of the LP. A scan may also be diagnostic and (such as in the case of intracranial bleeding) so that lumbar puncture may not be necessary. In addition to infection, lumbar puncture may be critical for the diagnosis of subarachnoid hemorrhage. It is included in the evaluation of many neurologic conditions (such as stroke and seizures) because abnormalities may point to various possible etiologies. There is usually an indication for doing a lumbar puncture; however, this should be weighed against the possible complications. Often (as in the diagnosis of tumor or abscess) better and less risky tests are available and should be done first.

Contraindications Infection overlying the site of lumbar puncture is a relative contraindication. The puncture should be shifted to another level. A spinal tap should be contraindicated by the reasonable suspicion of an intracerebral mass, unless the suspicion of acute infection is stronger and time does not allow for CT scanning within a couple of hours to exclude the possibility of a mass lesion. This should be a very rare situation in modern emergency medicine. This is a particular issue with cerebral abscess, where both mass and infection are present. Other contraindications or cautions are listed in Table 23-7.

Complications (Table 23-8) Post-tap headaches are fairly common. Their incidence may be reduced by: (1) using a small needle (20 or 22 gauge) and forcing fluids after the tap. It is presumed that post-tap headaches are caused by leakage of CSF from the puncture in the dura in excess of CSF production, so that a low-volume, lowpressure environment is created in the intracranial space. The headache is typically present only when the patient is in the sitting or erect position, indicating that it is caused by the brain settling against basal structures with stretching of pain-sensitive surface blood vessels and meningies. Rarely, the puncture hole may remain open for long periods (weeks or months) and injection of homologous blood into the site (a "blood patch") or even surgery may be necessary to stem the leak and alleviate the debilitating headaches. Meningitis and significant hemorrhage, while possible, is exceedingly rare. Occasionally the sixth nerve(s) will be stretched enough by the settling to cause a partial or complete palsy.

We presented this information in some detail because the lumbar puncture is an important test that is frequently performed, often by a nonspecialist. Failure to measure pressure, count cells properly, note the presence of xanthochromia, or request the appropriate tests from the laboratory results in inadequate or frankly misleading information. Unfortunately, such failures are common, even in good hospitals. It is therefore important to master the preceding information.

Cisternal Puncture This is an exceedingly rare procedure. When CSF cannot be obtained from the lumbar space (and when its analysis is considered critical to treatment), a cisternal tap may be required. The needle is placed in the midline, passing just under the occipital bone, into the (usually large) cisterna magna (Fig. 23-2). This is technically fairly easy; however, if the needle is advanced too far it can enter the medulla, sometimes causing sudden respiratory arrest and death. The test should therefore be carried out only by experienced physicians (usually neurosurgeons or neurologists). An alternative route that may be used by neurosurgeons and neuroradiologists is lateral to C-1 with penetration through the large C-1 intervertebral hiatus. The cisternal tap may be used in myelography when the upper margin of a spinal block needs to be defined, however, magnetic resonance imaging (MRI), has become the procedure of choice for defining the upper and lower limits of spinal cord or spinal cord compressing lesions. It is necessary at times in the intrathecal administration of irritating medications, such as amphotericin B. Medications are diluted more rapidly in the larger and more rapidly circulating volume of cisterna magna than in the smaller lumbar sac.

Imaging modalities

Skull X-Rays Routine skull x-rays are often of little clinical value because the skull is not affected by most intracranial events. Skull x-rays may be useful under certain circumstances, particularly trauma (Tables 23-9 and 23-10). However, the role of radiographs in detecting conditions such as fracture or sinusitis has largely be supplanted by CT scans.

Spine X-Rays X-rays of the cervical, thoracic, and lumbosacral spine may detect misalignment, fractures, metastatic lesions, degenerative changes, and occasionally enlargement of a foramen or of the walls of the spinal canal from tumors. Considerable discrepancy may exist between the x-rays and the clinical picture; severe degenerative changes in the cervical and lumbar spine may be almost asymptomatic, whereas a protruded intervertebral disk may produce considerable pain or focal neurologic deficit without causing any abnormality on the plain x-ray. Oblique views of the cervical spine demonstrate the neural foramina. The lateral cervical spine x-ray demonstrates the AP diameter of the spinal canal (Fig. 23-3). Persons with congenitally narrow canals (AP diameter of 12 mm or less (normal range is 14-22) are more likely to develop spinal cord compression with trauma or with the degenerative changes that occur with age (cervical spondylosis).

Radioactive emission tomography Positron emission tomography (PET) and less expensive single photon emission computerized tomography (SPECT) are imaging techniques using radioactive isotopes, which reflect brain

metabolism and can be useful in helping determine or confirm epileptic seizure foci, in particular in patients with intractable epilepsy who may be candidates for neurosurgical intervention to remove the focus. They also can help differentiate the various forms of dementia, which affect specific areas of cerebral cortex (e.g., Alzheimer's parietal-temporal preference and frontal lobe dementia). Such scans may be helpful in distinguishing neoplastic from other mass lesions. In addition to these clinical uses, PET has been used for studying normal brain functions but will likely be superceded by functional MRI (see below). PET is expensive and not likely to be of routine use (outside of examination for cancer) and SPECT will likely continue to have limited application.

Noninvasive Evaluation of Carotid Disease Numerous techniques have been developed to help detect stenosis or occlusion of the carotid arteries. Turbulent and accelerated flow in a narrowed carotid artery can be detected using Doppler imaging techniques; B-mode ultrasonography can visualize carotid stenosis and may be able to detect ulcerations in the wall of the carotid artery; M-mode can detect accelerated flow in the stenotic region. While ultrasound is rapid, convenient and non-invasive, it is not as accurate as some of the imaging techniques and should be considered a screening modality. Magnetic resonance angiography and CT angiography are newer techniques visualizing the extra- and intracranial vasculature and, although not as accurate as conventional angiography, are gaining acceptance as they become technically more sophisticated and reliable. In the case of CT angiography, images can be obtained that are nearly as accurate as conventional angiography.

Myelography *

In this procedure, water-soluble contrast is introduced into the lumbar subarachnoid space (via lumbar puncture). Because the contrast used is heavier than spinal fluid, it can be moved up and down the spinal canal by tilting the patient appropriately. Normally, one sees the outline of the spinal canal, the spinal cord, and the proximal part of the nerve roots. The following abnormalities also may be seen (Fig. 23-6):

1. Extradural defects (from herniated disks, tumors, etc.), which indent the thecal sac. 2. Intradural extramedullary defects (as from meningiomas or neurofibromas), which appear between the edge of the thecal sac and the shadow of the spinal cord. 3. Intramedullary masses (syringomyelia, ependymoma, glioma, etc.), which expand the shadow of the spinal cord. 4. A-V malformations and fistulas on the surface of the cord may be seen as serpiginous filling defects.

Complications are the same as those for lumbar puncture. Contrast use occasionally is associated with seizures and encephalopathy if it is allowed to spill into the intracranial subarachnoid space, but because of its water solubility it is absorbed rapidly and arachnoiditis is an unlikely complication. Standard myelography is being replaced today by low-volume dye injection into the subarachnoid space followed by a delayed CT scan which gives a much more detailed picture of the spinal canal contents and by spinal MRI which delineates soft tissue pathology better than CT myelography (CT myelography shows the bone structure).

Arteriography (angiography) *

Contrast material can be injected through a catheter passed into the aorta (from the femoral artery usually). It is possible to visualize both carotids and both vertebrals simultaneously (arch aortogram, four-vessel study) or one may selectively catheterize each of the four vessels.

Indications

Angiography is the most accurate method for visualizing vascular pathology. This includes abnormalities in the extracranial cerebral circulation (the carotid and vertebral arteries and their origins) and intracranial vascular abnormalities (aneurysms, AV malformations, vasculitis and occlusive disease). In addition, displacement of arteries or veins can be seen with tumors or other mass lesions, or with ventricular enlargement. Some neoplasms (for example meningiomas and metastatic hypernephromas) are heavily vascularized and will show as a blush on arteriography. Extracerebral mass lesions such as subdural hematomas can be clearly delineated. In addition to defining lesions, an increasing number of intracranial conditions can be treated by endovascular techniques, requiring angiography. Although the CT scan and MRI (see below) can study blood vessels without the morbidity of angiography, they are not as accurate as angiography in defining vascular anatomy. However, improvements in CT angiography have made it nearly as good for defining vascular lesions. Angiography is still better at defining the vascular anatomy of a lesion (such as a tumor) that is to be treated surgically. The new technique of magnetic resonance angiography (MRA) is attractive in that it is not invasive and, therefore, not associated with risk. Additionally, MRA is often coupled with imaging of the brain structure to provide a more complete picture of intracranial disease. The advent of very fast CT scanners has promoted the development of CT angiographic procedures (CTA) that include the

relatively low-risk administration of intravenous contrast. These less invasive techniques are still in development, although they will likely supersede conventional diagnostic angiography to a large degree in the future. On the other hand, conventional, catheter angiography will continue as a way to treat certain conditions.

Complications

Permanent morbidity or death (usually from stroke) occurs in less than 0.5% of patients, depending on the experience and skill of the arteriographer and the condition of the patient. Persons with vascular disease (e.g., hypertensives, diabetics) have a higher incidence of complications than other patients. Patients must be selected with some care for this procedure; the benefits must be weighed against the risks. The use of computer assisted digital subtraction technique has decreased the amount of dye needed for angiography and therefore the risks.

Computerized Tomography

Technique

A thin beam of x-rays is scanned across the patient's head in a large series of angles around the entire head and at sequential cross-sectional planes (termed "slices") (Fig. 23-7). The results, instead of being developed on x-ray film, are fed into a computer, which solves simultaneous equations for each of many thousand points. The computer thereby determines the radiographic density for each of these points and results can be printed out as an image or numbers (in Hounsfield units - after the Nobel prize winning inventor of the CT scan) can be determined for any point. Differences in density that are too

small to be detected by plain x-rays are demonstrated. The resulting picture consists of a section through the brain in which the subarachnoid spaces, brain, ventricles, and other details of brain anatomy are seen. Tumors, hemorrhages, cysts, hydrocephalus, and other conditions can be identified. The dose of radiation is similar to that of a routine skull series. Intravenous injection of positive contrast material may increase the yield of the procedure by increasing the density of lesions that have a defective blood-brain barrier (some neoplasms, chronic subdural hematomas, abscesses, infarcts, some demyelinating plaques, etc.). Because computerized axial tomography is noninvasive, it has become an important screening test. It is useful in the diagnosis of infarction, tumor, trauma, hemorrhage, hydrocephalus, atrophy, and other processes. It makes the diagnosis of cerebellar hemorrhage, heretofore difficult, relatively easy. It makes it possible to follow ventricular size (and thereby to detect progressive hydrocephalus) without subjecting the patient to discomfort or risk. Water-soluble contrast (metrizamide) injected into the lumbar subarachnoid space can provide adequate contrast so that the shape of the spinal cord and of lesions impinging on the subarachnoid space can be visualized on the CT scan. Scans of the lumbosacral spine, reconstructed in crossection, without contrast, give good resolution of herniated and bulging discs, but are especially good for demonstrating bony spinal stenosis, usually the result of chronic osteoarthritic changes in the facet joints. CT scanning has become an essential evaluation tool in acute trauma not only because it can define fractures and dislocations very accurately, but also due to the fact that extravasated blood is quite dense and readily visible.

Limitations

Some intracranial lesions may be missed. For example, subdural hemorrhages may be missed because they lie close to the skull, and both blood and bone appear dense. In fact, some chronic subdural hematomas may be of the same radiographic density as the surrounding brain (isodense) and appear only as a shift of brain substance to the opposite side. Vascular lesions, such as aneurysms and AV malformations, are better diagnosed by arteriography (or CT angiography). Small irregularities in the ventricular system and some pituitary fossa abnormalities are better detected by magnetic resonance imaging (MRI), because MRI resolution is greater. Lesions in the posterior fossa and near the base of the skull are difficult to observe on CT scans due to distortion of the x-rays by the very thick bone in the skull base. Lesions in these locations are much better visualized by MRI scanning, as are lesions within the brain paraenchyma (i.e., strokes, demyelinating plaques, etc.).

Magnetic Resonance Imaging (MRI) This newer system follows on the heels of CT scanning, which was hailed as the greatest neurodiagnostic advance of the century. MRI is even more impressive, however, it has not replaced CT scanning which continues, for the time being, to be more available, less expensive, quicker, and better at defining some things (e.g., it images bone and recent hemorrhage better than MRI).

Techniques

MRI, as its name implies, uses electromagnetic waves (not ionizing radiation) to form reconstructions of tissue and is especially suitable for imaging the intracranial and intraspinal contents. A powerful magnetic field is used to align hydrogen-containing dipoles (almost exclusively water molecules). A radiofrequency pulse is delivered to the body, adding energy to the molecules and moving them away

from their position of alignment. Following the pulse the water molecules return to their resting (aligned) state, releasing quanta of energy (or "echos") which can be detected. This energy release is proportional to the concentration of water molecules present in the tissue and the timing of release is dependent on the freedom of the water molecules to move in the environment (which is dependent on the chemical environment in which the molecule exists). Computer analysis of the emissions allows construction of an image with excellent soft tissue contrast resolution which can be displayed in virtually any plane and which is free from bony artifact (there is no signal from compact bone).

Indications

Small ischemic, demyelinating and neoplastic lesions are much better shown then by CT scan. Additionally, newer procedures have been developed (diffusion- and perfusion-weighted images) that are capable of detecting strokes as they are happening and define their stages and the amount of brain that is at risk. Intravenous contrast materials have been developed, such as gadolinium (DTPA), which enhance the signal from any lesions that contain disrupted blood-brain barrier. Areas where bony artifact obscures CT images such as the temporal lobes, cerebellum and brainstem, the region of the foramen magnum, pituitary gland and acoustic nerve are more clearly delineated by MRI. The movement of blood leaves a void on the reconstruction because the protons do not remain available for emission, once flipped. This can be seen as a "flow void" on the scans and allows some analysis of the patency of the larger arteries at the base of the brain and in the neck. Several techniques have been developed to incorporate the information in the MR image into a detailed image of the blood vessels, processes that are generically called magnetic resonance angiography (MRA). This has become an improving and increasingly important technique for imaging aneurysms and arteriovenous

malformations although, at least for aneurysms, it does not yet match conventional angiography. Special MRI techniques are now available for measuring functional localization in the cortex (functional MRI - fMRI). The amount of deoxygenated hemoglobin in a brain region will affect the amount of magnetic signal that is obtained. Therefore, comparing the signal from a brain region before and during some stimulus, action or thought can detect a change in blood flow (blood oxygen level detection BOLD imaging). This information can be superimposed on a highly detailed MR image of the brain. For example, attention-getting visual stimulation of either the left or right visual fields will increase metabolism in, and therefore blood-flow to, the appropriate calcarine cortex, which can be mapped. Magnetic resonance spectroscopy can provide information on tissue chemical makeup of a brain region. This technique is becoming increasingly useful in differentiating various pathologies such as neoplasms, ischemic lesions, abscess and demyelinating plaques.

Limitations

In addition to some limitations in availability of MRI scanners (and issues of cost), there are several practical and theoretical limitations. Because bone has a paucity of hydrogen ions it is poorly seen. Bony lesions such as fractures and osteoarthritic changes are best seen with CT. MRI scans are susceptible to many artifacts based on motion, or magnetic distortion (particularly by any metal in the region). The scanner itself may damage or reprogram the circuits of pacemakers, implanted stimulators or automated defibrillators. It also may traction ferromagnetic implants or clips. Some old aneurysm clips could be dislodged (more recent clips are made of titanium, which is not ferromagnetic). Usually larger implants (such as hip replacements, etc) are not a problem (although they may warm up a bit in the scanner). Very recent steel vascular clips may be dislodged.

There are quite severe issues of patient tolerance. The patient must be very still and the space is quite small (there are larger, "open" scanners, but they are less available and the image is not as good). Confused, young or uncooperative patients may not tolerate this procedure and patients with claustrophobia also have difficulty. General anesthesia can be used but the patient is difficult to monitor during this rather long procedure. This issue of difficult monitoring also complicates the use of MR scanning of patients who are acutely ill and makes it less helpful in trauma cases. Monitoring or therapeutic equipment that has any ferromagnetic components has to be kept out of the room with the scanner, providing dome difficulty in use.

Electrodiagnostic tests

Electroencephalography (EEG) The electric activity of the brain can be recorded from electrodes applied to the scalp. The pattern of the EEG varies with age and with the state of attention. In the normal adult, the EEG consists of lowvoltage, fast activity when the patient is alert and attentive; alpha rhythm (8-13 cps) is more prominent when the eyes are closed and the patient is not concentrating. Slower activity is seen in persons who are drowsy, and specific patterns characterize the different stages of sleep. Pathologic processes may produce EEG abnormalities (Table 23-11). Minor abnormalities are seen in a high percentage of brain-damaged persons, but since they are also seen in as many as 10-15% of normal persons, they are of little diagnostic value. Conversely, a normal EEG does not rule out serious organic disease affecting the hemispheres and certainly does not "rule out" epilepsy (about 40% of patients with documented epilepsy have normal EEGs in between seizures).

Special "activating" techniques may to bring out abnormalities, especially in the diagnosis of seizure disorders. Hyperventilation is used routinely. Photic stimulation (flashing lights) may evoke synchronous discharges in normal persons ("photic driving") and may provoke seizures in susceptible individuals. Sleep is useful in bringing out seizure discharges in many persons. Special placement of electrodes may help diagnose conditions that are not apparent on the routine EEG. Nasopharyngeal electrodes (inserted through the nose, Fig. 23-4) record activity from the orbitofrontal and mesial temporal regions remote from electrodes placed on the scalp. These are used principally in the diagnosis of limbic (temporal lobe) complex partial epilepsy. Increasingly, prolonged, continuous monitoring of the EEG is useful in the assessment of "spells" that may be seizures. This is often accompanied by video monitoring of the patients behavior. This may be done with scalp electrodes, however, the EEG is attenuated and diffused by the meningies, skull and scalp. Intracranial electrodes, either applied to brain surface by positioning in the subdural space (electrocorticogram), or from electrodes in the substance of the brain (depth electrodes) may increase accuracy in detecting and localizing abnormal activity. These measures are sometimes used in the evaluation of refractory seizure disorders, especially prior to surgery.

Evoked Responses (evoked potentials) Electrical responses to sensory stimuli are usually too small to be detected in the routine EEG. By computer averaging responses to repeated stimuli, however, clear-cut potentials can be demonstrated to visual, auditory and somatosensory stimuli. By changing the placement of the recording electrodes, the evoked potential can be made to reflect cortical (as in the case of the standard visual evoked response), brain stem (as in the brain stem auditory evoked response) or spinal cord (as with

somatosensory evoked responses) electrical events. Changes in latency or amplitude of specific components of the evoked response reflect abnormalities in conduction in specific sensory pathways, and thus can help to document the presence and location of lesions. This may be used to particularly good effect in patients with suspected demyelinating disease. Since areas of demyelination markedly slow conduction velocity, evoked responses have proved sensitive in detecting subclinical lesions in persons with multiple sclerosis. The visual evoked response (VER) has been shown to be the most useful in providing evidence for multifocality of lesions, a criterion for diagnosing multiple sclerosis (see Chap. 14).

Electrodiagnostic Tests of Peripheral Nerve Function

Nerve conductions

Motor and sensory nerve conductions can be determined from peripheral nerves superficial enough to be stimulated transcutaneously. The technique for determining motor nerve conductions is illustrated in Figure 23-5. The muscle action potential is recorded from C, the median nerve is stimulated at B, and the latency (time from stimulus to response) is recorded. Similarly the latency from stimulating the nerve at A is determined. Latency A minus latency B represents the time it takes for the nerve impulse to travel from A to B. The distance from A to B divided by this time is the conduction velocity. The nerve conduction velocity is normal (about 40-70 m/second) as long as there are some fast-conducting fibers left in the nerve. A normal nerve conduction does not, therefore, rule out a peripheral neuropathy. Demyelinating neuropathies (see Chap. 12) produce marked slowing of the nerve conductions. Axonal neuropathies may produce some increase in distal latency, but usually the nerve conductions are

normal or only slightly reduced. Focal slowing may be detected in cases of nerve compression which as a rule initially cause a demyelinating lesion. Sensory nerve conductions are determined by stimulating the skin and recording from the appropriate nerve. The potential recorded is very small, and consequently very mild nerve injuries alter or abolish it.

Electromyogram (EMG)

A needle electrode is inserted in the muscle. Normally there is no muscle activity at rest, but with minimal voluntary contraction, individual motor unit potentials are seen. These represent the summation of the membrane action potentials of many muscle fibers, all innervated by the same anterior horn cell (the motor unit). With increasing contraction, more motor units are recruited, the firing rate increases, and a dense interference pattern is seen in which the baseline of the EMG is no longer visible.

Changes with neuropathy

When the muscle is partially denervated, there are changes in the excitability of muscle fibers, so that after about three weeks muscle fibers may fire at rest (fibrillations). If denervated fibers are reinnervated by neighboring healthy nerve axons (a process that takes place over months), motor units are formed that are larger than normal. As the number of motor units decreases, the interference pattern seen with maximal contraction becomes less dense, and large polyphasic cross innervation units are seen.

Changes with myopathy

The number of motor units remains normal, and therefore the interference pattern is normal except in the very late stages. The individual units are smaller because some muscle fibers have dropped out. The motor unit potentials are, therefore, on the average, smaller in amplitude and shorter in duration. More units must be fired to produce a particular strength of contraction, so the full interference pattern is achieved earlier. Polyphasic potentials are also seen. The EMG picture of brief, small-amplitude, abundant, polyphasic potentials (BSAPP) is characteristic (although not pathognomonic) of myopathy. Although usually the muscle is silent at rest, fibrillations can occur, and are often seen in persons with polymyositis, perhaps a result of denervation caused by damage to the intramuscular nerves. In normal persons muscle activity ceases abruptly with muscle relaxation. In patients with myotonia, repetitive afterdischarges are seen. This correlates with clinical myotonia (see Chap. 12) but is more sensitive. Cases of myotonic dystrophy can therefore be diagnosed by EMG before clinically obvious myotonia is present.

Neuromuscular junction

Repetitive stimulation of a nerve produces little attenuation of the summated muscle action potential at rates of 3 to 30 per second. In persons with myasthenia gravis, however, this attenuation is marked because neuromuscular transmission is marginal at the start. Conversely, in the "myasthenic" syndrome associated with carcinoma (the Eaton-Lambert syndrome), repetitive stimulation augments the muscle response.

* Note: The procedure is invasive because a radio-opaque dye must be injected. In general, it carries a

higher morbidity than the foregoing procedures so they are not used as screening tests.

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Chapter 24 - Depression of consciousness

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Definitions

Definitions

❍

Coma

Some definitions are necessary because medical and lay jargon for the various

❍

Stupor

levels of depression of consciousness is legion and loosely applied. The

❍

Coma-like

subject's behavior or absence of behavior as determined by careful observation and described in simple terms is most informative.

states

●

Reticular formation

●

Cerebral hemispheres

●

Evaluation of the

Coma Coma is a pathologic state of unconsciousness from which a person cannot be

comatose patient

aroused to make purposeful responses. As a rule light coma is present when ❍

reflex motor response (i.e., decorticate and decerebrate posturing) can be

level of

elicited by noxious stimulation. In deep coma there is no response.

