CHAPTER 43—NEUROLOGIC DISEASES AND DISORDERS
A number of neurologic signs increase in frequency with age. One study of nearly 500 older adults noted that, among those over the age of 84 years, the following signs could not be attributed to a medical or a neurologic disease: diminished arm swing (present in 29% of those examined), diminished toe vibration sense (21%), hyperreflexia in arms (10%), unequal nasolabial folds (9%), absent pupillary response (9%), Babinski’s sign (7%), diminished toe position sense (7%), and reduction in arm strength (5%). One implication of these findings is that the diagnosis of neurologic disease may be more difficult in the setting of these “normal” signs.
Stroke is a leading cause of disability and death. The incidence of stroke increases with advancing age, approximately doubling with each decade. The incidence of stroke for men is 2.1 per 1000 at ages 55 to 64 years, 4.5 per 1000 at ages 65 to 74 years, and 9.3 per 1000 at ages 75 to 84 years. The incidence of stroke in women is 25% to 30% lower than that of men in comparable age groups, but it surpasses that of men in the group who are ≥ 85 years old.
Throughout the latter half of the century the incidence of stroke has decreased. This decline may be attributable to better control of modifiable risk factors. These risk factors include hypertension, heart disease, diabetes mellitus, cigarette smoking, elevated blood lipids, and alcohol use. Hypertension is the most prevalent risk factor for stroke, and its treatment results in a substantial reduction in the risk of stroke. Treatment of isolated systolic hypertension in elderly persons reduces the risk of stroke by nearly 40%. (See Hypertension.) Heart disease is also an important risk factor for stroke, including atherosclerotic coronary heart disease, left ventricular hypertrophy, valvular heart disease, valve replacement, and valvular and nonvalvular atrial fibrillation. (See Cardiovascular Diseases and Disorders.) Several studies have confirmed a two- to fourfold increased risk of stroke in patients with diabetes mellitus. Studies have suggested that tight control of blood sugar levels reduces the risk of stroke in patients with diabetes mellitus, although the evidence is less compelling than that for reduction of other vascular complications (eg, retinopathy, nephropathy) with tight glucose control. (See Endocrine and Metabolic Disorders.) Cigarette smoking independently increases the risk of stroke as much as threefold, according to the Framingham Study. The incidence of stroke declines significantly even after 2 years of cessation of smoking, and after 5 years the level of risk returns to that of nonsmokers. Elevated blood lipids and alcohol use are other important risk factors for stroke. (See Substance Abuse.)
The fatality rate within 1 month of an acute stroke is 20% to 30% across all age groups. Survival in part depends on the location and severity of the stroke. Common causes of death are myocardial infarction, arrhythmia, congestive heart failure, all due to comorbid coronary artery disease, and aspiration pneumonia. Age in itself does not influence the gross neurologic aspects of stroke, but older age is associated with lesser recovery in activities of daily living. Older stroke patients can benefit from formal rehabilitation.
A lesion in the internal carotid artery may present as transient monocular blindness (amaurosis fugax) or a cerebral hemispheric deficit (eg, focal motor, sensory, or cognitive symptoms or signs) because both the retina and cerebral hemispheres derive their blood supply from the internal carotid artery. Cerebral hemispheric deficits may include hemiparesis, hemisensory loss, aphasia, or apraxia. The initial evaluation of patients with these symptoms or signs usually includes a neuroimaging study (computed tomography or magnetic resonance imaging) and noninvasive imaging of the carotid arteries (B-mode ultrasonography and Doppler ultrasonography or magnetic resonance angiography). Data from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) indicate that the optimal treatment for symptomatic carotid stenosis of greater than 70% is carotid endarterectomy, provided the patient has few comorbidities and the institution performs a high number of endarterectomies. The optimal treatment for symptomatic carotid stenosis of less than 70% or of asymptomatic carotid stenosis is still not clear; treatment options include carotid endarterectomy or medical management with antiplatelet agents (aspirin, clopidogrel) or anticoagulation (warfarin).
Aspirin is the mainstay of stroke prevention in cases of carotid artery disease where surgery is not indicated or is declined. Many studies on the use of aspirin in stroke prevention suggest that higher dosages than 325 mg of aspirin per day do not add therapeutic benefit, but the minimum necessary dosage has not been fully investigated. Many physicians routinely prescribe 81 to 650 mg per day; as little as 75 mg per day may be as effective, although even the lower dosage may also cause gastrointestinal irritative symptoms and blood loss. Clopidogrel 75 mg once daily is an alternative for patients who cannot tolerate aspirin. Warfarin is used for stroke prevention in elderly patients with atrial fibrillation.
Syndromes associated with vascular lesions in the posterior circulation (vertebral and basilar arteries) result in cranial nerve involvement or involvement of the descending motor or ascending sensory tracks within the brain stem. Because of the large number of pathways passing through the brain stem, vertebrobasilar occlusion may result in a myriad of syndromes, including drop attacks; abnormal eye movements; Horner’s syndrome; motor and sensory abnormalities in the face, arm, or leg; and even stupor or coma. Treatment of posterior circulation cerebrovascular disease is medical, as no surgical approach to improving the posterior circulation has been shown to improve outcomes. Many clinicians prefer warfarin anticoagulation over antiplatelet agents for patients with vertebrobasilar disease. However, no formal studies have confirmed better clinical outcomes with warfarin.
Lacunar disease, the occlusion of small penetrating vessels, is presumably the consequence of lipohyalinosis (lipid deposition and hyalinization). Lacunar strokes may result in several well-defined syndromes, including pure motor hemiplegia, pure hemisensory stroke, ataxic hemiparesis, and dysarthria–clumsy hand syndrome. Risk factors include hypertension and diabetes mellitus, and the most effective means of managing lacunar disease is aggressive treatment of these risk factors. Many clinicians prescribe aspirin for stroke prevention in patients who have suffered lacunar strokes, although it has not been shown to prevent lacunar strokes specifically. Lacunar strokes may occur independently or concurrently with large-vessel cerebrovascular disease.
