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CHAPTER 31 NERVOUS SYSTEM DISEASE

CHAPTER 31 NERVOUS SYSTEM DISEASE
Practice of Geriatrics
CHAPTER 31 NERVOUS SYSTEM DISEASE
Raymond J. Baddour, M.D., and Leslie Wolfson, M.D.
The Neurology of Aging: Normal Versus Pathologic Change
Neurologic Evaluation
Disorders of Mobility
Paroxysmal Disorders
Structural Disease of the Brain
Spinal Cord Diseases
Neuromuscular Disease
In the past century, life expectancy has increased from 50 to 75 years. In an aging society, disorders of the nervous system are becoming increasingly important in producing functional incapacity. This has made the recognition, evaluation, and treatment of these conditions of real clinical importance. This chapter begins with a review of some age-related changes in function to make the disease-related changes that follow more meaningful.
THE NEUROLOGY OF AGING: NORMAL VERSUS PATHOLOGIC CHANGE
Awareness of the effects of age on the nervous system is fundamental because it is the basis for determining the presence of disease. Age-related changes are additive to disease in producing functional incapacity. Knowledge of what constitutes normal and abnormal function is critical in deciding when medical evaluation is indicated.
Age-related changes in cognitive and sensorimotor function should not interfere with everyday activities. Elderly patients frequently complain of memory and learning deficits, difficulty in recalling names, and poor short-term recall, although the cognitive decline that occurs in normal aging is modest. Short-term recall is the function that is most impaired and requires otherwise intact older persons to devise adaptive strategies (e.g., making lists). By contrast, dementias produce maladaptive decline, and functional independence is ultimately lost.
Cognitive Function
Verbal intelligence peaks in the third decade and then remains stable until the eighth decade. Language function (e.g., vocabulary and comprehension) is generally well preserved, and deficits noted on routine examination should prompt formal mental status evaluation. Psychomotor skills that are speed based (i.e., finger tapping or mental calculation) peak at age 20 and show a steady decline thereafter. Personality changes are unusual in healthy older persons (less than 10% have them), and therefore the possibility of underlying brain dysfunction should be considered in patients who demonstrate such changes (e.g., depression).1 Although personality change is unusual as a presenting symptom, 80% of patients with Alzheimer’s disease experience such changes during the course of the illness.
Sensory Function
Age-related alterations in vision and hearing commence in the third decade. Visual acuity decreases because of degeneration of photoreceptors, presbyopia results from diminished lens accommodation, and cataracts occur. Also, pupillary size is decreased, pupillary response to light and accommodation is sluggish, and upgaze is restricted. Hearing changes do not become significant until after the age of 65, but presbycusis is found in approximately 40% of people over the age of 75.2 Patients often complain of an inability to understand speech. This can be attributed to both cochlear degeneration and slowed central processing of auditory information.
Clinical and psychophysiologic measurement studies have demonstrated modest age-related decrements in pain and thermal sensitivity, tactile sensation, two-point discrimination, joint position sense, and stereognosis. By contrast, diminished vibratory perception is encountered in more than half of older persons and is of much greater magnitude. This loss of vibratory sensation is much greater than losses of other large-fiber sensory modalities and thus may be caused by receptor changes, although loss of large myelinated sensory fibers of the peripheral nerves remains a possible explanation.
Motor Function
Visual, vestibular, and tactile-proprioceptive data form the inward portrayal of a person’s location, movement, and environment and are therefore central to the motor skills that support balance. Age-related changes in these primary sensory modalites are well documented, although they are not of sufficient magnitude to seriously compromise locomotion. Changes in sensory function are not without consequences because they influence the occurrence of sensory misperception, which may be an important factor in causing falls. Furthermore, decreased sensory input may influence our ability to produce an effective balance response. Interpretation of sensory input and the choice of a motor response, termed sensorimotor processing, is influenced by the number and complexity of choices as well as by increasing age.3 The time needed to perform complex choice reaction tasks in older persons increases more than that needed for simple tasks. Although they increase with age, afferent and efferent transmission times are not responsible for the bulk of the increases in processing time.3 Changes in sensorimotor processing time or its effectiveness under adverse or complex conditions (e.g., with limited or inappropriate sensory information or in the presence of a severe hazard) may thus be of practical importance in relation to mobility.
Cross-sectional studies show a decrement in strength from young adulthood to older adulthood of 20% to 40%, which is even greater than the losses in muscle mass observed.4,5 Age-related loss of strength is probably unimportant for routine activities but could be a factor in the greater strength demanded when swift responses are necessary to act on environmental hazards.
Most older adults have diminished ankle jerks, but otherwise deep tendon reflexes are only modestly decreased, and plantar responses are typically unaffected by age. Conversely, brisk ankle reflexes with clonus accompanied by extensor plantar responses suggest pyramidal tract dysfunction. The occurrence of reflexes such as palmomental and snout reflexes increases with advancing age, but they are of limited diagnostic use.
Essential tremor, which frequently involves the distal upper extremities and head, is common in older persons. The tremor is maximal when a position is maintained by the involved parts (i.e., postural tremor). When the tremor results in physical disability or social embarrassment, treatment with beta-blockers is warranted.
Balance
Under conditions of quiet standing, sway as a measure of balance is only marginally greater in older adults than in younger persons.6 By comparison, the extent of one’s ability to lean in the anteroposterior plane (i.e., the limit of sway or the functional base of support) decreases by about a third from the third to the eighth decades.7 Similarly, during this age span, the ability to stand on one leg decreases from more than 30 seconds to slightly less than 15 seconds.8 Finally, under test conditions with limited sensory input (one modality) or with a vigorous perturbation, older persons lose their balance much more frequently than younger persons, although both groups adapt effectively during repetitive testing.6 Thus, quiet standing is associated with marginal changes in balance, although activity may push an older person toward the limit of stable stance, thereby activating responses to maintain posture. Under most conditions, the balance of older persons functions effectively and can even improve with repetitive testing. By contrast, the dysfunctional balance associated with impaired mobility is of such magnitude that it can only result from age-related diseases. Furthermore, frequent losses of balance in older persons during testing under challenging conditions (limited sensory input or vigorous perturbation) suggest that these modest age-related decrements may be an element in the increased occurrence of falls in older people.6 We conclude that age-related balance decrements are analogous to those of other central nervous system (CNS)–dependent functions (e.g., cognition) that do not by themselves lead to significant compromise of function (e.g., immobility).
NEUROLOGIC EVALUATION
In older persons, in addition to a general neurologic assessment one must often evaluate cognition as well as the sensorimotor skills required for mobility. The evaluation of patients with cognitive impairment is described in Chapter 26, as well as in numerous other sources. The key elements of an evaluation suitable for patients with mobility disorders are described in the following paragraphs.
Mental status should be evaluated in these patients because it may be an indication of a degenerative or multifocal disease. For similar reasons, the cranial nerves should be carefully tested. How should a clinician approach the evaluation of sensorimotor function? Strength assessment (i.e., manual motor testing) is particularly difficult in older persons because of the agerelated changes noted earlier as well as differences in gender and activity levels. To assist in interpreting manual motor test results examiners should compare muscle groups within the same patient (e.g., left versus right or proximal versus distal). Atrophy of intrinsic hand muscles that is unassociated with weakness or other neurologic dysfunction is also frequently present. Due to these problems, functional testing of the motor system is particularly useful in evaluating the strength of older persons.
Functional motor testing should include the following exercises:

1.
Rising from a low chair without using the arms. This exercise tests hip and knee extensor strength and balance.

2.
Standing on heels and toes. This maneuver tests dorsi and plantar extension strength and balance.

3.
Performing a single, tandem, or semitandem stance. Such a stance tests lower extremity strength and balance (e.g., 10 seconds of single stance are normal for an 80-year-old).

4.
Graded forward and backward pushes. Pushes test balance. Subjects should always be pulled toward the examiner.

5.
Gait and turns. This exercise tests all facets of sensorimotor function and mobility skills. The examiner should observe for patterned dysfunction (e.g., lurches during walking and multistep turns suggest a balance disorder).
Other components of motor function should be assessed as well (tone, coordination, rapid alternating movements, and the presence of intention, postural, or resting tremor). If cognitive function is intact, sensory testing should not be difficult. Age-related changes in pin, touch, joint position sense, and stereognosis are modest. Lower extremity sensory function is an important component in maintaining mobility and balance. The deep tendon reflexes of older persons become less reactive, and the ankle jerk sometimes cannot be elicited.9 Brisk reflexes and ankle clonus are unusual in older persons. Their existence should lead the clinician to suspect lesions of the pyramidal neurons or tracts. The presence of extensor plantar responses (Babinski’s signs) should be similarly interpreted. The frequency of snout and palmomental reflexes doubles between the fifth and ninth decades.10 These frontal lobe release signs may be present in otherwise normal older persons, and therefore their significance is uncertain. Evaluation of older patients requires medical assessment as well as neurologic evaluation. The examiner should keep in mind that arthritis can produce a surprising amount of immobility, although pain and joint dysfunction usually make this diagnosis evident.
In the sections that follow a number of neurologic disorders with significant impact on older persons are reviewed. For certain conditions, specifically those relating to movement disorders and vascular disease, the reader is referred to Chapter 32 and Chapter 33, respectively, for a more detailed discussion.
DISORDERS OF MOBILITY
Ischemic White Matter Disease
It is common for persons in their eighth or ninth decade to experience progressive impairments in gait and balance. Frequently, the pattern of gait and balance dysfunction suggests a bifrontal syndrome. The gait of these patients consists of small steps with the feet adhering to the floor (magnetic gait). Balance is severely impaired. Bradykinesia and rigidity are often present. There may be associated urinary dysfunction as well as slowed cognitive processing, although dementia, if present, is mild. It is likely that this syndrome is caused by the presence of subcortical lesions that compromise the complex frontal processing required for gait and balance. The combination of signs and symptoms can be difficult to distinguish from parkinsonism, and often these patients receive an unsuccessful trial of L-dopa.
The causes of the bifrontal syndrome include ischemic small vessel disease, bilateral frontal disease (e.g., tumor) and normal pressure hydrocephalus. Ischemic small vessel disease involving the subcortical frontal white matter is associated with increased age, hypertension, and the occurrence of silent strokes.11 The patient develops a progressive bifrontal syndrome that evolves over a period of years. Several studies have demonstrated a relationship between white matter lesions demonstrated on computed tomography (CT) or magnetic resonance imaging (MRI) and impaired gait and balance.12,13 A recent clinicopathologic correlative study determined that these lesions may represent astrocytosis within the white matter that the authors suggest may be activated by localized ischemic changes.14 Although the pathology described in this study does not clearly indicate a cause for the white matter lesions, localized ischemia fits with clinical and pathologic data and thus is a logical point of departure.
Normal Pressure Hydrocephalus
There are patients with hydrocephalus associated with gait disturbance, dementia, and urinary incontinence who improve after performance of a cerebrospinal fluid (CSF) shunting procedure. For the past 30 years clinicians have attempted to find a means to predict who will respond to a shunt. Although much clinical experience has accumulated in the intervening years, this question remains only partially answered today.15
Normal pressure hydrocephalus (NPH) is not a common disease. The incidence has been estimated at 2.2 per million per year, and the prevalence has been estimated at 5000 to 10,000 patients in the United States.
Studies have shown that the underlying defect in NPH is impaired CSF flow because of obstruction of CSF pathways in the basal cisterns. Acquired communicating hydrocephalus can be produced by subarachnoid hemorrhage, meningitis, cranial trauma, or intracranial surgery, although the cause is unknown in about half the cases. To compensate for the obstruction, alternative absorptive pathways develop, producing a reversal of CSF flow through the ependymal lining of the ventricle into the extracellular space of the white matter, from where it is absorbed through the capillary bed into the venous system. This causes disruption of the periventricular white matter, perhaps by the production of localized ischemia. It is this damage to the periventricular tissue that produces the clinical manifestations of NPH.16
Difficulty with gait is often the first and occasionally the only clinical manifestation of NPH. It is also the sign that is most likely to respond to a shunting procedure. Patients have difficulty in initiating gait, walk with small steps, and are unable to lift their feet (“magnetic gait”). These gait abnormalities are associated with postural instability.
Cognitive impairment is usually mild and consists of poor memory, inertia, inattention, decreased speed of processing complex information, and impaired manipulation of acquired knowledge. The mini-mental state examination is not useful for detecting cognitive loss in patients with NPH because the degree of mental impairment is mild and the test is insensitive to subcortical frontal impairment. Both the cognitive impairment and the gait abnormalities resemble those seen in patients with disorders caused by subcortical frontal lobe dysfunction. When intellectual impairment is pronounced, other causes of dementia should be considered. Urinary incontinence is a late sign and has been attributed to damage to the periventricular pathways extending to the bladder control center; the result is an inability to control bladder contractions despite normal sphincteric function.17