Stupor

Evaluation of

consciousness

❍

Evaluation of respiration

Stupor is a state of pathologic reduced consciousness from which the patient ❍

can be aroused to purposeful response only with persistent external

pupils

stimulation. This covers the broad range from persistent drowsiness from which the patient can be aroused by constant stimulation for periods of alert wakefulness to deep stupor from which the patient can be aroused only to the

Evaluation of

❍

Evaluation of oculomotor-

vestibular

level of poorly directed defense against noxious stimuli.

function

Sleep is a nonpathologic depression of consciousness from which the subject can be aroused to persistent alert wakefulness with appropriate non-noxious

❍

Evaluation of motor function

stimuli. Sleep is an active and reversible suppression of reticular arousal. ●

Summary

Coma-like States

●

Reference

Hysterical coma or stupor is feigned or subconsciously assumed depression of

●

Questions

consciousness differentiated clinically from true coma or stupor by a normal and alert electroencephalogram, the presence of nystagmus on caloric irrigation of the external auditory canal (see Chap. 6) and the absence of abnormal neurologic signs. The de-efferented state, in which a person has lost most if not all motor behavior, can occur with several conditions. Diffuse neuromuscular dysfunction as with myasthenia gravis (myasthenic crisis or overmedication with cholinesterase inhibitors) and diffuse polyradiculoneuropathy (the Guillain-Barre syndrome, porphyria) can make a patient behaviorally unresponsive, although s/he may be perfectly lucid with respiratory support. The history and presentation of these disorders are such that the patient is unlikely to be considered comatose. When the base of the pons (less often the midbrain) is transected or the lower pons is transected in its entirety by hemorrhage or infarction, a state of deefferentation occurs that renders the patient acutely unresponsive (despite being awake and aware). Such patients are unable to move except for vertical and convergent eye movement and eye-opening systems (these functions are located in the preserved tegmentum of the midbrain). The auditory system, lying laterally along the brain stem, usually is not affected by the central hemorrhage or infarction, which often arises from involvement of the

paramedian vasculature. Thus the patient hears and sees. Unless the clinician asks them to look up or down, the patient may be said to be "locked in", a term aptly applied to this state by Plum and Posner. These patients' minimal ability to communicate is often unrecognized, so they are usually considered and treated as if comatose. Table 24-1 lists examples of the more common processes leading to pathologic depression of consciousness.

Substrates of consciousness Consciousness requires normal activity of the cerebral cortex since the hemispheres are the substrate for awareness of self and environment and embody the sentient functions that define human intellectual existence. Therefore, anything that diffusely depresses the activity of cerebral cortical neurons will produce stupor and coma. In general, this can be due to actual destruction of cortical neurons or can be due to conditions that suppress the activity of the cortex, which is generically called "encephalopathy". However, this normal activity of the cerebral cortex also requires normal activity in the reticular formation of the rostral brain stem extending from the midpons through the diencephalon (Fig. 24-1), termed the reticular activating system. The reticular formation can function normally even after destruction of the cerebral cortex (such as following diffuse cerebral anoxia from cardiac arrest). In general, the reticular formation and brain stem are more resistant to damage than is the cerebral cortex. In the case of the patient with diffuse cerebral cortical damage, the surviving reticular formation and brain stem may be capable of supporting a crude sleep-waking vegetative state. In contrast, the cerebral hemispheres cannot function in the absence of reticular activation. Bilateral loss of the reticular formation at the midbrain level (for

example from ischemic or hemorrhagic transection of the upper brain stem), will terminate all sentient cerebral activity. In this chapter we concern ourselves with processes that depress consciousness either by diffusely suppressing cerebral cortical activity or by damaging the reticular formation (or both). We will consider these two potential substrates for stupor and coma and how we approach the evaluation of such patients.

Cerebral Hemispheres Stupor and coma can result from depression of function of both cerebral hemispheres. This depression is almost invariably the result of metabolic abnormality or toxic effect on the cortex and is termed "encephalopathy". Depending on the type and degree of metabolic insult, this may also depress the function of the reticular formation. Generally, the reticular formation is substantially more resistant to metabolic and toxic influences than the cerebral cortex. Metabolic depression of brain function is the most common cause of stupor and coma and may manifest itself in a number of ways. The various manifestations of metabolic encephalopathy are discussed in greater detail in Chapter 25. Table 24-1 lists the basic categories of metabolic dysfunction associated with depression of consciousness that must be considered.

Reticular Formation As described above, the midbrain reticular formation (reticular activating system) is necessary for maintenance of consciousness. The reticular formation can be suppressed by the same processes that are suppressing cerebral cortical function. Commonly, the reticular formation is somewhat more

resistant to suppression than are the more sophisticated functions of the cerebral cortex, but will be affected if the suppression is greater. However, in addition to this kind of suppression of function, the reticular formation is also susceptible to direct damage because of the fact that it is contained in a relatively small area of the brain stem. There are several types of lesions that damage the reticular formation. The most common of these injuries include ischemia-infarction, hemorrhage, neoplasm, abscess, or direct traumatic disruption. In addition to these primary injuries, the reticular formation can also be damaged by compression. This usually results from a space-occupying lesion that forces part of the temporal lobe (usually the uncus) through the tentorial notch. Recall that the midbrain passes through this notch. This process, termed "transtentorial herniation" (or "uncal herniation") usually occurs due to neoplasms, hemorrhage (intracerebral, subdural, or epidural hematomas), abscess, or other conditions that cause brain edema. In the case of herniation, the initial lesion is usually unilateral and many cases present with focal lateralizing signs and symptoms (e.g., hemiparesis, hemihypoesthesia, dysphasia) that precede secondary brain stem compression (which results in the depression of consciousness). Brain stem compression occurs because the vectors of force from an expanding supratentorial mass are ultimately directed toward the tentorial notch, which is the only significant exit from the otherwise closed, rigidwalled, supratentorial space. This progression of transtentorial herniation results in a rostrocaudal deterioration in function. Progressively, the diencephalon, mesencephalon, and finally the pons and medulla are compromised.

Evaluation From the above discussion, you should be aware that depressed consciousness might result from either

bilateral cerebral cortical depression (often with later suppression of reticular function) or from damage to the brain stem reticular activating system. The conditions that produce diffuse cortical suppression are very different from the conditions that damage the reticular activating system. Therefore, the initial evaluation of the comatose patient focuses on differentiation of patients with these two causes of coma. This permits the immediate and correct selection of further diagnostic tests and institution of appropriate therapeutic management of the patient. Table 24-2 lists the major steps taken by the physician from the time the patient enters the emergency department. The neurologic evaluation of the comatose patient can be a relatively rapid and efficient procedure and should enable the examiner, with little difficulty, to differentiate between the two basic causes of depression of consciousness: (1) brain stem reticular formation depression, and (2) bilateral cerebral cortical depression (with or without accompanying brain stem reticular depression). Of course, it is not possible to examine all elements of the nervous system in the patient with depressed levels of consciousness. It has been found that careful observation of five categories of neurologic function in most cases is adequate for these purposes: (1) level of consciousness, (2) respiratory rate and pattern, (3) pupillary function, (4) oculomotor-vestibular function, and (5) motor function. The evaluation of these levels of functioning can help to ascertain what levels of the nervous system are and are not working and serial observation of these can detect progression of the condition.

1. Level of consciousness

This analysis permits determination of the degree of impairment of consciousness ranging from awake and alert to stuporous and comatose. It is based on observation of the degree of response to stimulation. Of course, the patient who is awake and alert responds appropriately and normally to

questions and commands. The patient who is drowsy opens their eyes to verbal stimulation and responds appropriately, but drifts back to a condition with their eyes closed when not stimulated. A deeper stupor requires more vigorous stimulation in order to get the patient to open their eyes and attend to stimuli. And finally, in a deep coma, there is no response to even noxious stimulation (such as tickling the nares or squeezing the fingernail). This level should be recorded so that it can be determined whether the patient is deteriorating as time passes.

2. Respiration (see Fig. 1-1).

The inspiratory and expiratory centers are located in the medullary reticular formation. These areas are under control from higher levels of the neuraxis and different patterns of respiration will occur as progressive levels of the nervous system are suppressed or damaged. These respiratory patterns have a general, although not perfectly reliable, relationship to involvement of different levels of the brain stem.

●

a. Diffuse cerebral cortical dysfunction is often accompanied by drowsiness with sighing respirations and yawning.

●

b. When the diencephalon or upper mesencephalon is suppressed or damaged, Cheyne-Stokes respiratory pattern is often seen (this is a crescendo-decrescendo pattern of respirations which is punctuated by periods of apnea of variable length). This type of respiration may also be seen with diffuse bilateral cerebral involvement as well and may be most prominent when the patient is sleeping (i.e., presumably when further cerebral depressing mechanisms are in effect). It is also seen during sleep in some normal individuals.

●

c. Damage to the lower mesencephalon or upper pons produces central neurogenic

hyperventilation (rapid [20-40 per minute], deep breathing, usually significant enough to cause respiratory alkalosis if no pulmonary compromise is present. ●

d. Damage to the lower pons produces a change to ataxic respirations (irregularly irregular) that have inconstantly varying rhythm and rate. With primary pontine tegmental involvement. There may also be central neurogenic hyperventilation or apneustic breaths (which consist of a long arrest of breathing at the end of inspiration and resemble breath holding).

●

e. When the medulla is significantly involved, there is depression and final cessation of respiration (apnea).

Obviously, the changes between these types of respirations can attend changes in the patient's condition and progression down the list (from Cheyne-Stokes to central neurogenic hyperventilation, for example) is a sign of a worsening state.

3. Pupils.

Pupil size and reactivity are mediated through variations in the equilibrium between sympathetic dilation and parasympathetic constriction (see Chap. 4).

●

a. Isolated damage or suppression of the cerebral cortex will not change the pupil or its reflexes.

●

b. If the diencephalon is severely damaged the pupils are constricted due to suppression of the hypothalamic origins of the sympathetic pupillodilator system. However, they will still react to light.

●

c. As the caudal diencephalon and rostral mesencephalon begins to be involved, the region of the pretectal nuclei may be compromised, causing a sluggishness of pupillary reactivity when the

pupil may still be small. ●

d. Damage to the mesencephalon will often damage the oculomotor complex or the third nerve. This will cause the pupils to be widely dilated (7-9 mm) because of remaining sympathetic dilator tone and they do not react to light.

●

e. Damage to more caudal levels of the midbrain will damage the sympathetics as well, resulting in a pupil that is midposition in size (4-7 mm, varying from individual to individual) and unreactive to light.

●

f. If the brain stem down through the pons-medulla is involved, the pupils continue to be midposition and fixed.

●

g. However, if the pons or medulla is selectively involved (with preservation of midbrain function) the pupils will be small and reactive because only the descending sympathetic pathways are damaged. For example, with pontine transection the pupils are frequently 1mm or smaller. There remains very little potential for further pupil constriction, and for practical purposes at the bedside, the pupils appear unreactive to light unless a very bright light is used and observations are made with a magnifying glass. A similar situation occurs with narcotic overdose, where the pupils may be maximally constricted (pinpoint, 0.5 mm or less) and therefore unreactive to light.

●

h. Suppression of brain stem function (such as by drugs, toxins or metabolic upsets) can abolish the pupillary light reflex. However, this reflex is the most resistant brain stem function when it comes to metabolic encephalopathy. It may require a very strong light and a magnifying lens (such as on an otoscope) to see the constriction, however.

4. Oculomotor-vestibular function (see Chap. 6).

One of the most important determinations that can be made in the comatose patient is whether there is normal oculomotor-vestibular function. This is because the reflexes involved traverse the brain stem adjacent to the reticular activating system. Additionally, in the patient with an awake and alert cerebral cortex, there are competing reflexes that produce a distinctive pattern of eye movements. Therefore, this single assessment can determine whether the brain stem reticular formation is intact and how alert the cerebral cortex is.

●

a. Diffuse cerebral cortical damage or suppression of cortical function results in loss of the fast component of the vestibulo-ocular reflex. The degree of suppression of this fast component is proportional to the degree of suppression/damage. Tonic conjugate horizontal deviation of the eyes during caloric or oculocepahlic testing indicates preserved brain stem reflex activity (and, by extension, intact reticular activating system) with loss of cortical input.

●

b. Damage to the mesencephalon produces loss of medial rectus response to caloric and oculocephalic stimulation, with intact lateral rectus function. The corneal reflex will be preserved since this is mediated at the pontine level.

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c. With brain stem damage through the lower pons there is loss of all response to caloric and oculocephalic stimulation because the paramedian reticular formation subserving conjugate horizontal gaze and the sixth-nerve nuclei are affected. At this stage there will be no corneal reflex.

5. Motor function (see Chap. 8).

●

a. With impairment of cerebral cortical function, paratonia is present. This is an active

perseveration of position in the limbs when passively manipulated (it feels like the patient is actively resisting your attempts to passively move the limbs and presents as irregular resistance). The mechanism of this phenomenon is not known but is also present in normal children (and therefore may represent a normal primitive response). It can be seen in some normal individuals. In addition to paratonia, the patient with depressed cortical function may have a range of motor responses to noxious stimuli. They may localize the stimulus, reaching to remove the irritant, or they may simply withdraw the body part. The latter response is less organized and occurs, to some extent, even with complete cessation of cerebral cortical function. ●

b. With damage to the diencephalon decorticate posturing may be seen following noxious stimulation (see Fig. 8-1). Decorticate posturing includes flexion of the arm, wrist and fingers, with extension of the lower limbs. This posturing may be asymetrical initially (appearing first on the more damaged side).

●

c. With damage to the mesencephalon or upper pons, decerebrate posturing begins to appear following noxious stimulation. This consists of extension and internal rotation of the arms and legs (see Fig. 8-1).

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d. Damage to the lower pons and medulla eliminates the response to noxious stimuli. Acute crosssectional loss of the lower pons almost invariably results in flaccid quadriplegia. The flaccid state, as noted in Chapter 8, is considered a diaschisis or shock phenomenon and is seen to a greater extent and lasts longer the farther down the neuraxis that the acute damage occurs. Later on (if the patient survives such an acute lesion) spastic tendon reflexes may appear, along with primitive spinal withdrawal reflexes (such as the Babinski response).

Rostral-caudal deterioration Expanding masses are a model for discussion of the effects of damage to the various levels of the nervous system. Masses include tumors, abscesses or hemorrhage but also can include edema, whatever the initial cause of the injury. Expanding masses result in rostral-caudal deterioration of neural function which can be observed in patients in whom the process cannot be stopped. In this model, cortical function is affected first, followed by dysfunction of the diencephalon, then midbrain (often due to herniation of the uncus of the medial temporal lobe), then pons and medulla. Fig. 24-2 depicts an expanding right intracerebral hemorrhage and its effect on the rostral brain stem. The sequential effects of such a lesion on functions in the 5 categories (consciousness, respirations, pupils, oculomotor/ vestibular function and motor response) are listed in Table 24-3. The first effect of such an expanding lesion would be due to its local effects on sensory and motor function (i.e., left hemiparesis, left hemisensory defect, left visual field deficit). However, when expansion of the mass results in bilateral pressure on the upper brain stem (i.e., diencephalon), characteristic changes in these 5 variables will begin to occur. The progression of deterioration usually occurs in sequence, although steps can be skipped, particularly in rapidly evolving lesions. For example, consciousness will progress from stupor to coma; respirations will progress from eupnea through Cheyne-Stokes respirations, central neurogenic hyperventilation, ataxic breathing and, finally apnea; pupils will progress from normal reactive, through small reactive, to midposition/fixed; the vestibuloocular response will go from normal nystagmus through loss of the fast component, to dyconjugate response and then loss of the tonic phase of the reflex (usually with loss of the corneal reflex); and the motor response will go from normal mobility, through paratonia, to localizing noxious stimuli to withdrawal responses, then decorticate posturing and decerebrate responses before losing all motor

response other than simple spinal reflexes. The chart usually allows you to determine the level of preserved function (Table 24-3). It is a useful didactic exercise to understand these levels of function. However, for practical purposes, the determination of progressive levels of rostrocaudal deterioration has prognostic but little therapeutic value when the process has extended beyond the midbrain. When loss of midbrain function is complete in acute deterioration, secondary hemorrhages (Duret hemorrhages) develop into the midbrain and pontine tegmentum in most patients, signaling the permanent cessation of reticular activating system function. These are presumed to occur secondary to traction and tearing of the paramedian vessels penetrating from the major basal arteries (basilar and posterior cerebral arteries). Therefore it is extremely important to recognize rostrocaudal deterioration early in order to institute therapy to prevent progression.

Metabolic encephalopathy The cerebral cortex is more susceptible to toxic, metabolic or drug-related suppression of activity than is the brain stem. Therefore, metabolic suppression of neural functions initially tends to spare brain stem reflexes and, until very late in the process, spares primitive brain stem functions (oculovestibular, respiratory and pupillary functions) until late. The pupils are usually the last reflex to be detected with metabolic suppression, although a magnifying lens (or otoscope) and a very bright light may be necessary to detect the pupillary response. Chapter 25 will elaborate on the various presentations of metabolic encephalopathy. We would like to draw your attention to a single important reference for further reading on the subject of stupor and coma. The information in this chapter and also in Chapter 25 is considered a primer

based largely on the classic text: Diagnosis of Stupor and Coma by Fred Plum and Jerome Posner. Clarity and comprehensive coverage make their book required reading and reference for all physicians who deal with patients who have depressed levels of consciousness.

Dementia vs. encephalopathy We have already discussed dementia (Chapter 2 and Chapter 16), which results from bilateral degeneration of the cerebral hemispheres. Of course, this causes varying degrees of loss of cognitive and emotional function. However, if this is very severe, there may be so much loss of cortical function as to produce depressed consciousness. However, more often, depressed consciousness in a patient with dementia is due to the presence of one or more metabolic dysfunctions. Patients with dementia are very susceptible to conditions such as may result from hypoxia (often due to pneumonitis), sepsis or renal failure from chronic urinary tract infection, or simply malnutrition, all of which depress further the functions of the cerebral hemispheres.

Reference

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Plum, F., Posner, J.B.: Diagnosis of Stupor and Coma, ed. 3. Philadelphia, F.A. Davis Co., 1980.

Questions Define the following terms:

stupor, coma, delerium, encephalopathy, reticular activating system, decorticate posture, decerebrate posture, "locked-in", Cheyne-Stokes respirations, central neurogenic hyperventilation, ataxic respiration, vestibulo-ocular reflex, diencephalic pupils.

24-1. What are the two potential causes of coma? 24-2. What are the causes of diffuse cerebral cortical suppression? 24-3. What physical findings would indicate that coma was due to diffuse cerebral cortical dysfunction rather that to brain stem damage? 24-4. What are key physical exam findings in patients with coma? 24-5. What is transtentorial herniation? 24-6. What are common symptoms of transtentorial herniation? 24-7. What is the "locked-in" syndrome? 24-8. How can you recognize "locked-in" syndrome?

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TABLE 23-1. TESTS FOR EVALUATING NEUROLOGIC ILLNESSES

1. Lumbar puncture, cisternal tap, lateral cervical tap 2. X-rays of skull and spine 3. Radioisotope brain scan 4. Cisternography 5. CSF drainage 6. Duplex ultrasonography of cervical and intracranial vessels 7. Electroencephalography (EEG) 8. Electromyography (EMG) 9. Nerve conduction studies 10. Averaged evoked responses (brainstem auditory, visual, somatosensory) 11. Psychological testing 12. Others (audiometry, cystometrograms, etc.) 13. Computerized axial tomography (CT scan) 14. Magnetic resonance Imaging (MRI) 15. Arteriography (catheter, magnetic resonance or CT) 16. Biopsy (nerve, muscle or brain)

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Chapter 25 - Metabolic encephalopathy

On this page ●

The format of this chapter is different from the preceding ones. Case reports

Depression of consciousness -

and their analyses to will be used to create a more realistic problem-solving

Case 1

environment. This approach gives a fuller understanding of each case problem ❍

Initial findings

❍

Discussion

❍

Differential

and its ramifications. For practical purposes, metabolic encephalopathy is defined as a potentially reversible abnormality of brain function caused by processes of extracerebral

diagnosis

origin. These processes usually involve some metabolic upset (electrolytes, ❍

Management

❍

Outcome

serum osmolarity, renal function or hepatic dysfunction), some deficiency (metabolic substrates, thyroid hormone, vitamin B12, etc), some toxic ●

Delerium and

exposure (drugs, alcohol, medicines, etc) or systemic toxic states (sepsis, for dementia - Case 2

example). Therefore, in metabolic encephalopathy, there is diffuse cerebral ❍

Initial findings

❍

Evaluation of

dysfunction. Of course, the degenerative diseases of the brain that result in dementia also produce diffuse dysfunction of the brain (see Chap. 16).

delerium

Although both the degenerative disorders and metabolic encephalopathy must ❍

be considered in the differential diagnosis of diffuse cerebral dysfunction, dementing conditions progress slowly, while metabolic encephalopathy often

●

Treatment

Dementia - Case 3

presents rapidly and usually with fluctuating levels of alertness (attention and

❍

Initial findings

concentration). The primary cerebral degenerative disorders do make patients

❍

Discussion

more susceptible to metabolic upsets and dementia and encephalopathy may

❍

testing

coexist (complicating diagnosis). Patients with metabolic encephalopathy may present in several ways

Diagnostic

●

Focal neurological abnormality - Case 4

depending on the magnitude and temporal course of the abnormality, the individual's age and neuronal reserve (i.e., the capacity to compensate for

❍

Initial findings

dysfunction). Ironically, patients with many causes of encephalopathy can look

❍

Discussion

very similar, and it is usually not possible to determine the cause based on

●

symptoms alone. The evaluation of the patient with encephalopathy intersects

Stupor and twitching - Case 5

with the evaluation of stupor and coma, since they have many of the same

❍

causes (see Chap. 24) and often coexist. In addition to presenting with

Iniital assessment

depressed consciousness, metabolic encephalopathy can present with

❍

Clinical course

❍

Discussion

progressive loss of intellect (dementia), hyperexcitable states such as agitated dementia (delirium) or seizures (multifocal and generalized myoclonus, ●

Summary

●

Reference

generalized tonic-clonic seizures). Rarely, encephalopathy can present with focal abnormalities of brain function, entering into the differential diagnosis of stroke and slowly expanding masses (such as tumor or subdural hematoma).

In general, the presence of metabolic encephalopathy can be detected by physical examination, however, the etiology is usually not clear based on the exam. A reliable medical-neurologic history often delineates the diagnostic possibilities. Appropriate laboratory tests should then define the etiologic factor or factors. Table 25-1, modified from Plum and Posner, is a comprehensive listing of the major processes capable of producing metabolic derangement of brain function. Analyses of examples of the various

presentations of metabolic brain dysfunction follow. The plan is to give you a general approach to the diagnosis and management of metabolic encephalopathy.

Depression of Consciousness

Case #1 A 54-year-old single man was brought to the emergency room by ambulance. He had been found unresponsive in his apartment. He was last seen 24-hours earlier by his friends at a social gathering, where his behavior was apparently normal. No medical or neurologic history was known.

Initial findings and management

The following were the initial findings:

1. Mucous membranes were dusky and respirations were shallow at 10 per minute; within minutes the rate fell further. Nasotracheal intubation was achieved and respiration was supported mechanically. 2. Blood pressure was 110/70, pulse 88 and regular, rectal temperature 36.0 C. 3. Blood glucose was drawn and an intravenous started with 5% dextrose and water; 50 gm glucose was given by vein. 4. There was no evidence of head trauma (i.e., there was no soft-tissue swelling or depression of the cranium and no contusion or lacerations over the face or scalp). There was no blood behind the tympanic membranes.

5. The ocular fundus had flat disks, and venous pulsations were present. 6. The patient's neck was supple to flexion. 7. An indwelling urinary catheter was placed.