Intracerebral hemorrhage accounts for 15% to 20% of all strokes. Approximately 80% occur during the 40s, 50s, and 60s. A racial distribution suggests that black Americans and Chinese Americans may be at slightly higher risk than white Americans.
The most common cause of intracerebral hemorrhage is hypertension, which accounts for 75% to 80% of the cases. Excessive use of alcohol is also associated with a higher incidence. Common locations for hypertensive bleeds are the putamen, thalamus, cerebellar hemisphere, pons, and cerebrum. Treatment is primarily control of hypertension and supportive care. In elderly patients a common cause of cerebral lobar hemorrhage is cerebral amyloid angiopathy, which usually occurs without systemic amyloidosis. In these cases intracranial bleeds tend to be recurrent. Acute treatment is supportive; prevention is limited to controlling hypertension.
The current protocol for acute care of the elderly stroke patient includes optimizing hydration status; controlling blood pressure while avoiding acute hypotension; preventing deep-vein thrombosis; detecting and treating coronary ischemia, congestive heart failure, and cardiac arrhythmias; and initiating full anticoagulation in patients with nonhemorrhagic embolic strokes. For large embolic strokes (eg, involving most of the middle cerebral artery territory or involving both middle and anterior cerebral artery territories), one generally waits 48 hours before beginning anticoagulation. Dehydration on presentation is common, but rehydration must be gradual because of the risk of fluid overload. In patients with clinically evident cerebrovascular disease immediately after the occurrence of an ischemic cerebral infarction, it is appropriate to withhold treatment of hypertension (unless blood pressure is very high, eg, > 200/100 mm Hg) until the situation has been stabilized. Even when treatment has been withheld temporarily, the eventual goal is to reduce blood pressure gradually while avoiding orthostatic hypotension. The target systolic blood pressure should be 10 to 20 points higher than the patient’s baseline pressure; if the baseline is unknown, systolic pressure should not be lowered beyond 160 mm Hg. Patients with acute ischemic stroke who are treated with fibrinolytic agents require careful blood-pressure monitoring, especially over the first 24 hours after treatment is started. Elevated blood pressure should gradually be brought down to the upper end of the normal range. Patients with a history of ischemic heart disease or arrhythmia and patients with large strokes should be monitored by electrocardiography for several days.
Many medical centers and physicians are now using recombinant tissue–plasminogen (rt-PA) in the treatment of acute ischemic stroke. The benefits of this treatment, however, must be weighed against the increased the risk of intracranial hemorrhage, which can be fatal or can result in neurologic disability. If the patient presents within 3 hours of onset of stroke symptoms, has been assessed by a physician with expertise in stroke, and has CT evidence of less than major vessel infarction, thrombolysis with rt-PA should be considered.
A seizure is a paroxysmal excessive or hypersynchronous cerebral neuronal discharge, or both, that results in a transient change in sensation, motor function, and mental state. Recurrent seizures are the defining feature of epilepsy. Seizures may be broadly classified as partial (eg, simple focal seizures, partial complex seizures) or generalized (eg, absence attacks, generalized tonic-clonic seizures).
New-onset seizures occur in a bimodal pattern with respect to age, with an initial peak in incidence within the first year of life and a second peak after the age of 60 years. Disease-specific causes of epilepsy are more common in older adults, and one-half or more of older adult patients with new-onset epilepsy have an underlying cause. Common causes include vascular disease, neurodegenerative diseases, and brain tumors. Related to this is the observation that the incidence of partial seizures increases in older adults, whereas the incidence of generalized tonic-clonic seizures remains constant with respect to age. Beyond the age of 65, approximately one half of new-onset cases of epilepsy have a complex partial pattern. This pattern may be explained by the greater incidence of underlying focal lesions in older age groups.
Because of this propensity for new-onset cases of epilepsy to be harbingers of focal lesions, the work-up of older adults to exclude an underlying treatable cause is particularly important. The neurologic history and examination should aim to clinically characterize the seizure and localize its source, as well as elicit other signs of a focal lesion or a metabolic disturbance (eg, uremia, hepatic failure). Blood studies (blood urea nitrogen; serum levels of sodium, glucose, creatinine, magnesium, and calcium; and liver function tests), neuroimaging studies, and electroencephalogram (either a standard study with drowsiness or sleep, if possible, or a longer term 24- to 48-hour ambulatory monitoring) play important roles.
The treatment of epilepsy in older adults is particularly challenging, for a variety of reasons. First, the prevalence of adverse drug-disease and drug-drug interactions increases with age. For example, because of the tendency of lamotrigine to prolong the PR interval on the electrocardiogram, caution should be used when using it in patients with concomitant cardiac disease. Cimetidine and propranolol increase the serum concentrations of phenytoin and carbamazepine, respectively. Second, age-related changes in renal and hepatic function may alter drug metabolism significantly, so that older adults must often be placed on lower doses of antiepileptic drugs (AEDs). A sizable fraction of many AEDs is bound to plasma-binding proteins (eg, albumin). Since aging causes a reduced synthesis of albumin, it may be important to monitor free (unbound) levels of AEDs (eg, phenytoin). Third, older adults may be particularly sensitive to medication side effects. For example, AEDs may intensify an underlying dementia or exacerbate mild cognitive decline. Finally, there are a variety of reasons why older adults may have difficulty with adherence. It is particularly important in treating older adults to involve caregivers so that the goals of the treatment, side effects, and monitoring of progress may be understood.
There are a variety of AEDs, and most must be started slowly and the dose increased gradually (see Table 43.1). Reduction in seizure frequency and severity and the onset of side effects are the parameters that should be followed, not the blood level. If monotherapy has not adequately controlled the seizures and the dose has been maximized, then add-on therapy may be tried. Epilepsy surgery has become an increasingly common choice of patients whose seizures have proven refractory to pharmacologic management. Discontinuing AEDs should be considered if the patient has not had a seizure for several years, particularly if the original seizure activity was a single or poorly characterized event.
There is evidence to suggest that the prevalence of headaches diminishes with age. One study demonstrated that although 74% of men and 92% of women between the ages of 21 and 34 years had headaches, these proportions dropped to 22% and 55% after the age of 75 years. Headache is one of the most common medical complaints in young persons, and yet one study suggests that it is the 10th most common symptom in older women and the 14th most common symptom in older men. Headache incidence also declines with age; only 2% of all sufferers of an initial migraine are over the age of 50 years.