Computed tomographic (CT) scans in patients with NPH usually show ventricular enlargement that is out of proportion to cortical atrophy. The frontal horns are rounded and the temporal horns are enlarged, but there is no hippocampal atrophy. Atypical features such as mild or moderate cortical atrophy or periventricular abnormalities of white matter suggestive of ischemic lesions are sometimes present but do not preclude the possibility of clinical improvement after a shunt.
Lumbar puncture with removal of 40 to 50 mL of CSF may be followed by a transient or, rarely, prolonged clinical improvement. This procedure has been used as a method of preoperative assessment of the likelihood of operative success. Recent analysis, however, has raised questions about the predictive value of the procedure, although use of the test is still widespread. Continuous external lumbar drainage, in which approximately 150 to 200 mL of CSF are removed daily for 3 to 5 days, has been suggested to predict the outcome of shunt placement more accurately. Other techniques used in investigation, including isotope cisternography, which measures CSF flow dynamics, and single-photon emission computed tomography (SPECT) scanning, which determines the pattern of cerebral blood flow, have been inconsistent in predicting shunt success.
A recent review, which assessed more than 1000 patients with NPH retrospectively, found that 30% of patients who underwent shunting procedures for idiopathic NPH showed significant improvement. When a cause was identified, the success rate increased to 50% to 70%. Approximately 35% of patients with shunts had surgical complications, and approximately 10% of these resulted in death or severe residual morbidity.18
Ataxia
A wide-based, unsteady gait characterized by poorly controlled turns and staggering is associated with cerebellar or brain stem dysfunction but sometimes is seen as part of a sensory ataxia (limited proprioceptive and visual input) or in patients with acute vestibular abnormalities (often benign positional vertigo). The history and physical examination often allow one to differentiate among the possibilities. Abnormal neurologic findings suggest brain stem or cerebellar abnormalities, whereas positionally dependent vertigo and nausea associated with gaze-evoked nystagmus and an otherwise normal examination suggest benign positional vertigo. Sensory ataxia can be produced by proprioceptive and visual loss. An MRI is often warranted to look for lesions within the posterior fossa. In older patients, ataxia is often produced by brain stem or cerebellar infarction, multisystem atrophy, or alcoholism.
PAROXYSMAL DISORDERS
Seizure Disorders
After the age of 60, the incidence of seizures increases.19 The annual incidence of epilepsy in persons aged 65 years and older is 134 per 100,000.20 The majority of seizures occurring in this population are secondary to strokes, brain tumors, toxic-metabolic disturbances, and Alzheimer’s disease. Primary seizure disorders with a late-life onset are rare. Stroke accounts for 30% to 50% of seizures occurring in the elderly population. Tumors and toxic-metabolic causes (e.g., renal failure, alcohol, medication) are each responsible for approximately 10% to 15%. Head trauma may cause another 10%, and 30% are idiopathic.21,22
Initial evaluation of elderly patients with seizures should include a history, and information should be obtained from family members or caregivers whenever possible. A medication history should be elicited as well as information about previous head injuries. Physical examination, serum electrolyte determination, electrocardiography, electroencephalography, head CT scans without and with contrast should also be done. MRI is helpful when CT is negative or inconclusive and the patient’s history suggests the possibility of seizures of focal onset. MRI is also effective for identifying abnormalities such as mesial temporal sclerosis and other small cortical scars as well as abnormalities such as hippocampal atrophy. Because MRI provides high-resolution images that are sensitive to differences in tissue constituents, it may also be effective in evaluating patients with underlying brain tumors. Depending on the history and physical findings, other studies that may be considered include lumbar puncture, blood cultures, and toxicology screening tests.
Management of seizures should focus on minimizing the impact of this disorder on the patient’s lifestyle while setting guidelines to maximize the patient’s safety. Patients should be instructed to avoid driving until they have been free of seizures for 3 to 6 months, avoid swimming alone, and use a shower for bathing.
In patients with toxic or metabolic abnormalities, correction of the abnormality usually suffices for preventing further seizures. In other circumstances, anticonvulsant therapy may be indicated, taking into consideration the fact that drug metabolism changes in older persons, and careful observation of blood levels, is required. The aim should be to control the seizures with a single drug at the lowest effective dose. Phenytoin (Dilantin), carbamazepine (Tegretol, Epitol), and valproic acid and its derivatives (Depakene, Depakote) are all effective against a wide range of partial and generalized seizures and are generally well tolerated in older patients. Benzodiazepines should be avoided because of their potential for accumulation and toxicity in older patients. Barbiturates should also be avoided because of their sedating potential.21
Older patients who develop seizures have an excellent prognosis. In one study, 62% of patients in whom epilepsy began after age 60 remained seizure free for at least 1 year while they received anticonvulsants.23
Trigeminal Neuralgia
The pain from trigeminal neuralgia can be among the worst pain that can be experienced. It is lancinating and usually has a duration of seconds. The central and lower portions of the face are commonly affected. These areas are innervated by the maxillary (cranial nerve V2) and mandibular divisions (V3) of the trigeminal nerve. The pain can be elicited by stimulation of trigger points. Talking, chewing, shaving, and applying cosmetics, among others actions, can provoke an attack. Early in the course of the disease remissions are common, but later the frequency and severity of the attacks often increase.
Females are affected more than males in a 3:2 ratio. The incidence in the United States is estimated to be 15,000 new cases per year.24 Onset is most common in the fifth to seventh decades of life.
For many people (particularly older patients) the cause of trigeminal neuralgia is probably demyelination of the retrogasserian ganglionic fibers in the pontine root entry zone.24 In most patients, this demyelination is initiated by vascular compression (especially compression of the superior cerebellar artery). In a small number of patients (particularly younger patients) other precipitants (e.g., multiple sclerosis or tumor) may damage the nerve, so that neuroimaging may be warranted.