Neurologic evaluation was carried out simultaneously and revealed the following:

1. No response to noxious stimulation (irritation of the nares with a cotton wisp and supraorbital pressure). 2. No spontaneous respiration off the respirator for one minute. 3. Pupils 1 mm in diameter that constrict consensually to bright light. 4. Eyes in neutral position and immobile; no oculocephalic or cold caloric oculomotor-vestibular response. 5. No reflexes or motor responses of any type observed or elicited.

Discussion

Two diagnoses should be entertained for this dramatic picture. Acute transection of the pons and medulla by hemorrhage or infarction and, less likely, trauma could explain all the findings. Severe metabolic depression of hemisphere and brain stem (reticular formation) function is a much more likely diagnosis. Even if these conditions were equally common, one should approach the problem primarily from a therapeutic viewpoint and consider metabolic disorder the working diagnosis since acute transection is unlikely to be treatable. Table 24-2 is an outline for the basic emergency room evaluation of patients with depressed consciousness of unknown cause. The emergency measures and laboratory studies are standard and

straightforward. The neurologic examination, as formulated by Plum and Posner, is brief but comprehensive enough to tell the examiner whether the depression of consciousness has been caused by a process involving the contents of the supratentorial, infratentorial, or both compartments. Repeated examinations determine the evolution of the process. Last, the examination, when supplemented by selected laboratory studies, helps determine the specific diagnosis. Let us further analyze our patient and determine why, on the basis of the neurologic examination alone, we should consider his condition typical of metabolic coma. The specific diagnostic possibilities can then be discussed and the laboratory procedures for making the final diagnosis reviewed.

Consciousness

Alone, stupor or coma (particularly the latter) provides very little to differentiate metabolic from structural involvement of the reticular formation and cerebral hemispheres.

Respirations

Excessive sighing and yawning, Cheyne-Stokes respirations, hyperventilation, hypoventilation, and apnea are nonspecific presentations of bilateral brain stem involvement whether it be structural or metabolic. On the other hand, ataxic respirations and apneustic breaths are seen uncommonly, if at all, with metabolic disease; if present, they indicate structural disease of the pons or medulla (see chapter 1). Our comatose patient, who has progressed from hypoventilation to apnea, must have bilateral involvement of the reticular formation of at least the mesencephalon or upper pons. Involvement of the diencephalic reticular formation alone would more likely be reflected as stupor, whereas involvement of the reticular formation of the lower pons and/or medulla in isolation would not cause depression of

consciousness. The apnea reflects loss of function of the medullary reticular formation containing the respiratory center. Therefore, we have evidence for involvement of at least the midbrain or pons and the medulla. If the involvement of this extensive amount of brain stem tegmentum were destructive or compressive, we would expect to see evidence of, or involvement of cranial nerve systems that lie therein. Specifically in our examination we should look for abnormalities of the oculomotor, abducens, and vestibular systems. Metabolic depression first involves the reticular formation and consciousness. Cranial nerve and vital function (respiration and cardiovascular support) abnormalities tend to occur late. Let us proceed with the examination.

Pupils

The pupils of our patient were small (1 mm) and reacted to light. There is very little constriction possible from a resting size this small; therefore, it is necessary to use a strong light and at times a magnifying glass (an otoscope lens is handy) to confirm reactivity. With the exception of a few rare conditions (e.g., the Argyll Robertson pupils of tertiary syphilis or advanced diabetes), 1 mm pupils react to light. The pupil in narcotic overdose is usually maximally constricted (less than 1 mm) and cannot constrict further. Occasionally the pupils are maximally constricted following transection of the pons because of loss of the descending sympathetic systems and presumably a disinhibition and possibly an active facilitation of the Edinger-Westphal complex in the midbrain. As a rule the last major reflex system lost with metabolic encephalopathy is the light reflex. The parasympathetic system is quite resistant, whereas the sympathetic system, an integral part of the reticular activating system, is depressed early in parallel with depression of consciousness. Small pupils are the rule with metabolic involvements, with the exception of toxicity from drugs that excite the

sympathetic system (e.g., amphetamine) or depress the parasympathetic system (e.g., atropine, meperidine, glutethimide). A primary destructive or secondary compressive lesion transecting the diencephalon could cause the pupillary abnormality in our patient, but it is likely that he would be stuporous and not comatose and it is highly unlikely that respiration would be lost. This would have to be caused by a separate lesion involving the medulla and sparing the midbrain. Midbrain transection causes loss of both sympathetic and parasympathetic systems, thus leaving the pupils in midposition (approximately 4-7 mm) and unreactive to light. Rarely, intraventricular dissection from an intracerebral arterial hemorrhage causes a skip picture. The hemorrhagic mass compresses the diencephalon, depressing consciousness, while it is hypothesized that the intraventricular hemorrhagic pressure wave causes depression of medullary functions when it is reflected against the floor of the fourth ventricle after passing down the ventricular channel. The midbrain and pons might then be initially spared. Acute respiratory arrest from medullary dysfunction is the most likely cause of sudden death associated with intraventricular hemorrhage. Transection of the pons and the medulla could cause the changes in respiration, consciousness, and pupillary function observed in our patient. It is reasonable to leave this unusual possibility for a diagnosis of exclusion and consider the diagnosis metabolic until proved otherwise. It is statistically much more likely and is usually amenable to therapy.

Vestibular-oculomotor systems

With metabolic encephalopathy the basic oculomotor-vestibular reflex system (see Chap. 6) first becomes disinhibited as cerebral hemispheric and reticular formation influences are lost. These disinhibited reflexes present as tonic eye deviation when caloric tests are performed or as movements of

the eyes away from the direction of head movement (oculocephalic reflex). The saccadic or checking component of the oculocephalic response is lost as is the fast or checking component of nystagmus elicited by caloric irrigation is also lost (the fast component is dependent on cerebral cortical function). With severe depression of brainstem function, this relatively resistant brain stem reflex system may be suppressed and, eventually, there is no oculomotor-vestibular response. On occasion bilateral medial rectus function may be lost first, with preserved pupil function. In metabolic encephalopathy, total suppression of the oculomotor-vestibular system occurs at about the same time as respiratory suppression. However, there is some individual variation. Our patient had no oculomotor response at all, which is compatible with destruction of the medulla or pons or severe metabolic suppression of brain stem function.

Motor systems

As a rule, the motor abnormalities of metabolic encephalopathy are symmetric. In progression from stupor through coma, diffuse paratonia (perseveration of motor tone) is seen first, followed by diffuse weakness, and ultimately flaccid quadriplegia as the condition worsens. Decorticate and decerebrate reflex posturings with noxious stimulation are commonly seen with progressive metabolic suppression of any type. An excellent model for observing these motor changes is the patient undergoing general anesthesia. For that matter, the anesthetized patient is an excellent model for observing all the changes so far mentioned. In the patient with early stages of metabolic encephalopathy, there may be some motor signs that are relatively specific for metabolic encephalopathy. Tremulousness, asterixis (usually symmetric, irregularly episodic loss of maintained motor tone of the limbs, less commonly of the axial muscles),

multifocal myoclonus (diffuse, asynchronous twitching of portions of muscles often strong enough to cause movement at the joints, of larger magnitude than fasciculations), and generalized myoclonic jerks that may or may not lead to major motor seizures should all alert the examiner to the presence of metabolic disorder. Our patient was flaccid, areflexic, and unresponsive to noxious stimulation, which is compatible with one of two scenarios: the motor shock state produced by acute transection of the lower brain stem or severe metabolic encephalopathy with suppression of the brain stem. This flaccid, areflexic condition is not caused by a supratentorial lesion with secondary compression and rostrocaudal deterioration of brain stem function since the pupils were small and reacted to light.

Summary of neurologic findings in case #1

The neurologic examination showed a patient who was flaccid, areflexic, and unresponsive to noxious stimulation, who was apnic off the respirator, and who had no oculomotor-vestibular response. His pupils were small and reactive to bright light. Although his pons and medulla may have been transected by a destructive lesion, the statistically likely and therapeutically oriented working diagnosis is metabolic encephalopathy. The former diagnosis can wait until we have disproved metabolic disease. Even if the picture were more abnormal - with the blood pressure needing exogenous pressor support and the pupils midposition and unreactive - one would still assume severe metabolic depression until proved otherwise. This latter situation, if it was secondary to a known destructive process, would indicate brain death. Metabolic conditions can totally depress brain function and still be compatible with full recovery if appropriate physiologic support is provided. Therefore, it is critical to rule out toxic

and metabolic conditions in any patient meeting criteria for brain death.

Differential diagnosis

The evaluation of the patient with coma and likely metabolic encephalopathy involves the consideration of a wide array of possibilities while, at the same time, treating acute issues that can complicate or worsen the coma. What toxic and metabolic categories must be considered for our patient? Table 25-1 gives essentially all the possibilities that might cause brain depression of this degree. Reviewing quickly the major categories should permit us to narrow the possibilities for our patient and carry out the laboratory tests necessary to define a specific cause. Obviously, the sooner the cause is identified, the sooner corrective actions can be instituted. Some nonspecific measures may be initiated as a matter of routine. For example, respiratory and cardiovascular support is initiated even before the patient reaches the emergency department (by first responders). Also, a quick survey of the place in which the patient was found often turns up clues (medicines, pill bottles, signs of trauma, etc). In the ED, after drawing blood for testing, thiamine followed by glucose is often given as a nonspecific measure in consideration of hypoglycemia. Naloxone (Narcan) is often given to reverse possible narcotic overdose. At that point, the detective work begins (including discussions with witnesses, acquaintances or family members). We will consider the thought process using this case as an example.

Basic support systems

These include oxygen, substrate, and cofactors.

Oxygen

Cardiorespiratory insufficiency caused by acute cardiac arrhythmia with spontaneous reversal might have occurred. Progressive subsequent deterioration with no good evidence for midbrain involvement (i. e., pupils remain reactive and small) to implicate rostrocaudal deterioration and good evidence (normal disks and venous pulsations) against progressive postanoxic cerebral swelling essentially rule out this possibility. Blood gases drawn on the respirator with room air revealed normal pH, Po2, and Pco2. An electrocardiogram showed only mild, nonspecific abnormalities and a regular rhythm.

Substrate (glucose)

Hypoglycemia seems an unlikely possibility; there is no history of insulin-dependent diabetes (overdose of insulin is a common cause). It must be remembered that it is quite possible to become severely hypoglycemic during prolonged alcohol drinking (days) with no intake of carbohydrates. Glucose and finally glycogen are depleted, gluconeogenesis from protein-amino acid sources is blocked by ethanol, and the blood glucose progressively drops and may reach low enough levels to cause encephalopathy. An insulin-secreting tumor is also a rare cause of severe hypoglycemia. Hyperglycemic, nonketotic coma is usually preceded by days of progressive deterioration but must be considered a possibility as well as late-stage, hyperglycemic, ketotic coma. A blood glucose determination was carried out on blood drawn prior to the infusion of glucose. A dipstick test done within minutes showed a level of approximately 200 mgm%. The laboratory value, available one hour later, was 180 mg%. The normal arterial blood pH ruled out significant ketosis along with other major causes of metabolic acidosis severe enough to cause depression of consciousness (lactic acidosis, uremia, and exogenous acid poisoning).

Cofactor deficiency

We have been unable to determine the alcohol intake history of our patient. Wernicke's encephalopathy, a condition caused by thiamine deficiency and usually seen in chronic malnourished alcoholics, could cause this level of depression but seems unlikely because no obvious illness was noted by friends at a cocktail party 24 hours before. Nevertheless, a multivitamin preparation was added to the glucose infusion because this history was inadequate, and because glucose infusion can precipitate Wernicke's encephalopathy in alcoholics or other malnourished individuals with borderline thiamine stores. The glucose initiates Krebs cycle activity, which places high demand on residual thiamine stores and deprives the brain of thiaminedependent metabolic systems.

Diseases of organs other than the brain

Significant renal and pulmonary failure has been ruled out by pH and blood gas determinations. Hepatic failure with secondary shunting of large-bowel-produced toxins into the systemic circulation must be considered. In a child, Reye's syndrome (parainfectious hepatic insufficiency and secondary brain failure) might appear this rapidly. Also, fulminant hepatic necrosis (toxic or infectious) could result in acute cerebral depression. Hepatic necrosis is unlikely to occur without significant jaundice, and 24 hours from alertness to this deep coma would seem unlikely. The condition of a patient with chronic cirrhotic liver disease and portal hypertension with significant portal-systemic shunting could rapidly deteriorate under certain stresses. A common scenario in cirrhosis is acute deterioration due to hemorrhage into the bowel (e.g., from varices or acute gastritis), causing a massive increase in

metabolic toxins (including ammonia) due to the action of large-bowel bacteria on blood products (particularly protein). No stigmata of chronic liver disease were seen, there was no jaundice, and the liver was not palpably enlarged or small to percussion. No stool blood was detected, a nasogastric tube aspirate showed only mucus, and the hematocrit was reported to be normal. A clue to the presence of chronic portacaval shunting and encephalopathy in less severely depressed patients is respiratory alkalosis secondary to chronic mild hyperventilation. Elevation of the level of blood ammonia or cerebrospinal fluid glutamine (a reflection of elevated amounts of blood ammonia), are usually present to confirm the diagnosis. Other than abnormalities of glucose metabolism, endocrine disease is unlikely to present as acute coma. Our patient's hypothermia (36 degrees C) was not low enough to consider deep coma caused by hypothyroidism. Also, a long history of progressive dementing deterioration would be likely. Mild hypothermia is nonspecific for deep-coma states. With lesser depression of brain stem function, this degree of hypothermia is probably most commonly seen with sedative intoxication, particularly the barbiturates. There are other, rare considerations. The remote effects of cancer cause a chronic, occasionally subacute depression of brain function. Porphyria is unlikely to present primarily as depression of consciousness unless, as with other acute neuromuscular disorders (e.g., Guillain-Barre syndrome, occasionally myasthenia gravis), respiratory failure supervenes to cause hypoxia. These categories are unlikely in our patient, who did not lose independent respirations until after arrival in the emergency room and after respiratory support was established.

Abnormalities of ionic and acid-base environment of the brain

Significant abnormalities of the acid-base environment have been ruled out by pH determination. Relative hyponatremia secondary to excess water accumulation from excess intake of water or inappropriate secretion of antidiuretic hormone is the only ionic abnormality likely to cause this rapid and severe neurologic deterioration. Potassium abnormalities will effect cardiac and muscular function before they would affect the brain. Phosphorus deficiency would affect muscle function (strength) before it would impact the brain. Elevated serum calcium can suppress the brain (as can elevated magnesium levels), however, this is usually slowly evolving in the patient with serious endocrine or neoplastic disease. However, all of these were essentially ruled out since electrolyte values were available within an hour from admission and were all normal.

Infectious disease and subarachnoid hemorrhage

Meningitis or encephalitis could cause depression of brain stem function this severe. One might expect fever and possibly some nuchal rigidity; however, by the time these processes cause deep coma, both the fever and nuchal rigidity may be lost. Encephalitis would be the less likely of the two possibilities because severe cerebral swelling would be expected to have compressed the midbrain and caused pupil enlargement and loss of the light reflex. The presence of normal venous pulsations and flat optic disks, reflecting normal intracranial pressure, also rules strongly against this possibility. Coma due to bacterial meningitis would also be unlikely for these reasons, although rarely bacterial toxin could suppress brain function without causing major cerebral swelling or acute communicating hydrocephalus. Subarachnoid hemorrhage may cause depression of consciousness to the level of stupor, but unless it

dissects into the cerebral hemispheres and causes secondary compression of the brain stem, deep coma is unlikely in the acute stage. Evidence for increased intracranial pressure would be expected. Involvement of the midbrain (midposition and fixed pupils) would have occurred as part of the rostrocaudal process with the exception of the rare intraventricular hemorrhage phenomenon described earlier. To rule out the distant possibility of bacterial meningitis, and with the security of a normal CT scan, a lumbar puncture was performed. The opening pressure was 140 mm cerebrospinal fluid (CSF). The fluid was clear and colorless. Three red cells were present in the first collection tube, none in the third; no white blood cells were present. No organisms were seen on gram stain (individuals with alcohol in their blood or who have for other reasons a poor white blood cell response to bacterial invasion may have a delayed CSF pleocytosis, but bacteria should be demonstrable on gram stain). The level of CSF glucose was 100 mg% and the protein level was 45 mg% (both normal). Rarely, LP can be done without cranial imaging if the fundi are normal and particularly if there are venous pulsations detected. This is usually only in the case of high suspicion of meningitis and no prospect of obtaining a cranial image in a timely fashion.

Disordered temperature regulation

This is unsupported by findings.

Postseizure (postictal) depression

This is unlikely because the level of depression of brain function is too severe, and because it has progressively worsened in the absence of apparent seizure activity. However, unchecked major motor

status epilepticus could result in this severity of brain dysfunction because of a mixture of associated metabolic dysfunctions. Hyperthermia, hypoxia, lactic acidosis, and prolonged excessive neuronal activity probably all contribute to brain depression and damage caused by generalized motor status. If our patient's seizures had arrested spontaneously some hours before he was discovered, these metabolic abnormalities might have been cleared. The lack of seizure history, although sedative (ethanol) withdrawal must be kept in mind, and the lack of evidence of expected brain edema make this possibility unlikely.

Exogenous poisons

In a busy hospital emergency room, this is the most common diagnosis for patients admitted with coma of unknown etiology. The most common single subgroups are the sedative drugs (such as benzodiazepines and barbiturates) and aspirin. For the various reasons given earlier, this major category would be strongly suspected by exclusion in our patient and a serum drug screen carried out. The general serum barbiturate level was determined and found to be in the high toxic range.

Management

Management of the patient with metabolic coma should support vital systems -- respiratory and cardiovascular -- and, if possible and necessary, remove the metabolic abnormality or allow for its natural dissolution as with sedative excess. One of the major complications of prolonged coma is pneumonitis. It can usually be avoided by diligent pulmonary toilet. Another complication to be avoided

is deep vein thrombosis and pulmonary embolism, and therefore pressure stocking should be used routinely and low dose heparin considered if not medically contraindicated.

Outcome

The patient in this case made a full recovery, subsequently admitting to a reactive depression during which he had taken an overdose of pentobarbital, a relatively short-acting barbiturate. Hemodialysis is rarely necessary for treating overdoses of short- and even long-acting barbiturates. If careful physiologic support is continually available, the mortality from barbiturate or other sedative overdose should be less than 1%. With long-acting sedatives, the coma may be so prolonged (many days) that physiologic support is strained to the utmost, and then dialysis can shorten the period of critical care. The complications of hemodialysis appear minor enough now to warrant this aggressive approach.

Delirium and dementia

Case #2 A 60-year-old woman in an agitated, confused state was brought to the hospital by her husband. She had been ill with fever, chills, and muscle aches and pains for about a week and confined to bed, treated symptomatically with aspirin for "influenza". Her husband reported her to have been rational until early in the morning of admission, when she awakened and appeared agitated and frightened. She resisted her husband's attempts to take her to the hospital. There was no past history of significant medical illness. She had been taking no regular medications, although her husband claimed she occasionally took chlordiazepoxide (Librium) for insomnia. She smoked one pack of cigarettes a day and was considered a social drinker, consuming one or two drinks of wine or beer per day in the

company of others.

Initial findings

Hospital findings and initial management:

1. Blood pressure was 160/90; pulse was 110 per minute and regular; temperature was 38.5 C; respirations were 20 per minute and regular. 2. General physical examination was resisted by the patient, who insisted on leaving, more than once walking toward the door wearing only her nightgown. She was disheveled, agitated, and frightened. As best could be judged there were no stigmata of chronic illness. Skin and mucous membrane color was normal. Nuchal mobility was irregularly limited in all ranges in keeping with diffusely present paratonia. No grimacing or Brudzinki's sign was elicited on neck flexion to suggest meningeal irritation. 3. Neurologic examination revealed her to be confused about where she was, the time of day, and the day of the week. She was unable to remember the examiner's name and did not recognize him when he returned after stepping out of the room for several minutes. Essentially she was unable to imprint new information. Her attention span was shortened, reversals (e.g., saying days of week in reverse order or spelling WORLD in reverse) were impossible, and she was unable to interpret proverbs at all. She appeared to be episodically actively hallucinating, pointing to and identifying moving objects that were not present. Physical signs of diffuse cerebral dysfunction included the presence of diffuse paratonia (gegenhalten), disinhibited regressive feeding reflexes (snouting, sucking and rooting), bilaterally disinhibited palmomental responses, loss of checking

on oculocephalic testing, and a bilateral forced-grasp response on palmar stimulation. The upper extremities were tremulous when outstretched, and asterixis was noted at the wrists when extended. The deep-tendon reflexes were symmetrically 3+. No other abnormalities were elicited.

Evaluation of delirium

Acute and agitated diffuse loss of cognitive function (delirium) is almost always a reflection of toxic, metabolic or infectious disorder. This presentation and also acute quiet or apathetic encephalopathy may be caused by most of the categories listed in Table 25-1 and is most likely to occur in the early stages of acute metabolic dysfunction. Frequently periods of agitation alternate with periods of apathy and depression of consciousness, ultimately culminating in stupor or coma if the dysfunction magnifies. Sedative (including alcohol, barbiturates, benzodiazepines, etc.) withdrawal states, hypoglycemia, hypoxia, hypermetabolic states including sepsis and hyperthyroidism, hypocalcemia, hypomagnesemia, and hepatic failure appear to be more commonly associated with a hyperexcitable state than other conditions. The excited stage of general anesthesia is a fair model of agitated dementia. Underlying progressive degenerative brain processes such as Alzheimer's disease can emerge acutely as a florid dementia, agitated or quiet, under the influence of only mild metabolic stress, which alone is not enough to cause cognitive or emotional defect in a normal brain. This is true also for the aged brain, which under normal stress is able to function adequately. The 80-year-old with a temperature of 39 C is much more likely to be confused than the young adult whose neuronal safety factor (volume of neuronal processes and numbers of active neurons) is greater. Elderly patients admitted to the hospital on medical or surgical services are frequently seen in consultation for defective cognitive function. CT scans and MRIs reveal atrophic changes that are compatible with the patients' age but have not been

well correlated with studies of cognitive function. Mild metabolic dysfunctions are frequently found such as minimal renal dysfunction, anemia, low-grade fever, mild sedative intoxication (e.g., from tranquilizers and sleeping medications), mild hypoxia from chronic pulmonary disease, and congestive heart failure, usually in various combinations. Correction of the disorder or disorders frequently leads to an improvement in cognitive function. We have several clues from the history and examination of our patient. She has had a febrile illness and continues to be febrile. A temperature of 38.5 C is inadequate alone to cause clinically obvious cerebral dysfunction. Central nervous system infection, encephalitis or meningitis, could produce this picture. The absence of Brudzinski's sign or behavioral evidence for pain on neck flexion does not support meningeal irritation but does not rule it out either. A lumbar puncture should be done when there is: (1) suspicion of infection or (2) suspicion of subarachnoid hemorrhage in a patient with no focal neurologic defect. Lumbar puncture in our patient revealed normal pressure, no cells, normal protein and glucose levels, and normal results from gram stain and India ink preparations. Although the absence of elevated white cell count in the CSF does not entirely rule out meningitis or encephalitis, it does make CNS infection extremely unlikely, particularly in the face of normal pressure and normal CSF protein and glucose levels. Routine studies of blood revealed a white blood cell count of 15,000 with a shift to the left -- i.e., predominance of neutrophils and their precursors. Further fever workup included urine evaluation and culture, blood cultures, and chest x-ray, all of which showed normal results. Routine blood chemistries including glucose, electrolytes, BUN, Ca2+, Mg2+, liver function tests, and a screen for sedative drugs were normal. The patient's husband was questioned closely concerning her use of chlordiazepoxide. The possibility that she could be physiologically dependent was emphasized, with the present picture being one of

sedative withdrawal delirium (delirium tremens). He had been ministering to her illness during the week and was sure she had not had any sleeping medication. On our instruction he returned home and on careful searching found three partly empty bottles of 25-mg chlordiazepoxide capsules secreted in various parts of the house. They were prescribed by three different physicians; a general practitioner that the husband did not know, the patient's gynecologist, and their family physician. Each prescription had been filled at a different drugstore. This circumstantially confirmed the suspicion of withdrawal delirium, a condition that appears to be rebound hyperexcitability in a nervous system that has compensated for chronic sedative depressant effects (typically drugs or alcohol).