Persistent headaches are more likely to represent systemic or intracranial lesions (ie, nonbenign conditions) in older adults than in younger adults. One study demonstrated that among younger patients, 10% of headaches represented systemic or intracranial lesions; in older adults, this proportion was 34%. These nonbenign conditions include intracranial masses (eg, primary or secondary tumors, subdural hematomas), cervical spondylosis, chronic obstructive pulmonary disease, carbon monoxide poisoning, and giant cell arteritis. In addition, many commonly used medications can cause headaches that are dull, diffuse, and nondescript, including vasodilators (eg, nitrates), hypotensives (eg, reserpine, atenolol, methyldopa), anti-Parkinsonian agents, and stimulants.
As in younger persons, the common primary headache disorders may be classified into migraines (with or without aura) and tension-type headaches. Migraines are often unilateral, pulsating headaches of moderate or severe intensity associated with nausea, vomiting, or photophobia. Auras, when they occur, usually precede the headache and are manifested by transient neurologic symptoms that are localizable to the cerebral cortex or brain stem. Visual phenomena are among the most common types of auras. In contrast to migraines, tension-type headaches are often more diffuse, have a pressing or a tight quality, and are not associated with nausea or vomiting.
Headaches in older adults, however, may present in atypical ways. With migraines in particular, auras tend to disappear with age, and in some individuals, the reverse occurs (headaches disappear while auras remain). The occurrence of an isolated visual or sensory aura in the absence of a headache can be diagnostically challenging in the sense that these symptoms may be signs of transient ischemic attacks as well.
The treatment of headaches may be categorized as either abortive (ie, treating an attack that has already begun) or preventive. Apart from various over-the-counter preparations, abortive therapies include ergotamines or triptans (eg, sumatriptan, zolmitriptan), which act by central serotonergic mechanisms. These medications are available as injections, tablets, or nasal sprays. Though injections have the most rapid onset and carry the highest efficacy rates, oral and nasal preparations are more convenient. Preventive therapies include β-blockers (propranolol, timolol), valproic acid, methysergide, tricyclic antidepressants, calcium channel blockers, and selective serotonin-reuptake inhibitors. The choice of an agent should be guided by an effort to avoid side effects and drug interactions.
Older adults may not be tolerate headache medications as well as younger patients do; moreover, in some older patients a medication may be contraindicated by comorbidities or existing drug regimens. For example, β-blockers and tricyclic antidepressants, which are often used as preventive therapy, may be associated with lethargy or sedation, and the use of ergotamines and sumatriptan are contraindicated for patients with coronary artery disease.
A movement disorder may be defined simply as abnormal involuntary movements. These movements are not the result of weakness or sensory deficits; they are the result of dysfunction of the basal ganglia or the extrapyramidal motor system. Movement disorders may be classified as hyperkinesias (excessive movement) or hypokinesias (paucity of movement). A particular movement disorder (eg, Parkinson’s disease) may be characterized by several types of involuntary movements (eg, tremor, bradykinesia, dystonia). Several movement disorders are especially common among older persons.
Essential tremor is the most common form of abnormal tremor. The tremor is an action tremor, which is present when the limbs are in active use (eg, while writing or while holding a cup). The tremor most commonly involves the arms, although the head and voice are also commonly involved. Other areas of the body may include the chin, tongue, and legs. The tremor is often slightly worse in one arm than in the other. One of the striking features of the tremor is that is has a varying amplitude so that during some moments the tremor is mild or even absent and during others it can be severe. The tremor disappears when the arms are relaxed, that is, when the person is sitting with hands in his or her lap or when standing or walking with arms held at the sides. Functionally, the tremor may interfere with many daily activities, such as eating, writing, or fastening buttons, and stress or anxiety can exacerbate the tremor. The frequency of the tremor is in the 4- to 12-Hz range; because age is inversely related to the frequency of the tremor, older persons have slower tremor, which is often in the 4- to 8-Hz range.
The prevalence of the disorder increases with advancing age, with as many as 1% to 5% of persons aged 60 years and older affected. The age of onset seems to have a bimodal distribution, with peaks in the teens and 20s and in the 50s through the 70s. The prevalence rates among men and women are similar, although head tremor may be more common among women.
Between 17% and 100% of affected persons report having an affected relative, which suggests that there is a familial form of the tremor. In some families, many individuals are affected over several generations. Familial forms of the tremor have been linked to regions on chromosomes 2p and 3q. There are no apparent clinical differences between the familial and sporadic forms of essential tremor. The cause of the sporadic form of the illness is not known; age is the only known risk factor for essential tremor.
It may be difficult to distinguish essential tremor from several other conditions. Physiologic tremor, which is present in all people, varies in amplitude, and it may be more noticeable in some individuals. It may also be enhanced by anxiety, stimulants, hypoglycemia, medications, or certain illnesses (eg, hyperthyroidism). The tremor is often faster than that of essential tremor (8 to 12 Hz) and the amplitude lower. Inertial loading during a tremor analysis recording may also reveal differences between the two conditions. Although patients with Parkinson’s disease most typically have a tremor at rest, they may also have an action tremor, and in some instances have only an action tremor. In addition, if essential tremor is severe enough, it may even be present at rest. However, other features of Parkinson’s disease (bradykinesia and rigidity) should not be present in persons with essential tremor.