Carbamazepine is an effective treatment for trigeminal neuralgia, producing relief that begins within hours of administration. Side effects are uncommon but can include impaired hematopoietic and liver function, lethargy, and ataxia. There are analogs of carbamazepine that have shown promise in controlling pain and have fewer side effects.25 Phenytoin has been used successfully, although it is not as effective as other medications. Its effectiveness can be enhanced by using it in combination with carbamazepine and baclofen. Baclofen may be successful in patients who have become resistant to carbamazepine or phenytoin. Its mechanism of action is similar to that of carbamazepine; it depresses excitatory transmission input from the afferent trigeminal fibers and facilitates segmental inhibition of the trigeminal complex.
In some patients drug therapy becomes ineffective, or the side effects become intolerable. For these patients, ablative surgical lesions of the trigeminal nerve should be considered. These procedures provide transient relief accompanied by sensory loss as well as occasional formation of neuroma with anesthesia dolorosa. The best long-term results have been achieved by microvascular decompression of the posterior circulation. This is a major surgical procedure that has a 60% to 80% chance of producing long-term relief and up to a 95% chance of producing a partial remission.26 The procedure is most appropriate for younger and healthier patients.
Transient Global Amnesia
Transient global amnesia (TGA) is a benign syndrome characterized by sudden onset of memory loss with retention of personal identity. Consciousness and motor skills are unimpaired.27 The amnesia may last up to 24 hours. In patients over the age of 50 the incidence of transient global amnesia is 23.5 to 32 per 100,000 per year.28 The prevalence of risk factors for vascular disease, stroke, and dementia are not increased in these patients.27 Patients are left with an amnestic gap for the event.
Transient memory loss can also occur following seizures, drug intoxication, head trauma, or ischemic events. Epilepsy, migraine, and cerebrovascular accidents have been implicated as causes of TGA, although no cause is generally accepted. Electroencephalograph studies after a TGA episode are usually normal. Epileptic discharges have not been identified.27 Imaging studies are also commonly normal,29 although MRIs with signal abnormalities in one or both temporal lobes have been reported.30,31 SPECT scans have shown temporary regional hypoperfusion, most commonly localized to the medial temporal lobes.27 Several reports have noted that the incidence of TGA in patients with migraine is higher than expected, although the exact relationship is unclear.27
The prognosis of TGA is good. Other than a permanent memory gap for the attack itself, no neuropsychological sequelae have been noted.29 There is a 3.6% chance of recurrence.32
Vertigo
Dizziness represents a spectrum of symptoms that requires clarification by the examiner during the course of the medical history. For older patients, dizziness may represent (1) lightheadedness, which is a nonspecific symptom, (2) presyncope, (3) unsteadiness while walking, which is usually a product of impaired mobility skills, or (4) vertigo, which is an illusion of motion, usually rotational. The diagnostic approaches to and medical implications of the four sensations are quite different. Evaluation of ligtheadedness is rarely productive. A pre-syncope assessment should be directed at entities that produce loss of consciousness. Unsteadiness while walking is often related to impaired sensorimotor function of the lower extremities. Vertigo is produced by brainstem or vestibular dysfunction.
Unlike the situation in younger persons, persistent dizziness in the great majority of older persons has a demonstrable cause.33 Approximately half have peripheral vestibular abnormalities, and more than 20% have dizziness related to cerebrovascular disease.33 A key part of the examination is the Nylen-Bárány maneuver, in which a sitting patient is rapidly moved to a prone position with the head hanging downward and is then rotated 45 degrees to one side and then to the other side. In patients with vestibular dysfunction, this maneuver often elicits contralateral rotatory nystagmus from the dependent horizontal canal. Patients with labyrinthitis show a combination of positional vertigo associated with nausea and vomiting, positionally induced rotatory nystagmus, and an absence of associated neurologic signs and symptoms. Approximately half of patients have idiopathic labyrinthitis, and one third have a recent history of head trauma or findings suggestive of viral labyrinthitis.33 Although vertigo due to vertebrobasilar ischemia can occur in isolation,34 it is almost always associated with other neurologic findings.
STRUCTURAL DISEASE OF THE BRAIN
Tumors and Chronic Subdural Hematoma
In the past 23 years, the incidence of brain tumor has doubled in patients over age 70 and quintupled in those over 85. It is likely, however, that this increase in the rate of occurrence is related both to an increased incidence of tumors (including malignant glioma) and improvements in diagnosis and attitudinal changes to disease in older persons.35,36 and 37 Other tumors commonly encountered in older persons include metastatic cancer, meningiomas (brain and spine), and neurilemomas, all of which have a higher incidence in persons older than 65 years. Chronic subdural hematomas occur predominantly in the very old and the very young. In recent years neurosurgeons have been increasingly willing to operate on older persons. In one series of operations for removal of a meningioma (elective first-time surgery), older persons had approximately 25% more postoperative complications, although overall, the outcome at 4 months was no different in patients aged 45 to 64 years than in those aged 65 and over.38 In one series of 103 older patients (median age, 76; range, 70 to 89) with a diagnosis of malignant supratentorial glioma, the overall outcome was worse than the outcome in younger patients; patients who were functionally impaired or over 80 years old were less likely to benefit from radiotherapy.38 Surgery is more often considered in older patients who are symptomatic or have impending major complications from the tumor. The data indicate that it is these patients who tend to have the poorest outcome. The more medically impaired or frail the patient or the more difficult the surgery, the stronger the indications for surgery must be.