Treatment

Treatment consisted of sedative replacement; in this case, diazepam was given intravenously until it had a calming effect. Gradual withdrawal was then undertaken, decreasing the drug dose by 10% each day. An uneventful recovery occurred, and subsequently the patient described how she had gradually become dependent on chlordiazepoxide. It is of some interest and instructive that the delirium occurred approximately one week following withdrawal. Sedative withdrawal states, which include hyperirritability, seizures, hallucinations, and frank delirium tremens, usually appear within 96 hours but sometimes delirium may emerge as late as 14 days after terminating or diminishing intake.

Dementia

Case #3 A 65-year-old man was referred to the neurology clinic for evaluation of his progressive loss of cognitive

ability. His wife had noted forgetfulness, carelessness in dress and daily hygiene, and an increasing lack of spontaneity for at least six months.

Initial findings

Examination revealed evidence of diffuse cerebral dysfunction with difficulties in all aspects of cognitive function, and there was a short-term (recent) memory deficit with preservation of remote memory and out of proportion to other cognitive defects. This is rather nonspecific because both degenerative and metabolic processes may affect the memory areas of the medial temporal lobe more severely than other neocortical regions. Multiple regressive reflexes were easily demonstrated including forced grasping, disinhibited oculocephalic responses, snouting and sucking responses to labial stimulation, and a disinhibited glabellar blinking response. Diffuse mild paratonia was also present. No asterixis or myoclonus was present.

Discussion

Approximately 80-85% of persons with progressive dementia without focal signs are shown to have a degenerative process, most often Alzheimer's disease. Unfortunately, none of these degenerative conditions can be stopped (although there are some treatments that should be considered, see Chapter 16). The most important initial consideration is to identify the 15-20% who have potentially treatable disorders. There are some clues that can help identify these treatable conditions and with the aid of laboratory screening most can be ferreted out. If the patient is younger than 50, the chances of having a treatable disorder are greater. If the disorder is of recent onset and rapidly progressive and if there are frequent fluctuations in the level of function, chances are higher that a treatable disorder is present. If

motor stigmata such as tremulousness, asterixis, and multifocal myoclonus are present, it is very likely that a metabolic problem is, at least in part, responsible for the loss of cognitive function. Focal sensory or motor signs are not characteristic of metabolic disorders, and if they are present with the signs of diffuse dysfunction, they should suggest the possibility of a mass lesion, which may be amenable to therapy. Although our main purpose is to discuss metabolic disorders that cause brain dysfunction, it is hardly realistic or practical to isolate only metabolic causes of diffuse cerebral dysfunction (dementia) from the other treatable causes. Table 16-3 lists the major causes of dementia. An asterisk marks the treatable categories, which are numerous. Some diagnostic clues and approaches to therapy are also listed. Our patient appeared to have had a recent onset of his dementia, which leads one to believe there is a fair chance of finding a treatable disorder. However, it is reasonable to equivocate about the time of onset of his dementia because family members may not notice a slowly dementing process until some obviously unacceptable disinhibited social behavior or blatant confusion occurs. The patient was 65 years old at the time of evaluation. He had taken early retirement at age 62 and had been relatively inactive with few hobbies or outside interests for the past three years. Business or work associates are more likely to notice dementia in a compatriot because it may affect productivity early (although a fairly routinized job may be accomplished effectively by a person well into the dementing process). The inactivity of retirement can easily veil deteriorating brain function, and therefore it is reasonable to suspect that deterioration of our patient's mental capacity may have been occurring for as long as three years. Even if this were true, a screening battery of tests should be conducted to identify any treatable disorder behind the decline. The specific tests should be guided by the history and examination, but a comprehensive battery should include at least the following:

TEST

TO RULE OUT

Complete blood count (CBC)

General

Erythrocyte sedimentation

Vasculitis (collagen disease),

rate (ESR)

infection, occult tumor

BUN, creatinine

Renal insufficiency

Serum calcium

Hyper-or hypocalcemia Hepatic insufficiency; metastatic

Liver function tests tumor Thyroid function tests

Hyper- or hypothyroidism

Serum B12 level and/or B12 deficiency Schilling test Serum folate

Nutritional deficiency

VDRL

Tertiary syphilis Increased number of cells (hemorrhage, infection), high level of protein (tumor, etc.), low level of

Lumbar puncture sugar (infection, etc.), increased pressure (tumor, etc.), + VDRL (syphilis)

Lung tumor or other metastasized Chest x-ray

malignancy, diffuse pulmonary disease Mass, hydrocephalus, atrophy,

CT scan or (better) MRI (if infarctions, bilateral subdural tolerated) hematoma Metabolic encephalopathy; focal lesions; seizure activity; EEG of metabolic encephalopathy is liable to have diffuse slowing in the deltaEEG theta frequencies, while degenerative disease may cause little (some theta slowing diffusely) or no abnormality

Frequent runs of diffuse delta activity were seen on our patient's EEG, making a metabolic disorder highly suspect. A CT scan showed dilatation of the lateral, third and probably also the fourth ventricles; no cortical atrophy was evident. A lumbar puncture showed an opening pressure of 160 mm CSF, 10 lymphocytes, a protein of 130, and a glucose of 40 with a concomitant fasting blood glucose count of 100. Although an India ink preparation showed no cryptococci and the organisms did not grow on CSF culturing, cryptococcal antigen was detected in the spinal fluid. A course of treatment with amphotericin B was given, and within three weeks the spinal fluid protein and glucose levels had

returned to normal and no cells were detected. Some improvement in the patient's dementia had occurred after two months, but a repeat CT scan showed a continued hydrocephalus. A ventriculoperitoneal shunt was placed and further improvement in mentation followed.

Focal Neurologic Abnormality

Case #4 A 62-year-old man was brought to the emergency room on January 3 by ambulance, accompanied by his wife. He had been noted to be weak and uncommunicative that morning. Preliminary examination by emergency room personnel revealed a right hemiparesis and aphasia. The neurology consultant was called to evaluate the presumed stroke. The findings were confirmed. The patient was severely dysphasic; his communication was limited to a few perseverated and unintelligible jargon words. He appeared to have a right-sided hemianopsia to threat, responded poorly to noxious stimulation of the right extremities, and had a right-sided hemiparesis including the right lower facial muscles. The right deep-tendon reflexes were hyperactive and a Babinski response was present on the right.

Initial assessment

General examination revealed an otherwise healthy-appearing individual. No evidence of arterial disease was present. A sweetish odor of the breath was present and this prompted the examiner to think of the possibility of metabolic disorder, specifically hyperglycemia with ketosis. The patient's wife volunteered that the previous January a similar event had occurred under the same circumstances, partying over the New Year. He had been found "blacked out", seen at another hospital, "sugared up,"

and sent home no worse for wear. He had not been nor was he being treated chronically for any illness. Within ten minutes after the patient was first seen, a dip-stick analysis of blood glucose was available. A blood specimen was sent to the laboratory for more accurate evaluation. The finger-stick value for glucose was less than 40mg%. Fifty grams of glucose were given intravenously, and within thirty minutes the patient was sitting up in bed conversing normally with only minimal residual evidence of right hemiweakness, which subsequently cleared. A laboratory glucose level was available within an hour and was 24 mg%. It transpired that the patient was a once-a-year heavy drinker, and that this and the previous year he had avoided eating anything over the three days that he was continually drinking hard liquor. As noted, progressive depletion of glucose and glycogen stores would be expected and symptomatic hypoglycemia would ultimately occur because gluconeogenesis from amino acids is blocked by ethanol.

Discussion

Focal signs, suggesting destructive lesions of the brain, are unusual neurologic manifestations of metabolic disease. Hypoglycemia, hepatic encephalopathy, and hypoxia are the most frequently diagnosed conditions producing this confusing picture. Because hypoglycemia is easily treated early, because it can cause permanent neurologic defects if it is prolonged, and because it can present as coma, stupor, delirium, dementia, generalized and rarely focal seizures, and focal ablative disease, it is reasonable to demand that a blood glucose determination be made early in the evaluation of patients with these symptoms. In patients with coma, stupor, or delirium of unknown etiology, it is reasonable to give 25-50 gm glucose intravenously after drawing blood for glucose evaluation. In patients having a stroke picture or seizures, early determination of the glucose level would appear adequate. If a finger-

stick determination shows hypoglycemia, 50 gm glucose should be given. Why do patients with metabolic disorders develop focal loss of function? Some have underlying structural disease such as old areas of infarction or contusion, borderline adequate focal blood supply, or neoplasms. It is presumed that neurons that are defective but functional within or surrounding these structural lesions are depressed early by metabolic stress. There are some patients, however, in whom there is no evidence of an underlying focal lesion and, particularly with hypoglycemia and hepatic encephalopathy, the focal abnormalities may shift during the same or other episodes. If shifting does occur, it makes a metabolic problem seem more likely. No good explanation for this asymmetric metabolic suppression of brain function is available.

Stupor and "twitching"

Case #5 A 56-year-old man who was previously well was admitted to the hospital in a stupor with clonic twitching of his left extremities and face. He had been feeling ill for several days and his wife had noted him to be lethargic on the morning of admission. At about 8 a.m., when she went to check on him, she noted that his left side was intermittently twitching.

Initial assessment

Examination in the emergency room showed respirations were 20 per minute and regular, temperature was 38.5 C, blood pressure 150/90, and pulse was 90 and regular. He was stuporous with appropriate withdrawal responses on the right, and he had continuous clonic twitchings of the left extremities and

face, which were synchronous. No other pertinent findings were noted on the remainder of the neurologic examination. On general examination the only feature of note was dryness of the mucous membranes, decreased skin turgor, and myoedema (a bulging of subcutaneous and muscle tissue on percussion), suggesting dehydration. The major laboratory finding was hyperglycemia (blood glucose 1,100 mg%) in the absence of ketosis.

Clinical course

In the absence of a history of diabetes mellitus, which is typical for persons developing nonketotic hyperglycemic coma, it was elected to treat him with small doses of insulin and fluid replacement with careful attention to electrolyte levels. Some patients like this are found to be extremely sensitive to insulin and others fairly resistant. Therefore it is important to begin therapy with small doses of insulin to avoid a precipitous drop in the blood glucose level, which may result in rebound cerebral edema. This complication probably occurs because of a buildup of polyols (sorbitol, fructose, etc.) or other osmotically active substances intracellularly in the brain in the presence of prolonged hyperglycemia. When the amount of blood glucose is rapidly dropped, causing decreased serum osmolality, the polyols are only slowly metabolized and do not readily diffuse into the extracellular or intravascular space. This creates a relative intracellular hyperosmolality and water is imbibed by the cells, causing edema and dysfunction. The glucose level in our patient was gradually reduced over two days. When the level reached approximately 500 mg% at the end of the first day, the focal seizures ceased and the stupor cleared. Mild left-sided hemiparesis and confusion persisted for some hours after the seizures stopped. Twenty-five mg diazepam stopped the seizures only transiently when given intravenously in divided doses. Diphenylhydantoin was given intravenously in a dose of 750 mg over the first day and had no

obvious effect on the seizures. However, no bilateral generalization of the seizures occurred. No maintenance anticonvulsant was given. It is typical for focal status epilepticus of metabolic origin to be poorly responsive to anticonvulsant medication. As rule, the best therapy is to clear the metabolic abnormality if possible.

Discussion

Focal status epilepticus (epilepsia partialis continua) has been associated with multiple metabolic abnormalities. Nonketotic hyperglycemic hyperosmolar coma is one of the more common underlying disorders, but we have seen it with uremia, hepatic encephalopathy, hypoxia, hypoglycemia, hyponatremia, encephalitis, meningitis, and theophylline excess, and it has been reported associated with others. It appears to be a rather nonspecific and unusual manifestation of metabolic disorder. It has also been associated with structural lesions, particularly infarction, neoplasms, and other masses unaccompanied by systemic metabolic abnormality. Irritative dysfunctions (such as focal seizures) appear in some cases to be associated with minor subclinical cerebral lesions such as old areas of encephalomalacia (ancient infarcts or hemorrhages) and neoplasms. Presumably damaged but viable neurons surrounding such lesions have a relatively low threshold for seizure activity, and this threshold is exceeded by the metabolic stressor. In other cases, even the best examination has shown no obvious structural defect to account for the focal seizures.

Summary In summary, we have given case examples of the various cerebral manifestations of metabolic disorders. Depression of consciousness, progressive loss of intellect, hyperexcitable states such as delirium and

seizures, and less often focal abnormalities of brain function may be the behavioral presentations of metabolic disorders either alone or in combination, and these patterns may coexist in a single patient or may progress from one to another state in a single patient.

Reference

●

Plum, F., Posner, J.B.: Diagnosis of Stupor and Coma, ed. 3. Philadelphia, F.A. Davis Co., 1980.

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TABLE 23-2. CAUSES OF RAISED CSF PRESSURE *

1. Intracranial masses (neoplasms, hemorrhages, abscess, or brain edema) 2. Obstruction to the flow of CSF 3. Elevated intracranial nervous pressure 1. Secondary to high systemic venous pressure (congestive heart failure, Valsalva) 2. Obstruction of venous flow ■

Poor relaxation (high intra-abdominal pressure transmitted to venous plexuses around the cord)

■

Obesity (as above; also compression of jugulars by obese neck)

■

After radical neck surgery (where the major jugular vein, usually the right, has been sacrificed)

■

Thrombosis of a major venous sinus

*Pressure >180-200mm of water

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This page is under construction We greatly appreciate any and all feedback on this site. All suggestions and corrections will be responded to. Please address your comments and concerns to the site editor: Rand.S. [email protected]

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Fig. 1-1. Patterns of breathing associated with various levels of bilateral brain stem involvement (see also chapter 24).

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Fig. 1-2. head shapes associated with premature closure of sutures. a, sagittal; b, coronal; c, sagittal and coronal.

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Fig. 1-3. Subhyaloid hemorrhages following an acute and catastrophic rise of intracranial pressure. With the patient seated or standing, one may see the formation of the meniscus in these superficial collections of blood.

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Fig. 1-4. Spurling's maneuver. With the neck extended and flexed to the side, downward pressure causes narrowing of the spinal formina on the flexed side. No symptoms of root compression occur unless one or more foramina are already compromised.

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Fig. 1-5. Straight leg raising test. (a) sciatic nerve (L4-S2) stretch. (b) femoral nerve (L2-4) stretch.

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Fig. 1-6. Patrick's maneuver. Rotation of the leg on the hip with the heel on the knee does not stretch the sciatic or femoral nerves. Pain elicited should be considered to be of musculoskeletal origin and not caused by root or plexus involvement.

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Fig. 1-7. Curvature of the vertebral column associated with unilateral paraspinal muscle spasm. A, lumbosacral; B, cervical, dorsal, dorsolumbar.

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CompreType of dysphasia Spontaneous speech

Repetition

Naming

Associated signs

hension Transcortical Sensory

Fluent

Variable (signs of

severe

Echolalic

Poor

Good

Poor

"watershead" infarct);

mild-anomia

Circumlocution

Good

Good

Poor

may have Gerstmann's syndrome

Nonfluent except Motor

Can be Good

Good

when repeating Mixed

Nonfluent

May have right hemiparesis good

Poor

Good

Poor

Signs of "watershead"

sensorimotor

lesion (weakness in

"isolation of

proximal upper limb

speech area"

etc.) May be normal; may be visual

Wernicke's

Fluent, paraphasic

Poor

Poor

Poor

field defect or coprtical sensory loss; may have hemiparesis.

Poor (but can be better than Broca's

Nonfluent

Good

Poor spontaneous speech)

Right hemiparesis

Variable; often cortical sensory Conduction

Fluent, paraphasic

Good

Poor

Poor

loss or lost pain sensation on right side

Global

Nonfluent

Poor

Poor

Poor

Right hemiparesis

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Fig. 2-1. Diagramatic representation of major left cortical regions associated with verbal language functions. Key: 1, Heschel's gyrus (auditory cortex); 2, Wernicke's area; 3, arcuate fasciculus; 4, Broca's area; 5, angular gyrus; 6, motor cortex.

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Fig. 2-2. Zone of left cortical destruction causing isolation of the speech area.

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Fig. 2-3. Infarction of the left visual cortex and splenium of the corpus callosum causing dyslexia without agraphia (pure word blindness). Words seen only in the left visual field cannot be transmitted via the interrupted callosal pathways to the verbal language regions on the left.

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Fig. 3-1. Basal view of cerebral hemispheres showing the olfactory system. Lesions of the trigone, tract, bulb, olfactory filaments (schematically represented by dots on olfactory bulb) and olfactory epithelium cause unilateral loss of olfaction. Unilateral lesions of the lateral stria or olfactory cortex do not cause loss of olfaction because of the bilateral temporal lobe distribution of each olfactory apparatus through the anterior stria and anterior commissure.

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Fig. 3-2. Shearing of olfactory nerve filaments with occipital trauma: it is less prominent with frontal trauma.

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Fig. 3-3. 1, retinal defects (scotomata): (a) vascular-ichemic, hemorrhagic. Typical and pathognomonic altitudinal defect s seen with branch arterial occlusion; appropriate for altitudinal distribution of retinal ateries. Complete blindness occurs and is associated with central retinal artery occlusion by atherosclerosis, emboism, arteritis or the arterial compression of severe papilledema. (b) Inflammatory - choroiditis, granuloma; neooplastic - primary or metastatic; mechanical - retinal tear or detachment. (c) Glaucoma - frequent selective nerve fiber bundle loss causing a crescent scotoma. 2, Loss of central (macular) visual bundle (central scotoma): (a) Demyelination - multiple sclerosis, isolated optic

neurities. (b) ischemia of optic nerve. (c) Metabolic - vitamin B12 deficiency; alcoholic - nutritional amblyopia. 3, Transection of optic nerve(monocular blindness): (a) Tumor - subfrontal (sphenoid wing meningioma, optic glioma. (b) Trauma - laceration. 4, loss of lateral portion of optic chiasma (nasal hemianopia): mechanical compression by enlarged, atheosclerotic carotid artery; can be unilateral or bilateral. 5, Loss of the medial portion of chiasma (bitemporal hemianopsia: (a) Tumor - pituitary neoplams, most often chromphobe adenoma with suprasellar extension or suprasellar neoplasm such as craniopharyngioma. (b) Hydrocephalus with ballooning of floor of third ventricle. 6, Optic tract or lateral geniculate loss (contralateral homonymous hemianopsia) - frequently incongruous): vascular infarction in distribution of anterior choroidal arerty. 7, monocular crescent bundle (contralateral superior monocular crescent defect): tumor, infarction or hemorrhage in anterior temporal pole or potentially also with involvement of anterior inferior calcarine cortex. 8, loss of temporal radiations, i. e., Meyer's loop (contralateral homonymous superior quadantanopia): tumor, infarction or hemorrhage in temporal lobe. 9, loss of upper monocular crescent bundle (contralateral inferior monocular crescentic defect): tumor, infarction or hemorrhage in parietal lobe or anterior superior calcarine cortex. 10, loss of parietal radiations (contralateral homonymous inferior quadrantanopia): tumor infarction or hemorrhage in lower parietal region or upper calcarine cortex. 11, loss of total optic radiations (contralateral homonymous hemianopia, usually congruous): tumor infarction or hemorrhage in the temporo-parietal junction. 12. loss of anterior and middle calcarine cortex (contralateral homonymous hemianopia with macular sparing: macular sparing occurs when calcarine infarction is caused by posterior cerebral artery occlusion if the middle cerebral artery supplies the posterior calcarine cortex. 13, loss of middle and posterior calcarine cortex (contralateral homonymous hemianpoia with monocular crescent sparing: tumor infarction or hemorrhage in unilaterally in

calcarine cortex. 14, loss of anterior and middle calcarine cortex bilaterally (loss of all peripheral vision with sparing of central vision - keyhole vision.): parasagittal tumor bilaterally compressing both anterior and middle portions of calcarine cortex; this type of defect is more commonly seen with bilateral peripheral retinal encroachment such as progressive retinitis pigmentosa and occasionally chronic papilledema. Bilateral posterior cerebral artery occlusion may leave a similar field if middle cerebral artery collateral is adequate posteriorly. 15, bilateral loss of posterior calcarine cortex (bilateral central visual field loss): parasagittal tumor bilaterally compressing posterior calcarine cortex; this type of defect is more comonly seen following bilateral optic nerve involvement (see 2). 16, bilateral complete loss of calcarine cortex (cortical blindness): bilateral posterior cerebral artery occlusion, usually at or near the bifrucation from the basilar artery. This type of blindness is frequently associated with denial of visual loss (Anton's syndrome), presumably a result of bilateral mesial temporal lobe ischemia-infarction. Parasagittal tumor and trauma with extensive mesial occipital calcarine compression or contusion are less common causes of cortical blindness.

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Fig. 3-4. Lateral view of right visual radiations. See figure 3-3 for details of lesions 7, 9, and 13.

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Fig. 3-5. Schematic representation of visual fields.

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Fig. 3-6. Visual acuity chart. Standardized pocket versions of this chart are used to test visual acuity at 14 inches (the distance equivalents are approximate).

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Fig. 3-7. Use of pinhole to correct for abnormalities of visual refraction when measuring visual acuity.

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Fig. 3-8. Tangent screen examination of visual field.

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Fig. 3-9. Perimetric examination to determine complete visual field. In the example, only peripheral vision is measured, To measure central vision, a small (e.g., 2 mm), colored object is used.

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Fig. 3-10. Technique for confrontation examination of visual fields.

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Fig. 4-1. Eye positions for testing extraocular muscle function.

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Fig. 4-2. Appropriate eye positions for initiating oblique and vertical rectus muscle versions in relative isolation and for testing up- and down-gaze.

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Fig. 4-3. Eye findings with isolated unilateral loss of function of cranial nerves III, IV and VI. Broken arrows represent lost function; solid arrows represent tone in unaffected muscles. Compensatory head adjustments frequently are seen with loss of IV and VI.

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Fig. 4-4. Red glass test. When the direction of gaze uses the weak muscle, the image is always displaced away from the macula of the retina so that the brain interprets the abnormal, blurred (off-macula) image as being farther out in the field of gaze than the normal image. The examiner needs only to detemine which eye sees the farthest displaced image to determine the abnormal side. Blurring is less useful because it is usually minimal and not noticed by the patient.