The main indications for treatment of essential tremor are embarrassment and disability. The latter may manifest itself either as difficulty performing certain tasks such as eating and writing, the use of two hands to perform these tasks, modification in the way the task is performed (eg, only drinking with a straw out of closed cups), and even avoidance of certain tasks. Initial therapy includes β-blocking agents (eg, propranolol, atenolol), primidone, phenobarbital, diazepam, and newer agents, including gabapentin and clozapine. The response to these agents is patchy (ie, some patients experience moderate to marked improvement, whereas others experience none), and the tremor is rarely reduced to asymptomatic levels. Depression and male impotence are side effects of propranolol (less so with atenolol), and β-blockers are contraindicated for those with asthma. Primidone, phenobarbital, and diazepam are associated with unwanted sedation. Clozapine has been shown to be effective in one placebo-controlled trial, but there is a need to monitor the white blood cell count weekly because of the risk of agranulocytosis. Gabapentin has shown mixed results in placebo-controlled trials but is an attractive option, given the paucity of drug interactions or side effects. Some patients with severe, medically refractory tremor may undergo deep brain (thalamic) stimulator surgery in which the VIM nucleus of the thalamus is stimulated at high frequency with an implanted electrode. The treatment has been shown to be highly effective in controlling tremor.
Parkinson’s disease is a progressive neurodegenerative disease in which cell death in the substantia nigra and consequent reduction in brain dopamine levels results in a constellation of signs, including tremor at rest, bradykinesia, rigidity, and postural instability. The pathologic hallmark of the disease is the Lewy body, an intracellular inclusion body found in the substantia nigra.
The incidence increases dramatically with age, and the incidence rate among people in their 70s and 80s in the United States is approximately 200 cases per 100,000 (0.2%). The incidence among those in their 70s and 80s in other countries (Iceland, India, Scotland, Australia) has been estimated to be even higher, approaching 1000 to 2000 per 100,000 (1% to 2%). The disease most commonly appears between the ages of 50 and 79 years. In a small proportion of cases, the disease clusters within families and has a genetic basis. In a small number of these families, the disease has been linked to a region on the long arm of chromosome 4 that encodes the neuronal protein α-synuclein. In addition, environmental toxins (eg, manganese and pesticides) have been associated with some forms of the disease.
The disease begins insidiously and asymmetrically. The clinical manifestations include tremor, usually in one hand or sometimes in both, classically involving the fingers in a pill-rolling motion. The tremor (usually 3 to 5 Hz) is present at rest and usually decreases with active, purposeful movement. Muscular rigidity is usually readily evident on passive movement of a limb. Passive movement may demonstrate a smooth resistance or superimposed ratchet-like jerks (cogwheel phenomenon). The term bradykinesia is often used to describe either a slowness in initiating movement (ie, a paucity of spontaneous movements) or movements themselves that are slow, and the term freezing is used to describe sudden interruption of movement. Tachykinesia, which is the tendency for movements to become smaller and faster, may accompany speech (tachyphemia is the tendency during a sentence to speak more and more rapidly until all of the words run together into a mumble), handwriting (as the person attempts to draw loops across a page, the loops become smaller and tighter), gait (festination is the process by which the steps may inadvertently quicken and become smaller, and the patient may break into a run), and rapid finger taps in which the amplitude of the movements lessen and the movements become more rapid until the fingers seem stuck together. Postural abnormalities are evident in the erect and sitting positions; an erect posture is not readily assumed or maintained. The head tends to fall forward on the trunk. The tendency to fall forward (propulsion) or backward (retropulsion) results from the loss of postural reflexes. Bradykinesia prevents the patient from stopping the fall, either by taking a step or moving the arms. The face can become mask-like, with lack of expression and diminished eye blinking. Micrographia and difficulty with activities of daily living (eg, tying shoes) often develop.
Mood abnormalities, usually depression or anxiety, are common, as is cognitive impairment and dementia. These may place severe restrictions on the medications that might be used to relieve the tremor, bradykinesia, and rigidity.
One of the diagnostic challenges may be distinguishing mild early parkinsonism from the changes that often accompany normal aging (slowing down, loss of balance, stiffness, difficulty walking, stooped posture). However, the bradykinesia and rigidity of Parkinson’s disease are usually asymmetric at onset, with one side slightly affected and the other remaining normal. In addition, tremor at rest is not a feature of normal aging, and although elderly persons may complain of stiffness, true extrapyramidal rigidity is uncommon.
The diagnosis is made clinically, although deoxyglucose positron emission tomography (FDG-PET) scan of the brain often reveals an abnormal pattern of increased glucose metabolism in the globus pallidum, which is characteristic of Parkinson’s disease.
Treatment programs should be individualized. This caution applies especially to elderly patients, who have reduced tolerance for dopaminergic and anticholinergic agents, the mainstays of parkinsonism therapy. Nonpharmacologic therapy includes a regular exercise program. An elderly patient who is limber and active will have more reserve when facing a disease associated with progressively increasing stiffness and slowness. Many elderly patients benefit from a course of physical therapy aimed at restoring their confidence in walking and maintaining balance, as well as teaching them simple tricks to help them manage unpredictable and disabling freezing episodes, and, when needed, selecting a cane or walker of the appropriate size and weight. A home visit by an occupational therapist may help to plan the appropriate placement of wall rails, grab bars, and other such assistive devices that reduce the possibility of falling.
Treatment of the motor manifestations of parkinsonism is important, but many elderly patients also complain of difficulty with constipation and insomnia. Constipation is particularly bothersome to elderly patients taking levodopa, which tends to exacerbate the constipation associated with reduced levels of physical activity. Treatment includes a diet rich in fruit and fiber, prune and other juices, frequent consumption of liquids, and use of medications. It is important to emphasize to patients that they should take medications for constipation on a daily basis as part of a regular routine and not wait to take the medications as a response to severe constipation. One medication that is particularly effective is senna concentrate, one to six tablets per day. Elderly Parkinson’s disease patients with insomnia should also be given individualized treatment. Some patients wake up at night because of a low dopamine state, which results in feelings of stiffness, malaise, low energy, and doom that are severe enough to awaken the patient from a light sleep. Higher bedtime doses of levodopa or even sustained-release forms of levodopa are appropriate. Patients may also experience insomnia because they are sleeping too much during the day, which may be a side effect of levodopa therapy. In these cases, it may be important to reduce the dosage of levodopa and correct the reversed sleep-wake cycle. Because urinary urgency may be a feature of Parkinson’s disease, many patients must wake up at night to micturate, and this may be the cause of their frequent night-time awakenings.