Glioblastomas and metastatic tumors often present with focal or multifocal symptoms occurring over weeks to months, whereas meningiomas and neurilemomas often have a history that extends over a period of years. Glioblastomas and metastatic lesions usually occur within the hemispheres and produce characteristic deficits (e.g., hemiparesis, sensory loss, hemianopsia, aphasia). Metastatic involvement of the extradural spinal canal resulting in rapidly evolving spinal cord compression is common. Meningiomas and neurilemomas are extrinsic to the nervous system but also compress the brain or spinal cord. The myelopathy produced by metastatic lesions, meningiomas, and neurilemomas can usually be distinguished by clinical and imaging criteria.
Subacute subdural hematomas are formed within 2 weeks of an acute bleeding episode by blood breakdown, membrane formation, and accumulation of additional fluid, forming a mass. The symptoms associated with subacute and chronic subdural hematoma evolve over days to weeks. A substantial portion of older persons (30%) have no history of head trauma, and one quarter are taking antithrombotic medications (warfarin [Coumadin], heparin, or platelet antiaggregants).39 Subdural hematomas may become quite large, compressing the hemispheres over a wide area and producing both diffuse (e.g., headache, delirium) and focal findings. Although subdural hematomas may resolve on their own, patients who are symptomatic should have surgical treatment. In two recent studies that evaluated the clinical factors associated with mortality, the level of consciousness was most predictive of mortality, but age was still a factor.39,40
SPINAL CORD DISEASES
Cervical Spine
With advancing age, the water content of the nucleus pulposus, the central portion of the disk, decreases, resulting in loss of the disk space, bulging of the annulus, increased movement of the vertebral bodies, and osteophyte formation. In addition, the mobility of the cervical spine, in particular the C5 to C6 interspace, predisposes the patient to degenerative joint changes. As a result, patients develop radiculopathy, myelopathy, or a combination of both. Acute cervical radiculopathy is usually caused by disk herniation. It rarely occurs after the age of 50. When radiculopathy secondary to degenerative spine disease occurs in older people it is usually secondary to spondylitic changes. It presents with neck pain that radiates to one or both arms. Irritation of the C6 root causes paresthesias over the thumb and index finger, whereas a C7 lesion involves the middle three fingers. Associated numbness and weakness may be present. Deep tendon reflexes corresponding to the involved nerve roots may be depressed. A history of prior similar episodes that have resolved is often present in patients with spondylitic radiculopathy. Neck movements may be restricted.
Chronic cervical myelopathy results in a spastic paraparesis. Although they are sometimes present, sensory symptoms and urinary dysfunction are not prominent. A cervical radiculopathy is often present. Examination may reveal signs of spastic paraparesis with diminished reflexes in the upper extremities.
The differential diagnosis of cervical radiculopathy includes primary or metastatic tumors in the cervical region, lesions of the brachial plexus (e.g., Pancoast’s tumor), and mononeuropathy (e.g., carpal tunnel syndrome). The differential diagnosis of cervical myelopathy includes cervical tumors, combined system disease, and motor neuron disease. Radiographic evaluation includes spinal radiographs, MRI, and CT myelography.
A trial of analgesics, rest, and use of a soft collar should first be tried in patients with cervical radiculopathy. If this treatment is not beneficial, surgical intervention may be indicated. Surgical decompression is often used for cervical myelopathy, although in patients with high-risk medical conditions and slowly progressive myelopathy, immobilization with a collar may be preferred.41
Motor Neuron Disease
Motor neuron disease (MND, amyotrophic lateral sclerosis [ALS]) is produced by degeneration of the anterior horn and cortical motor neurons that results in asymmetrical limb weakness, atrophy, bulbar signs and symptoms, and pyramidal tract dysfunction. The diagnosis can be suspected from the history based on the evolution and distribution of weakness and is supported by the combination of upper and lower motor neuron signs. Patients may also report paresthesias, pain, and muscle cramps.42 The presence of electromyographic (EMG) evidence of chronic denervation in the absence of neuropathy further supports this diagnosis. Occasionally nerve or muscle biopsy (or both) are required. Progression of the weakness, which is variable, is a feature of the illness. The differential diagnosis of MND includes neoplastic disease of the brain stem and spinal cord, cervical spondylosis, multiple sclerosis, and neuropathy and myopathy. The time course as well as other associated clinical and laboratory features allows the correct diagnosis. In addition to EMG studies, other tests that should be considered include a complete blood count, erythrocyte sedimentation rate, serum chemistries, muscle enzymes (creatine kinase, alanine amino transferase), cryoglobulins, serum protein electrophoresis, urinalysis, chest radiograph, CSF examination, head and spine MRI, and myelography.43
Pathologically, the primary feature of MND is the degeneration and loss of the anterior horn and cortical motor neurons. Glial replacement also occurs, resulting in atrophy of the spinal cord and motor cortex as well as gliosis of the lateral columns of the spinal cord.
The etiology of MND remains unknown, although in familial cases abnormalities in the superoxide dismutase gene suggest the possibility of oxidative cell death.44
Symptomatic therapy is of great value in augmenting both the quality and duration of life. Treatments to slow the progression of the disease are being developed. Riluzole, a glutamate antagonist, has shown marginal benefit in prolonging survival, and insulin growth factor has also shown some promise.45
NEUROMUSCULAR DISEASE
Neuropathy
Peripheral neuropathies may affect predominantly the sensory fibers, motor fibers, or a combination of both. The underlying pathologic process may be demyelination, or it may involve the axon (axonopathy). Electrophysiologic studies are valuable in characterizing the neuropathy and quantifying its extent and severity, although they rarely provide a precise diagnosis. The rate of progression, modality (motor, sensory, mixed, or autonomic), pattern of nerve involvement, past medical history, and laboratory evaluation often allow a correct diagnosis. Following is an overview of three of the neuropathies most often seen in the elderly population.
About 15% of patients with diabetes mellitus have both signs and symptoms of neuropathy. Onset usually occurs after age 50. Several clinical patterns have been identified,46 although the slowly progressive, distal, symmetrical, predominantly sensory, lower extremity neuropathy is commonly encountered. The axon is the primary site of involvement. In general, patients who are able to maintain strict control of blood glucose levels have fewer neuropathic complications.