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Fig. 4-5. NOTE: In all diagrams you are looking out thorugh the subjects eyes. Pathways for

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conjugate horizontal gaze with schematic representation of eye-movement abnormalities occuring with lesions (shaded areas) in various parts of this system. 1, occipital cortical lesion associated with depression of contralateral visual pursuit gaze (this may be variable, with some test parameters indicating difficulty with gaze toward the side of the lesion). 2, premotor frontal lobe lesion encompassing area 8, associated with depression of contralateral voluntary nontracking gaze. 3, basis pontis or cerebral peduncle lesion associated with depression of contralateral pursuit and voluntary gaze. 4a, paramedian pontine reticular (pontine gaze center) lesion associated with loss of ipsilateral gaze. 4b, lesion also encompasses medial longitudinal fasciculus (MLF), causing loss of contralateral adduction. This combination of ipsilateral horizontal gaze deficiency with MLF involvement as aptly called the one-and-a-half synrdrome. 5, lesions in medial MLF between abducens and oculomotor nuclei associated with loss of adduction of ipsilateral eye on contralateral horizontal gaze. However, convergence is intact because it is controlled through the upper pons and pretectal region of the midbrain using the intact oculomotor nucleus and nerve. The name for this isolated medial rectus weakness is internuclear ophthalmoplegia (INO).

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Fig. 4-6. Diagrammatic representation of the major regions involved with conjugate vertical and convergent gaze and eye opening. Eye findings with lesions in different region are illustrated. Broken arrows represent loss of function; solid arrows represent normal function. (a) Diffuse bilateral cerebral cortex disease or severe bilateral involvement of the basal ganglia as in parkinsonism is associated with difficulty in upward gaze, convergence and, later, downward gaze, essentially a deafferentation of the pretectal vertical gaze zone. Unilateral cortical or basal ganglia disease does not cause clinically apparent problems with vertical or convergent gaze. (b) Pretectal destruction (e.g., compression by pineal tumor causes more severe difficulty with vertical upgaze and convergence to complete loss of these functions. Deeper involvement in the region medial to the red nucleus is necessary to cause significant loss of downgaze. Involvement of the pupillary light reflex region in the pretectum and also the descending sympathetic pathways results in mid-position, fixed-to-light pupils, frequently beginning with small reactive pupils because the sympathetic pathways are more dorsal and possibly more sensitive to compression. Lesions, usually ischemic restricted to the periaqueductal region of the

midbrain cause similar abnornalities and, in addition, a peculiar nystagmus that is convergent or involves all the eye muscles simultaneously and causes a jerky retraction of the eyes into the orbit (nystagmus retractorius) on attempted voluntary gaze. (c) A central lesion in the lower pons transection both the basis pontis and the tegmentum (most often infarction or hemorrhage) leaves a person quadriplegic and mute with loss of all horizontal gaze function. Vertical gaze and convergence (also eye opening) are the only remaining means of communication. If this goes unrecognized, the patient will be essentially locked in. A higher bilateral lesion (e.g., midpons) interrupts the reticular formation necessary for the maintenance of consciousness and causes coma. Lesions that transect the basis pontis or the basis pedunculi, sparing the tegmentum do not depress consciousness but leave the patient quadriplegic with no voluntary horizontal gaze (see Fig 4-5, lesion 3, but bilateral); reflex vestibularoculomotor connections are preserved because they are located entirely within the tegmentum and therefore caloric irrigations or the oculcephalic maneuver gives reflex conjugate horizontal and vertical gaze of the eyes (see the section on nerve VIII).

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Figure 4-9. Circuitry for voluntary conjugate horizontal gaze to the left. Roman numerals indicate cranial nerve nuclei.

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Figure 4-10. Circuitry for voluntary vertical eye movements. Note that there is no single cerebral cortical vertical gaze center.

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Fig. 4-7. Parasympathetic innervation of the iris with afferent pathway for light reflex. Note the bilateral distribution of each retinal input to the pretectal region and therefore the Edinger-Westphal nucleus.

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Fig. 4-8. Sympathetic innervation of the iris and sweat glands of the face.

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Fig. 5-1. Trigeminal innervation of facial sensation.

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Fig. 5-2. Dorsal view of trigeminal system in the brain stem, showing acoustic tumor compressing the lateral aspect of the brain stem and the spinal tract and nucleus of the fifth nerve. The most superficial fibers of the tract are from the ophthalmic division, thus explaining the early loss of the corneal reflex.

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Fig. 5-3. Diagram of pterygoid function in jaw opening (some physiologic license is taken). Arrows indicte normal vectors of jaw opening.

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Fig. 5-4. Deviation of the jaw on opening to side of weakened pterygoid muscles. Broken arrow represents loss of right pterygoid strength.

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Fig. 5-5. Filter paper tests for symmetry of lacrimal secretion. The length of paper soaking in a set time period is measured.

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Fig. 5-6. Supranuclear innervation of facial nerve nuclei.

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Fig. 5-7. Left facial weakness following lesion of the right motor cortex. After a delay of weeks to months, hypermimia (excessive emotional expression) may appear on the left side of the face which remains weak to voluntary grimacing and with speech.

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Fig. 6-2. Dorsal view of brain stem and cerebral hemispheres. Eyes are also seen from behind, as if reader is looking through eyes from the intracranial position. Loss of right vestibular influence releases the left vestibular apparatus to unopposed tonic driving of eyes to the right through neuronal apparatus illustrated by solid lines. Opposing phasic impulses that constitute the fast or checking component of nystagmus and arise from the right hemisphere are illustrated by broken lines.

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Fig. 6-3. The horizontal semicircular canals lie in the petrous portion of the temporal bone at an angle of approximately 20 degrees from Reid's anatomical horizontal baseline.

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Fig. 6-4. Horizontal canal in vertical orientation for caloric testing.

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Fig. 6-5. A, mechanism for contralateral tonic deviation of eyes on irrigation of external auditory canal with hot water (horizontal canal in vertical position, see Fig. 6-4). B, ipsilateral tonic deviation of eyes on irrigation of external auditory canal with cold water. Increased temperature decreases endolymph specific gravity in the horizontal semicircular canal and endolymph flows ampulopetally - toward the crista - increasing its rate of firing. Cold water causes the opposite effect, essentially a temporary ablation of the irrigated apparatus.

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Fig. 6-1. Distribution of horizontal semicircular canal cristae to oculomotor system (looking out through the subjects eyes).

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Fig. 6-6. Simple apparatus and technique for irrigating auditory canal.

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Fig. 6-7. Lesions causing pathologic depression of consciousness and associated vestibular-oculomotor changes elicited by caloric irrigation or the oculocephalic maneuver.

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Fig. 6-8. Mechanism for reflex vestibular-oculomotor response to oculocephalic maneuver. Checking component from the right hemisphere (as seen in alert patient with intact pathways) is not illustrated.

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Table 6-1. Peripheral vs. central vestibular dysfunction DISEASE

Peripheral

NYSTAGMUS

VERTIGO

ASSOCIATED

PHENOMENA CALORIC

SYMPTOMS

IRRIGATION

Horizontal or

As severe as

Hearing loss and Long-tract

Depressed

rotatory;

nystagmus

tinnitus frequent sensory, motor

response

unidriectional

involvement unusual

Central

Horizontal,

Relatively mild

Tinnitus and

Associated

rotatory or

or absent

hearing loss rare sensory, motor,

vertical; multi-

cerebellar, other

directional

cranial nerve

Variably affected and unreliable

involvement more common

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Fig. 6-9. Upbeat nystagmus best seen in upgaze.

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Fig. 6-10. Technique for testing macula-otolith apparatus (Nylan-Barany or Hall Pike maneuver) and rotary nystagmus elicited in patients with abnormal apparatus. The patient should be dropped from the sitting position to his head hanging in each of three positions: head to the right, head to the left and head facing straight up. As a rule, nystagmus is best elicited with the head turned toward the abnormal side and less intensively in the head straight up position.

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Fig. 7-1. Normal, symmetrical elevation of soft palate.

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Fig. 7-2. Elevation of palate away from weakened right side (Rideau or curtain sign).

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Fig. 7-3. Indirect (through miror) laryngoscopy. Mirror warmed to avoid fogging by patient's breath.

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Fig. 7-4. A, testing of right sternomastoid muscle. B, testing upper portion of trapezius muscles.

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Fig. 7-5. A, normal vectors of tongue protrusion. B, weakness without atrophy of right side of tongue with left corticobulbar lesion. C, weakness and atrophy (and fasciculations) with lesion of hypoglossal nucleus or nerve. The tongue always deviates toward the weak side whether the lesion is nuclear or supranuclear.

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TABLE 8-1.- THE MOST COMMONLY TESTED REFLEXES (*These reflexes are considered part of a routine screening examination for neurologic disease. The other reflexes are examined when suspicion of abnormality exists on the basis of history or screening examination.) Stretch reflexes (deep

Jaw jerk

tendon reflexes)

Superficial reflexes

V sensory (s) and motor (m)

Biceps*

C5-6 (s,m)

Triceps*

C6-7 (s,m)

Brachioradialis*

C6,7,8 (s,m)

Finger flexor

C6,7,8 (s,m)

Knee*

L2,3,4 (s,m)

Ankle*

S1,2 (s,m)

Corneal *

V (s) and VII (m)

Nose tickle

V (s) and VII+ (m)

Gag*

IX, X (s,m)

Abdominal

T7-TI2 (s,m)

Cremasteric

S1 (s,m)

Plantar*

S1,2 (s,m)

Anal wink

S4,5 (s,m)

Visceral (autonomic)

Pupillary-light &

II (s) and III (m)

reflexes

accommodation* Oculocardiac

V (s) and X (m)

Carotid sinus

IX (s) and X (m)

Bulbocavernosis

S2, 3, 4 (s,m)

Rectal (internal sphincter) S2, 3, 4 (s,m) Orthostatic blood pressure IX (s), X & sympathtics (m) and pulse change "Primitive" reflexes

Glabellar

Associated with bilateral

Forced grasping (feet and

hemispheric dysfunction

hands)

(especially frontal lobe; see

Feeding reflexes (sucking,

Chaps. 2 and 16).

biting, rooting) Oculocephalic and nuchocephalic disinhibition Miscellaneous

Vestibulo-ocular responses VIII (s) and extraocular (see Chap. 3) Oculocephalic reflex Caloric irrigations

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(III, IV, VI) (m)

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Fig. 9-1. Distribution of typical sensory loss with diffuse symmetrical peripheral neuropathy (polyneuropathy). Darker stippling represents greatest deficit.

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Fig 9-2. Approximate dermatomal separation lines.

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Fig. 9-3. Dermatomal distribution pattern on trunk showing overlap. Herpetic lesions on the right demarcate the major distribution of the single dorsal root involved (T4 in this instance).

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Fig 9-4. Characteristic pattern of sensory loss with extradural lesion compressing the lateral aspect of cord and T1 dorsal root.

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Fig. 9-5. Findings with cervical intramedullary lesion restricted to region of central canal. Loss of pain and temperature perception is noted in the segments involved and is not associated with other abnormalities because only the spinothalamic decussation is distrupted.

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Figure 9-6. A, findings following stab wound hemisecting the spinal cord at T5 on the right (BrownSequard syndrome). B, segmental overlap of Lissauer's tract allowing pain-temperature bypass of lesion from several segments below the lesion on the left and explaining the lowered demarcation of paintemperature loss on the left.

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Fig. 9-7. Ipsilateral segmental and crossed long-tract deficits associated with left pontine lesion. Of note and frequently missed is the bilateral decrease in facial perception. There is anesthesia on the left from from involvement of the trigeminal complex and hypoesthesia on the right associated with total hemihypoesthesia from involvement of the crossed trigeminothalamic, spinothalamic and medial lemniscal systems. Review the section on conjugate gaze in chapter 3 to explain gaze paresis.

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Table 10-1. Motor system components with examples of isolated involvement COMPONENTS OF MOTOR

EXAMPLES OF ISOLATED

SYSTEM

INVOLVEMENT

Muscle

Myopathy

Neuromuscular junction

Myasthenia gravis

Peripheral and cranial nerve

Neuropathy

Ventral root

Polyradiculopathy, motor type

Anterior horn cell and cranial nerve

Poliomyelitis, amyotrophic lateral

motor neuron

sclerosis

Pyramidal system

Primary lateral sclerosis

Extrapyramidal Cerebellum Reticular Basal ganglia

Alcoholic degeneration Decerebrate rigidity Parkinsonism, Huntington's, chorea, ballism

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1. Observation 1. Muscle group size, symmetry; limb and trunk posture (e.g. contractures) 2. Involuntary movements ■

Adventitious movment disorder (e.g., chorea dystonic posture, tremor, myoclonus, seizure).

■

Fasciculation

■

Myotonia on attempted active movement

2. Palpation and percussion 1. Tenderness, consistency (less reliable in differential) 2. Response of muscle to direct percussion (?myotonia) 3. Passive resistance to manipulation 1. Spasticity, rigidity (plastic, cogwheel or perseverative/paratonic) 2. Hypotonia 4. Strength 1. Sampling of distal and proximal musculature of extremities in addition to cranial, neck and trunk muscles (e.g., cranial nerve exam, trepezius and sternomastoids, neck extensors, deltoids, bidceps, triceps, wrist dorsiflexion, grip, interosseous finger spread, abdominals, psoas, quadriceps, hamstrings, triceps surae, tibialis anterior, dorsiflexion of foot and large toe). If weakenss or other indication of motor involvement is observed, more detailed exam is necessary.

2. Grading of strength: ■

0 - No evidence of movement (try reinforcement)

■

1 - Trace muscle contraction

■

2 - Able to move the limb when gravity is eliminated

■

3 - Complete range against gravity (but no added resistance)

■

4 - Complete range against gravity with some resistance

■

5 - Normal

5. Coordination 1. Rapid rhythmic alternating movements (RRAM) of upper and lower limbs (e.g., tapping thumb against index finger, tapping heel on opposite knee). 2. Finger-to-nose, eyes open and eyes closed, heel-to-shin 6. Gait 1. Basic observation - ataxa, spasticity, weakness, apraxia, rigidity in extension or flexion; turning behavior, en-bloc, ataxic, apraxic 2. To test anterior tibialis and coordination: walk on heels. 3. Coordiantion: tandem heel-toe, walk backward, hop on one foot at a time 7. Deep-tendon (myotatic), superficial and pathologic reflexes

Ancillary studies as indicated (see chapters 12 and 23)

1. Electromyography and nerve conduction studies (EMG/NCV) 1. To differentiate neuronal disease from muscle disease, to differentate axonal from demyelinating neuropathy

2. To substantiate or rule out neuromuscular junction disorders 2. Neostigmine or edrophonium tests in myasthenia gravis suspect (e.g., a patient with nontender muscle disease, particularly if he has increasing weakness on exercise or unexplained extraocular muscle or bulbar weakness even if only one or a few muscles are involeved) 3. Neostigmine IM to enhance fasciculations in anterior horn, ventral root and peripheral nerve disease 4. Muscle - nerve biopsy 5. Enzyme studies: creatinine phosphokinase (CPK) elevated in acute and subacute disease of muscle; minimally or not elevated with slowly progressive muscle disease and peripheral or central nervous system disease 6. Vitamin B12, folate; T3/T4/TSH levels; glucose tolerance; K+; urine porphobilinogen; lead levels 7. Lumbar puncture 8. Electroencephalogram 9. Neuroradiologic studies; skull and spine x-rays; angiography; myelography; cisternography; computerized axial tomography; magnetic resonance imaging

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TABLE 10-3-ISOLATED MOTOR SYSTEMS INVOLVEMENT: GENERAL CHARACTERISTICS ON EXAMINATION COMPONENTS OF THE MOTOR EXAMINATION: 1. Observation. 2. Palpation and percussion. 3. Passive resistance. 4. Strength. 5. Coordination: a. rapid repeating alternating movement; b. finger to nose, etc. 6. Gait. 7. Deep-tendon reflexes. MUSCLE: MYOSITIS AND DYSTROPHY Examination

1. Proximal wasting prominent. 2. Myositic muscle may be tender to palpation. 3. Decreased resistance. 4. Proximal weakness predominant with late distal involvement. 5. Coordination 1. Slow and irregularly clumsy. 2. Slow, but accurate if strong enough. 6. Difficulty climbing and descending stairs, running, rising from chair or floor, or crossing obstacles; waddling gait. 7. Tendon reflexes usually present, but depressed in parallel to weakness.

Special Studies

1. EMG and NCV: Decreased units diffusely with small, fast, myopathic potentials; normal conduction time. 2. Normal edrophonium or neostigmine test (e.d., no increased strength). 3. No fasciculations with neostigmine. 4. Biopsy: diffuse muscle degeneration, inflammatory infiltrate in myositis, noninflammatory degeneration if dystrophy. 5. Elevated level of serum muscle enzymes (creatine phosphokinase most sensitive); may not be elevated in late or chronic myositis and dystrophy. A useful measurement in evaluating course of disease and results of therapy. 6. Thyroid deficiency or excess may be present.

NEUROMUSCULAR JUNCTION: MYASTHENIA GRAVIS Examination

1. Extraocular muscle system most frequently involved early. Other bulbar muscles frequently involved, distal and proximal muscles of extremities affected less and later as a rule. Atrophic changes occur from disuse; dystrophic features in long-standing disease, possibly related in part to chronic anticholinesterase effect. 2. Nontender. 3. Decreasing tone with increasing weakness. 4. Characteristic increasing weakness with exercise with unusually prompt recovery to almost normal strength on resting early; increasingly irreversible weakness with progression of disease.

5. Slow but usually accurate. 6. As with diffuse weakness, but frequently not severely involved because extremity muscles are less affected. 7. Progressive decrease in DTR response with repeated tendon tapping.

Special Tests

1. EMG and NCV: Progressively decreasing muscle potentials with exercise or repeated motor nerve stimulation. 2. Neostigmine and edrophonium cause prompt strengthening and resistance to fatigue in affected muscles (less reliable with extraocular myasthenia). 3. Biopsy nonspecific.

Special Study Neuromuscular postsynaptic membrane antibodies detectable in serum. PERIPHERAL NERVE: NEUROPATHY Examination

1. Distal atrophy prominent, occasional fasciculations. 2. Sensory abnormalities usually associated, and therefore patients have concomitant sensory symptoms (hypoesthesia, paresthesia, etc.) 3. Decreased tone. 4. Distal weakness predominates. 5. Where proprioception is lost, closure of eyes results in misplacements (if in lower extremities,

positive Romberg sign). 6. As with distal weakness and proprioceptive loss. 7. Depressed to absent DTRs.

Special Studies.

1. Decreased conduction time with demyelinating neuropathies, occasional fasciculations and giant summation potentials on EMG. 2. Neostigmine may bring out fasciculations. 3. Biopsy reveals motor unit dropout and neuronal damage. 4. Evidence of malnutrition (folic acid level decreased), diabetes mellitus, thyroid deficiency, vitamin B.2 deficiency, uremia, porphyria, heavy metal poisoning to be sought among others by appropriate blood, urine and stool studies.

VENTRAL ROOT: ACUTE AND SUBACUTE POLYNEUROPATHY Examination

1. Nonspecific, occasional fasciculations. 2. Nonspecific, nontender. 3. Decreased tone. 4. Ascending weakness frequent (Landry, Guillain Barre, and carcinomatous radiculopathy) with distal prominence through occasional major proximal prominence early. 5. Slow, but accurate if able. 6. Nonspecific.

7. Usually absent DTRs.

Special Tests

1. Nerve conduction slowed; EMG with occasional fasciculations and decreased mass response (interference pattern). 2. Neostigmine may increase fasciculations. 3. Level of protein in cerebrospinal fluid up; cells normal (if cells are increased or not, cytologic tests should be done for malignant cells).

ANTERIOR HORN CELL: POLIOMYELITIS, AMYOTROPHIC LATERAL SCLEROSIS Examination

1. Patchy atrophy from single muscles to large masses; fasciculations not prominent. (In amyotrophic lateral sclerosis, there tends to be symmetric involvement with prominent fasciculations.) 2. Tender early in polio. 3. Decreased tone, unless contractures. (in ALS, tone may be increased, decreased, or normal depending on balance of anterior horn/long-tract involvement) 4. Weakness appropriate to distribution and severity of atrophy. 5. Nonspecific. 6. Depends on muscle groups involved. 7. Depressed to absent DTRs in proportion to weakness. (in ALS, increased, decreased, or normal

depending on balance of anterior horn/long tract involvement)

Special Studies

1. EMG: fasciculations, fibrillations, and giant summation potentials in involved muscles. 2. Neostigmine may cause marked increase in fasciculations. 3. Throat, stool virus cultures for polio suspect. Most recent cases of polio are related to live virus vaccine complications.

PYRAMIDAL SYSTEM: PRIMARY LATERAL SCLEROSIS* Examination

1. Minimal atrophy; prominent flexor hypertonus; flexor spasms occur with severe involvement. 2. Nonspecific. 3. Clasp-knife rigidity. 4. Distal muscles tend to be predominantly involved with unilateral involvement. 5. Slow, irregularly clumsy. 6. Spastic-scissors and stiff leg gait; decreased arm swing. 7. DTRs hyperactive with clonus; abdominals depressed; Babinski response present

Special Studies

1. To determine site of lesion, neuroradiologic studies such as myelogram, angiography, CT scan, MRI may be needed to supplement more routine tests (i.e., lumbar puncture, EEG, skull and spine x-rays) when diagnosis is not secure.

CEREBELLUM Examination

1. Intention tremor (rhythmic oscillatory tremor three to eight per second, absent at rest) on side of lesion. 2. Nonspecific. 3. Decreased tone. 4. May see mild weakness of diffuse nature in involved extremities. 5. Past and under pointing, severe dyscoordination on RRAM. 6. Wide-based ataxic (drunk) gait with falling to side of lesion; may see narrow or normally based gait with severe retropulsion when lesion is in midline vermis region. 7. DTRs usually normal but may be pendular.

Special Tests

1. CT scan, MRI, angiography of vertebrobasilar system, lumbar puncture.

BASAL GANGLIA: PARKINSONISM Examination

1. Hyper and hypokinesia 1. Three to eight per second tremor, present with tonic posturing and at rest. (Muscle must, however, have resting tonus to see tremor.)

2. Bradykinesia (e.g., difficulty initiating movement, masked facies). 2. Nonspecific. 3. Cogwheel-plastic rigidity. 4. May have some weakness of disuse. 5. Bradykinesia; may be quite coordinated after movement is initiated. 6. Flexed trunk, small steps; retropulsion if pushed backward or walks backward. 7. Normal reflexes, occasionally depressed.

BASAL GANGLIA: HUNTINGTON'S CHOREA Examination

1. Irregular, jerky, involuntary movements associated with progressive dementia; autosomal dominant so family history is the rule.

Special Test

1. CT scan and MRI reveal caudate nucleus atrophy.

BASAL GANGLIA: HEMIBALLISM Examination

1. Gross flailing to mild choreic movements (contralateral to subthalamic nucleus lesion) make diagnosis obvious. Patient may die of exhaustion; however, movements are normally self-limited if caused, as is frequently the cause, by ischemia-infarction.

BASAL GANGLIA: ATHETOSIS Examination

1. Slow, writhing movements, particularly involving proximal muscles and trunk, associated with 'progressive dementia. (Huntington's chorea frequently has athetoid components.)

RETICULAR FORMATION Examination

1. Lesions characterized by decerebrate or decorticate rigidity if between low pons and low diencephalon (see text).

*A form of motor neuron disease presumed to be part of the spectrum of amyotrophic lateral sclerosis with little detectible anterior horn cell involvement.

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TABLE 10-4. GENERAL DIFFERENTIATING CHARACTERISTICS OF NEURONAL VERSUS MUSCLE DISEASE.