Depression is also a common feature of parkinsonism. However, the side effects of many antidepressant medications limit their use, particularly the anticholinergic side effects of tricyclic antidepressants. The selective serotonin-reuptake inhibitors (including fluoxetine, sertraline, paroxetine) are preferred because of their favorable side-effect profiles.
The major factor impacting the treatment of elderly patients with Parkinson’s disease is their propensity to develop confusion and toxic psychosis on antiparkinsonian medications. In general, the therapeutic regimen should be kept simple. Rather than prescribing small doses of multiple medications, prescribe higher doses of one or two medications; toxic side effects are less likely to occur. Levodopa provides the most improvement in the motor manifestations of Parkinson’s disease relative to its toxic side effects on the central nervous system, whereas those with stronger anticholinergic properties (anticholinergic agents such as trihexyphenidyl and amantadine) provide the least benefit. The dopamine agonists (bromocriptine, pergolide, ropinirole, pramipexole) fall in between. Although low levels of toxic psychosis may be treated effectively with clozapine, olanzapine, or quetiapine, which have fewer extrapyramidal side effects than other antipsychotic agents, confusion and disorientation may be treated only by lowering the doses of antiparkinsonian medications. In this setting, anticholinergic medications should be the first to be discontinued, followed by selegiline, dopamine agonists, and, finally, levodopa.
The first step in treating the elderly patient with Parkinson’s disease is to accomplish dopamine replacement by using levodopa combined with carbidopa. Levodopa is converted to dopamine in both the central nervous system and the periphery. To reduce peripheral conversion, use levodopa combined with carbidopa (a peripheral decarboxylate inhibitor), which does not cross the blood-brain barrier. Treatment usually begins with a half tablet of the 25:100 combination (ie, 25 mg carbidopa to 100 mg levodopa) once or twice a day. Every 1 to 2 weeks, the dose can be increased by one half to one tablet, to reach a dose of one full tablet three times a day, if needed and if side effects are tolerable. If disabling bradykinesia, rigidity, postural instability, or tremor are still present, the dose can be gradually increased further, with cautious observation of side effects. Older adults, particularly if cognitively impaired, rarely tolerate more than 1000 mg per day of levodopa. Common side effects include nausea, abdominal cramping, orthostatic hypotension, and confusion. A controlled-release form (25:100 and 50:200) generally requires a slightly higher total daily dose. Although levodopa is generally very effective in treating idiopathic Parkinson’s disease, it is less effective in treating symptoms of secondary parkinsonism, which usually requires higher doses to achieve a mild benefit.
Levodopa-carbidopa is often given in combination with dopamine agonists (eg, bromocriptine, pergolide, ropinirole, pramipexole), although these other drugs may also be used as single therapies. A cautious induction period with each is required, as nausea, orthostatic hypotension, and confusion are common side effects. Bromocriptine is begun with 1.25 mg per day and gradually increased by 1.25-mg increments every 2 to 5 days, to a total daily dose of 10 to 30 mg. Pergolide is begun at 0.05 mg per day, with increments of 0.05 mg every 2 or 3 days until a daily dose of 1 to 3 mg is reached. Other newer dopamine agonists include ropinirole (given in starting dosages of 0.25 mg per day and increased as needed to dosages of 3 mg per day) and pramipexole (given in starting dosages of 0.125 mg per day and increased as needed to dosages of 4.5 mg per day). The latter two have been associated with sudden sleep attacks in which patients fall asleep at the steering wheel while driving. COMT (catechol O-methyltransferase) inhibitors such as tolcapone extend the benefit of levodopa-carbidopa by inhibiting the metabolic breakdown of dopamine.
Amantadine, a drug particularly useful for treating tremor, is generally prescribed at 100 mg two to three times daily. Amantadine’s mild anticholinergic effects appear to play a role in its antiparkinsonian effects. It also promotes dopamine release in the corpus striatum.
Selegiline (a monoamine oxidase-B inhibitor) in dosages of 5 mg twice a day may be used in an early stage to prevent or slow disease progression. The drug inhibits oxidative metabolism of dopamine. Trials indicate that selegiline can delay the need for additional antiparkinsonian agents. However, whether selegiline slows the disease progression or just suppresses symptoms is controversial. The drug is generally well tolerated, although some patients may experience side effects, including nausea, insomnia, confusion, anxiety, and feeling “revved up.” Although chemically related to other monoamine oxidase inhibitors, selegiline does not require dietary restrictions.
A new approach to replenishing the dopamine deficit by transplantation or grafting of fetal nigral cells to the corpus striatum shows promise, although data from a double-blinded, placebo-controlled trial are still being collected. Nigral cells harvested from aborted fetuses are stereotactically inserted in the striatum of patients with Parkinson’s disease. These cells appear to remain viable, to form neural connections, and to be capable of producing dopamine. Other surgical therapies include stereotactic pallidotomy (primarily to reduce severe dyskinesias as well as improve bradykinesia and rigidity) and either thalamotomy or implantation of deep brain (thalamic) stimulator electrodes to treat disabling, pharmacologically refractory tremors.
Shy-Drager syndrome is a multisystem degenerative disease with involvement of central (preganglionic) autonomic, cerebellar, basal ganglia, pyramidal, and spinal motor neurons. The major feature differentiating Shy-Drager syndrome from Parkinson’s disease is the prominence and severity of the autonomic failure. The mean age of onset is 55 years, and more men than women are affected. No genetic predisposition has been shown. The disease is progressive, and death occurs 7 to 10 years after the onset of neurologic symptoms. Cardiac arrhythmias, aspiration, sleep apnea, and pulmonary emboli are common causes of death.
The major manifestation is autonomic insufficiency, with wide swings in blood pressure with little or no change in pulse rate. Patients complain of dizziness, lightheadedness, or syncope on standing, and of postexertional weakness, gait unsteadiness, and dimming of vision. Impaired temperature control, reduced sweating, sphincter disturbance with urinary or fecal incontinence, diarrhea, constipation, nocturnal diuresis, impotence, iridic atrophy, impaired eye movements, Horner’s syndrome, and anisocoria may also occur. Central neuron degeneration is manifested by parkinsonian features, intention tremor, ataxia, dysarthria, and, in some cases, corticobulbar and corticospinal tract signs. Anterior horn cell degeneration leads to wasting and fasciculation of distal muscles. Intellectual and emotional function is preserved until late in the disease course. Laboratory studies are usually normal. The electromyogram may show anterior horn cell involvement.