Uremic neuropathy presents as a slowly progressive, distal symmetrical, sensorimotor neuropathy whose initial symptoms include numbness or tingling in the legs.47 Burning dysesthesias in the feet may occur. Motor symptoms begin with distal lower extremity weakness. The condition occurs in at least 60% of patients on dialysis. Electrophysiologic and pathologic studies have shown that the condition is an axonopathy with secondary demyelination. The neuropathy is probably produced by toxins, usually excreted by the kidneys. Renal transplantation may result in resolution of the neuropathy, although recovery may be incomplete. Chronic hemodialysis may halt progression or improve the neuropathy.48
Guillain-Barré syndrome (GBS) or acute inflammatory demyelinating polyneuropathy (AIDP) is presumably the result of an aberrant immune response to a preceding infection or other trigger.49 It has an annual incidence of up to 2 cases per 100,000 population. The condition often begins with paresthesias in the toes and fingers, followed over a period of days by weakness of the lower extremities. Arm, facial, and oropharyngeal weakness may follow. Pain, which is described as aching or sciatica, is common. Neurologic examination reveals symmetrical weakness, absent or diminished deep tendon reflexes, and little loss of sensation despite the presence of paresthesias. In severe cases, respiration, deglutition, and autonomic function may be affected. Progression of weakness reaches a plateau in 1 to 3 weeks. Approximately two thirds of cases occur following an infection, usually a viral upper respiratory tract infection. Complete or near-complete recovery over a period of weeks or months is seen in the majority of patients.
Nerve conduction abnormalities indicating demyelination of the roots and proximal nerves are the most specific and sensitive laboratory findings in GBS. To demonstrate these abnormalities, one must request a specific neurophysiologic test that examines proximal nerve function (i.e., F waves and H reflexes). This test has supplanted the CSF examination, which reveals an elevated protein concentration and few or no cells, as the primary diagnostic tool.
Patients with GBS should be observed in the hospital. Those with very mild cases involving only distal paresthesias and mild limb weakness may not need treatment, but it is advisable to wait approximately 2 weeks before concluding that there will be no progression. Patients with a declining vital capacity or cardiovascular dysautonomia should be observed in an intensive care unit.
Plasma exchange is an effective treatment for GBS, although intravenous immunoglobulin (IVIG) has become the preferred treatment because of its relative safety and equivalent efficacy.50 Corticosteriods are of no benefit in the treatment of GBS.
Neuromuscular Transmission
Myasthenia gravis is produced by impaired cholinergic transmission due to autoimmune destruction of the nicotinic receptors of the motor end plates. In addition to its high incidence in young women, myasthenia gravis also occurs frequently in older men. The usual symptoms, which may be accentuated by fatigue, include diplopia, ptosis, dysarthria or dysphagia, and weakness. Once suspected, the diagnosis can be confirmed by the occurrence of improvement following an intravenous dose of a short-acting anticholinesterase agent (edrophonium). Elevated cholinergic receptor antibodies and EMG may be useful in supporting the diagnosis. Other autoimmune problems (e.g., thyroiditis, systemic lupus erythematosus) as well as thymoma may be present in these patients. Effective treatment options include anticholinesterases, thymectomy, steroids, and plasmapheresis.
Myopathy
Myopathies result in weakness of the proximal muscles and cause difficulties in arising from a chair or climbing stairs. The medical history may indicate the presence of an endocrinopathy, collagen vascular disease, or cancer. The presence of myopathic findings on EMG confirms the clinical impression. Laboratory evaluation should include creatine kinase determination, erythrocyte sedimentation rate, serum electrolytes, phosphorus and calcium levels, complete blood count, liver enzymes, and thyroid function tests. Muscle biopsy is used to confirm the presence of a specific myopathy for which no other diagnostic test will suffice (e.g., polymyositis or inclusion body myositis).
Idiopathic inflammatory myopathies are the most common histologically proven muscle diseases affecting the elderly. The incidence of dermatomyositis and polymyositis is 2 to 5 per million. The peak incidence of polymyositis occurs in the fifth decade, whereas dermatomyositis peaks in childhood as well as in the fifth decade. Females are more frequently affected than males.
Both conditions typically present with a subacute to chronic progression of proximal weakness. The neck flexors are commonly affected, whereas the facial, respiratory, and extraocular muscles are not. Patients may report myalgias and dysphagia. Patients affected by dermatomyositis have a butterfly facial rash or a rash over the knuckles. They may develop cardiomyopathy, interstitial lung disease, or gastric ulcers. Connective tissue diseases are present in 20% of cases. In 10% to 15% of cases there is an associated malignancy.51 Diagnosis is based on the clinical features, myopathy on EMG, elevated creatine kinase, and histologic evidence of muscle inflammation and necrosis.
Treatment consists of steroid therapy (prednisone 60 to 100 mg/day), the length of therapy being determined by improvement in strength, a decrease in creatine kinase levels, and the occurrence of side effects. Most patients require low-maintenance doses of prednisone for years. Immunosuppressive agents such as azathioprine are sometimes required in patients who do not respond to corticosteroid therapy or in whom such therapy is contraindicated. IVIG may be useful in patients with dermatomyositis.52
Two thirds of patients improve with corticosteroid therapy and have no functional deficits at 3-year follow-up. In patients without cancer, the 5-year mortality ranges from 11% to 25%. Patients with dysphagia or severe weakness have a less favorable outcome.
Inclusion body myositis is another idiopathic inflammatory myopathy that is seen predominantly in the older population; its onset occurs after 50 years of age. Men are affected more frequently than women. Patients present with a slowly progressive, painless weakness that involves both distal and proximal muscles. Dysphagia is a common component. Muscle enzymes may be normal or mildly elevated. EMG is myopathic. Muscle biopsy reveals marked variation in fiber size, endomysial inflammation, grouped atrophy of muscle fibers, and fibers with rimmed vacuoles containing amyloid and abnormal filamentous material. Unlike the idiopathic inflammatory myopathies, inclusion body myositis does not usually respond to immunosuppressive therapy, although a trial of corticosteroids is reasonable. IVIG may be of benefit.53
CHAPTER REFERENCES