NEURONAL

MUSCULAR

Examination

Examination

Distal weakness and atrophy predominate

Proximal weakness and atrophy predominate

Sensory abnormalities common

No sensory abnormalities

Fasciculations common with anterior horn No fasciculations cell degeneration, less often present with radiculopathy or peripheral neuropathy Hyperactive response of muscle to direct

Decreased response to percussion;

percussion

myotonic response to percussion in myotonias or hypothyroidism

Special studies

Special studies

EMG: fasciculations, fibrillations, giant

EMG: myotonic potentials (high frequency,

potentials; slowed nerve conduction with

low amplitude); decreased motor units in

demyelinating peripheral neurpathy

general; normal conduction velocity.

Neostigmine: increased fasciculation

No response to neostigmine

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Muscle enzymes usually not increased in

Muscle enzymes (CPK most sensitive)

blood

usually not increased in active disease.

Biopsy: atrophy and degeneration of

Biopsy: diffuse, patchy atrophy and

groups of muscle fibers (motor units);

degeneration of muscle fibers;

degeneration of nerve fibers occasionally

inflammatory infiltrates seen in active

seen.

myositis

Sedimentation rate (ESR) normal in most

Sedimentation rate (ESR) elevated in some myositis

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Fig. 10-1. Postures and major motor reflexes associated with lesions at different levels of the central nervous system. These postures usually appear with some delay after the lesion and following a period of acute shock (with lack of response). The lower the lesion in the nervous system, the longer the shock.

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Fig. 10-2. Relationship of motor cortex somatotopic representation to the anterior and middle cerebral arterial supply.

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Fig 11-1 Tempo of various disorders of the nervous system.

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Electrodiagnosis There are several procedures that fall under the rubric of “electrodiagnosis”.

On this page ●

Electromyography

●

Nerve Conduction

These include electromyography, nerve conduction studies (including late

Studies

potentials) and evoked potentials.

Electromyography

❍

Motor NCV

❍

Sensory NCV

●

Evoked Potentials

●

Late Potentials

Electromyography (EMG) refers to the electrical detection of signals arising from the depolarization of skeletal muscle. These signals may be detected from

❍

H-Reflexes

❍

R-Response

skin surface electrodes or from needles placed directly within the muscle. These two types of recordings are used for different purposes, with needle

recording used to detect the behavior of individual muscle fibers and motor units while surface recordings are used to detect overall muscle activity in particular positions or actions. Surface EMG is not a common clinical procedure, though it may be used in rehabilitation. Needle electromyography is used to determine whether there is damage to nerve fibers to individual muscles.

Needle Electromyography Needle electromyography (EMG) is designed to investigate the amplitude and morphology of the electrical signal within skeletal muscle. There are specific findings that appear as a result of diseases of muscle and due to denervation of muscles. Some of these findings are seen spontaneously when simply

recording from a needle placed in the muscle. Some findings appear when the needle is moved in the muscle (insertional activity). Some appear during voluntary contraction of the muscle. A normal muscle is electrically silent when recording from a needle electrode. Movement of the needle normally elicits a brief burst of depolarization from muscle fibers (called insertional activity). This burst of activity ends immediately upon termination of the movement, with restoration of electrical silence. The only place within the muscle that is not electrically silent is the motor end-plate. There are two types of electrical activity that can be seen in the motor end-plate at rest, miniature end-plate potentials and end-plate spikes. These can be distinguished from abnormal resting discharges, but this distinction requires some care. This presents a particular challenge for beginning electromyographers, since end plate spikes can be misinterpreted as evidence of denervation or of increased insertional activity and membrane instability. This is the reason that it is recommended that electromyographers take care to avoid the end plate region. The usual electromyographic test will examine at least ten locations within any single muscle before making a determination as to the normality of insertional activity or presence of abnormal activity at rest. After the resting electromyographic activity and insertional activity is assessed, the patient is asked to voluntarily contract the muscle. Contraction takes place by activating motor neurons to the muscle, each of which is connected to many muscle fibers scattered throughout the muscle (termed a motor unit). The electrical signal that is recorded as a “motor unit potential” (MUP) arises from the integration of the electrical signals arising from the discharge of the several muscle fibers within recording distance of the tip of the needle (typically 1-3mm) that are attached to the same motor neuron (Figure 1A). The amplitude of the MUP is dependent on the density of the muscle fibers attached to that one motor neuron (also to the proximity of the MUP). This is remarkably uniform for most clinically

tested muscles, the amplitude roughly being between 200 and 2000 microvolts. Additionally, MUPs usually have only one or two upward peaks. As the strength of contraction is slowly increased, motor units are recruited in a very orderly sequence. Each active motor unit increases its firing frequency to a defined level (usually around 10 cycles/second or hertz, at which point an additional motor unit is recruited. This process is quite orderly and can be quantified (recruitment pattern). Delayed recruitment (i.e., excessive firing rate of individual units prior to the recruitment of an additional unit) is a reflection of loss of motor units within the muscle. The final step in the EMG assessment of a muscle (a step which may not be necessary if everything else has been normal) involves maximal contraction of the muscle. During such contraction, the electrical activity should fully obscure the baseline (termed a full interference pattern). Incomplete interference pattern is considered to be a reflection of loss of motor units in a muscle, though it can also be seen with diminished effort. Needle EMG evaluates the integrity of the motor unit, i.e., the motor neuron, motor axon and the muscle to which it is attached. Muscle diseases can produce some membrane instability if the disease is very active. This can result in the appearance of "fibrillation potentials" that represent the contraction of individual muscle fibers. As a rule, these contractions are much too small to be seen clinically. However, fibrillations are seen more commonly in diseases of the nerves. Muscle disease changes the motor unit, as and in some case can be associated with fibrillations due to damage of the distal motor axon. Due the fact that muscle fibers are “sick” in myopathy, the MUPs tend to be of low amplitude short duration. During even minimal contraction a greater number of these sick muscle fibers are needed to maintain the force of contraction, so “early recruitment” of motor units is seen (more motor units firing at higher rate than expected for the force). Damage to motor axons (either at the level of the anterior horn cell, the motor root or the peripheral

nerve) results in a series of quantifiable changes in the EMG. It is noteworthy that these changes are triggered by actual disruption of the motor axon and develop in an orderly sequence that can help determine the timing of the injury. These changes are not seen with damage to the myelin of the motor axon (assuming that the axon, itself, is undamaged). This is interesting because damage to myelin can result in complete block of motor conduction and even produce complete paralysis of the muscle without any of the changes that are associated with denervation. Additionally, damage to the central nervous system above the level of the motor neuron (such as by cervical spinal cord trauma or stroke) can result in complete paralysis without any abnormality on needle EMG except incomplete (or absent) interference pattern. A series of events take place in the individual, denervated muscle fibers that can be detected as abnormal electrical signals. First of all, over the period of a week or two, the denervated muscle fiber becomes progressively more mechanically irritable. Therefore, electrical discharges provoked by movement of the needle can outlast the actual movement by more than a second. This is termed “increased insertional activity.” Although this finding is not particularly specific, it does indicate that the muscle is excessively irritable. Muscle fibers also become chemically sensitive to their microenvironment and their membranes can also become unstable enough to produce spontaneously activity. This is recorded as depolarization of individual muscle fibers. The spontaneous depolarizations of the individual fibers appear as fibrillation potentials (Figure 1B) and positive sharp waves (Figure 1C). These do not occur in normal muscles since the normal muscle fibers are only responsive to the activation of their motor unit by neuromuscular transmission. Typically, it takes more than a week for such potentials to develop and they will disappear with complete degeneration of the denervated muscle fiber.. Needle EMG is very sensitive for the detection of these signals and they most often reflect

denervation, although they may also occur in severe muscle disease or injury. The finding of fibrillations and positive sharp waves is the most reliable and objective test that there is for damage to motor axons to the muscle after one week at least up to 12 months after the damage. If there is ongoing damage such as in Amyotrophic Lateral Sclerosis one can see ongoing denervation. Unfortunately, the finding of fibrillations and positive sharp waves is often termed “acute denervation”, although “acute” in this case refers to weeks and months. Reinnervation of muscle is an ongoing process, occurring whenever a muscle is partially denervated. This process typically involves the development of sprouts from adjacent, unaffected motor nerve fibers that ultimately contact at least some of the denervated muscle fibers. These reinnervated muscle fibers cluster right in the area of other, normally innervated muscle fibers. This process results in the development of clumps of reinnervated muscle fibers attached to individual motor neurons (remember, the normal motor unit innervates muscle fibers scattered throughout the muscle). Typically these motor units become significantly larger both in amplitude and duration, since the needle is likely to be recording from more muscle fibers in this clump. Also, the MUPs often become more irregular (termed “polyphasic”) (Figure 2). This process takes months to develop and indicates the presence of chronic denervation. It should be noted that the needle study is much less sensitive to the process of reinnervation than it is to the findings of fibrillations and positive sharp waves that are seen with recent denervation. The typical needle EMG examination requires sampling several muscles. Its ability to localize a lesion depends on sampling muscles innervated by the same nerve but different nerve roots, muscles innervated by the same nerve root but different nerves and muscles innervated at different locations along the course of the nerves. Paraspinal muscles can be very useful in this regard because nerve root

damage will tend to produce abnormalities in these muscles as well as within the muscles of the limbs (helping to distinguish a radiculopathy from a plexopathy or peripheral neuropathy, for example). Sometimes precise localization can be difficult due to the overlap in innervation of the various nerve root levels. Usually MUPs and recruitment patterns are not assessed in the paraspinal muscles.

Nerve Conduction Velocity (NCV) Studies Nerve conduction studies can test sensory or motor nerve fibers and can determine both the speed of conduction as well as the amplitude of the electrical signal evoked following stimulation of a nerve. They can detect areas of focal nerve damage.

Motor Conduction Studies Motor conduction studies are performed by stimulating a motor nerve while recording the response from its target muscles (Figure 3). It is important to note that the electrical signal that is being recorded following motor nerve stimulation (called the compound muscle action potential - CMAP) is actually generated by the muscle, and therefore it is quite large. When motor nerve fibers are stimulated close to the muscle, the amount of time before the muscle starts depolarizing is called the “terminal latency”. The term “latency” in electrodiagnosis is used to define the time between a stimulus and the appearance of a response. In the case of “terminal latency,” this value includes both the amount of time that it takes the nerve to conduct from the point of stimulation to the motor end plate area and the amount of time for the neuromuscular junction transmission to activate the muscle. Strictly speaking, the terminal latency does not directly measure nerve conduction (because it includes the neuromuscular junction activation phase also) but it is a reasonable reflection of nerve conduction over this segment of the

nerve in the absence of uncommon neuromuscular diseases. There are tables of normal for the terminal latencies of defined lengths for each of the major motor nerves of the limb. Abnormal prolongation of this value is often of benefit in the detection of distal entrapment neuropathies. Once a terminal latency has been recorded, the motor conduction velocity can be determined by stimulation of another, more proximal site along the motor nerve. The computation of motor nerve conduction velocity requires knowing the distance between the two simulation sites and the difference in the terminal latencies recorded from the more distal and more proximal sites. Dividing the distance by the time gives the nerve conduction velocity over the segment in between the stimuli.

Sensory Conduction Studies Sensory conduction velocity is an easier measure to compute, but is more technically difficult to record (Figure 4). This test can be done in either an orthdromic (i.e. distal stimulation and proximal recording) or antidromic (i.e. proximal stimulation and distal recording) direction. Sensory nerves that can be recorded are: radial, median, ulnar, sural nerve and superficial peroneal nerve. The recording is made directly from the sensory nerve (the evoked response is called the sensory nerve action potential SNAP) and therefore is quite small (about a thousand times smaller than the CMAP). The distance between the site of stimulation and recording is divided by the latency (i.e., the amount of time from the electrical stimulus to the SNAP) to determine the sensory nerve conduction velocity over the segment. Of course, the SNAP is quite small in amplitude, and recordings must be done in a rather meticulous fashion to avoid artifact. If the extremity is too cold the SNAP may not be recordable.

NCV Limitations

The sites from which nerves can be directly stimulated and from which the nerve or appropriate muscles can be recorded limit sensory and motor nerve conduction studies. For example, this makes the technique poorly suited to the investigation of nerve root problems since it is difficult to directly stimulate nerve roots in patients and similarly challenging to record from individual nerve roots. This is due to several factors, but mostly due to the deep location of the roots and the multiple surrounding structures. Other common technical problems in nerve conduction studies include difficulties locating the nerves and in measuring the course of a nerve (particularly for those nerves that follow a winding or bending course).

Measuring NCV results The results of nerve conduction studies are compared to tables of normal and also to the values in an unaffected limb of the same individual. There are normal values for both sensory and motor conduction (as well as for terminal latency). For example, a good rule of thumb is that motor nerve conduction should be at least 40 meters/second in the lower limb, while sensory conduction should be at least 40 meters/second. Normal aging can slow the conduction velocity as can low temperature of a limb. In the very elderly it may be very difficult to record some the sural SNAP. There are tables that can be used to adjust normal values with extremes of age. For the F response there are tables factoring in height (see below). The two values that are most important in a nerve conduction study are the speed of conduction and the amplitude of response. The speed is a reflection of the diameter of the axons and, most importantly, the thickness of the myelin sheath. Most of the conditions that damage nerves result in at least some injury to the myelin covering the axons. During recovery from focal neuropathy a thinner and less well-

developed myelin sheath is produced, slowing conduction. Of course, this slowing would be greatest in the area of the damage. Additionally, other conditions such as Charcot Marie Tooth Disease or Guillian Barre Syndrome preferentially damage the myelin of the largest, fastest conducting fibers. This causes slowing as manifest by decreased conduction velocity. Actual blockage of conduction can occur due to damage to the myelin of 3-4 internode segments. When remyelination occurs conduction velocity is still decreased to the shorter internode distance (see diagram). Axonal neuropathies can occur in toxic neuropathies. In these situations the amplitude of the CMAP and SNAP are much more affected than velocity. Diabetic distal symmetrical neuropathy, the most common neuropathy, has features of both demyelination and axonal damage.

Evoked Potentials Evoked potentials are responses in the nervous system to stimulation of a sensory pathway. Clinically, this includes stimulation of a sensory nerve in the limb (somatosensory evoked potentials - SSEPs), the visual system (visual evoked potentials) or the auditory system (brain stem auditory evoked potentials). These techniques have the potential for evaluating the integrity of the pathways of sensory transmission all the way from the point of peripheral activation through the cerebral cortex. The procedure for recording evoked potentials requires placement of low-impedance surface electrodes over several portions of the nervous system, followed by repeated activation of the sensory pathway. The minute electrical responses that are evoked by stimulation (for SSEPs, this usually consists of electrical stimulation of sensory or mixed nerves in the limbs) are recorded and averaged over many trials. This averaging eliminates background “noise” and the normal ongoing electrical nervous system activity that is often much larger than the signal evoked by the stimulus. In the case of SSEPs, usually

over at least 256 stimuli are needed in order to obtain reliable, reproducible responses. Damage to the sensory pathway decreases the speed of conduction (much as was described in the section on nerve conduction studies), although diminished amplitude (which normally has a higher degree of inherent variability) may also be seen.

Somatosensory evoked potentials SSEPs are produced by activation of the large diameter peripheral nerve sensory fibers (Figure 5). These nerve fibers include many that are conveying sensation from muscles as well as those from touch and pressure receptors in the skin and deeper tissues. Pain fibers contribute little (if anything) to the normal, clinical evoked potential. This limits the utility of the procedure for investigation pain physiology or for detecting damage to pain pathways. As described previously, repair of damaged myelin results in an axon that conducts more slowly than before the damage. Just as with nerve conduction studies, decreased amplitude of evoked signals may also reflect damage. However, since amplitude is a significantly more variable in evoked potential testing, only large differences in the amplitude of SSEPs are significant. Most clinical SSEPs are evoked by stimulation of large-diameter mixed nerves of the periphery (such as the median, ulnar, peroneal or tibial). These nerves are composed of sensory nerve fibers from many nerve roots, limiting the ability to identify damage to a single nerve root. While there has been some discussion of the value of mixed nerve SSEPs in the identification of radiculopathy (such as by using the fibular [peroneal] nerve SSEP for the L5 nerve root) most investigators have not found this to be of particular value. SSEPs are used predominately in intraoperative monitoring during spinal surgery and instrumentation. If SEP abnormalities occur during the surgery the surgeon is alerted and changes in

the operative procedure are implemented. In addition SSEPs can be used to assess the prognosis of patients suffering severe anoxic brain injury.

Late Potentials Late potentials are electrodiagnostically-elicited responses in muscle that appear more than 10-20 milliseconds after stimulation of motor nerves. They have been termed “late-potentials” because they take substantially longer to appear than the direct responses to stimulation of motor nerves (described in the section on nerve conduction studies as the CMAP). There are two distinct types of late responses, the H-reflex (Figure 6) and the F-response (Figure 7).

H-Reflex The first type of “late response” is called the H-reflex, named in honor of Hoffmann, who first described this response in 1918. The pathway for this reflex and the significance of abnormalities is easiest to understand by recognizing that it is basically the electrophysiologic equivalent of the muscle stretch reflex. The H-reflex is most commonly tested by electrical stimulation of the tibial nerve, with recordings from the gastrocnemius/soleus muscle complex (i.e., the triceps surae) (Figure 6). Therefore, this response utilizes the same neural pathway as the ankle jerk reflex. Understanding of the H-reflex it is aided by some knowledge of the technical details of the procedure. Electrical stimulation will depolarize the largest, most heavily myelinated nerve fibers at a lower stimulus intensity than is required to activate other smaller nerve fibers. Since the largest nerve fibers in a peripheral nerve are those arising from muscle stretch receptors, there should be a stimulus intensity that activates muscle stretch afferent nerve fibers without directly activating many motor

nerve axons (which are slightly smaller in diameter). When muscle stretch sensory fibers are stimulated (whether it be by electrical impulse or by tapping the tendon of the muscle), a monosynaptic reflex contraction will be elicited in the muscle. Because this response must traverse the sensory axon all the way back to the spinal cord before synapsing on the motor neuron, and since the motor response must then traverse the length of the motor axon to reach the triceps surae muscle, this reflex takes a long time (at least in electrodiagnostic terms). That is where the designation of “late potential” comes from. Theoretically, this reflex can be elicited from virtually any muscle. However, in practical terms, only the triceps surae muscle produces H-reflexes that are reliable enough to be clinically useful. Therefore, when a clinical electrodiagnostic procedure reports an H-reflex, the test has evaluated the integrity of the reflex arc from the tibial nerve through the spinal cord and back to the triceps surae. Damage to any portion of the reflex arc, including the sciatic nerve or the S1 sensory or motor nerve root, can result in loss or slowing of the reflex response. Additionally, the amplitude of response (expressed as a ratio of the reflex response to the maximum direct motor response - the so-called H/Mmax) is also reliable enough to be of diagnostic value. Since the H-reflex is mediated primarily over the S1 nerve root (just like the ankle jerk reflex), it is a sensitive test for S1 radiculopathy. However, once the reflex arc has been damaged, it often does not return to normal (making the test less useful in investigating the question of recurrent radiculopathy). While the H-reflex may be viewed as an electrical test of the ankle jerk, or Achilles’ tendon reflex, there are some differences that should be noted. For example, as opposed to the clinical ankle jerk, the H-reflex and be precisely quantified (both in terms of latency and amplitude) and, therefore, may be a more useful index to follow with time or treatment. Additionally, the H-reflex can be elicited from many patients even when the ankle jerk can not be elicited due to age. With the notable exception of the triceps surae muscle, the H reflex is very difficult to elicit. This limits

the H-reflex to being a sensitive specific and quantitative test of sciatic nerve and S1 nerve root function. This may be of utility in investigating patients with suspected S1 radiculopathy.

F-response The second type of late potential is the F-response. This is a response that occurs in muscles during a motor nerve conduction study long after the initial contraction of the muscle (the CMAP, see above), While the CMAP usually appears within several milliseconds (depending on how close the stimulus point is to the muscle), depending on the stimulus site, another response can be normally recorded in the muscle approximately 25 -55 milliseconds later (Figure 7). Since this response was first recorded in foot muscles, it came to be known as the F-response. Over time it was found that this late response was not a reflex in the usual definition.. The electrical impulse is trasmitted proximally along the motor axon from the site of initiation of the action potential. When this antidromic (opposite to the normal direction of conduction) depolarization reaches the motor neurons in the spinal cord, a percentage of these motor neurons are activated a second time. This results in an orthodromic electrical signal being conducted in the normal (orthodromic) direction from the spinal cord to the muscles innervated by the nerve. This second, later activation produces a small muscle contraction that is termed the F-response. Because the number of motor neurons that are re-activated is somewhat unpredictable, the amplitude of this signal is variable and, therefore, amplitude measurements are usually not used. However, delay in the F-response indicates some slowing of conduction of the motor axon. Since the F-response traverses more proximal portions of the motor axons (twice, in fact) it may be useful in the investigation of proximal nerve pathology such as root pathology seen in radiculopathy, Guillian Barre Syndrome, or Chronic Inflammatory Demyelinating Polyradiculopathy (CIDP).

The F–response is also very helpful in the confirmation of demyelinative peripheral neuropathies. In these neuropathies the F-responses may be quite prolonged.

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Fig 12-2 Effect on amplitude of the compound muscle action potential by nerve stimulation at low (2-3 per second) and high (50 per second) frequencies. MG=myasthenia gravis, MS=myasthenic syndrome.

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Fig 12-1 Schematic of anatomic and electrical characteristics of the normal and diseased motor unit.

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TABLE 13-1. - MAJOR SEIZURE CATEGORIES

1. Seizures of general onset 1. Grand mal (generalized motor) 2. Petit mal (absence) 2. Seizures of focal (partial) onset with or without secondary generalization to major motor manifestations. 1. Simple partial (focal) seizures (elementary cortex involvement). 1. Motor cortex (Jacksonian) 2. Sensory cortex ■

Somatosensory

■

Auditory-vestibular

■

Visual

■

Olfactory-gustatory (uncinate)

2. Complex partial (focal) seizures (limbic seizures) 3. Continuous seizures 1. Generalized (status epilepticus) 2. Focal (epilepsia partialis continua)

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Fig 13-1 Electroencephalogram pattern of grand mal seizure.

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Fig 13-2 Electroencephalogram pattern of petit mal seizure (3/second spike-wave).

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Fig 13-3 Diagram of mode of unilateral cortical spread (march) of seizure focus in the motor cortex prior to bilateral generalization via the corpus callosum and/or brain stem reticular formation.

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TABLE 14-1.-DEMYELINATING DISORDERS

1. Allergic ❍

Experimental allergic encephalomyelitis

❍

Acute disseminated encephalomyelopathy

❍

Acute hemorrhagic encephalomyelopathy

❍

Experimental allergic neuritis

❍

*Guillian-Barre syndome (probable)

2. Unknown etiology ❍

*Multiple sclerosis

❍

Devic's disease

3. Infectious etiology (slow virus infections) ❍

Progressive multifocal leukoencephalopathy

❍

Visna (in sheep)

*These are the more common conditions.

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TABLE 15-1. SOME INBORN ERRORS OF METABOLISM

1. Aminoacidurias (phenylketonurias, etc.) 2. Disorders of lipid metabolism ❍

Sphingolipidoses (Tay-Sachs, etc.)

❍

Leukodystrophies (metachromatic leukodystrophy, Krabbe's disease, etc.)