Orthostatic hypotension is often the most disabling symptom. Nonpharmacologic treatment of the autonomic dysfunction includes avoiding large meals, getting up rapidly, and excessive straining at stool. Compressive clothing and elastic stockings, increased salt and fluid intake, and sleeping in a reverse Trendelenburg position may ameliorate some of the orthostatic symptoms. Drugs that are sometimes useful in treating the orthostatic hypotension include midodrine and fludrocortisone. Use of these medications sometimes results in supine hypertension so that blood pressure needs to be monitored closely. Treatment of the parkinsonism with dopamine agonists or with levodopa usually worsens the orthostatic hypotension.
Progressive supranuclear palsy is a rare disorder characterized by parkinsonian symptoms, a supranuclear gaze palsy, square wave jerks (defined next page), and cognitive impairment. Approximately 4% of patients with parkinsonism have progressive supranuclear palsy. Onset usually occurs during or after the 50s. The pathogenesis is unknown. Evidence of a transmissible cause is lacking, and familial cases are rare. The disease usually progresses rapidly, with marked incapacity occurring within 3 to 5 years and death within 10 years, generally as a result of intercurrent infection or other complications of immobility.
Pathologic examination shows degenerative changes in the brain stem, diencephalon, basal ganglia, and cerebral cortex. Microscopic findings include nerve cell loss and neurofibrillary tangles, which are different from those seen in Alzheimer’s disease.
The clinical manifestations include progressive impairment of voluntary gaze of supranuclear origin, with vertical-gaze palsy (downward more than upward) being most prominent. The progressive supranuclear palsy patient is unable to fully direct his or her gaze on command, but eye movements are less impaired when the patient’s gaze is fixed on a point while the head is moved by the examiner. Square wave jerks (fixation instability) are also prominent. Other findings are gait unsteadiness with falling (often backward), dysarthria, dysphagia, rigidity, bradykinesia, deep nasolabial folds, and dystonic neck extension. Tremor at rest is often not prominent.
No fully effective treatment is available. Treatment with levodopa, amitriptyline, or anticholinergic medications may be partially effective, although the dramatic response to levodopa that is experienced by patients with Parkinson’s disease is usually lacking. Idazoxan, an α2 presynaptic inhibitor that increases norepinephrine transmission, may improve the motor manifestations of this disorder. Electroconvulsive therapy has been of limited benefit as well for improving bradykinesia, rigidity, and gait difficulties, although transient confusion is a common side effect.
Chorea is a flowing, continuous, random movement that flits from one part of the body to another. A variety of conditions are associated with chorea in the elderly patient (Table 43.2). The pathologic basis for chorea is dysfunction of the striatum.
Choreiform movements that sometimes occur as an isolated symptom in persons 60 years and older are then called senile chorea. Involuntary complex movements of the face, mouth, and tongue may occur alone or with unilateral or bilateral limb movements. Neither mental disturbance nor family history of Huntington’s chorea is associated with senile chorea. Pathologic findings often include degeneration of the putamen or caudate nucleus, or both.
Chorea may be treated with dopamine-receptor blocking medications (eg, haloperidol), but a potential side effect is tardive dyskinesia. Agents that block the release of dopamine presynaptically (eg, reserpine) are another option, as they are not associated with tardive dyskinesias; however, reserpine can be associated with depression and orthostatic hypotension. Metyrosine is an agent that inhibits the enzyme tyrosine hydroxylase, which catalyzes the conversion of tyrosine to dihydroxyphenylalanine (DOPA). Therefore, metyrosine blocks the formation of dopamine and can be effective in treating chorea. Though not associated with tardive phenomena, the medication may cause some somnolence. All of these medications can produce parkinsonism as a side effect, which is usually dose-dependent and reversible when the medication is discontinued.
A variety of different types of involuntary movements may arise as a result of the use of medications (Table 43.3). It is important to distinguish acute drug effects, chronic but reversible drug effects, and chronic and irreversible drug effects. The most common acute drug effect is an acute dystonic reaction that occurs with exposure to antipsychotic medications and often results in oral, lingual, or nuchal dystonia. If it is severe enough, treatment with intravenous diphenhydramine is required, although this approach in older adults should be exercised with caution, given the propensity for this agent to produce somnolence or confusion. Chronic reversible drug effects (effects that resolve upon discontinuation of the causative medication) include action tremor (eg, lithium, theophylline, valproic acid), parkinsonism (antipsychotic medications), chorea (estrogen, antiepileptic medications), or dystonia (dopamine replacement therapy in Parkinson’s disease). Chronic irreversible drug effects or tardive phenomena often begin after the medication (usually an antipsychotic medication) has been in use for weeks to months. Movements may include orobuccal dyskinesias, dystonia, akathisia (sensation of needing to move), myoclonus, and tics. Advanced age and duration of treatment with antipsychotic medications are the only well-established risk factors for developing tardive movement disorders. Once the diagnosis of a tardive phenomenon is established, the clinician should attempt to reduce the dosage of medication or discontinue it. Treatment for tardive dyskinesia or tardive dystonia includes anticholinergic agents (trihexyphenidyl), baclofen, reserpine, or clozapine, each of which must be used with caution in older adults. In cases of severe tardive dystonia in which there is neck jerking or sustained eye closure, intramuscular injections of botulinum toxin may reduce the frequency and severity of movements. The Abnormal Involuntary Movement Scale (see the Appendix) can be helpful in assessing and monitoring drug-induced movement disorders.