1.
Rubin EH, Kinscherf DA, Morris JC: Personality and dementia. Bull Clin Neurosci 1989;54:88–94.

2.
Rees TS, Ducker LG: Auditory and vestibular dysfunction in aging. In Hazzard WR, Andres R, Beirman EL, Blass JP (eds): Principles of Geriatric Medicine and Gerontology. New York, McGraw-Hill, 1990, pp. 432–44.

3.
Welford AT: Reaction time, speed of performance and age. Ann NY Acad Sci 1988;515:1–17.

4.
Stalberg E, Borges O, Ericsson M, Essen-Gustavsson B, Fawcett PRW, Nordesjo LO, Nordgren B, Uhlin R: The quadriceps femoris muscle in 20–70 year old subjects: Relation between knee extensor torque, electrophysiologic parameters and muscle fiber characteristics. Muscle Nerve 1989;12:382–389.

5.
Frontera WR, Hughes VA, Lutz KJ, et al: A cross-sectional study of muscle strength and mass in 45- to 78-year-old men and women. J Appl Physiol 1991;71:644–650.

6.
Wolfson L, Whipple R, Derby CA, Amerman P, Murphy T, Tobin JN, Nashner L: A dynamic posturography study of balance in healthy elderly. Neurology 1992;42:2069–2075.

7.
King MB, Judge JO, Wolfson L: Functional base of support decreases with age. J Gerontol Med Sci 1994;48:M258–M263.

8.
Bohannon RW, Larkin PA, Cook AC, Gear J, Singer J: Decrease in timed balance test scores with aging. Phys Ther 1984;64:1067–1070.

9.
Klawans HL, Tufo HM, Ostfeld AM: Neurologic examination in an elderly population. Dis Nerv Syst 1971;32:274–279.

10.
Jacobs L, Gossman MD: Three primitive reflexes in normal adults. Neurology 1980;30:184–188.

11.
Longstreth WT Jr, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA, Enright PL, O’Leary D, Fried L: Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. Stroke 1996;27:1274–1282.

12.
Baloh RW, Yue Q, Socotch TM, Jacobson KM: White matter lesions and disequilibrium in older people. l. Case-control comparison. Arch Neurol 1995;52:970–974.

13.
Masdeu JM, Wolfson L, Lantos G, Tobin J, Grober E, Whipple R, Amerman P: Brain white matter changes in the elderly prone to falling. Arch Neurol 1989;48:417–420.

14.
Baloh RW, Vinters HV: White matter lesions and disequilibrium in older people. II. Clinicopathologic correlation. Arch Neurol 1995;52:975–981.

15.
Vanneste J: Three decades of normal pressure hydrocephalus: Are we wiser now?. J Neurol Neurosurg Psychiatry 1994;57:1021–1025.

16.
Turner D, McGeachie R: Normal pressure hydrocephalus and dementia—Evaluation and treatment. Clin Geriatr Med 1988;4(4):815–830.

17.
Ahlberg J, Norlen L, et al: Outcome of shunt operation on urinary incontinence in normal pressure hydrocephalus predicted by lumbar puncture. J Neurol Neurosurg Psychiatry 1988;51:105–108.

18.
Vanneste JAL, Augustin P, Davies GA, Blomstrand C: Shunting normal pressure hydrocephalus: Do the benefits outweigh the risks? A multicenter study and literature review. Neurology 1992;42:54–59.

19.
Hauser WA, Annegers JF, Kurland LT: Prevalence of epilepsy in Rochester, Minnesota: 1940–1980. Epilepsia 1991;32:429–445.