3. Lipoprotein disorders ❍

Tangier disease

❍

Abetalipoproteinemia (Bassen-Kornzweig disease)

4. Disorders of glucose and glycogen metabolism ❍

Mucopolysaccharidoses

❍

Glycogenoses

❍

Galactosemia

5. Miscellaneous disorders ❍

Wilson's disease

❍

Porphyria

❍

Refsum's disease

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TABLE 15-2. - SOME DEGENERATIVE DISORDERS

1. A. Causing dementia primarily 1. *Alzheimer's disease 2. Pick's disease 3. Marchiafava-Bignami disease 2. B. Causing basal ganglia degeneration primarily 1. #Parkinsonism 2. #Huntington's chorea 3. Progressive supranuclear palsy (Steele-Richardson-Olchewsky) 4. Hallervorden-Spatz disease 5. Others 3. C. Causing visual deficit 1. Leber's optic atrophy 2. Retinitis pigmentosa 4. D. Spinocerebellar degenerations 1. *Friedreich' s ataxia 2. Olivopontocerebellar degeneration 3. Familial Spastic paraparesis

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4. Others 5. E. Motor neuron diseases 1. *Amyotrophic lateral sclerosis (ALS) 2. Werdnig-Hoffmann disease 3. Kugelberg-Welander disease 6. F. Causing peripheral neuropathy 1. Charcot-Marie- Tooth disease (peroneal atrophy) 2. Dejerine-Sottas disease 7. G. Causing myopathy 1. *Duchenne's muscular dystrophy 2. Fascio-scapulo-humeral 3. Limb-girdle 4. *Myotonic dystrophy 5. Others

*Common conditions you should know # see chapter 18.

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TABLE 16-1. - CAUSES OF SELECTIVE LOSS OF RECENT MEMORY

1. Hippocampal damage 1. Postanoxic or posthypoglycemic 2. Posttraumatic 3. Infectious (herpes simplex encephalitis) 4. Vascular (posterior cerebral artery occlusion) 5. Temporal lobe epilepsy (ictal or postictal): transient 6. Surgery: bilateral temporal lobectomies 7. Degenerative disease: Alzheimer's disease 2. Fornix (debatable) 3. Mamillary bodies and/or dorsomedial thalamus (bilateral lesions) 1. Wernicke-Korsakoff disease 2. Tumors of the third ventricle, hypothalamus, or parasellar region 4. Anticholinergic drugs

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TABLE 16-2 - ROUTINE SCREENING EVALUATION FOR THE DEMENTED PATIENT

Test

Indication

Complete blood cell count Anemia; polycythemia; vitamin B12 deficiency (hypersegmentation) ESR

Vasculitis; tumor; infection

VDRL & FTA-ABS

Syphilis (in tertiary lues serum VDRL may be negative and FTA positive)

Blood sugar

Hypo- or hyperglycemia

Blood urea nitrogen

Renal Failure

Electrolytes

Water intoxication; Adrenal disease

Calcium/Phosphorus

Hyper- or hypocalcemia; hypophosphatemia

Antinuclear antibody

Vasculitis

Protein electrophoresis

Hyperviscosity syndrome from paraproteinemia

T4/TSH

Hyper-or hypothyroidism

Cortisol

CushingÕs disease

Serum B12/Folate

Pernicious anemia

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Ascorbate/Carotene

Malabsorption; Malnutrition

Cholesterol/triglycerides

Hyperlipidemic dementia

Liver function tests

Hepatic encephalopathy; Metastases

Arterial blood gases

Acidosis; Anoxia

Lyme titer

Lyme disease

EEG

Slowing or triphasic waves (in most metabolic encephalopathies); focal abnormalities (such as strokes or tumors); constant seizure activity.

CT scan or MRI

Mass (neoplasm, subdural hematoma, etc), inflammatory process, stroke, hydrocephalus

Lumbar puncture:

(if not contraindicated):

evaluation of protein,

Inflammatory disease; infection;

glucose, cells, culture,

hydrocephalus

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Table 16-3. MAJOR CAUSES OF DEMENTIA

* Indicates potentially treatable causes

Infectious

1. *Acute bacterial meningitis ❍

Diagnosis: Fever, stiff neck; purulent CSF, + gram stain

❍

Treatment: Appropriate antibiotics

2. *Viral encephalitis ❍

Diagnosis: Fever, confusion; lymphocytes in CSF

❍

Treatment: Nonspecific: steroid support; antiviral agent (acyclovir) for herpes simplex encephalitis

3. *Tuberculous meningitis ❍

Diagnosis: Headache, stiff neck, malasie, weight loss; CSF: pleocytosis (modest, mainly lymphocytes), low glucose, high protein

❍

Treatment: INH, ethaambutol, streptomycin, other antibiotics, and steroids

4. *Cryptococcal meningitis ❍

Diagnosis: Headaches; CSF as in tuberculous meningitis; demonstration of organisms or antigen in CSF

❍

Treatment: Amphotericin B and 5-fluorocytosin

5. *Tertiary syphilis (general paresis rarely seen today) ❍

Diagnosis: CSF Poor judgment, grandiosity, frontal release signs; Argyll Robertson pupils; cells in CSF; + CSF VDRL

❍

Treatment: Penicillin

6. Prion infections 1. Creutzfeldt-Jakob disease ■

Diagnosis: Dementia, basal ganglia signs, startle myoclonus, etc.

■

Treatment: None

2. Kuru ■

Diagnosis: . Cerebellar degeneration; dementia late; acquired by eating victims

■

Treatment: None

7. Atypical virus infections 1. Subacute sclerosing panencephalitis ■

Diagnosis: Dementia, myoclonus: under 20 years old (caused by measles-like virus); high CSF gamma globulin level

■

Treatment: None

2. Progressive multifocal leukoencephalopathy ■

Diagnosis: Multifocal hemispheric signs usually in immunosuppressed patient (HIV, on immunosuppressive drugs or with malignancy particularly of reticuloendothelial origin)

■

Metabolic

Treatment: None

1. Lack of substrate 1. *Tissue hypoxia 1. Low blood PO2 ■

Diagnosis: Cyanosis; blood gases

■

Treatment: Oxygen, respiratory support; treat infection and spasm

2. Severe anemia ■

Diagnosis: Hemoglobin, hematocrit

■

Treatment: Tranfusion, etc.

3. Decreased perfusion 1. Decreased cardiac output ■

Diagnosis: Hypotension; signs of congestive failure

■

Treatment: Appropriate cardiac medicatioins or fluids for hypovolemia; treatment of septic shock, etc.

2. Arterial obstruction ■

Diagnosis: Usually focal signs

■

Treatment: Support, anticoagulation if progressive without hemorrhage

3. Increased viscosity (polycythemia) ■

Diagnosis: Hematocrit

■

Treatment: Phlebotomy

2. *Hypoglycemia ■

Diagnosis: Varied clinical picture: often dizziness, syncope; but may have focal signs or

seizures; low blood glucose; 5-hour glucose tolerance test to rule out reactive hypoglycemia ■

Treatment: IV glucose

3. *Nutritional deficiency 1. Vitamin B12 deficiency ■

Diagnosis: Pernicious anemia and/or spinal cord involvement (not always present); lab: low serum B12 levels; positive Schilling test; achlorhydria (usually)

■

Treatment: IM vitamin B12 adminstration

2. Thiamine deficiency ■

Diagnosis: Wernicke's encephalopathy; confusion, amnesia, truncal ataxia, disconjugate eye movements; fatal if untreated: Korsakoff's psychosis (residual of Wernicke's): amnesia, confabulation

■

Treatment: IM/IV thiamine; vitamin treatment is only partially, if at all, effective for Korsakoff's

2. Endocrine 1. *Hypothyroidism ■

Diagnosis: Myxedema, hung-up reflexes, hypothermia; high TSH, low T4, etc.; hyponatremia

■

Treatment: Thyroid hormone replacement

2. *Hyperthyroidism ■

Diagnosis: Weight loss, tremor, etc.; high T4, etc.

■

Treatment: Thyroid suppressants; surgery

3. *Cushing's disease ■

Diagnosis: Hypertension, diabetes, Cushingoid features; hypokalemia; high cortisol

■

Treatment: Surgery

4. *Parathyroid abnormalities 1. Hyperparathyroidism ■

Diagnosis: Hypercalcemia (lethargy, etc.)

■

Treatment: Treat hypercalcemia; remove parathyroids

2. Hypoparathyroidism ■

Diagnosis: Hypocalcemia; diffuse, soft tissue calcification; tetany

■

Treatment: Vitamin D

3. Pseudohypoparathyroidism ■

Diagnosis: Hypocalcemia, skeletal abnormalities, basal ganglia calcification, tetany unusual despite very low calcium levels

3. Electrolyte imbalance 1. *Hyponatremia (water intoxication), inappropriate antidiuretic horome secretion, renal sodium wasting ■

Diagnosis: Lethargy, seizrures, low serum sodium

■

Treatment: Water-restriction; hypertonic saline (sometimes)

2. *Hypercalcemia ■

Diagnosis: Lethargy, confusion; high serum calcium

■

Treatment: Lower calcium (phosphate, steroids, mithromycin, etc.); treat underlying condition

3. *Hypomagnesemia ■

Diagnosis: Confusion, seizures; in setting of persistent diarrhea (especially in infants), or of IV therapy without Mg supplements; serum Mg may not reflect deficiency; calcium usually also low

■

Treatment: Magnesium sulfate

4. *Hypocalcemia ■

Diagnosis: Confusion; tetany seizures; serum calcium low

■

Treatment: Replace calcium; treat underlying condition

5. *Hyperosmolar coma ■

Diagnosis: High blood glucose, severe dehydration with associated electrolyte abnormalities

■

Treatment: Fluids, insulin

4. Toxic 1. Endogenous 1. *Hypercapnia (pulmonary insufficiency) ■

Diagnosis: Signs of respiratory insufficiency, asterixis

■

Treatment: Assist respirations, pulmonary toilet; antibiotics

2. *Hepatic encephalopathy ■

Diagnosis: Lethargy, dementia, asterixis; hyperventilation with respiratory alkalosis (? central); high serum ammonia; high CSF glutamine; if chronic may see dementia plus choreiform movements and dystonia

■

Treatment: Treat infections, gastrointestinal bleeding (when present); cleanse bowel (neomycin enemas, acetic acid enemas, lactulose), L-dopa

3. *Renal insufficiency ■

Diagnosis: Multifocal myoclonus, seizures, asterixis; signs of uremia; high BUN, creatinine

■

Treatment: Treat primary disease; dialysis

4. *Acidosis ■

Diagnosis: Hyperventilation, low pH

1. Diabetic ketoacidosis ■

Diagnosis: Hyperglycemia, ketosis

■

Treatment: Fluids, insulin, bicarbonate

2. Lactic acidosis ■

Diagnosis: Acidosis without hyperglycemia, seen wtih sepsis, shock, idiopathic

■

Treatment: Treat underlying cause; bicarbonate

5. *Wilson's disease ■

Diagnosis: Dystonia, choreiform movements; cirrhosis; high liver copper, low ceruloplasm; high urine copper excretion

■

Treatment: Copper-binding agent (penicillamine), low copper diet, liver transplant?

6. *Hyperlipidemia ■

Diagnosis: Greatly increased serum cholesterol and triglycerides

■

Treatment: Lower serum lipids

7. Limbic dementia (remote effects of carcinoma) ■

Diagnosis: Memory loss, agitation; may have cerebellar or brain stem signs

■

Treatment: None

2. Exogenous toxins 1. *Drugs ■

Diagnosis: Serum levels, history

1. Hypnotics ■

Diagnosis: Ataxia, dementia, lethargy, comatose

■

Treatment: Reduce dose slowly if comatose; fluids, respiratory and blood pressure support; dialysis when appropriate; benzodiazepine antagonists (with caution for acute withdrawal)

2. Aspirin ■

Diagnosis: Metabolic acidosis plus respiratory alkalosis

■

Treatment: Fluids; alkalinize urine

3. Anti-convulsants ■

Diagnosis: Ataxia, dementia, lethargy

■

Treatment: Reduce dose

2. *Toxins: Methanol, ethylene glycol, old paraldehyde ■

Diagnosis: Severe metabolic acidosis, blindness with methanol, hippurate crystals in urine with ethylene glycol

■

Treatment: Bicarbonate; ethanol for methanol intoxication

Vascular disease

1. *Strokes (multiinfarct dementia) ❍

Diagnosis: Focal signs or story, CT scan or MRI positive with completes strokes

❍

Treatment: Controversial (see chap. 19)

2. *Hypertensive encephalopathy

❍

Diagnosis: Papilledema, proteinuria, diastolic blood pressure usually above 120; headache, cortical visual loss

❍

Treatment: Lower blood pressure

3. *Vasculitis (lupus, etc.) ❍

Diagnosis: Dementia with or without focal signs; may or may not have other systems involved; high sedimentation rate almost always

❍

Treatment: No effective treatment for most; steroids used and proved effective only for giant cell cranial arteritis

Mechanical

1. *Mass lesions 1. Neoplasms ■

Diagnosis: Focal signs, except in "silent areas" (i.e., frontal lobes); positive brain scan (over 80%); CT scan and MRI positive in most

■

Treatment: Surgery, XRT, Chemotherapy (depending on the type); steroids if edema

2. Subdural hematoma ■

Diagnosis: Often headache, lethargy; mild focal signs; history of trauma (not always); increasing CSF protein; positive brain scan; positive CT scan

■

Treatment: Surgery

3. Intracerebral hematoma ■

Diagnosis: Focal signs, usually; if hematoma is subcortical, in a silent area (less than 10% of spontaneous intracerebral hematomas), focal signs may be minimal; CT scan positive

■

Treatment: Surgery (in rare cases)

2. *Hydrocephalus ❍

Diagnosis: If acute: headache, lethargy, increased intracranial pressure. If chronic: dementia, gait disorder (frontal "apraxic" and spastic gait), and urinary incontinence; normal CSF dynamics, but look for changes indicative of chronic meningitis; CT scan with minimal cortical atrophy and enlarged ventricular system

❍

Treatment: CSF shunt; appropriate antibiotics or chemotherapy if chronic meningitis of infections or neoplastic origin

"Degenerative" diseases

1. Without elementary neurologic findings 1. *Alzheimer's disease ■

Diagnosis: Memory loss usually prominent early; very common, the usual senile dementia; CT scan positive

■

Treatment: Symptomatic agents, ?Vitamin E

2. Pick's disease ■

Diagnosis: Same; not clinically separable from Alzheimer's: can only be separated pathologically; very rare in United States

■

Treatment: None proven

2. Demyelinating disease 1. *Multiple sclerosis

■

Diagnosis: Evidence clinically of lesions separated in time and space; dementia common late in illness; frequently high CSF gamma globulin percentage of total CSF protein

■

Treatment: High dose steroids briefly in acute exacerbations; disease modifying drugs (see Chpt. 14)

2. Schilder's disease ■

Diagnosis: Usually in children; dementia most prominent sign, but soon cortical blindness, long-tract signs, etc.

■

Treatment: None

3. Inborn errors of metabolism 1. Lipid storage diseases ■

Diagnosis: Tay-Sachs, etc.

■

Treatment: None

2. Metachromatic leukodystrphy ■

Diagnosis: Dementia, peripheral neuropathy; absent arylsulfatase A

■

Treatment: None

3. *Amino acidurias (many of them) ■

Diagnosis: Variable, urine for amino acids

■

Treatment: Restrictive diet for many

4. Prominent basal ganglia or cerebellar signs. 1. *Parkinsonism ■

Diagnosis: Typical basal ganglia signs (see chaps. 8 and 18)

■

Treatment: L-dopa (does not help dementia), amantidine, dopamine agonists

2. Huntington's chorea ■

Diagnosis: Dementia may precede chorea; family history (autosomal dominant)

■

Treatment: None, control behavioral symptoms, genetic counseling

3. Some spinocerebellar degenerations ■

Diagnosis: Cerebellar, posterior column, pryamidal, and peripheral nerve disease depending on which variant (Friedreich's ataxia most common example)

■

Treatment: None

4. Myoclonic epilepsy (certain forms) ■

Diagnosis: Progressive form with Lafora's inclusion bodies produces dementia

■

Treatment: None; control seizures

5. Parkinson-dementia complex (Guam) ■

Diagnosis: May be associated with ALS

■

Treatment: None

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TABLE 17-1. INTRACRANIAL BACTERIAL INFECTIONS OF THE CNS CONDITION (ORGANISM)

THERAPY

Neonatal meningitis Group B beta-hemolytic streptococci

Penicillin

Enteric bacilli (Escherichia coli, Proteus, 3rd generation cephalosporin Klebsiella) Listeria (also in elderly)

Ampicillin or penicillin

Unknown

Gentamicin plus ampicillin or penicillin

Meningitis in children and adults H. influenzae

Penicillin

Meningococcal

Ampicillin or chloramphenicol

Streptococcus pneumonia

Penicillin (chloramphenicol, erythromycin)

Unknown

Ampicillin + cefataxime = cefataxime

Meningitis under unusual circumstances Staphylococcal (penicillinase-positive)

Cloxacillen (Nafcillen, vancomycin)

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Gram-negative meningitis

Gentamicin and chloramphenicol

Pseudomonas

Tobramycin, ticarecillin

Tuberculous meningitis

INH and streptomycin plus PAS or ethambutol or rifampin

Neurosyphilis

Penicillin (erythromycin, tetracycline)

Brain abscess (organism unknown) Staphylococci not suspected

Penicillin and either tetracycline or chloramphenicol

Staphylococci suspected

Cloxacillin and chloramphenicol

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TABLE 17-2. COMPLICATIONS OF PURULENT MENINGITIS

1. Cerebral edema (may lead to herniation) 2. Vasculitis ❍

Arteritis (stroke)

❍

Cortical venous thrombosis (stroke, seizures)

❍

Venous sinus thrombosis (increased intracranial pressure)

3. Hydrocephalus 4. Cranial nerve palsies 5. Subdural effusion or empyema 6. Disseminated intravascular clotting 7. Lactic acidosis 8. Inappropriate ADH secretion 9. Diabetes insipidus 10. Residual findings ❍

Cranial nerve palsies

❍

Mental retardation

❍

Seizures

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TABLE 17-3. SOME CAUSES OF VIRAL ENCEPHALITIS

1. Arthropod-borne (arbovirus) infections 1. Group A 1. Western equine encephalitis 2. Estern equine encephalitis 3. Venezuelan equine encephalitis 2. Group B 1. St. Louis encephalitis 2. Japanese B. encephalitis 3. Yellow fever 4. Dengue 3. Arthropod tick-borne encephalitides 1. Russian tick-borne complex 2. Colorado tick fever 4. Miscellaneous 1. California encephalitis 2. Others 2. Picorna virus (enterovirus) infections

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1. Poliomyelitis 2. Coxsackievirus infections 3. Echovirus meningoencephalitis 4. Mengo (encephalomyocarditis virus) encephalitis 3. Myxovirus infections 1. Influenza 2. Mumps 3. Measles 4. Rabies 5. Rubella 6. Newcastle disease 4. Herpesvirus infections 1. Herpes simplex 2. Herpes zoster and checkenpox 3. Virus B (herpesvirus simiae) 4. Cytomegalic inclusion disease 5. Poxvirus infections 1. Smallpox encephalitis 2. Vaccinia encephalitis 6. Others

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TABLE 17-4. ATYPICAL INFECTIONS OF THE CNS

1. Prion diseases ❍

Scrapie (sheep)

❍

Kuru (human, tribes of New Guinea)

❍

Creutzfeldt-Jakob disease (human)

❍

Bovine spongiform encephalopathy (cows, humans)

❍

Transmissible mink encephalopathy

2. Atypical presentations of conventional viruses ❍

Visna-maedi (sheep)

❍

Subacute sclerosing panencephalitis (SSPE) (human) ■

❍

Progressive multifocal leukoencephalopathy (PML) (human) ■

❍

Rubella

Parvovirus (warts)

Acquired immune deficiency syndrome (AIDS) (human)

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TABLE 17-5. CSF FINDINGS IN MAJOR CNS INFECTIONS PURULENT

VIRAL

GRANULOMATOUS

MENINGITIS (ACUTE

MENINGO-

MENINGITIS (tuberculosis,

BACTERIAL

ENCEPHALITIS

fungal meningitis, sarcoid,

MENINGITIS)

syphilis, Listeria, Brucella, ETC.)

WBC's

More than 1,000/cu

Less than 500/cu Less than 200/cu mm;

mm; mostly polys

mm; first polys;

mostly lymphs

then lymphs Protein

High

Normal or slightly High elevated

Sugar

Low (often less than 20 mg%)

Normal

Low (rarely as low as in bacterial meningitis)

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TABLE 17-6. CAUSES OF LYMPHOCYTIC MENINGITIS*

1. Viral meningitis or encephalitis 2. Indolent bacterial meningitis (sugar level often low) 1. Partially treated purulent meningitis 2. Tuberculous meningitis 3. Listeria meningitis 4. Brucella meningitis 5. Syphilitic meningitis 6. Lyme meningitis 3. Fungal meningitis (sugar level often low) 4. Sarcoidosis (sugar level often low) 5. Various protozoal or helminthic infections 6. Some rickettsial infections 7. Parameningeal infection 1. Epidural abscess 2. Subdural abscess 3. Brain abscess 4. Venous thrombosis

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8. Noninfectious causes 1. Chemical meningitis (after pneumoencephalography, myelogram, cisternogram, spinal anesthesia, intrathecal therapy, etc.) 2. Toxins (lead, arsenic) 3. Tumors 4. Demyelinating disease 5. Vascular diseases ■

Vasculitis

■

Stroke

■

Subarachnoid hemorrhage

*A modest pleocytosis, mostly lymphocytic, with normal or elevated levels of protein and normal or low amounts of sugar

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TABLE 17-7. CAUSES OF LOW LEVELS OF SUGAR IN THE CSF

1. Sugar level characteristically low 1. Bacterial meningitis 2. Fungal meningitis 3. Sardoiosis 2. Sugar level occasionally low 1. Viral meningitis or encephalitis 2. Chemical meningitis 3. Subarachnoid hemorrhage 4. Meningeal carcinomatosis

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Fig 18-1 Anatomical schematic illustrating various experimental and clinical evidences for the theoretical bases of basal ganglia disorders.

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Fig 18-2 Demonstration of lack of normal response from a patient with parkinsonism to table tilting.

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Fig 19-1 Major arterial branches of the vertebrobasilar and carotid systems and the interconnecting circle of Willis.

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Fig 19-2 Diagram of the zone of cerebral cortical arterial overlap, the so-called watershed area. With single-vessel occlusion, the overlap helps to preserve cortical integrity within its territory. With systemic hypotension, this zone suffers most because it is at the farthest reaches of the three major arterial supplies.