Myelopathy or spinal cord dysfunction is most often a result of either intrinsic or extrinsic compression of the spinal cord. The region most commonly involved in older patients is the cervical spinal cord. Intrinsic compression is often the result of spinal cord tumors or vascular events (infarcts or hemorrhages). Extrinsic compression is more prevalent; common causes among older patients are cervical spondylosis (with resultant osteophyte formation and degenerative disc disease), disc prolapse or herniation, rheumatoid arthritis resulting in vertebral body subluxation, or spinal metastases. Nearly 80% of patients aged 70 years or older have radiographic evidence of osteophyte formation with significant narrowing of the cord; the majority of these cases are asymptomatic. Spinal stenosis is a congenitally abnormally narrow spinal canal. When disc protrusion occurs in a patient with spinal stenosis, it further compromises the capacity of a spinal canal that is already limited. Narrowing of the cervical canal may lead to neck stiffness and pain; radicular pain, sensory loss, or weakness in the arm; and weakness and upper motor neuron signs (hyperreflexia, spasticity, Babinski’s sign) in the lower extremities. Narrowing of the lumbar canal may lead to lower back pain, to radicular pain, sensory loss, or weakness in the leg(s), and to upper motor neuron signs in the legs.
Other symptoms of spinal cord compression include gait disturbance, falls, or complaints of “numb, clumsy hands.” On examination, the patient may exhibit spastic paraparesis (symmetric or asymmetric), sensory loss at a particular cord level, or problems with micturition.
Evaluation is most commonly in the form of magnetic resonance imaging of the spine. If the patient cannot tolerate this because of the presence of metallic objects, a pacemaker, or claustrophobia, then spinal computed tomogram with intrathecal contrast should be performed.
Conservative management, particularly if neck pain is an associated feature, includes activity modification, neck immobilization with a cervical collar, massage, heat treatment, physical therapy, and medications (muscle relaxants and pain medications including nonsteroidal anti-inflammatory agents). Decompressive surgery is recommended for persistent pain or a progressive neurologic deficit. Older patients are more prone to have multiple levels of involvement, and some studies have suggested that their prognosis after surgery is poorer than that of younger patients.
Motor neuron disease (MND) is a neurodegenerative condition involving both upper and lower motor neuron cell bodies; it is characterized clinically by a progressive weakness and wasting of skeletal muscles, often in combination with bulbar palsy and respiratory failure. The incidence increases with age but reaches a plateau in the 60s. To date, age remains the single most clearly identifiable risk factor for this progressive and fatal disorder.
Patients frequently present with gait disturbance, falls, foot drop, weakness in grip, dysphagia, or dysarthria. On neurologic examination, patients may have a combination of weakness with upper motor neuron signs (hypertonia, hyperreflexia, clonus, extensor plantar responses) and lower motor neuron signs (atrophy, hyporeflexia). In addition, there are signs of involvement of the lower motor neuron cell bodies (fasciculations). Although cranial nerves may be involved, with resulting facial weakness, palatal weakness, and tongue weakness, the extraocular movements are usually spared. The electromyogram demonstrates findings consistent with diffuse denervation (diffuse fibrillation potentials, positive sharp waves) and poor recruitment of motor units. The differential diagnosis includes lesions at the level of the foramen magnum or the high cervical cord and vitamin B12 deficiency. The prognosis is poor, with the average survival on the order of 2 to 3 years. The presence of bulbar signs carries a poorer prognosis.
Although most new cases of MND occur in older adults, the incidence and prevalence of this disorder relative to other more common neurologic disorders is low. Therefore, gait disturbance and focal motor weakness may be attributed to the more common cerebrovascular diseases or to cervical radiculomyelopathy rather than to MND. Older adults are also more likely to have coexisting neuropathology, adding to the challenge of and delay in diagnosing MND. One study showed that those over the age of 65 years were diagnosed after 19 months, in comparison with those who were less than 65 years of age, who were diagnosed after 3 months.
The treatment is mostly supportive. Riluzole, which has demonstrated modest effects upon survival or time to tracheostomy, is now in widespread use. The action of riluzole is thought to protect against glutamate toxicity, which may be involved in the pathogenesis of MND.
Radiculopathy is a disruption of the peripheral nervous system at the level of the spinal roots after they exit the spinal cord. Among older adults, this may be the result of herniated discs or osteophyte formation. Symptomatic nerve root compression may result in complaints of pain radiating down the neck, back, arm, or leg, and on neurologic examination, this may be accompanied by motor and sensory deficits as well as diminution of reflexes in the distribution of a particular spinal root or roots.
The prevalence of peripheral neuropathy in older adults has been estimated to be as high as 20%, and some degree of subclinical decrement in peripheral nerve function on electromyography is probably universal in healthy older adults. Peripheral neuropathy may be particularly devastating in older adults because of gait impairment due to sensory and motor deficits and thus a propensity to fall. In developed countries, diabetic neuropathy is the most common form of neuropathy, with up to 60% of patients who have diabetes mellitus and who are over the age of 60 years having a peripheral neuropathy. Several types of neuropathy are associated with diabetes mellitus, including a distal symmetric neuropathy, asymmetric neuropathies that may involve cranial nerves, roots, or plexus, and mononeuropathy multiplex. Other common causes of peripheral neuropathy in older adults are medications (eg, amiodarone, colchicine, phenytoin, lithium, vincristine, isoniazid), alcohol abuse, and nutritional deficiencies (eg, vitamins B6 and B12 deficiency, as well as deficiencies of thiamine, folate, and niacin), renal disease (ie, uremia), monoclonal gammopathy (eg, multiple myeloma), and neoplasm (eg, infiltration of peripheral nerves by malignant cells, paraneoplastic syndromes associated with oat cell carcinoma of the lung, breast cancer, ovarian cancer, renal cell carcinoma, and prostate cancer).
The treatment of the neuropathy depends on the cause, ranging from withdrawal of the causative agent (alcohol, medications) to nutritional supplementation (nutritional deficiency), or treatment of the primary cancer (neoplastic neuropathy). There is some evidence that optimizing glucose control may lessen the severity of diabetic neuropathy. Treatment of neuropathic pain includes the use of tricyclic antidepressants, AEDs (eg, carbamazepine, phenytoin, clonazepam, gabapentin), selective serotonin-reuptake inhibitors, and topical agents. Topical agents include capsaicin analgesic cream and local anesthetic agents.