20.
Hauser WA, Annegers JF, Kurland LT: Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia 1993;34:453–468.

21.
Drury I, Beydoun A: Seizure disorders of aging: Differential diagnosis and patient management. Geriatrics 1993;48:52–58.

22.
Scheuer ML, Cohen J: Seizures and epilepsy in the elderly. Neurol Clin 1993;11:787–804.

23.
Luhdorf K, Jensen LK, Plesner AM: Epilepsy in the elderly: Prognosis. Acta Neurol Scand 1986;74:409–415.

24.
Rosenkopf KL: Current concepts concerning the etiology and treatment of trigeminal neuralgia. Craniomandib Pract 1989;7:312–318.

25.
Farago F: Trigeminal neuralgia: Its treatment with two new carbamazepine analogues. Eur Neurol 1987;26(2):73–83.

26.
Janetta PJ: Microvascular decompression for trigeminal neuralgia. Surg Rounds 1983;6:24–35.

27.
Frederiks JAM: Transient global amnesia. Clin Neurol Neurosurg 1993;95:265–283.

28.
Zorzon M, Antonutti L, Mase G, Biasutti E, Vitrani B, Cazzato G: Transient global amnesia and transient ischemic attacks: Natural history, vascular risk factors and associated conditions. Stroke 1995;26:1536–1542.

29.
Hodges JR, Warlow CP: The aetiology of transient global amnesia. A case control study of 114 cases with prospective follow up. Brain 1990;113:639–657.

30.
Zinelli P, Nasuto S, Miari A: Transient global amnesia: Case reports. Ital J Neurol Sci 1988;9(Suppl 9):19–20.

31.
Friend HC: Transient global amnesia (letter). Neurology 1987;37:1889–1890.

32.
Hinge HH, Jensen TS: The prognosis of transient global amnesia. In Markowitsch HJ (ed): Transient Global Amnesia and Related Disorders. Toronto, Hogrefe & Huber, 1990, pp. 172–180.

33.
Baloh RW, Honrubia V, Johnson K: Benign positional vertigo: Clinical and oculographic features in 240 cases. Neurology 1987;37:371–378.

34.
Gomez CR, Cruz-Flores S, Malkoff MD, Sauer CM, Burch CM: Isolated vertigo as a manifestation of vertebrobasilar ischemia. Neurology 1996;47:94–97.

35.
Boyle P, Maisonneuve P, Saracci R, Muir CS: Is the increased incidence of primary malignant brain tumors in the elderly real? J Natl Canc Inst 1990;82:1594–1596.

36.
Bodan B, Wegner DK, Feldman JJ, et al: Increased mortality from brain tumors: A combined outcome of diagnostic technology and change of attitude towards the elderly. Am J Epidemiol 1992;135:1349–1357.

37.
Meckling S, Dold O, Forsyth PAJ, Brasher P, Hagen NA: Malignant supratentorial glioma in the elderly: Is radiotherapy useful? Neurology 1996;47:901–905.

38.
Maurice Williams RS, Kitchen N: The scope of neurosurgery for elderly people. Age Ageing 1993;22:337–342.

39.
Rozzelle CJ, Wofford JL: Predictors of hospital mortality in older patients with subdural hematoma. J Am Geriatr Soc 1995;43:240–244.

40.
Krupp WF: Treatment of chronic subdural hematoma with burr-hole craniotomy and closed drainage. Br J Neurosurg 1995;9:619–627.

41.
Cartlidge N, Al-Hakim M, Bradley W: Disorders of bones, joints, ligaments, cartilage, and meninges. In Bradley W, Waroff R, Finichel G, Marsden C (eds): Neurology in Clinical Practice, 2nd ed. Boston, Butterworth-Heinemann, 1996, pp. 1804–1806.

42.
Gubbay SS, Kahana E, Zilber N, Cooper G, Pintov S, Leibowitz Y: Amyotrophic lateral sclerosis: A study of its presentation and prognosis. J Neurol 1985;232:295–300.

43.
Williams DB, Windebank AJ: Motor neuron disease (amyotrophic lateral sclerosis). Mayo Clin Proc 1991;66:54–82.

44.
Siddique T, Figlewicz DA, Pericak-Vance MA, Haines JL, Rouleau G, Jeffers AJ, Sapp P, Hung WY, Bebout J, McKenna-Yasek D, et al: Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N Engl J Med 1991;324:1381–1384.

45.
Bensimon G, Lacomblez L, Meininger V, and ALS/Riluzole Study Group: A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med 1994;330:585–591.

46.
Adams R, Victor M: Diseases of the peripheral nerves. In Principles of Neurology, 5th ed. New York, McGraw–Hill, 1993, p. 1136.

47.
Asbury AK: Neuropathies with renal failure, hepatic disorders, chronic respiratory insufficiency and critical illness. In Dyck PJ, Thomas PK, Griffin JW, Low PA, Paduslo JK (eds): Peripheral Neuropathy, 3rd ed. Philadelphia, WB Saunders, 1993, pp. 1251–1265.

48.
Fraser CL, Arieff A: Nervous system complications in uremia. Ann Intern Med 1988;109:143–153.

49.
Ropper AH: The Guillain-Barré syndrome. N Engl J Med 1992;326:1130–1136.

50.
Van Der Meche FGA, Schmitz PIM, and the Dutch Guillain-Barré Study Group: A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. N Engl J Med 1992;326:1123–1129.

51.
Sigurgeirsson B, Lindelof B, Edhag O, Allander E: Risk of cancer in patients with dermatomyositis or polymyositis. N Engl J Med 1992;326:363–367.

52.
Dalakas MC, Illa I, Dambrosia JM, et al: A controlled trial of high dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1993–2000.

53.
Soueidan SA, Dalakas MC: Treatment of inclusion body myositis with high dose intravenous immunoglobulin. Neurology 1993;43:876–879.

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