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TABLE 19-1. DIFFERENTIAL CHARACTERISTICS OF INTRACEREBRAL HEMORRHAGE AND ISCHEMIC STROKE ISCHEMIA-INFARCTION HEMORRHAGE Stepwise progression

Common

Unusual

Reversible episodes

Common

Rare, if ever

Rare (occasionally with

75%

CSF Blood

embolus) Elevated pressure

Rare

75%

High pressure or blood

Rare

95%

Infrequent

Frequent, severe

With vertebrobasilar

Common

Headache Nausea and vomiting

occlusive disease Rapid loss of

10%

50%

50%

90%

consciousness Elevated blood pressure by history

Fundi: papilledema

Rare

Common; can occur within 1/2 hour of catastrophe

Subhyaloid hemorrhage

Rare

Common

Leukocytosis > 20,000

10%

50%

Fever

Uncommon

Common

Mortality

20-30%

75%-80%

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TABLE 20-1. MOST COMMON NEOPLASMS TO INVOLVE CENTRAL NERVOUS SYSTEM (by location and type)

1. Cerebral hemispheres 1. Primary 1. Glioma 2. Glioblastoma 3. Astrocytoma 4. Oligodendroglioma 5. Meningioma 2. Secondary 1. Metastatic carcinoma

2. Cerebellum

■

Lung

■

Breast

■

Bowel

■

Kidney

■

Ovary

■

Melanoma

1. Primary 1. Glioma 2. Gliomas of childhood 3. Medulloblastoma 4. Astrocytoma 5. Hemangioblastoma 2. Secondary 1. Metastatic carcinoma ■

Lung

■

Breast

■

Other

3. Pituitary 1. Adenoma ■

Functional

■

Eosinophilic

■

Basophilic

■

Invasive

2. Nonfunctional ■

Chromophobe

3. Craniopharyngioma 4. Brain stem 1. Childhood gliomas

2. Ependymoma 5. Cranial nerves 1. Neurilemoma Acoustic-vestibular 2. Other nerves 6. Spinal cord 1. Ependymoma 2. Astrocytoma 3. Meningioma 4. Metastatic 7. Peripheral nerve 1. Neurofibroma 2. Neurilemoma

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TABLE 21-1. CLASSIFICATION OF HEADACHES

1. Potentially dangerous headaches 1. Meningeal irritation 1. Subarchnoid hemorrhage 2. Meningitis and meningoencephalitis 2. Intracranial mass lesions 1. Neoplasms 2. Intracerebral hemorrhage 3. Subdural or epidural hemorrhage 4. Abscess 5. Acute hydrocephalus 6. Other 3. Vascular headaches 1. Temporal arteritis 2. Hypertensive encephalopathy (e.g., malignant hypertension, pheochromocytoma) 3. Arteriovenous malformations and expanding aneurysms 4. Lupus cerebritis 5. Venous sinus thrombosis 4. Cervical

1. Fracture or dislocation 2. Occipital neuralgia 3. Vertebral artery dissection 4. Chiari malformation 5. Metabolic 1. Hypoglycemia 2. Hypercapnea (lung disease, sleep apnea) 3. Carbon monoxide 4. Anoxia 5. Anemia 6. Vitamin A toxicity 6. Glaucoma 2. Extracranial lesions 1. Sinuses (infection, tumor) 2. Cervical spine disease 3. Dental problems 4. Temporomandibular joint 5. Ear infections, etc. 6. Eye (glaucoma, uveitis) 7. Extracranial arteries 8. Nerve lesions 9. Other 3. Other secondary headaches

1. Altitude 2. Fever 3. Ice cream headache 4. Alcohol and hangover 5. Dynamite headache (nitrate exposure) 6. Hot dog headache 7. Chinese restaurant syndrome (glutamate) 8. Aspartame 9. Cough headache 10. Coital headache 11. Other 4. Specific syndromes 1. Migraine 2. Cluster headaches 3. Neuralgias ■

Trigeminal (tic douloureux)

■

Glossopharyngeal

4. "Tension-type" headache 5. Indomethicin responsive headaches 1. Chronic paroxysmal hemicrania 2. Hemicrania continua 3. SUNCT - short-lasting, unilateral, neuralgiform headache with conjunctival injection

and tearing 6. Others 5. Nonspecific headaches 1. Post-traumatic/postconcussion 2. "Analgesic rebound" headache 3. Psychiatric 4. Other

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TABLE 21-2. IHS CRITERIA FOR COMMON HEADACHE SYNDROMES Part of the criteria for all benign headaches is ruling out serious underlying organic disease causing headache (see text).

1. Common migraine 1. Must have headache with at least two of the following: 1. Unilateral (one side) location 2. Pulsing/pounding quality 3. Nausea 4. Light and sound sensitivity 2. History of similar headaches in the past 2. Classic migraine 1. Must meet criteria for common migraine but with warning symptoms before HA (usually 5 to 30 minutes) 1. Spots in front of eyes (often colored spots) 2. Fortification spectra 3. Wavy lines in vision 4. Flashing lights 5. Paresthesia 6. Weakness

7. Aphasia 2. History of similar headaches in the past 3. Cluster headache 1. Severe unilateral orbital, supraorbital and/or temporal pain 2. Pain lasts 15-180 minutes 3. At least one of the following on the side of headache: 1. Conjunctival injection 2. Facial sweating 3. Lacrimation 4. Miosis 5. Nasal congestion 6. Ptosis 7. Rhinorrhea 8. Eyelid edema 4. History of similar headaches in the past 4. Tension-type headaches 1. Headache pain accompanied by two of the following characteristics: 1. Pressing/tightening (nonpulsing) quality 2. Bilateral location 3. Not aggravated by routine physical activity 2. Headache should be lacking: 1. Nausea or vomiting

2. Photophobia and phonophobia (one or the other may be present) 3. Episodic tension-type headache should be present less than 15 days per month and chronic tension-type headache is present more than 15 days per month. 4. History of similar headaches in the past

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Fig 22-1 Horizontal section of cranium to show vectors of force (arrows) caused by supratentorial mass (epidural hematoma). The right uncus is shown herniating over the tentorial edge and compressing the ipsilateral third nerve and midbrain.

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Table 22-1. PROGRESSION OF DECREASING CONSCIOUSNESS

1. Alert and oriented. 2. Confused and drowsy but awakens to verbal stimuli. 3. Drowsy and awakens to noxious stimuli only. 4. Unconscious but responds appropriately to noxious stimulation by reaching in attempt to remove the stimulus. 5. Unconscious and responds inappropriately to noxious stimulation by random arm and leg movements. 6. Unconscious but responds to noxious stimulation with leg extension and arm flexion posturing (decorticate) or arm extension and internal rotation posturing (decerebrate). 7. No response to even noxious stimulation.

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Table 22-2. Glasgow Coma Score The GCS produces score between 3 and 15 (3 being the worst, and 15 the best). There are 3 elements based on the BEST response in three domains: eye opening, verbal response and motor response (it is best to record the score for each domain rather than only one global score)

1. Best Eye Opening. (4) 1. No eye opening. 2. Eye opening only to pain. 3. Eye opening to verbal command. 4. Eyes open spontaneously. 2. Best Verbal Response. (5) 1. No verbal response. 2. Incomprehensible sounds. 3. Inappropriate words. 4. Confused speech. 5. Orientated and normally responsive. 3. Best Motor Response. (6) 1. No motor response. 2. Extension to pain (decerebrate posture). 3. Flexion to pain (decorticate posture). 4. Withdrawal from pain. 5. Localising pain. 6. Follows Commands.

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Fig 22-2 Impingement of the cerebral peduncle against the rigid tentorial edge opposite an expanding high-convexity supratentorial lesion (subdural hematoma) causing hemiparesis ipsilateral to the mass. This occurs in as many as one third of persons who have subdural hematoma.

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Fig 23-1 Position for lumbar puncture illustrating the constant level of cerebrospinal fluid in the manometer with tilting, validating correct communication with subarachnoid space.

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TABLE 23-3. CAUSES OF XANTHOCHROMIA

1. Hemolyzed blood 2. Serum (if more than 150,000 RBC's from a traumatic tap, etc.) 3. High level of serum bilirubin 4. High level of serum carotene 5. High level of CSF protein (more than 150 mg% or so, depends on proportion of chromagens) 6. Old age (very slight xanthochromia from increased proportion of chromagens)

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TABLE 23-4. CELLS IN THE CSF

1. RBC 1. Traumatic tap 2. Subarachnoid bleeding prior to tap (trauma, ruptured aneurysm, etc.) 3. Ventricular leakage of intracerebral hemorrhage 2. WBC (see chap. 17) 3. Tumor cells (must request cytology)

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TABLE 23-5. CRITERIA FOR IDENTIFYING A TRAUMATIC TAP

1. The number of RBC's diminishes greatly between the first and last tubes. 2. The supernatant is not xanthochromic. 3. The CSF white blood cell count is not higher than expected. (When blood has been in the CSF for hours or days, it acts as an irritant and excites a CSF pleocytosis. In a traumatic tap, there should be 1 or 2 WBC's for every 1,000 RBCs if the patient's peripheral blood counts are normal.)

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TABLE 23-6. CAUSES OF ELEVATED CSF PROTEIN*

1. From serum accompanying hemorrhage or a traumatic tap: add approximately 1 mg% protein for every 700 RBCs. 2. Intracerebral hemorrhage (the amount of protein is usually elevated disproportionately to the amount of blood). 3. Many inflammatory conditions. 4. Many neoplasms. 5. Occasionally with degenerative diseases (but usually the level of protein is normal or only minimally elevated). 6. Sometimes with cerebral infarction (usually not greater than 100 mg%). 7. Many peripheral neuropathies. 8. Diabetes mellitus. 9. Guillain-Barre syndrome. 10. Hypothyroidism. 11. Stagnant CSF, as below an obstructing spinal tumor or after a ventricular shunting procedure. 12. Laboratory error.

*Levels >45mg%

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TABLE 23-7. CONTRAINDICATIONS TO LUMBAR PUNCTURE PROBLEM

REASON

Infection over the puncture site

May cause meningitis

Intracerebral mass lesion

May cause herniation

Increased intracranial pressure

May be indicative of a mass (see text); if there is no mass, puncture is usually safe

Before planned myelography (7-10 days)

May produce subdural collection of CSF, making studies impossible

Suspected spinal tumor

May produce deterioration; may make myelogram impossible

Coagulation deficit

May result in epidural or subdural hemorrhage, with resulting root and/or cord compression (rare complication)

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TABLE 23-8. COMPLICATIONS OF LUMBAR PUNCTURE

1. Post-tap headache (from fluid leakage through dural tear) 2. Traumatic tap (obscuring the clinical picture) 3. Subdural collection of fluid (may interfere with subsequent studies [cisternogram, myelogram] or with subsequent lumbar punctures, may show falsely elevated level of protein from stagnation) 4. Herniation with cerebral mass lesions 5. Deterioration of spinal compression with cord tumors 6. Subdural or epidural hemorrhage (in patients with coagulation deficit)

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Fig 23-2 Cisternal subarachnoid puncture, indicated when cerebrospinal fluid cannot be obtained from lumbar space and when myelography is used to determine the upper level of the complete subarachnoid space block by a mass lesion.

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TABLE 23-9. SKULL X-RAYS IN THE DIAGNOSIS OF INTRACRANIAL DISEASE

1. Calcified pineal or habenular commissure: this is often shifted with lateralized intracranial masses. Remember, however, that bilateral cerebral masses or masses that are far frontal or occipital may not shift the pineal appreciably. 2. Abnormal calcifications (tumors, aneurysms, arteriovenous malformations, etc.) 3. Increased vascular markings in the skull, when tumors (such as meningiomas) are fed from the external carotid circulation. 4. Sclerosis or erosion from underlying tumors (such as meningiomas). 5. Erosion of the drosum sellae as a sign of increased intracranial pressure. 6. Enlargement of the sella turcica from an intrasellar mass. 7. Enlargement of the optic foramen or of the internal auditory meatus or canal from tumors of the second or eighth cranial nerves. Erosion of other foramina may also be detected with special views (foramen rotundum, ovale, jugular foramen, etc.). 8. In children, spreading sutures, indicative of increased pressure.

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TABLE 23-10. OTHER ABNORMALITIES OF SKULL X-RAYS

1. Fractures: A fracture across the course of the meningeal arteries should lead one to suspect an epidural hematoma. Not all fractures can be seen on x-ray, basilar fractures may be particularly difficult to see. 2. Lytic or blastic lesions, indicative of metastatic tumors. 3. Clouding of the sinuses, often indicative of infection. 4. Osteomyelitis. 5. Structural changes, which may result in CNS damage, such as platybasia, basilar impression, or (in children) synostoses. 6. Some systemic diseases: Paget's disease, osteopetrosis, sickle cell anemia, thalassemia, etc.

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Fig 23-3 Anterior-posterior diameter of bony spinal canal.

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Fig 23-6 Myelogram showing displacement of subarachnoid space containing radiopaque substance (black). A, intramedullary mass (or midline dorsal or ventral extramedullary, intra- or extradural mass) showing spindle-shaped enlargement of spinal cord. B, extradural mass causing complete block. Substance introduced from lumbar and cisternal punctures to delineate lower and upper extent of block.

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Fig 23-7 Schematic representation of the principle of computerized axial tomographic x-ray technique.

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TABLE 23-11. MAJOR USES OF THE ELECTROENCEPHALOGRAM

1. Diagnosis of epilepsy. ❍

Paroxysmal spikes, sharp waves, and/or slow waves may be diagnostic of epilepsy. The EEG can help identify the type of seizure disorder, and it may help localize a seizure focus.

2. Diagnosis of focal structural lesions. ❍

Focal slowing in the EEG may help localize a lesion. The EEG pattern is not specific for any particular type of pathology.

3. Metabolic encephalopathies. ❍

Slowing is seen with most metabolic encephalopathies. Again the EEG pattern is not helpful in diagnosing the type of encephalopathy.

4. Drugs. ❍

Barbiturates and minor tranquilizers frequently produce an excessive amount of low-voltage fast activity.

5. Degenerative disease. ❍

Unusual EEG patterns are seen in a number of degenerative diseases (SSPE and Creutzfeldt-Jakob disease, for example). In the others, the EEG changes are nonspecific and often very slight.

6. Cerebral death. ❍

Two flat EEGs taken 24 hours apart are diagnostic of cerebral death in the absence of hypothermia or drug overdose.

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Fig 23-4 Placement of nasopharyngeal lead for recording the electroencephalogram in proximity to the anterior temporal lobe.

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Fig 23-5 Skin electrode sites for determining median nerve conduction velocity (see text).

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TABLE 24-1. PROCESSES LEADING TO PATHOLOGIC DEPRESSION OF CONSCIOUSNESS

1. Reticular formation involvement (common cause of depressed consciousness) 1. Supratentorial mass lesions that secondarily compress brain stem (e.g., neoplasm, abscess, herpes simplex encephalitis, infarction with swelilng, and hemorrhage) (See Fig 24-2) 2. Subtentorial mass or destructive lesions that compress or directly destroy brain stem (e.g., infarction, hemorrhage - primary brain stem or cerebellar - tumor, abscess) 2. Bilateral hemispheric and reticular formation depression (most common cause of depressed consciousness) (see also Table 16-3), almost always metabolic depression 1. Oxygen, substrate, or cofactor deficiencies (e.g., ischemia, hypoxia, hypoglycemia, vitamin deficiency) 2. Toxic ■

Endogenous - renal failure, hepatic failure, pulmonary failure (carbon dioxide narcosis), endocrine hyper- or hypofunction

■

Exogenous (most often diagnosed cause of coma) - sedative drug overdose (e.g., barbiturates, alcohol, tranquilizers, opiates, etc.); acid poisons (e.g., methyl alcohol, paraldehyde, ethylene glycol); enzyme inhibitors (e.g., arsenic, lead and other heavy metals, insecticides, cyanide, salicylates)

■

CNS infection (meningitis, encephalitis)

3. Acid-base or ionic abnormalities in CNS environment 4. Postictal (epileptic) diffuse depression 5. Traumatic dysfunction without histologic structural change (concussion)

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Fig 24-1 Diagram of the reticular activating system extending from the midpons through the diencephalon to alert the cerebral hemispheres diffusely.

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TABLE 24-2. BASIC EVALUATION OF PATIENT WITH DEPRESSED CONSCIOUSNESS OF UNKNOWN ETIOLOGY

1. Emergency evaluation. 1. Establish airway 2. Blood pressure. - If hypotension is present, determine whether hemorrhage is present; if so, stem and replace lost blood volume. Severe hypertension should be treated by avoiding precipitous drops to hypotensive level. 3. Temperature. - If febrile and head trauma and potentially associated cervical spine injury are not factors, chin should be flexed on chest to determine the presence of rigidity of meningeal irritation (meningitis, meningoencephalitis). During chin-on-chest maneuver observe for knee and hip flexion (Brudzinski's sign), which when present confirms meningeal irritation. 4. Observe and plapate for evidence of head trauma. - Evaluate tympanic membranes for presence of middle-ear blood (indicates skull fracture) and infection (suggests possible portal of entry for bacterial meningitis). If trauma is evident or suspected, manipullation of the neck should be minimized (head-neck-shoulders fixed with blocks or sandbags if possible) until cervical spine films rule out fracture or dislocation. 5. Glucose level in blood. - This can be carried out in several minutes using dip-stick

technique, confirmed later by more accurate laboratory analysis. After drawing lbood, give 50 gm glucose intravenously to avoid any delay in greating possible hypoglycemia. 6. Intravenous (5% dextrose in water) to be started with large-gauge needle also capable of delivering whole blood rapidly. 7. Indwelling urinary catheter to be placed in the patient who is deeply stuporous or comatose. 8. History, if available from relatives, bystanders, or patient himself. 2. Neurologic evaluation. 1. Level of consciousness. 2. Respiratory pattern. 3. Pupil size and function 4. Oculomotor-vestibular function. 5. Motor function. 3. Laboratory evaluation (as indicated by history, emergency, and neurologic evaluations) (see also chap. 23). 1. Computerized axial tomography (CT scan) of cranium if available and indicated. Emergency indications include suspected trauma, stroke, or mass lesions. If not available, echoencephalography may be useful in determining presence of mass lesion causing shift of intracranial structures. 2. Skull x-rays to determine presence of fractures, shift of calcified pineal gland or other calcified structures (more reliable than echoencephalogram). 3. Cervical x-rays if evidence or suspicion of head trauma. 4. Blood chemistries. - Arterial: oxygen, carbon dioxide, pH; venous Na, Cl, K, bicarbonate,

BUN, creatinine, Ca, Mg, liver function tests, drug screen. 5. Urinalysis. 6. Lumbar puncture. - Only indicated as an emergency in comatose patient if suspect CNS infection; otherwise contraindicated for fear of precipitation of rostrocaudal deterioration with supratentorial and occasionally subtentorial mass lesions. 7. Electroencephalogram. - To aid in differentiating true coma (diffuse electric slowing) from hysterical coma (normal pattern). This is not an emergency procedure as a rule. However, if herpes simplex encephalitis is suspected, temporal lobe slowing may be seen before the CT scan or MRI are positive. For the patient with hysterical coma, the neurologic examination is adequate to make the distinction from true coma. The neurologic examination is adequate to make the distinction. Occasionally comatose patients with destruction of the reticular formation in the pons, midbrain, or lower diencephalon have a persistent alpha frequency (8-13 cps) background rhythm that normally is associated with an alert, sentient state. However, the alpha rhythms of normal individuals disappear on sensory stimulation, while those of "alpha coma" persist. The normal alpha pattern tends to be seen predominantly in the posterior cranial (occipital) leads, while in alpha coma the rhythm is diffusely present. Under any circumstance one should determine with utmost care the presence or absence of the "locked-in" state when an alpha pattern is present by evaluating vertical eye functions (see above and chap. 4) before assuming the presence of alpha coma.

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Fig 24-2 Right cerebral expanding mass (hematoma) originating in the basal ganglia. Arrows represent vectors of force impinging with rosrocaudal progression on the brain stem.

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TABLE 24-3. ROSTROCAUDAL BRAIN STEM DETERIORATION SECONDARY TO EXPANDING RIGHT SUPRATENTORIAL MASS ANATOMICAL

CONSCIOUSNESS RESPIRATION

PUPILS

LEVEL (the level

OCULOMOTOR-

MOTOR

VESTIBULAR

reached by progressive damage) Upper

Drowsy (dull)

diencephalon

Eupnea with

Small,

Depression of ocular

Left

yawns and sighs

reactive

checking and fast

hemiparesis,

component of nystagmus

bilateral paratonia

Lower

Coma

diencephalon

Cheyne-Stokes

Small,

(CSR)

reactive

Loss of above

Left hemiparesis, decorticate

Mesencephalon

Coma

CSR or central

Midposition, Dysconjugate response; loss Decerebrate

neurogenic

fixed (MPF) of medial rectus function on

hyperventilation

horizontal gaze; may see

(CNH)

loss of lateral rectus function also (see text)

Upper pons

Coma

CNH or ataxia

MPF

As above

Weak decrebrate

Lower pons

Coma

Ataxia or eupnea

MPF

None

Flaccid, areflexic

Medulla

Coma

Apnea

MPF

None

Same

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Table 25-1 Causes of metabolic encephalopathy*

1. Deprivation of oxygen, substrate, or metabolic cofactors 1. Hypoxia (interference with oxygen supply to the entire brain - cerebral blood flow [CBF] normal) 1. Decreased oxygen tension and content of blood ■

Pulmonary disease/ Alveolar hypoventilation

■

Decreased atmospheric oxygen tension

2. Decreased oxygen content of blood, normal tension ■

Anemia

■

Carbon monoxide poisoning

■

Methemoglobinemia

2. Ischemia (diffuse or widespread multifocal interference with blood supply to brain) 1. Decreased CBF resulting from decreased cardiac output Stokes-Adams, cardiac arrest, cardiac arrhythmias ■

Myocardial infarction

■

Congestive heart failure

■

Aortic stenosis

■

Pulmonary infarction

2. Decreased CBF resulting from decreased peripheral resistance in systemic circulation

■

Syncope: orthostatic, vasovagal

■

Carotid sinus hypersensitivity

■

Low blood volume

3. Decreased CBF due to generalized or multifocal increased vascular resistance ■

Hypertensive encephalopathy

■

Hyperventilation syndrome

■

Hyperviscosity (polycythemia, cryoglobulinemia, paraproteinemia, macroglobulinemia, sickle cell anemia, thallassemia)

4. Decreased CBF due to widespread small-vessel occlusions ■

Disseminated intravascular coagulation

■

Systemic lupus erythematosus

■

Subacute bacterial endocarditis

■

Fat embolism

■

Cerebral malaria

■

Cardiopulmonary bypass

■

Sickle cell crisis

3. Hypoglycemia ■

Resulting from exogenous insulin

■

Spontaneous (endogenous insulin, liver disease, etc.)

■

Alcohol consumption, prolonged with no carbohydrate intake

4. Cofactor deficiency ■

Thiamine (Wernicke's encephalopathy), niacin, pyridoxine, cyanocobalamin

2. Diseases of organs other than brain 1. Diseases of non-endocrine organs ■

Liver (hepatic coma)

■

Kidney (uremic coma)

■

Lung (CO2 Narcosis)

2. Hyperfunction and/or hypofunction of endocrine organs ■

Pituitary

■

Thyroid (myxedema-thyrotoxicosis)

■

Parathyroid (hypoparathyroidism and hyperparathyroidism)

■

Adrenal (Addison's disease, Cushing's disease, pheochromocytoma)

■

Pancreas (diabetes, hypoglycemia)

3. Other systemic diseases ■

Cancer (remote effects), porphyria

3. Exogenous poisons 1. Sedative drugs ■

Barbiturates, nonbarbiturate hypnotics, tranquilizers, bromides, ethanol, anticholinergics, opiates

2. Acid poisons or poisons with acidic breakdown products ■

Paraldehyde, methyl alcohol, ethylene glycol, ammonium chloride, salicylates

3. Enzyme inhibitors ■

Heavy metals, organic phosphates, cyanide, salicylates

4. Abnormalities of ionic or acid-base environment of CNS

❍

Water and sodium (hypernatremia and hyponatremia)

❍

Acidosis (metabolic and respiratory)

❍

Alkalosis (metabolic and respiratory)

❍

Postassium (hyperkalemia and hypokalemia)

❍

Magnesium (hypermagnesemia and hypomagnesemia)

❍

Calcium (hypercalcemia and hypocalcemia)

5. Diseases producing toxins or enzyme inhibition in CNS ❍

Meningitis, encephalitis, subarachnoid hemorrhage

6. Disordered temperature regulation ❍

Hypothermia, heat stroke

7. Postepileptic (postictal) depression 8. Traumatic dysfunction without histologic structural change (concussion)

*After Plum and Posner

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