Myopathies are characterized by proximal muscle weakness, wasting, and diminished or absent reflexes, and they may be accompanied by elevations in serum enzymes (creatinine kinase) and a myopathic pattern on electromyogram and on muscle biopsy (ie, fiber degeneration follows a random pattern). Older adults may attribute mild or moderate muscle weakness to aging and therefore may not immediately consult a physician. Proximal muscle weakness, which results in difficulty rising from a chair, difficulty in climbing stairs, or difficulty washing the hair, is particularly likely to be attributed to aging or arthritis.
The most common myopathies in older adults are polymyositis, endocrine myopathies, toxic myopathies, and myopathies associated with carcinoma. Polymyositis is a disorder of skeletal muscle of diverse causes characterized by an infiltration of the muscles with lymphocytes. Muscle biopsy usually shows signs of degeneration, regeneration, and infiltration by lymphocytes. Treatment with prednisone should be used with caution in older adults because of its propensity to produce psychosis. In thyrotoxic myopathy, weakness and wasting are greatest in the pelvic girdle muscles and to some extent in the muscles of the shoulder region. Reflexes may be normal, and the diagnosis is made by the distribution of muscle weakness in a patient with thyrotoxicosis. Improvement of the myopathy follows treatment of the underlying endocrine disorder. Hypothyroidism may also cause a myopathy that improves with thyroid replacement therapy. Myopathy may occasionally be the result of a remote effect of a cancer (ie, a paraneoplastic disorder), with complaints of weakness often preceding the establishment of a diagnosis of cancer. Several drugs are known to cause myopathy, including corticosteroids, lipid-lowering agents, procainamide, and diuretics that produce hypokalemia.
A collection of blood between the dura and the arachnoid is referred to as a subdural hematoma. It is usually due to head trauma, although the trauma may be mild, particularly in older adults. In approximately 15% of cases, the hematomas are bilateral.
Perhaps most relevant in the elderly patient is the chronic subdural hematoma. The incidence of chronic subdural hematoma increases with age, from 0.13 per 100,000 for those in their 20s to 7.4 per 100,000 for those in their 70s. In 50% of chronic subdural hematomas, there is no history of head injury, although other risk factors include clotting disorders, shunting procedures (eg, ventriculo-peritoneal shunting for normal-pressure hydrocephalus may separate the blood vessels from the dura, resulting in tears), and seizures.
The symptoms of chronic subdural hematoma are headache, slight or severe impairment in cognition, and hemiparesis. Some patients may have seizures. Focal neurologic signs (weakness, sensory loss, change in sensation) may be present. Neuroimaging studies reveal an extra-axial collection of blood.
The treatment of the hematoma varies depending on whether it is symptomatic or an incidental finding on a neuroimaging study. If symptomatic and the patient’s condition is worsening, then removal of the clot may be attempted. If asymptomatic or if the patient’s condition is improving, then clinical monitoring is appropriate, as the hematoma may shrink and disappear without surgery.
See Sleep Problems.
■ Cancellor AM, Hendry A, Caird FI, et al. Motor neuron disease: a disease of old age. Scot Med J. 1993;38:178–182.
To date, age remains the single clearest identifiable risk factor for sporadic forms of motor neuron disease. The age-specific mortality rate rises exponentially during the middle decades of life and eventually reach a peak in the 60s. The authors report four patients with motor neuron disease who presented within a 6-month period to a geriatric medical unit and also present data from a population-based registry of adult-onset cases of motor neuron disease in Scotland. The authors highlight problems in the initial diagnosis and management of motor neuron disease in an older population.
■ Edmeads J. Headaches in older people. Postgraduate Medicine. 1997;101:91–100.
Although there is a decline in the prevalence of headaches with age, headaches are still a common condition in older adults. There are a number of special considerations in the diagnosis and management of older adults with headaches, including recognition of atypical ways that migraines may present, treatment with special regard for a reduced tolerance to medications, and diagnosing underlying systemic illness. The author discusses the more common causes of headaches in older adults, including migraine and tension headache, as well as those caused by diseases (for example, chronic obstructive pulmonary disease, intracranial mass lesions).
■ Odenheimer G, Funkenstein HH, Beckett L, et al. Comparison of neurologic changes in “successfully aging” persons vs the total aging population. Arch Neurol. 1994;51:573–580.
In this study the authors administered a neurologic examination to participants and were able to calculate for each neurologic sign the proportion of elderly persons in the population with each abnormal finding and the proportion with each finding but without evidence of medical or neurologic disease that was likely to produce the finding. The authors examined 467 persons over the age of 64 years. They found that numerous neurologic signs were present in their cohort and that there was an increase in the prevalence of these signs with advancing ages. Primitive reflexes and abnormalities in gait, in particular, showed significant increases in prevalence with age, suggesting a selective age-related vulnerability of certain neurologic systems.
■ Pancioli AM, Broderick J, Kothari R, et al. Public perception of stroke warning signs and knowledge of potential risk factors. JAMA. 2000;279:1288–1292.
Using random digit dialing, the authors interviewed 1880 persons to determine respondents’ knowledge of stroke warning signs and risk factors. Over 1000 of the respondents were aged 65 years and older. Only 57% of the respondents correctly knew at least one of the established stroke warning signs, and 68% correctly listed at least one established stroke risk factor. Older patients, especially those 75 years or older, were less likely to correctly identify stroke warning signs or risk factors. The study implies that the education of adults, especially those who are elderly, regarding stroke warning signs and risk factors would improve stroke prevention and the timely management of acute strokes.
■ Wilmore JL. Management of epilepsy in the elderly. Epilepsia. 1996;37 (suppl 6):S23–S33.
Seizures occur in a bimodal age-dependent pattern, with peaks in the first year of life and then again after the age of 60 years. As the population ages, epilepsy in elderly patients is a growing challenge. Special considerations when treating elderly patients with epilepsy include the identification of an underlying cause, which is often a vascular or a neurodegenerative disease, and the choice of a treatment regimen in the setting of reduced tolerance for antiepileptic drugs. The author discusses the mechanism of action, pharmacokinetics, efficacy, and side effects of the older and newer antiepileptic medications, with a goal of optimizing the pharmacologic management of epilepsy in older adults.
Elan D. Louis, MD, MS
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